Arthur D. Riggs, City of Hope's Contribution to Early Genentech Research, 2006
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Regional Oral History Office University of California The Bancroft Library Berkeley, California Program in Bioscience and Biotechnology Studies ARTHUR D. RIGGS CITY OF HOPE’S CONTRIBUTION TO EARLY GENENTECH RESEARCH Interviews Conducted by Sally Smith Hughes in 2005 Copyright © 2006 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 legal agreements between The Regents of the University of California and Arthur D. Riggs, dated March 28, 2005. 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, The Bancroft Library, Mail Code 6000, University of California, Berkeley 94720-6000, and should include identification of the specific passages to be quoted, anticipated use of the passages, and identification of the user. It is recommended that this oral history be cited as follows: Arthur D. Riggs, “City of Hope's Contribution to Early Genentech Research,” an oral history conducted in 2005 by Sally Smith Hughes, Regional Oral History Office, The Bancroft Library, University of California, Berkeley, 2006. Copy no. ______ Dr. Arthur D. Riggs. In background photo: Keiichi Itakura, Riggs, David Goeddel, and Roberto Crea, City of Hope/Genentech team that cloned human insulin gene. iv Table of Contents—Arthur D. Riggs Biotechnology Series History vii Biotechnology Oral History List ix Interview History xi Interview 1, January 12, 2005 Tape 1, Side A 1 Family background and early life in California—Education and early research—Major in chemistry at University of California at Riverside Tape 1, Side B 8 Doctoral work at Caltech on DNA replication—Mycoplasma genome research Tape 2, Side A 15 State of molecular biology in mid-1960s—Research on DNA replication— Postdoctoral work on the lac repressor in Melvin Cohn’s laboratory at the Salk Institute—City of Hope Medical Center, Duarte, California—Research on X- chromosome inactivation and the lac repressor—Susumu Ohno and Charles Todd—Collaborating with Caltech on lac repressor crystallography Tape 2, Side B 21 Keiichi Itakura and DNA synthesis at Caltech and City of Hope—Richard Scheller, DNA synthesis, and DNA linkers—Collaborating with Herbert Boyer on lac operator cloning—Riggs’ inspiration to combine DNA synthesis and recombinant DNA Tape 3, Side A 29 Showing synthetic DNA to function in vivo—Itakura and Riggs imagine DNA synthesis of insulin—Authors of the lac operon cloning paper Interview 2, January 13, 2005 Tape 4, Side A 32 Proof-of-principle research on somatostatin—NIH grant application failure— Contracting with Genentech on somatostatin and insulin—Collaboration with Boyer lab—Novelty of corporate relationships in academia—Keiichi Itakura’s synthesis of DNA coding for somatostatin v Tape 4, Side B 40 Boyer lab contributions to somatostatin project—Initial failure and Robert Swanson’s reaction—Reorienting the experiments—Successful cloning and expression of somatostatin—Imagining practical applications and corporate research contracts—Roberto Crea—Recombinant DNA controversy and a changed research plan—The press conference—Publishing and patenting in basic science Tape 5, Side A 48 Tom Kiley, drafting the patent application, and choosing inventors—City of Hope’s contract with Genentech—New patent claims over time—Broad methods patents—Riggs prioritizes the somatostatin project—Moving to research on human insulin—Three-way institutional race for insulin—Swanson pressures the scientists Tape 5, Side B 58 Intense research by David Goeddel, Herbert Heyneker and Dennis Kleid— Riggs, Louise Shively and the molecular biology component of human insulin research—Protein purification work—Poor assays for insulin—Tom Perkins encourages the City of Hope-Genentech contract—Impressions of Swanson and the UCSF scientists—Swanson’s concept of a fully integrated company—Riggs views Genentech as a source of research contracts— Publishing the research Interview 3, January 14, 2005 Tape 6, Side A 66 Justifying two publications on human insulin—Speculating on why Boyer was not an author—Genentech’s youth culture—Human growth hormone project— Combining complementary DNA and DNA synthesis techniques—License agreements with KabiGen and Eli Lilly—Vision of a large market for growth hormone—Riggs’ choice to remain in basic science—Antibody research in collaboration with Genentech Tape 6, Side B 74 Reconstituting, humanizing, and cloning recombinant antibodies with Herbert Heyneker and Shmuel Cabilly—Potential use of CEA antibodies in cancer therapy—The Cabilly patents—Chakrabarty Supreme Court decision on patenting life forms vi Tape 7, Side A 81 Riggs’ opinion about commercializing biology—Genentech’s publishing policy— Belief that technology is more important than hypothesis–driven research— Epigenetics research—Administrative duties—Two major scientific contributions Appendix 1—Significant Research Accomplishments 91 Appendix 2—Curriculum Vitae 93 vii Biotechnology Series History—Sally Smith Hughes, Ph.D. Genesis of the Program in Bioscience and Biotechnology Studies In 1996 The Bancroft Library launched the forerunner of the Program in Bioscience and Biotechnology Studies. The Bancroft has strong holdings in the history of the physical sciences--the papers of E.O. Lawrence, Luis Alvarez, Edwin McMillan, and other campus figures in physics and chemistry, as well as a number of related oral histories. Yet, although the university is located next to the greatest concentration of biotechnology companies in the world, the Bancroft had no coordinated program to document the industry or its origins in academic biology. When Charles Faulhaber arrived in 1995 as the Library's new director, he agreed on the need to establish a Bancroft program to capture and preserve the collective memory and papers of university and corporate scientists who created the biotechnology industry. Documenting and preserving the history of a science and industry which influences virtually every field of the life sciences and generates constant public interest and controversy is vital for a proper understanding of science and business in the late twentieth and early twenty-first centuries. The Bancroft Library is the ideal location to carry out this historical endeavor. It offers the combination of experienced oral history and archival personnel and technical resources to execute a coordinated oral history, archival, and Internet program. It has an established oral history series in the biological sciences, an archival division called the History of Science and Technology Program, and the expertise to develop comprehensive records management and to digitalize documents for presentation on the Web in the California Digital Library. It also has longstanding cooperative arrangements with UC San Francisco and Stanford University, the other research universities in the San Francisco Bay Area. In April 1996, Daniel E. Koshland, Jr. provided seed money for a center at The Bancroft Library for historical research on the biological sciences and biotechnology. And then, in early 2001, the Program in Bioscience and Biotechnology Studies was given great impetus by Genentech’s major pledge to support documentation of the biotechnology industry. Thanks to these generous gifts, the Bancroft is building an integrated collection of research materials--oral history transcripts, personal papers, and archival collections-- related to the history of the biological sciences and biotechnology in university and industry settings. A board composed of distinguished figures in academia and industry advises on the direction of the oral history and archival components. The Program's initial concentration is on the San Francisco Bay Area and northern California. But its ultimate aim is to document the growth of molecular biology as an independent field of the life sciences, and the subsequent revolution which established biotechnology as a key contribution of American science and industry. viii Oral History Process The oral history methodology used in this program is that of the Regional