Oral History Center, The Bancroft Library, University of California Berkeley Oral History Center University of California The Bancroft Library Berkeley, California Keith Robert Yamamoto, PhD Politics, Ethics, and Transcription Regulation in the UCSF Biochemistry Department Interviews conducted by Sally Smith Hughes, PhD in 1994 & 1995 Copyright © 2018 by The Regents of the University of California Oral History Center, The Bancroft Library, University of California Berkeley ii Since 1954 the Oral History Center of the Bancroft Library, formerly the Regional Oral History Office, has been interviewing leading participants in or well-placed witnesses to major events in the development of Northern California, the West, and the nation. Oral History is a method of collecting historical information through tape-recorded interviews between a narrator with firsthand knowledge of historically significant events and a well-informed interviewer, with the goal of preserving substantive additions to the historical record. The tape recording is transcribed, lightly edited for continuity and clarity, and reviewed by the interviewee. The corrected manuscript is bound with photographs and illustrative materials and placed in The Bancroft Library at the University of California, Berkeley, and in other research collections for scholarly use. Because it is primary material, oral history is not intended to present the final, verified, or complete narrative of events. It is a spoken account, offered by the interviewee in response to questioning, and as such it is reflective, partisan, deeply involved, and irreplaceable. All uses of this manuscript are covered by a legal agreement between The Regents of the University of California and Keith Yamamoto dated August 27, 2014. 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://ucblib.link/OHC-rights. It is recommended that this oral history be cited as follows: Keith Robert Yamamoto, “Keith Yamamoto: Politics, Ethics, and Transcription Regulation in the UCSF Biochemistry Department, conducted by Sally Smith Hughes in 1994 & 1995, Oral History Center, The Bancroft Library, University of California, Berkeley, 2018. Oral History Center, The Bancroft Library, University of California Berkeley iii Keith Yamamoto, 1982 Photograph taken at Cold Spring Harbor by Herb Parsons Courtesy of the Cold Spring Harbor Laboratory Archives Oral History Center, The Bancroft Library, University of California Berkeley iv This oral history with Keith Yamamoto is one in a series documenting science and technology in Northern California. Its focus is Yamamoto’s years in the UCSF Department of Biochemistry which he joined in 1973 as a postdoc, rising to full professor in 1983. He recounts in detail his research on the glucocorticoid receptor and, more generally, on DNA transcription regulation. He was a first-hand witness to the invention and early application of recombinant DNA technology and the research breakthrough it represented as well as the public controversy it raised in the 1970s over its safety and commercialization. Yamamoto remains a persistent voice in issues pertaining to research ethics and responsibility in science. A second oral history recorded in 2014 chronicles his later career as UCSF Vice Chancellor for Research, Keith R. Yamamoto: UCSF Biochemist, Vice Chancellor for Research, and the Mission Bay Campus. A third oral history was recorded as part of the Sandler Foundation Project, Keith R. Yamamoto: The Sandler Foundation and the Program in Breakthrough Biomedical Research at UCSF. Oral History Center, The Bancroft Library, University of California Berkeley v Table of Contents— Keith Yamamoto Interview History by Sally Smith Hughes Interview 1: September 26, 1994 1 Early Influences — The Internment of the Japanese during World War II — Parents and Sister — Religion — Family Values — Interest in Science — Undergraduate, Iowa State University, 1964-1968 — Research as an Undergraduate — Attraction to Molecular Biology Interview 2: October 5, 1994 18 Graduate Student, Princeton University, 1968-1973: Assignment to Bruce Alberts' Laboratory — First Research Problem — Paper Presentation, Cold Spring Harbor — The Princeton Milieu — The Biochemistry Faculty — Interdisciplinary Tensions — Bruce Alberts — Choosing to Focus on Eukaryotes — Research on the Estrogen Receptor — Finding that the Estrogen Receptor Binds to DNA — Combining Scientific Approaches — Political Involvement: Campaign for Eugene McCarthy — Campaign for George McGovern — Alberts' Program in Science Education — The Dissertation Project — Detecting Specific Binding Sites for the Estrogen Receptor — Arthur Riggs' Discovery — Two Theoretical Papers — Fellow in Biochemistry, UCSF, 1973-1975 — Gordon M. Tomkins, M.D., Ph.D. — Research on the Glucocorticoid Receptor — The Tomkins Lab — Early Impressions of the Department — Scientific Communication Interview 3: November 4, 1994 55 More on Postdoctoral Fellowship in Biochemistry at UCSF, 1973-1975 — The UCSF Department of Biochemistry — Faculty Recruitment — Decision to Emphasize the Basic Sciences at UCSF — Tensions — Biophysics — Biomathematics — Postdoc Factory — Postdoc Competition — Research Problem as a Postdoc — UCSF faculty member — Opinions about Cell — Order of Authorship — Different Understandings about Authorship — Pierre Chambon — Harold Varmus — Directing His Laboratory Group — — Less Time in the Lab — Science Manager — Institutional Context Interview 4: November 14, 1994 79 Program in Biological Sciences as a Model for the Clinical Sciences — Role of Genetics at UCSF — Division of Genetics, Department of Biochemistry and Biophysics — Debate about the Campus Role of Human Genetics — Departmental Retreats — The Ralston Center Retreat, Mill Valley, ca.1976 — Early Asilomar Conferences — Current Asilomar Retreats — Social Occasions in the Department — Howard Goodman's Wine Gatherings — The Chelsea Pub — Spring and Halloween Parties — Departmental Camaraderie — Building a Departmental Reputation — Administrative Styles — Utilizing Joint Appointments — Comparing Biology at Berkeley, Stanford, and UCSF — Open versus Hierarchical Governance — The Collective Model — New Technology Oral History Center, The Bancroft Library, University of California Berkeley vi Interview 5: November 28, 1994 101 The Recombinant DNA Controversy — Cohen-Boyer Experiments — Paul Berg's Experiments with SV40 — Hearing of Early Recombinant DNA Research — First Public Announcement of Recombinant DNA, June 1974 — The Asilomar Meeting, February 1975 — The Recombinant DNA Research Moratorium — Communicating Scientific Knowledge — NIH Recombinant DNA Guidelines — Threat of Federal and State Regulation — The pBR322 Plasmid Episode in the Race for Human Insulin— Possible Commercial Applications — The Scientific Process in the U.S. — The UCSF Biosafety Committee — Changes in Laboratory Safety Procedures — The UCSF P-3 Laboratory — The Public's Role in Science — Ownership of Ideas in Science Interview 6: December 22, 1994 125 A Conversation with Gordon Tomkins — Personal Problems with Ownership: Gordon Ringold — Goal-oriented versus Open-ended Research — Competition — Issues around Distribution of Biological Materials — Publication and Public Domain — Authorship Claims — Requesting Information — Requesting Payment — More on Authorship — Ethics in Science — Research on DNA Transcription Regulation — Bacteriophage and Universality Interview 7: January 24, 1995 154 DNA Binding Sites — Long-range and Combinatorial Regulation — Insertion Sequences — A Mechanism for Evolution — Allan Wilson — More on Transcription Regulation— The Binding Site — Discovery of Three Classes of Glucocorticoid Receptors — Cell- specific Gene Expression — Research in Yeast — Long-range Regulation as an Evolutionary Driving Force — Stories about Signaling — Steroid Molecules as Cholesterol Derivatives — The UCSF Collaborative Spirit Interview 8: February 20, 1995 184 Controversy over the Commercialization of Academic Biology — Technology Transfer and Patenting at the University — Scientific Advisor to Tularik — More on Commercial Ties in the Biochemistry Department — More on the pBR322 Plasmid Episode Interview 9: March 27, 1995 207 The UCSF Biomedical Resource Center — The Biochemistry Department’s Administrative Structure — Chairmanship Styles: Bill Rutter and Bruce Alberts — Dan Koshland and the Reorganization of Biology at Berkeley — The University’s Growing Leniency for Faculty Outside Commitments — Faculty Community Service — U.S. Military Use of Recombinant DNA Technology — Testimony on Biological Defense Research before the Senate Government Affairs Committee — Writing Scientific Papers — Science Journals and the Shaping of Science Oral History Center, The Bancroft Library, University of California Berkeley vii Interview 10: April 13, 1995 235 Determining Author Order on Science Publications — Graduate School as a Time to be Daring in Research — Issues as Editor of Science Journals — Misconduct