Cell Biologist and UC Berkeley Nobel Laureate
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Oral History Center University of California The Bancroft Library Berkeley, California Randy Wayne Schekman: Cell Biologist and UC Berkeley Nobel Laureate Interviews conducted by Sally Smith Hughes in 2014 Copyright © 2015 by The Regents of the University of California 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 Randy Wayne Schekman dated April 5, 2013. 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://bancroft.berkeley.edu/ROHO/collections/cite.html It is recommended that this oral history be cited as follows: Randy Wayne Schekman, “Randy Wayne Schekman: Cell Biologist and UC Berkeley Nobel Laureate” conducted by Sally Smith Hughes in 2014, Oral History Center of the Bancroft Library, The Bancroft Library, University of California, Berkeley, 2015. iii Randy Wayne Schekman, 2011 Photo courtesy Hadar Goren, Hadar Goren Photography iv Randy Schekman has devoted his research career at UC Berkeley to working out the biochemistry, genetics, and molecular biology of the intricate system that transports proteins through the living cell. For this body of work, he was awarded the Nobel Prize in Physiology or Medicine in 2013. He is a vocal advocate of the public university and the editor-in-chief of eLife, an open-access, electronic journal in bioscience. v Table of Contents—Randy Wayne Schekman Interview History by Sally Smith Hughes x Randy Wayne Schekman Curriculum Vitae xiii Interview 1: February 10, 2014 Audio File 1 1 Parents Alfred and Esther Schekman, both from Minnesota — maternal grandparents from Bessarabia, paternal grandparents from Russia — father’s post WWII engineering training at University of Minnesota on the GI Bill — Randy’s birth in 1948, nine years in Minneapolis — younger sister, two brothers — sister’s death from leukemia as a college sophomore — father’s 1959 Southern California job offer — his work in early computer science — early fascination with electron microscope images — parents were labor democrats but largely a- political — more on maternal grandparents’ 1927 immigration to Minnesota, observant but not orthodox Judaism — childhood in a Jewish enclave of Minneapolis — move to California and becoming an atheist as a teenager: “I think my interest in science overwhelmed any belief in religion.” — earliest interest in science: seventh grade — determination to save money for a professional microscope — culturing pond scum — the importance of science fairs — conducting bigger and more complex experiments at home — support from family friend who worked as a medical technician — long-time support from high school biology teacher Jack Hoskins — winning at county science fairs —starting UCLA with plans to go to medical school — choosing UCLA — freshman year: living in a co-op, chemistry instructor Kenneth Trueblood, honors chemistry with Willard Libby, working in the lab — influence of James Watson’s Molecular Biology of the Gene, recommended by Michael Konrad — summer lab project with Dan Ray exploring bacteriophage DNA — sophomore year graduate genetics class and decision to study abroad in Edinburgh with William Hayes — genetics work in 1969: limitations, new discoveries, scientists working in the field — Watson’s controversial The Double Helix Audio File 2 18 More on the year in Edinburgh at the Medical Research Council Unit: exciting times for bacterial genetics and molecular biology — feeling the need for biochemistry, exposure to and admiration for Arthur Kornberg — completing the Edinburgh year — summer job at Harvard’s Biological Laboratories with David Denhardt — the contentious interpersonal climate at Harvard: “I knew there was another way that people could relate to each other” — return to UCLA for senior year, work with Dan Ray, focus on lab work and publication, neglecting classes and grades — leaving UCLA without completing foreign language requirement, starting Stanford — background on Kornberg’s DNA polymerase work and Nobel Prize controversy surrounding Cain’s subsequent work in 1969-1970 — vi beginning graduate school at Stanford — socializing, youthful arrogance, meeting Costa Georgopoulous and being brought down to earth: “It didn’t diminish my passion, but I had to behave myself.” — collaboration with Doug Brutlag on M13 and then phiX174 — bringing Denhardt’s work on dnaB and Yukinori’s research into the mix — resultant publication in PNAS — working with Kornberg: “I learned a great deal from Kornberg…but that didn’t mean I got along with him.” — Kornberg’s reaction to Schekman’s thesis defense Interview 2: February 26, 2014 Audio File 3 37 Developing an interest in biological membranes at Kornberg’s Stanford lab — discovering the electron microscopy work of S. J. Singer at UC San Diego — wife Nancy’s nursing schooling, decision to move to San Diego in 1974 — Palade’s work and Nobel Prize, attending the 1974 American Society for Cell Biology annual meeting — frustrations of switch to mammalian cells after years of E. Coli research — interest in yeast and the work of Lee [Leland] Hartwell — applying to UC Berkeley in the early months of UCSD postdoc — other notable applicants: Roger Kornberg, Keith Yamamoto, Janet E. Mertz — working in Singer’s lab — Günter Blobel’s signal hypothesis — planning work on yeast for UC Berkeley job, a rejected NIH grant proposal — job offers with UCLA and Berkeley, negotiating start-up grant money with Dan Koshland — meeting Lee Hartwell during a three week Cold Spring Harbor yeast genetics class — starting at Berkeley with small grants from the NSF and Cancer Research Coordinating Committee — later (1978) successful NIH grant — 1977 Peter Novick joins the lab to study yeast secretion — early frustrations: “So at this point I said all right, well I guess I’ve got to isolate mutants.” — investigating temperature-sensitive colonies and producing the first mutant sec1 — visit from George Palade, suggestion to Novick to examine by thin-section microscopy — eureka moment and publication in April 1979 Proceedings — skeptical Dan Koshland became an advocate — publishing in PNAS and Cell Audio File 4 57 Seymour Benzer’s cis-trans test, gene-mapping in yeast — Novick’s 1979 Cell paper on sec1 — continued research on temperature-sensitive mutants — using Susan A. Henry’s findings on using Ludox floor polish and a centrifuge to separate cells by density — Novick’s experiments to map genes — possible tactical error in focusing lab tech Charles Field on genetic mapping of existing mutants rather than on isolating more — Novick’s continued work applying a genetic epistasis test to the mutants and findings published in 1981 in Cell — kudos from the yeast community, some skepticism from mammalian field — early method for cloning yeast genes in 1978 — 1970s recombinant DNA scare and research moratorium — Schekman’s reluctance to spend time on DNA sequencing, mid 1980s trying to convince researchers to focus on biochemistry — background with Jim Rothman — competition, similar objectives and divergent vii approaches — “My approach is to develop a technique that will lead to discovery of the truth.” — Rothman’s work on clathrin Interview 3: March 7, 2014 Audio File 5 73 Early to mid-1980s work on translocation engine, exceptional grad students and postdocs: Ray Deshaies, David Baker, Linda Hicke, Chris Kaiser, Greg Paine — Deshaies’ translocation study, discoveries about hsp70s — discovery of SEC61 — David Baker’s breakthroughs — “It was just a wonderful time. I just got these great people and my job was to stay out of their way.” — morale in the lab, competition and cooperation — Chris Kaiser’s SNARE hypothesis — stipulations of the Nobel: recent work, discovery vs a body of work — graduate student Michael Rexach — Linda Hicke’s discovery — Akihiko Nakano, Nancy Pryor, Nina Salama — collaboration