University of California Berkeley Regional Oral History Office University of California The Bancroft Library Berkeley, California Program in the History of the Biosciences and Biotechnology Arthur Kornberg, M.D. BIOCHEMISTRY AT STANFORD, BIOTECHNOLOGY AT DNAX With an Introduction by Joshua Lederberg Interviews Conducted by Sally Smith Hughes, Ph.D. in 1997 Copyright 1998 by The Regents of the University of California Since 1954 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 indexed, 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 Arthur Kornberg, M.D., dated June 18, 1997. 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. No part of the manuscript may be quoted for publication without the written permission of the Director of The Bancroft Library of the University of California, Berkeley. Requests for permission to quote for publication should be addressed to the Regional Oral History Office, 486 Library, University of California, Berkeley 94720, and should include identification of the specific passages to be quoted, anticipated use of the passages, and identification of the user. The legal agreement with Arthur Kornberg, M.D., requires that he be notified of the request and allowed thirty days in which to respond. It is recommended that this oral history be cited as follows: Arthur M.D. Kornberg, , "Biochemistry at Stanford, Biotechnology at DNAX," an oral history conducted in 1997 by Sally Smith Hughes, Ph.D., Regional Oral History Office, The Bancroft Library, University of California, Berkeley, 1998. Copy no. Arthur Kornberg, ca. 1987, Cataloguing information Arthur Kornberg, M.D. (b. 1918) Biochemist Biochemistry at Stanford and Biotechnology at DNAX. 1998, xiv, 268pp. Early career at National Institutes of Health: nutrition research, mentored by Severo Ochoa and Carl Cori; chairman, microbiology, Washington University, St. Louis: C.B. van Niel's microbiology course, faculty, Erwin Chargaff, nucleotide chain synthesis research, DNA as genetic material; chairman, biochemistry, Stanford University: renovation of Stanford Medical School, founding and staffing of biochemistry department, interaction of basic and clinical sciences, departmental operational style, new biochemistry curriculum, industry ties, Industrial Affiliates Program; research programs: DNA polymerase, DNA replication, viral synthesis, polyphosphate, Nobel prize; recombinant DNA: Senate testimony, 1968, patenting in biotechnology, controversy, Stanford biochemistry contributions to/failure to recognize commercial potential of, Peter Lobban's research on; ALZA Corporation; DNAX: foundation, funding, and staffing, purchase by interactions with Schering-Plough, antibody and interleukin research; anti-Semitism; Paul Berg; Dale Kaiser. Introduction by Joshua Lederberg, Ph.D., Rockefeller University, New York. Interviewed 1997 by Sally Smith Hughes for the Program in the History of the Biosciences and Biotechnology, Regional Oral History Office, The Bancroft Library, University of California, Berkeley. TABLE OF CONTENTS --Arthur Kornberg, M.D. PREFACE i INTRODUCTION by Joshua Lederberg vi INTERVIEW HISTORY x BIOGRAPHICAL INFORMATION xiv I EARLY CAREER AT THE NATIONAL INSTITUTES OF HEALTH 1 Research in Nutrition 1 Mentors 2 II CHAIRMAN, DEPARTMENT OF MICROBIOLOGY, WASHINGTON UNIVERSITY SCHOOL OF MEDICINE, ST. LOUIS, 1953-1959 5 Decision to Leave the National Institutes of Health [NIH] 5 Cornelius B. van Niel's Course in General Microbiology 6 Teaching Microbiology to Medical Students 7 Members of the Department 9 Erwin Chargaff and Base Pairing 12 Early Work on Nucleotide Chain Synthesis 13 DNA as the Genetic Material 14 Jacques Monod and DNA Polymerase 16 Obtaining Diverse Scientific Expertise 16 III CHAIRMAN, DEPARTMENT OF BIOCHEMISTRY, STANFORD MEDICAL SCHOOL, 1959-1969 18 Renovation of Stanford Medical School 18 The University Administration 18 Creation of the Biochemistry Department 18 Offer of the Chairmanship, 1957 19 Recruiting Other Major Scientists 20 Reluctance to Establish Joint Appointments 22 Relations with Clinical Scientists 23 Financial Aspects 25 Tensions 26 The New Department of Biochemistry 27 Choosing Faculty Members 27 Leaving St. Louis 29 Melvin Cohn 30 Relations with the Two Biochemists in the Chemistry Department 32 Communal Structure 32 Later Changes in Departmental Faculty 34 Interaction Between the Basic and Clinical Sciences at Stanford 37 Limited Success 37 The Beckman Center for Molecular and Genetic Medicine 37 Clinicians as Basic Scientists 38 Bridging the Basic Sciencies 40 The Medical Center as an Intrusion 40 The Basic Science Environment, circa 1959 41 Later Efforts to Strengthen Basic Science at Stanford 42 Joshua Lederberg 43 More on the Department of Biochemistry at Stanford 44 Intellectual Focus on DNA 44 Joint Appointments 45 Broadening the Focus on DNA 45 The DNA Club 46 The Chairmanship 46 More on the Department's Distinctive Operational System 49 The Biochemistry Curriculum 51 The Laboratory for Medical Students, 1959-1965 51 The Medical Science Training Program 52 The Department's Relations with Industry 53 Industry Relations in Academic Science 53 Genesis of Biochemistry's Industrial Affiliates Program [IAP] 55 The Chemistry Department's Industrial Affiliates Program 56 Biochemistry's Industry Affiliates Program 57 Current Attitudes About Industrial Affiliations 59 Proposing a Scientists' Lobby 60 More on the Department's Program 61 More on the Chemistry Department's Program 62 Current Status of Biochemistry's IAP 63 Smith Kline & French 65 Potential Conflicts of Interest 66 Kornberg's Relationships with Industry 66 IV RESEARCH PROGRAMS 68 DNA as the Genetic Material 68 Research on DNA and RNA Polymerase 69 Joseph Fruton's Reaction to DNA Polymerase 71 E. coli Mutants Without Polymerase 72 Tom Kornberg's Contributions 74 Severe Ochoa's Research on RNA Polymerase 75 Kornberg's Research on DNA Synthesis 77 Synthesis of Viral DNA, 1967 79 Scientific and Popular Responses 79 Science and the Public 81 Publicist of Science 81 Advocate of Support for Basic Biomedical Research 82 Collaboration with Gobind Khorana 83 Changing Emphases in Biochemistry 85 Conference on the Chemical Basis of Heredity, 1956 87 More on the Synthesis of Viral DNA 88 Searching for Biological Activity 88 Sinsheimer's Phage Assay 90 Vitalism 91 Reductionism 92 Research on Polyphosphate 95 Attraction to the Field 95 Rejection at Berkeley 96 Medical and Developmental Implications 98 Unpopularity of the Research Field 99 More on DNA Polymerase 100 Early Interest in Nucleic Acids 100 More on Chargaff s and Avery's Contributions 102 More on Viral DNA Synthesis 103 Use of the Term "Genetic Engineering" 103 Trying to Produce a Biologically Active Molecule 104 Early Concerns About Genetic Engineering 106 Senate Testimony, March 1968 106 Critics of Genetic Engineering 107 Benefits and Dangers 108 The Nobel Prize 110 Stardom 110 Mistakes of Commission and Omission 111 Factors in the Nobel Committee's Decision 111 Drawbacks 113 Professional and University Service 114 Scientific Repercussions 115 RECOMBINANT DNA AND BIOTECHNOLOGY 117 Patenting in Biotechnology 117 Negative Influence on Academic Science 117 Secrecy in Industry 118 Decisions Regarding Product Development 119 Secrecy in Academia 120 Commercial Applications of Biology 120 Recombinant DNA Research 122 Concerns in the 1960s 122 Asilomar and the NIH Guidelines for Research on Recombinant DNA 124 Scientists Opposing Recombinant DNA Research 125 Concern about the A-T Polymer 126 Conference on Biohazards in Cancer Research, Asilomar, January 1973 127 The Moratorium 128 Potential for Scientific Research 128 An Interview with Dr. Kornberg in 1975 130 Controlling and Monitoring Research , 131 Potential Legislation 133 The Public's Role 135 The Department's Scientific Contributions 136 Dispersion of the Technology 137 Failure to Anticipate Commercial Applications 138 Industry Skepticism about Recombinant Products 139 Missing the Significance of the Lobban-Kaiser and Berg Research on Recombinant DNA 140 Peter Lobban's Research 140 Cohen and Boyer's Research 142 Mort Handel's Technique 143 Bestowing Credit on Lobban 144 Janet Mertz 145 Summary 146 Rewards and Omissions 147 The Pajaro Dunes Conference on Biotechnology, March 1982 148