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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

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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.

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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.

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J. Michael Bishop with a model of DNA Photograph courtesy of UCSF Archives and Special Collections.

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In Memoriam Kathryn Ione 1937-2016

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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.

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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

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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

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Interview 3: January 19, 2017

Audio File 3

Hour 1 78

Reiterating importance of Rous discovery — First indication of normal genes in human DNA that if modified can become cancer genes — Arthur Levinson’s enzyme discovery — Levinson’s choice to join Genentech — Stigma attached to academics joining biotech firms — Genentech’s manufacture of Herceptin, first targeted therapy for cancer — Proto- oncogene discoveries — Amplified DNA regions — The gene NMYC— Connection between gene amplification and survival rate — Research meetings/consortia with outside labs— Peter Duesberg’s resistance to the oncogene concept — More on switching from polio to Rous sarcoma research — Funding sources for cancer research and grant writing — Cold Spring Harbor meetings — Change in focus of meetings with AIDS outbreak — Shift in interest from replication of cancer virus to oncogenes — Beginnings of long partnership with Harold Varmus

Hour 2 95

Necessary ingredients to successful partnership; mutual generosity and credit — Division of labor and interests in partnership with Varmus — Varmus’ interest in the details; his in the big picture — Weekly lab meetings — Asilomar meeting and possible dangers of recombinant DNA research — Commercialization of biology; founding of Genentech in 1976: “I understood that if this [discovery of the oncogene] was going to reach a stage of development that it could be used in the clinic, that was going to happen in the corporate world” — Use of restriction enzyme in research

Interview 4: February 27, 2017

Hour 1 105

On the possibility of winning a Nobel Prize: “It was never a strong expectation on my part” — Family’s reaction to the award — Nobel Prize committee’s phone number mix up — Stehelin’s frustration for not being included in the award— Family and friends invited to Nobel reception in Sweden — Anxiety of giving an address, coming down with bronchitis — Pros and cons of awarding prizes in science — Politics and the Nobel Prize — Changes in public stature after the prize — Founding the Coalition for Life Sciences — Goal of increasing public understanding and federal funding of the National Institute of Health and National Science Foundation — Coalition hires a lobbyist, reaction of some professional societies — Forming a biomedical research caucus — Identifying speakers to meet with legislators and their staff — Viewing lobbying as an “educational exercise” — Gradual withdrawal from bench work — Becoming director of the G.W. Hooper Research Foundation — Redesigning research space — Varmus’

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desire to “cut the umbilical cord” — Increasing divergence in research interests — History and aims of the Hooper Foundation

Hour 2 124

More on joining UCSF and its status as a “mediocre” institution at the time — Becoming chancellor of UCSF — Division of administrative responsibilities; chancellor simply makes “the trains run on time” — Conversation that inspired consideration of chancellorship — Structure and organization of chancellor search — Reasons for being offered and then assuming the role — Commitment to UCSF as foremost motivator — Turning down directorship of the National Cancer Institute to stay at UCSF — Building national academic standing of UCSF — Holly Smith’s plan of transforming UCSF from a “trade school” — Crediting Smith for UCSF’s rise to eminence — Beginning of Mission Bay campus — Donation of land by a developer — Hesitance on the part of some university administrators to build, ambitious push by others — Mission of building a facility large enough to house a research community: “We knew that if we could constitute a real community down there from the get-go, it would work” — Researchers and departments begin to move in; people who stay end up feeling like “second-rate citizens”

Interview 5: March 10, 2017

Audio File 5

Hour 1 137

Conversation with Susan Montrose on taking on the chancellorship — Overcoming resistance from the UC President’s Office to create position of executive vice chancellor — Eugene Washington’s tenure as executive vice chancellor/provost — Comprehensive strategic plan of 2007 to encompass “every facet of the institution” — Washington’s role in driving the strategic plan agenda — The administrative body behind the strategic plan — Key objective: “Provide a supportive work environment to recruit and retain the best people and position for UCSF in the future” — Goal of moving away from department-focused graduate programs to a “horizontal” community of faculty — Dean Rudi Schmid encourages PIBS [Program in Biological Sciences] to apply for a Markey Foundation grant — Receiving $13 million grant — Increasing graduate student stipends — “The most powerful thing it [the grant] did was to change the approach to faculty recruiting” — Persuading basic science and clinical departments to give PIBS a hiring veto — More on the conceptual and structural novelty of PIBS — Role of PIBS in helping raise the stature of UCSF — Colleagues’ inauguration of the J. Michael Bishop Fellowship in 2014 — Creation of PIBS a testament to the “social altruism” of its faculty — Cornelia Bargmann, first PIBS-endorsed hire in anatomy — Revamping “traditional” departments — Executive vice chancellor responsibilities — Delegating responsibilities and managing executive positions as chancellor — Applying

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experiences as a lab director — Limited interactions with the UC president — Dealing with indirect costs issue — UC campuses’ high degree of autonomy and self-sufficiency — Working with vice chancellors, “decision makers” — Funding for Mission Bay construction — Fund raising work — Demands of entertaining guests on wife Kathryn — Experience of chancellorship “more pain than pleasure” — Feelings of inadequacy and frustration in face of institutional limitations

Hour 2 155

Chancellorship as “the most demeaning position” — Failure of the Stanford- UCSF medical center merger — Merger thought to solve the competition of HMOs — Diversity program led by Washington — Problem of minority underrepresentation at multiple levels: faculty, students, employees — Establishing program on women faculty — Washington’s commitment to “accountability by measurement” — Setting aside one percent of Mission Bay budget for public art — Committee to commission site-specific art — California Institute for Quantitative Biosciences (QB3), an interdisciplinary consortium of UCSF, UC Berkeley, and UC Santa Cruz — Remembering the forbearance of Kathryn, trials of medical school and internships endured together — Kathryn rents a farm north of Bethesda during NIH appointment — Memories of early mornings feeding her horse — Drifting away from the church as children of Lutheran ministers — Childhood memories of rudimentary living facilities — Never feeling deprived, joy of school made up for it all

J. Michael Bishop CV and list of publications 168

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Interview History

For almost anyone familiar with the history of recent bioscience, the discovery of the proto- oncogene by J. Michael Bishop and Harold E. Varmus is a turning point in understanding the genesis of cancer as a fundamental genetic event. In this oral history, we have only Dr. Bishop’s view of the research leading to the discovery, but his emphasis on the importance of the partnership with Dr. Varmus leaves no doubt that it was indeed the collaboration of two extraordinary scientists that contributed to the breakthrough why and when and where it happened. Although both men—Varmus in telephone conversations with the interviewer— acknowledge the role of talented students, visiting scientists, and departmental colleagues at the University of California, San Francisco and elsewhere, it was Bishop and Varmus who inspired and led the effort and who received the Nobel Prize in Physiology or Medicine in 1989.

Bishop’s arrival at UCSF in 1968 is an amusing tale better left to him to describe. The university was a sleepy institution at the time, nothing close to the powerhouse of today. But Bishop spotted a place to grow and found compatible colleagues, including Warren Levinson who was working on Rous sarcoma virus, a cancer-causing retrovirus. Retroviruses were a hot area of research, spurred on by Nixon’s National Cancer Act of 1971 and the increased visibility and funding it entailed for the field. For reasons he provides, Bishop recognized Rous sarcoma virus as a promising subject for research on cancer and began to collaborate with Levinson. His near miss of the discovery of reverse transcriptase, the enzyme capable of converting RNA to DNA, brought him lasting pain. He grieved for months; he had failed himself, or so he thought. When I commented that the Nobel Prize was surely a consolation, his immediate response was, “Two’s better than one.” His reaction provides insight into an individual even more demanding of himself than others. In 1970, Varmus joined the Bishop lab as a postdoctoral student, having found Bishop “the most energized” of the scientists he considered joining.1 Almost from the start a partnership of equals, they instituted weekly meetings of colleagues and students and later established free-flowing meetings with colleagues elsewhere in which they exchanged unpublished information in an unusually free fashion for its time. How the research proceeded Bishop discusses in interviews two and three, culminating in establishing the proto-oncogene as a normal cell component.

After the appearance of the path-breaking paper in 1976,2 colleagues began to suggest a likely Nobel Prize, a possibility heightened when Bishop and Varmus received the Lasker Award in 1982. In classic fashion, the call from Stockholm came in the dead of night, not to Dr. Bishop but rather to his son Dylan. Fed up with middle-of-the-night calls from teenage girls waking them, the Bishops had had turned off their bedroom telephone. Dr. Bishop maintains that winning a Nobel “was never a strong expectation on my part” -- a statement that leaves an opening for a mild expectation? When I asked Dr. Varmus for his thoughts, he admitted he felt a Nobel was

1 Telephone conversation October 3, 2016. 2 D. Stehelin, H.E. Varmus, J.M. Bishop, and P.K. Vogt. “DNA Related to the Transforming Gene(s) of Avian Sarcoma Viruses is Present in Normal Avian Cells,” Nature 260:170, 1976.

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likely to happen: “We’d won everything else.”3 Bishop relives in these pages the pomp and glory of the Nobel ceremony, which his family and entire laboratory attended, and describes how in a lull in the swirl of activity only then did the import of his and Varmus’s achievement truly sink in.

The partnership with Varmus, one of the longest and most significant in bioscience, was clearly central to Bishop’s scientific life. It was characterized by high scientific productivity, personal compatibility, mutual generosity and credit, and interest in the fine arts. As Bishop described the partnership, “The whole is greater than the sum of the parts, although I may have underestimated Harold.” Nonetheless, when Bishop became director of the G. W. Hooper Research Foundation in 1981 and moved to a new laboratory upstairs, Varmus chose to stay behind in his lab on the fourth floor. The relationship of the two labs loosened over time as each pursued its own research agenda.4 The broader message the reader might take from Bishop’s lucid account is that top-level bioscience is a passionately driven affair, dependent on contributions within and outside the laboratory, the availability of relevant technologies, the interplay of broad concept and experimental detail, and exacting and insightful leadership at the top.

The chronicling of cutting-edge scientific research is a major contribution of this oral history. But it is not the only one. The interviews portray a man with a finger in many pies. A consummate teacher, Bishop speaks of his formative role in UCSF’s interdisciplinary Program in Biological Sciences and its significance for attracting quality faculty and students. He also describes his political activities at the federal level with the Coalition for Life Sciences. In 1998, Bishop with some reluctance accepted the chancellorship of UCSF. Wooed into believing it would be an easy ride, he was soon faced with major issues: creation and staffing of the new Mission Bay campus (1999), disintegration of the UCSF and Stanford medical school merger (2000), foundation in 2000 of California Institute for Quantitative Biosciences (QB3), adoption of UCSF’s first comprehensive strategic plan (2007), and a campus public arts program. In 2004, he fought for and won approval to establish the position of executive vice chancellor/ provost at UCSF, thereby placing UCSF on an equal administrative basis with other University of California campuses. His appointment of Dr. Eugene Washington was an inspired choice. With Bishop’s full backing, Washington drove implementation of the strategic plan which established UCSF as a horizontally integrated, cross-disciplinary institution prioritizing global health, diversity, and work-life balance. A consummate fundraiser, Bishop not only headed a record- setting $1.7 billion campaign but also thrived on meeting and entertaining prospective donors. Orchestrated largely by his wife Kathryn, occasions at the chancellor’s residence brought potential donors and key scientists together in a relaxed setting. Kathryn’s role was crucial. Susan Montrose, former Assistant Chancellor, observed, “I’m not sure he could have done it without her.”5 All in all, Bishop’s years as chancellor (1998-2009) marked a highpoint in the university’s growth, funding, and achievement.

3 Telephone conversation October 10, 2016. Bishop and Varmus received a Lasker Award in 1982, commonly taken to predict a possible Nobel Prize. 4 Telephone conversation October 10, 2016. 5 Telephone conversation March 5, 2017.

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Acknowledgements

Bruce Alberts, Bishop’s accomplished UCSF colleague and friend, suggested and underwrote this oral history. We are immensely grateful to Dr. Alberts for his generosity. The project was inspired to celebrate Dr. Bishop’s 80th birthday in 2016 at a trying juncture in his life. He had recently lost his beloved wife Kathryn and the same year retired from the university, both events central to his personal and professional lives. Despite these losses, he was far from inactive (under any circumstance probably an impossibility for a man of his makeup). Several times, the interviews were interrupted by his trips to give talks in the U.S. and abroad.

I am grateful to Harold Varmus for taking time from his hectic schedule to have two lengthy telephone conversations with me about his former collaborator and friend, Mike Bishop. I also thank Susan Montrose, former UCSF Assistant Chancellor, and Eugene Washington, former UCSF Vice Chancellor and Provost, both of whom served with Dr. Bishop during his chancellorship. Because of their close working and personal relationship with Dr. Bishop, they provided valuable insight into his goals, management style, and issues faced as top administrator.

The five interviews were conducted between September 2016 and March 2017 in Dr. Bishop’s modest home in Belvedere, with its sweeping views of San Francisco Bay and Angel Island. I thank Paul Burnett and Julie Allen for videotaping the interviews and Julie for final processing of the transcripts. While Dr. Bishop demanded absolute accuracy and precision of himself, he also seemed to enjoy reminiscing and telling a good story, evident especially in accounts of his early life as a Lutheran minister’s son. His emotions seemed close to the surface when he spoke of his wife Kathryn. His accuracy and precision—a character trait—extended to his review of the interview transcripts. He double-checked and added information to his original statements and would have preferred to check the almost-finished oral history not once but twice. He reluctantly agreed to be dissuaded.

Sally Smith Hughes

Berkeley, California

December 2017

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Introduction by Harold Varmus and Bruce Alberts

When Mike Bishop arrived at UCSF fifty years ago, the school was still viewed as a relative backwater in the geography of American medical research. To be sure, there were a few long- term stars and a few recent senior recruits, like Bill Rutter, Gordon Tomkins, and Brian McCarthy, building a foundation for its future appeal. But for a new junior faculty member like Mike, who had offers from more conventionally reputable institutions on the East Coast, UCSF must have seemed a daring choice. His idea—that he would be more useful at a place with a long way to go than at an Ivy League institution with a long list of laurels—was an early sign of what proved to be a persistent determination to help build the institution and to serve its faculty, staff, and trainees.

As the public record shows, he honored that intention supremely well for many years —as scientist, teacher, colleague, administrator, and scholar—until he closed his laboratory and took up emeritus status in 2016. This oral history now offers at least a partial view of what he was thinking privately during that time. We are pleased to provide a few introductory words about what it was like for us to be his colleagues for many of the nearly fifty years that he worked at UCSF.

One thing that may not be as evident from an edited transcript of an oral history as from a direct conversation with Mike in person is his abundant energy and enthusiasm. For those of us who have known him well—and even for those who have had a single encounter—the dominant impression is of a quick intelligence, an unflagging curiosity, and a lack of pretension. Not a joke-teller, but a person of general good humor. Not a pedant, but someone who knows lots of things, enjoys telling others about what he knows, and wants to know more. A reader of almost everything, a discerning collector of prints. A realist, a critic, sometimes a cynic, but also an optimist about most things. Reflective and sometimes quiet, but forceful in conversation and interested in what others have to say. Crisply articulate and inspiring as a lecturer, both in the classroom and scientific symposia, on a wide range of topics: his own scientific work, the history of infectious diseases, the politics of science, and more.

Mike’s commitment to group efforts, well before “partnerships” and “team science” were widely recognized as virtues, was a prominent feature of his years doing and overseeing laboratory work. That facet of his character was especially important to one of us (H.V.) who worked closely with Mike for nearly a quarter of a century (from 1970 to 1993)—initially as a post-doctoral fellow learning from a more experienced mentor; then for about a dozen years as a faculty colleague in an extensive and productive partnership in shared facilities on the fourth floor of Health Sciences East; and later as a consistent collaborator, when laboratories were separated by eleven floors.

This unusual relationship prospered because of shared traits recognized at a first meeting in the summer of 1969: broad interests in the arts and humanities as well as the sciences; recognition of the potential of molecular biology to improve our understanding of living systems and ultimately the practice of medicine; and a belief that good things would happen faster if scientists worked together and exchanged information and ideas freely.

These principles not only affected the way that Mike pursued science with faculty colleagues and trainees in the microbiology labs at UCSF, where shared facilities, funds, and ideas were routine.

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They extended also to relationships with cancer virologists and biologists at other institutions, especially those on the West Coast who convened and worked together regularly as a RNA tumor virus cooperative. They also profoundly affected the ways in which graduate training was conducted throughout UCSF. Mike led the creation of a trans-departmental Program in Biological Sciences (PIBS), an approach that ultimately influenced how many other graduate schools throughout the country broke down departmental boundaries.

There are very few major institutions that have risen so quickly from obscurity to fame as the University of California, San Francisco, did in the second half of the 20th century. Henry Bourne, who chaired the UCSF Department of Pharmacology from 1984 to 1992, has laid out some of this remarkable history in an admirable book (Paths to Innovation: Discovering Recombinant DNA, Oncogenes, and Prions, in One Medical School, in One Decade; University of California Press, 2011). In parallel, our friend Mike Bishop experienced a similar rise from obscurity to fame, beginning as a lowly UCSF assistant professor in 1968 to eventually serve as UCSF Chancellor from 1998 to 2009.

We have written about Mike as a scientist, but he also became an important academic leader. Only a deep feeling of moral obligation could have caused him to accept the many difficult, non- scientific responsibilities that the Chancellorship entails -- a job that Mike would repeatedly (and secretly) describe to his friends as "the most demeaning job that I have ever had". For UCSF faculty members, it was extremely reassuring to know that Mike, with his great judgment and deep moral principles, was in charge. From a selfish point of view, this meant that none of us had to devote time to worrying about the institution. But much more importantly, the scientific enterprise requires constant attention and a great deal of effort to keep its unique culture healthy, and Mike served both as a role model and a symbol that all was well at UCSF.

Fame is fleeting for us all, and science moves very quickly, with new discoveries constantly building on old ones whose importance is rapidly forgotten. But there are important lessons from both past successes and failures that we all overlook at our peril. In 2017, there are many young faculty and students at UCSF who know little or nothing about Mike Bishop, lacking an appreciation for what he has done both for science and for the university. We are both very pleased that he has been able and willing to contribute this invaluable oral history, which should serve as inspiration for many generations to come.

Harold Varmus (UCSF 1970-1993) and Bruce Alberts (UCSF 1976-2017).

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Harold Varmus, M.D. is co-recipient with J. Michael Bishop of the 1989 Nobel Prize in Physiology or Medicine for the discovery of the cellular origin of retroviral oncogenes. Following his years at UCSF, he served as Director of the National Institutes of Health (1993- 1999), President of Memorial Sloan-Kettering Cancer Center (2000-2010), and Director of the National Cancer Institute (2010-2015). He is currently the Lewis Thomas University Professor at Weill Cornell Medicine, a senior associate at the New York Genome Center, and Visiting Professor at Macaulay Honors College of the City University of New York. His memoir, The Art and Politics of Science (W.W. Norton), was published in 2009.

Bruce Michael Alberts, Ph.D. served as President of the National Academy of Sciences,1993- 2005, and as Editor-in-Chief of Science magazine, 2009-2013. He is a co-author of The Molecular Biology of the Cell, now in its sixth edition. In 2014, President Obama awarded him the National Medal of Science. For research in DNA replication and protein biochemistry, leadership of scientific organizations, and advocacy of science education, he received the Lasker- Koshland Special Achievement Award in 2016. He is currently Chancellor's Leadership Chair in Biochemistry and Biophysics for Science and Education, UCSF.

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[The transcripts do not exactly match the original recordings due to editing.]

Interview 1: September 29, 2016 Location: Dr. Bishop’s home in Belvedere, California

Hughes: This is Sally Hughes, and I have the privilege of conducting the first interview with J. Michael Bishop. It is September 29, 2016. Let’s start way back, even before your wonderful book.6 Please tell me a little about your parents. I know your father was a Lutheran minister and that you lived in a very small town in Pennsylvania.

01-00:00:53 Bishop: Yes. I was born and raised in a town of four hundred, a place called Goldsboro, whose only claims to fame were an erstwhile pinch hitter for the Philadelphia Phillies, and the fact that it’s right across the Susquehanna River from Three Mile Island. I was long gone by the time of the disastrous meltdown at the atomic power plant on Three Mile Island.

My father (John Schwartz Bishop) was the first of his family to attend college. He then went on to seminary and became a Lutheran minister. My mother (Carrie Gray Bishop) came from a family of fourteen siblings. They were virtually impoverished farmers in the area. Four of the children survived to adulthood. The rest of the family, including the parents, died of tuberculosis, diphtheria, or hemophilia. By the time my mother graduated from high school, she was in charge of the family because both parents were dead. She happened to be in my father’s parish. She went to work, and before long, one thing led to another and they were married. For a new young minister who comes to town and within, I don’t know, a couple years maybe, marries a young parishioner—that was a bold act, I would say, in those days.

In any event, my first schooling was in a two-room schoolhouse. One room had the first four grades, and the second room had five through eight. There was one teacher in each room, which meant that there was absolutely tyrannical rule by the teacher, or there would’ve been utter chaos, right? I suppose the most memorable thing for my first four years is that I was such a boisterous youngster that I was constantly, apparently, interrupting the recitations by people in the second and third grade when I was in the first grade. The teacher’s solution to this was to bump me into the third grade. So I skipped the second grade. I think I’d be medicated if this were happening now, right?

Hughes: Yes.

6 J. Michael Bishop, How to Win the Nobel Prize: An Unexpected Life In Science. Harvard University Press, 2004.

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Bishop’s parents in the Stockholm airport, December 1989

Grief etched in stone: gravestone for nine Gray siblings lost in childhood

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01-00:03:35 Bishop: In all likelihood, placing me in third grade was challenging enough to keep me under control.

01-00:03:43 Hughes: Do you think that the teacher was recognizing what we would call nowadays hyperactivity or, rather, intelligence?

01-00:03:54 Bishop: No, she just knew I was bored.

Hughes: You were too smart for first grade.

01-00:04:09 Bishop: My father was reasonably well educated. He had a master’s degree in theology. So for whatever reason, I was probably ahead of the others. This was a small school. So she recognized that if she just challenged me intellectually, I’d be fine. No, I wasn’t hyperactive. I was energetic, but not hyperactive.

Hughes: Do you have brothers and sisters?

01-00:04:40 Bishop: Yes. A brother Stephen Gray Bishop who’s three years younger and who became a physicist, and a sister (Catharine Elizabeth Bishop) who’s even younger than that, who was a schoolteacher and is now retired in Virginia.

Hughes: Was it a close-knit family?

01-00:04:56 Bishop: Reasonably so, although the sister came along so much later that she was a little removed from the two boys. I don’t remember much about her childhood as a result. But the three of us are certainly close now.

Hughes: What role did religion play, with a minister father?

01-00:05:34 Bishop: Well, it permeated our lives. My father wasn’t a proselytizing sort. He was a thoughtful, extremely kind individual. He had two small parishes about twenty-five miles apart. He spent most of his time visiting, making house calls, if you will. Just like doctors, ministers did that too in those days. I went to church every Sunday of course and was involved in some church activities during the course of the week as well. The most important impact that environment had on me was it seeded an interest, really a passion, for good music, classical music, because my father had good taste. Bach was prominent in the incidental music that was played. Neither church had an organ, and he was eager to have an organ because he did play the piano and organ a bit. Eventually, he managed to get a Hammond electric organ for one of the parishes, and he actually played for the services for a while. Then a young

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man came along who could play—better than my father, actually—and he took over the job.

The Lutheran hymnal is full of tunes by Mendelssohn and other people like that, to which the religious texts have been set. So at a young age, I started to sing. I had a godmother my aunt, Catharine McCaffray, my mother’s younger sister, one of the four survivors, who actually lived with my mother and father and was still in the household, as I recall, when I was born. She became a force in my life because she was a very aspirational individual. They heard me sing, and they realized I had a nice soprano voice. My aunt insisted that I get vocal lessons. So I started taking vocal lessons. Meanwhile, I also started taking piano lessons. I was just good enough to play a recital, which I absolutely hated. I was in high school by that point. Then I took up the organ, and I fell deeply in love with the pipe organ. Took lessons from a very fine organist. By that point, we had moved from this little town to a metropolis of a thousand. My father had a bigger church with a fine three-manual Moller organ, and I had a very good teacher. We were close to Harrisburg, the state capital. I was soon playing for the services, so my father had a free organist for about four years, till I went away to college.

01-00:09:29 Hughes: In your book you wrote that it was hard for you to choose between science and music, and if you had had to choose at that point, you might have chosen music.

01-00:09:40 Bishop: Well, what I said at that point was that I soon realized I didn’t have the talent to be a first-class musician. I clearly had academic talent. So by the time I was in college, I had given up any formal training in music. Really, it’s not easy to get access to a pipe organ when you’re in college, even the small college where I went to school, because the music majors have first call on it, right? So I gave it up and concentrated on deciding what I was going to do with my head, with my brain.

Hughes: Well, there were reasons why you leapt to science. But I’m looking at the bank of musical equipment in your living room.

01-00:10:28 Bishop: Yes, right. Well, I love music.

Hughes: So music still figures in your life.

01-00:10:34 Bishop: Absolutely. I’d be lost without it, I think. I miss performing, but it’s a long way in the past.

As a boy soprano, I sang at major events around Central Pennsylvania, as a soloist. I would say the high point of my high school career was singing in the

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state chorus under the direction of Robert Shaw, who was one of the great choral directors of that era. That was a huge thrill for me. I was a tenor, by that point. Not a really great tenor, but good enough to sing in a state chorus.

05-01:39:59 [For better continuity, the following paragraphs were moved from the end of the interview.]

To begin with, my childhood was anything but luxurious. We had an outhouse and a chamber pot. We had no running hot water. The house was heated by a coal-fed furnace with a grate in the floor over it, and that was it. The heat came into the living room and then diffused around the house more or less effectively. We bathed once a week in a galvanized tub in the kitchen. My mother would heat the water on an iron coal stove she had. When I was a freshman in high school, my father got a somewhat more prosperous parish, and we actually had a bathroom, which was a really big deal. In fact, it was the largest room in the house, as I recall, for some bizarre reason. Those early days, I think back on them. I certainly as a kid had no sense of depravation living the way we did. Just, this is what it was when I became sentient. But after we moved and got a— Well, first I saw showers in high school. I thought, wow, what is this? Okay! The little two-room schoolhouse did not have showers. We were lucky to have bathrooms. Which were, incidentally, unisex. How about that for 1943 or so?

My father was paid very, very little. We were provided with this munificent house without indoor plumbing, right? We had a half-acre lot behind us in which my father grew most of the produce that we would eat. My mother would can it for the winter. We got a lot of provisions once a year around Thanksgiving time. Our Harvest Home, it was called. Dad had two small parishes. The one parish was mainly farmers. So we would arrive at the church on that day, and there would be, spread out in front of us, this pile of food—the kind of food you could preserve and keep. That helped us get through the winter. We had no television until I was a senior in high school, when the parish decided that they all had TVs and the reverend didn’t have a TV, so they bought us one, a black and white TV. So I got to watch Milton Berle. But I remember never feeling deprived because I was thriving in school and having a wonderful time in school. I had admirable parental influences. I had a mother I was trying to please because she was the more demanding. I had this gentle, thoughtful father. It never occurred to me that I was to some extent not fully blessed, right? Because I was fully blessed with what mattered.

Hughes: Did that frugality continue in some form into your more mature life?

05-01:43:48 Bishop: Only to the extent necessary.

Hughes: Meaning?

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Grades 5-8, Goldsboro Elementary School, circa 1945. Mike Bishop first row, 4th from left. Teacher Robert Shupp is in the back.

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05-01:43:53 Bishop: Witness our print collection.

Hughes: Right.

Hughes: This question jumps way ahead in time, but I’m afraid I might forget to ask you later. I’m thinking of Gordon Tomkins’ effort to have musical events at UCSF. Were you a performer in any of those?

01-00:11:37 Bishop: No.

Hughes: Do you know what I’m talking about?

01-00:11:39 Bishop: Yes, I do. No, I wasn’t part of that. I couldn’t have been. I wasn’t performing by that point.

Hughes: But you could’ve been participating in other ways.

01-00:11:49 Bishop: Yes. But I wasn’t part of it.

Gordon came about a year after I had arrived and was in a different department [Biochemistry and Biophysics]. I got to know him and his wife Millicent, but not exceptionally well before his tragic death. But he was a supporter and did encourage me at a time when I thought maybe our research was just too wild to be tolerable. Gordon is famous for the comment that— He said he reached a point in his career when he had to decide between music and science, and he still wonders to this day what would’ve happened if he had chosen science. [Hughes laughs] In other words, he really never made up his mind.

Hughes: Well, he passed his gene for music, if there is such a thing, to one of his children, who is quite a cellist, as you probably know.

01-00:12:50 Bishop: Yes, I know. Both daughters are fine musicians.

Hughes: Let’s talk about your mother, because she doesn’t come into the book very much.

01-00:13:07 Bishop: Well, the book is not an autobiography.

Hughes: I know it’s not. But that’s one reason for asking you.

01-00:13:12 Bishop: My mother was very bright. She was valedictorian of her high school class, and I think lived all her days quietly, really very sad that she was never able to

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go to higher education because she was in charge of the household. When she graduated from high school, she had to go to work immediately, and then married and started a family. She was much more the disciplinarian than my father. The family still laughs about my father chasing me around the dining room table in order to spank me and finally giving up in a gale of laughter because he just couldn’t catch me and I wouldn’t give in. But she was, in her quiet way, also aspirational. She expected all three of her children to perform well in school. I just took to it. I just loved learning new things. I just loved it from the beginning, and I still do.

The second teacher, Robert Shupp, I had in the fifth through eighth grades, was a remarkable man. He was a local, born and bred. He was extremely rigorous and demanding and really just inspired me, because I could see that this man, despite his rough-hewn nature, loved knowledge. What he particularly liked and taught with great vigor was history. That inspired in me a life-long love of history, and I in college gave serious thought to becoming a historian. Decided that they probably didn’t do as much good for humankind as maybe a doctor does. But I’m not so sure that’s correct now. In any event, that’s getting ahead of the story a bit. So my mother was a very important figure because she was the one I was trying to please. My father was whatever you— Really unspoken [was] you’re in charge of your future. But my mother was the one I was trying to please as a youngster.

Hughes: And then you had this great teacher to carry you forward.

01-00:16:02 Bishop: Yes. He was a deer hunter, as was my father-in-law, and part of his contract was, he got the first day of deer hunting season off. So school was out that day. At least his part of the school was out that day. If he didn’t get a deer the first day, he got another day. So we were cheering for the deer the first day. I remember that so vividly because at the time it seemed perfectly natural that he should have a day off to go deer hunting.

Hughes: Now, is he the one that you reconnected with after the Nobel Prize award?

01-00:16:50 Bishop: No, that was my high school track coach and physics teacher.

Hughes: Well, maybe we are at high school. Are we?

01-00:16:58 Bishop: Yes.

Hughes: Do you want to say more about your family or early education?

01-00:17:06 Bishop: When the time came, I entered Gettysburg College.

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01-00:17:06 Hughes: And why?

01-00:17:18 Bishop: Because my father had gone to Gettysburg College and because as a child of a Lutheran minister, I got a nice scholarship to go to Gettysburg College. It was about fifty miles from home. Far enough away for me to be comfortably independent, but close enough for my parents to come on weekends and get the laundry. I am grateful to this day for the fact that I went to a small liberal arts college. First of all, given my background, if I had by any chance gone to a powerhouse school, an Ivy or a big state university, I would’ve probably been lost. So this small liberal arts college was the perfect place for me to really find myself and polish my intellect. Many of the teachers became my friends, and several of them I visited in Gettysburg until they died. I love the liberal arts. I went into college as a nominal pre-med, which meant I became a chemistry major. At Gettysburg College, that was the best way to get into medical school, they told me. I was a pre-med for a somewhat serendipitous reason. It wasn’t on my mind as a high school student until that aspirational aunt of mine, Catharine McCaffray, hooked me up with her general practitioner. He just happened to be a man of exceptional intellect who had gotten his MD and some advanced training at the University of Pennsylvania and decided he wanted to try his hand at family practice in a small town. So he was practicing in this town where my aunt lived, a place called Boiling Springs, which is known to trout fishermen but probably no one else. He took me under his wing. He would take me on house calls. He did a lot of his own laboratory work. He read his own cardiographs. He did his own urinalysis and so forth, all in a little laboratory in his home. So I saw all of that going on. He was just insistent that I consider medicine. And I came to admire him so much that I thought, okay, I will take a cue from this man and just line myself up for it in case that’s what I want to do. So I started as a chemistry major at Gettysburg College.

Hughes: Had you had any science in elementary or high school?

01-00:20:14 Bishop: Oh, pitiful little in elementary school. I can only remember the biology. I don’t remember anything from the first four years. In the grades five through eight, the only biology I remember is that we all had to go out and find so many different types of wildflowers and dry them and press them, preserve them. To what end, I don’t remember. I do remember making the press.

In high school, we had the usual chemistry, physics, and biology classes. Typically for that time, the physics class was taught by the football and track coach. He was actually a fairly stimulating teacher. He had some very imaginative ways of portraying sophisticated experiments, like the Michelson- Morley experiment. But in any event, I liked science. It was fun. I immediately took to it. But I still was liking the other stuff. The teaching of English literature, I remember vividly. It was dreadful. The main expectation

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of us, that we would memorize certain lines from major authors and be able to recite them and identify them. We weren’t reading. I didn’t become an avid general reader until I was in college. I did read as a youngster. I had some adventure series that were given to me. But major books of literature, history, politics, they just weren’t in the household. There were books of theology in the household. There was Reader’s Digest on the coffee table. That was a start, that was a start.

Hughes: What caught your attention about science?

01-00:22:39 Bishop: Well, that’s like trying to define love. Just I enjoyed it.

Hughes: But not everybody has that immediate attraction. There must’ve been something—

01-00:22:51 Bishop: Well, I didn’t fall in love with every woman I met. Only one. Science was fun. I liked it. I liked thinking about how things work in nature at a very elemental level, on the one hand. So chemistry and physics appealed to me from that standpoint. But on the other hand— As I think back on this; it’s really, really interesting to me. As a pre-med, I had to take more biology than usual. So I took an elective course in comparative anatomy. The man who taught it, taught it as an exercise in evolution. I had never heard of this before. This wasn’t in the household. My father never had any objection to it. I found a letter from him as I was going through our effects here recently, written to me many, many years ago. I don’t remember what precipitated it, but in it he explained his views of evolution. He said he never thought there was any conflict between his theology and the science of evolution. And he was taught that in seminary. Now, that was a long time ago.

Hughes: Wow.

01-00:24:06 Bishop: Yes. So the point being, I hadn’t thought about it. But this course was just eye-opening to me. I was just fascinated by how you could look at the anatomy of vastly different creatures and see how they could have somehow started from the same seed.

Hughes: Were you looking at the embryology?

01-00:24:30 Bishop: No, we were dissecting cats and dogs and rats and frogs and—

Hughes: Oh, I see.

01-00:24:34 Bishop: Yes, comparative anatomy. To what extent do our leg muscles and leg bones resemble those of a chicken? That sort of thing. That was what comparative

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anatomy was all about. It was really about evolution. This very fine teacher taught it from that vantage point.

Hughes: Do you think that was unusual for the time?

01-00:24:59 Bishop: Yes.

Hughes: Comparative anatomy had been around for a while, but putting the emphasis on evolution—

01-00:25:03 Bishop: Well, I can’t say. It just hits you in the face, the obvious way to teach it is from the vantage point of evolution.

Hughes: Obvious to you, but not necessarily to other people.

01-00:25:17 Bishop: Who didn’t take comparative anatomy when they were still at an impressionable age.

Hughes: I was a TA in histology at UCSF as a means to support myself through graduate school, and I don’t remember any talk about evolution.

01-00:25:43 Bishop: Right. Times have changed a little bit now. There’s both scholarship and even instruction in evolution and medical problems and how to think about illness from an evolutionary standpoint.

Hughes: Really?

01-00:26:09 Bishop: I have several books on it on my shelves.

So on the one hand, I’d fallen in love with understanding things on a very fundamental level; and on the other, there was this macroscopic phenomenon of evolution. It took me about a nanosecond to think, well, of course. Here, look at all this evidence. I knew nothing about fossils, for example. But just the simple anatomy lesson—semester-long, I might add—was enough to open my eyes and convince me.

Hughes: Do you think that had anything to do with what I understand is your ability to see the big picture? Is there any chance that it started about that time?

01-00:27:07 Bishop: Frankly, I think that sort of thing is innate. And it was being taught. This was not an insight original with me, right? It was something that the teacher— The whole course was structured that way, around the evolutionary principles that were apparent in comparative anatomy. So I think how people approach things,

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some very focused, detailed, and to the exclusion of everything else, as opposed to more of a generalist approach, which I am innately drawn to. Although you’ve got to get beyond that to succeed in science; at some point, you do have to focus.

Hughes: I think probably some of your classmates could’ve taken that course with the evolutionary overlay and paid less attention to it than you did.

01-00:28:39 Bishop: This was an advanced course, so most of the people in the course were biology majors.

Hughes: Oh, were they?

01-00:28:43 Bishop: I don’t remember anyone raising a religious objection to the instruction, even in that era. I graduated from college in 1957, right?

In any event, to go back to why I took to science: I took to science because I liked what I saw and found it satisfying and fun. Organic chemistry, which was supposed to be this draconian filter for pre-meds—still viewed that way—was just fun. You were asked to start with these simple components and build a complicated molecule. Now, I was taught very classical organic chemistry, not nearly as exciting as what you would be taught today, which is very mechanistically oriented. There wasn’t enough known mechanistically at that time to build a whole course on it. What was known was taught. But it was all about putting molecules together. It was fun. I practiced relentlessly, and I still have the big legal tablets—well, I actually sent them to the UC[SF] archives—the legal tablets where I did my final practice for the exams. They’re quite elegant, actually. I was very careful and meticulous. I’m not that way anymore, but in any event. Yes, so I took to science just naturally, I must say.

But my enthusiasm for the humanities did not diminish at all. I was thrilled with several history courses I took. I took courses in literature. I took several courses in philosophy, particularly formal logic. College was just a lot of fun for me. I worked very hard, I did very well, and it was fun. I thought learning was just a kick. Gettysburg College was big enough and the student body diverse enough, except ethnically, so that it was expanding my social horizons as well. I was learning to deal with larger groups of people. I wound up as a member of the academic senate and was a leader of a couple other organizations. I had a misbegotten career as a cheerleader.

I wasn’t good enough athletically to compete for varsity athletics. This was a time when you were worrying about whether you might get drafted into the armed forces. So I started in the ROTC, the officer training course, rather than doing phys[ical] ed[ucation], where I would do at least some sports. I did well. The colonel who was in charge of the ROTC program— I did the Air Force

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ROTC, because I thought I wanted to fly airplanes. In any event, after the first year was over, he called me in, this colonel, and he said, “What are you doing in ROTC?” I said, “Well, I thought if I get drafted, maybe I would want to fly airplanes.” He said, “You’re too smart to do that.” He said, “Get out of ROTC and get on with your career. Get on with your life.”

Hughes: Kind of amazing.

01-00:32:44 Bishop: Yes. I went out of there, my head was spinning. Because I was good at it, I was named outstanding freshman cadet, I’m proud to say. In any event, that interview with the colonel was an eye-opener. So college was just overall a transformative experience for me.

Hughes: And there’s another reason for it being transformative.

01-00:33:12 Bishop: Well, of course. I met my wife (Kathryn Ione Putnam) to be. Yes. Right.

Hughes: The love of your life.

01-00:33:17 Bishop: Yes.

Hughes: Do you want to say more?

01-00:33:20 Bishop: Yes. Well, I guess I was a junior, and she entered as a freshman. So there’s a backstory to this. Her father was a minister as well, a Lutheran minister as well.

Hughes: Any reason that brought the two of you together?

01-00:33:37 Bishop: Well, that’s the story. Her mother (Agnes Putman), who was a very dynamic woman, was active in a ladies aid society, as they were called, that worked on behalf of Gettysburg College. I was drafted by the administration to be one of the student emissaries to this kind of group. At one point, I appeared before her group in Harrisburg. Her husband (Dwight Putman) had a major administrative post in the local Lutheran church. He was akin to a bishop, I guess, in the Catholic church. So my father knew him, but as a more or less subordinate. I had never met them, knew nothing about them. So I make my appearance at this dinner meeting with Kathryn’s mother and her lady friends. She goes home. Kathryn has at this point decided she’s going to Gettysburg College. Daughter of a Lutheran minister, right? Her father had attended what was the precursor to Gettysburg College. In any event, her mother goes home to Kathryn and says, “I met this young man from Gettysburg College. You should look him up when you get there.” She said, “Oh, Mother! Stop trying to arrange my—”

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Then Kathryn arrives on campus. Among the other things I was in charge of was the student orientation for the entering class. So I had to make a little speech, and then I played my ukulele and sang some folksongs. I had a big baritone uke. Kathryn’s in the audience, and she doesn’t yet know that this is the person her mother had urged her to look up. But she turns to a friend of hers who’s in my fraternity and says, “Would you introduce me to that guy?” All else followed. Her mother never crowed about this, but she used to chuckle about it with me occasionally. She would say, “I picked you out and Kathryn followed up.”

Hughes: Was it love at first sight?

01-00:36:11 Bishop: Oh, yes. I had been playing the field, as they put it, and I dropped the field.

Hughes: Were your married right away?

01-00:36:24 Bishop: No.

Hughes: You were married as an undergraduate, weren’t you?

01-00:36:27 Bishop: No. I went on to medical school. She was at that time two years behind me. I was a junior and she was a freshman. But she went to summer school to accelerate so she could get out school and move to Boston and keep an eye on me. We didn’t marry until after my second year in medical school.

Hughes: I see.

01-00:36:55 Bishop: So I had a great time in college. I think a liberal arts education is a wonderful preparation for being a physician or a scientist. There was a very interesting compilation done some years ago by Tom Cech, a Nobel laureate, a chemist, who’s at the University of Colorado, Boulder, and for a while was president of Howard Hughes Medical Institute. Tom went to a small liberal arts college, and, like me, fervently believes in how valuable that kind of education can be. He wrote an essay for Daedalus in which he assembled the numbers that showed that on a per capita basis small liberal arts colleges contribute more people to the scientific workforce in the United States than large research- intensive universities. I think one of the reasons for that is that your introduction to science in a small liberal arts college is leavened by other things. It’s gradual. You go to a place like Berkeley, and if you’re not a real hot shot when you get in there, you’re likely to feel lost. Now, that’s an exaggeration, a generalization. But I know for a fact that a lot of people who enter large research-intensive universities with a thought about careers in science don’t wind up doing science.

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Hughes: Interesting.

01-00:38:37 Bishop: Yes. Now, I was the opposite. I went into college thinking I would be a physician and wound up being a scientist. But not before I trained as a physician, which was not totally uncommon in my time.

Hughes: Well, you had some peers. I’m thinking of Arthur Kornberg. I’m interested in NIH [National Institutes of Health] as a sort of cauldron for training MDs who then go into research.

01-00:39:07 Bishop: Well, of course that’s where I eventually got my credentialing as a research scientist, right.

So the big deal was where to go to medical school. My original mentor (Robert Kough), that general practitioner, had meanwhile gone back to University of Pennsylvania and become a trained hematologist/oncologist and wound up as the chief of that service, and at some point had even a higher administrative position in the Geisinger healthcare system in Pennsylvania, which to this day remains a model for good health care. It’s a very admired. It’s in relatively rural Pennsylvania. It’s large. Anyway, I visited him there several times.

Hughes: Is it like Kaiser Permanente?

01-00:40:09 Bishop: Yes, it’s put together after Kaiser Permanente. It’s not as large as Kaiser. It’s in just that one place in Pennsylvania. In any event, he was a very accomplished individual is the bottom line. So he thought I should be going to Penn [University of Pennsylvania] of course, right? He had me down there to see Penn. It was a little dingy, I have to say. I remember thinking, ooh. It was in a kind of dingy part of town. It’s just now in the last decade that the University of Pennsylvania has helped to bring that part of town up by its bootstraps. But that’s another story.

That all changed when my advisor Glenn Weiland in the chemistry department called me in. I guess early in my junior year, it must’ve been. He was my assigned advisor, and he became a beloved friend, he and his wife. Kathryn and I would go visit them in Gettysburg. My parents moved to Gettysburg after I graduated because of my father’s change in his position. In any event, he called me in and said, “Well, Mike, what do you want to do with your career?” I said, “Well—” This was all based on my experience with a small liberal arts college faculty, right? “I’m kind of interested in an academic career.” I had no clue what that meant. I hadn’t seen a research lab. I’d never met a research scientist. I thought in an academic career, you taught. That’s what these people in this college were doing, right? So he said, “Well, I know that you’re thinking about Penn, and it’s true that anybody we recommend to

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Penn, they take.” It was a channel. “But you should think about going to Harvard.” I said, “Where’s that?” I had never heard of it. Literally never heard of it. People will not believe that to this day, but it’s true. He said, “In Boston somewhere, I think.” He wasn’t quite sure whether it was in Boston or over in Cambridge.

So I applied to three medical schools. When I tell this to current medical students, they don’t believe it. I applied to three medical schools—that wasn’t uncommon in those days—Penn, [Johns] Hopkins, and Harvard, and I was promptly interviewed by all three. The interview at Hopkins came first. I took one look at the neighborhood and withdrew my application. Where I came from, I’d never seen anything like it. Then I was interviewed at Penn, and that went all right. I didn’t have the money to travel to Boston, so they had a Harvard alumnus who was on the Penn faculty interview me at Penn. In due course, I got accepted to both Penn and Harvard. And there the first inkling of a difference appeared, because my acceptance came by regular mail from Penn and by telegram from Harvard. Telegrams were in then, right? So back to Penn for a scholarship interview. The interviewer in due course says, “What do you want to do?” I said, “Well, I’m interested in an academic career.” I was still saying that. I still had no clue what it meant. He said, “Where’ve you been admitted?” I said, “Well, Penn and Harvard.” He, Penn faculty, said, “You should go to Harvard.”

Hughes: Now, what was he seeing in you?

01-00:44:15 Bishop: No, no, he realized that if I wanted to be an academician—

Hughes: Oh, it was more that. What you didn’t say is you graduated summa cum laude from—

01-00:44:30 Bishop: Gettysburg College.

Hughes: —Gettysburg. You had a stellar academic background.

01-00:44:38 Bishop: No, this was all about, where’s the best place to get launched in an academic career at that time. Penn wouldn’t like hearing this now; they didn’t like hearing it fifty years ago. But it was true at the time. My old mentor agreed. He was thrilled when I was admitted to Harvard, and all urging that I go to Penn disappeared. There was just no comparison at the time. Hopkins was another matter. Hopkins was also a major player and highly esteemed. Penn was esteemed, too. But in those days, if you wanted to launch an academic career and had a shot at Harvard, you did it.

Hughes: But that would be less true if you’d gone to Hopkins? Hopkins was producing clinicians?

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01-00:45:21 Bishop: No, it wouldn’t have been less true. I don’t think so. It had equally stellar academic credentials, sure. And for that matter, Penn. But anyway, for whatever reason, this man told me I should go to Harvard. So I said, “Well, I haven’t even been there.” He said, “Well, tell them you want to come up and see it.” So I wrote a letter to the dean. It said simply, “I’ve been admitted to Penn and Harvard, and I haven’t visited Harvard, so I’m having trouble deciding between the two. Could I come visit?” They said, “Oh, yes. Sure. We’ll pay your way. Come up by train. We’ll put you in the dorm and everything.” Well, it was a phenomenal weekend. They assigned the All-Ivy League tennis champion, who was in the fourth-year class of Harvard, to be my host. One thing led to another. I was taken to see open-heart surgery, where a medical student was allowed to put his finger into the mitral valve of a patient. Dwight Harken, who had invented the mitral valvulotomy, was operating. My head was spinning with this.

Now flash forward five years when I was in my last year of medical school. The dean of students has an exit interview with every member of the class, which I thought was a pretty good thing. Still do. When I went in, he, Joseph Gardella, said, “Mike, before we talk about your experience here, I just have to ask you, do you remember that letter you wrote?” I did not remember it. I said, “What letter?” He said, “The one about how you were having trouble choosing between Penn and Harvard.” “Oh, yes.” He said, “The staff found that so funny they put it on the bulletin board.” So there you are. Telegram and a letter on the bulletin board at Harvard.

In any event, Harvard at the outset was a real challenge to me. All of a sudden I was surrounded by people who were— None of them were dumber than I was and a lot of them were smarter than I was. Many of them with very sophisticated backgrounds. I just naturally fell into friendship with a few of them, who were research-oriented because of their undergraduate experience, and a couple of them remain life-long friends. That immediately got my attention, and I began to figure out what being an academician really was all about. So I palled around with these fellows. And they were fellows. There were probably a hundred-plus in our class; there were six women at the time, one of whom became a wonderful friend, while we were there at least.

By midway through my second year in medical school, I was really beginning to get uneasy with the idea that I was destined to be a practicing physician. What I really liked about what I saw was how people had learned what we knew. To Harvard’s credit, there were some faculty that— Instruction generally was not great. But there were some faculty who taught that way and who gave you some historical feeling for how the stuff they were teaching you was actually learned. I took that to heart, and that’s the way I’ve tried myself to teach over the years. That got me to thinking. I had a very perceptive— Edgar Taft was a full professor, laboratory instructor in pathology, in second year. One day when I was looking down my microscope, he came over to me

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and he said, “Mike, I’ve picked up on the fact that you really like basic science and you really are interested in research .” He said, “Would you like—? We have something at the pathology department at the Massachusetts General Hospital”—which was a shrine, of course; was and is a shrine— “called a post-sophomore fellowship. It’s sponsored by NIH. You would take the year off from medical school. You’d have a good stipend.” And he wasn’t kidding; it was a good stipend, compared to what my wife and I were facing. We had just gotten married. Or we weren’t quite married yet. But anyway, suffice it to say I jumped at the opportunity. I tinkered in his laboratory. It didn’t amount to much. But I was also treated as a resident [physician]— literally. I did fifty postmortem examinations. The first one, I had an instructor. From then on, I was on my own. I did all the microscopic examinations. I reviewed them with a member of the faculty, the attending [physician]. I was treated like a resident. I learned a tremendous amount doing that, which made the third year of medical school very, very easy for me.

That opened up the opportunity to try my hand at a more intensive research experience. I had become enamored of molecular biology, which I don’t think even had a name yet, but was just emerging. When I entered medical school in 1957, the double helix was only four years old and wasn’t being taught yet at Harvard. We were taught how the nucleotides were produced, which was kind of boring, but we weren’t taught about the double helix, which was vividly exciting.

Hughes: And that was probably in the biochemistry course, was it not?

01-00:51:34 Bishop: Yes. But through my sort of off-hours reading, Scientific American and the occasional reference that might be cited in a lecture—which most medical students ignore, but I went trundling over to the library and read them—I got more and more excited about doing research and had taken a first gambit at it.

At that time, I was infatuated with neuroscience. I just loved neuroanatomy. What we were taught in neuroscience, which was mostly physiology at the time, I just loved it. So I went to the principal member of the neuroscience faculty—Harvard wasn’t super strong in neuroscience in those days; it became strong soon thereafter—and asked him whether I could work in his lab that summer. He was singularly uninterested, given my background, my naïveté and inexperience. So he said, “Well, yes, you can hang around the lab if you want to.” Well, that didn’t exactly thrill me. Anyway, by the second year, I had been introduced to molecular biology, because the microbiology course that was taught included lessons on how microbes had been used to figure out how genes were controlled. It was just coming into its own.

Hughes: You mean bacteriophage and all that?

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01-00:53:12 Bishop: Yes, right. I found some of the literature absolutely impenetrable. It was full of jargon that I didn’t know and what have you. Then we turned to animal viruses. It was clear that that field was primitive, compared to bacteria. So I thought, here’s a place where I might catch on. So I took an elective course in animal viruses, and it included the first experience in not only reading a series of papers but presenting them to the class. I’d never done that before. One of the teachers in this course was a young instructor named Elmer Pfefferkorn, who had been a Rhodes Scholar, and was a truly unusual man. I asked him whether I could work in his laboratory in my spare time, in my third year. This was in my third year that I was taking this elective course. He said, “Sure.” Now, this lab was just a little bigger than my kitchen-dining room [ie. small]. He had one technician and nobody else, and soon thereafter he let the technician go for budgetary reasons. He was working on an RNA virus, Sindbis. We didn’t know anything about its genome at the time, other than it was RNA. He wanted me to try to isolate mutants—temperature-sensitive mutants, we call them—that would allow us to examine the genome of the virus in more detail from a genetic vantage point. I set about to do that, and the bioassay promptly stopped working, and it never worked again during my first year with him. So I proposed to tinker with molecular aspects of the virus.

Now, at this point the third year was over or almost over, and I was facing divorce from this experience. So I went to the dean of students, the man who eventually did that exit interview I told you about, and proposed to him that instead of taking my clinical courses in the fourth year of medical school, I’d do research in the lab. He looked at me like I was from outer space, and he gathered himself and said, “Well, that’s probably professional suicide.” So we kept talking and he said, “Okay, I’ll cut a deal with you. Do you have a specialty in which you’re going to do your internship?” I said, “Well, it’ll be internal medicine.” “Okay. You take the clerkship in internal medicine and you can have the rest of the year to do research with Pfefferkorn. The only thing I ask is that you go and explain this to the chairs of the departments that you’re not taking the clerkships in.” He said, “They won’t be able to veto it, but you have to go explain yourself.” So I did.

Hughes: With any trepidation on your part?

01-00:56:41 Bishop: I was just bound and determined to do this. Some of these were very distinguished figures, but I didn’t know that yet. They were just chairs of departments, right? And I had to go tell them I was going to do this. I had the dean behind me and they couldn’t talk me out of it. I heard the term professional suicide more than once. So I took my clerkship in the Mass[achusetts] General Hospital, and a year later I was an intern there. So much for professional suicide. This was one of the most sought-after positions in training. So there’s a lesson there I think. I’m not sure it applies today; things are so structured. But to me, the fact that the chief of medicine and the

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Bishop and Elmer Pfefferkorn, Thiel Gallery, Stockholm, December 1989

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other faculty made this decision at the Mass General, were willing to do that, just spoke wonders about them. There were all these incredibly talented people trying to get in there. Most of them had taken every conceivable elective and they were just primed to go. They already knew all the drugs, the doses—ready to go. And yet they wanted someone like me.

I vividly remember the interview. There was this long table and all the division chiefs were sitting around the table. Then there was the chief of the department, who was a man named Walter Bauer, who was a died-in-the wool curmudgeon. I had seen him in action because I’d done my clerkship there, right? I’d seen him with students, and with students he was very pleasant and reasonable. Demanding, but pleasant and reasonable. Nevertheless, I sat down in the chair; I was scared. He started the questioning. He said, “Well, what did you do with your fourth year?” I said, “Well, I had my clerkship here and then I spent the rest of the year working in the lab.” And he said, “God damn! How did you pull that off?” I thought, this is going to be okay. And it was. Yes. So it was just a lesson that I think you have to follow your nose, and people are going to be helpful if they think it’s reasonable.

Hughes: Maybe somewhere in that equation is you also have to be very bright. I don’t think just anybody coming up to Bauer would’ve gotten this reaction.

01-00:59:36 Bishop: Well, I only graduated cum laude from Harvard.

Hughes: Tell the story.

01-00:59:44 Bishop: What?

Hughes: You chose not to do a paper.

01-00:59:52 Bishop: Oh. Well, I’m not sure that’s true. That’s what I was told by colleagues. See, none of the work I did in the lab ever panned out. But I was having a great time. I was teaching myself to do molecular biology. Elmer was not a molecular biologist. The amazing thing is that he let me do this, because it was not fostering his career. He wound up as chair of microbiology at Dartmouth [Geisel] School of Medicine and switched from viruses to studying parasites. Anyway, I thought, what’s the point of writing this up? We didn’t learn anything. It didn’t work. But if I had just written what I had done and set up and learned, I was told I probably would’ve been magna [cum laude]. I don’t believe that. That was just the bias of the students. I could not have cared less. I was on a track. I was going to an internship that would credential me for training at NIH afterwards. I knew that by that point because I had consulted some people on the basic science faculty. I didn’t care what distinction the degree carried. Now, whether I would succeed, I didn’t know. But I knew that after completing two years at the Mass General, I could

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almost certainly—and it turned out to be the case—go into what was called the physician-scientist training program at the NIH, which would take relative naïfs like me with an MD and turn them into research scientists.

Hughes: Yes. Let’s go back to that year in Pfefferkorn’s lab.

01-01:01:57 Bishop: Two years. One year part-time and one year, ten of the twelve months.

Hughes: Okay. There may have been two turning points. As far as I know, this was the first time you had encountered viruses, at least in terms of research. The second, and maybe even more important, was your introduction to molecular biology.

01-01:02:27 Bishop: Well, the introduction to molecular biology came in, of all places, a second- year microbiology course.

Hughes: Okay, you encountered for the first time the practice thereof in Pfefferkorn’s lab.

01-01:02:36 Bishop: Yes. Well, I had done a lot of reading on my own during that year off. That was one of the great blessings of that year off at the Mass General. Pathologists—it’s a slight exaggeration—they work nine to five. I had a lot of time to read.

Hughes: Had James Watson written his textbook yet?

01-01:03:02 Bishop: No. It didn’t exist then.

Hughes: So what were you reading?

01-01:03:09 Bishop: Well, there was a wonderful medical bookstore nearby. By this point, Kathryn and I were married. We married the day after I took the second-year boards in medical school and then spent the summer living in a tent in Yellowstone Park. That was our honeymoon. I was pumping gas and fishing, and she was selling underwear at the little general store. It was a great summer, except the bears destroyed our tent.

Hughes: Nothing happens in your life, I can tell.

01-01:03:47 Bishop: Yes, right. In any event, yes, the doing of microbiology— I taught myself how to purify the virus.

Hughes: This was by the reading that you had done?

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01-01:04:09 Bishop: Yes.

Hughes: Because you said Pfefferkorn was not a molecular biologist. .

01-01:04:12 Bishop: Right. So there was this bookstore nearby, and I would go over there and prowl the shelves and find, okay, here’s a book about nucleic acids; I’ve got to read that. Here’s a book about [bacterio]phage; I have to read that. Okay. So I’d done a lot of sort of ad hoc reading. Maybe the first culmination was—I just thought of this the other evening— I belonged to a student-formed group called the Boylston Society my third and fourth years.

Hughes: Boston physicians?

01-01:04:56 Bishop: No, this was just Harvard Medical School students.

01-01:05:04 Bishop: Anyway, this was a reading group, and the senior members wrote a paper on anything they wanted. One guy wrote on early Greek history; one guy wrote on the mathematics of music. This was an eclectic group of young people and it was very stimulating. The student body at Harvard was generally that way. It just opened my eyes in so many ways. I regularly credit my fellow students at Harvard with having a much greater influence on my aspirations than the faculty, because they were a daily presence, right?

In any event, I had taught myself how to purify the virus. I wanted to try to extract the RNA from the virus and translate it in vitro into protein, as a way of showing that the genome was also messenger. I made it work with the control materials. I got the in vitro translation working. But nothing happened with the Sindbis virus RNA. I will never know why, and it is embarrassing because it turns out that the genome actually is also the viral messenger RNA.

Hughes: How were you hoping to isolate the RNA strand?

01-01:06:54 Bishop: Oh, that was easy; I just read about how to do it in the literature. You extract off the protein and lipid coat of the virus, separate the RNA out. You do that chemically and physically.

Hughes: So that part wasn’t difficult.

01-01:07:21 Bishop: Well, a least I didn’t have to invent the technique for extraction of the RNA, but the experiment had clearly failed.

Hughes: I see. That didn’t discourage you at all?

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01-01:07:47 Bishop: No, not at all. In fact, it was fun to do. I figured at some point, I’d hook onto a project that would work. That all got set aside for two years because the two years at Mass General [1962-1964] were an absorbing experience. Those were the days of every other night, every other weekend.

Hughes: You weren’t resentful about that?

01-01:0 Bishop: No.

Hughes: You were headed towards research. So why did you need to do the clinical work?

01-01:08:25 Bishop: Well, the bottom line is, I had to perform in those two years if I wanted to go on to the research training. But I also enjoyed it. I enjoyed caring for patients. I enjoyed the whole experience. It was terrifying at times and exhausting and I had a new wife at home. She was working, teaching school. I didn’t see too much of her for two years; just every other weekend, when I was bone tired. Yes, it was an important experience. It prepared me, I think, in important ways for the teaching of medical students. And it prepared me, I think subconsciously almost, to at some point in my research career find something that pertained to human disease.

But I didn’t start out with any direct study of a human disease; I started out with study of the human pathogen, poliovirus. I was interested in the microbiology of it. How does it replicate itself? We already had a vaccine that was in the process of eliminating the disease from the United States for all intents and purposes. But it was still a wonderful molecular challenge. That’s when I went to NIH eventually, after my two years at the Mass General. That’s the experimental system that was in use in the lab that took me in, Leon Levintow’s, who [later] came out here [UCSF]. It was the reason I came out here eventually. Leon had a very small lab, too. It was me and a technician when I entered the lab. He worked with poliovirus. Again, I took the work in a more molecular direction than it had been going at the time I entered the lab. He had had previous postdocs who went on to very distinguished careers, and collaborators who did molecular work with polio. But there wasn’t anything molecular going on in the lab at the time I arrived. The first project was very biological in nature. But as soon as I could, I worked a study of the molecular mechanism of replication into what I was doing. When I moved to San Francisco, that’s what I used to set up my lab and get my first grant support.

Hughes: Well, let’s not go to UCSF quite yet. Had you chosen Levintow’s lab because you were interested in poliovirus?

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Leon Levintow

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01-01:11:28 Bishop: No. He chose me. The way this worked was that there would be a group of applicants to the [NIH] Research Associate program every year from various clinical training programs around the country. There’d be a large consortium of potential mentors, and you would check off which ones you might be interested in working with. At the time, Marshall Nirenberg was very prominent because he was in the midst of his remarkable success in deciphering the genetic code. So everybody wanted to work in his lab, myself included, because I knew about that stuff. I’d been reading about it and that was one of the things that got me interested in molecular biology. But I also checked off Leon because he worked on animal viruses, and that’s where I was living intellectually in the lab. So Leon took me. I could’ve wound up in Marshall Nirenberg’s lab, but didn’t.

Hughes: Oh, that’s interesting to think about, isn’t it?

01-01:12:46 Bishop: Yes. Well, everything worked out. My original thought that animal viruses were a niche that I might be able to fit myself into just carried right through to that point and beyond.

Hughes: Was animal virology a coming area of virology? Maybe a clearer question is, what state was animal virology in at that point?

01-01:13:28 Bishop: Well, it was in the beginnings of molecular dissection. There was a lot to be done.

Hughes: What had Levintow been doing, if he wasn’t a molecular biologist? With poliovirus, I mean.

01-01:13:50 Bishop: Well, the previous work that he was known for was done with people like Jim Darnell and Don Summers. They were studying how polio[virus] takes over the cell to use it for its own purposes; how the genome is translated into viral proteins. But they were gone, and there was no one in the lab except the technician at the time I arrived. I honestly don’t remember the details of what Leon first suggested I do. I only remember it involved something about the conditions in which different cells were grown and what they did to the replication of the virus. It wasn’t of any great interest to me, and he realized that, recognized that, and gave me a full lead to do whatever I wanted.

Hughes: Do you think he picked you because he foresaw that taking the molecular approach was a new and promising avenue?

01-01:15:05 Bishop: I think he picked me because I had some experience with animal viruses— growing them and assaying them and doing plaque assays and purifying a

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virus and so forth. I never asked him why he picked me. Knowing Leon, I thought that I should let well enough alone.

Hughes: He looms as this large but to me amorphous figure, both at NIH and then later at UCSF. So fill us in a bit about what he was like as a person and why he seems to have had a formative influence on you and others. Am I right in that?

01-01:16:10 Bishop: Well, yes. So Leon abandoned me after a year, right?

Hughes: Abandoned you because?

01-01:16:20 Bishop: He was offered a job at UCSF and took it because he liked what he saw, liked San Francisco. He had been at NIH long enough so he could get a pretty handsome retirement and then come out here and get a new salary. So all those things blended, meshed together. He came out here, and then immediately started to recruit me to come out.

Hughes: It was not because he thought the UCSF microbiology department was a stellar institution?

01-01:16:53 Bishop: Well, it wasn’t.

Hughes: Well, right. I wanted you to say that.

01-01:16:56 Bishop: It had the makings, because Herb Boyer preceded me by one year in the department.

Hughes: Yes, and he was thinking about leaving, as you well know from reading his oral history.[Dr. Bishop wrote the introduction to the Boyer oral history.]7

01-01:17:04 Bishop: Yes. We became good friends, and we worked many nights together in a cold room and so forth.

Anyway. Well, Leon was sort of like a Renaissance patron. He had set up the lab out here so that when I moved I could go to work immediately. They had set up for the purification of the virus, just as they had done it at NIH; they had set up the assay for the virus and so forth. So it was easy for me to move in. There was brand new equipment. I didn’t have to ask for a lot of stuff on

7 Herbert W. Boyer, Recombinant DNA Research at UCSF and Commercial Application at Genentech, an oral history conducted in 1994 by Sally Smith Hughes, Regional Oral History Office, The Bancroft Library, University of California, Berkeley, 2001.

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my first grant request. I did have to ask for a scintillation counter, which the current graduate student probably wouldn’t recognize if they saw it. I

remember the program officer for the grant. It was approved, and he tried to talk me out of the scintillation counter. I got my first lesson in realpolitik because I said, “No, I need it.” He had to back down. He did not have the authority to overrule it; he just thought he could bluff me into ceding.

Hughes: He was trying to save money.

01-01:18:25 Bishop: Yes, absolutely, for his program, yes.

Hughes: It must’ve been that nobody in the department had a scintillation counter?

01-01:18:32 Bishop: No.

Hughes: Well, we moved too quickly to UCSF, because I do want to talk more about NIH. It seems to me that some amazing people came out of that program.

01-01:18:52 Bishop: Well, in part that’s because of the draft. There was a powerful selection going on. If you went into that program, you became a commissioned officer in the Public Health Service and that satisfied your draft requirement. During my second year at the Mass General Hospital, I was informed by the Harrisburg Selective Service Board—which was still my home area; I was still registered to vote in Pennsylvania—that I was due to be drafted and should appear at such and such a time, at such and such a place, for an induction physical. My appointment at NIH had not come through yet, so I actually went through the induction physical before my commission came. The Selective Service Board in Harrisburg had to concede and let me become a lieutenant commander in the Public Health Service. I never wore a uniform. There was this whole cadre of people who were trained in that context. They had a name for us, the Yellow Berets.

Hughes: Which was not a compliment, was it?

01-01:20:20 Bishop: No, it isn’t a compliment.

Hughes: You draft dodgers.

01-01:20:22 Bishop: But it didn’t bother me. I was doing what I wanted to do, and I wasn’t happy with what our military was doing.

Hughes: Was this already the build up to Vietnam?

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Title page of Dr. Bishop's firsst publication

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01-01:20:38 Bishop: Yes. In any event, the NIH appointment was what I wanted and needed for my career, so I took it.

Hughes: The picture that I have gotten from talking to people like Arthur Kornberg, Stan Cohen, Paul Berg, all of whom I believe preceded you in the NIH program, is that intellectually it was rich and stimulating. People walked down the hall if they had a problem, talked it over with somebody. There was a ferment of new information. I’m putting words in your mouth.

01-01:21:29 Bishop: Well, in my experience, it wasn’t any different than what I eventually had at UCSF. There was a microcosm of people on my floor. It boiled down to one person eventually, Aaron Shatkin. I almost never left the floor except to go to seminars or the cafeteria. So I think it depended on the immediate laboratory context.

Hughes: I can’t remember where all those people I mentioned were located.

01-01:22:06 Bishop: Well, they were in a different institute than I was.

Hughes: You were in allergy and infectious disease?

01-01:22:14 Bishop: That’s right. There was a weekly meeting when the whole section met. A man named Karl Habel oversaw the section. We’d all get together and present our research. But day to day, I saw mainly Aaron Shatkin, who was working on reovirus—which is a virus with a double-stranded RNA genome, which was at the time really bizarre. Aaron made very important discoveries. He was a very distinguished scientist who died, sadly, of pancreas cancer a few years ago. We became very good friends. After Leon left to come out here, Aaron became my mentor. He’s the person I talked over all my results with and who passed on some techniques to me and I passed on some to him and so forth. It’s a very big place. If you were working day and night in the lab on your own project, it’s true that whoever’s down the hall, people you will run into can be a great help. The person I ran into was Aaron Shatkin and rarely anyone else.

Hughes: I see.

01-01:23:39 Bishop: Not much beyond that.

Hughes: But that was enough, it sounds.

01-01:23:45 Bishop: That was enough, yes.

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Hughes: Somebody said—maybe you yourself—that it was an audacious experiment at that time to try to figure out how the poliovirus replicates in the cell. Were those your words?

01-01:24:19 Bishop: Well, I didn’t use those words because it was happening very quickly. It was happening very quickly. A guy named David Baltimore was running away with it. Did we talk about this before?

Hughes: No.

01-01:24:37 Bishop: Okay. That lecture I’m writing is on my mind. Anyway, David was a preternaturally talented scientist.

Hughes: Is he an age mate, more or less?

01-01:24:54 Bishop: Yes, he’s three years younger than I am. But he’d been in science since high school. He had spent a summer at Bar Harbor in their program for high school students. Howard Temin was the college guru for that group that summer. They didn’t realize it at the time, but eventually they would co-discover reverse transcriptase, which was a stunning insight. In any event, David had as a graduate student discovered the enzyme that’s responsible for replicating the RNA genome of polio. He had done it in eighteen months, I think. I told you this.

Hughes: Mm-mm.

01-01:25:55 Bishop: No? Okay. I may have the numbers a little bit off but the story’s correct, I think. So he accomplished this in about eighteen months. That was his PhD thesis. It was a major discovery. That was the first enzyme of its type found. But Rockefeller thought it was undignified to give somebody a Ph[D]—

Hughes: Oh, you did talk about it off tape.

01-01:26:32 Bishop: Yes. So Rockefeller thought it was undignified to give somebody a PhD after only 18 months, so they sent him off to do his postdoctoral work at MIT, and then gave him his PhD sometime later. There’s one biography of David that I’ve read, and that’s the story that’s in it. I’ve never talked to him about this myself. So he by that point was working on what turned out to be a rather complicated way that the genome is translated into proteins, and it was just one major discovery after another that set him up for the discovery of reverse transcriptase eventually.

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In any event, things were moving very quickly by that point in the microbiology of polio. At least the outline of how it all happens was probably completed within the next decade. There are still puzzles about it, still people working on it. But I moved on when I got to UCSF.

Hughes: All right, one more step before we get to UCSF. Are you doing all right? It’s a lot of talking for you.

01-01:27:53 Bishop: Yes, it is a lot of talking. [interruption]

Hughes: Before arriving at UCSF, you spent a year [1967-1968] in Gebhard Koch’s lab in Hamburg.

01-01:28:05 Bishop: Yes.

Hughes: Why did you do that?

01-01:28:09 Bishop: My wife and I wanted to live in Europe. And Gebhard and I had a collaboration in midstream. Probably midway through my first year in Leon’s lab at NIH, Gebhard showed up on a sabbatical leave. He was interested in— and this was pretty avant-garde stuff actually—how to get nucleic acids, pure nucleic acids, inside of cells and expressed. The model he was using was viral RNA, poliovirus RNA. How can you take that isolated genome and make it infectious? He had discovered that if you simply neutralize the negative surface of a cell, the cell will not repel the viral RNA but instead allow it to stick to its surface –won’t repel the nucleic acid and will take it up. The cell’s constantly taking stuff up. It’s rather indiscriminate, actually. He and a colleague had pioneered this concept of infectious RNA. Downstream, this became a very important sort of thing to do because people wanted to introduce naked DNA into cells. That became called transfection. It’s a billion-dollar patent for Columbia University. But that wasn’t Gebhard’s work.

So he wanted to come to Leon’s lab and tinker with this. He knew that I was working with the double-stranded RNA that’s formed when the viral RNA is replicated. The first thing that has to be done, you have to make a copy of the RNA genome. So if you call the genome positive, which means it’s like the message—as it is in the case of polio[virus]—then the copy of it is negative- stranded. Baltimore had found this, and I was studying it independently. You could isolate not only this complete double-stranded molecule representing the genome, but also you could isolate intermediates in the synthesis of the negative strand. That’s what I was working on at the time I moved out here.

Hughes: Can you summarize how you would isolate those different segments?

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Gebhard Koch

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01-01:30:59 Bishop: Yes. It’s very simple in concept, although it was not easy to set up. You take advantage of the fact that the single, the double-stranded, and the partially completed things all have different buoyant densities. The famous Meselson- Stahl experiment, for example, exploited that. But it was not being done with RNA. The reason is that the material in which DNA is studied is cesium chloride. It has a high enough density so that the nucleic acids will actually reach their density point and stay there. You can put it in a centrifuge and spin it, and you’ll get a density gradient. In any event, the point is that we had to use cesium sulfate for RNA, and nobody was doing that. There wasn’t reagent-grade cesium sulfate available. So I had to recrystallize it myself and then it worked.

Hughes: Why did you think that it was a better medium?

01-01:32:21 Bishop: Well, the densities are different between DNA and RNA, so cesium chloride won’t work with RNA.

Hughes: Oh, okay.

01-01:32:31 Bishop: So cesium sulfate was what we used.

Hughes: That wasn’t a discovery of yours.

01-01:32:39 Bishop: No. But it was not widely appreciated. In fact, it was virtually not applied at the time. Most people were using rate-zonal centrifugation. They’d make a gradient of sucrose and then spin things through it. In contrast, in the technique I was using, the mixture of RNA and cesium sulfate is centrifuged until there’s a gradient of density and the nucleic acid molecule seeks its right place in that gradient. This was called equilibrium centrifugation.

Hughes: And then you can read it.

01-01:33:09 Bishop: Right. Then you collect it and find the RNA. So that was the technology that I first set up when I got into Leon’s lab. I realized that this was how I would have— If I was going to try to isolate these replicative intermediates, as we called them, I’d have to be able to purify them. The best way to do that would be by equilibrium centrifugation. It was exciting because it reached a point where I could make enough of the stuff [so] I could see the band visually. In any event, that’s the sort of thing I was doing with polio when I came to UCSF.

So Koch came, and we first showed that the double-stranded RNA was infectious, and we published a paper about that. You take the purified double- stranded DNA; you put it onto cells, along with some positive-charged

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molecule, like DEAE-Dextran is what we were using at the time; the cells take it up, and they make virus.

Hughes: The cell is infected because it makes the virus.

01-01:34:20 Bishop: Yes, right. So that was a puzzle. No one knew of any enzyme that manipulated RNA the way we knew about enzymes that manipulate DNA in cells. But there had to be something going on that when you put a double- stranded RNA in, eventually, somehow, the positive strand gets translated into viral protein and replicated into single-stranded RNA genome and virus is formed. That was the puzzle that I was working on when I got out here.

Hughes: That sounds rather major.

01-01:35:01 Bishop: Perhaps. I don’t think we understand it completely to this day.

Hughes: So you conclude that it’s a wider-spread mechanism.

Bishop: Absolutely. It has to be because a normal cell has not produced an enzyme like that just for the benefit of the foreign invader poliovirus. That’s Darwinian nonsense, right? Yes. But that was it, because at that point I had been seduced by Rous sarcoma virus and, yes, I phased out my polio work.

Hughes: Well, maybe we should stop there.

01-01:37:59 Bishop: Well, we should finish the story with Gebhard Koch.

Hughes: Oh, I didn’t realize you hadn’t.

01-01:38:03 Bishop: So we were charging along with the study of the infectivity of double-stranded poliovirus RNA, and he had to go home to Hamburg. So he said, “Why don’t you come over for a year and work in the lab?” I said, “Well, that’s fine, but how am I going to get paid?” Here again, an enlightened soul—like that dean who gave me the fourth year to work in a research lab, and Walter Bauer who blessed my going to the Mass General Hospital—Karl Habel, who was the Übermensch in the command structure [at NIH] that I was in, he said, “We’ll pay your salary for you to—” They had already offered me a permanent position in NIH, after about two years of my being a postdoc there; the second year on my own, with Aaron kind of holding my hand. The Germans said they’d pay my travel expenses, Kathryn and mine. So off we went to Germany to work in the Heinrich-Pette Institute, which at the time was no great shakes. It became much more successful again in later years, and now is excellent. So there were Gebhard and I sort of— Once again,[it was] just a little microcosm, just like it was in NIH for me. And nothing worked. Nothing. We couldn’t get

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the virus to grow; we couldn’t get the cells to grow. Nothing worked. So Kathryn and I did a lot of traveling.

Hughes: There’s always a silver lining.

01-01:39:45 Bishop: I steeped myself in Romanesque architecture and German Expressionist art and Bavarian beer and what all. I had a wonderful technician, and we kept trying, but nothing, absolutely nothing, worked. Never figured it out. At the end of the year, I resigned from NIH and came out here, everything worked again. Must’ve been some aspect of the reagents. We did our best to figure it out, but it just wasn’t working in Hamburg.

Hughes: You had a wonderful year, but not scientifically.

01-01:40:17 Bishop: Right. It was a cypher, scientifically. Yes. But fortunately, I published a few good papers from NIH during my postdoc, including my first paper in the Journal of Molecular Biology, a publication that had greatly fueled my original interest in molecular biology and was considered a premier place to publish at the time, .

Hughes: Which was on the poliovirus research?

01-01:40:32 Bishop: Yes, it had to do with, again, another indication that the cells had enzymes that manipulate RNA. I had been reading about the effect of radiation on nucleic acids. One of the ways you’d demonstrate that cells have the ability to repair DNA at the time was that you could introduce, say, a phage DNA, double-stranded DNA, into a cell, and you could irradiate it and show that the cell actually could revive the double-stranded DNA. I wondered whether this would happen with double-stranded polio[virus] RNA. This was, I thought, a gambit. But it worked. It was very clear that the cell repaired damage from ultraviolet light in the double-stranded RNA. This involved using the infectivity assay that Gebhard and I had worked out with double-stranded RNA. It was fun because that was my first really provocative result.

Hughes: The Journal was fairly young, was it not?

01-01:42:10 Bishop: No, I was reading it when I was in medical school.

Hughes: Okay. So we’re now up to 1968.

01-01:42:19 Bishop: Well, I published that while I was still at NIH, so it would’ve been before ’68. [It was in fact 1967.]

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Hughes: Was the Journal like PNAS [Proceedings of the National Academy of Sciences] in that you had to have a sponsor to publish?

01-01:42:33 Bishop: No, the Journal of Molecular Biology was a standard journal. It was a peer- reviewed journal. You sent a paper in, and they reviewed it, and they accepted it or rejected it or requested revisions, etc. Anyway, that too suggested that there must be an enzyme that could manipulate double-stranded RNA. I don’t think that anything’s been done on that, actually. But again, once I met Rous sarcoma virus, I abandoned all that. Not immediately. But as soon as I had finished what I had underway with polio, then I devoted myself full-time to Rous. Initially, it was part-time.

Hughes: Well, knowing what’s to come, I don’t think that was probably a bad decision.

01-01:43:29 Bishop: No. [They laugh]

Hughes: Let us end at that high point, and we’ll talk about UCSF and your arrival there at the beginning of the next session.

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Interview 2: December 9, 2016

Hughes: It is December 9, 2016, and we are in the home of Dr. J. Michael Bishop for the second interview. Dr. Bishop, when we left off last time, you were about to arrive at UCSF, in 1968. I’m wondering, did you consider any other institution?

02-00:00:44 Bishop: Well, yes. I was a postdoctoral fellow in the laboratory of Leon Levintow at the National Institutes of Health.

Hughes: Right.

02-00:00:53 Bishop: I was in the so-called research associate program, which was designed to introduce mere MDs like myself to fundamental laboratory research. I had dabbled in it, as we talked about before, as a medical student and had convinced myself that I wanted to be a research scientist. Having convinced myself that I wanted to be a biomedical scientist while I was in my residency in internal medicine at the Massachusetts General Hospital, I applied to this program at NIH and went down and was interviewed. Because of my experience with animal viruses as a medical student, the essentially two years I spent in Elmer Pfefferkorn’s laboratory during my third and fourth years in medical school, I was attracted to—and the attraction was mutual—Leon Levintow, who was working on poliovirus and had been a collaborator with Jim Darnell, to name one prominent scientist who passed through Leon’s orbit. It was a small lab. There was one technician and myself. I wanted to do molecular biology of the virus, so I began setting up techniques that I needed to do that. So the point being [is] that I was reasonably well established after two years. I had published several papers in credible journals.

My first job offer came from Dan Nathans at Johns Hopkins, soon to become a Nobel Laureate. A marvelous human being. And it was quite attractive. I had visited Hopkins and given the requisite seminar. I was also invited and gave a job-market seminar at the microbiology department at Harvard Medical School. Meanwhile, Leon decamped, retired from the Public Health Service, and came to UCSF.

Hughes: Now, why did he do that?

02-00:03:21 Bishop: I think he did it because he wanted a change of scene. He had long been interested in perhaps having an academic career. I think the city of San Francisco had a lot to do with it as well.

Hughes: It was more than the department of microbiology per se.

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02-00:03:45 Bishop: Well, yes. The department of microbiology at the time was not much.

Hughes: Right.

02-00:03:50 Bishop: We can talk about that a little later perhaps. In any event, at that point I had been at NIH two years. Leon left after I had been there one year. So the second year, I was essentially on my own, except I had a wonderful informal mentor in Aaron Shatkin, who was working right next door to me doing path- breaking work on reovirus. Among other things, he discovered the capping of messenger RNA, which is a central part of the translational apparatus. He was just wonderfully supportive, and I relied on him for critique of what I was doing and suggestions about technology. He and his wife, Joan Shatkin, became good friends with Kathryn and me. About the end of that second year, I was offered a permanent position at NIH.

But meanwhile, during my second year, Gebhard Koch had come to the NIH on a sabbatical leave. He came to Leon’s lab because Gebhard was interested in persuading cells to take up naked nucleic acids. He had been in on the very first experiments to show that the RNA genomes of animal viruses can be infectious in and of themselves—at least some RNA viruses. He was interested in looking at the RNA molecules that I was isolating from cells infected with polio, so-called replicative intermediates, to see whether they would be infectious. So he and I collaborated while he was on sabbatical, and he invited me to come back and finish the collaboration in Germany, in Hamburg. So I went to Hamburg. Kathryn and I decided, well, this is a chance to live abroad. We’d never done that. The NIH very graciously, in my very first year on their payroll, agreed to pay my salary, and the Germans paid my transportation to go over. So I left town. Well, meanwhile, Leon had contacted me from San Francisco and said, “You ought to come out here and look at a job. We’d hire you in a heartbeat.” So I left town to go to Hamburg with three—well, two—job offers, and Harvard was vacillating. To my good fortune, it turns out. So while I was the year in Germany, I mulled all this over. I was aware that places like Hopkins and Harvard have a pretty stern academic pyramid. I didn’t know anyone at Hopkins except Dan Nathans, who by that point was chair of the department and was not going to be a major day-to-day figure in my life there. Whereas out in San Francisco there was Leon, with whom I was friends—we shared a passion for good music as well as science and literature—and I made a visit. I think I was in town about twelve hours before I decided I had to live in this place.

Hughes: Which was the city itself, right?

02-00:07:13 Bishop: The city itself, yes. I can dramatize that by recounting my first night in town. I arrived, and my first glimpse was not encouraging. I was being driven up from the airport [in South San Francisco] and there’s that sign on the hill there. It’s

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still there. It says, South San Francisco, the Industrial City. I went, boy, really? But anyway, before the evening was over, I had been taken to dinner at Doro’s, which was then an iconic seafood restaurant. I had eaten abalone, which I’d never heard of before. I had been to see topless.

Hughes: Carol Doda?

02-00:07:56 Bishop: Yes, Carol Doda, the original. The inventor of topless. I have to say, Leon’s wife Regina was with us, so it was perfectly kosher. And I’d been introduced to the City Lights Bookstore. At that point, I was sold. I hadn’t even seen the lab yet, right? So the next day, I go to campus and I’m shown these spanking- new labs, totally empty and space for probably three or four modest-sized research groups.

Hughes: That was in the new tower?

02-00:08:28 Bishop: That was in the new tower. They were just populating it, as they say. It was in Health Science East tower.

Hughes: Right.

02-00:08:35 Bishop: It turned out that the microbiology department had one or two immunologists in it. It had Ernest Jawetz, the chair, who was a very distinguished classical microbiologist, whose textbook was translated in a gazillion languages and used all over the place; and Herb Boyer, who had arrived about six months before I did; and then Warren Levinson, who was in part of the space that Leon essentially commanded. I was attracted to the fact that this was not a huge monolith. This was a modest-size group of people, one or two of whom—Herb and Warren—were my age and at my stage of the career, and cordial and affable and open; and Leon, who was essentially my patron. I thought, what better circumstance in which to be myself and to do exactly what I want to do, try to do what I want to do, without feeling the intense academic pressure I would almost certainly feel at Hopkins and the relative loneliness that I might encounter there.

Hughes: The whole microbiology department had moved to Health Science East?

02-00:10:00 Bishop: No. Well, I think one of the immunologists was on the same floor in the West tower, and Herb Boyer was down in the old Health Science Building in a rather dreary space.

Hughes: And not happy about it.

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Warren Levinson

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02-00:10:19 Bishop: Yes. Apparently before I came it was decided—I think between Leon and Ernest—that since the lab suite I was going to be in and that Warren Levinson was already in, and there was also another young member Bruce Woodson of the faculty working on a pox virus, that since we all worked with animal cells in culture, which are very susceptible to bacterial and fungal attack, contamination, that it would be unwise to have a bacterial laboratory in the same setting. Now, I think there’s some legitimacy to that argument, but certainly I would not have made it myself. Herb was definitely offended by it, and he was put into rather dingy quarters.

Hughes: Yes, because he was working with E. coli.

02-00:11:06 Bishop: Yes, he was working with bacteria. I was not aware of this at the time. I learned about this later, when Herb made the decision to change departments and move to the biochemistry department. By that point, he had substantial stature because of his invention, along with Stan Cohen, of recombinant DNA.

Hughes: Exactly.

02-00:11:37 Bishop: So it just looked to me like a really comfortable situation. I have to say, another point was that it looked to me as if this was a place that really needed me. I wouldn’t be under the gun all the time. I wouldn’t be thinking every day of the week, am I going to earn a place here? If I came here, I thought, I’m clearly going to have a place.

Hughes: Because of the nature of your research?

02-00:12:16 Bishop: No, because the institution was building. It really had very little distinction at the time. Very little. There were a couple of standout exceptions to that, neither of whom figured much in my career.

Hughes: Who are you thinking of?

02-00:12:34 Bishop: Well, certainly, Isidore Edelman, who eventually became chair of biochemistry at Columbia. And the director of the Cardiovascular Research Institute, Julius Comroe.

Hughes: CVRI was pretty strong, was it not?

02-00:12:48 Bishop: Yes, right. But that was it. That was it, pretty much. But that didn’t bother me. Actually, the whole experience and how it worked out has influenced how I counselled my postdoctoral fellows over the next forty-five, forty-six years about looking at jobs. Not to be preoccupied with the reputation of the place,

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but rather whether it’s a place where they could do what they want to do and be wanted from the get-go.

Hughes: Very good advice. Do they listen to you?

02-00:13:25 Bishop: Yes, indeed. Well, I have some pretty strong evidence that the equation works.

I accepted the job at UCSF while I was in Germany. When I returned to the U.S., I spent one day on the NIH campus and resigned; moved to San Francisco in February of 1968.

Hughes: [interruption] Levintow was never directly involved with your research. Am I right?

02-00:14:11 Bishop: First, Leon and I were both interested in poliovirus. In fact, when I came here, I was working on poliovirus.

Hughes: That’s right.

02-00:14:20 Bishop: I was continuing the kind of work I had established in his laboratory at NIH, and I continued after he moved to San Francisco. So we were essentially intellectual colleagues in that. He counselled me in some of my first writing. By the time I came here, I was an experienced writer, but he had contributed greatly to my approach to writing scientific manuscripts. And he continued to be a critic.

Hughes: How did he propose that a scientific article should be written?

02-00:14:55 Bishop: Well, just his approach to putting the paper together, things that I knew from my college education, some of it, like the importance of outlining, which I could never, ever get most of my postdocs to do. It was clear that people were not learning what I had learned. Subsequent generations were not necessarily learning what I learned about composition in college, because I’d ask them to make up an outline, and they really did not know how to do it. So outlining and where to start; and the crisp, clear expository prose that’s important to a clear scientific article; and then just a critique of the prose once it’s there and put together, and how the paper’s organized and so forth. That was pretty much done at NIH before Leon moved out here. In any event, we were essentially intellectual colleagues. He knew what I was doing; we talked about it, and we began to assemble a little technical staff to support it.

Hughes: Had you taken your grant from NIH to UCSF?

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02-00:16:17 Bishop: Well, I didn’t have a grant at NIH; I was on the staff. I had a budget from them. I wrote my first grant while I was in Germany.

Hughes: And that was supporting the polio research?

02-00:16:27 Bishop: Yes, it was for polio.

Hughes: Who was the grantor?

02-00:16:25 Bishop: The National Institute of Allergy and Infectious Diseases. That was an interesting experience. I sent a draft of the grant application to Leon. He and others who read it said, “Oh my goodness, this is way too ambitious, and you’re asking for way too much money. It’ll never fly.” I said, “Well, it’s done. It’s in.” Oh, and the other thing is, “You shouldn’t ask for five years; that’s too long at your stage of your career. You should ask for three.” So I asked for five. I got five years. I got every penny I asked for. I have always used that experience anecdotally in counselling my postdocs because they tend to get very pessimistic advice. Now, people will say, well, that advice is justified in this day and age. But it was not justified fifty years ago when NIH was in one of its glory periods of funding. In any event, that certainly strengthened my self-confidence, right?

Hughes: Right.

02-00:17:41 Bishop: I remember the program officer at NIH who was responsible for administering my grant. I had applied for a scintillation counter, which was an expensive instrument. There was none other anywhere near me. I’m not sure there was one on campus at the time. He tried to talk me out of it, and I refused to bend. That taught me another lesson: that the NIH administrators aren’t as powerful as you necessarily think they are, because there was simply nothing he could do. The study section had approved the grant, the budget, and I could have my scintillation counter—which immediately other people started using. So it was a shared resource, in truth.

Hughes: You were pretty cocky for a young man.

02-00:18:25 Bishop: I wasn’t cocky. I knew what I needed, and I was going to take the gamble. My ego would be able to withstand the grant being cut to three years and having money cut out of it, as long as I got the grant. So why not try for the gold ring or whatever?

Hughes: Yes, I see.

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02-00:18:52 Bishop: Actually, I had no major presence. I hadn’t been invited to any major research conference yet and so forth. I was published in good journals, but I was just at sort of the inflection point of my career. No one remembers me as cocky at the time; they remember me as energetic and sometimes boisterous.

Hughes: Well, I should’ve said self-confident rather than cocky.

02-00:19:26 Bishop: Yes. Well, I was anxious. I was nowhere certain that I’d get the grant. But I knew what I needed, and that’s what I put down.

Hughes: Now, do you think it made a difference that you were coming from NIH and that incredible program that so many scientists of your age went through?

02-00:19:49 Bishop: No. Look, remember that the study sections that sit in judgment, they’re not on the NIH payroll. They make the decision; they make the judgment.

Hughes: Well, yes, but look at the people who came through that program. The study section must’ve known about that.

02-00:20:00 Bishop: Well, yes, but that doesn’t mean that they got favorable treatment once they were in the R01 [Research Project Grant] competition.

Hughes: I’m not saying necessarily favorable treatment, but it was a factor that might have been in your favor.

02-00:20:12 Bishop: No, actually, no. The two years at NIH, I was clueless about R01 grants. I never had to think about a source of money. We had a budget, and we lived on it. So I knew nothing about grant applications when I left the place. Absolutely nothing about the extramural process.

Hughes: Did it make a difference to Levintow, or whoever was going to usher you into UCSF, that you came with money?

02-00:20:40 Bishop: I didn’t come with money. I don’t think I got the approval till after I got here.

Hughes: Oh, okay.

02-00:20:45 Bishop: But I had a start-up package essentially, like everybody does these days. It was modest in those days. The main start-up package was, the lab space was there, and there was most of the equipment required to work with poliovirus. But there was no scintillation counter and a few other things that I had to ask for.

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Hughes: You’d had a scintillation counter at NIH?

02-00:21:04 Bishop: Oh, of course. I had everything I wanted at NIH. It was and remains one of the best places to do research.

Hughes: UCSF, as you were implying, was not a cutting-edge institution. Wasn’t Jawetz still chairman of microbiology? He was a more classical microbiologist, and maybe he didn’t think you needed that counter.

02-00:21:27 Bishop: Yes, but Ernest was not in my immediate orbit. I could point to Leon.

Hughes: But if you had had somebody more like yourself as department chair, he or she might have seen, well, of course, we’re going to have to have a scintillation counter.

02-00:21:46 Bishop: Well, but Ernest wasn’t involved at all in my application. Leon was there and would have said, “Of course”. But this was between me and the study section and the program officer.

Hughes: The culture of the department that you were coming into wasn’t very cutting edge.

02-00:22:05 Bishop: Well, it wasn’t, except for Leon and Herb.

Hughes: So you were changing things.

02-00:22:11 Bishop: Well, it turned out that way. I don’t think it was necessarily perceived that way at the outset.

Hughes: [William J.] Rutter came approximately the time you did, in 1968, 1969. One of the first things he did was to get far-thinking molecular biologists and the equipment that went along with them.

02-00:22:52 Bishop: Well, that was just a very different enterprise. Bill was recruited. The place was desperate for a good biochemistry chair. He got a huge recruitment package. It was just a very different situation. The effort to recruit me was just essentially by Leon. Leon had recruited me. He had convinced Ernest that I would be a good addition to the department. It was just a very different scale.

Hughes: I see.

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02-00:23:20 Bishop: A very different arrangement. I think I said hello to Ernest in my recruitment visit, but we spent virtually no time together. He didn’t go to dinner or— I’m not even sure I gave a seminar. I don’t remember giving a job seminar.

Hughes: That would be strange.

02-00:23:41 Bishop: No, not in those days. In any event, I came to UCSF because Leon initiated it. Leon sold me to the only person who would be able to say no, Ernest.

It turns out Ernest and I shared one thing, and that is a passion for teaching. One of the things that motived my move into an academic career was my affection for the teaching I had received over the years, and my desire to continue that tradition. So I remember I arrived at work, when I moved here in February— In those days, we could still park up on Medical Center Way behind the campus. It took about five minutes or less to get from my car to my lab desk, through the back door. We had to come down a set of wooden steps. Ernest arrived at the same time, so we were walking down the steps. This is my first day on the job. Ernest said, “Well, welcome. We were hoping that you would give lectures on virology to the pharmacy students in three weeks.” I said, “Oh.” What I thought but didn’t say is, that wasn’t in the job description. So I did. I discovered it was fun, because it turned out pharmacy students are more interested in chemical structure of viruses than medical students are, by far.

I pretty much devoted the first several weeks of my time here developing those lectures. My sister came out here to see what was going on. We built a scale model of the adenovirus particle out of Styrofoam balls—it eventually appeared in Time magazine, actually—and that was the centerpiece of my lecture to them on the structure of viruses. So Ernest became aware that I was a better-than-average lecturer, actually came to some of my lectures. He cared a great deal about the quality of the teaching in the department. That’s how I earned his respect. He clearly warmed to me when he saw how I enjoyed teaching and the amount of effort I put into it and that it seemed to be effective.

I cherish one moment with Ernest, because some years later the people in charge of the curriculum became concerned that there wasn’t any drama in the medical school course on microbiology, something to excite the students. So Leon came up with the idea that I could give an opening lecture. So I took that on. It’s chapter two in my book, essentially, expanded, thirty years later.8 I just had a wonderful time. I put hundreds of hours into it, in the library and reading some books that I had not read and wanted to read. I put together

8 J. Michael Bishop, How to Win the Nobel Prize: An Unexpected Life in Science, Harvard University Press, 2003.

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essentially a history of microbiology in fifty minutes, beginning with the bubonic plague and preceding up through penicillin. Ernest came to hear it. When it was over, he came up to me, he says, “Mike, I don’t think anyone else could possibly do what you just did. It was wonderful.” I am still moved when I recall that compliment.

Hughes: Quite a compliment.

02-00:27:43 Bishop: Yes. He was at the time a highly respected teacher by the students, who gave a very different— His approach was pragmatic. That experience cemented my belief in storytelling as a fundamental teaching device, and I always worked historical narrative into my lectures to the medical students, no matter what they were about. There was always a story to be told about how the disease appeared, the extent that it had been mastered, how that was accomplished. You can do that in five or ten minutes in a fifty-minute lecture, and the students just love it. They really receive it very, very well.

Hughes: Well, you’ve got a good audience here. The two of us are historians of science [referring to Paul Burnett, the videographer].

02-00:28:34 Bishop: Yes. So in retrospect, it was not a difficult decision at all to come to UCSF.

Hughes: Was that more or less your first experience with teaching or at least formal teaching?

02-00:28:56 Bishop: Yes, absolutely. The course to the pharmacy students was the first.

Hughes: I know teaching’s going to become one of the things that you pride yourself in.

02-00:29:05 Bishop: Yes.

Hughes It’s a little bit off the track, but I was a student there in the early sixties, and I remember religiously going to Chauncey Leake’s historical talks. Did you have any interaction with him?

02-00:29:29 Bishop: Oh, no. He really was not much of a presence by the time I arrived. But I was aware of him. I used to see him picking up litter on the campus.

Hughes: Really?

02-00:29:39 Bishop: He did that religiously, every little scrap of paper. He took pride in the campus. We overlapped, but I had no contact with him.

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Hughes: I thought maybe history drew you together.

02-00:29:50 Bishop: I never even met him. I do have—I turned it over to the library—an edition of his translation of De Mortu Cordis, On the Motion of the Heart and Blood. I blocked on the man’s name. The British physician who first figured out what arterial and venous blood was all about.

Paul Burnett: [William] Harvey?

02-00:30:32 Bishop: Yes. Chauncey did a modern edition of it, which was highly esteemed. I found a copy of it somewhere; I don’t remember where.

Hughes: And you gave it to the UCSF library.

02-00:30:43 Bishop: I had it on my shelf my whole career, and when I emptied my office out, I gave it to the— It should be in the archives.

Hughes: Let’s get into the actual science, which I believe starts with your collaboration with Warren Levinson. Am I right about that?

02-00:31:03 Bishop: Yes. Oh, absolutely.

Hughes: Well, maybe we should finish the poliovirus story. Did you bring that to a conclusion of sorts?

02-00:31:12 Bishop: No, not at the outset. After all, I had just gotten a grant to work on polio.

Hughes: So how did—?

02-00:31:17 Bishop: Well, Warren was here before me, by six months or so, I don’t remember, having trained with Harry Rubin in Berkeley. So he was skilled with the biology of the virus—how to assay it, how to propagate it. But he was not a molecular biologist. Maybe even before I arrived, but certainly after I arrived, it was Leon who said, “You ought to team up with Warren Levinson, who works on Rous sarcoma virus, because these viruses have been neglected. There are not a lot of people doing molecular biology on them.” That was correct. So Warren and I began to talk, and it blossomed into a collaboration. We put together a technical staff that would work with Rous sarcoma virus. Over the course of my first two years, while I was conducting poliovirus research, we gradually introduced Rous sarcoma virus into the laboratory as well. Warren had a technician who could do all the bioassays, and I began to teach others in the lab what I knew about molecular biology. So we set up propagation of the virus on a large scale, really huge scale, which is what I

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was accustomed to doing for poliovirus; and the purification of the virus so that we could assess its structure and— We were making crude efforts to

understand how the virus replicates, but they were frustrated by our inability to identify the viral nucleic acids inside the cell. That just wasn’t possible at that time. The next few years opened that up to us.

Hughes: What technology was missing at that point?

02-00:33:10 Bishop: Well, the technology that broke it open was molecular hybridization. Which I was doing to studio polio.

Hughes: Were you?

02-00:33:17 Bishop: I was already using it. It was a standard part of molecular biology.

Hughes: So molecular hybridization was not a new technology?

02-00:33:25 Bishop: The way I deployed it was a new assay, but molecular hybridization was well established.

Hughes: Why was it new, the way you were doing it?

02-00:33:36 Bishop: Because reverse transcriptase was discovered, and we were immediately able to make radioactive copies of the genome that are complementary to the genome and would hybridize with the genome. I had to devise ways to detect those hybrids; they didn’t exist at the time. All the molecular hybridization that had been done to that point was done in a different kind of way. It was a modest innovation. But the whole point is that we were doing this interdigitated with Warren’s own grant-supported work on the biology of the virus and my grant-supported work on the poliovirus. But we didn’t have any money yet to do Rous sarcoma virus, the molecular biology of it. So essentially I was pirating funds from my polio grant to do Rous sarcoma virus work. It didn’t matter at all. In due course, I phased out polio over the next several years because the work with Rous sarcoma virus was just burgeoning dramatically. And it was pioneering stuff; it was on the cutting edge. It was helping to open a brand new field, whereas the polio was a very established field of research, and I was making modest, novel contributions, but nothing compared to the prospects in Rous sarcoma virus.

Hughes: At this very early stage of your work on Rous sarcoma, were you glimpsing the fact that this might lead to some understanding about the genetic mechanism of cancer?

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02-00:35:22 Bishop: Well, of course. That’s why I decided I should work on the virus.

Hughes: But why would choose Rous sarcoma?

02-00:35:27 Bishop: All you have to do is look and see what happens when Rous sarcoma virus infects cells in culture. Within twenty-four hours, they’re neoplastic. Now, what more could you ask for as a starting point to explore how cancer arises? That’s why people were interested in these viruses. That’s the bottom line: they cause cancer. Viruses are simple. Rous sarcoma virus has four genes, essentially. So that’s a pretty simple setting in which to try and dissect how cancer arises.

Hughes: So that’s why Harry Rubin and Warren Levinson and I don’t know who else were looking at Rous.

02-00:36:01 Bishop: Yes, that was the motivation. That was the motivation for studying these viruses.

Hughes: Oh, okay. [Peyton] Rous in 1911 indicated that this was a fruitful virus for studying oncogenesis. But then nobody did anything much with it, until when?

02-00:36:25 Bishop: Well, Rous sarcoma virus was rescued, I guess, by Harry and Howard Temin. The study of RNA tumor viruses languished because no one really, essentially, believed it. When Rous first published his claims that he had isolated a filterable infectious agent, he didn’t even call it a virus at first. The concept of the virus was about a decade old, maybe. He was ridiculed. Nobody took it seriously. When he proposed this might be happening in humans, that was beyond the pale.

Hughes: That was the death knell.

02-00:37:12 Bishop: Right. Witness the fact it took fifty years to get his Nobel Prize. That speaks for itself.

Hughes: Yes.

02-00:37:18 Bishop: Okay. I think the next event, which happened, oh, fifties or sixties—I can’t remember—was the discovery of a leukemia virus in mice. That was by a man named Ludwik Gross. He had the luck or insight or both to use inbred strains of mice, some of which were carrying this kind of virus which caused leukemia in them. I would say after Rous that was the next step that drew attention to the possibility that these viruses might be valuable experimental reagents in studying cancer. Then the reason I mentioned Rubin and Temin

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before is that when Howard was a graduate student with Renato Dulbecco at Caltech, Renato worked on DNA tumor viruses, but Harry Rubin was a postdoc in the lab at the time. I’ve never explored this, but he was interested

in Rous sarcoma virus. He and Howard teamed up to create the bioassay as we know it today. That really was based on the principles that Dulbecco had used

many years before to create the classic assays for poliovirus and other viruses that kill cells.

Hughes: Can you summarize what the assay is composed of?

02-00:39:00 Bishop: Yes. Let’s take poliovirus as an example. You grow the cells that are vulnerable to infection and killed by poliovirus. You create a monolayer of vulnerable cells on a dish, and then you apply dilutions of the sample that may have the virus in it. You reach a point where only a limited number of virus particles are being deposited on the plate—let’s say ten or fifty or a hundred. After exposing the cells, you put a layer of agar over them, and three or four days later you look. Where every virus particle has landed, there’s a hole in the monolayer. So that’s a plaque assay, let’s call it. What Temin and Rubin did was to develop an analogous assay for Rous sarcoma virus in which at this adequate dilution each particle elicited a focus of transformed cells, easily recognized with the microscope. You can count those, and that would quantify the virus for you.

Hughes: I see.

02-00:40:03 Bishop: So at that point, Rous sarcoma virus became, odds on, the most favorable RNA virus to study neoplastic transformation, because there was a bioassay; you could grow it in large quantities. We made grams of the stuff. The bioassay in turn facilitates quantitation. It facilitated genetic analysis, which was absolutely crucial to the field and to our work eventually.

Hughes: How would you be doing genetic analysis? With molecular hybridization?

02-00:40:46 Bishop: No. You look for mutants that change the form of the transformed cell or that take away the transformation. That defines the gene that’s responsible for it. We’ve skipping ahead here a little bit, but I just want to finish this. So what I was confronted with was a virus that was capable of rapid transformation in an experimental system, quantitation, genetic analysis, preparation in large quantities. No other RNA tumor virus at the time offered that. Most people who were working in the field—and it wasn’t large—were working with the leukemia viruses, and they didn’t have that kind of assay. It was limited to animals. So this was a fabulous experimental system. Furthermore, it was safe.

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Rous Sarcoma Virus does not infect human cells, so no special precautions are required to work with the virus.

Hughes: Yes.

02-00:41:43 Bishop: So we worked with impunity.

Hughes: Now, did you come from NIH with that knowledge?

02-00:41:49 Bishop: No, I learned it when I got here. I didn’t know this virus existed beforehand.

Hughes: That was research starting with Harry Rubin probably, and then transmitted to Levinson.

02-00:42:01 Bishop: Yes, that would be the lineage. It was Leon who called my attention to the prospects, and Warren who readily collaborated. We were struggling until the discovery of reverse transcriptase, which then—

Hughes: Well, step back a little. I gather that Warren had the technology, so to speak. He could grow it and assay it and all that.

02-00:42:40 Bishop: Yes.

Hughes: So what was your contribution to that earlier work, before you had RT [reverse transcriptase]?

02-00:42:48 Bishop: Well, I oversaw the development of the purification of the virus. We were doing experiments with inhibitors of RNA and DNA synthesis, fairly similar to what Howard Temin was doing at the same time, to at least ask what kind of macromolecular synthesis was required for the virus to be replicated. But we were struggling. We were able to analyze the genome in the virus, but it hardly— We had just begun when reverse transcriptase was discovered. That just changed the whole picture for us.

Hughes: Well, shall we go into that story?

Bishop: Well, Howard Temin spent ten years arguing that RNA tumor viruses in general—but he worked with Rous sarcoma virus—replicated by means of a DNA intermediate. When he first proposed that, it was based on circumstantial evidence, and it was heresy because what was abroad in the field at the time was called the Central Dogma. Dogma is a very bad word in science. It should never appear. But anyway, the Central Dogma was that information in biology was transferred in only one direction, from DNA to RNA to protein. Now, it turns out—and I just learned this in the last couple

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years, preparing some lectures—that Francis Crick had written out in some things that were never published until a recent book dredged them out of the archives— In his diagram of the Central Dogma, there’s a dotted line from RNA back to DNA. His point was that chemically, it should be possible to copy RNA into DNA, but not protein into RNA or DNA. But generally speaking, it was not believed that RNA was ever copied into DNA in nature.

Howard kept building the circumstantial evidence for this idea, and people kept either ignoring him or ridiculing him. Harry was very tough on him. Harry Rubin was very harsh in this. I was at lectures where Howard would talk about this, and Harry would be, say, the chair of the session, and then criticize Howard. Howard was imperturbable. He was a remarkable individual. Imperturbable. Died, sadly, quite prematurely.

Hughes: Now, was Rubin attacking him on the basis of what was considered—?

02-00:45:47 Bishop: First of all, he thought the idea was ridiculous. That’s just personal prejudice, right? Secondly, he didn’t like the—

Hughes: Well, to be fair to Rubin, most people accepted the Central Dogma.

02-00:45:59 Bishop: Well, that’s all personal prejudice. There really was no reason to definitively think that you couldn’t copy RNA into DNA. Scientists are guilty of this kind of preconception. It’s what holds them back. It’s the ability to overcome it that makes a great scientist.

Hughes: But also isn’t it true that Temin’s evidence wasn’t rock hard?

02-00:46:31 Bishop: I was about to say, Rubin would base his criticisms on the fact that there was no— Howard didn’t have a direct demonstration that this would be happening. He actually did publish some experiments with molecular hybridization that were with a relatively primitive technique, and the data were very marginal. When I looked at them, it didn’t persuade me even; but I had a completely open mind about this because I had not been immersed in the field.

So what happened was that we, Leon and Warren and I, mounted a course in tumor viruses for graduate students. Now, there were only a handful of graduate students at UCSF at the time, but we mounted this course and put it on in a little room in the Health Sciences Building, I remember. Warren would do the biology of RNA tumor viruses, and I would do what was known about the molecular biology of it, which was essentially a little bit about the structure of the viral particle and the viral genome. But I did present the Temin idea. I read the literature, and I couldn’t see any reason not to test the idea. It seemed to me a reasonable idea, and some of Howard’s data were certainly provocative.

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Oh, the other important thing is that I was under the influence of Aaron Shatkin, who had been my mentor after Leon left NIH. Aaron had discovered an enzyme within the reovirus particle that’s encoded by the viral genome and participates in the replication of the virus. That had been preceded by a discovery by Brian McAuslan and Joe Kates that pox viruses have a polymerase, an enzyme inside their particle, that copies the DNA genome of the virus into viral messenger RNA as an essential step. So that was a landmark discovery because previously people thought of virus particles simply as a package for the genome, nothing else. Just a way to protect the genome when the virus is outside of a cell, and to get the genome into the cell, and then all else happens after that. When I first heard about the polymerase in pox, it was riveting, the discovery. This happened while I was at NIH. Aaron was working next door to me, and he knew that reovirus did strange things, and it could be explained by a polymerase, an enzyme inside the viral particle, and he found it. So I had that direct example in mind. I saw that discovery made, okay? So that was in my mind.

I thought, why don’t we look at the virus for a polymerase that transcribes RNA into DNA? Because we were able to make huge amounts of this virus, more than enough to do enzyme assays. I set up some assays, had a technician run them. Of course I was busy trying to fulfill my obligations to the polio grant. I put together the reaction mixture based on my experience with the polio replicase. One of the things that I was trying to do with polio was to purify the so-called replicase, the virus-coded enzyme that replicates the RNA genome. It was a really ridiculously ambitious undertaking, which I abandoned as the work with Rous expanded. So I had experience running this enzyme assay for the replicase, and it worked like a charm. I knew that Rous sarcoma virus had an envelope, a lipid envelope around it, which polio does not, so I would have to break that envelope open. So I put a nonionic detergent in. That turned out to be crucial. But I made one mistake. That was, I listened to somebody else, who told me— I had no experience with DNA polymerases, okay? So in running the replicase assay for polio, you have to put in the four nucleotides that are going to be incorporated into it, okay? One of those is radioactive. In order not to dilute out the radioactivity, you don’t put any nonradioactive version of that. It was the uridine, okay?

Hughes: Okay.

02-00:51:47 Bishop: It was what was typically used. So I was told—I don’t even remember the details anymore—that there was something about DNA polymerases, their affinity for the nucleotides and so forth, you couldn’t do that with a DNA polymerase. You had to bolster it with unlabeled nucleotide. In that case, thymidine, okay? The radioactive stuff was too expensive to up the concentration to the same level as the nonradioactive stuff. So yes, so I did that and the assays didn’t work, and we gave up after two or three times, and I went back to polio virus. I kept the notebooks, because when I eventually

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heard by the grapevine that Howard and David Baltimore had found this enzyme, I left my office immediately, set up the reaction mix as before, put in only hot thymidine, and there it was. In twenty minutes. That happened in 1970. So it was an awful lesson. I knew that that was the next step, okay? But I never did it because I didn’t have enough faith in the idea, I guess, or myself. I was hearing about how I really ought to be pushing the polio work in order to get my grant renewed and so forth.

Hughes: And then you got the misleading advice as well.

02-00:53:25 Bishop: Yes. But I was willing to discard that. It had been trivial. In retrospect, I don’t know why I didn’t include—it would’ve been one more test tube—a control where I just put in the radioactive stuff.

Hughes: May I quote from your book? Because I think it’s significant, how missing reverse transcriptase affected you. “I grieved for months; I still grieve in weaker moments.” 9

02-00:53:56 Bishop: Right.

Hughes: What was it that was such a disappointment to you?

02-00:54:10 Bishop: You called me cocky and then self-confident. So I failed myself. This was a case where if I had just been myself, I would’ve kept on it for a little bit, right?

Hughes: Yes.

02-00:54:30 Bishop: So I think what I was so upset about was that I had it right, and I just didn’t have enough trust in my reasoning to push it a little bit. But there’s no question that one of the problems was that this project was kind of peripheral to what my core effort was. I did have a grant that I wanted to get renewed and so forth. But that’s a bad excuse because although Howard discovered the enzyme because of his relentless pursuit of the idea, David—typically of David; he’s a preternaturally brilliant scientist—he just took an afternoon off, essentially. He had to get the virus from other people. He wasn’t working with RNA tumor viruses at the time, and never had.

Hughes: Is that so?

02-00:55:26 Bishop: Yes. He had to get the virus from other people, including Rous sarcoma virus.

9 How to Win the Nobel Prize, p. 53.

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Hughes: That was salt in the wound, wasn’t it?

02-00:55:40 Bishop: Well, I don’t begrudge it at all.

Hughes: I mean for you.

02-00:55:44 Bishop: Yes, for me, right. It was a commentary on what kind of scientist I might be.

Hughes: Do you remember how you heard—?

02-00:56:03 Bishop: Oh, I certainly do. I got a phone call from Gordon Tomkins, who had been Bill Rutter’s first recruit to the biochemistry department after he took the job as chairman. I had nothing to do with it. UCSF had tried to get Gordon Tomkins to come from NIH to be biochemistry chair. Gordon wasn’t interested in being a chair, but when Bill Rutter called him and said, “Well, just come here and be a professor,” Gordon came. And I knew Gordon casually. I wasn’t talking to him every day. I knew he had this very lively and productive laboratory, and he was devoted to wild ideas. If I had bounced this idea of reverse transcriptase off him, he would’ve really been encouraging. But I never did because I just wasn’t seeing much of him. If I can remember, I’ll tell you how he reacted when I told him about cell src, two, three, four years later. In any event, I got a phone call one day from Gordon, and he was at a Cold Spring Harbor symposium. He had just heard Temin and Baltimore talk. He said, “Mike, I didn’t get the details, but they’ve found a DNA polymerase in the virion.” I said, “Gordon, I looked for that a year ago.” He hung up, and I literally left the office and went out and set up the enzyme reaction, and twenty minutes later, I knew I had blown the chance of a lifetime. Because this time I put in only undiluted radioactive thymidine triphosphate.

Hughes: Well, you said in your book that you grieved. Did the grieving stop your momentum on Rous sarcoma?

02-00:57:44 Bishop: Oh, no. It was exhilarating. Within weeks, we were detecting viral RNA within cells and being able to monitor its synthesis. Harold [Varmus] got into the picture because he came to the lab. He arrived within a few months of the announcement of reverse transcriptase in 1970.

Hughes: Yes, May 1970.

02-00:58:10 Bishop: Yes. The papers were published in Nature, after about a week’s review, in the spring of 1970, and Harold arrived a few weeks later. So we knew there was an enzyme, but nobody knew anything about what the product looked like in a cell and how it persisted. Did it persist outside the genome of the cell, or was

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Harold Eliot Varmus

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it integrated into the genome of the cell? That’s what Harold took on first when he arrived. That’s what needed to be done next. I had set up an assay for the RNA inside the cell, using radioactive DNA as a probe, with molecular hybridization. It was an easy transition to go looking for the DNA, and that’s what Harold took on, and it became a major project of his. He built his career on that initially.

Hughes: Well, before we get into Harold, which I know is a critical part of the story, let’s backtrack a little. Could you set the scene about the several theories of cancer causation. I’m thinking of [Robert] Huebner and [George] Todaro, and even Temin and his provirus. What were the theories out there as you were getting into the Rous sarcoma research?

02-00:59:41 Bishop: In ’68, when I started thinking about Rous sarcoma virus for the first time, fundamental cancer research was abysmal. There was no driving theory. There were all sorts of ideas about— Causation was even more of a mystery than it is now. The idea that cigarette smoke caused lung cancer was just becoming acceptable. It had been credible for a while, but it was just becoming acceptable. In particular, although we knew that some families transmitted some cancers in a heritable manner, for some reason or other that was never extrapolated into the idea that all cancer must arise from genetic origins. Well, viruses kind of gave the lie to that theory because it’s the genome of the virus that’s responsible in some way—or the virus infection, if you wish, that’s responsible in some way—for the tumors that arise from these viruses.

Hughes: But only in certain diseases was that evident, right?

02-01:01:03 Bishop: What do you mean?

Hughes: Well, you spoke about the work with leukemia virus, but it wasn’t as though every type of cancer that was out there was thought to be caused by a virus.

02-01:01:11 Bishop: No. But the simple fact is that there were both DNA and RNA viruses that caused cancer in animals and experimental systems. So that brings us to a key point that we’ve overlooked until now. Because in the very same brief period of time of the discovery of reverse transcriptase—and this brings me back to the virtue of Rous sarcoma virus as an experimental system—Steven Martin, working in Harry Rubin’s lab— Harry was no fan of genetics. But Steven in his spare time treated Rous sarcoma virus with mutagen and isolated strains of the virus in which the transformation to neoplastic cells in that bioassay invented by Temin and Rubin was temperature-sensitive. So if you infect the cells— This is a chicken virus, so it grows best at 42 degrees centigrade because that’s the body temperature of a chicken. Evolution’s wonderful. All our enzymes have a maximum efficiency of 37 degrees centigrade, right?

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Hughes: Yes.

02-01:02:35 Bishop: So the reverse transcriptase for Rous sarcomas has a maximum efficiency at 42 degrees. So if you infect with these viruses at 35 degrees, they transform the cell. If you raise the temperature to 42 degrees, the transformation reverses. Now, that’s really amazing.

Hughes: You mean it reverses, not just stops?

02-01:02:59 Bishop: It reverses. Then if you drop the temperature back down, it comes back, okay? That’s a classic “conditional mutant.” That kind of mutation had been used for decades in bacterial genetics. It says without question that there is a viral- encoded protein, or more than one, that’s responsible for the transformation. That’s what a temperature-sensitive mutant tells you. So Steven was the first person to publish that kind of evidence. Peter Vogt and Hidesaburo Hanafusa were doing superb genetic analysis, and they were reaching the same conclusion: that there must be a gene. But Harold and I both feel that Steven, certainly for us, had produced the first really decisive evidence. It was his paper in Nature in 1970 that nailed it: there’s got to be at least one gene. And there was eventually. It was dubbed src, [spells] S,R,C, because it causes sarcomas.

Hughes: Harold told me something interesting, probably not news to you.10 He feels that Steve Martin’s very critical work, as you’re describing, was overlooked because it was presented at the same conference at which RT was described.

02-01:04:18 Bishop: Well, I think it was overlooked not only because of the conference but because reverse transcriptase was such a riveting experiment, discovery, that it just took over everyone’s emotional persona. But the significance of Martin’s work wasn’t lost on, I think, most people in the field. And I think furthermore, the credit was somewhat diluted by the fact that there were Hanafusa and Vogt coming to the same conclusions. So in terms of credit, I think Steven has suffered. But in terms of impact on the field, it’s undeniable. To me, it immediately was of course. Right? How else could a virus be doing this? The structural proteins of a virus are not responsible for this, and it wouldn’t persist, right? That brings up the point that it is a persistent infection. That was part of Howard’s reasoning that there might be a reverse transcriptase, because he kept pointing out by various means—and this was undeniable; people were just ignoring it—that when you infect some cells with Rous sarcoma virus, the genome must persist through endless numbers of cellular divisions without any evidence that the virus is replicating. Okay?

10 Telephone interview, October 3, 2016.

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Hughes: I’m listening.

02-01:06:00 Bishop: So how else can you explain that? If the virus is not replicating, then it ought to be diluted out by countless divisions. So the genome must be stabilized in some way and replicated in some way that is not viral replication per se but preservation of the viral genes in some way in the cells that’s stable.

Hughes: And Temin recognized that.

02-01:06:26 Bishop: That’s his provirus. The provirus was the DNA form copied from the RNA genome that was replicated then by the cell as a DNA molecule.

Hughes: As part of the cellular DNA, right?

02-01:06:41 Bishop: Well, whether it was integrated or not was a moot point. Because we know that some DNA tumor viruses, their DNA persists as an extra genomic entity, a so-called episome that is replicated in that form. But the point is that Howard had very good biological evidence that the genes of the virus were being sustained through countless cellular divisions without apparent viral replication.

Hughes: Well, then why were his results more or less pooh-poohed for a while?

02-01:07:14 Bishop: It’s called personal bias, preconception, the Central Dogma. It’s one of the fatal flaws of scientists. It was bewildering to me, I have to say, witnessing it. Because as I said, in all honesty, if you go back and look at my lectures from the time I first read the literature, I thought, well, this is a perfectly reasonable idea. I think part of it was that the Central Dogma was identified with Francis Crick. He didn’t invent it, but he promulgated it. He was such a dominating figure. Scientists are very susceptible to that sort of thing. I am susceptible to it. I used to fight it all the time during my career. Some intellectually powerful figure, potent figure, and something inside you just doesn’t want to run against it unless you’re put together in the right way.

Hughes: Crick could’ve said, guys, just look back at my dotted line.

02-01:08:30 Bishop: Yes. This wouldn’t bother him. Francis was beyond that. He could have cared less.

Hughes: It’s interesting, isn’t it, how the aura of the figure in science isn’t necessarily always beneficial.

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02-01:08:52 Bishop: Well, that’s a nice way of saying what I was trying to say. Yes, it’s a fatal flaw for a scientist. You’ve got to be willing to push the dogma, to challenge the dogma in the field, if you’re ever going to make a major contribution. It’s the paradigm shift of [Thomas] Kuhn, right?

Hughes: Yes, the famous paradigm shift.11

02-01:09:18 Bishop: This is a premier example. Unfortunately, it didn’t exist when Kuhn wrote his book, because it would’ve been a wonderful illustration for him.

Hughes: Yes. So we’ve got Temin’s provirus idea.

02-01:09:42 Bishop: Once it became apparent that transformation of cells to a neoplastic phenotype by viruses was based on viral genes, then people began to pay attention. This all happened very quickly. So the theory that you raised previously came out of George Todaro and Robert Huebner, who were both at the National Institutes of Health at the time, and were major figures in tumor virology. They were influenced by the existence of what we call endogenous retroviruses. We have them in our genome. It turns out, lots of them. These viruses hook rides in species. Their genome gets integrated, and it’s of no use to the cell, so typically it starts to deteriorate over many generations. So there are bits and pieces littered throughout our genome, and a few that are capable of actually jumping from one place to another in our genome. So it was clear—and this work was done mostly in mice, although it was true also in avians, chickens—that different mouse species actually perpetuated murine, mouse, leukemia viruses in their genomes. These could become manifest as leukemia in an adult mouse, and it’s being caused by a virus that was actually inherited from the previous generation. These were endogenous retroviruses.

Hughes: I see.

02-01:11:42 Bishop: So Huebner and Todaro proposed that all cancer arose from the activation of viral oncogenes that were perpetuated in the species. This required an amazing feat of phylogenesis because it suggested that viral oncogenes had been introduced so early in evolution that they’re in all species, because essentially all metazoan species get cancer of one sort or another. So I never found it credible. But the idea was out there. It was called the oncogene hypothesis. The best thing about it was the word. The worst thing about it was, if you thought it through, it was really dubious. I never thought it was too credible.

11 Thomas S. Kuhn, The Structure of Scientific Revolutions, University of Chicago Press, 2nd enlarged edition, 1970.

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Robert Huebner and George Todaro’s viroogene/oncogene hypothesis, as portrayed in its original publication

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I’m sure at this point what influenced Harold and me more in our thinking was just the desire to test that theory and we thought probably debunk it. Or the other line of thought, which was, what’s that gene doing in Rous sarcoma virus? It’s of no use to the virus. If you propagate that virus in the laboratory without selecting for neoplastic transformation, it quickly loses the src gene.

If you experimentally remove the src gene, which we could do once recombinant DNA was available, the virus still replicates normally. And Vogt was doing that with spontaneous mutants. He had deletion mutants that took out a piece of the genome that appeared necessary for the virus to transform cells, but the virus grew perfectly fine. Why would that transforming gene be there? Why would it be sustained? One obvious thought was that— Well, the real point emerges from thinking about where viruses came from in the first place. As viruses were evolving, why would they acquire and maintain something like the src gene, which is of no use to them. All right? So the alternative possibility, particularly in the context of, say, Harold’s work, where he was among the first to demonstrate that the provirus is integrated into the chromosomal DNA of the host cell— That’s an extraordinarily intimate interaction, and it’s a setup for genetic recombination. So it’s easy to imagine that during the course of that interaction between the viral provirus and the cellular genome that the virus might accidentally pick up a piece of the cellular genome into its own genome.

Hughes: Just randomly?

02-01:14:57 Bishop: Yes, absolutely random. But if it happens to have oncogenic potential, it’s going to become manifest. All right? Otherwise, it’s going to disappear in the experiment so we’ll never see it.

Hughes: Because evolution is conservative.

02-01:15:16 Bishop: Yes, there’s no selective pressure, right?

Hughes: Yes.

02-01:15:19 Bishop: So that was it. Prompted by either or both of those lines of thought and driven by Harold’s previous experience as a postdoctoral fellow at NIH where he had worked with deletion mutants to make gene-specific probes, we teamed up with Peter Vogt. We ought to talk a little bit why we had a relatively close association with Peter then, because Peter had these deletion mutants that we knew took out a piece of src. Turns out they take out virtually all of the gene. We could use these mutants to take out all of the non-src DNA copy of the Rous sarcoma virus genome and just leave radioactive DNA that was complementary to the src gene, to the oncogene. This was before recombinant DNA, so it was an extremely laborious process. It capitalized on the

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Peter Vogt

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technology that we had developed originally for assaying the hybridization of viral DNA to viral RNA. But we got enough of this probe to test whether there were genes like this in normal cells, and there it was. It took four years to make it truly credible and to extend it from chicken to other avians, and then eventually to mammals, even humans. Originally, we thought it was not in mammalian DNA, which was a little troubling. But we also realized that the assay—

Hughes: Troubling because then how does cancer occur in human beings?

02-01:17:14 Bishop: Sorry?

Hughes: You had to have it apply to mammals and Homo sapiens to explain why we get cancer.

02-01:17:24 Bishop: Well, we weren’t that extreme in our reasoning yet; we just wanted to know how conserved this gene was. We were encouraged to look at some more primitive birds, the ratites--ostriches, emu. In order to make the hybridization work, you have to drop the stringency of the assay, because as you get farther and farther away from the bird in phylogeny, you’re going to have more and more divergence of the nucleotide sequence. So we simply dropped the stringency. That’s a perfectly legitimate thing to do. But people who were not familiar with and experienced with molecular hybridization just found it outlandish.

Hughes: How do you technically do that?

02-01:18:21 Bishop: You change the salt concentration and the temperature to stabilize less perfect matches. You drop the temperature and you increase the salt to stabilize less perfect matches.

Hughes: Okay.

02-01:18:31 Bishop: And bingo, there it was in ratites. But we still weren’t finding it in mammals. We hadn’t tried all that hard, I have to confess. One day in a group meeting, one of our research associates, technicians, pointed out in one of the experiments that we didn’t have a control, and why didn’t we use a mammalian nucleic acid (mouse RNA) for this control? We did that, and lo and behold, it wasn’t a control. There was src in mouse RNA and DNA.

Hughes: Was that Deborah Spector?

02-01:19:13 Bishop: No, the suggestion came from Karen Smith, a very bright woman who eventually became a lawyer.

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Hughes: And lost to science.

02-01:19:33 Bishop: Well, patent law, biological patent law.

But Deborah did the experiments. And there it was in mammals and humans. Still people were fretting about, was it really a gene? We couldn’t nail that until we could clone the gene and show its structure.

Hughes: Well, you’ve run over a lot of very interesting science that I want to go into in a little more detail. But let’s get Harold Varmus collaborating with you. Can you tell the amusing story of how you first met him?

02-01:20:19 Bishop: Yes. I met Harold because Harold is brash. [They laugh.] As I remember the story, he had been a postdoctoral fellow in the same program I was in [at NIH]. He’s four years younger than I am, so he was a few years behind me in that. He worked with Ira Pastan, and he had experience with molecular hybridization. He had taken a course at NIH in which he heard about RNA tumor viruses and the provirus theory and so forth, and so he thought maybe he’d want to work in the field. And he was interested in coming to California. He was in love with the outdoors and loved to fish and what have you. At the time, Harry Rubin was the name in RNA tumor viruses out here. Harold came out and had a scheduled interview with Rubin, and it quickly became apparent that the kind of things Harold wanted to do, Rubin was not interested in. Harry was very candid about that. As I recall, he suggested that Harold talk to Peter Duesberg, who was in the same department in Berkeley, because Peter was doing chemistry on the virus. But he was out of town. I’d never met Harry Rubin at the time. Harry said, “Why don’t you check out these folks at UCSF”—we hadn’t published yet— “who I understand are doing work on the molecular biology of Rous Sarcoma virus.”

Hughes: Rubin must’ve had a vague idea of what Warren Levinson was doing.

02-01:22:16 Bishop: I don’t think so.

Hughes: I thought Warren was a student of Harry Rubin’s.

02-01:22:25 Bishop: Yes, but we had no connection to Harry at the time. In any event, Harry suggested Harold check us out. So he came over unannounced and we sat down and talked. It took about five minutes to realize this guy was really smart and would be fun to work with. It also turned out we shared extracurricular interests. Harold, after all, has a master’s degree in English literature from Harvard. We both love literature and the arts. So I said right away, “Well, come with us.”

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The next time I saw him was at a Gordon conference. The Gordon conference was held in New Hampshire the week that reverse transcriptase was published. Talk about rubbing it in, right? I was at the conference, and Baltimore and Temin were there. By that point, I had a lot of data myself about it, so I was added to the program. Harold was there, and he came up to me. I’ll never forget. He came up to me afterwards, and he and Connie, his wife, I think they were driving and were going to take a long time to come out here. He was going to arrive later that year to work. He said, “Well, good luck with reverse transcriptase,” and took off.

Hughes: Did you find that annoying?

02-01:24:01 Bishop: No, not at all. I vividly remember being in the lunchroom when someone brought the copy of Nature to David Baltimore, who was at the table with me, in which the papers were published. They had just come out that week. So no one knew that I was working on this subject. Leon was at the meeting. He knew. So they called me and said, “Could you come?” I had to take an overnight flight in order to get there in time. So I went there, and I was the third person on the program to talk about reverse transcriptase. I had a lot of data on the nature of the enzyme and its product and so forth by that point. That sort of established me.

Hughes: So Harold wasn’t being derogatory?

02-01:24:59 Bishop: No, I think he was just being cordial. At that point, I’m not sure he knew about my failure.

Hughes: But he must’ve known, because you had had the conversation in the lab that you were working on reverse transcriptase.

02-01:25:10 Bishop: Oh, yes, he knew what we were doing. Absolutely. That’s why he decided to come work [with us], because we were using molecular hybridization and so forth.

Hughes: Did it ever occur to you that except for the work in Pastan’s lab that he hadn’t really done any basic science? Did that bother you at all?

02-01:25:34 Bishop: We’re talking about me before I came to UCSF.

Hughes: Good point.

02-01:25:40 Bishop: I was not at all concerned about that sort of thing. Harold was plowing the same path I did. Right?

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Hughes: Yes. What did Harold look like?

02-01:25:50 Bishop: Well, what he looks like now. He claims he didn’t have a beard at the time; I thought he did.

Hughes: Well, I’ve seen pictures of him with not only a beard but with hair out to here.

02-01:26:02 Bishop: Yes. Well, I have such a picture. It’s somewhat underexposed. One of his long-term research associates dubbed it the Veil of Turin.

Burnett: The shroud?

02-01:26:20 Bishop: The Shroud of Turin, right. Anyway, Harold looked like Harold looks now. He’s not aged very much, except he’s losing hair at the same rate I am. I’m four years ahead of him.

Hughes: Let’s go a little more slowly through the research that you and Harold then did. It sounds to me as though it was almost an immediate attraction as far as your interests matching. But what about your science? In this partnership, which becomes quite famous, did it become apparent who was going to be doing what? Did you talk about who would do what?

02-01:27:13 Bishop: Well, from the get-go that was always the case with my postdocs. I made a point of letting them carve out a place of their own within the context of the lab. I never ever made an explicit assignment of work. The most I did with Harold was to suggest that the one thing that was missing from the lab’s effort at the moment was the search for the provirus in the cell, and he might think about that. Eventually, that’s what he picked up on, He was independent from the beginning; he already had postdoctoral experience. I was the person people were applying to for postdoctoral fellowships obviously, because I had already published in the field. Harold had not yet. But we fell into the pattern of sharing the mentorship of all the postdocs and students in the lab. The lab was growing at a considerable rate. Harold, I think, was my third postdoctoral fellow. You could hardly do better. I suppose that Harold would say, “I [Bishop] couldn’t do better.” But the lab started to grow like Topsy. So we were sharing mentorship of the postdocs.

Hughes: From the moment he arrived more or less?

02-01:28:41 Bishop: Within six months maybe, yes. I don’t remember. Maybe he does. As he has said in Henry’s book,12 he never considered himself a postdoc with me, which

12 Henry Bourne, Paths to Innovation: Discovery Recombinant DNA, Oncogenes, and Prions in One Medical

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is fair; he had had a postdoctoral fellowship with Pastan, and our relationship developed quickly into one of equals.

Hughes: But technically, he was a postdoc? That was his job title, right?

02-01:29:02 Bishop: I don’t know what his job title was. He hadn’t had a chance to get a fellowship yet because he arrived within six months of our first meeting. But within a year or two, we had engineered a soft-money position for him, and he had gotten the Career Development Award from NIH. So he became self- sufficient very quickly.

Hughes: I want to quote from your book again, because I do find that you have some charming ways of expressing things. This describes how Harold ends up on your doorstep. “Harold had not chosen me, nor I him. He had been deflected to me by a senior figure”—whose name we know [Rubin]—

02-01:29:50 Bishop: Yes.

Hughes: —“who apparently thought that neither Harold nor I deserved any better.”13

02-01:30:00 Bishop: That was pretty much the situation, I would say.

Hughes: Well, could you go into some detail about the very first experiments when it became apparent—or was it apparent from the start?—that what you were looking for was the cellular gene. Am I right in that?

02-01:30:31 Bishop: Yes. Developing the probe was, as I intimated before, a laborious and challenging undertaking. It required large amounts of virus. We had to use radioactive phosphorous in order to get the probe radioactive enough to be usable for our purposes. Radioactive phosphorous decays rapidly, so we’d make a batch of probe, and then we’d have to hurry up and do experiments with it, and then make another batch of probe and hurry up to do experiments with it.

Hughes: The short half-life is because of the type of radiation?

02-01:31:10 Bishop: Yes. Radioactive phosphorous decays rapidly, has a half-life of about two weeks.

Hughes: Why did you have to use that particular isotope?

School, Over One Decade, University of California Press, 2011. 13 How to Win the Nobel Prize, p. 54.

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02-01:31:24 Bishop: Because we could get it so much more radioactive, which increases the sensitivity of the assay. And increases the number of assays you can do with a given amount of probe as well. So the first experiments were done by Ramareddy Guntaka, who eventually wound up on the faculty of University of Missouri at Columbia. He was working with Harold on integration of the provirus. He was persuaded to sort of take this on on the side and see whether we could get a probe that’s specific for src by making lots of radioactive copy of the Rous sarcoma virus genome, hybridizing it with the RNA from the deletion mutant from Peter Vogt, and then—

Hughes: Which Vogt had given you.

02-01:32:17 Bishop: Yes. Well, it was published. We had a close affiliation with him that we ought to talk about. So we hybridized the radioactive copy of the Rous sarcoma virus genome. You hybridize that with the RNA of the deletion mutant that doesn’t have src in it, and you separate the hybridized from the unhybridized probe—and you probably have to do it a couple times in sequence to really have it pure—and you’ve got a probe that only picks up src. You can show that by showing that it hybridizes with the Rous sarcoma virus genome in a new assay but does not hybridize with the deletion mutant.

Hughes: So that mutant was really central, wasn’t it?

02-01:33:05 Bishop: Oh, it was crucial. There were four authors on the paper. Dominique Stehelin, who we’ll get to; Harold, myself, and Peter Vogt, on the paper in Nature.

Hughes: Which is the 1976 paper.14

02-01:33:21 Bishop: Yes. We had our first positive results in ’74.

Hughes: And what were they?

02-01:33:26 Bishop: Well, we knew it was there by then, but in order to make it credible, we had to do a lot more experiments.

Hughes: I see.

14 D. Stehelin, H.E. Varmus, J.M. Bishop and P.K. Vogt, “DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian cells,” Nature 260, 170-173, 1976.

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Early portrayal of how the v-src oncogene of Rous Sarcoma Virus originated. Not known at the time was that the viral gene contains a mutation responsible for its ability to elicit tumorss.

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02-01:33:32 Bishop: A two-year lapse now with a stunner like that is unthinkable because the technology is so much better. It would’ve taken just a few weeks with recombinant DNA to do these experiments.

Hughes: Well, we want to talk about that.

02-01:33:45 Bishop: I’d rather not; it’s painful. Ramareddy Guntaka had a probe that looked to us like it might well be tending to a specific reaction with src. But he had acareer to foster, and he had something going with the integration project that was productive. So meanwhile, another postdoctoral fellow from France, Dominique Stehelin, was working on a project that was not going too well. So Harold and I decided to ask him whether he’d like to take this on. He took it on and ran with it and did a fabulous job, working eighteen-hour days. I was usually working well into the evening in those days. He and I, typically four times a week, would drift down to the little sandwich shop down the street—I forget what it was called; it’s had several reincarnations since—for our evening meal, and then go back to the lab and be talking science and looking at data.

Hughes: How did your wife like that?

02-01:34:51 Bishop: She was forbearing. She knew she had company with other scientific spouses. But anyway, that stopped when we had children. I was home every evening to read to the boys and so forth.

In my book, I quote his [Stehelin’s] description of the first positive results. It was a Saturday night, really late—no one else was around—when he got the first positive results with chicken DNA. So we obviously looked then to see whether there was RNA in normal cells. We missed it at first because we hadn’t pushed the assay hard enough. We had a line of, I think it was, quail cells that had been transformed by a chemical carcinogen. So Dominique looked at those transformed cells, and he could pick up src in the RNA. But he couldn’t pick it up in normal chicken RNA. So he thought—he was absolutely ebullient—we’ve proven the Huebner-Todaro theory, right? I said, “It can’t be. No, it can’t be.” We used to argue over the evening dinner, sandwich table, about this for months, until we found it in mammalian RNA.

Hughes: So it was finding the mammalian gene that was critical?

02-01:36:35 Bishop: No, it’s just we had to push the assay harder to find it in normal chicken RNA.

Hughes: How did you push the assay?

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02-01:36:53 Bishop: Oh, you just drive it harder, with more material. For some reason or other, src RNA was high in the quail cells. That’s consistent with the idea that it might be part of the transforming mechanism. But the idea that it was originating from a viral genome, which is what the Huebner-Todaro theory would argue, was wrong. We had already shown that that was probably not the case; that it was indeed a normal cellular gene and highly conserved from one species to another.

So the long and the short of it is that Dominique did a spectacular job making the probe, perfecting it and doing the definitive experiments. And it was Deborah Spector who did the experiments that finally showed it was in mammals, including humans, as well.

Hughes: Was she a postdoc at that point?

02-01:37:57 Bishop: Yes, she was a postdoctoral fellow.

Hughes: That was quite a finding for a postdoc.

02-01:38:02 Bishop: Yep. She did what I think is a very healthy thing. In her last year in the lab, she started thinking about a job. She said, “You know, Mike, this field is— It was an exciting frontier, but now it’s established, and I want to do something different. I want to work with herpes viruses. But everyone I’ve talked to about this,” including her former graduate student mentor, “has discouraged me, saying if I write a grant about herpes viruses, the study section’s going to criticize it because I don’t have any prior experience with it.” So I said, “Well, look, Deborah, go work in a herpes virus laboratory for a few months and then come back and start looking for a job. She did that. She got a job; she got a grant in herpes. That was another good lesson for me. That advice came off the top of my head, right? In any event, Deborah did the experiments that extended our findings to mammalian cells, and started her family at the same time.

Hughes: Quite a woman.

02-01:39:07 Bishop: Yes, indeed.

Hughes: Well, is this the time to talk about your collaboration with Peter Vogt?

02-01:39:15 Bishop: Yes. Okay, so early on, when Harold and I started to work together—

Hughes: Although it’s one o’clock. Are you getting tired of talking?

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02-01:39:27 Bishop: Maybe. Let’s finish up with this.

Hughes: Oh, all right.

02-01:39:29 Bishop: I have a date at the bank at three o’clock, and I haven’t showered yet.

Hughes: Now you’re telling us!

02-01:39:40 Bishop: Well, I shower every day, and on my walk, I don’t even break a sweat these days. But anyway, I took a walk this morning, in the rain, an hour walk. It’s just water. There were a surprising number of people roughly my age out there on the path.

Hughes: Well, I ran this morning before I came over here.

02-01:40:05 Bishop: Good for you, yes.

Hughes: And it was raining.

02-01:40:07 Bishop: Well, I’m not a runner. My back is too bad for that. I gave running up after I learned what it does to people’s knees and hips.

But anyway, Harold struck up a collaboration with Robin Weiss, then a postdoc in Peter Vogt’s lab. Peter was in Seattle at the time, and he and I certainly knew each other. Of course, we were seeing each other regularly. There were endless numbers of meetings in this field at the time; it was so hot, a rapidly expanding field.

I think it was Harold who sired the idea that we ought to get together; the whole labs ought to get together every so often and talk about unpublished data. Now, this was a very competitive field, all right? But we started doing that, and lo and behold, it proved successful. The postdocs were a little uneasy about it at first: I’m going to talk about my unpublished work with this competing lab? It wasn’t really a problem. Peter’s lab was not doing the same thing we were. That’s why the partnership, the collaboration between Harold and Robin, was so logical. But then we thought, well, let’s expand it. So we invited Duesberg lab from Berkeley; we invited people from the Salk [Institute for Biological Studies] who were working in this area; we invited other people from Seattle. This thing turned into what was called the West Coast Tumor Virus Cooperative. We met several times a year. We alternated locations. Most of the time, it was either here or in Los Angeles because of the now defunct airline PSA. Thirty-two dollars round trip to L.A. from San Francisco, right? That went on for a number of years. So we were intimately

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familiar with what was going on in Peter’s lab, intimately familiar with all the mutants he had. Long before they were published, we were aware of them.

Hughes: Also the two names that you didn’t mention—Inder Verma who was—

02-01:42:14 Bishop: That’s the Salk group.

Hughes: Where was Hung Fan?

02-01:42:18 Bishop: Salk.

Hughes: So you also were up to date on what was happening at the Salk.

02-01:42:23 Bishop: Yes, absolutely.

Hughes: Well, that’s interesting when you consider you were potential competitors.

02-01:42:29 Bishop: Well, I can’t say that it’s unprecedented, because there was that sort of interactions in the early days of the phage research. But on this scale? I don’t think so, ever. The key thing was that we really were talking about unpublished data. Things would get a little tense at times because there could be overlap. It wasn’t a problem with Peter’s lab, but with the other labs, they were doing the same genre of work we were doing.

Hughes: I see.

02-01:43:02 Bishop: But it held up.

Hughes: Do you know of situations like that in bioscience nowadays?

Bishop: No, but I’m not that familiar— I would not say it was unique. But at the time, I think it was definitely distinctive in the level of candor and the frequency of the meetings, and the fact that everybody got to really like them.

Hughes: Remarkable.

02-01:43:38 Bishop: Yes.

Hughes: Everybody must’ve been getting information that was helpful to their own research.

02-01:43:47 Bishop: Yes, absolutely.

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Hughes: Is that a good place to stop for today?

02-01:43:52 Bishop: Yes, I think so.

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Interview 3: January 19, 2017

Hughes: It is January 19, 2017, and we are once again in the home of Dr. Bishop, for the third session. Dr. Bishop, last time we stopped with a discussion of the scientists pretty much within your own group who had contributed to the oncogene concept. When you went over the transcripts, did you find anything that you wanted to elaborate upon?

03-00:00:49 Bishop: Actually, I don’t think so. In terms of the discovery itself?

Hughes: Yes.

03-00:00:54 Bishop: The important things were, one, the almost unique virtue of Rous sarcoma virus as an experimental reagent in the pursuit of how cancer arises. Then the progress towards identifying a gene within the virus that causes its ability to initiate cancer. That led to the discovery of the proto-oncogenes, the fact that the oncogene of Rous sarcoma virus had actually been derived by a sort of piracy in which the virus had essentially copied that gene into its own genome and was carrying it along for the ride. It’s not a purposeful act; it’s just a chance of nature. But it was extraordinarily good fortune for cancer research that it happened because it was the first clear indication that there were genes in human DNA that if modified in certain ways could become cancer genes. There had not been any direct experimental evidence for that before. So that’s why the discovery attracted such attention.

The other important discovery that was made contemporaneously addressed an almost equally important question. And that is, here’s a single gene that can cause cancer; how does it do that? That problem was taken on in my laboratory by Arthur Levinson. Art eventually became the CEO of Genentech and is presently the chair of the Apple board. But at the time, he was a hypermanic and extraordinarily smart and skilled postdoc. He and a postdoc named Mark Collette in Ray Erickson’s lab in Denver contemporaneously discovered that the protein encoded by the src oncogene is a protein kinase. It catalyzes the phosphorylation of proteins. That was a riveting discovery because the phosphorylation of protein is one of the most diversified ways in which the cell can influence its behavior. An enzyme like the src enzyme may and does phosphorylate numerous proteins in the cell. So that provides the opportunity to profoundly change the behavior of the cell. It was absolutely immediately apparent that this was probably an important part of the general picture of how cancer arises. Indeed, this class of enzyme has now been implicated in a large number of different varieties of cancers and is a major therapeutic target. At the time, it was just an extraordinarily exciting discovery. Of course, the discovery was made first with the viral gene, and then it was imperative that we find out whether the cellular gene was doing that too. And the answer is yes, it is doing that but in a controlled manner. In

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due course, it became apparent that the gene in the virus is tumorigenic because it’s suffered changes in its nucleotide sequence; it’s suffered mutations that unleashed it, essentially jammed an accelerator, if you will.

Hughes: How do those changes occur? In the way it integrates with the DNA?

03-00:05:27 Bishop: No, the kind of changes— These are point mutations, single nucleotide changes. So they’re errors that are made during the copying of the gene, not by translocations or deletions or what have you.

Hughes: Where in this system do some of the external influences that are supposed to beget cancer operate? Such as solar radiation, that sort of thing. How are they getting from the external environment to the cell to affecting the actual DNA?

03-00:06:18 Bishop: I’m sorry, Sally, I’m not quite sure I understand. Let’s just start with a fundamental point. Our DNA is suffering damage every moment. I’ve forgotten the numbers; there are an astronomical number of mutations introduced into our DNA by the time we pass on. Most of them are repaired. We have, I’d say, a half-dozen different gadgets that repair different kinds of damage in our DNA. But they don’t all get repaired, and the ones that linger can influence the way a protein performs. So the mutation in the src gene in the virus which makes it an unregulated enzyme probably occurred as a mistake during the course of either the initial copying of the cellular gene into the viral genome or during subsequent replication of the virus.

Hughes: I see.

03-00:07:22 Bishop: Now, there are other forms of genetic damage that have since been implicated in cancer, such as swapping pieces between chromosomes; acquisition of whole copies, additional copies of chromosomes—three, four copies; amplification or overgrowth, if you want, of small regions of chromosomes; deletions within chromosomes; loss of whole chromosomes. The typical cancer cell is what we call aneuploid. It’s got an abnormal number of chromosomes and abnormally shaped chromosomes. So there are a variety of forms of genetic damage that can influence a gene’s function either by directly affecting the gene or by affecting a control mechanism that governs the gene. It gets more complicated as each month passes, I’d say. Beyond that are changes that are— Well, suffice it to say that anything that can cause a gene to malfunction, either to run when it should not be running or to take away the function, (and that’s a whole separate story that wasn’t learned by studying viruses, that was learned by studying human genetics), can lead to cancer. But this form was the most elemental, a single-point mutation.

Hughes: I see.

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03-00:09:03 Bishop: We couldn’t figure that out until we had the ability to clone the gene with recombinant DNA and acquire the quantities required to do the full nucleotide sequence of the viral gene and the cellular gene. By that point, the field had burgeoned and lots of people were doing that sort of thing. So for several years we had to struggle with very primitive technologies in deciding whether the cellular gene was really a gene. Was it functional? Did it have the same function as the viral gene? And more than anything else, was it as dangerous as the viral gene, or was it really a normal and well-behaved cellular gene? None of these things were completely approachable until recombinant DNA came along. And we had to wait several years while they sorted out— It was thought, it was imagined—I guess reasonably—that if we made a molecular clone of either the viral oncogene or the cellular gene, the vector in which the clone was prepared and propagated might get loose and get into somebody and cause cancer. The argument was just that simple-minded. So our field of research, tumor virus in general, both DNA and RNA, was among the last major field of biomedical research in which the use of recombinant DNA was finally sanctioned.

Hughes: We’re all told to use a sunscreen, wear a hat, don’t bake in the sun. How do these—?

03-00:11:21 Bishop: Well, ultraviolet light damages DNA. There’s lots of UV in sunlight and it damages DNA. If you look at the cancers that we know beyond a reasonable doubt are caused by sunlight, such as melanoma, the DNA of a melanoma is riddled with damage that is characteristic of ultraviolet light, damage elicited by ultraviolet light.

Hughes: Did that knowledge come only after—

03-00:11:54 Bishop: Yes.

Hughes: —the oncogene paradigm?

03-00:11:56 Bishop: That knowledge only came recently when we were able to clone and sequence DNA at a level that was unimaginable at the time we were doing the src work.

Hughes: Let’s go back to Arthur Levinson and Erickson. Were those two independent discoveries?

03-00:12:22 Bishop: Yes, they were. Art made the discovery. He and I and Harold of course were excited about it. We were putting together a manuscript, and I got a preprint in the mail from Ray. I’ve known Ray Erickson from almost the inception of our two careers, and we were friends. Ray sent me this preprint that was going to be published in the Proceedings of the National Academy of Sciences. It

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described their discovery of this enzyme, and we thought, holy cow! So we finished our manuscript and acknowledged that we were aware of theirs. This was the time when publication in the Proceedings of the National Academy of Sciences was highly expedited. There was virtually no review. We sent our paper to Cell, so it appeared later, and I felt that was fine. That was something of a gesture, if you will, to Ray and Mark’s independent claim and perhaps even, I don’t know, chronological priority. It’d be hard to say. This all took place over very few months. Once you discover an enzyme, things happen real fast because you can do an enzyme assay in thirty minutes, and you can do six or eight experiments a day, depending on what you’re trying to find out.

Hughes: You knew their work because they were also doing research on oncogenes?

03-00:13:50 Bishop: Yes. In Ray’s lab, a postdoc (Joan Brugge) had actually discovered the protein encoded by src. That was not discovered in our lab. But of course, we went ahead and made the reagents necessary to study the protein. This was kind of our gene, right? The cellular gene was our gene, at least. So we made reagents to study the gene, and while using those reagents, Art more or less serendipitously discovered the function of src, as I think was true in Collette and Erickson’s case, too. It took some very shrewd inference on both parts to recognize what was there. But once that inference had been made, things tumbled out pretty quickly.

Hughes: What was your feeling when Art, who obviously could’ve been—perhaps already was—a very promising basic scientist, when he decided to leap the traces, so to speak, and join a company [Genentech]?

03-00:15:10 Bishop: I had no problem with it at all. I encouraged him to do it. Art came to me to talk about it. He had already talked about it with his former thesis advisor [Arnold Levine]. It was very early in the biotech days. It was still unusual for a postdoc of Art’s caliber to go [to a company].

Hughes: It was about 1980,wasn’t it?

03-00:15:30 Bishop: Well, yes, roughly. We published cell src in ’76, so it was several years thereafter that the kinase was discovered. In any event, Art was worried. One, that his reputation would suffer, and two, that if he didn’t like it at Genentech, he could still get back into academia. People were telling him that this was not a smart move, that it at the time was not totally acceptable. Working in industry, for reasons that have always escaped me, had a certain stigma to it, okay? Many of the people who raised that stigma at the time have since benefitted from biotech in highly lucrative ways. But in any event, at the time there was a stigma. I told Art I didn’t see any problem with it. I thought it was an interesting adventure, typical of him; that he might want to undertake it; and he should rest assured that if he wanted to come back to academia, we’d

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take him back in a heartbeat. There would be no problem with that. So off he went.

Hughes: You didn’t feel you were losing a basic scientist forever?

03-00:17:01 Bishop: No, not at all. He went to Genentech, and we continued to correspond. He took some molecular clones with him, and we collaborated for a while because Genentech could do things we couldn’t do yet. For example, make proteins in large quantity with recombinant DNA. We just hadn’t set that up. I have a notebook with about 300 pages of hard copy from what was the predecessor of email. He and I were corresponding. I think probably I was the only person at UCSF doing this at the time. It went through a mainframe computer sitting in the basement somewhere. I couldn’t print what I sent to him; I could only print what he sent to me. So I have 200-plus pages of this ongoing conversation about what they were doing and the collaboration we had, and, in general, life. So I didn’t lose him. Or put it another way: what I’m trying to say is that the world didn’t lose a first-rate biomedical scientist to the graveyard of the corporate world.

Art, I think, is the principal person who got Genentech interested in cancer. They didn’t see a market there at the time. But the research at Genentech that Art drove initially led ultimately to Herceptin. The molecular clone from my lab was used to initiate that research.

Hughes: Is that so? I had never heard that story.

03-00:19:04 Bishop: Yes. They made a nice video about it. I have it. There’s a good interview with Art and me together about the early days and other patient advocates. The whole story is there, including how Genentech managed some of the bad press they were getting at the time. Handled it very well. Herceptin’s really, with the exception of the antiestrogens, the first of what we call targeted therapy for cancer. That is to say, it’s aimed at a specific molecule. We know the molecule, we know how to test for the molecule, and Herceptin is attacking that molecule.

That molecule is related to another viral oncogene (erbB) that had been found to have a proto-oncogene. So the precedent was already there. Herceptin attacks one member of a family of proteins that are very similar to each other. And the proto-oncogene in question encoded another member of that family. So the fact that there was a proto-oncogene that had given rise to a viral oncogene, and that a protein very closely related to that could be implicated in human breast cancer, was extremely valuable intellectually. It helped motivate people. It lent credibility to the idea that the protein in human breast cancer might be involved in driving the tumor.

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Hughes: Well, also, even broader than that perhaps, the oncogene paradigm, a major step in basic science, could also have practical applications. Did people go that far in their thinking?

03-00:21:19 Bishop: Well, practical utility of recombinant DNA was demonstrated first with growth hormone and insulin.

Hughes: No, not recombinant DNA; the fact that the idea of the oncogene, which was a tremendous breakthrough in basic science, could also have practical applications.

03-00:21:36 Bishop: No, we already had evidence, other sorts of evidence, that this ever-growing class of genes, proto-oncogenes, was involved in human cancer. And it took three forms. The first, which got the most attention because it was what everyone imagined, that is, that there was a point mutation in the proto- oncogene of certain human cancer cell lines and eventually in certain human cancers. That’s the so-called ras gene. It was an early proto-oncogene, discovered once the general principle was established. Several laboratories discovered mutant ras in human cancer cells. The one that has the most visibility is Bob Weinberg’s at MIT. Bob pioneered the approach to identifying a biologically active oncogene in human cancer DNA. What they found ultimately was that what they had discovered was a mutant version of the ras proto-oncogene that was already known from studying retroviruses. That was the kind of powerful connection you’re talking about.

Hughes: I see.

03-00:22:53 Bishop: And it was a point mutation, and that’s what everybody thought of in terms of mutations, right? But second, within the same period of time, several laboratories discovered that in certain human leukemias and lymphomas, chromosomal translocations affected the activity of known proto-oncogenes. Third—and we were among the labs that discovered this—many tumors contain amplified DNA, regions where the DNA of a chromosome is replicated many times over and expands into a huge piece of chromosome. It can be a hundred copies of the gene, a thousand copies of the gene. It’s usually multiple genes in that domain. Which means that the protein is egregiously over produced. That kind of amplification is very common in human cancers.

In our instance, we discovered it in neuroblastomas, a nerve tumor of children. It was a gene that we had not seen before but was related to the second proto- oncogene we ever found, which was the so-called MYC proto-oncogene. Here it was, amplified in this human tumor and vastly over-expressed. We did a few studies on our own, getting clinical material, and eventually turned it over to the nationwide consortium of neuroblastoma laboratories. What emerged

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was that the amplification of this gene is a powerful prognostic indicator of whether the tumor’s going to respond or not to the therapy of the time. The data that accumulated were spectacular. We called the gene NMYC, for neuroblastoma MYC. At least that’s what I thought we meant. But the two postdocs responsible for this work (Manfred Schwab and Kari Alitalo) later told me that, no, it meant not MYC. Anyway, in any event, it’s now known as MYCN. If the gene is amplified, the survival rates plummet. If it’s not amplified, almost all the children who are treated with conventional therapy survive. It remains one of the most powerful—certainly one of the most powerful—genomic biomarkers. So you have three very different forms of genetic damage in human tumors, all affecting known proto-oncogenes: point mutations, chromosomal translocations, and gene amplification. This all emerged over the course of a year or so. At that point, what else do you need? Well, the answer to that is therapeutic response. That came along in due course.

Hughes: Did this do your physician’s soul good?

03-00:26:21 Bishop: Beg pardon?

Hughes: Well, I’ll put it differently. I imagine with your background as a physician that practical application was somewhere in your thinking. So to see it happening perhaps faster than you ever thought, how did you feel about that?

03-00:26:49 Bishop: Well, it was very gratifying. But we were just moving on every day, right? But yes, it was exciting and gratifying. More so in retrospect than at the time, I suspect, because it was only circumstantial evidence, and there was resistance to the idea still. But to those of us immediately in the field— Well, I remember I wrote a little one-page so-called mini review in Cell. It was 1981. It was called “Enemies Within: the Genesis of Retrovirus Oncogenes.”15 It essentially concluded with the suggestion that malfunction of these genes represented a final common pathway to cancer. I got some laudatory remarks, and I got some highly critical remarks about that. So in ’81, it was still a somewhat tenuous idea.

Hughes: What were your critics saying?

03-00:27:54 Bishop: Circumstantial evidence, basically.

15 J. M. Bishop, “Enemies Within: The Genesis of Retroviral Oncogenes”, Cell 23:5, 1981.

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Hughes: Oh, I see. I read in Dr. Varmus’ book that in the late 1990s, you and Dean Felsher were among the first to show that an oncogene, which was MYC, could be turned on and off under the influence of tetracycline.16

03-00:29:09 Bishop: After a fashion. We had engineered a mouse model in which the expression of an exogenous MYC gene in blood cells could be inactivated by tetracycline.

Hughes: Another potential therapy, right?

03-00:29:16 Bishop: Yes. But that was all in mouse models, Sally. The technology to do that had just become apparent, and it struck me in particular that here was a way to explore the role of oncogenes in tumorigenesis. The question I wanted to ask at the time was, is the oncogene that initiates tumors required indefinitely as the tumor develops or once the tumor’s established is it irrelevant? Okay? Because that would bear on what information you’d have to have in order to select the therapeutic target.

Dean was a new postdoc in the lab, and he took on this project. We knew already that if you took a molecular clone of MYC and introduced it into a mouse so that it was expressed in its lymph cells, they would get blood tumors—both lymphomas and a form of leukemia. The MYC gene that’s introduced into the mouse was heavily over-expressed, as if it were amplified or affected by chromosomal translocation, right? And that created a tumor very rapidly. So now we had the ability to rig the gene that we put into the mouse in such a way that we could turn it off and on. It was very easy to do the experiment. To my astonishment, you could take the mouse almost to the brink of death. But when you shut that gene down, the tumor melted away and the mouse survived with a normal lifespan. Now, that’s a highly refined context. When I first reported this at a meeting, I was told afterwards, “You guys aren’t studying cancer. That can’t possibly be cancer.” [laughs] I said, “Well, gee, guys, it’s killing the mouse. We can transplant it into another mouse and it’ll kill that mouse. What do you mean it’s not cancer?” They didn’t like the idea at all. It was a Keystone meeting [Keystone Symposia on Molecular and Cellular Biology]. That [criticism] went away quickly because other people were doing a similar kind of experiment with other oncogenes and getting similar results.

Hughes: What was their mental block to it being cancer?

03-00:32:04 Bishop: I have no idea. I have no idea. I was stunned by the point, yes.

16 Harold Varmus, The Art and Politics of Science, Norton, 2009, p. 107.

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Hughes: Interesting. Well, we’re taking a circuitous route to getting to the meetings and consortia that flowed out of the oncogene research. You had started to talk last time about the meetings.

Bishop: Those meetings with Peter Vogt and others had terminated by the time of the MYC experiments.

03-00:32:37 Hughes: This probably would’ve been the late seventies that you were meeting? There were a number of people involved.

03-00:32:56 Bishop: Yes.

Hughes: Peter Vogt and Steve Martin and Peter Duesberg and Inder Verma and—

03-00:33:04 Bishop: Tony Hunter and Bart Sefton and people from Seattle. I think Bob Eisenman came to a few. It was kind of a movable feast. But it petered out eventually because many of the people involved in it went their separate ways, and the thrust of the labs began to diverge so much that there wasn’t the kind of intense cohesion among the groups as to what was interesting.

Hughes: Who initiated the meetings?

03-00:33:48 Bishop: Well, I would say Harold probably gets the most credit. And of course Peter Vogt. Initially, it was Peter and Harold and me and our colleagues, and then we grew it.

Hughes: One of the things I read—or maybe you told me—was that because the discussion of results that may or may not have been published, usually not published, some of the trainees got a little nervous.

03-00:34:30 Bishop: Oh, there were tense moments, suffice it to say. There were tense moments. But it was much ado about nothing.

Hughes: Well, but it could’ve been ado if somebody rushed to publication, taking results that they had heard in these meetings.

03-00:34:54 Bishop: To my knowledge, that never happened. In any event they were going to hear these results at other meetings too. There was a time when as soon as we had something, we reported it at meetings. “We” being the community.

Hughes: Did you?

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03-00:35:06 Bishop: Oh, yes. Well, you had to because, to be very pragmatic about it, that’s where you first put your stake in the ground in terms of priority.

Hughes: So that established ownership.

03-00:35:24 Bishop: Well, not formally, but in the mind of the community: oh, Mike Bishop talked about that at a meeting four weeks ago.

Hughes: Would that kind of free-flowing discussion, talking about unpublished results, be likely to happen in biology today?

03-00:35:42 Bishop: Oh, it happens all the time, sure, still.

Hughes: So that hasn’t changed with all the emphasis on patenting and the commercialization of science?

03-00:35:50 Bishop: Well, it varies with the individual. I attend meetings of the Howard Hughes [Medical Institute] investigators where they present their work to each other. These are some of the leading biomedical scientists in the world— 400-and- some altogether. They have smaller meetings. You can rest assured they’re presenting the hottest stuff they’ve got.

Hughes: Knowing that they can claim it because they’ve presented the information?

03-00:36:31 Bishop: No, they want it known that they’ve done it, that’s all, and to share their excitement about the results.

Hughes: Thinking back to Art Levinson and his move to Genentech where CEO Bob Swanson was trying to keep the scientific results quiet until they were published—

03-00:36:55 Bishop: Well, that was a patent issue.

Hughes: Yes, it was.

03-00:36:57 Bishop: Well, it’s a different world. I was speaking only of the academic world.

Hughes: Did you ever have a conversation with Art about how he felt about the need to keep quiet until things were patented?

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03-00:37:11 Bishop: If I did, I don’t remember. But I know what he would’ve said: “Of course, we’re in business.” Generations of chemists are accustomed to this [patenting]. It was just relatively new to the world of biomedical science.

Hughes: Let’s talk a little more about reactions to the oncogene discovery. One, which surprised me, was that Peyton Rous wasn’t a big fan of the oncogene paradigm.

03-00:37:54 Bishop: Well, he never knew about the oncogene.

Hughes: He was dead by the time you published?

03-00:38:02 Bishop: Yes.17 He didn’t believe that cancer was a genetic problem. He was speaking of, quote, “genetics” in the most generic sense. I never met the man, so I never had a chance to talk to him about why he felt that way, and he never went into any great detail about it. It really only came to light in one or two of his late essay publications.

Hughes: I see.

03-00:38:43 Bishop: So I have no idea, really, why he felt that way.

Hughes: I bet you do have an idea of why Peter Duesberg was also resistant.

03-00:38:57 Bishop: No. You’ll have to ask him.

Hughes: I don’t know that I dare to. [laughter] There may be quite a tirade that follows. So you didn’t read Duesberg’s paper, or maybe papers, on the subject?

03-00:39:15 Bishop: Well, I don’t know whether I want to get into this. It seemed to boil down to, all the evidence is circumstantial. Which at the time he was writing was essentially true.

Hughes: It’s a pretty clear title.

03-00:39:36 Bishop: I’m all too familiar with these publications.

17 The publication of what became known as the oncogene occurred in 1976. D. Stehelin, H.E. Varmus, J.M. Bishop, and P.K. Vogt, “DNA related to the transforming gene(s) of avian sarcoma virus is present in normal avian cells,” Nature 260:170, 1976. Rous died on February 16, 1972.

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Hughes: Well, just for the record, it was a publication in Science called “Oncogenes are neither necessary or sufficient.”

03-00:39:47 Bishop: I know the paper, and there were others like it. Did you read it?

Hughes: No.

03-00:39:52 Bishop: Well, read it and I think you’ll see that Duesberg argued that basically there was no direct evidence at the time he was writing that genes are involved in cancer. But I never lost much sleep over it. Our job was to prove or disprove it, and we were just getting on with it.

Incidentally, he’s come awfully close now to our point of view, because Peter for the last ten years has been preaching that aneuploidy, the anomalous number and configuration of chromosomes in cancer, are the fundamental source of tumorigenesis. Now, that’s so close to genetic origin of cancer that there’s not much point in splitting hairs.

Hughes: Yes, I see that.

03-00:40:45 Bishop: Other workers have shown that aneuploidy can affect the control of gene expression. It’s a familiar theme. Anything that affects a malfunction of a genetic accelerator or genetic break could lead to cancer.

Hughes: I believe you wanted to be reminded to tell the story of encountering Gordon Tomkins and telling him about the discovery of cell src.

03-00:41:25 Bishop: Oh, that’s simple. Actually, it was on the phone. I think he called me; I don’t remember. We had just gotten the first data. Now I’m going to have trouble remembering this, his very new age comment. But anyway, I described it to him in about three sentences and told him that I just was really uneasy about it. It just didn’t seem credible. It was so strange. Oh, yes. What he said was, “Mike, let it be.” By which he meant run with it. Let it be could also be read as drop it, but that is not what he meant.

Hughes: Why were you unsettled about the finding?

03-00:42:15 Bishop: Well, it was astonishing.

Hughes: That a normal gene would be at the root of a cancer gene?

03-00:42:24 Bishop: Right. Well, not only that, but that it had found its way into a retrovirus.

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Hughes: It is amazing, isn’t it? What was the state of retroviral research? That’s a huge question, isn’t it? Was it pretty well known that retroviruses were picking up odd bits of DNA?

03-00:42:52 Bishop: No, no, no.

Hughes: So that was a revolutionary finding as well.

03-00:42:56 Bishop: Yes. We now know that they will pick up other genes, too. But this is random, and if the other genes have no effect on the cell in which the virus is replicating, they get lost in the wash. But here was a gene that causes cancer. So that comes to public view. Peter Vogt showed in due course that if you propagate cells infected with Rous sarcoma virus without applying any selective pressure on the cells to behave like a cancer cell— In other words, don’t ask them to grow crowded in a petri dish, keep passing them very dilute,[then] the src gene gets lost from the virus. Gets dropped out. That sort of the lesion is what we used in making the probe that allowed us to find cell src.

Hughes: Why does it get kicked out?

03-00:44:15 Bishop: Oh, it’s just— You can imagine that it’s a mistake in replication. Any other mistake in replicating the genome might be lethal to the virus in question; you’ll never see it. But src’s not essential to the virus. The virus that has lost src can still continue to grow. This is evolution in nature.

Hughes: It’s not the virus saying, I don’t need this gene.

03-00:44:46 Bishop: No. Viruses are not capable of teleology. No.

Hughes: Well, my comment is for the purpose of visualization.

03-00:45:00 Bishop: The fundamental point is that the replication of the virus is sloppy. This is true of all RNA viruses. It’s why flu is such a problem, with constantly changing immunology. They’re very sloppy in how they replicate their genome. Reverse transcriptase is a very sloppy enzyme in copying. So the viruses are generating mutants all the time. They can range from point mutations to deletions. So if there’s no pressure applied that requires src, src is going to get lost in the wash eventually.

Hughes: I see. I should have asked this question long before this, but in 1971 when you were still working on polio but beginning to move towards Rous sarcoma—

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03-00:46:17 Bishop: Oh, ’71, we had half the lab working on Rous already, probably. It was a small lab.

Hughes: Oh, did you?

03-00:46:22 Bishop: Yes, well, reverse transcriptase was published in ’70, and we already knew about it before it was published. That’s when I immediately decided, I’m going to wrap up polio and become a tumor virologist.

Hughes: Was there any thought on your part that this should be an easily fundable line of research.

03-00:46:44 Bishop: No. I did it because I wanted to study this virus. I wasn’t having any trouble getting money to study polio.

Hughes: But there was a general problem with funding?

03-00:46:54 Bishop: No, actually, the NIH was flush at the time. That was not a bad time for NIH.

Hughes: So it wasn’t that the War on Cancer was anywhere in your thoughts?

03-00:47:05 Bishop: No, although the war on cancer eventually became a help.

Hughes: [inaudible]

03-00:47:18 Bishop: Well, once we got going on Rous, we started burning through money real fast. But I had a grant only for polio, not for Rous sarcoma virus. Before we could muster the support by conventional means—say an R01 grant or an American Cancer Society grant, which could take a year or more at the time—the so- called War on Cancer— Nixon did not call it that. But in any event, the NIH was handing out money. The National Cancer Institute was handing out money more rapidly in the form contracts. So the idea was that if the leadership in Bethesda saw something that really needed to be done quickly, they could make the decision to give the investigator the money straight off. No elaborate peer review and so forth. We benefitted from that. We were able to get a contract, along with virtually everyone else working in retroviruses at that point, to shore us up until we got more conventional support. But support had nothing to do with my decision to work on the virus. I saw this spectacular entrée to the cancer cell.

Hughes: Well, there’s the basic scientist speaking again.

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03-00:48:42 Bishop: Well, sure. That’s what was needed at the time.

Hughes: Part of the wording in the National Institutes of Health mandate is something along the line of research for the benefit of the American public. Did that figure in your grant applications? Did you, at some point, feel it was necessary—or expedient maybe is a better word—to present the idea that this very basic research that you were doing would somewhere down the line have a practical application?

03-00:49:30 Bishop: At the time, did I think it was expedient or essential? No. Did I do it if I saw it? Sure. I was by that time serving on [NIH] study sections. If there was some sense that the investigator had a long-range vision of how their research could help human health, that was certainly to their credit. It was not going to get them very much by way of priority scores. But it was just intellectually satisfying. I never disliked writing grants. I liked it. It was a challenge. I like to write. It made you rethink what you were doing. So I would not hesitate to drop in some hope that this [proposed research] would be ultimately useful. Why do cancer research, in any event? That’s what cancer research is all about, right? Understanding the disease and how it happens. You want to do that so that you can ultimately control it.

Hughes: Quoting Dr. B from his book. It’s probably beating a dead horse—namely, the genetic paradigm—but I want to make sure that we get it in its fullness. The quote is, “It now appears that most if not all human cancers contain damage to one or another proto-oncogene.”18

03-00:51:21 Bishop: That remains correct.

Hughes: You went on to write, “In an extraordinary act of unintentional benevolence, retroviruses have brought to view cellular genes whose activities may be vital to many forms of carcinogenesis.”19

03-00:51:47 Bishop: Well, when was that written? Look at the date.

Hughes: Well, it was in your book. Why did you say, “may be vital?”

03-00:51:58 Bishop: Well, I wrote the book in 2000.

Hughes: Was it that long ago?

18 How to Win the Nobel Prize, p. 168. 19 How to Win the Nobel Prize, p. 169.

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03-00:52:02 Bishop: It was published in 2003. I just was being circumspect, that’s all.

Hughes: But you didn’t have any doubts.

03-00:52:13 Bishop: No.

Hughes: Is there something to say about the Cold Spring Harbor meetings? Were they producing any information that perhaps the ones happening in California were not?

03-00:53:16 Bishop: Well, yes, they were broader. There were people from all over the world presenting their results. The meeting that concerned us, it was called “Retroviruses” at the time. So it was about not only the tumorigenic capacity of the viruses but how they replicate. So that was the meeting of the year for us because it was the broadest representation of the field. There were other meetings, smaller meetings, like the Gordon conferences which were not solely about tumor viruses. But the annual [Cold Spring Harbor] retrovirus meeting, that just had to be on your calendar because it was the broadest representation of the field. All the major laboratories would have been there.

Hughes: What happened to the orientation of those meetings when the AIDS epidemic broke?

03-00:54:36 Bishop: I saw that mostly from the outside, but HIV came to dominate the agenda. Harold’s written about this in any event. But I can’t remember. The people at Cold Spring Harbor made a decision ultimately to stop having that meeting because it just no longer was serving the purpose it served originally.

Hughes: Because it was now focused on AIDS?

03-00:55:12 Bishop: Well, the main retroviral research was focused on HIV, and most of us had moved on to other things: cancer-related. Once we knew about oncogenes, I more or less dropped my interest in how the virus replicates. My purpose originally was to work on how the virus replicates. I dropped that in order to focus on the oncogene part of the story.

Hughes: So again stepping back in time, that decision, which we have talked about, where you shifted from polio to Rous sarcoma, it was with no idea that this was going to be a fruitful avenue towards teasing out knowledge about cancer causation?

03-00:56:23 Bishop: The whole point of studying Rous sarcoma virus was to figure out how cancer arises.

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Hughes: Was it not just how the virus replicated?

03-00:56:31 Bishop: Absolutely. But remember, my interest was in the replication of RNA viruses at the time. There was no obvious entrée to the tumorigenic potential. If I haven’t said this before, I’ll remind you that I certainly had the hope of being able to take on the question of how the virus causes cancer. I had my very first graduate student,Nola Jackson. The project I asked her to do was to isolate temperature-sensitive mutants, both polio and Rous virus. The temperature sensitivity there would be ability to replicate as assayed with the plaque assay that we’ve talked about in the past. In the context of Rous sarcoma virus, the temperature sensitivity that would be measured would be the sensitivity of the transformed cells. She never made much progress, and Steve Martin came along and did the job. Got the temperature-sensitive mutants along with the deletion mutations that Peter Vogt and work by Hanafusa performed. Together, these scientists secured the idea that the virus had at least one gene and maybe more than one, but it turns out one gene that’s responsible for the tumorigenesis. So that was on my mind from the very beginning. Absolutely.

Hughes: It’s important to establish that.

03-00:58:08 Bishop: Yes.

Hughes: All right. The partnership with Harold Varmus. Would you like me to start with what you said in your Nobel Laureate about Dr. Varmus?

03-00:58:22 Bishop: You can remind me.

Hughes: Well, I will because I thought it was very wonderful. This was in the acknowledgements. Quoting Dr. Bishop: “I owe a lifelong debt to Harold Varmus. The whole has been greater than the sum of the two parts, or so I believe.”20

03-00:58:51 Bishop: At other times, I have said— How did I put it? The whole is greater than the sum of the two parts, although I may have underestimated Harold. That was it, right. I like that one because it holds out the possibility that Harold was actually responsible for the fact that the whole was not more than the sum of the parts. It was only the sum of the parts. In any event, it was a heartfelt comment.

Hughes: What would you say about a partnership that has almost been made a paradigm of how partnerships might go, not only because of the closeness

20 J. Michael Bishop, “Retroviruses and Oncogenes II,” Nobel Lecture, December 8, 1989, p. 546..

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with which you apparently worked but for the longevity of the partnership? So what was it about the two of you that made that possible?

03-01:00:00 Bishop: I would say first of all, it was proven to be very productive. It began because I recognized that Harold was exceptional, and we fell into this pattern of co- supervising students and postdocs, and it proved to be very productive. Secondly, I think what was important to it was some level of generosity on both our parts about credit. That was a problem because I had a few years head start on Harold and was recognized as a lab leader already, so it took a while for Harold to become as visible, then eventually more visible. So there were some rough edges in there. But basically there was mutual generosity and credit. I think that, along with the fact that we were in other dimensions similar. We’re both interested in the fine arts; we had other interests that were rather similar by and large. I never became a maniacal biker the way Harold did, but I certainly like trout fishing, and I like the outdoors. But intellectually we were certainly on the same wavelength. Yes.

Hughes: Can you say anything about how the division of labor may have played out in terms of organizing and doing the research? Was one of you tending to do one thing and the other maybe taking up a different aspect of the research?

03-01:02:08 Bishop: There was a thread of that. Harold’s first work in the lab was to study integration of the viral DNA. The creation of Howard Temin’s provirus. In due course that became his bailiwick, the replicative aspects of the virus. He continued to contribute equally to our study of oncogenes. But as I said before, I more or less gave up my interest in the replication of the virus to focus on the genes. So that led eventually to a natural division of labor and eventually to the separation of the two labs when I moved up to the Hooper Foundation [George Williams Hooper Research Foundation].

Hughes: Dr. Varmus wrote that your former trainees viewed him as paying greater attention to experimental detail and you to the bigger picture.21 How do you feel about that description?

03-01:03:51 Bishop: Well, I never thought of Harold as lacking a broad view, and I never thought of myself as being disinterested in the details. In my book, I do say that— How did I put it? Basically, my preference was to think about the big picture, and that was probably to my detriment. That’s what I said in my book.

Hughes: Why would that be a detriment?

21 Harold Varmus, The Art and Politics of Science, p. 116.

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03-01:04:38 Bishop: Because you really have to pay attention to the details if you’re a scientist, right?

Hughes: Well, you had him to handle the details.

03-01:04:43 Bishop: Well, first of all, if you’re supervising someone ultimately you do pay attention to the details. Have they run the right control? Why did the experiment not work? They’ll run through with you what they did, and you say, “Well, what’s in that kit?” “Well, I don’t know.” “Well, maybe you should know what’s in the kit if you’re going to try to troubleshoot.” Anyway, I think it’s a fair description of our two inclinations, but I think neither of us lacks the other dimension.

Hughes: Were you both as active in overseeing the trainees?

03-01:05:24 Bishop: Well, for years, it was joint meetings with—

Hughes: We haven’t said much about those joint meetings.

03-01:05:32 Bishop: Well, the students and postdocs would go over their latest experiments, and Harold and I would listen and comment and do what one person would do if they were meeting with their postdocs and students regularly, except there were two of us in the room instead.

Hughes: I like this quote. Again, it’s from your book. “The arrangement between Harold and myself was unusual, widely recognized as such, and much admired. We became a hyphenated self that gave its name to a social organism—the “Bishop-Varmus” laboratory.22

03-01:06:29 Bishop: Or the Varmus-Bishop laboratory sometimes. The Bishop-Varmus was alphabetical.

Hughes: Yes, but you’d been there first.

03-01:06:38 Bishop: Yes, but it’s alphabetical. My ordering of it was alphabetical.

Back in the good old days—they were not so good old from this vantage point—when you gave a talk at a symposium, you had to submit a manuscript for a book, which no one would ever buy or read. They eventually did away with that. I was so glad they did away with that. I just stopped doing it. But

22 How to Win the Nobel Prize, p. 55.

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anyway, I used to introduce my talk with a title slide, and then I would tell the audience, “Anybody whose name begins with an A or W, X, Y, or Z shouldn’t apply to the lab, because it’ll be Bishop at the B and Varmus at the end.” Not of the original articles, but of the symposium article.

Hughes: I’m still struggling to find a description of those weekly meetings in my notes. One of the adjectives that stood out to me was “intimidating”.

03-01:08:01 Bishop: The only thing I know of that is Don Ganem, and he was talking about his meetings with Harold. He was studying hepatitis virus with Harold. I had nothing to do with that at all. And Don described them as they could be intimidating. It didn’t bother him, but it bothered a lot of other people.

Hughes: It didn’t bother Don?

03-01:08:20 Bishop: Right. It’s impossible to intimidate Don Ganem.

Hughes: Say something about why that would be. Was Varmus just so intense that it would put people off?

03-01:08:41 Bishop: Yes. Harold can rattle off quite a few criticisms in a minute and a half. I can too, incidentally. So you’d have to talk to Don about that.

Hughes: My meetings with Dr. Varmus have been so passing that I’m no judge of his personality. But I suspect that there is a fair difference in your two personalities.

03-01:09:27 Bishop: Well, I hope so; we’re not clones.

Hughes: Well, he’s a New Yorker; let’s put it that way. There’s a certain brashness that goes along with that.

03-01:09:44 Bishop: I’ve been known to be brash too, actually. I will grant you that Harold’s higher up on the scale than I am.

Hughes: By the way, he was so positive about the importance of those weekly meetings. What was the Rous lunch?

03-01:10:18 Bishop: Well, that was a weekly meeting when the entire ensemble of people—the students, postdocs, technicians, Harold and I—got together and people presented their work. So the typical lab calls this a group meeting. One or two people give what’s essentially a thirty-, forty-, fifty-minute lecture on the status of their work. That was it, plain and simple.

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Hughes: Would Warren Levinson be at that meeting?

03-01:10:57 Bishop: He probably was early on.

Hughes: But not anybody outside the lab group?

03-01:11:02 Bishop: No, that was just our research group, people working on Rous sarcoma virus.

Hughes: I’ve found the quote that I was searching for, and it came from Dr. Varmus’ book.23 Dr. Varmus has described the weekly meetings with trainees as, quote, “good-humored, intimidating, unrelenting, productive, stimulating, and seemingly essential to our increasing productivity as a laboratory group.” Pretty high compliments, right? But there’s that “intimidating” in there. I can see how a younger person coming up against the two of you would be—.

03-01:11:47 Bishop: Most of them faired pretty well, I’d say.

Hughes: Or they were out of there.

03-01:11:53 Bishop: I don’t think so. Most of the people that went through the lab feel pretty warmly about the place.

Hughes: Well, you’ve mentioned several times, the importance of recombinant DNA in easing the way to cloning the things that you needed to clone. How engaged were you in the controversy that surrounded recombinant DNA? Herb Boyer was just down the hall from you, after all.

03-01:12:26 Bishop: But more than that, we shared equipment, cold rooms, conversations. We were close during those early years. He and his wife Grace, Kathryn and I were friends.

Hughes: Well, what were you thinking of the tempest that was surrounding him?

03-01:13:01 Bishop: Oh, I remember. I was at the famous Asilomar meeting on the safety and regulation of recombinant DNA technology in February 1975. I spoke at the Asilomar meeting.

Hughes: Well, tell me about that. What was the atmosphere?

23 The Art and Politics of Science, p. 116.

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03-01:13:16 Bishop: Well, there are two kinds of controversy. This one was whether it was safe to do this research.

Hughes: But I thought you might be talking about the controversy around Herb in the forming of a company.

Bishop: Well, I was, but then it came to me that what came first was the supposed danger of the technology itself.

03-01:13:36 Bishop: No, au contraire. Genentech was already launched. That wasn’t the issue.

Hughes: No, not quite. The Asilomar conference was in 1975, and Genentech wasn’t founded until 1976. But it was in the air.

03-01:13:55 Bishop: I think it was in the works.

03-01:13:58 Bishop: When did they [Boyer and Robert Swanson] have their first conversation [about founding Genentech]?

Hughes: At the very end of 1975.

03-01:14:04 Bishop: Which of these do you want to talk about? They’re totally separate issues.

Hughes: Asilomar, as I understand it, was a way to get around the supposed danger of the technology and let recombinant DNA research advance.

03-01:14:40 Bishop: Well, the purpose of the meeting was to discuss how real the dangers might be and, if so, what to do about it. There were widely different opinions at that meeting about how real the dangers might be. The hardcore microbiologists frankly thought it was just much ado about nothing, because they felt that it would be— They knew these bugs and how you could control them, not just by physical means but genetically and so forth. So that would be people like Stan Falkow. But then you had the more public policy-oriented molecular biologists, like Paul Berg and Maxine Singer, David Baltimore—they were the key figures in putting this thing [conference] together—who rightly saw that there was going to be a PR problem at the least. So the discussion at the meeting by and large was scientific. When you got to the point of are there any real risks, it was a matter of opinion. There just wasn’t enough science yet.

Hughes: Right.

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03-01:16:11 Bishop: So that culminated in the embargo [on recombinant DNA research] and the formation of committees and the discussions at NIH and elsewhere that led to the oversight by the NIH and the eventual certification of this research. But it was some years before, several years before, the sorts of things we were working with got a green light.

Hughes: Because you were dealing with cancer?

03-01:16:46 Bishop: Yes. I could give you an example. At the Asilomar meeting I was asked to talk about this potential cancer gene in normal cells. So I did. At the end, Sydney Brenner, who was always intimidating, Sydney said, “Well, you’ve explained that you could isolate this gene by molecular cloning. Would you do that experiment now?” I responded, “Well, having heard you, Sydney, over the last two days, no.” Because he and others were adamant that we had to show some fundamental concern about the safety of recombinant DNA research to the public. They were right about that of course. No, we wouldn’t have done that experiment under the context, even though there were sound reasons for doing it. As long as there was any ferment about it, I don’t believe we would’ve done the experiment.

Hughes: Well, that must’ve impacted the trajectory, the speed, of your research if you couldn’t use recombinant DNA?

03-01:18:01 Bishop: Well, it’s only a matter of what could’ve been. We were moving at a certain rate, and we continued to move at a certain rate.

Hughes: But would you not have used recombinant DNA earlier on?

03-01:18:16 Bishop: We used it the day we were allowed to, yes. If I knew what we learned by using recombinant DNA when Sydney asked me that question, I could’ve answered it decisively. I wouldn’t be worried about cloning a normal cellular gene because it’s a normal gene; and the viral gene’s got a mutation in it, and that’s why it’s tumorigenic.

Hughes: I see.

03-01:18:43 Bishop: So let’s talk about whether I may clone the tumorigenic viral gene because the cellular gene is normal.

Hughes: But you didn’t have that information yet.

03-01:18:50 Bishop: Of course not. Couldn’t get it without cloning.

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Hughes: Do you remember the year when you were finally allowed to use recombinant DNA?

03-01:18:58 Bishop: No.

Hughes: But it must’ve slowed you down, because what were you using? You were mainly using probes?

03-01:19:08 Bishop: It didn’t slow us down; it didn’t allow us to accelerate, Sally. There’s a big difference.

Hughes: Yes, I see. There is a difference.

03-01:19:17 Bishop: As I’ve said in any number of contexts, if recombinant DNA had been available to us, we probably could’ve made the discovery in months, rather than taking us four years to nail it.

Hughes: You didn’t fester about the restriction?

03-01:19:37 Bishop: Well, by the time the cloning possibility came along, we were well advanced and fine. We were able to clone and show that yes indeed it is a normal cellular gene. Nobody but the most severe skeptics doubted that it was a cellular gene. It was expressed; we could show the protein was there; it was conserved over a huge phylogenetic spectrum. But when we showed it had introns, then everyone believed it was a cellular gene. Now, that’s kind of silly, but that is how it was. We had to clone the gene in order to show that.

Hughes: All right. Shall we go back to the other aspect of the recombinant DNA controversy? Namely, Herb Boyer and, putting it in broad terms, the commercialization of biology.24 Because he was a close colleague and friend of yours, how about focusing on what it meant for Herb Boyer who in 1976 cofounded Genentech?

03-01:21:04 Bishop: Well, Herb came to me and told me that they were going to do this, and I thought, well, that’s a really high-risk thing to do. But otherwise, I hadn’t had any qualms about it. I understood how things work in our system, right? I understood that if recombinant DNA was going to reach a stage of development that it could be used in the clinic, that was going to happen in the corporate world. That was not going to happen in the academic world. I think

24 For more on the foundation of Genentech and the issues it raised, see Sally Smith Hughes, Genentech: The Beginnings of Biotech, Chicago, 2011.

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my only reservation was whether it was a little premature to found a company based on recombinant DNA. But I didn’t try to talk Herb out of it at all.

There were some other folks at UCSF who immediately seized on the conflict- of-interest issue. This was all new to all of us. Herb hadn’t thought about that; I hadn’t thought about it. But they were very hard on Herb about anything that had to do with Genentech: “He’s got to get Genentech research out of the academic lab. You can’t have secure notebooks lying around an academic lab,” and so forth. My feeling was that all this was so new to us, we didn’t know the rules of the game. Herb, once this was brought to his attention, took appropriate action. So I wasn’t as exercised at all about it as some of my colleagues at UCSF. That may just represent my own naïveté at the time. But I knew that eventually this [commercialization] would have to be done to get it to the bedside.

Hughes: Was the main problem in terms of the critics that the very first set of experiments that Herb and the first scientists at Genentech performed was conducted in Herb’s lab? It was the somatostatin experiments, to see whether a protein indeed could be expressed.

03-01:23:26 Bishop: Well, at that point, frankly, all it represented was an academic laboratory doing experiments supported by corporate funds. Now, that is workaday reality. Had been for a long time in other disciplines.

Hughes: Yes. But not in bioscience.

03-01:23:50 Bishop: But it was just not with us. But I didn’t understand why the general principles didn’t apply. What’s so special about biomedical science that we shouldn’t have corporate support? The problem was that there wasn’t a developed rule book for biomedical scientists to play by, and so people were making up their own rules as things went along. Depending on which side of the fence you were on, they tilted one way or the other. But in principle that research in Boyer’s lab was simply academic research supported by corporate money. The detailed issue was, people who are accustomed to an academic lab, everything is nominally open and shared. We’re all humans; that in reality is not always the case. Whereas here were experiments that were supposed to be kept confidential because of patent potential and so forth. At that time, in that context, that was repugnant to many people. It was not repugnant to a professor of chemistry. But it was repugnant to a professor of molecular and cellular biology.

Hughes: And not repugnant to you.

03-01:25:17 Bishop: I didn’t find it repugnant. I realized that there were going to have to be some rules. I didn’t find it at all repugnant. It was something that had to be done.

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Had to be worked out somehow, because this was how this stuff was going to get to bedside. I never criticized Herb about it; I never spoke against him in public; I never had a problem with the whole idea. My feeling was, this is all new to us; let’s just get the rules straight and let Herb play by them.

Hughes: When you were talking, probably colleague-to-colleague, to Herb, was he baring his soul about why he felt attacked by this criticism?

03-01:26:03 Bishop: No, we never had that conversation.

Hughes: Oh, you didn’t?

03-01:26:06 Bishop: To my knowledge, to my recollection. I was very, very immersed in what we were doing. Herb asked me if I wanted to make a little investment in Genentech, and I said, “No, I don’t have the time to devote to it, to explore it, to think about it even.” That was a big mistake, but anyway.

Hughes: Did he even go so far as to explore whether you might be a consultant?

03-01:26:38 Bishop: I don’t recall that. I would have been a miserable consultant. That was not my cup of tea, what they were doing.

Hughes: Well, one more thing and then I think we should stop. Herb, as you well know, spent years in his early career on restriction enzymes. I haven’t heard you mention using them. But were you?

03-01:27:12 Bishop: Well, when we use the word recombinant DNA, it’s all about restriction enzymes.

Hughes: Well, that’s true. But before that, were you paying any attention to his work on restriction enzymes?

03-01:27:20 Bishop: Oh, absolutely. They just weren’t readily available. The enzyme that Herb studied most, he was purifying in quantities. We wanted to use it, so we got— When he did a purification run, he’d get a Gaussian curve of the material coming out of a column, and we got the little tails and would concentrate them. But you needed the whole battery of enzymes that cut in different ways in order to make it applicable.

Hughes: Was that EcoRI?

03-01:27:58 Bishop: Yes.

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Hughes: What I remember him saying in the oral history, for which you wrote a nice introduction, is that before you and Dr. Varmus arrived, he was dissatisfied with the scientific atmosphere in UCSF microbiology and considered going elsewhere.25

03-01:28:44 Bishop: I was never aware of the possibility that he would leave UCSF.

Hughes: Well, it was before you came. But you changed things, you and the people who were interested in a molecular-genetic approach.

03-01:29:00 Bishop: Yes, right.

Hughes: And there weren’t many before your arrival.

03-01:29:06 Bishop: I’m not sure there were any who were really at the molecular level.

Hughes: Yes, I don’t think there were.

03-01:29:12 Bishop: There were some good immunobiologists—Joel Goodman and Dean Linscott come to mind. That’s neither here nor there.

Hughes: All right. Do you think that’s a place to stop? Because my next topic is the Nobel Prize, and I think that’s probably going to take more time than we have today.

03-01:29:35 Bishop: Yes.

25 Herbert W. Boyer, Recombinant DNA Research at UCSF and Commercial Application at Genentech, an oral history conducted in 1994 by Sally Smith Hughes, Regional Oral History Office, The Bancroft Library, University of California, Berkeley, 2001.

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Interview 4: February 27, 2017

Hughes: We once again are in the home of J. Michael Bishop for the fourth interview. It is February 27, 2017. We will start, with your willingness, with the Nobel Prize. When did you begin to think that a Nobel might be a possibility?

04-00:00:55 Bishop: It was never a very strong expectation on my part, frankly. People can take that or leave it, as they wish. I would say on one or two occasions, someone— I could name them, but I won’t—had said to me, “You realize—” “Really?” That was it. I went to bed the night before, not knowing that the next day was when they [the Nobel Prize committee] make the announcement. I had never paid a lot of attention to this rigid schedule that they follow. So I was oblivious to the fact that the prize for medicine or physiology was going to be announced the next day. I was caught completely by surprise. In all fairness, I immediately understood why it had happened; but it had never been a very strong expectation. It wasn’t something that Kathryn and I ever talked about. Literally had never ever talked about it. And that I had never talked with colleagues about, except that somebody said it to me in passing, and I said, “Really?” That’s the long and short of it. It was not a strong expectation on my part.

Hughes: On the other hand, you and Harold Varmus had gotten the [Albert] Lasker [Basic Medical Research Award].

04-00:02:25 Bishop: Yes, some years before. Seven years before [1982].

Hughes: Often the Lasker is looked at as the preliminary to the Nobel Prize.

04-00:02:31 Bishop: Well, still, the majority don’t get the Nobel Prize.

Hughes: There aren’t enough Nobel Prizes.

04-00:02:37 Bishop: To go around, right? Well, there are. There’s a rule of three for the Lasker; there’s a rule of three for the Nobel. But the Laskers— I’m on the jury; have been for many years. We think we’re fairly prophetic, and we are. The record’s okay. But it’s not inevitable. I certainly didn’t think it was an imprimatur that guaranteed a Nobel Prize.

Hughes: Well, when I asked Dr. Varmus the same question, he replied that he thought it was likely to happen, quote, “We’d won everything else.”26

26 Telephone conversation with interviewer, October 10, 2016.

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04-00:03:28 Bishop: Fair enough.

Harold told me a funny story about this. He was on sabbatical at MIT, not too long before we got the prize. He’d witnessed a wagering game among some of the faculty. I find this sort of repugnant, really. They were so into the prize, they were wagering. They had a blackboard or a whiteboard with a list of possible candidates. I recall that Harold told me this story; I’m pretty sure I have it right. So it was kind of embarrassing. Our names were up there. But I didn’t hear about that, I don’t think, until after we got the prize, and I had answered the same question that you just asked the same way I answer it now. Harold said, “Oh, I was at MIT several years ago and there was this—” I don’t know, I think they were betting on who was going to get it that year, and they had a list of possibilities, something to that effect. It was something that was farthest from my mind when I was struggling to become a scientist. I just wanted to be able to do science.

Several of the things that we got done in the lab over the years were exciting to me. I recognized where this all might lead. I had put it in writing, like Harold had, that our discovery might be representative or a hint of the final common pathway to cancer, once all the various external influences have come to play. But suffice it to say, it was not even on my mind the night before I went to bed. It is on many minds. Lots of Nobels have confessed that they’ve been awake more than one year, the night before. That was not the case with me. I was oblivious at the time.

Hughes: What about Harold? Do you have any idea whether he was waiting?

04-00:05:46 Bishop: That I don’t know. No, I don’t actually know. Well, I’m sure we talked about it; I just don’t remember.

Hughes: What was the reaction of your family?

04-00:06:00 Bishop: Well, my wife was pleased but circumspect. We had two boys and the older one was in high school, early high school, and the younger one was still here in middle school. The complicating factor was that we were going to see a playoff game between the Giants and the Cubs that day, so Dylan, the older one, had already decided he was cutting class and staying home. He took the phone call actually. We had turned the phone off in our bedroom because too many girls were calling too late at night, and we only had one line. So we had disconnected the phone line in our bedroom. There’s still no landline in our bedroom. Well, there is now, but it’s a portable. But the younger one had agreed to help his coach. That’s Eliot. I think it was to sort basketball jerseys or something like that, early in the morning before school started. Kathryn said, “Oh, Eliot, you should stay home. This is a special day. Go to the ballgame and so forth.” “Nope.” So she had to drive him down there. I guess

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they got sort of halfway down there and Eliot had been really quiet. Finally he said, “Mom, what is this Nobel stuff about anyway?” They’d never heard. We hadn’t talked about it. He had no clue. He gets to school, and one of the secretaries is Swedish, and this is a big deal to the Swedes. She greets Eliot at the front door like he’s a long lost child. “Eliot!” Eliot says, “What’s going on?” She says, “What are you doing here? You’ve got to go home. This is a big day!” So he agreed to come home and go to the playoff game, which the Giants won in a dramatic manner. So that’s how the family responded, each in their own way. Dylan didn’t quite get it until he went to school the next day. There was an assembly that day, and when he walked in there was this huge banner. “Congratulations.” The school was excited. One of the parents had won the Nobel Prize. Dylan was like, what’s going on? I’m no sports hero.

Hughes: Well, this shows another interest of yours—baseball. I got this from your book that you had planned to be at the Giants’ batting practice. The original press conference was scheduled for eleven a.m., and you said, “No way. I have to go to the batting practice.” The press conference was rescheduled.

04-00:09:13 Bishop: Well, my sons wanted to be at batting practice, that’s for sure. It was the ritual. Also the traffic. So they moved the press conference to earlier in the morning. The reporters were delighted because it made it easier for them to make their deadlines. But the national press gets you on the phone at three a.m., and they’ve already written their pieces by the time the press conference has happened here.

Hughes: It was CBS, as I recall, that broke the news to Dylan, rather than the Academy.

04-00:09:52 Bishop: Well—and this is not the first time this has happened—that’s because the Nobel committee had the wrong phone number. There was another J. Michael Bishop who lived in Belvedere.

Hughes: Oh, you’re kidding!

04-00:10:07 Bishop: He’s an engineer. So they called him at three o’clock in the morning. He said, “You’ve got the wrong man. I’m an engineer; we don’t get Nobel Prizes. But I have their phone number because these girls keep calling here, and I have to refer them to your house.” That’s true. [laughter] So our phone line was dead in the bedroom. But he was taking calls for them apparently. Because he literally gave them [the Nobel Committee] the right phone number.

Hughes: Right.

04-00:10:41 Bishop: They announce [the Nobel Prize winner(s)] at noon in Stockholm. The press immediately gets on the phone.

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Varmus and Bishop Nobel Prize press conference

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Hughes: As you well know, the Nobel Prize can be awarded to a maximum of three living people. If it had been a third person, do you care to say who you think it might’ve been?

04-00:11:45 Bishop: No. I don’t think that’s fair, and I’m not sure I could limit it to one additional person.

Hughes: One reason I ask that is because Harold Varmus volunteered that Dominique Stehelin was disturbed that he wasn’t included.27

04-00:12:15 Bishop: Well, he’s not the first.

Hughes: Is that so?

04-00:12:17 Bishop: Others have disputed the Nobel committee’s decisions, right? Far from being the first, nor the last.

Hughes: He had done some really critical—

04-00:12:29 Bishop: He did the crucial experiments, right. He did not conceive them. And the work had been in progress in the lab for a year or more before he picked it up.

Hughes: He was a postdoc at that point?

04-00:12:46 Bishop: Yes, by American standards. I forget now; it’s a long time ago. I think he had had some postdoctoral work in France and then applied to me. So nominally in the U.S. system, he was a postdoctoral fellow. But he may have seen himself in a slightly different light because of the way the French academic system works.

Hughes: Has that all been smoothed over now?

04-00:13:10 Bishop: It’s history.

Hughes: I read that each laureate can invite up to twelve people to attend the actual ceremony in Stockholm.

04-00:13:26 Bishop: Yes.

Hughes: Whom did you invite?

27 Telephone call with interviewer, October 10, 2016.

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Bishop family at the Nobel Ceremony, Stockholm, December 1989. Left to right: brother Stephen, son Eliot, sister Catherine, wife Kathryn, mother Carrie, JMB, son Dylan, father John.

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04-00:13:31 Bishop: Well, first of all, this is the stuff of legend. Most laureates wheel and deal vigorously to up the ante. The record’s in excess of twenty-five. Because if you have friends in Sweden who’ve got some tickets, and they don’t want to use them— I got some from a good friend, a couple of them. Et cetera, et cetera. So we had more than a dozen.

Hughes: I presume your whole family went.

04-00:14:04 Bishop: Yes. My brother and sister, of course my parents, and my aunt and uncle, the aunt who was my godmother. We talked about her, I think.

Hughes: Yes.

04-00:14:21 Bishop: Then Harold and I, we jointly invited the technical staff that had been part of the lab and kept it running and so forth. There were, I’d say, roughly five.

Hughes: What a thrill for them!

04-00:14:44 Bishop: Oh, they had a wonderful time. They stopped in London and partied first, as I recall, and then went on to Stockholm. And I invited—and he came with his wife—Elmer Pfefferkorn. Remember?

Hughes: Yes, I remember.

04-00:14:58 Bishop: My first long-term research mentor, at Harvard. And the two medical deans who presided over the school at the time of the research. And Warren and Barbara Levinson. As I recall, those were the people who were there as my guests.

Hughes: Not your mentor from the two-room schoolhouse?

04-00:15:19 Bishop: You mean the teacher.

Hughes: Yes, the teacher.

04-00:15:20 Bishop: I think he was deceased by then. He would definitely have been a duck out of water.

Hughes: Unfortunately, I never knew your wife. But I get the impression that she wasn’t easily impressed by folderol. Am I right about that?

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04-00:15:56 Bishop: You’re quite right about that, yes. One of the reasons I loved her.

Hughes: So how was she responding to all this?

04-00:16:03 Bishop: Well, she was pleased. She didn’t take it too seriously; witness the fact that she waited till we got to Stockholm to buy a gown. She bought it the day before the ceremony and banquet, the dance. Well, needless to say, the department store was the best one in town. It had been arranged by Nobel staff. Everybody who was anybody in the store was waiting for her. She had all kinds of help choosing the gown. But she was not about to run around San Francisco and shop. Actually, you can see the gown in that picture over there. It’s a photograph of her dancing with Eliot at the Nobel ceremony.

Hughes: From the various accounts that I’ve heard, including from your book where you give quite a full account of the ceremony, that she could hardly fail to be impressed by the formalities.

04-00:17:24 Bishop: I guess that’s fair to say. As I said, she was very circumspect about the whole thing.

Hughes: How were you feeling?

04-00:17:31 Bishop: Well, it was a stressful time because you have to give your address. There you are, a Nobel Laureate, and you damn well better do well.

Hughes: A lot of pressure.

04-00:17:45 Bishop: Yes. And jet lag. And I was ill. I arrived with severe bronchitis. I lost my voice completely two days before I was to give my lecture. Of course, the Nobel Foundation was frantic about that, and so they took me to see the physician who takes care of the opera singers at the Stockholm opera. On the day he was to see me, he was visiting at a very large mental hospital. So I was taken to that facility and walked through the lobby with these people looking at me, wondering what my problem was. [laughter] I just wanted to scream, “I have laryngitis!”

Hughes: I’m not crazy!

04-00:18:42 Bishop: Right. So he said, “Now, I know you’re trained as a physician, and you’re not going to like what I’m going to do, but I’m going to put you on antibiotics and steroids. You almost certainly have a super infection, and the steroids will shrink your vocal chords, because that’s why you’re hoarse, enough so you’ll be able to talk.” He says, “I do that for the opera singers all the time.” Then I

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had the vivid recollection of that vocal teacher that I had when I was a youngster. If I showed up and wasn’t in good voice, she would spray this obnoxious stuff down my throat, which I think had some sort of a vasoconstrictor in it. God knows what. The old image from my childhood of an opera singer is they’ve got a squirt bottle. But anyway, I took the steroids by mouth, and indeed I was able to talk. Barely. It was really difficult. But I was able to talk.

Hughes: That was an anxiety.

04-00:19:52 Bishop: Oh, yes, on top of everything else.

We had tickets to one of my favorite operas, Tosca. I went to the opera, and we had a lovely dinner scheduled afterwards. We had several friends there as well. But I just had to go back to the hotel and go to bed.

But we had a good time. They’ll take you to anything, let you do anything. There’s a small, exquisite gallery [Thiel Gallery] there that they took me to, because I knew it from before and liked it a lot. They took me to it on a closed day so I could have it to myself. My brother and I went. We had it to ourselves. That was quite something. In my book, I recall this moment. I’m in a room with a death mask of Mahler. I think that’s right. I’m looking out over the snow-covered park this little museum is in. I think that’s the first time it really hit me, the magnitude of what had just happened to me.

Hughes: Really?

04-00:21:11 Bishop: Yes. Because of the frenzy of preparing, the endless hours working on the talk beforehand, and still doing the other things we do. You finally get there. For me at least, it was the withdrawal from my daily quotidian affairs that this thing really struck me, finally.

Hughes: Were those feelings mixed? Or was it more elation?

04-00:21:52 Bishop: Well, they certainly weren’t mixed. I was perfectly delighted that Harold and I had been recognized in that way. So I can’t say that there was anything troubling about it. I have to say this because I’m on the record in my book about this: I have my reservations about prizes for science. I think they can distort motivation. I get uncomfortable sometimes with how students, trainees invest perhaps too much importance in all this. Not to mention established scientists. That’s not why we do science. But it’s still portrayed and widely viewed as the be all and end all, the culmination that you aspire to, and once it’s done, you’re done.

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Hughes: It’s not a profound thought on my part, but science is portrayed as a collaborative venture, right? And in most cases it is, including in yours.

04-00:23:26 Bishop: Yes.

Hughes: You’ve said that there were other people who definitely contributed to the discovery.

04-00:24:03 Bishop: Yes. It’s not the collaborative nature of science that can be misrepresented by something like a prize; it’s the cumulative nature. We all stand on the shoulders of previous people and giants, in the legendary words of Newton. But there are these singular discoveries that stand out. I just saw this again in the New York Times yesterday, actually, and it’s what I said in my book: that if these things [prizes] have any lasting value at all, it may be cultural in nature. The fact that the public pays so much attention to the Nobel Prize, for example, means that for a brief moment every year science is front and center in the news. People are in some way or another thinking about, oh, why is this important? So I think there’s value in that. And it’s true of the Lasker Award. I also have heard others justify singling out particular discoveries because it does get the attention of the general public. It’s the sort of thing the public can identify with. They don’t have to worry about understanding the details of science. So I think if there’s cultural value to it, that’s it. That’s the principal one.

Hughes: My question about whether you might have had mixed feelings when you were in a room with Mahler—and I think it’s significant that it was Mahler—.

04-00:26:08 Bishop: Oh, yes. He’s number two on my list, right after Bach.

Hughes: The prize comes with a lot of political and statesmanship responsibilities. I think of you as a basic scientist; that has been the underlying momentum of your career. Was it occurring to you that maybe all these extra-scientific responsibilities would divert you from your first professional love, namely laboratory science?

04-00:27:07 Bishop: Well, I wasn’t exactly a political naïve to begin with. Scientists notoriously want to stay out of the political fracas, right? But I had been fairly active already in advocating science for the public in various ways. Even as an assistant professor, the American Cancer Society took me around California to around six venues, mostly state college campuses. I went up to Eureka; I went to Fresno, places like that, and gave a public lecture on cancer and the research that was being done on cancer. I had experience going to the Hill, Capitol Hill in Washington. So I didn’t feel like a new mantle had settled on me.

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Hughes: I see.

04-00:28:08 Bishop: I’ve always been a little uneasy about this bully pulpit thing. I wouldn’t want to have to count the number of things, each one of them meritorious— resolutions, pleas to the public, pleas to this or that dictator—that laureates are asked to sign. And every time you sign this, you’re kind of diluting your political capital. So I don’t sign most of them now. I think many laureates don’t sign most of them for that very reason. In any event, I didn’t feel as if some special mantle had settled on me.

Hughes: You didn’t have any second thoughts: do I really want this prize?

04-00:29:03 Bishop: Oh, no. You can’t help but think, do I really deserve this prize? But that’s easily dismissed, too.

Hughes: Once you had your feet back on the ground again, returned to UCSF and the responsibilities that that entailed, do you remember feeling, I’ve got to be very careful about what things I agree to do because the main thing I want to continue is my laboratory science and running my laboratory?

04-00:30:00 Bishop: I didn’t find any exorbitant demands being made on my time because I was accustomed already. Sure, high schools might not have thought of inviting me beforehand, but now they did, and I was perfectly willing to do that because I was doing a bit of it already. I don’t recall feeling that I had been extravagantly burdened by the award.

Hughes: I thought maybe the chancellor— Would it have been [Joseph B.] Martin at that point? Well, whoever was chancellor in the late eighties might have been parading you before potential donors.

04-00:30:51 Bishop: Juli [Julius R.] Krevans paraded me before I received the Nobel Prize, as did Rudi Schmidt and Joe Martinafterwards. Well, yes. Again, it wasn’t excessive. I was already doing it because I was a prominent scientist already. I was glad to go and chat with donors and talk to donor groups, yes. I felt it was part of the responsibility of being a prominent scientist. It’s part and parcel of our obligation as scientists. I just viewed it as another opportunity to educate the public about fundamental research, what the university is all about, why it’s important. That’s the case you make to a donor, just as it’s the case you make to the general public, in an effort to get their good will in terms of having both the government and philanthropists support research.

Hughes: What happened to applications from graduate students and postdocs with your increased visibility?

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04-00:32:01 Bishop: Well, first of all, Harold and I already were quite visible.

Hughes: Yes, you were.

04-00:32:07 Bishop: So I think we were already enjoying about as much success, as much attractiveness, as we would after the prize. The really good students and potential postdocs, they don’t tell you they want to work with you because you’re a Nobel Laureate, right? They tell you they want to work with you because they’re interested in your work, and they’ve heard you’re a good mentor, and so forth. So I did not sense there was a big impact from that. Some [laureates] who might have been less visible for whatever reason, I know it has had an effect. It has had an impact on their attractiveness. It’s unfortunate in a way because it’s kind of a false value.

Hughes: Right. It should be scientific achievement—

04-00:33:20 Bishop: Yes.

Hughes: —rather than fame that attracts people.

I read about the Coalition for the Life Sciences. Was that one of the aftermaths of receiving the Nobel? Or was that an independent occurrence?

04-00:33:58 Bishop: That occurred simply because this thing [the Coalition] was nucleated at UCSF, and I was one of the faculty who would obviously participate. As I remember it, it was Professor Marc Kirschner who got us together first. There had been conversation among us about being more active politically. These discussions went pretty much hand in hand with the group of senior faculty who were trying to put together an umbrella graduate program, which we eventually succeeded in doing, called PIBS [Herbert W. Boyer Program in Biological Sciences].

Hughes: PIBS was that late in founding?

04-00:34:43 Bishop: No, but it was the same group of people who talked to each other about such things. I think Marc got us together originally, and it was just natural that I would be part of the group that would do this.

Hughes: What were you hoping to accomplish?

04-00:35:04 Bishop: Increase the public understanding of science and increase the funding of National Institutes of Health and the National Science Foundation by the federal government.

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Hughes: Did the group lobby?

04-00:35:15 Bishop: Yes, we hired a lobbyist. That caused quite a ruckus with some of the professional societies we worked through since quite a number of us were members and Marc was a leader at the time, and I too was going to be president of the American Society of Cell Biology. So that’s where we found our first organizing capacity.

Hughes: Meaning embracing that—

04-00:35:50 Bishop: Well, they had an infrastructure we could work with. We needed organizing assistance. We couldn’t do it through the university.

Hughes: Why not?

04-00:36:05 Bishop: It’s a political act for which we could not use university resources. So it didn’t take us long to figure out that we were not going to get through the right doors on the Hill alone. We certainly weren’t going to see members (senators and representatives) very often. So we hired a lobbyist. Low-profile man, Peter Kyros, who was a former member of the House of Representative from Maine. He and a female colleague, Belle Cummings; they were a lobbying firm of two. And doors started opening. A number of the professional societies that we were trying to—and often eventually successfully—recruit into this coalition were appalled. Lobbying? That’s dirty stuff. It’s ugly. It’s politics. Exactly, we are playing politics. That’s exactly what we’re doing, we’re playing politics. That’s the way a republic works. You have to figure out how to reach your representatives, and in this day and age, you can use professional assistance. You use professional assistance for other things; why not use professional assistance to reach members of Congress? So I was part of it because I was part of a little community of faculty who had been talking, friends, and working together for years on things of common interest in academia.

Hughes: Was the main push of the two lobbyists more funding for basic science?

04-00:38:07 Bishop: Yes, that was our goal. They taught us a few things. We didn’t know about caucuses. Some of us knew they existed. For example we had heard of the Congressional Black Caucus. Caucuses are self-formed special interest groups within Congress who share some common concerns. There might be the coal mining caucus or whatever. The first thing that our advisors said, “We have to get together a congressional biomedical research caucus. It doesn’t exist on the Hill. We know a few members who we might be able to persuade to be chairs. They’re figureheads. We will do the organizing work, get the room on the Hill for the meetings; you guys should do the program.” I did the program

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for nineteen years myself. I identified six or seven speakers each year from the academic community—the biomedical community in our case mainly—who

we thought could probably communicate with non-scientists who were legislators. It’s the congressional staff you’re really reaching most of the time, and that’s important because they’re telling the boss what to do, in all honesty.

[interview interruption]

Hughes: Did that work pretty well?

04-00:39:47 Bishop: Oh, yes. It’s still running. Various speakers over the years. No one has ever turned us down on principle. And a very wide variety of topics. The attendance is typically staff. If it’s a subject that hits home to a member, like prostate cancer or breast cancer, they may show up. A few members of Congress who are truly vested in science, either have scientific background or they’ve made biomedicine their cause, like John Porter— He was a powerful assist in Congress when he was in Congress. But basically it was again an educational exercise. We told the speakers, “Don’t go there and beg for money. Just tell them about your world, your field. Bring them up to date.”

Hughes: The hope was that the staff might then go to the congressmen?

04-00:41:13 Bishop: Well, the staff is the people who participate in policy formation with the member. I’ll give you an example. We went to see Steny Hoyer who is still a senior figure in the Democratic party leadership. He was very cordial and receptive. However, before we met with him in person—this is Marc Kirschner and I—we had a long chat with his staff person assigned to health. A very bright woman. We got about three minutes into this, and she said, “So I get it. You want an increased funding for NIH.” We said, “Yes.” She said, “Well, great! Stick it to him. I’ve been working him on this for months.” Literally, that’s pretty much what she said. She said, “I really need your help.” So it was totally unexpected.

Hughes: And totally appreciated.

04-00:42:22 Bishop: Yes, right. She was competing with other staff who were more concerned about Social Security or the other things that are covered by the same department. They have all these agencies within the Department of Health and Human Services, and they’re all competing for the same pot.

Hughes: Did you get an audience with Hoyer?

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04-00:42:46 Bishop: Oh, yes, we were there to see him. It was just she came in and chatted with us in advance.

Hughes: So she wasn’t the gatekeeper; if she didn’t like your argument, you wouldn’t see Hoyer.

04-00:42:57 Bishop: No, we were set to see him.

Hughes: Are you still doing stuff like that?

04-00:43:04 Bishop: I stepped out of the coalition while I was chancellor, but I actually just rejoined it. It’s still running.

Hughes: We need it, if you don’t mind my saying.

04-00:43:16 Bishop: This only works with reasonable people.

Hughes: Up to the time of the chancellorship, were you still hands-on, doing basic research?

04-00:43:47 Bishop: No, I wasn’t at the bench anymore.

Hughes: When had that stopped?

04-00:43:52 Bishop: Well, I honestly can’t remember exactly. It was a gradual withdrawal as the lab got larger and my responsibilities increased. It’s so exceptional if this doesn’t happen to academic scientists. The ones who finally die having never left the lab bench and never having had more than three or four people working with them, that’s always a featured part of their obituary in the scientific journals. But in any event, I’d say I was doing nominal things in the lab until about the time of the Nobel Prize.

Hughes: Should we move to the Hooper Foundation [G. W. Hooper Research Foundation]? Googling the Hooper Foundation, all I could find was information on Karl Meyer.

04-00:44:55 Bishop: Well, it had shrunk so much that it was just one floor in Health Sciences West by the time I became director [1979-2016].

Hughes: Well, then why were you interested in becoming director?

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04-00:45:19 Bishop: It allowed expansion; it allowed more room for my research group. There was an endowment that could be used for my research and research of other people in the Hooper. Harold and I were in very bizarre research space. It had grown like Topsy, and some of it was without windows. It was a rabbit warren, we both called it. So this was an opportunity to redesign the whole floor. My objective was to augment the department of microbiology which was financially strapped and not adding new talent. So I used the Hooper to house three new recruits in the micro department at any given time. The first one just retired, Tony [Anthony] DeFranco, an immunologist.

Hughes: Spatially, the Hooper is on a different floor than microbiology?

04-00:46:39 Bishop: Well, microbiology, like other departments, is here, there, and everywhere.

Hughes: Yes. So it’s not just on the fourth floor anymore.

04-00:46:48 Bishop: No.

Hughes: Where is the Hooper?

04-00:46:52 Bishop: The Hooper’s on the fifteenth floor of HSW [Health Sciences West].

Hughes: In new space.

04-00:46:59 Bishop: Well, not now. We renovated at the time. I never wanted to put big money into it again, and it was still running quite fine. My last major project before I stepped down was housing three new faculty. Because the space had cleared by retirement. Don Ganem, who was on that floor with me, moved to Roche. So we renovated while I was still director. We renovated one of the lab spaces. The other two will be renovated, I presume, in due course, for the three faculty. They’re already there. They were all recruited by the department and me.

Hughes: Underlying everything you’re saying is the premium that was placed by faculty on space.

04-00:48:05 Bishop: Well, sure.

Hughes: So some of the motivation was to get more space?

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04-00:48:30 Bishop: Yes, and to help the microbiology department. The opportunity was there. I asked the micro department to fill the space that I wasn’t occupying. I said, “Please, recruit some new young faculty into this space.”

Hughes: Did you ever consider or were you ever asked to be chairman of microbiology?

04-00:48:57 Bishop: No.

Hughes: Weren’t you an obvious candidate? It could’ve been chairman of microbiology versus director of the Hooper.

04-00:49:20 Bishop: Well, director of the Hooper was a cushy job in a sense. My colleagues there were all tenure tracked in the micro department. Administering their academic career was the department’s job. The things a departmental chair worries about, I didn’t have to worry about as director of the Hooper. I wasn’t at all interested in being a departmental chair.

Hughes: Harold was in the Hooper—

04-00:49:59 Bishop: No, he was never in the Hooper. He stayed on the fourth floor and expanded his purview.

Hughes: He wasn’t technically in the Hooper.

04-00:50:07 Bishop: No, he declined. He wanted to have greater independence, or the perception of independence. Needless to say, Harold was fully independent from the get-go.

Hughes: He said as much to me over the phone, that he felt the time had come to cut the umbilical cord, if it ever existed.28 Maybe it existed in his mind but nobody else’s.

04-00:50:42 Bishop: It certainly didn’t exist in my mind.

Hughes: Geographic separation didn’t have any negative effects on the collaborative research that you had been doing?

04-00:51:05 Bishop: Well, as I mentioned I think in one of the previous interviews, we were diverging to some extent. Harold had well-identified spheres of influence that I was not involved with. He had his own postdoctoral fellows and so forth. So

28 Telephone call with interviewer October 10, 2016.

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it just meant that we weren’t on the same floor anymore. We still had some joint meetings for a while. Then he went off to NIH not too long after that [1993].

Hughes: Had your research begun to diverge, too?

04-00:51:50 Bishop: Yes, that’s what I’m saying. We were both interested in the same things, but the research in the labs was tending in different directions.

Hughes: But still the endurance of this team of you and Harold potentially set all records for its long longevity.

04-00:52:22 Bishop: No, I think the record holders are Mike [Michael S.] Brown and Joe [Joseph L.] Goldstein.

Hughes: Anybody else?

04-00:52:28 Bishop: No, I don’t know of anybody else.

Hughes: That’s still a pretty rarefied group.

04-00:52:31 Bishop: Rarefied’s another matter, but rare, yes.

Hughes: I don’t have a wealth of questions about the Hooper.

04-00:52:47 Bishop: I think it’s appropriate.

Hughes: One thing, though, because Karl Meyer is a name that stand out in UCSF history. The Hooper has always been associated with infectious disease, in one form or another, am I not right?

04-00:53:14 Bishop: Not really. Its charge is one clause: do medical research.

Hughes: That broad?

04-00:53:22 Bishop: Yes. It came to be because a very wealthy man’s wife, Sofrani Hooper, went to the Far East, came back with some ailment that was fixed by medical care here. So she and her husband decided that they wanted to put money into medical research. Their model was the Rockefeller Institute. It was not a university at the time; it was a freestanding research institute. So they endowed a research institute at UCSF, freestanding of the faculty, and it had its own building, long gone. A small building situated along Medical Center Way. If you’re on the fourth floor of the elevator lobby between Health

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Sciences West and Health Sciences East, and you were to look uphill towards the top of Mount Sutro, it was in that area. There’s still an empty lot there. It’s still called the Hooper Pad. That’s what left of the building. Nicholas Petrakis was the director for many years, and then the Hooper was an epidemiology unit.

Meyer was a microbiologist and particularly an infectious disease specialist. He was a formidable figure. The institute was his. It was Teutonic. Everybody in it was essentially his sycophants. He made his name with several things. In particular, one of his accomplishments involved the canning industry in California. They were having trouble with botulism, and he solved that for them. I don’t know the details. He discovered one of the equine encephalitis viruses that also infect humans. That’s a great story. I have a huge tin full of old-fashioned movie tape, his telling of how he discovered the virus. The UCSF archives have it. We used to show it. I endowed a lectureship in his name after I became director. It’s still running. It’s run by the infectious disease division.

This virus was killing horses right and left. No one had been able to isolate it. Meyer had tried and failed, and he decided the problem was that they were getting the brain tissue too late. They were getting it after the horse had died, and another day before the veterinarians s could autopsy. So he wanted to get one that was still alive but suffering from the disease and kill it and get the brain tissue. He had scouts out in the Central Valley, and they informed him about a small-time farmer who had a horse that was clearly on his last legs with equine encephalitis. So Meyer went down personally and asked the farmer whether he could take the horse, and the farmer declined. So I don’t remember the exact details, but somehow Meyer was able to get his wife aside, and he cut a deal with her. I think it was fifty bucks, I’m not sure. He would pay her fifty dollars if she would let him know when they were going to bed. This is a true story. They agreed on which window blind she would pull up when the lights go out. Then he went in and sacrificed the horse. He brought the head back and got the virus.

Hughes: That was the first isolation of that virus?

04-00:58:31 Bishop: Yes. So that’s the kind of character he was. He was at Penn before he came here, University of Pennsylvania. He had veterinary training. He is reputed to have made a bet and won the bet that he could autopsy an elephant in full evening dress.

Hughes: Which then he proceeded to do?

04-00:59:00 Bishop: Yes.

Hughes: I won’t ask where they got the elephant; I don’t want to know.

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04-00:59:04 Bishop: Well, elephants do die. And the Philadelphia Zoo had elephants.

Hughes: Just so long as he didn’t help it along.

04-00:59:10 Bishop: There’s no suggestion of that in his history.

He was very close friends with Sir [Frank] Macfarlane Burnet, a Nobel Laureate from Australia. In Burnet’s autobiography, he talks about visiting Meyer. They would climb Mount Tam [Tamalpais] from the bottom.

Hughes: Well, these colorful characters are wonderful, aren’t they?

04-00:59:36 Bishop: Yes. Meyer was still doddering around, I think, in my very first years at UCSF, and I may have passed him once or twice in a hallway, but I never met him.

Hughes: Another strong personality, whom I actually worked for very briefly, was Julius Comroe.

04-00:59:56 Bishop: Yes.

Hughes: Did you have much interaction?

04-00:59:58 Bishop: I knew Comroe once I got here; I didn’t know him before I came. But he quickly became known to me because he was one of the few credible scientists at UCSF at the time. He was a very different scientist than I was wanting to be. He was a physiologist essentially. He was known to be running an excellent unit, [the Cardiovascular Research Institute]. It was the one place at UCSF where there was really first-class science being done—with a few exceptions. But I never got to know him.

Hughes: So Comroe wasn’t a lure.

04-01:00:43 Bishop: No. I came here because of Leon Levintow. End of the story.

Hughes: When I was a student here in the 1960s, it was a mediocre biomedical institution.

04-01:01:07 Bishop: Holly Smith [Lloyd H. Smith, Jr.] was fond of saying, when he arrived here, it was a trade school.

Hughes: You came for the people doing microbiology. I gather you didn’t really care about the status of the institution.

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04-01:01:24 Bishop: I came because of Leon Levintow, period. I had never met Herb. There was no recruitment process. Leon had me come out and look around. I didn’t give a seminar or anything like that. I met Herb, who was the one other person in the department who was thinking the way I thought about science.

Hughes: Well, Warren Levinson as well, right?

04-01:01:48 Bishop: Yes. But Warren was not molecularly inclined. Herb was the one person who was doing molecular biology, as we knew it to be then.

Hughes: Well, you saved him in many ways, because I think I told you that he had been unhappy because he didn’t have colleagues that had the molecular interest.

04-01:02:15 Bishop: Right.

Hughes: With your arrival and then Harold’s, things really looked up.

04-01:02:23 Bishop: Yes

Hughes: And the rest is history.

When you retired at the beginning of the summer of 2016, the Hooper Foundation was disbanded. Why was that?

04-01:02:45 Bishop: Well, I think it still exists on paper. It’s simply, the chair of micro[biology], Lewis Lanier, is also the director of the Hooper. He’s chair of microbiology and director of the Hooper Foundation.

Hughes: So it isn’t completely disbanded?

04-01:03:04 Bishop: No, it’s still an entity because there’s money there, endowment funds. There’s FTE money.

Hughes: My misinformation.

04-01:03:16 Bishop: Well, it’s a subtlety. It’s always been part of the department of microbiology since I took over.

04-01:03:37 Hughes: Do you want to start on the chancellorship?

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04-01:03:56 Bishop: Well, why don’t we start and see how far we get.

Hughes: Please tell me how the idea and then the offer for you to step up as chancellor came about.

04-01:05:23 Bishop: Well, Joe Martin left rather abruptly [1997].

Hughes: Why was that?

04-01:05:28 Bishop: He became dean of Harvard Medical School. It seemed that was more attractive to him than being chancellor of UCSF. I can understand that. The dean, that’s the principal academic officer of a school, right? The chancellor’s job—to quote one of the most ignominious things I was told while I was chancellor—is to make the trains run on time. Don’t butt into the academic sphere. I will tell you that I was very surprised to find that chancellors at most if not all of the other [University of California] campuses have the ultimate sign-off on a faculty appointment. I never signed off on any faculty appointment. That was the dean’s business. In any event, Joe left abruptly, and Haile [Debas] stepped in as a chancellor for a year [1997] while he was still dean of the School of Medicine. He did both jobs, which is really quite something.

I think it was Haile; I can’t remember who first approached me about whether I had any interest in the chancellorship whatsoever. I know I had communication with Haile about it. I said no at first. Then Haile and I had another conversation. I think it was at the going-away party for Joe Martin which was held, I think, at the St. Francis Hotel. Haile and I had another conversation, and I said, “Okay. Well, listen, I’ll consider it. I’ll think about it.” Then in due course, the president [Richard C. Atkinson] contacted me and asked whether I was willing to stand as a candidate and be interviewed by the search committee. It’s a process that is rather remote from the campus. The search is run formally by the regents. The president runs it, but the regents participate wholeheartedly. Then there are representatives of the Academic Senate, both statewide and campus, on the committee, and a few others. But it’s not a family affair.

Hughes: They were appointing the top job for the UCSF campus, with a diversity of people, most of them not connected with UCSF, making an appointment that was going to affect people’s lives on this campus.

04-01:08:33 Bishop: I think given the governing structure of the University of California, it’s inevitable because the regents have the final fiduciary responsibility. The University of California is in the state constitution, right? That’s the reason that the University of California does things that the state universities cannot

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do because they are not in the constitution. So it’s very hard for the legislature to intervene in the affairs of the university, other than with the budgetary whip. The local community is reasonably well represented on the committee. But the key figure is the president. If the president has the pulse, he or she usually knows whom to call on a campus to talk about things. I know for a fact that the president called people like Holly Smith about the search. Suffice it to say, in due course I was appointed. I think there were three people who were interviewed.

Hughes: Do you know who the other two were?

04-01:10:08 Bishop: Yes. I don’t want to reveal that. It was common knowledge, I think, but I was pledged to confidence.

Hughes: Remind me who was president at that time.

04-01:10:22 Bishop: Dick Atkinson.

Hughes: So what happened next? You obviously were appointed.

04-01:10:32 Bishop: I was interviewed, and I got a call the next day from Dick, offering me the job. I had already been briefed by some of the senior officers on the campus about things that the president ought to come up with for the next chancellor, right?

Hughes: You mean money for this and that?

04-01:11:02 Bishop: Yes, sure. And some policy changes, like indirect costs, how much is staying in Oakland [location of the UC Office of the President] and how much is coming to the campus. That was a big issue when I took office, and we eventually cracked that nut. But I didn’t crack it on my first phone call with Dick Atkinson.

Hughes: Meaning that you negotiated more money coming to UCSF?

04-01:11:21 Bishop: Meaning we wanted a larger fraction of the indirect costs awarded on grants from the federal government. Yes. In any event, I started with my bill of particulars, and Dick said, “Forget about it. I’ve done all I can do for UCSF. Either take the job or leave it.” I said, “I’ll call you back.” So I called him back eventually and took the job.

Hughes: And why?

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04-01:11:48 Bishop: No profound reasons. I sometimes still ask myself that question. First of all, people in my confidence had made it clear that they thought I would be good for the job, and that they would be very happy if I did the job. I realized that I was not interested in being a departmental chair or even for that matter a dean. I knew this job pretty well because I spent a lot of time with [UCSF chancellors] Juli Krevans, Rudi Schmidt, and Joe Martin working on things. They called on me a lot to do things. So I had a pretty good sense of the job. I wasn’t wild about it, but I felt as if I could do it and some parts of it would be fun. Dealing with the extramural community, I would enjoy; I knew that.

Hughes: What do you think your colleagues saw in you that they thought made you a good choice for chancellor?

04-01:12:59 Bishop: Oh, I think the most important thing they saw in me was a real commitment to the campus because they knew I’d been offered all sorts of attractive possibilities, including the directorship of the National Cancer Institute, which I had turned down. That was two years before I took the chancellorship.

Hughes: Was that a hard decision?

04-01:13:24 Bishop: Yes. It was clear to me that Kathryn and I were so wedded to the Bay Area, we would never leave it. Well, I thought about taking the job at the NCI. Harold was director of NIH [1993-1999] at the time. It’s a presidential appointment. It was offered to me by the Secretary of Health and Human Services, Donna Shalala, an absolutely wonderful woman, the best that office has had in a long time, and certainly far better than what we’re going to have now. I thought about it and said no to that. So if I was ever going to have a leadership position, the chancellorship would be it.

Hughes: Was it any consideration of yours that if you became head of the NCI you would be reporting to Harold Varmus?

04-01:14:22 Bishop: No, you report to the president.

Hughes: It’s a direct line.

04-01:14:25 Bishop: It’s a presidential appointment.

Hughes: It’s not a hierarchical arrangement?

04-01:14:31 Bishop: Well, it is on paper, but the— I remember vividly; I was interviewed by the search committee for the directorship of NCI. One of the questions asked by the committee concerned the issue of that hierarchy. The governing structure

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is such that there’s always been difficulty between the director of the NIH and the director of the NCI because the director of NCI insists on his or her independence as a direct presidential appointment. That was a product of Nixon’s—

Hughes: War on Cancer?

04-01:15:06 Bishop: Yes.

Hughes: That’s not true of the other institutes?

04-01:15:09 Bishop: No. Hence the Secretary of Health and Human Services does the search. Now, Harold had a big role in the search, clearly. Anyway, the [search] committee said to me, “You probably are aware that there have been lots of tensions arising from that situation.” I said, “Yes.” They said, “Well, what do you think about that?” I said, “Well, if Harold Varmus and I can’t solve the problem, it probably can’t be solved.” They loved that of course. This was by phone incidentally. They were meeting in New York. I was in a motel at NIH. I was there because Harold had me chairing a review of the intramural program of the National Cancer Institute. The committee was meeting, and they couldn’t get me to New York. So they interviewed me by phone. Really, for a job like that, I thought, good grief.

Hughes: Never laid eyes on this guy.

04-01:16:25 Bishop: Oh, sure, they all knew me. I was on the National Cancer Advisory Board [1994-2000], and so the advocates who were on the search committee knew me, okay? The advocates even knew me in person. I had worked with them, befriended them, while serving. I chaired the National Cancer Advisory Board eventually [1997-2000]. So everyone on the committee knew me.

Hughes: Was it a slam dunk that you were going to be nominated?

04-01:17:04 Bishop: I have no idea. But in any event, I turned it down eventually. It was a difficult decision.

Hughes: Was it mainly your not wanting to leave the Bay Area?

04-01:17:14 Bishop: That was a big part of it. I was so fond of the UCSF community. I was so happy working there. I knew that if I took that job, I would have to diminish and dilute my efforts as a research scientist. Most directors keep labs, but it’s just not the same. Harold kept a lab as Director of NIH, but it was not the kind of lab he had had at UCSF. He was content with that, and I was very leery of it. I think also there was a certain edge of inadequacy. I thought, well, I

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haven’t worked my way up the administrative ladder of experience, right? To go directly and run something like the National Cancer Institute, I wasn’t sure that was a good idea. In any event, I turned the job down.

So the chancellorship looked like an opportunity to have an experience as a leader for an institution that I was quite attached to and where I knew that I would start with a pretty good reservoir of trust and respect and even enthusiasm that I was going to do the job.

Hughes: Expand a little on what you said just a moment ago about how happy you were at UCSF. What were the ingredients of that?

04-01:19:09 Bishop: People. Full stop. I had grown up with the institution. As we’ve talked about before, it was a trade school when I got here. Herb had preceded everybody by six months, and Warren by a year, maybe, and Leon by two years. You could count on the fingers of one hand, the other substantive people that were [at UCSF]. Holly of course preceded all of us and played such a huge role in the subsequent flourishing of the place. He was exceptional, I think, as someone in medical leadership because he didn’t restrict his concerns to his own department. He was worried about the whole institution. I’ve teased Holly in public a couple times by saying that he was almost always the first person in my little office when the word got out that I was being courted at Harvard or wherever. He’d show up immediately. “Let’s have a chat, Mike.”

Hughes: But that is unusual because he was chair of surgery, right?

04-01:20:37 Bishop: Medicine. As he said, his department was bigger than half the medical schools in the United States. Which is true.

Hughes: At the time you first came here and aside from the good people in microbiology, the other departments were pretty mediocre. A lot of it was because basic science wasn’t what the institution was fostering in those early days. Am I right?

04-01:21:08 Bishop: Absolutely. The clinical departments were adequate, but they also had no academic stature. Holly understood something that most people don’t appreciate. He understood that the way he could have an impact here, the first step was to build his own training program. If you have a department of medicine that has national stature for people who want to become internists or whatever to do their internship and residency, that is a huge step for an institution. Then he helped us solve the problem of who was going to chair biochemistry. That was the next step.

Hughes: That was [William J.] Rutter?

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04-01:22:06 Bishop: Ultimately, yes. They had several very attractive candidates. But the candidates turned them down, and Bill saw an opportunity and took it.

Hughes: Had Holly gotten those ideas from his time at Harvard?

04-01:22:23 Bishop: You’ll have to ask him. This is turning into a Holly session.

Hughes: I know it.

04-01:22:45 Bishop: He was a junior faculty member at the Mass General Hospital where I did my internship, and I think he was still there when I began; I’m not sure. Anyway, he was a prominent young physician scientist. He was in a department whose chair was Walter Bauer, who was an inspired clinician but no shakes as a scientist. He didn’t pretend to be one. He was a remarkable character. Actually, he was still chief of medicine when I did my senior clerkship in internal medicine there. He met with the students in a small group. In any event, Bauer’s credo was, he had to have science in his department. He wasn’t a scientist, but he was going to have good physician scientists in his department, and he built a department that was rich in physician scientists. I’m sure that made an impression on Holly. It was a dominant department nationwide. It was the place you wanted to intern.

Hughes: Would you credit Holly with the beginning of the rise of UCSF to eminence?

04-01:24:13 Bishop: Oh, everybody does.

Hughes: Rightly?

04-01:24:17 Bishop: Yes. For the reasons we just went over. He spread his standards and his concern for the entire institution. Then Juli Krevans came along and saw the opportunity to buy in and build the place into something. I was the token junior faculty member on the search committee that identified Juli. I remember that the several candidates whom we interviewed, all but Juli kept itemizing for us the serious problems the institution had that they’d have to solve. Juli came in and talked about the possibilities. Done deal.

Hughes: That was a diversion, but I think it was a good diversion.

So you agreed to the chancellorship. Did you have an overall agenda about what you wanted to accomplish as UCSF chancellor?

04-01:25:47 Bishop: Well, I didn’t have a choice in the matter. It was Mission Bay [the future UCSF second campus]. The land had been procured and it was sitting there.

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There was no academic plan. There was no sense of how it might be developed. The [UC] president’s office, for nominally fiscal reasons, thinking we would get in over our head, didn’t want us to do a big deal down there. They said in essence, why don’t you build a small research building and see what happens? See if anybody wants to go down there.

Hughes: Without a plan, why had they bought that property?

04-01:26:30 Bishop: The president’s office didn’t; we did. First of all, we didn’t buy it; it was donated.

Hughes: Well, that’s a little different. I thought it was strange to buy a piece of property without a clear idea what you were going to use it for.

04-01:26:43 Bishop: Well, we were desperately looking for a place to put a second campus. We explored the Presidio. I was on the committee [Mission Bay Task Force, 1996-1998] that did that. We looked at the East Bay; we looked at Brisbane. We’ve talked about this before, I think. We were desperate for space.

Hughes: Oh, yes, the space issue. But how early did that very targeted, we’ve got to find more property, begin?

04-01:27:12 Bishop: Twenty years before it happened. I don’t know how many strategic planning committees kept taking the message into the leadership: we need more space. So by the time I took office, we had the land. Now the job was to populate it.

Hughes: Who donated it?

04-01:27:36 Bishop: The development company, Catellus that owned the land at the time. It was a former railroad yard, and it had gone through several ownerships. Each one had failed to develop it successfully. Nelson Rising was the CEO of the development company that owned it at the time, and he was persuaded by some of our potent friends in the external community that if he got a UCSF presence down there, we would be “a strong attractor”, the term that I used to use with our donors once I got into the action. Turned out to be quite true, actually, if you look at what Mission Bay is now, whenever the papers write about it. So he donated a modest piece of what the whole holding was. The rest of it has gradually filled up to the point of saturation now with both corporate and residential development. But in any event, it was a wasteland, a few warehouses and nothing else when we got involved. So that was clearly the major challenge to me for the institution.

Hughes: And probably a motivator for you, too, having lived through the problems of the limited space at Parnassus.

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Bishop as chancellor with the newly opened UCSF campus at Mission Bay in the background Photo by Mark Estes

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04-01:29:10 Bishop: Yes, that’s fair to say. It was daunting. My first inclination was, well, nobody seems to have a real idea about what to do with all this space now that we have it. Maybe we should reexamine the idea of wanting to go down there. The inner circle said, “No, don’t do that. We have a little momentum here.” They were absolutely right. So that was the big challenge. I credit Zach Hall with making the planning work. He was initially in the dean’s office, and he became vice chancellor for research and eventually provost. We didn’t have a provost when I became chancellor. The personnel office in Oakland didn’t think we were “complicated” enough to have a provost. We happened to have the second largest budget in the whole [UC] system. Only UCLA’s was larger, right? We were not complicated enough for the president’s office to let us have a provost. I fought that battle for six years before I finally won it. It took a retirement in Oakland to get it. I remember I was still designate; I wasn’t in office yet. The two senior vice presidents, Larry Hirschman and Wayne Kennedy, at the time in the president’s office had me come over for lunch which consisted of one pitiful little sandwich in a barren room. I remember thinking, oh, this is what the president’s office is like? Not much grandeur here. The message was pretty simple. “Mike, you’ve got to calm these people down. They are overly ambitious.”

Hughes: In building up UCSF.

04-01:31:15 Bishop: Right. I went back and reported this to my colleagues in the campus leadership. They said, “Well, what are you going to do?” I said, “I’m going to forget about it.”

Hughes: Well, why would that even have been a suggestion?

04-01:31:31 Bishop: Because remember I said, they thought we’d get in over our heads financially. They might have to bail us out.

Hughes: So it was a money thing.

04-01:31:41 Bishop: Yes.

Hughes: Is that a good stopping point?

04-01:31:45 Bishop: Yes.

Hughes: There’s a lot more to say about Mission Bay. We’ll save that for what will be the fifth interview.

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04-01:31:51 Bishop: Yes, we should come back to Zach in his role. I asked him to lead a faculty effort to get an academic plan. I couldn’t do that on my own, and I didn’t want to. I just don’t think that’s the way an institution like UCSF should run. It should be a bottom-up sort of thing; academic planning should be done by the faculty. So Zach ran that, and very successfully. Before I knew it, we had a really substantive group of people who were willing to move down there en masse and pretty much fully populate Genentech Hall, which is a very big building. That’s what we set about to build, a really big building that would house a real community. We knew that if we could constitute a real community down there from the get-go, it would work. Zach engineered that process and carried it through. In essence, who moved down there was the bulk of the PIBS [Program in Biological Science] faculty. So it was a carryover or perpetuation of that kind of community building within UCSF that PIBS represented. And then lo and behold [the PIBS faculty] made it possible to nucleate the Mission Bay campus in a way that essentially guaranteed success. Because graduate students were going to flock there because they were flocking to the PIBS faculty. Well, within a year, the people who stayed behind, who had not put their hands up to move, were lamenting that they had become second-rate citizens. We said, well, you knew there were going to be new buildings down there and you declined to go, but other people volunteered.

Hughes: I think in those very early days, it wasn’t quite that clear to a lot of people that this second campus was really going to be on a par with the establishment at Parnassus. Or do you disagree with me?

04-01:34:10 Bishop: Well, we had built this huge, expensive building.

Hughes: Okay, but before that, when the debate was, who’s going to go, who’s going to stay.

04-01:34:20 Bishop: The people with vision are the people who bought in. It’s just that simple.

Hughes: More on Zach the next time?

04-01:34:34 Bishop: I made the basic point that he engineered the transition, the academic plan, if you will. Once Mission Bay was a success, Harvard was attempting to do the same thing. They had bought a large property across the Charles River from the [Harvard] Yard. They were having trouble figuring out what to do with it because one part of the faculty after another was voting unanimously that they would never move. So they came out here to ask us how to make it work. And we told them. They said, “How did you get an academic plan?” We said, “Well, the faculty did it.” They were a little surprised by that. In fact—

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Hughes: Yes. Well, don’t start on the academic plan because that’s a big deal.

04-01:35:44 Bishop: Well, that’s two sentences, really.

Hughes: Really? Okay.

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Interview 5: March 10, 2017

Hughes: This is the fifth and last interview with Dr. Bishop, and we are once again in his living room in Belvedere. Dr. Bishop, we started last time to discuss the chancellorship. Since then, I’ve talked to two of your key colleagues, Susan Montrose29 [former UCSF Assistant Chancellor] and Eugene Washington30 [former UCSF Vice Chancellor and Provost], so I have a bit more information.

Susan told me that previous to your chancellorship you and she had sat on several committees together. She knew from those situations how passionate you were about your research. So when she heard that you were considering accepting the offer to become chancellor, she said something to the effect, “Mike, are you sure you want to do this?” She thought that because you were so dedicated to research that this would be taking you away from your passion. Do you remember that?

05-00:02:01 Bishop: Actually, I don’t. I remember something very different actually. But it’s perfectly reasonable. First, I can well imagine Susan asking that, and it’s a perfectly reasonable question. But what I remember is, I was on sabbatical leave, as I recall, at the Salk Institute. Joe Martin was chancellor, and he recruited me, despite my sabbatical, to do a one-man investigation of a knotty problem involving a very distinguished faculty member and his use of his research to potentially start a company. The funders of the research were unhappy about this. Anyway, I won’t go into the particulars, but I did that.

After I had made my in-person report to Joe Martin, with Susan present, it may have been even— I don’t remember how this came about, but what Susan said to me was, “Why don’t you think about coming down here to the chancellor’s office and run things for a while?” I have a very vivid memory of that. I’m not exactly sure, but as I recall it happened after I had this meeting with Joe Martin about giving my report, and she was present. So she might well have later asked me whether I really wanted to do it. But she had also made a suggestion that I might think about being chancellor.

Hughes: You mean right then and there, before the idea of your being chancellor?

05-00:03:59 Bishop: Well, there must’ve been some reason for her to say that; I just don’t remember the context. People in a position like Susan’s, Assistant Chancellor, are always thinking about who’s next, right? And lo and behold, Joe didn’t stick around much longer after that. Joe was only in the job for four years.

29 Telephone conversation with interviewer, March 5, 2017. 30 Telephone conversation with interviewer, March 6 and 8, 2017.

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Hughes: You didn’t know that his departure was in the offing?

05-00:04:19 Bishop: I don’t think so.

Hughes: Well, the other person, as I mentioned, that I talked with, actually twice—he called me back two days later—was Eugene Washington. By the way, he is a huge admirer of J. Michael Bishop. “One of my most--”

05-00:04:45 Bishop: Well, the feeling is mutual.

Hughes: “He’s an extraordinary man and one of my favorite persons in the universe,” is what he told me.

05-00:04:54 Bishop: Well, thank you. We’re having lunch this coming Tuesday.

Hughes: Oh, well, thank him again for me, because he was so helpful.

Anyway, you created—and I think pretty early on in the chancellorship—the position of executive vice chancellor. Oh, here’s the date. It was 2004.

05-00:05:22 Bishop: Exactly. It was not early in the chancellorship because when I took office we didn’t have a provost. The campus did not have a provost, who’s essentially the COO [Chief Operating Officer] in the university setting. Every other campus had a provost, who was in the line of fire before the chancellor and who was essentially the chief operating officer, and also the chief academic officer for the campus as a whole. The chancellor is generally viewed, particularly by the regents, as the CEO [Chief Executive Officer]; and the deans view the chancellor the same way. They’re the academic leadership. And the chancellor, as one dean once put it to me, keeps the trains running on time. So I recognized soon that I wanted a provost-slash-executive vice chancellor. That’s the alternative term that’s used, which even has more of a chief operating officer ring to it, executive vice chancellor.

Hughes: You mean it’s comparable to provost?

05-00:06:23 Bishop: They’re one and the same. I brought this up with the [UC] president’s office, and they were adamant--no way. Now, this was below the [UC] president’s level that I was having these conversations, which was probably a mistake. It may’ve dragged things out. I was told that UCSF was not complicated enough to need an executive vice chancellor or provost. Now, they were talking about the second largest budget in the system. Only UCLA’s budget was larger (circa 3 billion dollars). And an institution with 22,000 employees.

Hughes: Four schools.

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05-00:07:02 Bishop: Four schools, right. So anyway, I eventually won the fight, but only after a key figure had retired. A person down the third echelon maybe, who was balking at this, as were the senior vice presidents.

Hughes: You mean a person who had been opposing a provost for UCSF got out of your way.

05-00:07:27 Bishop: I took office in ’98, and it was ’04 until I was allowed, was given an executive vice chancellor. See, the president’s office stands between the chancellor and what goes to the regents. So I couldn’t take my request for executive vice chancellor directly to the regents, although they have to approve any executive action like that, ultimately. They of course had no problem with it whatsoever; they’re mostly business types, and of course you want a COO.

Hughes: Was it [Mark] Yudof that you were dealing with?

05-00:07:57 Bishop: No, Dick Atkinson. Dick was never involved in the opposition. I was loath to go around the system too often to the president, let alone to the regents. I just figured I could win this battle eventually, and I did. So Zach Hall was the first person to occupy the position. Then he moved on, and I realized that I would be well served by having a clinician in that position.

Hughes: Because you were a basic scientist?

05-00:08:32 Bishop: Yes, exactly. I had this feeling, although I was making efforts to connect with the clinical enterprise, that they would be more comfortable having someone like that they could go to with their problems.

Hughes: I see.

05-00:08:47 Bishop: Gene had surfaced in the search for a dean for the School of Medicine. I had an opportunity to evaluate him in that context and decided that he would be ideal for the job. And he proved to be truly ideal for the job; witness his subsequent record: dean at UCLA, and now CEO [Chancellor, Health Affairs, Duke University] of one of the largest academic health systems in the country.

Hughes: I presume you delegated to him certain responsibilities. Am I right?

05-00:09:28 Bishop: Oh, yes. He reported directly to me.

Hughes: One of his responsibilities was what became UCSF’s first comprehensive strategic plan [Advancing Health Worldwide: A Strategic Plan, 2007].

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Bishop: One of the things that occurred to me right off was, why did it take UCSF until 2007 to come up with a comprehensive strategic plan? Well, I think the key word there is “comprehensive”, because I had been involved in endless series of strategic plannings over the years as a member of the faculty and in fact was becoming rather dubious about these statements of high aims that are never achieved because of usually very pragmatic issues.

Hughes: Like no money?

05-00:10:18 Bishop: Money and otherwise. Well, a lot of otherwise, too. So there were strategic plans for the School of Medicine; there were strategic plans for research. I think they just kind of sapped the energy for strategic planning, which most academics frankly are a little skeptical about because they are usually just beyond reach overall. The statements of ambitions and aims are abstractions to people. It’s not till you get a particular plan about a specific problem on paper that people really come to grips with it, I find.

But in any event, Gene and I felt—and others in my leadership team felt—that the campus could do well to prepare a comprehensive strategic plan. One of the wise things that was said to me about this was that it’s not the strategic plan that matters; it’s the process that matters because it gets people with very different constituencies and backgrounds together, talking about the institution—what it should be, what it should aspire to do, and how it could go about achieving these things.

Hughes: Which had not happened in the past?

05-00:11:49 Bishop: Well, it had happened, but I think in more focal settings. It had happened in more focal settings, but this was the first time, to my knowledge, that it had been done at a level that encompassed every facet of the institution.

Hughes: Was that your initiative?

05-00:12:15 Bishop: Yes, with Gene driving the agenda very much because he was a big believer in it.

Hughes: You mentioned a leadership team—

05-00:12:26 Bishop: Well, the other vice chancellors and the deans, because essentially that’s the executive committee.

Hughes: That’s the executive committee.

05-00:12:35 Bishop: Yes.

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Hughes: Was it called the advisory team for the strategic plan? Aren’t there two different teams happening here?

05-00:12:47 Bishop: Well, the comprehensive plan is done by a campus-wide representative group that’s entirely separate from the chancellor’s leadership team.

Hughes: Yes, that’s what I thought.

05-00:13:00 Bishop: I don’t remember the particulars anymore, but you tap all the constituencies— the academic constituency, all the schools, the academic staff, what people fondly call the worker bees. So it’s supposed to be— It’s a representative body. Then it breaks itself up into various sub-groups. And it worked for more than a year, I would guess.

Hughes: I think Dr. Washington said that it was something like three years from conception—

05-00:13:40 Bishop: Yes. Fair enough, right.

Hughes: —to the actual implementation.31 I brought a copy of the strategic plan, not that I expect you to go over all the points, but so that you could discuss points that you feel were particularly key to moving UCSF forward.

05-00:14:20 Bishop: Well, it’s not only that. I would want a little time to consider that document. It’s been a while since I’ve been immersed in this. What I remember first of all is, there were no surprises here. [scans document] These were all aspirations that were talked about incessantly on campus but had never been brought together in one place, I guess. For me, just glancing down this list here, a key to all this is the next-to-last one. They’re not listed in any special order. “Provide a supportive work environment to recruit and retain the best people and position UCSF for the future.” Because it’s the people who make the institution. As I said earlier in these series, it was the people who kept me at UCSF, my appreciation of the community, and respect for so many of its members. All these thing hinge together.

Hughes: As I said, I didn’t intend you to comment on each point but to have the document bring you back to that time in 2007.

31 Telephone conversation with Dr. Washington, March 6, 2017. As of 2017, Dr. Washington is Chancellor, Health Affairs, Duke University.

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Dr. Washington said that one of the points of the strategic plan was to move UCSF as an entirety from a department-centered campus to what he called a horizontal institution. Maybe you’d like to say a little more.

05-00:16:35 Bishop: Well, that was entirely consistent with my own previous experience. That was what forming the Program in Biological Science, this graduate program, was all about at the level of basic science. We wanted to go from department- focused graduate programs, most of which were floundering and even the very best of which was struggling, and create a horizontally integrated basic science community of faculty who were competent to be graduate advisors and had research programs that would be attractive to research students. So that was, if you will, a study in miniature for the eventual comprehensive plan for the whole campus.

Hughes: Well, since you mentioned PIBS, do you remember when that was started? You were one of the founders, right?

05-00:17:28 Bishop: Yes, and I was the first director. It all started with very informal conversations among just a few people, prominent figures in our faculty. I won’t name them in order to avoid embarrassing omissions. They were senior members of basic science departments. These conversations actually emerged out of teaching alliances. So people from various departments—teaching cell biology, for example, which was one of the contexts in which this emerged—because we said, well, why don’t we have just a cell biology program instead of these departments each having their own program? So having started with a horizontally integrated course, we began to think about having a horizontally integrated graduate program.

Most of the departments were having trouble attracting good graduate students. It was a very simple conclusion. If we wanted to compete with Berkeley, MIT, which have very large biology faculties—just to name one public and one private university—we would have to have a larger candy shop than any of the individual graduate programs offered. So we self-organized. This was all done really even without the knowledge of the dean, originally. We were just doing this all informally. At some point, the dean, Rudi Schmid, became aware of it, as I remember the history, and called the group in to talk about the Markey foundation [Lucille P. Markey Charitable Trust], which had just announced that they were going to spend out all their money on innovative programs. Rudi thought, looking around campus, that these conversations about forming a horizontally integrated graduate program — incidentally, that’s an organizational term we never, ever used. But anyway, it might be an ideal thing to present to the Markey, and could we formalize it in some way and get it to the Markey, like over the weekend? So I came home and wrote a proposal. We had all talked about this, and I volunteered to write it up. The following Monday, we passed it around and quickly revised it as necessary—

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not much. There was a governance plan; there were descriptions of how faculty would be admitted; there were— It was fully formed. That just was a testimony to how deeply and how often we had discussed all this. That went to the Markey and resulted in the largest grant they gave, something like $13 million, which was a huge boon because now we could offer excellent stipends. We couldn’t do that before. So we used this to offer stipends to graduate students.

Hughes: I imagine not only the number but the quality of your applicants soared.

05-00:21:31 Bishop: It took off immediately because the students were excited about the program. The idea was, they came into this program and only after that decided which subset—either genetics or cell biology or neuroscience or whatever—they wanted to affiliate with.

Hughes: Did that mean there were some very basic courses that everybody took?

05-00:21:52 Bishop: No. The curriculum was dictated by their major, if you will. I think the most powerful thing it did was to change the approach to faculty recruiting, which was being done on a departmental level because that’s where the FTE’s [Full Time Equivalent positions] are vested. But we persuaded all of the basic science departments, and in due course the clinical departments who wanted to play, that every search committee for a new member of their faculty should have a PIBS membership, not just their faculty. They would have a veto, and we would have a veto; the PIBS program would have a veto. The departmental faculty would also have a veto over any recommendation from the search committee, which probably would be on the grounds, it turns out, primarily of what this person could teach. The PIBS executive committee would ultimately have a veto over whether the person would be eligible for the PIBS program.

Hughes: How did the departments feel about that?

05-00:23:06 Bishop: Well, it’s pretty simple: money. We had money to offer stipends and assist faculty recruitment. The chairs, every one of them, showed remarkable vision and flexibility, right down through Pete [Henry J. Ralston] in the anatomy department, which you would consider to be probably the most traditional of all departments. They recognized that this would bring—or could possibly and did bring—very strong science into their departments which they were having difficulty building in the context of their traditional assignments, like anatomy.

Hughes: What era are we talking about?

05-00:23:58 Bishop: I don’t remember; we’d have to check.

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Hughes: Well, the reason I ask that question is, I’m wondering if PIBS is in the vanguard of the movement in basic science toward—

05-00:24:11 Bishop: We were the very first.

Hughes: But I mean even broader than that, in the sense that basic science was really becoming much more multidisciplinary.

05-00:24:22 Bishop: Well, but that’s what informed our attitude. We were already cognizant of that. We were living it in our research lives. So we thought, this is the obvious way to reorganize graduate education, with the benefit of being able to offer potential students the same kind of variety and quality that a place like MIT or Berkeley offered.

Hughes: They were already doing a sort of PIBS light?

05-00:24:24 Bishop: No, it was just that they had much bigger biology departments.

Hughes: Was anybody offering a program like PIBS?

05-00:24:59 Bishop: No, this was really, truly novel, and prompted change elsewhere over the next decade. Everywhere you go now graduate education is organized this way.

Hughes: Were you alone the major instigator of PIBS?

05-00:25:16 Bishop: No, no. I thought I made it clear. This emerged from a discussion among like- minded people.

Hughes: Well, yes, but somebody had to lead the charge, right?

05-00:25:24 Bishop: This charge was not led until Rudi Schmid said, “Somebody’s got to write this up for the Markey Foundation.” Five or six people in a room don’t need a leader necessarily if they’re all strong-minded, and this bunch was.

Hughes: There is something called the Herb W. Boyer Program that is somehow, I thought, linked to PIBS.

05-00:26:06 Bishop: My knowledge of this is superficial because the money was vested in the Department of Biochemistry and Biophysics originally. That department, wisely, decided to use the income from Herb’s patent [with Stanley N. Cohen on recombinant DNA technology] that he designated to the university to support graduate education. So they used it to support PIBS students. Sooner or later the Markey money was going to run out. We couldn’t create an

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endowment with the Markey money that would maintain the level of payout we wanted to maintain. We were really lavish in the beginning; we were offering, I think, five years of support at the time.

Hughes: Whoa.

05-00:26:56 Bishop: Three to five years, yes.

Hughes: That’s pretty nice.

05-00:26:58 Bishop: Yes, well, that made it very attractive for recruiting faculty, who were being told most other places that they’d have to be putting graduate students on their grants after one or two years. That slipped, of course, because—

Hughes: I wish I had looked up when PIBS started because—

05-00:27:15 Bishop: Well, it’s on my CV, which is upstairs, but I just don’t want to hazard a guess. [Dr. Bishop was founding director of the Herbert W. Boyer Program in Biological Sciences, 1987-1998.]

Hughes: Why I’m thinking about this is, there was a deliberate effort on the part of the administration and key faculty to move UCSF into the top tier of biomedical institutions.

05-00:27:44 Bishop: Well, that came earlier. That created this community of scientists who wanted to do PIBS.

Hughes: So PIBS came a little bit later.

05-00:27:52 Bishop: Yes. It couldn’t have happened if the institution hadn’t begun to bring in faculty of the quality who participated in PIBS.

Hughes: Well, one more thing on PIBS, unless you want to say more. I read that in 2014 the first J. Michael Bishop Fellowship was awarded. Who was behind that?

05-00:28:30 Bishop: The PIBS executive committee. I was no longer a member; I’d been chancellor. So I withdrew [as PIBS director]. I guess I served as director until I took the chancellorship. Then I withdrew completely. I had to. They approached me sometime later and asked whether I would be willing to have my name put on a fellowship for a graduate student. Of course, it would be fine. So it came from the PIBS executive committee after I had left it. Some years after I’d left it, actually.

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Hughes: And this fellowship was in addition to the Herb Boyer program?

05-00:29:12 Bishop: Yes. The Boyer program didn’t pay for all the students; it paid for some students.

Hughes: Is that enough on PIBS?

05-00:29:25 Bishop: As far as I’m concerned, it’s enough. You’re the historian.

Hughes: All right.

05-00:29:33 Bishop: I would just by way of summary make the statement that the fact that it was created and truly did succeed is a tribute to both the quality of intellect and the quality of, well, let’s call it a social altruism among the faculty who were involved. These were all people of major stature. Such people are known to have large egos, but they were intent on a common course. We had very difficult discussions about many things. I’m fond of saying—not truthfully, of course—that in order to get the whole thing to work, I just had to lock them in a room for encounter groups for week after week. But it’s really a tribute to them, and I think exemplifies the spirit of the place, that people of such distinction, almost every one of whom is now a member of the National Academy of Science, would come together and do this thing, which essentially allocates power that they might themselves exercise within a single department to a larger group. It was inspiring to watch.

Hughes: Right. PIBS diminishes the power of individual departments.

05-00:30:59 Bishop: Yes.

Hughes: It becomes a much more collective effort, right?

05-00:31:02 Bishop: Well, that was the whole point. That was the whole point. The departments remain important because they track, they oversee, the academic career of every individual faculty member. They hold the FTE’s. The school’s [UCSF School of Medicine] administered through departments, and we didn’t want to try to take that on. Probably wisely; maybe not. Because once the departments agreed to play ball— I have to say, that happened all pretty quickly because people were really very anxious to have a better graduate program. In any event, it really is a tribute to the spirit of the place as exemplified by the people who founded PIBS.

Hughes: Well, what did it do to different departments? Maybe we could look at Anatomy, which you characterized as being a more traditional department. So

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being part of PIBS and having presumably more qualified students, did that change the tenor of—?

05-00:32:13 Bishop: I can answer that question with one example, one word, one name, Cori [Cornelia] Bargmann. The first PIBS hire in the anatomy department was Cori Bargmann, who was one of the most attractive faculty candidates in the United States at the time. She is now, incidentally, president of the [biomedical part of the] Chan Zuckerberg [Initiative] effort. But anyway, she had a spectacular research career; still does. Was at UCSF for many years, moved to Rockefeller some years ago. But the point is that they would never have thought of or tried to or succeeded in recruiting Cori if Cori did not see what she was coming into in PIBS.

Hughes: What research did she come with?

05-00:33:12 Bishop: She does neuroscience on C. elegans worms.

Hughes: So was that the beginning of the molecular approach in the anatomy department?

05-00:33:19 Bishop: I’ll tell you a story about this since we’ve brought up Cori. I hope she’s not listening. As I recall, the search committee said, “Look, here’s this wonderful scientist who studies worms.” In Anatomy? So they said, “What would you teach in our department?” As I was told, without missing a beat Cori said, “Well, I’ve realized I need to know more about histology in my work, so I’ll teach histology to medical students.” That told us that this was the kind of person we really wanted in this show.

Hughes: Namely, flexible.

05-00:34:00 Bishop: Right.

Hughes: Was she maybe the first molecular biologist in Anatomy?

05-00:34:08 Bishop: I don’t know. I’ll leave it at that. Probably, but I don’t remember. The current chair of Anatomy is a neuroscientist, and he’s been chair for some time, Dr. [Allan] Basbaum. There may have been somebody in the anatomy department who was molecularly oriented at that time. I simply don’t remember.

Hughes: Returning to the creation of the two titles, provost and —

05-00:35:07 Bishop: Executive vice chancellor.

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05-00:35:10 Bishop: I don’t know how the campuses make this decision, but they use one or the other term, but not both.

Hughes: What did UCSF use?

05-00:35:21 Bishop: I made the decision and used provost/executive vice chancellor because I wanted to represent both the managerial and academic aspects of the position.

Hughes: The first one was Eugene Washington.

05-00:35:39 Bishop: First one was Zach Hall.

Hughes: Oh, that’s right; Zach Hall and then Dr. Washington. Was that primarily considered an academic position?

05-00:35:54 Bishop: No, the COO is the Chief Operating Officer. On all other campuses—and this was a point that I knew I’d have to yield on locally— On all other campuses, the deans report to the provost/executive vice chancellor. When I proposed having an executive vice chancellor on campus, my deans had a fit. I was ready for them. I said, “Oh, I have no intention of changing the reporting.” Because they each had their individual personal meetings with me, and they saw those going by the board. I had no intention of doing that, actually. But that was a big issue.

Hughes: You knew from the start that that would be a real sticky point?

05-00:36:43 Bishop: Yes, I knew from the start I didn’t want to change it because I really enjoyed my direct interactions with the deans. But they met with the executive vice chancellor as well, on a regular basis as far as I know. The deans and the vice chancellors together they constitute— For me at least—every chancellor’s had their own version of all this—they were the executive committee. That’s the group I assembled regularly to thrash out key issues, the deans and the vice chancellors.

Hughes: And you really used them.

05-00:37:48 Bishop: Yes.

Hughes: In a way that maybe was unique to you?

05-00:37:53 Bishop: Oh, no. Every campus has a body of that sort, constituted in various ways.

Hughes: Well, but I can imagine—

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05-00:38:02 Bishop: No, Sally, it’s not unique, okay? The membership might be unique. People vary it.

Hughes: Yes. What I was thinking when I asked that question is that some of it boils down to the personality of the chancellor, right? How much you are willing to listen to other people in executive positions.

05-00:38:35 Bishop: Well, I don’t think a chancellor would last six months if they weren’t meeting regularly with their direct reports. If the chancellor doesn’t pull them all together, they’ll pull themselves together. It’s such a well-established and obvious management tool, I just couldn’t imagine someone— If there’s anything that’s anathema to an academic community, it’s top-down governance. Granted, there has to be some of that; but better that it come from a representative group—the deans and the vice chancellors who represent both the academic side and the staff side of things—than it come from the chancellor alone.

Hughes: Well, one complementary thing that Eugene Washington said in the phone call was that you not only delegated responsibility to him but, more importantly, backed him up.32

05-00:39:56 Bishop: Oh, absolutely. But again, that’s just good management principle. If you’re going to delegate authority, you have to trust the individual, and you have to back them or it all comes apart.

Hughes: But is everybody as wise as you are?

05-00:40:20 Bishop: Again, it’s well-established management principle. I read a couple of books on management; they’re dreadfully boring. But all the chancellors I knew worked that way.

Hughes: It throws me back to the years you were lab director. Did any of that experience of running what was a fairly complicated organization help you when you became chancellor?

05-00:40:56 Bishop: Well, of course. I was dealing in intimate ways with people with ambition and personal needs, and I had to somehow keep them together as a community so that they interacted cordially and shared ambitions, supported each other, collaborated. In large measure, I think Harold and I succeeded in doing that, and we continued to succeed after Harold and I went our separate ways. It was

32 Telephone call with interviewer, March 6, 2017.

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manifestly clear when I took the chancellorship that that was going to be crucial to how I would govern; that I would want to create that same environment among my direct reports and across even the next level down in the campus, as far down as you could reach. You reach farther down by setting an example for your direct reports, if you will

Hughes: You mentioned that you had to go through the UC president to reach the board of regents. What were your dealings with Dean Atkinson?

05-00:42:50 Bishop: President Dick Atkinson.

Hughes: President Dick Atkinson. And then Mark Yudof, right?

05-00:42:55 Bishop: Yes.

Hughes: Was it important to cultivate a relationship with the president of the university?

05-00:43:12 Bishop: Well, actually, the opportunities are limited by geography. The chancellors in the Bay Area could in principle exploit that [the UC president’s office is in Oakland], and I think some have. I chose not to. When I had a real need that was appropriate to take to the president, I did. The one I remember well, the one that was the number-one issue for my vice chancellors when I took office—and the deans of course—was indirect costs. How much of the indirect costs from our grants were being kept by the president’s office? The short answer was, too much. It had been ever so, and every campus felt the same way, and no amount of pushback to the president had ever worked. That’s an issue I took to the president directly in due course, after he had been softened up by hearing through his direct reports, from my direct reports, that this was becoming an intolerable circumstance. So I credit my finance officer, Steve Barclay, for example, and others for pounding on the vice presidents about all this. In due course, Dick and I agreed to have lunch, and we talked this over in Oakland, at a restaurant actually, not in the president’s office. He agreed that something had to give, and it did. There was considerable improvement in the situation. But a chancellor who exploits that relationship to some obvious advantage over the other campuses is not going to be very popular. Nor do I think it’s appropriate. A few have, but very few, over the years.Hughes: Did you feel that one of the important things for you to establish was a working relationship with each of the chancellors?

05-00:45:14 Bishop: Well, the campuses have a surprising amount of self-governance— self- sufficiency and self-governance. The president’s really preoccupied, frankly, with the legislature and the regents. They’re perfectly happy to let the campuses run their own show as long as they’re successful and stay out of the newspapers, to use a standard phrase—covers a lot of territory. Frankly,

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cultivating the vice presidents who were interacting regularly with the campuses was just as important. See, every major executive appointment had to go through the president’s office because they oversaw the salaries that were offered. They were interested in maintaining parity among the campuses. To an extent, that was punitive because those of us who were in high-expense marketplaces had more difficulty hiring executives than those who were in lower-expense markets. So that was a big issue at the time I was chancellor. The president relied on the vice presidents to deal with those issues. So we spent a lot of time cultivating the vice presidents, a couple of whom I got to really like, who seemed like the enemy when I took office. But we worked things out. Every chancellor I know, that was their experience. They had to work the vice presidents. They had to deal with the vice presidents because they had decision authority; it had been delegated to them. So we spent time and effort, and most of it pleasant, on that.

Hughes: Did you feel that both Atkinson and Yudof recognized the unique needs of a medical campus?

05-00:47:54 Bishop: Well, frankly, yes, the presidents recognized that. But more to the point, they also view medical campuses as having a financial advantage because they get much more NIH funding than the general campuses without medical schools, which have smaller efforts in biomedical research as opposed to all sorts of other research. Whereas the medical campus is just rich with biomedical research and brings in huge amounts of NIH money, compared to, say, Santa Cruz, for example. So they [the president’s office] tended, as one of my vice chancellors used to say ruefully, “They see us as an ATM.” The clinical side of things—clinical salaries and so forth—that’s pretty remote from most presidents. We’re just expected to deal with it. The dean of the school of medicine and the CEO of the hospital deal with that problem, the clinical salaries.

Hughes: Well, something I read indicated that the bulk of the funds raised during your chancellorship caused some resentment because a large portion of it did go to the clinical side of the campus as opposed to basic science and maybe the other schools.

05-00:49:43 Bishop: Well, in my tenure, nothing could be further from the truth. The complaint was that too much of it was going to the buildings at Mission Bay.

Hughes: It wasn’t a clinical/basic science divide?

05-00:49:56 Bishop: Those were all basic science buildings at that time. That sentiment is as old as the university system, I would say. As was actually the sentiment about the buildings, even. If you look at the current fundraising by UCSF, it’s clear that a redirection was achieved, probably over the course of four chancellorships.

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UCSF just got the largest donation in the history of the campus, and one of the largest in the history of medical campuses, $500 million, from the Diller family. That’s all for faculty. It benefits the academic faculty and their salaries, recruitment and retention. That’s the principle purpose of that money. I knew the donors well. So through at least three chancellorships, they were cultivated and educated about the needs of the institution, and they decided to help in a big way. So it’s clear that the chancellors had been working on that problem.

Hughes: Fundraising is a major part of being the chancellor. How did you go about it? And did you like that part of your responsibility?

05-00:51:43 Bishop: Well, the second part’s easy to answer. Nobody likes asking—well, most people don’t like asking—for money. But I certainly enjoyed getting to know the folks we interacted with in the extramural community. Many of them are truly wonderful, accomplished individuals. Most of them I found to be fine human beings and deeply concerned about their own causes, be it fine arts or medical science or whatever. A few have remained friends still. I enjoy people, and these were very accomplished people. Some of them were very demanding, but so were some of my colleagues in science. So that was not new to me.

Hughes: Demanding in terms of the parameters in which any donation might be given?

05-00:52:51 Bishop: Well, yes, and expectations.

Hughes: You mean of what was to be achieved?

05-00:52:57 Bishop: I’ll give you an example. Coming from the business world, it’s a little hard to accept the fact that the chancellor or the dean just doesn’t say, okay, I want that person. That person for genetics, okay? No, no, that’s not how we work. Right? Academia wouldn’t work well if these were all autocratic decisions. We have a search committee. It’s a drawn-out process, no doubt; but it’s all based on the search for quality. There are CEOs who just can’t understand that. The business world works differently. There’s a lot more command control, line of authority, in the business world than there is in the campus world. So I would say that was the most problematic thing I confronted. I had to explain all this, and over and over and over again. Why don’t you just solve this problem? Oh, sorry, I can’t do that. First of all, I don’t make that appointment; the dean makes that appointment. You’re the chancellor; why can’t you make it? Now, the folks who know the institution well have, almost to a person, come to understand this once you point out to them that this is the ground from which the quality emerges, this search process.

Hughes: Well, say something more tangible about how you actually went about fundraising. First of all, whom did you choose to approach? Or was it obvious?

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05-00:54:44 Bishop: Well, you have a whole development office working on that for you.

Hughes: So they say, now it’s time to pick up the phone?

05-00:54:50 Bishop: Yes. They’re constantly saying, we have a new prospect, and it’s time that you see them and get to know them. My first year as chancellor was spent just meeting and getting to know all our established supporters. I knew some of them already. Previous chancellors had used me in fundraising, as they use other faculty members. So I knew some of them, a few of them. So the first year was just getting to know our existing stable, if you will. Then the [development] office and our friends in the community who work with us as members of the UCSF Foundation board—this is the fundraising enterprise— would bring new candidates in. So that was part of the job. That was one of the interesting parts of the job, yes.

Hughes: Did you have to entertain them, as well?

05-00:55:53 Bishop: Yes. My wife and I would entertain at the chancellor’s residence. That’s what the chancellor’s residence was designed for originally. We tended to do it in a way that would softly inform them about the mission and needs of the institution. In other words, they would be there with faculty, sitting next to the faculty, and talking to them about what they do. Occasionally, we’d have faculty make little talks after dinner, but I found that a bit problematic. It kind of dampened the joie de vivre of the event. They knew why they were there. They wanted to get to know me and they wanted to get to know faculty. So we did a lot of entertaining, thousands of people, over the eleven years that I was chancellor.

Hughes: How did Kathryn feel about that aspect?

05-00:56:41 Bishop: She enjoyed it, but it was very demanding on her. Kathryn was of a single mind about this. She had no staff. She maintained the house herself. She didn’t cook for these events, where there were thirty or more people. We had a caterer. But all other aspects of maintaining the house, Kathryn simply did.

Hughes: She was running the vacuum cleaner and all of that?

05-00:57:11 Bishop: She was running the vacuum cleaner and all of that. My heart sinks just to say it.

Hughes: Why do you suppose she wanted to run her life that way?

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05-00:57:19 Bishop: I refer you to Tanya Shavitz’s sixty-one articles about the lavish lifestyles of the chancellors. Kathryn saw that coming from the day we entered the job, and she was not about to be vulnerable. It didn’t matter; they still picked on us. But most chancellors have a house manager full time.

Hughes: Really?

05-00:57:39 Bishop: Absolutely. I’d go to UCLA to meet with the chancellors and the president. The chancellor and the president would meet around the system at different campuses at times. I’d go to the chancellor’s house for dinner that evening, and the manager was there and other staff was there, making sure that everything was in order. There was little of that at our place. Kathryn and I met the people at the door, et cetera. I would’ve been perfectly happy if she had a house cleaner, but she didn’t.

Hughes: Yes. Did you and she enjoy entertaining?

05-00:58:27 Bishop: I said I enjoyed it and I said she enjoyed it.

Hughes: But the chancellorship wasn’t just a series of, oh my God, I owe the university that I love this responsibility. You got a lot of pleasure out of the position?

05-00:58:48 Bishop: No, I think more pain than pleasure, because we went through, all academia went through, at least two financial crises during the course of my tenure. Those are really ugly. There are so many parts of the job where you simply can’t change things yourself. I would like our lowest-salaried people to make more money, but I couldn’t do that. I didn’t have the funds, and I didn’t have the authority. That’s negotiated in the president’s office. And I fully understood what the president’s office was up against in terms of legislative allocations and so forth. So that’s just one example where, from day one to the day I left, I felt inadequate and frustrated because I did not believe that our entry-level employees were paid enough. The benefits were good but the salaries were not, and that bothered me.

Hughes: Bruce Alberts wrote to me by email. He’s underwriting this interview series. Thank you. Wonderful gesture, on his part, and certainly says something about how he feels about you. Anyway, he said that you told him at one point that the chancellorship was the most demeaning job that you had ever held.33

33 Email, February 15, 2017.

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05-01:00:37 Bishop: Well, it was demeaning in the sense that there were all these things you couldn’t accomplish. As a scientist, I ran my lab, and I raised the money, and I and my junior colleagues spent it as I thought wisely. Things are very different when you’re a chancellor. You can make certain decisions that are important and have an impact; but a lot of things, you can’t do anything about, as I mentioned to you. You’re removed from the academic world. I maintained a foot in the world by keeping my lab open, which many chancellors actually do. I didn’t know that; I was surprised. When I took the job, the president said to me directly, “I hope you’ll continue to run your lab.” I said, “Oh, all right. I’d like to try that.” Turned out during my chancellorship, all but one chancellor were scientists or engineers, and they almost all had labs still running. But it’s a struggle. It really is a struggle.

Then you’re the target for all the slings and arrows, right? The merger. I stepped into the office, and there was the merger with Stanford and UCSF medical centers, profoundly just hated by legislators, by clinical faculty, at times seemingly the world. I had nothing to do with putting the merger together. It happened while I was on sabbatical leave. I didn’t know it was going to happen.

Hughes: Well, it happened before you were even chancellor.

05-01:02:25 Bishop: Oh, of course. Well, that’s what I said. I had nothing to with putting it together. It was a horror show because it wasn’t working.

Hughes: What was the basic reason why it didn’t work?

05-01:02:40 Bishop: Well, there’re two points of view. The popular point of view is that the cultures between the two places were too different, with the faculty, and there’s truth to that. Pediatrics, for example, had formed a reasonably good consortium between the two sites, but virtually no other specialty had achieved that. My view is that it was a leadership problem and an organizational problem, a management problem; that they tried to do everything all at once, put everything together all at once. They removed the leadership from the two campuses and put it in a separate site. I have this vivid recollection of my first meeting with the person who was the COO of our medical center at the time. We didn’t have a CEO. They had only COOs at the sites. The CEO was sitting down in Executive Park for both places, right? So our COO came in, and we had a chat. He said, “Mike, I have to tell you something. I just got a report that the medical center hired 400 new people recently, and no one can tell me who they are or where they are.” I thought, Wow, we have a problem! So the first few years, it was just really bad. Our clinical faculty ultimately had what they called—well, you’ve heard the term, I’m sure—a come-to-Jesus meeting with the dean, and I sat in on it. They voted unanimously to try to keep the merger running.

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But there was a different sentiment at Stanford. In due course, President Casper, Gerhard Casper, decided that he wanted to divorce. I quietly breathed a sigh of relief, although I did know that our medical center would go through a tough time. As soon as we got Mark Laret on board as the CEO of our medical center, things started to blossom.

Hughes: Had you said anything to the powers that be at UCSF that maybe it might be a great idea to get out of this merger?

05-01:05:11 Bishop: The powers at be at UCSF had nothing to do with it. This was a freestanding private entity, constituted on the authority of the regents.

Hughes: But you could’ve talked to your colleagues, to the people in executive positions, and said, this isn’t working for the University of California, San Francisco.

05-01:05:32 Bishop: That’s not who I would have to talk to. I would have to talk to the regents. They had gone through a huge turmoil over this because it was politically unpopular, because it removed the staff from union membership. It was politically very unpopular.

Hughes: Well, explain.

05-01:05:58 Bishop: It’s a private entity. It’s different than a public entity. It doesn’t report to the legislature through the regents.

Hughes: Well, I figured that that’s why the legislature was against it.

05-01:06:08 Bishop: Yes.

Hughes: It was removing a big entity from their power.

05-01:06:13 Bishop: Yes. Well, it’s very remote power. It’s the power of the budget and with the president, but the regents have the bulk of the power over the university.

Hughes: Well—

05-01:06:19 Bishop: No, the campus doesn’t usually hear directly from the legislature. Only in terms of the budget, do you feel anything from the legislature, typically. They don’t come to individual campuses and announce what the university should be doing. Well, you can get phone calls pressuring you about something, but they are of no consequence because they don’t have the authority. The University of California is in the state constitution as a freestanding institution.

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Then lo and behold, the medical center merger was removed from that and created as a private entity.

Hughes: I’m surprised it happened at all.

05-01:06:55 Bishop: Yes. Well, both places were in trouble. It was a time when HMOs were the elephant in the room, and both the UCSF and Stanford medical centers were struggling. What drove it was the competition between the two of us [UCSF and Stanford] for contracts. So we would be bidding against each other. And that’s the one thing that worked when they put the thing together. Contracts got better because we were the two best games in town—the town being the Bay Area—and they couldn’t bid us down anymore, against each other.

Hughes: Encompassed in that was the fact that the merger would allow a pooling of financial resources and professional resources, too. It was supposed to make an entity that was stronger than the individuals. Well, it didn’t work out that way, did it?

05-01:07:56 Bishop: It didn’t. It didn’t work out because the management was poor. They had red ink probably a year before they knew it.

Hughes: And you inherited that, too, didn’t you?

05-01:08:08 Bishop: No. As I said, the merger was up and running when I took office. So it wasn’t red ink on my books; it was red ink on their books, which was very threatening.

Hughes: Oh, it wasn’t red ink on your books.

05-01:08:22 Bishop: Sally, it was a freestanding entity, separate from the university. I had no authority over it at all, except I served on the board.

Hughes: Well, that turned out to be fortunate for you, didn’t it?

05-01:08:37 Bishop: Yes. Well, Casper was still the symbolic target for the enemies at Stanford, and I was the symbolic target for the enemies at UCSF. We had no authority over them other than our membership on the board. So when I took office, I felt the need to tread lightly. This thing was in its very earliest days. Haile Debas was working very hard to make it work. He felt deeply invested in it. I had to respect that. I had to let the thing try to make itself work. I couldn’t just walk in and announce, I’m pulling out today. First of all, the president would have probably fired me because the regents were deeply vested in the thing. They were convinced that this was an innovative approach to dealing with the threat of HMOs to academic medical centers, and the [UC] president had

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signed off on it. So they wanted to see it work. I never for a moment thought that I could walk in there and simply announce, I don’t like this; we’re pulling out. Because I couldn’t. I had to have the president’s approval to do it, and the regents’ approval to do it. I could take a bully pulpit and become singularly unpopular in Oakland and with the regents, and singularly popular in the legislature, which could do nothing about it, really. So yes, it was not fun. Example made. Point made.

Hughes: Unfortunately, we’re running out of time. Because of the kindness of Dr. Washington in giving me a lot of his precious time, let’s say a little more about the diversity program that he particularly was in charge of. Am I not right about that?

05-01:10:45 Bishop: Yes.

Hughes: What was the process of making UCSF into a much more diverse community, in all senses?

05-01:11:04 Bishop: Well, from time immemorial, we and many other places have had formal declarations that we want to be truly representative. I can remember back to the days when the Black Caucus at UCSF was founded, and its impact on admissions, particularly I think to the medical school. I was then a junior faculty member; I wasn’t even tenured yet. So UCSF specifically has been wrestling with this problem for a long time. It’s a very complicated problem because it exists in several different spheres, and each sphere has its own special problem. For example, hiring in the academic realm has always been a problem because—there’s just no beating around the bush—the available pool of faculty candidates for some—not women now, but other underrepresented groups—is not very good. So it is difficult. There’s a different set of problems at a staff level, say. Of course, we were more diverse the farther down the ladder you go. At least that was true when I was chancellor.

Hughes: Including students?

05-01:12:34 Bishop: No, I’m speaking of employees. But each school had its own diversity initiative in terms of bringing in students and obviously wanted to put the imprimatur of the chancellor on those as well.

Hughes: You mean prior to the formal ten-point plan on diversity?34

34 “Create a More Diverse University,” Strategic Planning Progress Report, 2008. Document courtesy of Eugene Washington.

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05-01:12:54 Bishop: Oh, yes. They certainly did. Were they working? Not so well. So one of the hopes of the diversity plan was we’d try to figure out how to make it work for a change. It was clear that that was going to be an ongoing problem for decades to come because at the academic level—many people view this as a rationalization; but it is a reality—to some extent we were going to have to wait while the pool grew, while the number of underrepresented students grew in graduate programs, to create the candidates for faculty. There just weren’t enough to go around. The numbers were very clear on that. The intense competition for medical students— I remember this. We would lose one attractive medical student after another to an Ivy [eastern college] that could offer full stipend—bed, board, tuition, everything. We just couldn’t do that at some point. So each sphere had its own set of problems.

Hughes: I see.

05-01:14:17 Bishop: One of the things that Gene and I wanted to do was to get all of these issues drawn together and looked at and then addressed, if they could be addressed. Or at least put on the books that they must be worked on as prospects for improvement as it becomes possible to do something about it. But there were many things that we could do something about. Gene was clearly passionate about this, and I was really grateful that I had someone I could call on to drive this agenda.

I’d made it very clear as chancellor about my concerns about diversity. I had established a major program about women on the faculty because there I saw something I could do. I put money into that and personally first commissioned a study by an external firm on the status of women on the faculty at UCSF across the board, not just the School of Medicine. Then I personally wrote a very lengthy document itemizing each of the problems that they had identified and what I could and could not do about it and sent that around to the whole campus, by email. So it was wonderful to have someone like Gene, who exemplified a successful [member of an] underrepresented minority, and who was passionate about this and who would take it on because I couldn’t address it the way he could address it. Well, for lack of time and lack of credentials, if you will.

But one of the nicest things that happened to me as I was leaving the chancellorship was that the affirmative action group— I have this charming little plaque they gave me, acknowledging my efforts on diversity as a chancellor. I was really pleased and surprised by that. It was very nice. It has a nice, homey touch. It was homemade. [The plaque is now in the UCSF archives.]

Hughes: One thing that I thought might have been one of the keys to the success of the diversity program was Dr. Washington’s insistence on what he called

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accountability by measurement. As you stated, there’d been a lot of talk about diversity and more women on the faculty but not very much implementation. I imagine that in both your minds was the fact that we’ve got to set up a process where you measure what kind of progress you are making. But I’m putting words into your mouth.

05-01:17:39 Bishop: I’m a scientist; I measure things. I believe in measurement. Accountability before the public is one powerful way to demonstrate your commitment. One of the things that Gene implemented was an annual report to the campus in person when all the leadership got up in front of whoever wanted to come.

Hughes: Oh, really?

05-01:18:11 Bishop: Each vice chancellor, each dean, made a public presentation on their scorecard for the last year on a variety of things. It was held in the largest auditorium we have, and it was always full. I don’t know whether they’re still doing it or not. It was very well received, and the leadership liked it, it turned out. They were a little leery of it at first and then realized it was quite gratifying to talk about this and to demonstrate to people that they were willing to talk about it in a public forum with detractors present. So that’s what accountability was all about. Because in turn it speaks to commitment.

Hughes: Susan Montrose told me about the public art program, which was established in 2000 at Mission Bay, so I learned.35 I imagine it was very close to your heart, just looking around your living room at all the art on the walls.

05-01:19:30 Bishop: Well, I would like to think that my personal interest in art, which is no different than countless others on campus, was not what drove me. What drove me was the sense that I was all too aware of public art. I had very strong feelings about its power to enhance the living environment of people. I had walked through the wonderful sculpture garden at UCLA; I had seen a world- class collection at [UC] San Diego. I saw what this could do for an academic community. Here was a chance to do it at UCSF because we were designing a whole new campus, and we could build into that the acquisition of public art and thereby really enhance the living environment of the place. The question became, how do you finance it? Now, in terms of the total construction budget it’s a pittance. In my toolkit was the knowledge that the City of San Francisco— and [Former Mayor] Willie Brown was very proud of this. I learned this from Willie, actually, from my wonderful meetings with him when he was mayor. He was one of the public officials I never ever regretted meeting. Even when he had an unhappiness with us, it was fun to meet with Willie. And enlightening.

35 Telephone conversation with interviewer, March 5, 2017.

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Hughes: Because of his exuberance?

05-01:21:26 Bishop: Well, he’s so smart and funny and perceptive. And truly dedicated to the city. Yes, he’s a wonderful person. We all have warts.

But in any event, the city has an ordinance that any new construction that has a public space, like a big lobby in a twenty-five story building, must put 2 percent of the construction budget into public art. (As a public institution, UCSF was exempted from this requirement.) I talked to my CFO Steve Barclay, and I said, “What about 1 percent?” “Oh, Mike, that’s a pittance. No problem. We’ll build that into the specified cost of the buildings.” And that’s what we did. So when we were raising money for the buildings, we knew that 1 percent of that money was for public art.

Now, how do you do it? Well, sure, I would love to have done it all alone; but I knew better. So the campus had its own little committee on arts and honors, a little broader scope. I felt this was a very big undertaking, and we needed professional help. So we assembled—and Susan Montrose was responsible for doing this—a committee of people from the art world, including Neal Benezra, who was then the relatively new director of the [San Francisco] Museum of Modern Art, and Mary Beebe, who’s the curator of the UC San Diego sculpture collection and well connected in the art world, and several other people who were well connected in the art world. They were able to reach out to major artists immediately.

We decided we wanted new commissions. We didn’t want what’s called off- the-shelf art. There’s one or two pieces off the shelf at Mission Bay now, but originally it was all site-specific. The artists came, looked around, said, I’d like to put something there. Some of them put stuff inside the buildings; some of them put it outside the buildings. The committee would sign off. Now, the campus committee—this was my compromise—got final say. So the professional committee would bring a new commission recommendation to the campus committee, and they would meet, and the artists would present to the committee. It was very gratifying to me that even some of the wackiest stuff—in my humble opinion wacky, which I actually liked. There’s this bizarre thing about academics’ taste in art. I’ve found that academics are generally—not all universally, but generally—very conservative about art. What I kept hearing when this stuff started going up, they were saying, art’s supposed to be beautiful. No, sorry, not necessarily. But anyway, the committee approved everything that was ever brought to them.

Hughes: Isn’t that something.

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05-01:24:27 Bishop: Yes. I thought when Richard Serra proposed to put those two immense metal slabs up that that would be laughed out of the house. They loved it. Now, he’s a brilliant salesman.

Hughes: You would attend these meetings, I gather.

05-01:24:47 Bishop: I did not usually. I went to the one by Serra; I just couldn’t resist. I was allowed to be there, but I just wanted not to be a presence. This was not my personal taste to volunteer. I’ve got nothing to do with it the choice of artwork, other than to commission it and authorize the payment for it.

Hughes: Well, a wonderful gift.

05-01:25:09 Bishop: It’s the largest public art collection in the city, that’s for sure.

Hughes: Quickly now, do you want to talk about QB3, which I think happened during your chancellorship.

05-01:25:25 Bishop: Oh, did it ever! That was another headache. Well, it all started with the governor.

Hughes: [Arnold] Schwarzenegger?

05-01:25:41 Bishop: No, Gray Davis.

He was convinced by a scientist of his acquaintance that if he wanted to leave a distinctive legacy to the state, he should literally fund an interdisciplinary research institute with its own research facilities on campuses of the University of California. The [UC] president, Dick Atkinson, knew that he could name in his sleep which campuses would succeed in a competition for this money because they already had great research strength, and he did not want any losers. So Dick decided that there would have to be a consortium, or several consortiums, and the one that— I can’t remember whether he designated it or we. I think he did. It was Berkeley, UCSF, and Santa Cruz had to come together, put in a single proposal. But here was the stickler. UCSF was to be the lead campus. Well, that stirred up a hornet’s nest across the bay [at UC Berkeley]. And I had to make it stick. It wasn’t fun.

Hughes: Why was that designation made? Why UCSF?

05-01:27:48 Bishop: I think because of our strong medical research and Dick’s recognition that left to our own devices we would compete very, very well. In any event, it came to pass. There was a committee of people. It was tremendously beneficial to

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Santa Cruz, and they had something very distinctive to contribute to us: a level at the time of biocomputing that we did not have. So I was very pleased with the idea. These things are never easy to make work. There’ve been countless examples around the country over the years. There’s nothing novel about efforts to make interdisciplinary research work, to create interdisciplinary research units. It’s just hard to make them into a reality because of the way science is organized into silos. And teaching is organized into silos and the thought processes are.

So I had Zach [Hall], who was then my second in command for academic matters. I think he may still have just been vice chancellor for research, before I was allowed to have an executive vice chancellor. He led that effort. It looked good on paper, but there was a lot of tension at first. Suffice it to say that over the years, things worked out for the better. And I would credit Reg [Regis] Kelly with much of this. The first director of QB3, Marvin Cassman, was from outside and just didn’t quite fit the bill, and he moved on of his own volition. Then Reg took over. Reg, although he’s impetuous, is also a man of immense patience. He just worked and worked and worked to win over people. I think now QB3 is a truly vibrant enterprise. I’m really out of the loop. But it’s very clear to me that it’s a vibrant enterprise that has engineers as well as the more typical biology people in Berkeley, working hand-in-hand with our folks, and Santa Cruz making its own contribution. But it was a while in the making.

Hughes: Was there any jealousy from other campuses?

05-01:30:36 Bishop: I wouldn’t want to use that word.

Hughes: What would you use?

05-01:30:43 Bishop: They wanted to be sure they were getting their share of the action.

Hughes: But they didn’t.

05-01:30:48 Bishop: Of course, they did. That’s why we had the joint planning.

Hughes: I’m thinking of people who were not part of QB3.

05-01:30:57 Bishop: Oh, I think people who were not part of it, I don’t think most of them cared or paid any attention whatsoever.

Hughes: Oh, really?

Bishop: Do you think a professor of history at Berkeley cared about this? No.

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Hughes: Well, no, but UCLA is a rather stellar scientific organization.

05-01:31:12 Bishop: So is Berkeley.

Hughes: UCLA could say, okay, why not me?

05-01:31:19 Bishop: Well, UCLA had its own. It had some consortium with—

Hughes: With the Salk?

05-01:31:26 Bishop: No, no, no, no, no. They were all UC campuses. UCLA was with San Diego and Santa Barbara.

Hughes: Oh, I didn’t know that.

05-01:31:43 Bishop: President Atkinson wanted everybody in the action in some way.

Hughes: Now we really have to wind up. But I do want to give you the chance to say whatever you like about your wife and boys.

05-01:32:01 Bishop: My what?

Hughes: Your wife and boys. Your family.

05-01:32:05 Bishop: Oh. Well, they put up with me, that’s the first thing. I was essentially a driven guy. Although I did find time for them. Kathryn reminded me of that not so long ago. I’ve told you what you need to know about Kathryn.

Hughes: Well, in terms of the chancellorship. How was she as a wife and a mother?

05-01:32:42 Bishop: I’ve said this more than once in public. She gave me forbearance that I’ll never be able to repay in terms of my commitment—time, energy, and attention—to science, which is not unusual for a scientist. But nevertheless, it does detract you from other things. But Kathryn and I shared a variety of things. We both loved good music; we both loved art. We both thought the world of our two sons. So all in all, it was a good marriage. You heard how we met.

Hughes: I did.

05-01:33:33 Bishop: I’ve already explained that to you. I think there was no question from day one that we would eventually get married. Our life together in Boston was a trial

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certainly for her because of my distractions as a medical student. The first year was good. That was during my fellowship at the Mass General Hospital, and I was in charge of my own life and time. So she and I had time together, although she was teaching school to help pay the bills. I think I mentioned before that I had a scholarship from Harvard Medical School the first two years. Then when I had to inform them that I was married and my wife was teaching school, they took the scholarship away. So Kathryn was supporting us, with a small amount of help from our parents. We lived in this basement apartment in the Back Bay neighborhood of Boston. It had two rooms and a little kitchenette that two people could not get in. It was below ground. We had to keep the windows closed at ground level even in the summer. The passing dogs were using the flowerbeds outside. But then when I went back to medical school, I got busier and busier. It culminated in two years as an intern and resident at the Mass General Hospital, when I was only home every other night and every other weekend. That was the schedule we had then, yes. And when I was home, I was exhausted.

So going to NIH as a postdoc changed things for us. There Kathryn began to have her way big time because I had gotten the appointment at NIH, but I couldn’t get away to go house hunting or apartment hunting or whatever. I said, “I have only one request, Kathryn. I want to walk to work.” She came back and she said, “You’re not walking to work. I’ve rented this little farm thirty miles north of Bethesda.” Why did she rent a farm? Well, when she was a teenager, she fell in love with horses—and she jumped them and she mucked the stalls and so forth—and she wanted a horse. And she got a Morgan horse, a gorgeous horse, a female. I wanted the stallion, and the owner said, “You’d be crazy to take the stallion.” We had it on this little farm, eighty-acre farm, and I was commuting to the lab and often coming home very late.

We had this horse which was untrained because we bought it as a yearling. Oh, it was a gorgeous animal. But it did not like being confined. It was confined by a barbed wire fence when it was out. I have this image of this horse going to the farthest corner, charging across the pasture—probably two acres—and leaping over the barbed wire fence and heading off across Montgomery County, which she did on more than one occasion. Kathryn had befriended a gentleman next door who had a horse farm and raced them at—where else?— Charles Town Racetrack. He would go off with her, with a horse van, and run down Contina, the first of her ten names. She had spectacular lineage. Suffice it to say that this went on for the two years I was a postdoc at NIH. I had to feed the horse in the morning, really early. Kathryn left for her job teaching school. So I fed the horse while she was in her stall, and she did not like being in her stall. So she would do her best to kill me when I came to feed her. However, when she was loose—now, this was really uncanny—if she was just hanging around the yard, she had gotten out but not run off — I was the only person she would come up to and allow to put a bridle on her. Now, go figure. In any event, when I got the opportunity to go to Germany for a year right

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after my second year as a postdoc, I dumped the little used Porsche that we had bought, and she dumped the horse. That horse went on to become the Northeast champion dressage horse.

Hughes: Amazing.

05-01:38:20 Bishop: Yes. She was a magnificent animal. But she was totally unschooled when we left her.

Kathryn was a spirited woman. And a wonderful mother, really. Neither of us was all that interested in starting a family at first, even after we got out here. But once she had her first child, Dylan, she was Earth Mother embodied. She was an absolutely splendid mother. So we shared interests. The hardest part for us was, we were both children of Lutheran ministers, and we sort of in parallel drifted away from the church, became apostate while we were in Boston, I guess. That was very hard for our mothers especially. Each mother blamed the other, right? Kathryn’s mother was convinced it was my fault, and my mother was convinced it was Kathryn’s fault. We shared the blame.

The boys are great. They’ve been a tremendous support to me after Kathryn’s death. Unstinting in their time and commitment and care. So it’s a family the way families should be.

Hughes: A good place to end?

05-01:39:56 Bishop: Sure.

Hughes: Well, I thank you.

End of interview

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CURRICULUM VITAE

J. MICHAEL BISHOP, M.D.

Position: University Professor Professor, Department of Microbiology and Immunology Director, G. W. Hooper Research Foundation Chancellor Emeritus University of California, San Francisco

Address: HSW 1501, Box 0552 University of California, San Francisco San Francisco, CA 94143

Phone: (415) 476-3211 Fax: (415) 476-6185 Email: [email protected] www: http://hooper.ucsf.edu/hooper/bishop_lab.html

Education

Swatara Township High School, Oberlin, Pennsylvania A.B., summa cum laude - Gettysburg College, Gettysburg, Pennsylvania, 1957 M.D., cum laude - Harvard University, Boston, Massachusetts, 1962 Research Fellow in Pathology, Massachusetts General Hospital, (Harvard University), 1959-60 Research Fellow in Dept. of Bacteriology and Immunology, Harvard Medical School, 1961-62 Intern and Assistant Resident in Internal Medicine, Massachusetts General Hospital, 1962-64 Research Associate in the Cell Biology Section, Laboratory of Biology of Viruses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 1964-67

Military Service

United States Public Health Service, 1963-67

Certification

Board Certification - National Board of Medical Examiners, all three parts

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Principal Positions Held

Senior Scientist, National Institutes of Health, 1966-68 Visiting Scientist in the laboratory of Dr. G. Koch, Heinrich-Pette Institute, Hamburg, Germany, 1967-68 Assistant Professor, Microbiology and Immunology, University of California, San Francisco, 1968-70 Associate Professor, Microbiology and Immunology, University of California, San Francisco, 1970-72 Professor, Microbiology and Immunology, University of California, San Francisco, 1973 – 2016; now Emeritus Director, The George Williams Hooper Research Foundation, University of California, San Francisco, 1981 - 2016 Professor, Biochemistry & Biophysics, University of California, San Francisco, 1982 - 2016 University Professor, University of California, 1994 -2016; now Emeritus Chancellor, University of California, San Francisco, 1998 - 2009 Arthur and Toni Rembe Rock Distinguished Professor, 2004 - 2009

Other Positions Held Concurrently

Founding Director of the Herbert W. Boyer Program in Biological Sciences, 1987 -1998 Member of the Graduate Programs in Cell Biology, Genetics, Developmental Biology, and Biochemistry and Molecular Biology, 1987 - 2016. Non-Resident Fellow, The Salk Institute for Biological Sciences, La Jolla, California, 1990 – 2009

Honorary Degrees

Doctor of Science, Honoris Causa, Gettysburg College 1983 Doctor of Science, Honoris Causa, University of Miami 1991 Honorary PhD, Peking University, People’s Republic of China 1993 Doctor of Science, Honoris Causa, Univ. of Rochester 1997 Doctor Honoris Causa, University of Helsinki, Finland 2000 Doctor of Science, Honoris Causa, Harvard University 2004 Doctor of Science, Honoris Causa, Gustavus Adolphus College 2006

Awards

U.S. Public Health Service Post-Sophomore Research Fellow 1959 Kaiser Award for Excellence in Teaching, UCSF 1969 Distinguished Alumnus Award, Gettysburg College 1980 AAMC Award for Distinguished Research in the Biomedical Sciences, from the

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American Association of Medical Colleges 1981 California Scientist of the Year, from the California Museum of Science and Industry 1982 Albert Lasker Basic Medical Research Award 1982 Passano Foundation Award 1983 Warren Triennial Prize, from Massachusetts General Hospital 1983 Armand Hammer Cancer Prize 1984 Alfred P. Sloan, Jr., Prize, from the General Motors Cancer Research Foundation 1984 Gairdner Foundation International Award 1984 American Cancer Society National Medal of Honor 1985 Lila Gruber Cancer Research Award, from the American Association of Dermatology 1985 Dickson Prize in Medicine, University of Pittsburgh 1985 Fellow, American Association for the Advancement of Science 1987 American College of Physicians Award 1987 Teaching Award, School of Medicine, UCSF 1989 Nobel Prize in Physiology or Medicine 1989 125th Anniversary Medal, UCSF 1990 Trustees Medal, Massachusetts General Hospital 1991 Rabbi Shai Shacknai Memorial Prize, Lautenberg Center of Hebrew University, Hadassah Medical School, Jerusalem 1991 University Professor, University of California 1994 Gold G. J. Mendel Honorary Medal for Merit in the Biological Sciences, Academy of Science of the Czech Republic 1995 Fifth Annual Public Service Award from the American Society for Cell Biology 1998 Joseph Priestley Award, Dickinson College 1999 Austrian Cross of Honor for Science and Art First Class from the Republic of Austria 1999 4th Alfred Knudson Award in Cancer Genetics 2000 National Medal of Science, USA 2003 Jill Rose Award from the Breast Cancer Research Foundation 2004 Honorable Mention, Medical Sciences, from American Association of Publishers, for book How to Win the Nobel Prize 2004 DiNA Lifetime Achievement Award 2009 Raymond and Beverly Sackler Award for Sustained National 2011 Leadership from Research!America University of California, Santa Cruz Foundation Medal 2011 2011-2012 Essential Core Teaching Award for Outstanding Lecture Series 2012

Honorary Societies

Phi Beta Kappa Alpha Omega Alpha National Academy of Sciences, USA

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American Academy of Arts and Sciences Institute of Medicine, USA American Association for the Advancement of Science, elected Honorary Fellow Fellow, American Academy of Microbiology Sigma Xi Scientific Research Society American Philosophical Society Royal Society of London

Professional Societies

American Society for Microbiology American Society of Biological Chemistry and Molecular Biology American Association of University Professors Federation of American Scientists American Society for Cell Biology American Association for Cancer Research

Service to Professional Publications

Associate Editor, Virology 1970-89 Editorial Board, Journal of Molecular Biology 1972-76 Advisory Board, BBA Reviews on Cancer 1973-85 Editorial Board, Journal of Biological Chemistry 1977-82 Editorial Board, Molecular and Cellular Biology 1982-93 Editorial Board, Genes, Chromosomes & Cancer 1989-98 Consulting Editor, Journal of Clinical Investigation 1991-94 Editorial Board, Current Opinion in Genetics and Development 1990 - 2006 Advisory Board, Cancer Cells 1989-91 Associate Editor, Molecular Biology of the Cell 1991-98 Editorial Board, Current Biology 1990-98 Editorial Board, Science 1993-98 Editorial Board, Chemistry & Biology 1994 - 1998 Ad hoc reviewer for Cell, Journal of Virology, Biochemistry, Science Nature, Biochimica Biophysica Acta, and others

Government and Other Professional Service

Virology Study Section of the National Institutes of Health 1972-75 Chair, Virology Study Section of the National Institutes of Health 1980-82 Committee of Fellowship Awards for California Division of the American Cancer Society 1975-80

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Subcommittee on Animal Viruses, Advisory to the NIH Committee on Recombinant DNA NIAID Task Force on Research Faculty Member, “The Biology of Cancer”, a series for general audiences sponsored by the American Cancer Society Co-organizer: Cold Spring Harbor Meeting on RNA Tumor Viruses 1978 Co-Chair: Gordon Conference on Animal Cells and Viruses 1979 Referee, Macy Faculty Scholar Award Program Co-organizer, UCLA Symposium, "Genes and Cancer" 1984 Commission on Life Sciences, National Research Council, (National Academy of Sciences) 1987-96 Joint Steering Committee for Public Policy/ Coalition for Life Sciences 1990 - 2009 American Society for Cell Biology: Public Policy Committee 1991 - 2000 President 1996 Scientists' Institute for Public Information (SIPI) Advisory Committee on Science and Technology Policy 1993 - 1998 Sigma Xi - The Scientific Research Society: Steering Committee on Forum, "Ethics, Values and the Promise of Science" 1993 Counselor, Institute of Medicine, (National Academy of Sciences) 1994-97 Co-Chair, Delegation for Biomedical Research 1994-96 Program Liaison, Congressional Caucus on Biomedical Research 1993 - present National Cancer Advisory Board, NIH 1994 - 2000 (Chairman, 1997 - 2000) Co-Chair, Committee to Review Intramural Program of the National Cancer Institute 1994 Cancer Centers Working Group 1996 Committee on Human Rights, (National Academy of Sciences) 1996-97 Senior Scientific Advisor to the National Center for Toxicogenomics (NCT) 2002 – 2005 Advisory Council for the Director, National Institutes of Health 2003-2008

Advisory Boards, Non-Profit

Board of Trustees, Leukemia Society of America 1973-78 University of Colorado Comprehensive Cancer Center 1975-78 St. Jude's Hospital 1978-82 Lawrence Berkeley Laboratory, University of California, Berkeley 1982-83 Department of Molecular Biology, Massachusetts General Hospital 1982-87 Harvard University Overseers' Committee to Visit the Medical School and School of Dental Medicine 1982-87 Frederick Cancer Research Facility, National Cancer Institute 1982-85

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External Advisory Committee, 39th Annual Symposium on Fundamental Cancer Research, Texas Medical Center, Houston 1985 Medical Advisory Board, Howard Hughes Medical Institute, Bethesda, Maryland 1985-90 Advisory Committee to the Director, NIH 1986-88 Board of Directors, Foundation for Advanced Cancer Studies, Frederick, Maryland 1988-95 Research Institute of Molecular Pathology (Vienna), 1990-99 Chairman 1994-99 Board of Trustees, The Salk Institute for Biological Studies, La Jolla, California 1991 - 2001 Aspen Cancer Conference Advisory Committee, 1991 - present Basel Institute for Immunology, Scientific Advisory Board 1992-2000 Roche Institute of Molecular Biology, Scientific Advisory Board 1992-96 Gladstone Institute of Virology & Immunology Scientific Advisory Board 1992-98 The Burroughs Wellcome Fund Career Awards Advisory Committee 1995-98 Board of Overseers, Harvard University 1995 - 2002 Research Institute of the Cleveland Clinic Foundation, Scientific Advisory Board 1997-98 European Institute of Oncology (IEO), Scientific Advisory Board 1997 - present International Advisory Board, San Francisco Exploratorium 1998 - present Swiss Institute for Cancer Research (ISREC), Scientific Advisory Board 2001 - present Spanish National Cancer Center Scientific Advisory Board (CNIO), Madrid, Spain 2004 – present American Association for Cancer Research - Council of Scientific Advisors (AACR-CSA) 2006 – present Sass Foundation for Medical Research, Scientific Advisory Board 2007 - 2009 Burroughs Wellcome Fund, Board of Directors 2007 - 2019 Aspen Cancer Conference, Board of Directors 2007 – present Howard Hughes Medical Institute, Medical Advisory Board 2009 – 2017 Faculty of 1000 Council of Scientific Advisors and Steering Committee 2011-2014

Advisory Boards, Corporate

Burrill & Company, San Francisco, California 1996-98 Canji, Inc., San Diego, California 1996-98 Cell Genesys, Inc., Foster City, California 1997-98 (formerly Somatix Therapy Corp., Alameda, California) 1991-97 Progenitor, Inc. (formerly Mercator Genetics, Inc), Menlo Park, California 1992-98 Mitotix, Boston, Massachusetts 1992-98

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The Molecular Sciences Institute, Palo Alto, California 1996-98 Syntex/Roche Bioscience, Palo Alto, California 1993-97 Terrapin Technologies, Inc., S. San Francisco, California 1991-98 Schering-Plough Biopharma (formerly DNAX Research Institute of Molecular and Cellular Biology), Palo Alto, California 1992 – 2011 Amgen, Thousand Oaks, California 2005 - 2007

University Service (A Partial List)

Curriculum Committee, School of Medicine 1969-73 Admissions Committee, School of Medicine 1973-76 Advisory Committee for Medical Scientists' Training Program 1977 - 1998 Advisory Committee for Program in Cell Biology 1982 - 1998 Major Search Committees: Dean, School of Medicine (twice); Chair, Anatomy; Chair, Pathology; Chair, Pharmacology (Committee Chair); Director, Hormone Research Laboratory; Director, Infectious Diseases; Chief, Division of Cell Biology; Department of Medicine (Committee Chair); Chancellor, UCSF Advisory Committee on Educational Policy, School of Medicine 1984-85 Stewardship Review Committee for Director, Cardiovascular Research Institute 1986 Director, Program in Biological Sciences 1987 - 1998 Executive Panel, Committee for the Future of UCSF, 1987-88 Steering Committee, Program in Developmental Biology 1987 - 1998 Planning Committee for the 21st Century 1990-98 Executive Committee, Science in Education Partnership 1990-98 Associate Director for Basic Research, UCSF Cancer Center 1992-98 Faculty Development Advisory Committee, School of Medicine 1992-98 UCSF Cancer Center Executive Working Group 1995-98 UCSF Cancer Center Director Search Committee 1996 UCSF Cancer Center Membership Committee 1994-98 Chancellor's Committee on Art, Honors and Recognition 1992-98 HHMI Research Resources Program Review Committee (Chair) 1996-98 Ethel and Jane Sokolow Memorial Cancer Endowment Committee 1997 Mission Bay (second campus) Task Force 1996–98 Senior Management Advisory Committee, University of California 2000 – 2009 Search Committee for Provost, University of California 2006 Chancellor’s Executive Board, UCSF 2010-2012

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Invited Presentations (a partial list)

International

EMBO Lecture on Tumor Viruses 1977 The Swedish Cancer Lecturer 1986 Leukaemia Research Fund (U.K.) Guest Lecturer 1987 Keynote Lecturer, Austrian Biochemical Society, Vienna 1989 Shacknai Memorial Lectureship, Hebrew University, Jerusalem 1991 Invited Lecturer, Institute of Molecular Biology, University of Hong Kong 1992 Invited Lecturer, Institute of Cell Biology, Shanghai, People’s Republic of China 1993 Keynote Speaker, 1st Symposium on Life Sciences, Peking University, Beijing, People’s Republic of China 1993 Guest Lecture, ICRF Colloquium, University of Warwick, United Kingdom 1993 Drummond Memorial Lecturer, University of Calgary 1993 Lecturer at 21st Century Forum, Yokohama City University, Yokohama, Japan 1993 Lecturer, Institute for Molecular and Cellular Biology, Osaka University, Osaka, Japan 1993 Lecturer, American Association for Cancer Research, Banff, Alberta, Canada 1994 Lee Kuan Yew Lectures, Singapore 1994 Miguel Aleman Lecturer, National University of Mexico, Mexico City, D. F. 1994 Hadassa Horn Lecturer, Weizmann Institute, Israel 1995 Visiting Professorship, University of Prague, Prague, The Czech Republic 1995 Louis Siminovitch Symposium Lecturer, University of Toronto 1997 Cancer Center Research Institute Lectureship, Tokyo, Japan 1998 Juan March Institute Lecturer, Madrid, Spain 1999 Lecturer, University of Hong Kong, Center of Genome Research 1999 Gairdner Foundation Symposium, Vancouver 1999 Harvard-Hebrew University Distinguished Lecture Series, Jerusalem 2000 Zhongnan University Symposium Keynote Speaker, Zhang Jia Jie, China 2002 “Modeling the Molecular Pathogenesis of Cancer,” University of Hamburg, Hamburg, Germany 2003 20th Anniversary of the Genes & Cancer Symposium, Warwick, England 2003 Jean Shanks Lecture, Academy of Medical Science, London, England 2003 Nobel Laureate Revisit Lecture, Stockholm, Sweden 2004 Blankenese Conference, Hamburg, Germany 2004 Jusélius 75th Anniversary Symposium, Sigrid Jusélius Foundation, Helsinki, Finland 2005 Centennial of French Cancer Society (Plenary Lecture), Bordeaux, France 2006 University of California Trust (UK), Inaugural Distinguished Lecture, London, England, and Paris, France 2007

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“Metastasis and Invasion,” Fondation IPSEN: Cancer Science Meeting Tuscany, Italy 2007 Lorne Cancer Conference, Melbourne, Australia 2008 “Metastasis and Metabolism,” Fondation IPSEN: Cancer Science Meeting, Costa Rica 2008 “Cancer in the Genomic Era”, Asia Society, Hong Kong, China 2008 20 Years IMP Conference, Vienna, Austria 2008 Fundacion BBVA-IRB Barcelona BioMed Conference, “Metastasis Genes & Functions,” Barcelona, Spain 2008 Cancer and Cell Cycle Conference, Lausanne, Switzerland 2008 Wright Science Colloquium, “Major Epidemics”, Geneva, Switzerland 2008 Nobel Lecture Series, Barcelona, Spain 2008 Frontiers in Biomedical Research Symposium, University of Hong Kong 2008 “Creating the Future: New Challenges in Biology and Medicine”, Fondation IPSEN, Paris, France 2009 “Molecular Targets of Cancer Therapy”, symposium, Fondation IPSEN: Cancer Science 5 Meeting, Jaipur, India 2009 “Advancement in our Understanding of the Biology & Treatment of Cancer”, symposium, Edmonton, Alberta, Canada 2009 50th Anniversary Celebration of the Gairdner International Awards, Toronto, Canada 2009 UCSF-Chile Collaboration, “Science & Friendship: The North Meets the South”, Santiago, Chile 2009 “Towards Personalized Cancer Medicine”, symposium, Keynote Address, Barcelona, Spain 2010 Karolinska Institute 200 Year Anniversary, Stockholm, Sweden 2010 Peking Union Medical College Hospital 90th Anniversary and Symposium, Beijing, China 2011 Alpach Technology Forum, Alpach, Austria 2011 Young Investigator Meeting, India 2012 IPSEN, “Mouse Models of Human Cancer,” Ouro Preto, Brazil 2012 Shanghai International Symposium, Shanghai, China 2012 Alpbach Technology Forum, Alpbach Austria 2012 ISREC, Lausanne, Switzerland 2012 7th Princess Chulabhorn International Science Congress,“Cancer from Basic Research to Cure”, keynote speaker, Bangkok, Thailand 2012 IPSEN, “Cancer Immunotherapy”, Sicily 2013 DFG (Deutsche Forschungsgemeinschaft) Cadenabbia Meeting,“From Molecular Mechanisms to Cancer Therapy”, Lake Como, Italy 2013 DKFZ, Schwab Symposium, Heidelberg, Germany 2013 ISREC, Lausanne, Switzerland 2013 Keynote Lecture, KSMCB Annual International Conf., Seoul, Korea 2013

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IPSEN Cancer Science Series, Paris, France 2014 ISREC, Lausanne, Switzerland 2014 International Scientific Advisory Board of Shanghai Research Center for Translational Medicine, Shanghai, China 2014 Cancer Cell Symposium, Beijing, China 2014 65th Lindau Nobel Laureate Meeting, Lindau, Germany 2015 ISREC, Lausanne, Switzerland 2015

National

22nd Faculty Research Lecture, University of California, San Francisco 1979 The William D. McElroy Lecture in Biology, University of California, San Diego 1982 Harvey Lecture, Rockefeller University 1983 James McGinnis Memorial Lecture, Duke University 1983 Culpepper Lectures, State University of New York, Stony Brook 1984 Smith, Kline and French Lectures, Vanderbilt University 1984 Storer Lectures, University of California, Davis 1984 Wendell Griffith Memorial Lecture, St. Louis University 1984 NIH Lecture 1984 The Jack Schultz Memorial Lecture, Fox Chase Cancer Center 1984 13th Marrs McLean Lecture in Biochemistry, Baylor College of Medicine, Houston 1985 G.E. Cartwright Visiting Professor of Medicine Lecture, University of Utah 1985 1st Bertram M. Marx Lecture, University of Alabama, Birmingham 1985 12th Annual Science in Medicine Lecture, University of Washington 1985 13th Carl Moore Lecture, Washington University School of Medicine, St. Louis 1985 3rd Annual Mark Hatfield Lecture, Oregon Health Sciences University 1985 Distinguished Lecturer, Lawrence Livermore Laboratories 1986 Abraham White Memorial Lecture, Syntex Corporation 1986 Hanna Lecturer, Case-Western Reserve University, Cleveland 1986 Hoffman-LaRoche Lecturer, Rutgers University 1986 Distinguished Achievement Award Lecture, UCLA 1987 Distinguished Lecturer, University of Cincinnati Medical Sciences 1987 Ida Beam Lecturer, University of Iowa 1987 10th Annual Chemerda Lecturer, Penn State University 1987 33rd Annual Cartwright Lecturer, Columbia University 1987 Karin Grunebaum Memorial Lecturer, Harvard Medical School 1988 General Motors Visiting Professorship, Dana-Farber Cancer Institute 1988 KROC Foundation Distinguished Lecturer 1988 Pew Scholars Lecture 1988 American Society for Biological Chemistry Lecture 1988

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Patricia R. Woodard Distinguished Lecturer, St. Francis Hospital 1988 Smithsonian Lecturer, “Frontiers in Genetics” 1988 Steenbock Lectureship, University of Wisconsin 1988 Stanhope Bayne-Jones Lecture, Johns Hopkins University School of Medicine 1988 Doisy Lecturer, University of Illinois at Urbana-Champaign 1988 Falk Distinguished Lecturer, NIH-Research Triangle Park, North Carolina 1988 Keynote lecturer, UCLA Symposium, “Genetic Mechanisms in Carcinogenesis and Tumor Progression” 1989 Pathogenesis Affinity Group-Ida M. Green Cancer Center Lecturer, Scripps Institute, La Jolla, California 1989 John Alexander Memorial Lecturer, University of Pennsylvania 1989 Honors Program Lecturer, NYU School of Medicine, New York 1990 5th Annual Colleen Giblin Memorial Lecturer, Columbia University, New York 1990 Harry Eagle Lecturer in Cancer Research, Albert Einstein College of Medicine, Yeshiva University, New York 1990 Chauncey Leake Lecturer, University of California, San Francisco 1990 S. Stanley Schneierson Memorial Lecturer, Mt. Sinai Medical Center, New York 1990 Thomas Watson, Jr. Lecture in Molecular Biology, Penn State University 1990 7th Annual Medical Research Forum Lecturer, University of Colorado 1991 Visiting Scholar's Lecture, National Institute of Dental Research 1991 Sigma Xi Lecturer, Wayne State University 1991 Craig Memorial Lecture in Microbiology, Oregon State University 1991 George Boxer Memorial Lecture, University of Medicine & Dentistry of New Jersey 1992 Capital Lecture in Science, The Carnegie Institution, Washington, D.C. 1992 Merck Centennial Lecture, Cornell University 1992 Charles A. Stuart Memorial Lecture, Brown University 1992 Distinguished Basic Science Lecture, Boston University, Boston, Massachusetts 1992 Cori Lecture, Roswell Park Cancer Institute, Buffalo, New York 1992 Distinguished Research Lecture, University of California, Santa Barbara, California 1993 GLAXO Lecture, Duke University, Durham, North Carolina 1993 Ralph R. Landes Lecture, University of North Carolina at Chapel Hill 1993 Allan Granoff Lecture, St. Jude's Children's Research Hospital, Memphis, Tennessee 1993 McGovern Lecture, Sigma Xi Forum, San Francisco, California 1993 Keynote Speaker, Aspen Cancer Conference, Aspen, Colorado 1993 Mike Hogg Award Lecture, University of Texas, M. D. Anderson Cancer Center 1993 Keynote speaker, 6th Scientific Meeting, Howard Hughes Medical Institute, Bethesda, Maryland 1993 Lecturer, American Association for Arts & Sciences, Stated Meeting, Berkeley, California 1994

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Horstmann Lecture, Yale University, New Haven, Connecticut 1994 Lecturer, Symposium on Gene Control, University of Maryland, Baltimore, Maryland 1994 Musselman Lectureship, Gettysburg College, Gettysburg, Pennsylvania 1994 Temin Lecture, University of Wisconsin, Madison, Wisconsin 1994 Eminent Scientist Lecture, University of Virginia, Charlottesville, Virginia 1994 Bren Fellows Lecturer, University of California, Irvine 1996 Sackler Foundation Distinguished Lecturer, Memorial Sloan-Kettering Cancer Center 1996 Lecturer, Institute for Cell and Developmental Biology, S.U.N.Y. 1996 10th Annual Richard C. Parker Lecturer, Columbia University 1996 Research Day Keynote Speaker, Cleveland Clinic Foundation 1996 Keynote Address, Chicago Society of Internal Medicine 1996 Freund Lecturer, Washington University School of Medicine 1996 Keynote Address, Keystone Symposium, “Genetics of Human Cancer” 1997 Wellcome Visiting Professorship, Medical College of Wisconsin 1997 "Frontiers in Development Biology" Lecture, Stanford University 1997 Speaker, Commencement Exercises, University of Rochester School of Medicine 1997 Keynote Lecture, 9th Usha Mahajani Symposium, University of California, San Diego 1997 National Academy of Sciences Distinguished Life Sciences Lecturer, Washington, D. C. 1997 Arizona Cancer Center Waddell Award Lecture, Tucson, Arizona 1998 Dean's Research Seminar Lecturer, University of California, San Francisco 1998 Distinguished Lecturer, Research Institute of Children's Hospital, Los Angeles 1998 Knox Memorial Lecture, Harvard University 1999 Priestly Award Lecture, Dickinson College, Pennsylvania 1999 Keystone Millennium Meeting, Colorado 2000 Aspen Cancer Conference 2000 University of Iowa Seminar, Iowa City 2000 John and Betty Moore Lecture, University of California, Riverside 2000 Hans Neurath Lecture, University of Washington, Seattle 2001 2001 Global Conference, Milken Institute, Los Angeles 2001 Lineberger Cancer Center Symposium, keynote address, Chapel Hill, North Carolina 2001 Hare Lecture, University of Rochester, New York 2001 Aspen Cancer Conference 2001 National MD/PhD Student Conference, Aspen 2001 American Association of Medical Colleges, Research Roundtable Nobelists, Washington, D. C. 2001 2001 Biomedical Sciences Graduate Program, Granlibakken, Lake Tahoe 2001

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Ted Couch Cancer Research Lectures, University of Southern Florida 2002 “Viruses, Oncogenes, and Cancer,” A Symposium in Honor of Peter K. Vogt, La Jolla, California 2002 2002 Timothy J. O’Leary, S. J., Distinguished Scientist Lecturer, Gonzaga University, Spokane, Washington 2002 American Association for Cancer Research, San Francisco 2002 Morton I. Grossman Distinguished Lectureship, San Francisco 2002 Aspen Cancer Conference 2002 “Mouse Models of Hematopoietic Malignancies”, workshop keynote speaker, National Cancer Institute, New York, New York 2002 Van Andel Research Institute Seminar Series, Grand Rapids, Michigan 2002 USA/Japan Cancer Seminar, Maui, Hawaii 2003 Sulkin Visiting Professor, University of Texas Southwestern Medical Center, Dallas, Texas 2003 Robert L. Sinsheimer Distinguished Lectureship, University of California, Santa Cruz 2003 Keynote lecturer, “Conquering Cancer Today,” symposium,Woodrow Wilson International Policy Center, Beverly Hills, CA 2003 Aspen Cancer Conference 2003 “The Double Helix and Biotech,” symposium, University of California, Berkeley 2003 Edward Rubenstein Lectureship, Stanford University 2004 Microbiology Seminar Series, University of Texas, Southwestern Medical Center, Dallas, Texas 2004 Keynote address, Keystone symposium, “Mouse Models of Human Cancer”, Keystone, Colorado 2004 Amgen Oncology Seminar Series, Thousand Oaks, CA 2004 BIO Convention-Plenary Session/Panel, San Francisco, CA 2004 Aspen Cancer Conference 2004 Keynote speaker, University of Pennsylvania School of Medicine 2004 Wayne State University Symposium, Detroit, MI 2004 Burnham Institute, Third Annual Outstanding Scientist Seminar, La Jolla, CA 2004 Morton Meyer Memorial Lecture, University of California, Berkeley 2004 Anthony Raimondi Lectureship, San Francisco, CA 2004 Keynote speaker, Johns A. Burns Medical School, Hawaii Bioscience Conference, Honolulu, Hawaii 2005 Genentech, Inc lecture, South San Francisco, CA 2005 Fields Lecture, Scripps Research Institute, La Jolla, CA 2005 Doreen J. Putrah Cancer Research Foundation Colloquium, University of California, Santa Barbara 2005 Keynote Speaker, Frederick Distinguished Scientist Series, National Cancer Institute, Frederick, MD 2005

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Symposium on Quantitative Biology, Cold Spring Harbor Laboratory, NY 2005 Aspen Cancer Conference 2005 Postdoctoral Society Distinguished Lecture, Lawrence Berkeley National Laboratory, Berkeley, CA 2005 Cancer Stem Cells Meeting, Banbury Center, Cold Spring Harbor Laboratory 2005 Dulbecco Lecture, Salk Institute, La Jolla, CA 2006 Penn State College of Medicine, Rod & Ceil Mortel Lectureship, Hershey, PA 2006 Aspen Cancer Conference, public lecture, “The Genomic Era in Health Care” 2006 “Winning the War Against Cancer: From Genomics to Bedside and Back,” Van Andel Research Institute, Grand Rapids, Michigan 2006 Nobel Conference 42, “Medicine: Prescription for Tomorrow,” Gustavus Adolphus College, Saint Peter, Minnesota 2006 Aspen Cancer Conference 2007 Aspen Institute Health Forum 2007, UC Irvine MD/PhD Lecture Series, Irvine, CA 2008 Aspen Cancer Conference 2008 Tony Hunter’s 65th Birthday Symposium, The Salk Institute, La Jolla, CA 2008 Honoring Elmer R. Pfefferkorn (two lectures), Dartmouth School of Medicine, Hanover, New Hampshire 2008 Lawrence Livermore National Laboratory (two lectures), Livermore, CA 2008 Kathleen Robison Huntsman Distinguished Lecture, University of Utah 2009 Aspen Cancer Conference 2009 Aspen Institute Health Forum 2009 Alando J. Ballantyne Distinguished Lectureship, MD Anderson Cancer Center, Houston, Texas 2009 Graduate School Distinguished Speaker Series, University of Wyoming 2009 Alando J. Ballantyne Distinguished Lectureship, MD Anderson Cancer Center, Houston, Texas 2009 UCLA Institute for Molecular Medicine, seminar 2010 Aspen Cancer Conference, keynote address 2010 HHMI Symposium, “Cell Signaling,” keynote address, Ashburn, Virginia 2010 Larson Lecture, University of Minnesota 2010 University of Miami Sylvester Comprehensive Cancer Center 2011 Distinguished Lecture Series, Intel International Science and Engineering Fair, Los Angeles 2011 Aspen Cancer Conference 2011 20th Annual AACR Aspen Workshop, “Molecular Biology in Clinical Oncology,” keynote speaker, Snowmass, Colorado 2011 Basic science seminar, Fred Hutchinson Cancer Center, Seattle, Washington 2011 New York University Colloquium 2012 Intel International Science and Engineering Fair, Pittsburgh, PA 2012

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Aspen Cancer Conference 2012 21st Annual AACR Aspen Workshop, “Molecular Biology in Clinical Oncology,” keynote speaker, Snowmass, Colorado 2012 26th Annual CABM Symposium, Rutgers University, New Jersey 2012 “Too Big to Fail,” Inder Verma’s symposium, The Salk Institute, La Jolla, CA 2012 Intel Science Fair, Phoenix, Arizona 2013 Aspen Cancer Conference 2013 Intel Science Fair, Los Angeles, CA 2014 “Metabolism, Diet & Disease” Organizing Committee, keynote speaker, Washington, D.C. 2014 Aspen Cancer Conference 2014 23rd Annual AACR Workshop, “Molecular Biology in Clinical Oncology,” keynote speaker, Snowmass, CO 2014 Nathan Award , Grand Rapids, MI 2014 Aspen Cancer Conference 2015 Banbury Center of Cold Spring Harbor Laboratory, “Tumor Cell Metabolism: Finding New Targets for Therapeutic Intervention”, New York 2015

Film and Television

Narrator and Host, "Cancer: The Pattern in the Genes", Horizon Science and Features Television, U.K. (BBC), 1983. Narrator and Host, "The Common Enemy", Armand Hammer Productions, Los Angeles, California, 1988. Narrator and Host, "How Do You Feel, Mr. Jacobs?"in the series "The Nobel Legacy," International Management Group/ Adrian Malone Productions, Nova and PBS, 1995 “The 100 Greatest Discoveries,” Discovery Science Channel, New York, New York, 2005.

Research Support Received

1. NIH, 5 R01 AI 08864, "Replicative Intermediates of Poliovirus RNA," 9-1-68 to 8- 31-73. 2. NIH, NCI-E-71-2147, "Study on the Role of Virion-Associated DNA Polymerase in Malignant Transformation by Avian Tumor Viruses," 10-1-70 to 5-2-73. 3. NIH CP 33293, "Study on the Role of Virion Associated DNA Polymerase," 5-1-73 to 8-30-76. 4. USPHS CA 12705, "Rous Sarcoma Virus: Replication and Cellular Transformation," 9-1-74 to 2-28-90. 5. American Cancer Society, VC70, "Biochemical Aspects of Rous Sarcoma Virus," 1-1-71 to 12-31-82.

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6. NIH, 1 T32 CA 09043, "The Molecular Analysis of Tumor Viruses," 7-1-75 to 6-30- 10. (Institutional Research Service Award for Postdoctoral Training, Program Director). 7. Bristol-Myers Corp. Program, "Development of Tyrosine-Specific Protein Kinase Inhibitors," 1-1-84 to 12-31-89. 8. NIH-NCI-DCT-DTP-83-6, “Northern California Cooperative Drug Discovery Project,”,7-1-84 to 6-30-89. 9. NIH, NCI-1-R35-CA-44338, "Retroviruses and Cancer Genes," 7-1-87 to 4-30-02.

Patents/Licenses

1994: Antibody Specific for Human GP130. Licensed as tangible materials (with Stephen Robbins) (UC Case No. SF94-B69).

1999: Monoclonal antibody against MYC. Licensed as tangible materials (with Gerard Evans) (UC Case No. SF99-110).

2001: Nes-Cre1 Transgenic Mouse Line. Licensed as tangible materials (with Andreas Trumpp) (UC Case No. SF02-001).

2002: Method for efficient RNA interference in mammalian cells. U.S. Patent Application Serial #10/448,612 (with Dun Yang) (UC Case No. SF-02-020).

2004: Construction of Plasmids Pmig Myc, Pmig Myc T358a/S373a/T400a, Pmig T358d/S373d/T400d". Licensed as tangible materials (with Zhongdong Huang) (UC Case No. SF05-048).

2005: Tre-Met/Lap-Tta Mouse Hcc Model. Licensed as tangible materials (with Rong Wang) (UC Case No. SF05-096).

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BIBLIOGRAPHY

J. Michael Bishop

Books

1. Genes and Cancer, Vol. 17 (Proceedings of UCLA Symposia on Molecular and Cellular Biology) (J. M. Bishop, M. Greaves and J. Rowley, eds.) New York: Alan R. Liss, Inc., 1984.

2. Proteins Encoded by Oncogenes, Cancer Surveys,Vol. 5, No. 2 (H. E. Varmus and J. M. Bishop, eds.) England: Oxford University Press, 1986.

3. Molecular Oncology (Bishop, J. M. and Weinberg, R. A., eds.). New York: Scientific American, Inc., 1996.

4. How to Win The Nobel Prize: An Unexpected Life in Science. Cambridge: Harvard University Press, 2003.

General Writings

1. Bishop, J. M. Infuriating Tensions: Science and the Medical Student. J. Med. Educ. 59: 91, 1984.

2. Bishop, J. M. Giant Leap Closes Gap in Theory of Evolution (review of Time Frames: The Rethinking of Darwinian Evolution and the Theory of Punctuated Equilibria, Niles Eldredge). San Jose Mercury News, July 14, 1985.

3. Bishop, J. M.: Too Scholarly to Inform (review of On the Shoulders of Giants: A Shandean Postscript, Robert K. Merton). San Jose Mercury News, September 22, 1985.

4. Bishop, J. M.: A Doctor Who Bailed Out Tells Why (review of Healing the Wounds: A Physician Looks at His Work, David Hilfiker). San Jose Mercury News, October 20, 1985.

5. Bishop, J. M.: How Queer Our World (review of How the World Works: A Guide to Science's Greatest Discoveries, Boyce Rensberger). San Jose Mercury News, March 23, 1986.

6. Bishop, J. M. Genes: The Answer to Cancer? (Presentation at the Congressional Biomedical Research Caucus Briefing). Congressional Record, 10/28/91.

7. Bishop, J. M. Teaching at UCSF: A Look at the Bright Side. (Adapted from remarks at the UCSF School of Medicine Leadership Retreat at Asilomar, 1992). UCSF Faculty- Alumni Bulletin, 1992: pp. 5-7.

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8. Bishop, J. M. Paradoxical Strife: Science and Society in 1993. In: Ethics, Values, and the Promise of Science (Proceedings of the Sigma Xi Forum, February, 1993), pp. 95-113, 1993.

9. Bishop, J. M. Lorenzo's Oil and Biomedical Research (prepared for the Op-Ed Service of the National Academy of Sciences and published in ca. 100 small- and middle-market U.S. newspapers), 1993.

10. Bishop, J. M., Kirschner, M. and Varmus, H. Science and the New Administration. Science 259: 444-445, 1993.

11. Bishop, J. M. Misguided Cells: The Genesis of Human Cancer (from a Friday Night Lecture, Marine Biological Laboratories, Woods Hole, Massachusetts, 8/6/93).Biol. Bull. 186: 1-8, 1994.

12. Bishop, J. M. An Unexpected Life in Science. The Washington Post, August 7, 1994.

13. Bishop, J. M. Wayward Cells: The Genesis of Human Cancer. (Lee Kuan Yew Distinguished Visitor Public Lecture Series, the University Liaison Office, National University of Singapore), pp. 1-65, 1994.

14. Bishop, J. M. The Crisis of Contemporary Science: Enemies of Promise. The Wilson Quarterly 19: 61-65, 1995.

15. Bishop, J. M. Cancer: The Rise of the Genetic Paradigm. Genes Dev. 9: 1309-1315, 1995.

16. Bishop, J. M. Paradoxical Strife: Science and Society. Bulletin of The American Academy of Arts and Sciences 48: 10-30, 1995.

17. Bishop, J. M. and Kirschner, M. Holding Health Research Hostage (Op-Ed article). Chicago Tribune and San Francisco Chronicle, December 27, 1995.

18. Bishop, J. M. Daniel Greenberg and Mammography: Unwarranted Interference. Published as a Letter to the Editor, The Washington Post, p. A27, May 24, 1997

19. Bishop, J. M. Cancer: What Should Be Done? Introductory Editorial, Science 278: 995, 1997.

20. Bishop, J. M. The How and Why of Stem Cells. San Francisco Chronicle. December 27, 2004.

21. Bishop, J. M. Mary Lasker and Her Prizes: An Appreciation, JAMA, 294:1418, 2005.

22. Bishop, J. M. and Varmus, H. Re-Aim Blame for NIH’s Hard Times, Science 312: 499, 2006.

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Reviews

1. Bishop, J.M., Koch, G. and Levintow, L.: Biological and physico- chemical aspects of poliovirus-induced double-stranded RNA. In: The Molecular Biology of Viruses (J. S. Colter, ed.) New York: Academic Press, p. 355, 1967.

2. Bishop, J.M. and Koch, G.: Plaque assay for poliovirus and poliovirus- specific RNAs. In: Fundamental Techniques in Virology (K. Habel and N.P. Salzman, eds.) New York: Academic Press, 1969.

3. Koch, G., Bishop, J.M. and Kubinski, H.: Fractionation of nucleic acids on columns built with methylated albumin-Kiselguhr. In: Fundamental Techniques in Virology (K. Habel and N. P. Salzman, eds.) New York: Academic Press, 1969.

4. Bishop, J.M. and Varmus, H.E.: The molecular biology of RNA tumor viruses. In: Cancer: A Comprehensive Treatise (F. F. Becker, ed.) New York: Plenum Press, p. 3, 1975.

5. Varmus, H.E., Shank, P.R., Kung, H.-J., Guntaka, R.V., Richards, O., and Bishop, J.M.: Mechanisms of synthesis and persistence of virus-specific DNA in cells infected by RNA tumor virus. In: Microbiology - 1977 (D. Schlesinger, ed.) Am. Soc. Microbiology, p.470, 1977.

6. Bishop, J.M.: Retroviruses. Ann. Rev. Biochem. 47:35, 1978.

7. Bishop, J. M.: The molecular biology of RNA tumor viruses: A physician's guide. New Engl. J. Med. 303: 675, 1980.

8. Bishop, J. M.: Enemies Within: The Genesis of Retroviral Oncogenes. Cell 23: 5, 1981.

9. Bishop, J.M., Gonda, T., Privalsky, M., Sheiness, D.K. and Vennstrom, B.: Avian retrovirus genes that cause leukemia. In: Differentiation and Function of Hematopoietic Cell Surfaces (Marchesi, V. T. and Gallo, R.C., eds.) New York: Alan R. Liss Inc., p. 263, 1982.

10. Bishop, J. M.: Oncogenes. Sci. Amer. 246 (3): 80, 1982.

11. Bishop, J. M. and Varmus, H. E.: Functions and Origins of Retroviral Transforming Genes, Chapter 9. In: Molecular Biology of Tumor Viruses, Part III RNA Tumor Viruses (Weiss, R., Teich, N., Varmus, H. E. and Coffin, J., eds.) New York: Cold Spring Harbor Press, p. 999, 1982.

12. Bishop, J. M.: Cellular Oncogenes and Retroviruses. Ann. Rev. Biochem. 52: 301, 1983.

13. Bishop, J. M.: Oncogenes and Proto-oncogenes. Hosp. Prac. 28: 67, 1983.

14. Bishop, J. M.: Cancer Genes Come of Age. Cell 32: 1018, 1983.

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15. Bishop, J. M.: Viruses, Genes and Cancer. The Harvey Lectures, Series 78: 137, 1983-84.

16. Bishop, J. M.: Retroviruses and Cancer Genes. In: Advances in Cancer Research, Vol. 37 (G. Klein and S. Weinhouse, eds.) New York: Academic Press, pp. 1, 1982.

17. Bishop, J. M.: Oncogenes. In: Cecil Textbook of Medicine, 17th Edition (J. B. Wyngaarden and L. H. Smith, Jr., eds.) Philadelphia: W. B. Saunders Publ. Co., p. 1066, 1985.

18. Bishop, J. M.: Retroviruses and Cancer Genes. In: Accomplishments in Cancer Research (J. G. Fortner and J. E. Rhoades, eds.) Philadelphia: J. B. Lippincott Company, 1985.

19. Bishop, J. M. and Varmus, H. E.: Supplement - Functions and Origins of retroviral Transforming Genes, Chapter 9. In: Molecular Biology of Tumor Viruses, Part III RNA Tumor Viruses (Weiss, R., Teich, N., Varmus, H. E. and Coffin, J., eds.) New York: Cold Spring Harbor Press, p. 249, 1985.

20. Bishop, J. M.: Viral oncogenes. Cell 42: 23-38, 1985.

21. Bishop, J. M.: Amplification of proto-oncogenes in tumorigenesis. In: Concepts in Viral Pathogenesis, Vol. II (A. L. Notkins and M. B. A. Oldstone, eds.) New York: Springer- Verlag, 1985.

22. Bishop, J. M. Trends in oncogenes. Trends in Genetics 1: 245-249, 1985.

23. Bishop, J. M.: Proto-oncogenes: Clues to the Puzzle of Purpose. Nature 316: 483, 1985.

24. Bishop, J. M.: Cancer Genes: An Enemy Within. The Third Annual Mark O. Hatfield Biomedical Research Lecture, Oregon Health Sciences University, 1986.

25. Bishop, J. M.: Oncogenes: Tricks with tyrosine kinases. Nature 319: 722-723, 1985.

26. Bishop, J. M.: Oncogenes as Hormone Receptors. Nature 321: 112-113, 1986.

27. Bishop, J. M.: From Proto-oncogene to Oncogene: The Molecular Genetics of Cancer. Adv. in Oncology 2: 3-8, 1986.

28. Bishop, J. M.: The Molecular Genetics of Cancer. Science 235: 305-311, 1987.

29. Bishop, J. M.: The Molecular Genetics of Cancer: 1988. Leukemia 2: 199-208, 1988.

30. Bishop, J. M. Oncogenes and Clinical Cancer. In: Oncogenes And The Molecular Origins of Cancer (R. A. Weinberg, Ed.). New York: Cold Spring Harbor Laboratories Press, pp. 327-358, 1989.

31. Bishop, J. M. Viruses, Genes and Cancer. Amer. Zool. 29: 653-666, 1989.

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32. Bishop, J. M. Retroviruses and Oncogenes II. In: Les Prix Nobel 1989, Almqvist & Wiksell International, Stockholm, pp.214-238, 1989, and Angewandte Chemie 102: 765- 773, 1990.

33. Varmus, H., Hirai, H., Morgan, D., Kaplan, J. and Bishop, J. M. Function, Location, and Regulation of the src Protein-tyrosine Kinase. In: Genetic Basis for Carcinogenesis: Tumor Suppressor Genes and Oncogenes (A. Knudson et al., Eds.), pp. 63-70. Tokyo: Japan Scientific Society Press/London: Taylor & Francis, 1990.

34. Bishop, J. M. Molecular Themes in Oncogenesis. Cell 64: 235-248, 1991.

35. Bishop, J. M. The Discovery of Proto-oncogenes. (Research Communication in the series "Milestones in Biological Research", FASEB J. 10: 362, 1996.

36. Bishop, J. M. and Weinberg, R. A. Chapter 1 - Introduction. In Molecular Oncology (J. M. Bishop and R. A. Weinberg, eds.). New York: Scientific American, Inc., pp. 1-11, 1996.

37. Bishop, J. M. and Hanafusa, H. Chapter 4 -Proto-oncogenes in Normal and Neoplastic Cells. In Molecular Oncology (J. M. Bishop and R. A. Weinberg, eds.). New York: Scientific American, Inc., pp. 61-83, 1996.

38. Kogan, S. and Bishop, J. M. Acute Promyelocytic Leukemia: From Treatment to Genetics and Back. Oncogene 18:5261, 1999.

39. Yang, D., Goga, A., and Bishop, J. M. RNA Interference (RNAi) with Rnase III-Prepared siRNAs. Methods in Molecular Biology 252: 471, 2004.

Research Articles

1. Bishop, J.M., Summers, D.F. and Levintow, L.: Characterization of ribonuclease-resistant RNA from poliovirus-infected HeLa cells. Proc. Nat. Acad. Sci. USA 54:1273, 1965.

2. Koch, G., Quintrell, N. and Bishop, J.M.: An agar cell-suspension plaque assay for isolated viral RNA. Biochem. Biophys. Res. Commun. 24:304, 1966.

3. Bishop, J.M. and Koch, G.: Purification and characterization of poliovirus-induced infectious double-stranded RNA. J. Biol. Chem. 242:1736, 1967.

4. Koch, G., Quintrell, N. and Bishop, J.M.: Differential effect of actinomycin D on the infectivity of single- and double-stranded poliovirus RNA. Virology 21:388, 1967.

5. Bishop, J.M., Quintrell, N. and Koch, G.: Poliovirus double-stranded RNA: Inactivation by ultraviolet light. J. Mol. Biol. 24:125, 1967.

6. Koch. G. and Bishop, J.M.: Poliovirus-induzierte Doppelstrang- und Mehrstrang-RNS. Zbl. Back. 1 (1967).

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7. Koch, G. and Bishop, J.M.: The effect of polycations on the interaction of viral RNA with mammalian cells: Studies of the infectivity of single- and double-stranded poliovirus RNA. Virology 35:9, 1969.

8. Bishop, J.M. and Koch, G.: Infectious replicative intermediate of poliovirus: Purification and characterization. Virology 37:521, 1969.

9. Bishop, J.M., Koch, G., Evans, B. and Merriman, M.: Poliovirus replicative intermediate: Structural basis of infectivity. J. Mol. Biol. 46:235, 1969.

10. Levinson, W., Bishop, J.M., Quintrell, N., Jackson, J. and Fanshier, L.: Synthesis of RNA in normal and Rous sarcoma virus-infected cells: Effect of bromodeoxyuridine. Virology 42:221, 1970.

11. Bishop, J.M., Levinson, W., Quintrell, N., Fanshier, L. and Jackson, J.: The low molecular weight RNAs of Rous sarcoma virus. I. The 4S RNA. Virology 42:182, 1970.

12. Bishop, J.M., Levinson, W., Sullivan, D., Fanshier, L., Quintrell, N. and Jackson, J.: The low molecular weight RNAs of Rous sarcoma virus. II. The 7S RNA. Virology 42:927, 1970.

13. Levinson, W., Bishop, J.M., Quintrell, N. and Jackson, J.: Presence of DNA in Rous sarcoma virus. Nature 227:1023, 1970.

14. Garapin, A.-C., McDonnell, J., Levinson, W., Quintrell, N., Fanshier, L. and Bishop, J.M.: DNA polymerase associated with Rous sarcoma virus and avian myeloblastosis virus: Properties of the enzyme and its product. J. Virol. 6:589, 1970.

15. McDonnell, J., Garapin, A.-C., Levinson, W. and Bishop, J.M.: DNA polymerase associated with Rous sarcoma virus: Delineation of two reactions with actinomycin. Nature 228:433, 1970.

16. Levintow, L. and Bishop, J.M.: Comparative aspects of poliovirus replication. J. Cell Physiol. 76:265, 1970.

17. Bishop, J.M. and Levintow, L.: Replicative forms of viral RNA: Structure and function. Prog. Med. Virol. 7:76, 1971.

18. Fanshier, L., Garapin, A.-C., McDonnell, J., Levinson, W. and Bishop, J.M.: DNA polymerase associated with avian tumor viruses: Secondary structure of the DNA product. J. Virol. 7:76, 1971.

19. Garapin, A.-C., Fanshier, L., Leong, J., Jackson, J., Levinson, W. and Bishop, J.M.: The DNA polymerase of Rous sarcoma virus: Kinetics of DNA synthesis and specificity of the product. J. Virol. 7:227, 1971.

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20. Faras, A., Fanshier, L., Garapin, A.-C., Levinson, W.E. and Bishop, J.M.: The DNA polymerase of Rous sarcoma virus: Studies on the mechanism of double-stranded DNA synthesis. J. Virol. 7:539, 1971.

21. Garapin, A.-C., Leong, J., Fanshier, L., Levinson, W.E. and Bishop, J.M.: Identification of virus-specific RNA in cells infected with Rous sarcoma virus. Biochem. Biophys. Res. Commun. 42:919, 1971.

22. Quintrell, N., Fanshier, L., Evans, B., Levinson, W.E. and Bishop, J.M.: The DNA polymerase(s) of Rous sarcoma virus: Effects of virion-associated endonuclease on the enzymatic product. J. Virol. 8:17, 1971.

23. Varmus, H.E., Levinson, W.E. and Bishop, J.M.: Extent of transcription by the RNA- dependent DNA polymerase of Rous sarcoma virus (RSV). Nature New Biol. 233:19, 1971.

24. Leong, J., Levinson, W. and Bishop, J.M.: Synchronization of Rous sarcoma virus production in chick embryo cells. Virology 47:133, 1972.

25. Best, M., Evans, B. and Bishop, J.M.: Double-stranded replicative form of poliovirus RNA: Phenotype of heterozygous molecules. Virology 47:592, 1972.

26. Varmus, H., Weiss, R., Friis, R., Vogt, P., Levinson, W. and Bishop, J.M.: Detection of avian tumor virus-specific nucleotide sequences in avian cell DNAs (Reassociation kinetics/RNA tumor viruses/avian DNA). Proc. Natl. Acad. Sci. USA 69:20, 1972.

27. Levinson, W., Varmus, H.E., Garapin, A.-C. and Bishop, J.M.: DNA of Rous sarcoma virus: Its nature and significance. Science 175:76, 1972.

28. Varmus, H.E., Bishop, J.M., Nowinski, R. and Sarkar, N.: Mammary tumor virus specific nucleotide sequences in mouse DNA. Nature New Biol. 238:189, 1972.

29. Faras, A.J., Taylor, J.M., McDonnell, J., Levinson, W. and Bishop, J.M.: Purification and characterization of the DNA polymerase associated with RSV. Biochemistry 11:2334, 1972.

30. Taylor, J.M., Faras, A.J., Varmus, H.E., Levinson, W. and Bishop, J.M.: RNA dependent DNA synthesis by the purified DNA polymerase of RSV: Characterization of the enzymatic product. Biochemistry 11:2343, 1972.

31. Leong, J., Garapin, A.-C., Jackson, J., Fanshier, L., Levinson, W.E. and Bishop, J.M.: Virus-specific ribonucleic acid (RNA) in cells producing Rous sarcoma virus: Detection and characterization. J. Virol. 9:891, 1972.

32. Taylor, J.M., Faras, A.J., Varmus, H.E., Goodman, H.M., Levinson, W.E. and Bishop, J.M.: Transcription of RNA by the RNA-directed DNA polymerase of Rous sarcoma virus and DNA polymerase I of E. coli. Biochemistry 12:460, 1973.

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33. Garapin, A.-C., Varmus, H.E., Faras, A., Levinson, W.E. and Bishop, J.M.: RNA- directed DNA synthesis by virion of Rous sarcoma virus: Further characterization of the templates and the extent of their transcription. Virology 52:264, 1973.

34. Levinson, W., Faras, A.J., Woodson, B., Jackson, J. and Bishop, J.M.: Inhibition of the RNA dependent DNA polymerase of Rous sarcoma virus by thiosemicarbazones and several cations. Proc. Natl. Acad. Sci. USA 70:174, 1973.

35. Faras, A.J., Taylor, J.M., Levinson, W., Goodman, J. and Bishop, J.M.: RNA-directed DNA polymerase of Rous sarcoma virus: Initiation of synthesis with 70S viral RNA as template. J. Mol. Biol. 79:163, 1973.

36. Varmus, H.E., Vogt, P.K. and Bishop, J.M.: Appearance of virus- specific DNA in mammalian cells following transformation by Rous sarcoma virus. J. Mol. Biol. 74:613, 1973.

37. Bishop, J.M., Jackson, N., Levinson, W.E., Medeiros, E., Quintrell, N. and Varmus, H.E.: The presence and expression of RNA tumor virus genes in normal and infected cells. Clinical Pathologists Symposium, Am. J. Clin. Pathol. 60:31, 1973.

38. Varmus, H.E., Quintrell, N., Nowinski, R., Medeiros, E., Sarkar, N. and Bishop, J.M.: Characterization of mouse mammary tumor virus specific RNA in murine tissues. J. Mol. Biol. 79:663, 1973.

39. Faras, A.J., Garapin, A.-C., Bishop, J.M. and Goodman, H.: The characterization of low molecular weight RNAs associated with 70S RNA of Rous sarcoma virus. J. Virol. 12:334, 1973.

40. Sullivan, D., Palacios, R., Stavnezer, J., Taylor, J.M., Faras, A.J., Kiely, M.L., Summers, N.M., Bishop, J.M. and Schimke, R.T.: Synthesis of a DNA sequence complementary to ovalbumin mRNA. J. Biol. Chem. 248:7530, 1973.

41. Varmus, H.E., Vogt, P.K. and Bishop, J.M.: Integration of Rous sarcoma virus specific DNA following infection of permissive and non-permissive hosts. Proc. Nat. Acad. Sci. USA 70:3067, 1973.

42. Faras, A.J., Levinson, W.E., Bishop, J.M. and Goodman, H.M.: Identification of a tRNA nucleotidyltransferase and its substrates in virions of avian RNA tumor viruses. Virology 58:126, 1974.

43. Haase, A.T., Garapin, A.-C., Faras, A.J., Varmus, H.E. and Bishop, J.M.: Characterization of the nuclei acid product of the visna virus RNA directed DNA polymerase. Virology 57:251, 1974.

44. Haase, A.T., Garapin, A.-C., Faras, A.J., Taylor, J.M. and Bishop J.M.: A comparison of the high molecular weight RNAs of visna virus and Rous sarcoma virus. Virology 57:259, 1974.

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45. Dahlberg, J.E., Sawyer, R.C., Taylor, J.M., Faras, A.J., Levinson, W.E., Goodman, H.M. and Bishop, J.M.: Transcription of DNA from the 70S RNA of Rous sarcoma virus: Identification of a specific 4S RNA which serves as primer. J. Virol. 13:1126, 1974.

46. Faras, A.J., Dahlberg, J.E., Sawyer, R.C., Harada, F., Taylor, J.M., Levinson, W.E., Bishop, J.M. and Goodman, H.M.: Transcription of DNA from the 70S RNA of Rous sarcoma virus: Structure of a 4S RNA primer. J. Virol. 13:1134, 1974.

47. Taylor, J.M., Garfin, D.E., Levinson, W.E., Bishop, J.M. and Goodman, H.M.: Tumor virus RNA-directed DNA synthesis: Nucleotide sequences at the 5'-terminus of nascent DNA. Biochemistry 13:3159, 1974.

48. Quintrell, N., Varmus, H. and Bishop, J.M.: Homologies among the nucleotide sequences of the genomes of C-type viruses. Virology 58:568, 1974.

49. Taylor, J.M., Varmus, H.E., Faras, A.J., Levinson, W.E. and Bishop, J.M.: Evidence for non-repetitive subunits in the genome of Rous sarcoma virus. J. Mol. Biol. 84:217, 1974.

50. Stavnezer, J., Huang, R.C.C., Stavnezer, E. and Bishop, J.M.: Isolation of mRNA for an immunoglobulin kappa chain and enumeration of the genes for the constant region of kappa chain in the mouse. J. Mol. Biol. 88:43, 1974.

51. Varmus, H.E., Heasley, S. and Bishop, J.M.: Detection of new and additional virus- specific DNA sequences in chick embryo fibroblasts after infection by Rous sarcoma virus. J. Virol. 14:895, 1974.

52. Varmus, H.E., Guntaka, R.V., Fan, W., Heasley, S. and Bishop, J.M.: Synthesis of viral DNA in the cytoplasm of duck embryo fibroblasts and in enucleated cells after infection by avian sarcoma virus. Proc. Natl. Acad. Sci. USA 71:3874, 1974.

53. Guntaka, R.V., Mahy, B., Bishop, J.M. and Varmus, H.E.: Ethidium bromide inhibits the appearance of closed circular viral DNA and integration of virus-specific DNA in duck cells infected by avian sarcoma virus. Nature 253:507, 1975.

54. Ringold, G., Lasfargues, E.Y., Bishop, J.M. and Varmus, H.E.: Production of mouse mammary tumor virus by cultured cells in the absence and presence of hormones: Assay by molecular hybridization. Virology 65:135, 1975.

55. Taylor, J.M., Cordell-Stewart, B., Rohde, W., Goodman, H.M. and Bishop, J.M.: Reassociation of 4S and 5S RNAs with the genome of avian sarcoma virus. Virology 65:248, 1975.

56. Ringold, G., Yamamoto, K.R., Tomkins, G.M., Bishop, J.M. and Varmus, H.E.: Dexamethasone-mediated induction of mouse mammary tumor virus RNA: A system for studying glucocorticoid action. Cell 6:299, 1975.

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57. Furuichi, Y., Shatkin, A.J., Stavnezer, E. and Bishop, J.M.: Blocked, methylated 5'- terminal sequences in avian sarcoma virus RNA. Nature 257:618, 1975.

58. Stehelin, D., Guntaka, R.V., Varmus, H.E. and Bishop, J.M.: Purification of DNA complementary to nucleotide sequences required for neoplastic transformation of fibroblasts by avian sarcoma viruses. J. Mol. Biol. 101:349, 1976.

59. Stehelin, D., Varmus, H.E., Bishop, J.M., Moscovici, C. and Vogt, P.K.: DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian cells. Nature 260:170, 1976.

60. Ringold, G.M., Blair, P.B., Bishop, J.M. and Varmus, H.E.: Nucleotide sequence homologies among mouse mammary tumor viruses. Virology 70:550, 1976.

61. Friedrich, R., Morris, V., Goodman, H.M., Bishop, J.M. and Varmus, H.E.: Differences between genomes of two strains of mouse mammary tumor virus as shown by partial RNA sequences analysis. Virology 72:330, 1976.

62. Stavnezer, E., Ringold, G., Varmus, H.E. and Bishop, J.M.: RNA complementary to the genome of RNA tumor viruses in virions and virus-producing cells. J. Virol. 20:342, 1976.

63. Cordell, B., Stavnezer, E., Friedrich, R., Bishop, J.M. and Varmus, H.E.: The nucleotide sequence which binds primer for DNA synthesis to the avian sarcoma virus genome. J. Virol. 19:548, 1976.

64. Guntaka, R.V., Richards, O.C., Shank, P., Kung, H.-J., Davidson, N., Fritsch, E., Bishop, J.M. and Varmus, H.E.: Covalently closed circular DNA of avian sarcoma virus: Purification from nuclei of infected quail tumor cells and measurement by electron microscopy and gel electrophoresis. J. Mol. Biol. 106:337, 1976.

65. Deng, C.T., Stehelin, D., Bishop, J.M. and Varmus, H.E.: Characteristics of virus-specific RNA in avian sarcoma virus-transformed BHK-21 cells and revertants. Virology, 76:313, 1977.

66. Stehelin, D., Fujita, D., Padgett, T., Varmus, H.E. and Bishop, J.M.: Detection and enumeration of transformation defective strains of avian sarcoma virus with molecular hybridization. Virology 76:675, 1977.

67. Tal, J., Fujita, D., Kawai, S., Varmus, H.E. and Bishop, J.M.: Purification of DNA complementary to the env gene of avian sarcoma virus and analysis of relationships among the env genes of avian leukosis-sarcoma viruses. J. Virol. 21:497, 1977.

68. Morris, V.L., Medeiros, E., Ringold, G.M., Bishop, J.M. and Varmus, H.E.: Comparison of mouse mammary tumor virus-specific DNA in inbred, wild, and Asian mice and in tumors and normal organs from inbred mice. J. Mol. Biol. 114:73, 1977.

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69. Tal, J., Kung, H.-J., Varmus, H.E. and Bishop, J.M.: Characterization of DNA complementary to nucleotide sequences adjacent to poly(A) at the 3' terminus of the avian sarcoma virus genome. Virology 79:183, 1977.

70. Shine, J., Czernilofsky, A.P., Friedrich, R., Goodman, M.H. and Bishop, J.M.: Nucleotide sequence at the 5' terminus of the avian sarcoma virus genome. Proc. Natl. Acad. Sci. USA 74: 1473, 1977.

71. Friedrich, R., Kung, H.-J., Varmus, H.E., Baker, B., Goodman, H.M. and Bishop, J.M.: Characterization of DNA complementary to nucleotide sequences at the 5' terminus of the avian sarcoma virus genome. Virology 79:198, 1977.

72. Stavnezer, J. and Bishop, J.M.: Synthesis and isolation of DNA complementary to nucleotide sequences encoding the variable region of immunoglobulin kappa chain. Biochemistry 16:4115, 1977.

73. Varmus, H.E., Padgett, T., Heasley, S., Simon, G. and Bishop, J.M.: Cellular functions are required for the synthesis and integration of avian sarcoma virus-specific DNA. Cell 11:307, 1977.

74. Weiss, S.R., Varmus, H.E. and Bishop, J.M.: The size and genetic composition of virus- specific RNAs in the cytoplasm of cells producing avian sarcoma-leukosis viruses. Cell 12:983, 1977.

75. Oppermann, H., Bishop, J.M., Varmus, H.E. and Levintow, L.: A joint product of the genes gag and pol of avian sarcoma virus: A possible precursor of reverse transcriptase. Cell 12:993, 1977.

76. Ringold, G.M., Yamamoto, K.R., Bishop, J.M. and Varmus, H.E.: Glucocorticoid stimulated accumulation of mouse mammary tumor virus RNA: Increased rate of synthesis of viral RNA. Proc. Natl. Acad. Sci. USA 74:2879, 1977.

77. Spector, D.H., Varmus, H.E. and Bishop, J.M.: Nucleotide sequences related to the transforming gene of avian sarcoma virus are present in the DNA of uninfected vertebrates. Proc. Natl. Acad. Sci. USA 75:4102, 1978.

78. Spector, D., Baker, B., Varmus, H.E. and Bishop, J.M.: Characteristics of cellular RNA related to the transforming gene of avian sarcoma viruses. Cell 13:381, 1978.

79. Spector, D., Smith, K., Padgett, T., McCombe, P., Roulland-Dussoix, D., Moscovici, C., Varmus, H.E. and Bishop, J.M.: Uninfected avian cells contain RNA related to the transforming gene of avian sarcoma viruses. Cell 13:371, 1978.

80. Varmus, H.E., Healsey, S., Kung, H.-J., Oppermann, H., Smith, V.C., Bishop, J.M. and Shank, P.R.: Kinetics of synthesis, structure, and purification of avian sarcoma virus- specific DNA made in the cytoplasm of acutely-infected cells. J. Mol. Biol. 120:55, 1978.

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81. Fujita, D.J., Tal, J., Varmus, H.E. and Bishop, J.M.: The env gene of chicken RNA tumor viruses: Extent of conservation in cellular and viral genome. J. Virol. 27:465, 1978.

82. Sheiness, D., Fanshier, L. and Bishop, J.M.: Identification of nucleotide sequences which may encode the oncogenic capacity of avian retrovirus MC29. J. Virol. 28:600, 1978.

83. Cordell, B., Weiss, S.R., Varmus, H.E. and Bishop, J.M.: A sequence of at least 104 nucleotides is transposed from the 5' terminus of the avian sarcoma virus genome to the 5' termini of smaller viral mRNAs. Cell 15:79, 1978.

84. Weiss, S.R., Hackett, P.B., Oppermann, H., Ullrich, A., Levintow, L., and Bishop, J.M.: Cell-free translation from the gag and pol genes of avian sarcoma virus: An amber suppressor tRNA causes read-through at the termination of gag but does not augment synthesis of the joint product of gag-pol. Cell 15:607, 1978.

85. Levinson, A., Oppermann, H., Levintow, L., Varmus, H.E. and Bishop, J.M.: Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein. Cell 15:561, 1978.

86. Shank, P.R., Hughes, S., Kung, H.-J., Majors, J., Quintrell, N., Guntaka, R.V., Bishop, J.M. and Varmus, H.E.: Mapping unintegrated avian sarcoma virus DNA: Termini of linear DNA bear 300 nucleotides present once or twice in two species of circular DNA. Cell 15:383, 1978.

87. Hughes, S., Vogt, P.K., Shank, P.R., Spector, D., Kung, H.-J., Breitman, M.L., Bishop, J.M. and Varmus, H.E.: Proviruses of avian sarcoma virus are terminally redundant, co- extensive with unintegrated linear DNA, and integrated at many sites in rat cell DNA. Cell 15:1397, 1978.

88. Hughes, S.H., Payvar, F., Spector, D., Schimke, R.T., Robinson, H.L., Bishop, J.M. and Varmus, H.E.: Heterogeneity of genetic loci in chickens: Analysis of endogenous viral and non-viral genes by cleavage of DNA with restriction endonucleases. Cell 18:347, 1979.

89. Cordell, B., Swanstrom, R., Goodman, H.M. and Bishop, J.M.: tRNATrp as primer for RNA-directed DNA polymerase, structural determinants of function. J. Biol. Chem. 254:1866, 1979.

90. Oppermann, H., Levinson, A.D., Varmus, H.E., Levintow, L. and Bishop, J.M.: Uninfected vertebrate cells contain a protein that is closely related to the product of the avian sarcoma virus transforming gene (src). Proc. Natl. Acad. Sci. USA 76:1804, 1979.

91. Sheiness, D. and Bishop, J.M.: DNA and RNA from uninfected vertebrate cells contain nucleotide sequences related to the putative transforming gene of avian myelocytomatosis virus. J. Virol. 31:514, 1979.

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92. Lee, J.S., Varmus, H.E. and Bishop, J.M.: Virus-specific messenger RNAs in permissive cells infected by avian sarcoma virus. J. Biol.Chem. 254:8015, 1979.

93. Sheiness, D., Bister, K., Fanshier, L., Moscovici, C. and Bishop, J.M.: Avian retroviruses that cause carcinoma and leukemia: Identification of nucleotide sequences associated with pathogenicity. J. Virol. 33:962, 1980.

94. Martin, G.S., Radke, K., Hughes, S., Quintrell, N., Bishop, J.M. and Varmus, H.E.: Mutants of Rous sarcoma virus containing extensive deletions of the viral genome. Virology 96:530, 1979.

95. Hughes, S.H., Robinson, H.L., Bishop, J.M. and Varmus, H.E.: The replication of subgroup E avian retroviruses is blocked at or before viral DNA synthesis in restrictive chicken cells. Virology 96:530, 1979.

96. Courtneidge, S.A., Levinson, A. and Bishop, J.M.: The protein encoded by the transforming gene of avian sarcoma virus (pp60src) and a homologous protein in normal cells (pp60proto-src) are associated with the plasma membrane. Proc. Natl. Acad. Sci. USA 77:3783, 1980.

97. Sheiness, S. H., Hughes, S. H., Varmus, H. E., Stubblefield, E. and Bishop, J. M.: The vertebrate homologue of the putative transforming gene of avian myelocytomatosis virus: Characteristics of the DNA locus and its RNA transcript. Virology 105: 415, 1980.

98. Quintrell, N., Hughes, S.H., Varmus, H.E. and Bishop, J.M.: Structure of viral DNA and RNA in mammalian cells infected with avian sarcoma virus. J. Mol. Biol. 143:363, 1980.

99. Cordell, B., DeNoto, F.M., Atkins, J.F., Gesteland, R.F., Bishop, J.M. and Goodman, H.M.: The forms of tRNATrp found in avian sarcoma virus and uninfected chicken cells have structural identity but functional distinctions. J.Biol. Chem. 255:9358, 1980.

100. Czernilofsky, A.P., DeLorbe, W., Swanstrom, R., Varmus, H.E., Bishop, J.M., Tischer, E. and Goodman, H.M.: The nucleotide sequence of "c": An untranslated but conserved domain in the genome of avian sarcoma virus. Nucl. Acid Res. 8:2967, 1980.

101. Gonda, T.J., Sheiness, D.K., Fanshier, L. and Bishop, J.M., Moscovici, C. and Moscovici, M.G.: The genome and the intracellular RNAs of avian myeloblastosis virus. Cell 23:279, 1981.

102. Hughes, S.H., Vogt, P.K., Bishop, J.M. and Varmus, H.E.: Endogenous proviruses of random bred chickens and ring-necked pheasants: Analysis with restriction endonucleases. Virology 108:222, 1981.

103. Hughes, S.H., Toyoshima, K., Bishop, J.M. and Varmus, H.E.: Organization of the endogenous proviruses of chickens: Implications for origin and expression. Virology 108:189, 1981.

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104. Hughes, S.H., Vogt, P.K., Stubblefield, E., Bishop, J.M. and Varmus, H.E.: Integration of avian sarcoma virus DNA in chicken cells. Virology 108:208, 1981.

105. Kung, H.-J., Shank, P.R., Bishop, J.M. and Varmus, H.E.: Identification and characterization of dimeric and trimeric circular forms of avian sarcoma virus-specific DNA. Virology 103:425, 1980.

106. DeLorbe, W.J., Luciw, P.A., Goodman, H.M., Varmus, H.E. and Bishop, J.M.: Molecular cloning and characterization of avian sarcoma virus circular DNA molecules. J. Virol., 36:50, 1980.

107. Swanstrom, R., Varmus, H.E. and Bishop, J.M.: The terminal redundancy of the retrovirus genome facilitates chain elongation by reverse transcriptase. J. Biol. Chem. 256:1115, 1981.

108. Levinson, A.D., Oppermann, H., Varmus, H.E. and Bishop, J.M.: The purified product of the transforming gene of avian sarcoma virus phosphorylates tyrosine. J. Biol. Chem. 255:11973, 1980.

109. Vennstrom, B., Fanshier, L., Moscovici, C. and Bishop, J.M.: Molecular cloning of the avian erythroblastosis virus genome, and recovery of oncogenic virus by transfection of chicken cells. J. Virol. 36:575, 1980.

110. Czernilofsky, A.P., Levinson, A.D., Varmus, H.E., Bishop, J.M., Tischer, E. and Goodman, H.M.: Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed amino acid sequence for gene product. Nature 287:198, 1980.

111. Kung, H.J., Fung, Y.K., Majors, J.E., Bishop, J.M. and Varmus. H.E.: Synthesis of plus strands of retroviral DNA in cells infected with avian sarcoma virus and mouse mammary tumor virus. J. Virology 37:127, 1981.

112. Sheiness, D., Vennstrom, B. and Bishop, J.M.: Virus-specific RNAs in cells infected by avian myelocytomatosis virus and avian myelocytomatosis virus and avian erythroblastosis virus: Modes of oncogene expression by defective leukemia viruses. Cell 23:291, 1981.

113. Swanstrom, R., DeLorbe, W.J., Bishop, J.M. and Varmus, H.E.: Sequencing of cloned unintegrated avian sarcoma virus DNA: Viral DNA contains direct and inverted repeats similar to those in transposable elements. Proc. Natl. Acad. Sci. USA 78:124, 1981.

114. Weiss, S.R., Varmus, H.E. and Bishop, J.M.: Cell-free translation of purified avian sarcoma virus src mRNA. Virology 110:476, 1981.

115. Hackett, P.B., Varmus, H.E. and Bishop, J.M.: The genesis of Rous sarcoma virus messenger RNAs. Virology 112:714, 1981.

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116. Hackett, P.B., Varmus, H.E. and Bishop, J.M.: Repair of lesions which cause premature termination of transcription in chicken embryo cells irradiated with ultraviolet light. Virology 112:752, 1981.

117. Payne, G.S., Courtneidge, S.A., Crittenden, L.B., Fadly, A,M., Bishop, J.M. and Varmus, H.E.: Analyses of avian leukosis virus DNA and RNA in bursal tumors suggest a novel mechanism for retroviral oncogenesis. Cell 23:311, 1981.

118. Oppermann, H., Levinson, W. and Bishop, J.M.: A cellular protein that associates with the transforming protein of Rous sarcoma virus is also a heat-shock protein. Proc. Natl. Acad. Sci. USA 78:1067, 1981.

119. Swanstrom, R., Hallick, L.M., Jackson, J., Hearst, J.E. and Bishop, J.M.: Interaction of psoralen derivatives with the RNA genome of Rous sarcoma virus. Virology 113:613, 1981.

120. Levinson, A., Courtneidge, S.A. and Bishop, J.M.: Structural and functional domains of the Rous sarcoma virus transforming protein (pp60src). Proc. Natl. Acad. Sci. USA 78:1624, 1981.

121. Oppermann, H., Levinson, A.D., Levintow, L., Varmus, H.E. and Bishop, J.M.: Two cellular proteins that immunoprecipitate with the transforming protein of avian sarcoma virus. Virology 113:736, 1981.

122. Baker, B., Robinson, H., Varmus, H.E. and Bishop, J.M.: Analysis of endogenous avian retroviruses DNA and RNA: Viral and cellular determinants of retrovirus gene expression. Virology 114:8, 1981.

123. Vennstrom, B., Moscovici, C., Goodman, H.M. and Bishop, J.M.: Molecular cloning of the avian myelocytomatosis virus genome, and recovery of infectious virus by transfection of chicken cells. J. Virology 39:625, 1981.

124. Hughes, S.H., Mutschler, A., Bishop, J.M. and Varmus, H.E.: A Rous sarcoma virus provirus is flanked by short direct repeats of cellular DNA which were present in only one copy prior to integration. Proc. Nat. Acad. Sci. USA 78:4299, 1981.

125. Parker, R.C., Varmus, H.E. and Bishop, J.M.: The cellular homologue (c-src) of the transforming gene of Rous sarcoma virus: Isolation, mapping, and transcriptional analysis of c-src and flanking regions. Proc. Natl. Acad. Sci. USA 78:5842, 1981.

126. Smart, J.E., Oppermann, H., Czernilofsky, A.P., Purchio, A.F., Erikson, R.L. and Bishop, J.M.: Characterization of sites for tyrosine phosphorylation in the transforming protein of Rous sarcoma virus (pp60v-src) and its normal cellular homologue (pp60c-src). Proc. Natl. Acad. Sci. USA 78: 6013, 1981.

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127. Coffin, J.M., Varmus, H.E., Bishop, J.M., Essex, M., Hardy, Jr., W.D., Martin, G.S., Rosenberg, N.E., Scolnick, E.M., Weinberg, R.A. and Vogt, P.K.: A proposal for naming host cell-derived inserts in retrovirus genomes. J. Virology 40:953, 1981.

128. Hackett, P.B., Swanstrom, R., Varmus, H.E. and Bishop, J.M.: The leader sequence of the subgenomic messenger RNAs of Rous sarcoma virus is approximately 390 nucleotides. J. Virol. 41:527, 1982.

129. Swanstrom, R., Varmus, H.E. and Bishop, J.M.: Nucleotide sequence of the 5' noncoding region and part of the gag gene of Rous sarcoma virus. J. Virology 41:535, 1982.

130. Payne, G.S., Bishop, J.M. and Varmus, H.E. Multiple arrangements of viral DNA and an activated host oncogene (c-myc) in bursal lymphomas. Nature 295:209, 1982.

131. Vennstrom, B. and Bishop, J.M.: Isolation and characterization of chicken DNA homologous to the two putative oncogenes of avian erythroblastosis virus. Cell 28:135, 1982.

132. Swanstrom, R., Bishop, J.M. and Varmus, H.E.: Structure of a replication intermediate in the synthesis of Rous sarcoma virus DNA in vivo. J. Virology 42:337, 1982.

133. Gonda, T.J., Sheiness, D.K., and Bishop, J.M.: Transcripts from the cellular homologues of retroviral oncogenes: Distribution among chicken tissues. Mol. Cell. Biol. 2:617, 1982.

134. Vennstrom, B., Sheiness, D., Zabielski, J., and Bishop, J.M.: Isolation and characterization of c-myc, a cellular homologue of the oncogene (v-myc) of avian myelocytomatosis virus strain 29 (MC29). J. Virology 42:773, 1982.

135. Privalsky, M.L. and Bishop, J.M.: Proteins specified by avian erythroblastosis virus: coding region localization and identification of a previously undetected erb-B polypeptide. Proc. Nat. Acad. Sci. USA 79:3958, 1982.

136. Klempnauer, K.-H., Gonda, T.J. and Bishop, J.M.: Nucleotide sequence of the retrovirus leukemia gene v-myb and its cellular progenitor c-myb: the architecture of a transduced oncogene. Cell 31:453, 1982.

137. Courtneidge, S. and Bishop, J.M.: The transit of pp60v-src to the plasma membrane. Proc. Natl. Acad. Sci. USA 79:7117, 1982.

138. Courtneidge, S., Ralston, R., Alitalo, K. and Bishop, J.M.: The subcellular location of an abundant substrate (p36) for tyrosine-specific protein kinases. Mol. Cell. Biol. 3:340, 1983.

139. Czernilofsky, A.P., Levinson, A.D., Varmus, H.E., Bishop, J.M., Tischer, E. and Goodman, H.: Corrections to the nucleotide sequence of the src gene of Rous sarcoma virus. Nature 301:736, 1983.

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140. Alitalo, K., Bishop, J.M., Smith, D. H., Chen, E. Y., Colby, W. W. and Levinson, A. D.: Nucleotide sequence of the v-myc oncogene of avian retrovirus MC-29. Proc. Natl. Acad. Sci. USA 80:100, 1983.

141. Gonda, T. and Bishop, J.M.: Structure and transcription of the cellular homologue (c- myb) of the AMV transforming gene (v-myb). J. Virol. 46:212, 1983.

142. Snyder, M.A., Bishop, J.M., Colby, W. and Levinson, A.D.: Phosphorylation of tyrosine- 416 is not required for the transforming properties and kinase activity of pp60v-src. Cell 32:891, 1983.

143. Privalsky, M.L., Sealy, L., Bishop, J.M., McGrath, J.P. and Levinson, A.D.: The product of the avian erythroblastosis virus erb-B locus is a glycoprotein. Cell 32:1257, 1983.

144. Simon, M.A., Kornberg, T.B. and Bishop, J.M.: Drosophila possesses three loci related to the oncogene of Rous sarcoma virus and has tyrosine specific protein kinase activity. Nature 302:837, 1983.

145. Alitalo, K., Schwab, M., Lin, C.C., Varmus, H.E. and Bishop, J.M.: Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proc. Natl. Acad. Sci. USA 80:1707, 1983.

146. Chen, L.-C., Courtneidge, S.A. and Bishop, J.M.: The immunological phenotype of lymphomas induced by avian leukosis viruses. Mol. Cell. Biol. 3:1077, 1983.

147. Swanstrom, R., Parker, R.C., Varmus, H.E. and Bishop, J.M.: Transduction of a cellular oncogene: the genesis of Rous sarcoma virus. Proc. Natl. Acad. Sci. USA 80:2519, 1983.

148. Schwab, M., Alitalo, K., Varmus, H.E., Bishop, J.M. and George, D.: A cellular oncogene (c-Ki-ras) is amplified, overexpressed, and located within karyotypic abnormalities in mouse adrenocortical tumor cells. Nature 303:497, 1983.

149. Klempnauer, K.-H., Ramsay, G., and Bishop, J.M.: The product of the retroviral transforming gene v-myb is a truncated version of the protein encoded by the cellular oncogene c-myb. Cell 331:345, 1983.

150. Luciw, P.A., Bishop, J.M., Varmus, H.E. and Capecchi, M.R.: Location and function of retroviral and SV40 sequences that enhance biochemical transformation after microinjection of DNA. Cell 33:705, 1983.

151. Sealy, L., Moscovici, G., Moscovici, C., Privalsky, M. and Bishop, J.M.: Site-specific mutagenesis of avian erythroblastosis virus: erb-B is required for oncogenicity. Virology 130:155, 1983.

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152. Sealy, L., Moscovici, G., Moscovici, C., and Bishop, J.M.: Site-specific mutagenesis of avian erythroblastosis virus: v-erb-A is not required for transformation of fibroblasts. Virology 130:179, 1983.

153. Klempnauer, K.-H. and Bishop, J.M.: The transduction of c-myb into avian myeloblastosis virus: locating the points of recombination within the cellular gene. J. Virol. 48:565, 1983.

154. Schwab, M., Alitalo, K., Klempnauer, K.-H., Varmus, H.E., Bishop, J.M., Gilbert, F., Brodeur, G., Goldstein, M. and Trent, J.: Amplified DNA with limited homology to the myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumor. Nature 305:245, 1983.

155. Alitalo, K., Ramsay, G., Bishop, J.M., Ohlsson, S., Colby, W.W., McGrath, J.P. and Levinson A.D.: Identification of nuclear proteins encoded by viral and cellular myc oncogenes. Nature 306:274, 1984.

156. Privalsky, M.L., Ralston, R. and Bishop, J.M.: The membrane glycoprotein encoded by the retroviral oncogene v-erb-B is structurally related to tyrosine-specific protein kinases. Proc. Natl. Acad. Sci. USA 81: 704, 1984.

157. Ralston, R. and Bishop, J.M.: The protein products of the oncogenes myc, myb and adenovirus E1a are structurally related. Nature 306:803, 1983.

158. Huang, C.C., Hammond, C. and Bishop, J.M.: Nucleotide sequence of v-fps in the PRCII strain of avian sarcoma virus. J. Virol. 50: 125, 1984.

159. Klempnauer, K.-H. and Bishop, J.M.: Neoplastic transformation by the E26 leukemia virus is mediated by a single protein containing domains of the gag and myb genes. J. Virol. 50: 280, 1984.

160. Symonds, G., Stubblefield, E., Guyaux, M. and Bishop, J.M.: Cellular oncogenes (c-erb- A and c-erb-B) located on different chicken chromosomes can be transduced into the same retroviral genome. Mol. Cell Biol. 4: 1627, 1984.

161. Schwab, M., Varmus, H. E., Bishop, J. M., Grzeschik, K.-H., Naylor, S. L., Sakaguchi, A., Brodeur, G. and Trent, J.: Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc. Nature 308: 288, 1984.

162. Klempnauer, K.-H., Symonds, G., Evan, G. I. and Bishop, J. M.: Subcellular localization of proteins encoded by the oncogenes of avian myeloblastosis virus and avian leukemia virus E26 and by the chicken c-myb gene. Cell 37: 537, 1984.

163. Brodeur, G. M., Seeger, R. C., Schwab, M., Varmus, H. E. and Bishop, J. M.: Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224: 1121, 1984.

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164. Evan, G. I., Lewis, G. K. and Bishop, J. M.: Isolation of monoclonal antibodies specific for the gene product of the avian oncogene myb. Mol. Cell. Biol. 4: 2843, 1984.

165. Lin, C. C., Alitalo, K., Schwab, M., George, D., Varmus, H. E. and Bishop, J. M.: Evolution of karyotypic abnormalities and c-myc oncogene amplification in human colonic carcinoma cell lines. Chromosoma (Berl) 92: 11, 1985.

166 Schwab, M., Ellison, J., Busch, M., Rosenau, W., Varmus, H. E. and Bishop, J. M.: Enhanced expression of the human gene N-myc consequent to amplification of DNA may contribute to malignant progression of neuroblastoma. Proc. Natl. Acad. Sci. USA 81: 4940, 1984.

167. Alitalo, K., Winqvist, R., Lin, C. C., de la Chapelle, A., Schwab, M. and Bishop, J. M.: Aberrant expression of an amplified c-myb oncogene in two cell lines from a colon carcinoma. Proc. Natl. Acad. Sci. USA 81: 4534, 1984.

168. Parker, R. C., Varmus, H. E. and Bishop, J. M.: Expression of v-src and chicken c-src in rat cells demonstrates qualitative differences between pp60v-src and pp60c-src. Cell 37: 131, 1984.

169 Luciw, P. A., Oppermann, H., Bishop, J. M. and Varmus, H. E.: Integration and expression of several molecular forms of Rous Sarcoma Virus DNA used for transfection of mouse cells. Mol. Cell. Biol. 4: 1260, 1984.

170. Snyder, M. A. and Bishop, J. M.: A mutation at the major phosphotyrosine in pp60v-src alters oncogenic potential. Virology 136: 375, 1984.

171. Privalsky, M. and Bishop, J. M.: Subcellular Localization of the v-erb-B Protein, the Product of a Transforming Gene of Avian Erythroblastosis Virus. Virology 135: 356, 1984.

172. Symonds, G., Klempnauer, K-H., Evan, G. and Bishop, J. M.: Induced differentiation of AMV-transformed myeloblasts: Phenotypic alteration without altered expression of the viral oncogene. Mol. Cell. Biol. 4: 2587, 1984.

173. Huang, C-C., Hammond, C. and Bishop, J. M.: The nucleotide sequence and topography of chicken c-fps: genesis of a retroviral oncogene encoding a tyrosine-specific protein kinase. J. Mol. Biol. 181: 175, 1985.

174. Ramsay, G., Evan, G. I. and Bishop, J. M.: The protein encoded by the human proto- oncogene c-myc. Proc. Natl. Acad. Sci. USA 81: 7742, 1984.

175. Parker, R. C., Mardon, G., Lebo, R. V., Varmus, H. E. and Bishop, J. M.: Isolation of duplicated human c-src genes located on chromosomes 1 and 20. Mol. Cell. Biol. 5: 831, 1985.

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176. Hammond, C I., Vogt, P. K. and Bishop, J. M.: Molecular cloning of the PRCII sarcoma viral genome and the chicken proto-oncogene c-fps. Virology 143: 300, 1985.

177. Moscovici, M. G., Klempnauer, K.-H., Symonds, G., Bishop, J. M. and Moscovici, C.: A transformation-defective mutant of avian myeloblastosis virus that is temperature sensitive for expression of the transforming protein p45v-myb. Mol. Cell. Biol. 5:3301, 1985.

178. Schwab, M., Ramsay, G., Alitalo, K., Varmus, H. E., Bishop, J. M., Martinsson, T., Levan, G. and Levan, A.: Amplification and enhanced expression of the gene c-myc in mouse SEWA tumor cells may be related to malignant progression. Nature 315: 345, 1985.

179. Snyder, M. A. and Bishop, J. M.: A mutation at the ATP binding site of pp60v-src abolishes kinase activity, transformation and tumorigenicity. Mol. Cell. Biol. 5: 1772, 1985.

180. Katzen, A. L., Kornberg, T. B. and Bishop, J. M.: Isolation of the proto-oncogene c-myb from Drosophila melanogaster. Cell 41: 449, 1985.

181. Schwab, M., Varmus, H. E. and Bishop, J. M.: The human gene N-myc contributes to neoplastic transformation of mammalian cells in culture. Nature 316: 160, 1985.

182. Simon, M. A., Drees, B., Kornberg, T. and Bishop, J. M.: Tissue-specific expression of Drosophila c-src. Cell 42: 831, 1985.

183. Jakobovits, A., Schwab, M., Bishop, J. M. and Martin, G. R.: Abundant expression of N- myc in teratocarcinoma stem cells and mid-gestation mouse embryos. Nature 318: 188, 1985.

184. Ralston, R. and Bishop, J. M.: The product of the proto-oncogene c-src is modified during the cellular response to platelet-derived growth factor. Proc. Natl. Acad. Sci. USA 82: 7845, 1985.

185. Schatzman, R. C., Evan, G. I., Privalsky, M. L. and Bishop, J. M.: Orientation of the v- erb-B gene product in the plasma membrane. Mol. Cell. Biol. 6: 1329, 1986.

186. Stanton, L. W., Schwab, M. and Bishop, J. M.: Nucleotide sequence of human N-myc. Proc. Natl. Acad. Sci. USA 83: 1772, 1986.

187. Huang, C.-C., Hay, N. and Bishop, J. M.: The role of RNA molecules in transduction of the proto-oncogene c-fps. Cell 44: 935, 1986.

188. Symonds, G., Klempnauer, K.-H., Snyder, M., Moscovici, G., Moscovici, C. and Bishop, J. M.: Coordinate regulation of myelomonocytic phenotype by v-myb and v-myc. Mol. Cell. Biol. 6: 1796, 1986.

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189. Ramsay, G., Stanton, L., Schwab, M. and Bishop, J. M.: The human proto-oncogene N- myc encodes nuclear proteins that bind DNA. Mol. Cell. Biol. 6: 4450, 1986.

190. Gerondakis, S. and Bishop, J. M.: The structure of the protein encoded by the chicken proto-oncogene c-myb: How c-myb and v-myb compare. Mol. Cell. Biol. 6: 3677, 1986.

191. Schwab, M., Klempnauer, K.-H., Alitalo, K., Varmus, H. E. and Bishop, J.M.: Rearrangement at the 5'-end of amplified c-myc in human COLO 320 cells is associated with abnormal transcription. Mol. Cell. Biol. 6: 2752, 1986.

192. Stone, J., de Lange, T., Ramsay, G., Jakobovits, E., Hay, N., Bishop, J. M., Varmus, H. and Lee, W.: Definition of regions in human c-myc involved in transformation and nuclear localization. Mol. Cell. Biol. 7: 1697, 1987.

193. Small, M. B., Hay, N., Schwab, M. and Bishop, J. M.: Neoplastic transformation by the human gene N-myc. Mol. Cell. Biol. 7: 1638, 1987.

194. Quintrell, N., Lebo, R., Varmus, H., Bishop, J. M., Pettenati, M. J., Le Beau, M. M., Diaz, M. O. and Rowley, J. D. Identification of a human gene (HCK) that encodes a protein- tyrosine kinase and is expressed in hemopoietic cells. Mol. Cell. Biol. 7: 2267, 1987.

195. Brown, P., Bowerman, B., Varmus, H. E. and Bishop, J. M.: Correct integration of retroviral DNA in vitro. Cell 49:347, 1987.

196. Hay, N., Bishop, J. M. and Levens, D.: Regulatory elements that modulate transcription from human c-myc. Genes & Develop.1:659, 1987.

197. Levin, D. E., Hammond, C. I., Ralston, R. O. and Bishop, J. M. Two yeast genes that encode novel protein kinases. Proc. Natl. Acad. Sci. USA 84:6035, 1987.

198. Stanton, L. W. and Bishop, J. M. Alternative processing of RNA transcribed from NMYC. Mol. Cell. Biol. 7: 4266, 1987.

199. Liu, E., Hjelle, B., Morgan, R., Hecht, F. and Bishop, J. M. Mutations of the Kirsten-ras protooncogene in human preleukemia. Nature 330: 186, 1987.

200. Chen, L., Lim, M. Y., Bose, Jr., H. and Bishop, J. M. Rearrangements of chicken immunoglobulin genes in lymphoid cells transformed by the avian retroviral oncogene v- rel. Proc. Natl. Acad. Sci. USA 85: 549, 1988.

201. Liu, E., Hjelle, B. and Bishop, J. M. Transforming genes in chronic myelogenous leukemia. Proc. Natl. Acad. Sci. USA 85: 1952, 1988.

202. Hjelle, B., Liu, E. and Bishop, J. M. Oncogene v-src transforms and establishes embryonic rodent fibroblasts but not diploid human fibroblasts. Proc. Natl. Acad. Sci. USA 85: 4355, 1988.

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203. Kaplan, J. M., Mardon, G., Bishop, J. M. and Varmus, H. E. The first seven amino acids encoded by the v-src oncogene act as a myristylation signal: lysine-7 is a critical determinant. Mol. Cell. Biol. 8: 2435, 1988.

204. Wells, A., Bishop, J. M. and Helmeste, D. Amplified gene for the Epidermal Growth Factor receptor in a human glioblastoma cell line encodes an enzymatically inactive protein. Mol. Cell. Biol. 8: 4561, 1988.

205. Wells, A. and Bishop, J. M. Genetic determinants of neoplastic transformation by the retroviral oncogene v-erbB. Proc. Natl. Acad. Sci. USA 85: 7597, 1988.

206. Schwab, M. and Bishop, J. M. Sustained expression of the proto-oncogene NMYC rescues rat embryo cells from senescence. Proc. Natl. Acad. Sci. USA 85: 9585, 1988.

207. Symonds, G., Hartshorn, A., Kennewell, A., O'Mara, M.-A., Bruskin, A. and Bishop, J. M. Transformation of murine myelomonocytic cells by MYC: Activation of the transforming potential of c-myc by point mutation. Oncogene 4: 285, 1989.

208. Shtivelman, E., Henglein, B., Groitl, P., Lipp, M. and Bishop, J. M. Identification of a human transcription unit affected by the variant chromosomal translocations 2;8 and 8;22 of Burkitt's lymphoma. Proc. Natl. Acad. Sci. USA 86: 3257, 1989.

209. Shtivelman, E. and Bishop, J. M. The PVT gene frequently amplifies with MYC in tumor cells. Mol. Cell. Biol. 9: 1148, 1989.

210. Brown, Patrick O., Bowerman, B., Varmus, H. E. and Bishop, J. M. Retroviral integration: Structure of the initial covalent product and its precursor. Proc. Natl. Acad. Sci. USA 86: 2525, 1989.

211. Wright, S. and Bishop, J. M. DNA sequences that mediate attenuation of transcription from the mouse protooncogene myc. Proc. Natl. Acad. Sci. 86: 505, 1989.

212. Hay, N., Takimoto, M. and Bishop, J. M. A FOS protein is present in a complex that binds a negative regulator of MYC. Genes & Devel. 3: 293, 1989.

213. Eilers, M., Picard, D., Yamamoto, K. R. and Bishop, J. M. Chimeras of the MYC oncoprotein and steroid receptors cause hormone-dependent transformation of cells. Nature 340: 66, 1989.

214. Bowerman, B., Brown, P. O., Bishop, J. M. and Varmus, H. E. A nucleoprotein complex mediates the integration of retroviral DNA. Genes & Devel.3: 469, 1989.

215. Downs, K. M., Martin, G. R. and Bishop, J. M. Contrasting patterns of myc and N-myc expression during gastrulation of the mouse embryo. Genes & Devel.3:860, 1989.

216. Weston, K. and Bishop, J. M. Transcriptional activation by the v-myb oncogene and its cellular progenitor, c-myb. Cell 58: 85, 1989.

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217. Morgan, D. O., Kaplan, J. M., Bishop, J. M. and Varmus, H. E. Mitosis-specific phosphorylation of p60c-src by p34cdc2-associated protein kinase. Cell 57: 775, 1989.

218. Bruskin, A., Jackson, J., Bishop, J. M., McCarley, D. J. and Schatzman, R. Six amino acids from the retroviral gene gag greatly enhance the transforming potential of the oncogene v-erb-B. Oncogene 5: 15, 1990.

219. Kaplan, J. M., Varmus, H. E. and Bishop, J. M. The src protein contains multiple domains for specific attachment to membranes. Mol. Cell. Biol. 10: 1000, 1990.

220. Schirm, S., Moscovici, G. and Bishop, J. M. A temperature-sensitive phenotype of avian myeloblastosis virus: determinants that influence the production of viral mRNAs. J. Virol. 64: 767, 1990.

221. Shtivelman, E. and Bishop, J. M. Effects of translocations on transcription from PVT. Mol. Cell. Biol. 10: 1835, 1990.

222. Feder, D. and Bishop, J. M. Purification and enzymatic characterization of pp60c-src from human platelets. J. Biol. Chem. 265: 8205, 1990.

223. Miller, M., Kennewell, A., Takayama, Y., Bruskin, A., Bishop, J. M., Johnson, G. and Symonds, G. Transformation of early erythroid precursor cells (BFU-E) by a recombinant murine retrovirus containing v-erb-B. Oncogene 5: 1125, 1990.

224. Ramsay, G. M., Moscovici, G., Moscovici, C. and Bishop, J. M. Neoplastic transformation and tumorigenesis by the human proto-oncogene MYC. Proc. Natl. Acad. Sci. USA 87: 2102, 1990.

225. Aghib, D. F., Bishop, J. M., Ottolenghi, S., Guerrasio, A., Serra, A. and Saglio, G. A 3' truncation of MYC caused by chromosomal translocation in a human T-cell leukemia increases mRNA stability. Oncogene 5: 707, 1990.

226. Morgan, D. O., Kaplan, J. M., Bishop, J. M. and Varmus, H. E. Production of p60c-src by baculovirus expression and immunoaffinity purification. Meth. Enz. 200: 645, 1991.

227. Katzen, A. L., Montarras, D., Jackson, J., Paulson, R. F., Kornberg, T. and Bishop, J. M. A gene related to the proto-oncogene FPS/FES is expressed at diverse times during the life cycle of Drosophila melanogaster. Mol. Cell. Biol. 11: 226, 1990.

228. Levin, D. E., Fields, F. O., Kunisawa, R., Thorner, J. and Bishop, J. M. A putative protein kinase C gene, PKC1, is required for the S. cerevisiae cell cycle. Cell 62: 213, 1990.

229. Katzen, A. L., Kornberg, T. and Bishop, J. M. Expression during Drosophila development of DER, a gene related to erbB-1 and neu: Correlations with mutant phenotypes. Devel. Biol.145: 287, 1991.

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230. Aghib, D. F. and Bishop, J. M. A 3' truncation of MYC caused by chromosomal translocation in a human T-cell leukemia is tumorigenic when tested in rat fibroblasts. Oncogene 12: 2371, 1991.

231. Katzen, A. L., Kornberg, T. and Bishop, J. M. Diverse expression of dsrc29A, a gene related to src, during the life cycle of Drosophila melanogaster. Devel.: 1169, 1990.

232. Eilers, M. and Bishop, J. M. The MYC protein activates transcription of the a- prothymosin gene. EMBO J. 10: 133, 1991.

233. Levin, D. E. and Bishop, J. M. A putative protein kinase gene (kin1+) is important for growth polarity in S. pombe. Proc. Natl. Acad. USA 87: 8272, 1990.

234. McMahon, M., Schatzman, R. C. and Bishop, J. M. The amino terminal fourteen amino acids of v-src can functionally replace the extracellular and transmembrane domains of v- erbB. Mol. Cell. Biol. 9: 4760, 1991.

235. Vetter, M. L., Martin-Zanca, D., Parada, L. F., Bishop, J. M. and Kaplan, D. R. NGF rapidly stimulates tyrosine phosphorylation of phospholipase C-q1 by a kinase activity associated with the product of the trk proto-oncogene. Proc. Natl. Acad. Sci. USA 88: 5650, 1991.

236. Feder, D. and Bishop, J. M. Identification of platelet membrane proteins that interact with amino-terminal peptides of pp60c-src. J. Biol. Chem. 266: 19040, 1991.

237. Shtivelman, E. and Bishop, J. M. Expression of CD44 is repressed in neuroblastoma cells. Mol. Cell. Biol. 11: 5446, 1991.

238. Magram, J. and Bishop, J. M. Dominant male sterility in mice caused by insertion of a transgene. Proc. Natl. Acad. Sci. USA 88: 10327, 1991.

239. Wright, S., Mirels, L. F. M., Calayag, M. C. B. and Bishop, J. M. Premature termination of transcription from the P1 promoter of the mouse c-myc gene. Proc. Natl. Acad. Sci. USA 88: 11383, 1991.

240. Radany, E. H., Brenner, M., Besnard, F., Bigornia, V., Bishop, J. M. and Deschepper, C. F. Directed establishment of rat cell lines with the phenotypic characteristics of mature type-1 astrocytes. Proc. Natl. Acad. Sci. USA 89: 6467, 1992.«PG»

241. Lichtenberg, U., Quintrell, N. and Bishop, J. M. Human protein-tyrosine kinase gene HCK: expression and structural analysis of the promoter region. Oncogene 7: 858, 1992.

242. Linstedt, A. D., Vetter, M. L., Bishop, J. M. and Kelly, R. B. Specific association of the proto-oncogene product pp60c-src with an intracellular organelle, the PC12 synaptic vesicle. J. Cell Biol. 117: 1077, 1992.

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243. Feder, D. and Bishop, J. M. A search for platelet components that interact with pp60c-src. Biotechnology of Cell Reg. 4: 256, 1991.

244. Shtivelman, E., Cohen, F. and Bishop, J. M. A human gene (AHNAK) encoding an unusually large protein with a 1.2-mm polyionic rod structure. Proc. Natl. Acad. Sci. USA 89: 5472, 1992.

245. Shtivelman, E. and Bishop, J. M. The human gene AHNAK encodes a large phosphoprotein located primarily in the nucleus. J. Cell Biol. 120: 625, 1993.

246. Finney, R. E. and Bishop, J. M. Predisposition to neoplastic transformation caused by gene replacement of Hras1 in Rat 1 fibroblasts. Science 260: 1524, 1993.

247. Lang, R. A. and Bishop, J. M. Macrophages are required for cell death and tissue remodeling in the developing mouse eye. CELL 74: 453, 1993.

248. Doyle, H. J. and Bishop, J. M. Torso, a receptor tyrosine kinase required for embryonic pattern formation, shares substrates with the Sevenless and Der pathways in Drosophila. Genes Dev. 7: 633, 1993. 1993.

249. Kalman, D., Whittaker, K., Bishop, J. M. and O'Lague, P. H. Domains of E1A that bind p105Rb, p130 and p300 are required to block Nerve Growth Factor-induced neurite growth in PC12 cells. Mol. Biol. Cell 4: 353, 1993.

250. Samuels, M., Weber, M. J., Bishop, J. M. and McMahon, M. Conditional Transformation of Cells and Rapid Activation of the Mitogen-Activated Protein Kinase Cascade by an Estradiol-Dependent Human Raf-1 Protein Kinase. Mol. Cell. Biol. 13: 6241, 1993.

251. Finney, R., Robbins, S. and Bishop, J. M. Association of pRas and pRaf-1 correlates with activation of a signal transduction. pathway. Current Biol.3: 805, 1993.

252. Dietrich, W. F., Radany, E. H., Smith, J. S., Bishop, J. M., Hanahan, D. and Lander, E. S. Genome-wide search for loss of hetero-zygosity in transgenic mouse tumors reveals candidate tumor suppressor genes on Chromosones 9 and 16. Proc. Natl. Acad. Sci. 91: 9451, 1994.

253. Kudoh, J., Wang, Y., Minoshima, S., Hashimoto, T., Amagai, M., Nishikawa, T., Shtivelman, E., Bishop, J. M. and Shimizu, N. Localization of the human desmoyokin/AHNAK gene to chromosome 11q12 by somatic cell hybrid analysis and fluorescence in situ hybridization. Cytogenet. Cell Genet. 70: 218, 1995.

254. Vetter, M. L. and Bishop, J. M. B PDGF receptor mutants defective for mitogenesis promote neurite outgrowth in PC12 cells. Current Biol. 5: 168, 1995.

255. Bishop, J. M., Determining the Causes of Cancer. Science: 267: 1613, 1995

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256. Robbins, S. M., Quintrell, N. A. and Bishop, J. M. Myristoylation and differential palmitoylation of the HCK protein-tyrosine kinases govern their attachment to membranes and association with caveolae. Mol. Cell. Biol. 15: 3507, 1995.

257. Therond, P. P., Knight, J. D., Kornberg, T. B. and Bishop, J. M. Phosphorylation of the Fused protein kinase in response to signaling from Hedgehog. Proc. Natl. Acad. Sci. USA 93: 4228, 1996.

258. Jackson, J. J., Paulson, R., Immergluck, K. and Bishop, J. M. The DFER gene of Drosophila melanogaster encodes two membrane-associated proteins that can both transform vertebrate cells. Oncogene 14: 641-652, 1997.

259. Wang, R., Kobayashi, R. and Bishop, J. M. Ligand-independent activation of the Met cell-surface receptor. Proc. Natl. Acad. Sci. USA 93: 8425, 1996.

260. Radany, E. H., Hong, K., Kesharvarzi, S., Lander, E. S. and Bishop, J. M. Strain-specific loss of heterozygosity involving a candidate novel tumor suppressor gene on mouse chromosome 4 in MMTV/v-Ha-ras transgene-induced mammary tumors. Proc. Natl. Acad. Sci. USA 94: 8664, 1997.

261. Katzen, A. L. and Bishop, J. M. myb provides an essential function during Drosophila development. Proc. Natl. Acad. Sci. USA 93: 13955, 1996.

262. Brown, D., Kogan, S., Lagasse, E., Weissman, I., Alcalay, M., Pelicci, P. G., Atwater, S. and Bishop, J. M. A PMLRARa transgene initiates murine acute promyelocytic leukemia. Proc. Natl. Acad. Sci. USA 94: 2551, 1997.

263. Weiss, W. A., Aldape, K., Mohapatra, G., Feuerstein, B. G. and Bishop, J. M. Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J.16: 2985, 1997.

264. Hogg, A., Schirm, S., Nakagoshi, H., Ishii, S., Bishop, J. M. and Gonda, T. J. Inactivation of a c-myb/estrogen receptor fusion protein in transformed primary haemopoietic cells leads to granulocyte/ macrophage differentiation and down regulation of c-kit but not c-myc or cdc2. Oncogene 15: 2885, 1997.

265. Bishop, J. M. From Cytosol to Protein Machines (cover blurb). Mol. Biol. Cell 8: Cover page (2/97).

266. Robbins, D. J., Nybakken, K. E., Kobayashi, R., Sisson, J. C., Scott, M. P., Bishop, J. M. and Therond, P. P. Hedgehog elicits signal transduction by means of a large complex containing the kinesin related protein Costal2. Cell 90: 225, 1997.

267. Katzen, A. L., Jackson, J., Harmon, B. P. and Bishop, J. M. Drosophila myb plays roles in the G2/M transition and in maintenance of diploidy. Genes Dev. 12: 831, 1998.

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268. Capobianco, A. J., Zagouras, P., Blaumueller, C. M., Artavanis-Tsakonas, S. and Bishop, J. M. Neoplastic transformation by truncated alleles of Human NOTCH1/TAN1 and NOTCH2. Mol. Cell. Biol. 17: 6265, 1997.

269. Foster-Barber, A. and Bishop, J. M. Src Interacts with Dynamin and Synapsin in Neuronal Cells. Proc. Natl. Acad. Sci. USA 95: 4673, 1998.

270. Kogan, S. C., Lagasse, E., Atwater, S., Bae, S.-C., Weissman, I., Ito, Y. and Bishop, J. M. The PEBP2MYH11 Fusion Created by Inv(16)(p13;q22) in Myeloid Leukemia Impairs Neutrophil Maturation and Contributes to Granulocytic Dysplasia. Proc. Natl. Acad. Sci. USA 95: 11863, 1998.

271. Guo, Q., Xie, J-W., Dang, C. V., Liu, E. T. and Bishop, J. M. Identification of a Large Myc-binding Protein that Contains RCC1-like Repeats. Proc. Natl. Acad. Sci. 95: 9172, 1998.

272. Zhu, J., Woods, D., McMahon, M. and Bishop, J. M. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev. 12: 2997, 1998.

273. Kalman, D., Gomperts, S. N., Hardy, S., Kitamura, M. and Bishop, J. M. Ras family GTPases control astrocyte process growth. Mol. Biol. Cell, 10: 1665, 1999.

274. Bates, B., Rios, M., Trumpp, A., Chen, C., Fan, G., Bishop, J. M. and Jaenisch, R. Neurotrophin-3 is required for proper cerebellar development. Nature Neuroscience 2: 115, 1999.

275. Zhu, J., Wang, H., Bishop, J. M. and Blackburn, E. H. Telomerase extends the lifespan of virus-transformed human cells without net telomere lengthening. Proc. Natl. Acad. Sci. USA 96: 3723, 1999.

276. Lallemand-Breitenbach, V., Guillemin, M. C., Janin, A., Daniel, M. T., Degos, L., Kogan, S., Bishop, J. M. and de The, H. Retinoic acid and arsenic synergize to eradicate leukemic cells in a mouse model of acute promyelocytic leukemia. J. Exp. Med. 189: 1043, 1999.

277. Felsher, D. W. and Bishop, J. M. Transient excess of MYC activity can elicit genomic instability and tumorigenesis. Proc. Natl. Acad. Sci. USA 96: 3940, 1999.

278. Kalman, D., Weiner, O., Goosney, D., Sedat, J., Finlay, B.B., Abo, A., and Bishop, J. M. Enteropathogenic E. coli acts through WASP and Arp2/3 complex to form actin pedestals. Nature Cell Biology 1:389, 1999.

279. Trumpp, A., Depew, M.J., Rubenstein, J.L.R., Bishop, J.M., and Martin, G.R. Cre- mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch. Genes & Devel. 13:3136, 1999.

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280. Smith-McCune, K., Kalman, D., Robbins, C., Shivakumar, S., Yuschenkoff, L. and Bishop, J. M. Intranuclear localization of human papillomavirus 16 E7 during transformation and preferential binding of E7 to the Rb family member p130. Proc. Natl. Acad. Sci. USA 96:6999, 1999.

281. Felsher, D. W. and Bishop, J. M. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol. Cell 4:199, 1999.

282. Kogan, S.C., Hong, S.H., Shultz, D.B., Privalsky, M.L., and Bishop, J.M. Leukemia initiated by PMLRARalpha: the PML domain plays a critical role while retinoic acid- mediated transactivation is dispensable. Blood 95:1541, 2000.

283. Weiss, W.A., Godfrey, T., Francisco, C., and Bishop, J.M. Genome-wide screen for allelic imbalance in a mouse model for neuroblastoma. Cancer Research 60:2483, 2000.

284. Felsher, D., Zetterberg, A., Zhu, J., Tlsty, T., and Bishop, J.M. Over-expression of MYC causes p53-dependent G2 arrest of normal fibroblasts. PNAS 97:10544, 2000.

285. Buchholz, F., Refaeli, Y., Trumpp, A. and Bishop, J.M. Inducible chromosomal translocation of AML and ETO genes through Cre/loxP mediated recombination in the mouse. EMBO Reports. 1:1333, 2000.

286. Kogan, S.C., Brown, D.E., Shultz, D.B., Truong, B-T H., Lallemand-Breitenbach, V., Guillemin, M.C., Lagasse, E., Weissman, I.L., and Bishop, J.M. BCL-2 cooperates with PMLRAR to block neutrophil differentiation and initiate acute leukemia. J. Exper. Med. 193:531, 2001.

287. Nybakken, K., Turck, C., Robbins, D.J., and Bishop, J.M. Hedgehog-stimulated Phosphorylation of the Kinesin-related Protein Costal2 Is Mediated by the Serine/Threonine Kinase Fused. Jour. Biol. Chem. 277: 24638-24647, 2002.

288. Trumpp, A., Refaeli, Y., Oskarsson, T., Gasser, S., Murphy, M., Martin, G.R., and Bishop, J.M. c-Myc regulates mammalian body size by controlling cell number but not cell size. Nature 414:768, 2001.

289. Buchholz, F., and Bishop, J.M. loxP directed cloning: Use of Cre recombinase as a universal restriction enzyme. Nature Biotechnology 19:1047, 2001.

290. Wang, R., Ferrell, L.D., Faouzi, S., Maher, J.J., and Bishop, J.M. Activation of the Met receptor by cell attachment induces and sustains hepatocellular carinomas in transgenic mice. J. Cell Biol., 153:1023, 2001.

291. Hahn, M., and Bishop, J.M. Expression pattern of Drosophila ret suggests a common ancestral origin between the metamorphosis precursors in endoderm and the vertebrate enteric neurons. PNAS 98: 1053, 2001.

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292. Cheng, Y. and Bishop, J. M. Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex. Proc. Natl. Acad. Sci. USA 99:5442, 2002.

293. Jain, M., Arvanitis, C., Chu, K., Dewey, W., Leonhardt, E., Trinh, M., Sundberg, C. D., Bishop, J. M., and Felsher, D. W. Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science 297: 102, 2002.

294. Padua, R. A., Larghero, J., Robin, M., le Pogam, C., Schlageter, M-H, Muszlak, S., Fric, J., West, R., Rousselot, P., Phan, T. H., Liesbeth, M., Teiserenc, H., Carpentier, A. F., Kogan, S., Degos, L., Pla, M., Bishop, J. M., Stevenson, F., Charron, D., and Chomienne, D. PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia. Nature Medicine 9: 1413, 2003.

295. Yang, D., Buccholz, F., Huang, Z.D., Goga, A., Chen, C.-Y., Brodsky, F. M., Bishop, J. M. Short RNA duplexes produced by hydrolysis with E. coli RNase III mediate effective RNA interference in vertebrate cells. PNAS 99: 9942, 2002.

296. Huang, Z., Traugh, J. A., and Bishop, J. M. Negative Control of the Myc Protein by the Stress-Responsive Kinase Pak2. Molecular and Cellular Biology 24: 1582, 2003.

297. Yang, D., Welm, A., and Bishop, J. M. Cell Division and Cell Survival in the Absence of Survivin. PNAS 101: 15100, 2004.

298. Kim, S., Chin, K., Gray, J. W., and Bishop, J. M. A Screen for Genes that Suppress the Loss of Contact Inhibition Induced by MYCN: Identification of ING4 as a Candidate Tumor Suppressor Gene in Human Cancer. PNAS 101: 16251, 2004.

299. Shachaf, C. M., Kopelman, A. M., Arvanitis, C., Karlsson, A., Beer, S., Mandl, S., Bachmann, M. H., Borowsky, A. D., Ruebner, B., Cardiff, R. D., Yang, Q., Bishop, J. M., Contag, C. H., and Felsher, D. W. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 431: 1112, 2004.

300. Refaeli, Y., Field, K. A., Turner, B.C., Trumpp, A., and Bishop, J. M. The Proto- oncogene MYC can break B-cell tolerance. PNAS 102: 4097, 2005.

301. Welm, A. L., Kim, S., Welm, B. E., and Bishop, J. M. MET and MYC cooperate in mammary tumorigenesis. PNAS 102: 4324, 2005.

302. Goga, A., Yang, D., Tward, A., Morgan, D., and Bishop, J. M. Inhibition of Cdk1 as a potential therapy for tumors over-expressing MYC. Nature Medicine 13: 820, 2007.

303. Welm, A. L., Sneddon, J. B., Taylor, C., Nuyten, D. S. A., van de Vijver, M. J., Hasegawa, B. H., and Bishop, J. M. The macrophage-stimulating protein pathway promotes metastasis in a mouse model for breast cancer and predicts poor prognosis in humans. PNAS 104: 7570, 2007.

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304. Tward, A. D., Jones, K. D., Yant, S., Cheung, S. T., Fan, S. T., Chen, X., Kay, M. A., Wang, R., and Bishop, J. M. Distinct pathways of genomic progression to benign and malignant tumors of the liver. PNAS 104:14771, 2007.

305. Swarbrick, A., Roy, E., Allen, T., and Bishop, J. M. Id1 cooperates with oncogenic Ras to induce metastatic mammary carcinoma by subversion of the cellular senescence response. PNAS 105: 5402, 2008.

306. Field, K. A., Charoenthongtrakul, S., Bishop, J. M., and Refaeli, Y. Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas. Molecular Cancer 7: 39, 2008.

307. Refaeli, Y., Young, R. M., Turner, B. C., Duda, J., Field, K. A., and Bishop, J. M. The B-cell antigen receptor and over-expression of MYC can cooperate in the genesis of B- cell lymphomas. PLoS Biology 6:1208, 2008.

308. Kim, S., Welm, A. L., and Bishop, J. M. A dominant mutant allele of the ING4 tumor suppressor found in human cancer cells exacerbates MYC-initiated mouse mammary tumorigenesis. Cancer Research 70: 5155, 2010.

309. Woods, S., and Bishop, J. M. A new transgenic mouse line for tetracycline inducible transgene expression in mature melanocytes and the melanocyte stem cells using the Dopachrome tautomerase promoter. Transgenic Research online 2010.

310. Yang, D. Liu, H., Goga, A., Kim, S., Yuneva, M., Bishop, J. M. Therapeutic potential of a synthetic lethal interaction between the MYC proto-oncogene and inhibition of aurora- B kinase. PNAS 107: 13836, 2010.

311. Nair, R., Junankar, S., O’Toole, S., Shah, J., Borowsky, A. D., Bishop, J. M., and Swarbrick, A. Redefining the expression and function of the inhibitor of differentiation 1 in mammary gland development. PLoS One 5 (8): e11947, 2010.

312. Liu, H., Radisky, D. C., Yang, D., Xu, R., Radsky, E. S., Bissell, M. J. and Bishop, J. M. MYC suppresses human cancer cell metastasis by direct transcriptional silencing of v and 3 integrin subunits. Nature Cell Biology 14 (6): 567, 2012.

313. Allen, T., Zhu, C. Q., Jones, K. D., Yanagawa, N., Tsao, M.-S., and Bishop, J. M. Interaction between MYC and MCL1 in the genesis and outcome of non-small cell lung cancer. Cancer Research 71 (6): 2212, 2011.

314. Allen, T., Rodriguez, E., Jones, K. D., and Bishop, J. M. Activated Notch1 induces lung adenomas in mice and cooperates with Myc in the generation of lung adenocarcinoma. Cancer Research 71 (18): 6010, 2011.

315. Qu, J. and Bishop, J. M. Nucleostemin maintains embryonic stem cell identity and promotes reprogramming of somatic cells to pluripotency. J. Cell Biol 197 (6): 731, (2012).

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316. Yuneva, M., Fan, T. W. M., Allen, T. A., Higashi, R. M., Ferraris, D. V., Tsukamoto, T., Matés, J. M., Alonso, F. J., Wang, C., Seo, Y., Chen, X., and Bishop, J. M. The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metabolism 15 (2): 157 (2012).

317. Chow, E. K.-H., Fan, L.-L., Chen, X., and Bishop, J. M. Oncogenic-specific formation of chemoresistant murine hepatic cancer stem cells. Hepatology 56 (4): 1331 (2012).

318. Moore, L., Chow, E. K.-H., Osawa, E., Bishop, J. M., and Ho, D. Diamond-Lipid Hybrids Enhance Chemotherapeutic Tolerance and Mediate Tumor Regression. Advanced Materials published online April 15, 2013.

319. Yang, D., Liu, H., Bhagwandin, V., Goga, A., Lock, R., Debnath, J., and Bishop, J. M. The autophagy gene atg5 facilities tumorigenesis by repressing the expression of let-7 microRNAs. In revision, 2016.

320. Bhagwandin, V., Bishop, J. M., Wright, W. E., and Shay, J. W. The Metastatic Potential and Chemoresistance of Human Pancreatic Cancer Stem Cells. PLOS ONE 2015

Juric, V., Ruffell, B., Evason, K. J., Junjie, H., Che, L., Wang, L., Chen, X., and Bishop, J. M. Monocyte-dependent liver injury promotes carcinogenesis in an oncogene- specific manner. Journal of Hepatology published online November 27, 2015. Symposia Proceedings

1. Bishop, J.M., Faras, A.J., Garapin, A.-C., Hansen, C., Jackson, N., Levinson, W., Taylor, J.M. and Varmus, H.E.: RNA-directed DNA polymerase and the replication of Rous sarcoma virus. M.D. Anderson Symposium on The Molecular Basis of Neoplasia, 1972, Baltimore: The Williams and Wilkins Co., p. 229, 1974.

2. Bishop, J.M., Faras, A.J., Garapin, A.-C., Goodman, H., Levinson, W.E., Stavnezer, J., Taylor, J.M. and Varmus, H.E.: Characteristics of the transcription of RNA by the DNA polymerase of Rous sarcoma virus. In: DNA Synthesis in Vitro, Proceedings of the Steenbock Symposium R. D. Wells and R. B. Inman, eds.) Baltimore: University Park Press, p. 341, 1973.

3. Bishop, J.M., Jackson, N., Quintrell, N. and Varmus, H.E.: Transcription of RNA tumor virus genes in normal and infected cells. In: Possible Episomes in Eukaryotes, Fourth Lepetit Symposium (L.G. Silvestri, ed.) New York: Elsevier/North Holland, p. 61, 1973.

4. Varmus, H.E., Hansen, C.B., Medeiros, E., Deng, C.T. and Bishop, J.M.: Detection of characterization of RNA tumor virus-specific nucleotide sequences in cell DNA. In: Possible Episomes in Eukaryotes, Fourth Lepetit Symposium (L. G. Silvestri, ed.) New York: Elsevier/North Holland, p. 50, 1973.

5. Bishop, J.M., Deng, C.T., Faras, A.J., Goodman, H.M., Levinson, W.E., Taylor, J.M. and Varmus, H.E.: Transcription of Rous sarcoma virus genome by RNA-directed DNA

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polymerase. In: Virus Research, Proceedings of the Second ICN-UCLA Symposium (C.F. Fox, ed.) New York: Academic Press, p. 15, 1973.

6. Varmus, H.E., Vogt, P.K. and Bishop, J.M.: Synthesis and integration of Rous sarcoma virus-specific DNA in permissive and non-permissive hosts. In: Virus Research, Proceedings of the Second ICN-UCLA Symposium (C. F. Fox, ed.) New York: Academic Press, p. 373, 1973.

7. Varmus, H.E., Stavnezer, J., Medeiros, E. and Bishop, J.M.: Detection and characterization of RNA tumor virus-specific DNA in cells. In: Proceedings of the Fourth International Symposium on Comparative Leukemia Research, 1973 (Y. Ito and R.M. Dutcher, eds.) Univ. of Tokyo Press, Tokyo/Karger, Basel, p. 451, 1975.

8. Bishop, J.M., Deng, C.T., Faras, A., Goodman, H., Guntaka, R., Levinson, W., Cordell- Stewart, B., Taylor, J. and Varmus, H.E.: Transcription of the Rous sarcoma virus genome in vitro and in vivo. In: Proceedings of the Fourth International Symposium on Comparative Leukemia Research, 1973 (Y. Ito and R. M. Dutcher, eds.) Univ. of Tokyo Press, Tokyo/Karge, Basel, p. 517, 1975.

9. Bishop, J.M., Deng, C.T., Faras, A.J., Goodman, H. M., Guntaka, R. R. Levinson, W.E., Cordell-Stewart, B., Taylor, J.M. and Varmus, H.E.: The provirus of Rous sarcoma virus: Synthesis, integration and transcription. In: Proceedings of the Symposium on Tumor Virus - Host Cell Interactions, NATO Advanced Study Institute, Monte Carlo, September, 1973 (A. Kolber, ed.) p. 255, 1975.

10. Cordell-Stewart, B., Taylor, J.M., Rohde, W., Goodman, H.M. and Bishop, J.M.: Transfer RNAs of Rous sarcoma virus and the initiation of DNA synthesis by viral reverse transcriptase. In: Proceedings of the 1974 Flexner Symposium on Viral Transformation and Endogenous Viruses (A. Kaplan, ed.) New York: Academic Press, p. 117, 1974.

11. Varmus, H.E., Guntaka, R.V., Deng, C.T. and Bishop, J.M.: Synthesis structure, and function of Rous sarcoma virus-specific DNA in permissive and non-permissive cells. Cold Spring Harbor Symposium on Quantitative Biology 39:987, 1974.

12. Guntaka, R.V., Bishop, J.M. and Varmus, H.E.: Synthesis and integration of Rous sarcoma virus proviral DNA in duck embryo fibroblast cells. In: Fundamental Aspects of Neoplasia, Symposium held at the Institute of Microbiology Rutgers State University 1974 (A.A. Gottlieb, O.J. Plescia and D.L. Bishop, eds.) New York: Springer-Verlag, p. 315, 1975.

13. Ringold, G., Bishop, J.M. and Varmus, H.E.: Stimulation of mouse mammary tumor virus (MMTV) productin by glucocorticoids: Studies on the mechanism of action of dexamethasone. In: Proceedings of the Fourth ICN-UCLA Symposium (McMann and Fox, eds.) p. 395, 1975.

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14. Bishop, J.M., Stehelin, D., Tal, J., Fujita, D., Roulland-Dussoix, D., Padgett, T. and Varmus, H.E.: The transforming gene of avian sarcoma virus. Symposium Proceedings, Molecular Biology of the Mammalian Genetic Apparatus (P. Ts'O, ed.) New York: Elsevier/North Holland, p. 263, 1977.

15. Varmus, H.E., Stehelin, D., Spector, D., Tal, J., Fujita, D., Padgett, T., Roulland-Dussoix, D., Kung, H.-J. and Bishop, J.M.: Distribution and function of defined regions of avian tumor virus genomes in viruses and uninfected cells. In: Proceedings of the Fourth ICN-UCLA Symposium: Molecular and Cellular Biology, Vol. 4 (D. Baltimore, A.S. Huang and C.F. Fox, eds.) New York: Academic Press, p. 339, 1976.

16. Bishop, J.M., Deng, C.T., Mahy, B.W.J., Quintrell, N., Stavnezer, E. and Varmus, H.E.: Synthesis of viral RNA in cells infected by avian sarcoma viruses. In: Proceedings of the Fourth ICN-UCLA Symposium, Molecular and Cellular Biology, Vol. 4 (D. Baltimore, A. S. Huang and C. F. Fox, eds.) New York: Academic Press, p. 1, 1976.

17. Bishop, J.M., Baker, B., Fujita, D., McCombe, P., Sheiness, D., Smith,K., Spector, D.H., Stehelin, D. and Varmus, H.E.: The genesis of a viral transforming gene. 3rd Decennial Review Conference: Cell, Tissue, and Organ Culture, Lake Placid, New York, NCI Monograph No. 48, p. 219, 1976.

18. Varmus, H.E., Spector, D.H., Stehelin, D., Deng, C.T., Padgett, T., Stubblefield, E. and Bishop, J.M.: The function and origin of the transforming gene of avian sarcoma virus. In: Cold Spring Harbor Conferences on Cell Proliferation, Vol. 4: Origins of Human Cancer, p. 1159, 1977.

19. Varmus, H.E., Spector, D.H., Stehelin, D., Deng, C.T., Padgett, T., Stubblefield, E. and Bishop, J.M.: The function and origin of the transforming gene of avian sarcoma virus. In: International Cell Biology 1976-1977 (B.R. Brinkley and K.R. Porter, eds.) Rockefeller Univ. Press, p. 553, 1977.

20. Bishop, J.M., Weiss, S.R., Oppermann, H., Hackett, P., Quintrell, N., Chen, L.-S., Levintow, L. and Varmus, H.E.: The strategy of retrovirus gene expression. In: Avian RNA Tumor Viruses (S. Barlati and C. De Giuli-Morghen, eds.) Piccin Medical Books, pp. 181, 1978.

21. Varmus, H.E., Shank, P.R., Hughes, S., Kung, H.-J., Heasley, S., Major, J., Vogt, P.K. and Bishop, J.M.: Synthesis, structure and integration of the DNA of RNA tumor viruses. In: Cold Spring Harbor Symposium on Quant. Biol., Vol. 43 :851, 1978.

22. Varmus, H.E., Shank, P.R., Hughes, S.H., Kung, H.-J., Heasley, S., Major, J., Vogt, P.K. and Bishop, J.M.: Structures of unintegrated and integrated forms of the DNA of RNA tumor viruses. In: Biochemistry of Genetic Engineering, Proceedings of the Symposium of the Biochemical Society 44: 103, 1979.

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23. Hughes, S.H., Vogt, P.K., Stubblefield, E., Robinson, H., Bishop, J.M. and Varmus, H.E.: Organization of endogenous and exogenous viral and linked non-viral sequences. Cold Spring Harbor Symp. Quant. Biol., Vol. 44:1077, 1979.

24. Bishop, J.M., Courtneidge, S.A., Levinson, A.R., Oppermann, H., Quintrell, N., Sheiness, D.K., Weiss, S.R. and Varmus, H.E.: The origin and function of avian retrovirus transforming genes. In: Cold Spring Harbor Symp. Quant. Biol.,Vol. 44:919, 1979.

25. Bishop, J.M.: The molecular basis of oncogenesis by retroviruses. In: The Molecular Basis of Microbial Pathogenicity (H. Smith, J.J. Skehel and M.J. Turner, eds.) Dahlem Konferenzen. Weinheim/Deerfield Beach, FL/Basel: Verlag Chemie, p. 211, 1980.

26. Varmus, H.E., Cohen, J.C., Hughes, S.H., Majors, J. and Bishop, J.M.: The origin and structure of endogenous retroviral DNA. In: Genetic Variation of Viruses - Annals of New York Academy of Sciences, Vol. 354, p. 379, 1980.

27. Bishop, J.M., Gonda, T., Hughes, S.H., Sheiness, D.K., Stubblefield, E., Vennstrom, B. and Varmus, H.E.: The genesis of avian retrovirus oncogenes. In: Mobilization and Reassembly of Genetic Information (W. A. Scott, R. Werner and D. R. Joseph, eds.) Twelfth Miami Winter Symposium, p. 261, 1980.

28. Bishop, J.M., Courtneidge, S., Czernilofsky, Levinson, A.D., Levintow, L., Luciw, P., Oppermann, H., Sheiness, D.K., Vennstrom, B. and Varmus, H.E.: Viral oncogenes as pleiotropic effectors. In: Genes, Chromosomes, and Neoplasia (33rd Ann. Symp. on Fundamental Cancer Res., M.D. Anderson Series) (F.E. Arrighi, P.N. Rao and E. Stubblefield, eds.) New York: Raven Press, p. 93, 1981.

29. Varmus, H.E., Majors, J.E., Swanstrom, R., DeLorbe, W.J., Payne, G.S., Hughes, S.H., Ortiz, S., Quintrell, N. and Bishop, J.M.: Structural and functional properties of DNA intermediates in the replication of retroviruses. Proceedings of the Juselius Symposium. New York: Academic Press, p. 93, 1981.

30. Majors, J.E., Swanstrom, R., DeLorbe, W.J., Payne, G.S., Hughes, S.H., Ortiz, S., Quintrell, N., Bishop, J.M. and Varmus, H.E.: DNA intermediates in the replication of retroviruses are structurally (and perhaps functionally) related to transposable elements. Cold Spring Harbor Symp. on Quant. Biol., Vol. 45, p. 731, 1980.

31. Bishop, J.M.: Retrovirus oncogenes. Developmental Biology Using Purified Genes. In: Proceedings of ICN-UCLA Symposia on Molecular and Cellular Biology, Vol. 23 (D. Brown and C. F. Fox eds.) New York: Academic Press, p. 515, 1981.

32. Bishop, J.M.: Viral Oncogenes: Curiosity or Paradigm? Research Frontiers in Aging and Cancer. National Cancer Institute Monograph No. 60:155, 1982.

33. Varmus, H.E., Payne, G.S., Nusse, R., Luciw, P., Westaway, D. and Bishop, J.M.: Insertional mechanisms in oncogenesis by retroviruses. In: Perspectives on Genes and

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the Molecular Biology of Cancer (Robertson, D.L. and Saunders, G. F. eds.) New York: Raven Press, p. 237, 1983.

34. Privalsky, M.L., Sealy, L., Vennstrom, B. and Bishop, J.M.: The molecular genetics of avian erythroblastosis virus. In: Gene Expression in Normal and Transformed Cells (Celis, J.E. and Bravo, R., eds) New York: Plenum Press, p. 193, 1983.

35. Bishop, J.M.: Oncogenes, leukemia and differentiation. In: Proceedings of the 1983 UCLA Symposia on Normal and Neoplastic Hematopoiesis (D. Golde and P. Marks, eds.) New York: Alan R. Liss Inc., p. 1, 1983.

36. Ralston, R. and Bishop, J.M.: Evolutionary relationships among oncogenes of DNA and RNA tumor viruses: myc, myb and adenovirus E1a. In: Cancer Cells Vol. 2: Oncogenes and Viral Genes (A. Levine, G. Vande Woude, W. Topp and J. D. Watson, eds.) New York: Cold Spring Harbor Press, p. 165, 1984.

37. Alitalo, K., Saksela, K., Windqvist, R., Schwab, M. and J. M. Bishop: Amplification and aberrant expression of cellular oncogenes in human colon cancer cells. In: UCLA Symposia on Molecular and Cellular Biology, New Series: Genes and Cancer, Vol. 17, (J. M. Bishop, M. Greaves and J. Rowley, eds.) New York: Alan R. Liss, Inc., p. 383, 1984.

38. Parker, R., Swanstrom, R., Varmus, H.E. and Bishop, J.M.: Transduction and alteration of a cellular gene (c-src created an RNA tumor virus: The genesis of Rous sarcoma virus. In: Cancer Cells Vol. 2: Oncogenes and Viral Genes (A. Levine, G. Vande Woude, W. Topp and J. D. Watson, eds.) New York: Cold Spring Harbor Press, p. 19, 1984.

39. Schwab, M., Alitalo, K., Varmus, H.E. and Bishop. J.M.: Amplification of cellular oncogenes in tumor cells. In: Cancer Cells Vol. 2: Oncogenes and Viral Genes (A. Levine, G. Vande Woude, W. Topp and J. D. Watson, eds.) New York: Cold Spring Harbor Press, p. 215, 1984.

40. Bishop, J. M.: Exploring carcinogenesis with retroviruses. In: The Microbe 1984: Part I Viruses (B.W.J. Mahy and J. R. Pattison, eds.), Society for General Microbiology Symposium Vol.36, Cambridge University Press, p. 121, 1984.

41. Bishop, J. M.: Exploring carcinogenesis with retroviral and cellular oncogenes. In: UCLA Symposia on Molecular and Cellular Biology, New Series: Genes and Cancer, Vol. 17, (J. M. Bishop, M. Greaves and J.Rowley eds.) New York: Alan R. Liss, Inc., p. 255, 1984.

42. Bishop, J. M.: Exploring carcinogenesis with retroviral and cellular oncogenes. In: Proceedings of the Xth Sigrid Juselius Symposium on Gene Expression during Normal and Malignant Differentiation (L. C. Andersson, C. G. Gahmberg and P. Ekblom, eds.) New York: Academic Press, p. 151, 1985.

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43. Bishop, J. M.: Retroviruses and Cancer Genes. In: Genetics, Cell Differentiation, and Cancer - Bristol-Myers Symposia Series, Volume 7 (Paul A. Marks, M.D., ed.) New York: Academic Press, 135-142, 1985.

44. Snyder, M. A. and Bishop, J. M. Site-specific mutants of pp60v-src. In: UCLA Symposium on Molecular and Cellular Biology: Protein Modification and Design (D. Oxender and C. F. Fox, eds.) New York: Alan R. Liss Inc., 1986.

45. Bishop, J. M.: Exploring carcinogenesis with retroviral and cellular oncogenes. In: Progress in Medical Virology, Vol. 32: Viruses, Oncogenes and Cancer (J. L. Melnick, ed.) Proceedings of the Third Annual Duran Reynals Symposium, Barcelona. Basel: S. Karger AG, 1985.

46. Bishop, J. M.: Oncogenes and Proto-oncogenes. In: Cancer - Perspectives in Control (T. W. Mak and T.-T. Sun, eds.), Proceedings of an Inter- national Symposium held in Beijing, China, 8/18-8/21/85. New York: Alan R. Liss Inc., 1-5, 1986.

47. Bishop, J. M., Drees, B., Katzen, A. L., Kornberg, T. B. and Simon, M.A.: Proto- oncogenes of Drosophila melanogaster. In: Cold Spring Harbor Symp. Quant. Biol., Vol. 50: 727, 1986.

48. Bishop, J. M.: Proto-oncogenes: The pursuit of Dr. Jekyll. In: Proceedings of the Eli Lilly Dedicatory Symposium, "A Perspective on Biology and Medicine in the 21st Century" (Ed.: I. Johnson). The Royal Society of Medicine International Congress and Symposium, Series No. 121, published by the Royal Society of Medicine Services Ltd., London, pp. 49-56, 1987.

49. Bishop, J. M.: The Pathobiology of Proto-oncogenes. In: Proceedings of the 17th International Symposium of the Princess Takamatsu Cancer Research Fund (Eds. S. A. Aaronson et al.), published by the Japan Scientific Societies Press, Tokyo, pp. 3-9, 1987.

50. Bishop, J. M.: Viruses, Genes and Cancer. (Prepared for Proceedings of the SAAWOK Symposium, "Science As A Way Of Knowing", San Francisco, December, 1988.) Amer. Zool. 29: 653-666, 1989.

51. Bishop, J. M. Molecular Biology of Oncogenes. In: Molecular Mechanisms and their Clinical Application in Malignancies (Eds. D. E. Bergsagel and T. W. Mak) - Proceedings of the 13th Annual Bristol-Myers Symposium on Cancer Research, Ontario Cancer Institute, Toronto, Canada. Academic Press, Inc., pp. 137-154, 1991.

52. Bishop, J. M., Eilers, M., Katzen, A. L., Kornberg, T., Ramsay, G. and Schirm, S. MYB and MYC in the Cell Cycle. In: The Cell Cycle - Volume 56 (Proceedings of the 1991 Cold Spring Harbor Symposia on Quantitative Biology). Cold Spring Harbor Laboratory Press, pp. 99-107, 1991.

53. Bishop, J. M. The Functions of MYC and MYB. In: Nuclear Processes and Oncogenes (Ed. P. Sharp) - Proceedings of the 14th Annual Bristol-Myers Symposium on Cancer

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Research, Massachusetts Institute of Technology, Cambridge, Massachusetts. Academic Press, Inc., pp. 11-22, 1992.

54. Bishop, J. M., Capobianco, A. J., Doyle, H. J., Finney, R. E., McMahon, M., Robbins, S. M., Samuels, M. L. and Vetter, M. Proto-oncogenes and Plasticity in Cell Signaling. In: The Molecular Genetics of Cancer - Volume LIX (Proceedings of the 1994 Cold Spring Harbor Symposia on Quantitative Biology) pp. 165-171. 1994.

55. Bishop, J. M. Viruses, Genes and Can cer: A Lineage of Discovery. In: The DNA Provirus: Howard Temin's Scientific Legacy (Eds. G. M. Cooper, R. G. Temin and B. Sugden) - Proceedings of the Howard Temin Commemorative Symposium, October, 1994. Wash., D.C.: ASM Press, pp. 81-94, 1995.

56. Tward, A. D., Jones, K. D., Yant, S., Kay, M. A., Wang, R., and Bishop, J. M. Genomic Progression in Mouse Models for Liver Tumors. Cold Spring Harbor Symposia on Quantitative Biology: Molecular Approached to Controlling Cancer, Vol. 70, 2005.