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Bruce N. Ames Oral History Center University of California The Bancroft Library Berkeley, California Bruce N. Ames Bruce N. Ames: The Marriage of Biochemistry and Genetics at Caltech, the NIH, UC Berkeley, and CHORI, 1954–2018 University History Interviews conducted by Paul Burnett in 2019 and 2020 Copyright © 2021 by The Regents of the University of California Oral History Center, The Bancroft Library, University of California, Berkeley ii Since 1953 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 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 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 Bruce N. Ames dated January 20, 2021. 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. For information regarding quoting, republishing, or otherwise using this transcript, please consult http://ucblib.link/OHC-rights. It is recommended that this oral history be cited as follows: Bruce N. Ames, "Bruce N. Ames: The Marriage of Biochemistry and Genetics at Caltech, the NIH, UC Berkeley, and CHORI, 1954–2018" conducted by Paul Burnett in 2019 and 2020, Oral History Center, The Bancroft Library, University of California, Berkeley, 2021. Copyright © 2021 by The Regents of the University of California Oral History Center, The Bancroft Library, University of California, Berkeley iii Bruce Ames, 2008 Photo courtesy of Giovanna Ferro-Luzzi Ames. Copyright © 2021 by The Regents of the University of California Oral History Center, The Bancroft Library, University of California, Berkeley iv Abstract Bruce N. Ames is Professor of the Graduate School at the University of California, Berkeley. Dr. Ames studied with George Beadle at the California Institute of Technology at the beginning of the revolution in molecular biology. He joined the National Institutes of Health in 1953 as a fellow, and became Chief of the Microbial Genetics section in 1962. In 1968, he joined the faculty in biochemistry and genetics at UC Berkeley, where he developed the Ames test of the mutagenic potential of chemicals. In 2000, he became a senior research scientist at the Children's Hospital of Oakland Research Institute until his retirement in 2018. With over 550 publications, he is among the top two hundred most highly cited scientists across all disciplines. Acknowledgments We wish to acknowledge the generous support from those below who made this oral history possible. Giovanna Ferro-Luzzi Ames Mike Botchan Richard Harland Caroline Kane Randy Katz Judith Klinman Douglas Koshland Steve Martin Edward Penhoet Randy Schekman Jeremy Thorner Copyright © 2021 by The Regents of the University of California Oral History Center, The Bancroft Library, University of California, Berkeley v Table of Contents Foreword by Randy Schekman ix Foreword by Gerald Fink xi Interview 1: August 16, 2019 Hour 1 1 Paternal family's Jewish origins in Ukraine (German speaking) — Father's education and career — Anglicization of last name — Maternal family's Jewish origins in Russia, Poland (Russian speaking, possibly of Spanish descent) — Childhood during the Great Depression and later in New York City — Attending the Bronx High School of Science and conducting first science experiment — Performance and learning environment during high school — Younger sisters Sylvia and Beth Ames — World War II — Entering Cornell in 1946 — Interest in folk dancing and reading — Summer trips to Upstate New York —Interest in classical music at Cornell — Socialization through folk dancing — Undergraduate experience at Cornell — Influential professors — Experiments with crop genetics and mutations — Use of both biochemistry and genetics in biosynthesis research — Taking classes in both fields — Early genetics research with Drosophila at the California Institute of Technology (Caltech) Hour 2 21 Doctoral research at Caltech — Support from Herschel K. Mitchell and Max Delbrück — Structure and culture of research at Caltech — Interest in history — Newfound freedom during college years at Cornell Interview 2: September 25, 2019 Hour 1 30 Acceptance to Caltech in 1950 — Small-school dynamic at Caltech — Emerging molecular biology paradigms — Benefits of experimenting on simpler organisms — Isolating mutants — Histidine and paper chromatography — Ribose phosphate and imidazole glycerol in biological pathways — Enrollment in C.B. van Niel's courses during summers — Public Health Service during WWII and the Korean War — Postdoc at the National Institutes of Health (NIH) in 1953,working with Bernard Horecker — Bridging the gap between experimental biochemists and theoretical geneticists — Influence of Professor Max Delbrück — Experiences outside of classroom at Caltech — Work habits as a graduate student — Arrival at NIH for postdoctoral fellowship — Publications of new studies on histidine in 1950s — Visits from François Jacob and Jacques Monod—Working under Gordon Tomkins at NIH — Lack of recognition for contribution to Monod's published research — Early work on feedback inhibition of genes in Salmonella Copyright © 2021 by The Regents of the University of California Oral History Center, The Bancroft Library, University of California, Berkeley vi — Bringing genetics to fellow biochemists — Sharing of ideas in science —Year in Europe with his wife Giovanna Ames — Discovery of messenger RNA in histidine enzymes — Work of Marshall Nirenberg — Family life at NIH — Colleagues and friends during NIH years Hour 2 49 Collaboration with Robert G. Martin on sucrose gradient centrifugation — Return to NIH in 1961 as section chief of molecular biology lab — Ames-Hartman paper, 1963 — Research on preservatives in potato chips, first step in mutagen research, early 1960s — Mutants and transfer RNA — Raising children during time at the NIH — Acceptance of professorship at UC Berkeley in 1967 — Giovanna's research and ultimate professorship at Berkeley Interview 3: November 14, 2019 Hour 1 61 At a remove from the counterculture unrest at Berkeley — Importance of working with undergraduate researchers in laboratory — Carcinogens as mutagens — Ames as an "odd fish" in cancer research community: biochemistry vs. biomedicine and epidemiology — Genetic toxicology — DDT as special case of environmental toxin — Development of the Ames Test — Support from Office of Naval Research — Undergraduates' flexibility in working on unconventional projects — More on histidine research from late 1950s, early 1960s — More on Ames Test and addition of mammalian enzymes in early 1970s — Comparison with older, costlier animal models for testing carcinogenicity of substances — A free-marketer working for free — Political orientation and distrust of government institutions — Natural vs. artificial toxicity — Comparative cost of Ames Test — Misleading data from animal models — Response from critics to comparative toxicology research — Richard Doll and Richard Peto — Other research using the Ames Test to reveal toxicity of plant foods — Beginning of interest in oxidation Hour 2 88 Cigarette smoke as an oxidant — Undergraduate researchers Bill Durston and Frank Lee — Joyce McCann and Edith Yamasaki — Collaborator Lois Gold — Immediate uptake of Ames Test by industry, slow uptake by regulatory agencies — Befriending Milton and Rose Friedman — Testing hair dyes for carcinogens — Fighting against flame-resistant pajamas — Collaboration with Richard Peto to revise conventions around carcinogen testing— Human Exposure/ Rodent Potency index (HERP) — More on Lois Gold— Uric acid as anti-oxidant, 1983 — Oxy-R and the network of enzymes to protect cells Copyright © 2021 by The Regents of the University of California Oral History Center, The Bancroft Library, University of California, Berkeley vii Interview 4: December 6, 2019 Hour 1 109 Personal philosophy of science — The ground floor of genetic toxicology — Economic view of scientific research, searching for efficiencies — Refusing to accept funding from private sources — Excessive criticism of industry — Talents of Lois Gold and Joyce McCann in polishing and tempering Ames's arguments — Bureaucracy of scientific research institutions — "You don't want the administrators telling you what to do, because it's the person who thinks differently that changes the direction of science" — Comparative flexibility of national institutes of health — Influence of Friedrich Hayek,
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