THE RECENT HISTORY OF TUMOUR NECROSIS FACTOR (TNF) The transcript of a Witness Seminar held by the History of Modern Biomedicine Research Group, Queen Mary University of London, on 14 July 2015 Edited by A Zarros, E M Jones, and E M Tansey Volume 60 2016 ©The Trustee of the Wellcome Trust, London, 2016 First published by Queen Mary University of London, 2016 The History of Modern Biomedicine Research Group is funded by the Wellcome Trust, which is a registered charity, no. 210183. ISBN 978 1 91019 5208 All volumes are freely available online at www.histmodbiomed.org Please cite as: Zarros A, Jones E M, Tansey E M. (eds) (2016) The Recent History of Tumour Necrosis Factor (TNF). Wellcome Witnesses to Contemporary Medicine, vol. 60. London: Queen Mary University of London. CONTENTS What is a Witness Seminar? v Acknowledgements E M Tansey and A Zarros vii Illustrations and credits ix Abbreviations xi Introduction Professor Jon Cohen xv Transcript Edited by A Zarros, E M Jones, and E M Tansey 1 Appendix 1 Timeline of important events in the history of TNF 73 Appendix 2 Simplified overview of the main biological actions of TNF in rheumatoid arthritis 75 Appendix 3 Overview of TNF inhibitors mentioned in the current Witness Seminar transcript 77 Glossary 79 Biographical notes 83 References 93 Index 105 Witness Seminars: Meetings and publications 111 WHAT IS A WITNESS SEMINAR? The Witness Seminar is a specialized form of oral history, where several individuals associated with a particular set of circumstances or events are invited to meet together to discuss, debate, and agree or disagree about their memories. The meeting is recorded, transcribed, and edited for publication. This format was first devised and used by the Wellcome Trust’s History of Twentieth Century Medicine Group in 1993 to address issues associated with the discovery of monoclonal antibodies. We developed this approach after holding a conventional seminar, given by a medical historian, on the discovery of interferon. Many members of the invited audience were scientists or others involved in that work, and the detailed and revealing discussion session afterwards alerted us to the importance of recording ‘communal’ eyewitness testimonies. We learned that the Institute for Contemporary British History held meetings to examine modern political, diplomatic, and economic history, which they called Witness Seminars, and this seemed a suitable title for us to use also. The unexpected success of our first Witness Seminar, as assessed by the willingness of the participants to attend, speak frankly, agree and disagree, and also by many requests for its transcript, encouraged us to develop the Witness Seminar model into a full programme, and since then more than 60 meetings have been held and published on a wide array of biomedical topics.1 These seminars have proved an ideal way to bring together clinicians, scientists, and others interested in contemporary medical history to share their memories. We are not seeking a consensus, but are providing the opportunity to hear an array of voices, many little known, of individuals who were ‘there at the time’ and thus able to question, ratify, or disagree with others’ accounts – a form of open peer-review. The material records of the meeting also create archival sources for present and future use. The History of Twentieth Century Medicine Group became a part of the Wellcome Trust’s Centre for the History of Medicine at UCL in October 2000 and remained so until September 2010. It has been part of the School of History, Queen Mary University of London, since October 2010, as the History of Modern Biomedicine Research Group, which the Wellcome Trust 1 See pages 111–117 for a full list of Witness Seminars held, details of the published volumes, and other related publications. v funds principally under a Strategic Award entitled ‘The Makers of Modern Biomedicine’. The Witness Seminar format continues to be a major part of that programme, although now the subjects are largely focused on areas of strategic importance to the Wellcome Trust, including the neurosciences, clinical genetics, and medical technology.2 Once an appropriate topic has been agreed, usually after discussion with a specialist adviser, suitable participants are identified and invited. As the organization of the seminar progresses and the participants list is compiled, a flexible outline plan for the meeting is devised, with assistance from the meeting’s designated chairman/moderator. Each participant is sent an attendance list and a copy of this programme before the meeting. Seminars last for about four hours; occasionally full-day meetings have been held. After each meeting the raw transcript is sent to every participant, each of whom is asked to check his or her own contribution and to provide brief biographical details for an appendix. The editors incorporate participants’ minor corrections and turn the transcript into readable text, with footnotes, appendices, a glossary, and a bibliography. Extensive research and liaison with the participants is conducted to produce the final script, which is then sent to every contributor for approval and to assign copyright to the Wellcome Trust. Copies of the original, and edited, transcripts and additional correspondence generated by the editorial process are all deposited with the records of each meeting in the Wellcome Library, London (archival reference GC/253) and will be available for study. For all our volumes, we hope that, even if the precise details of the more technical sections are not clear to the non-specialist, the sense and significance of the events will be understandable to all readers. Our aim is that the volumes inform those with a general interest in the history of modern medicine and medical science; provide historians with new insights, fresh material for study, and further themes for research; and emphasize to the participants that their own working lives are of proper and necessary concern to historians. 2 See our Group’s website at www.histmodbiomed.org. vi ACKNOWLEDGEMENTS We are very grateful to Professor Jon Cohen, Professor Sir Mark Walport, and Professor Fran Balkwill for independently suggesting the topic for this seminar, and also for advising us on suitable participants and the intended programme for discussion. Many thanks also to Professor Fran Balkwill for chairing the meeting so successfully. As with all our meetings, we depend a great deal on Wellcome Trust staff to ensure their smooth running: the Audiovisual Department, Catering, Reception, Security, and Wellcome Images. We are also grateful to Mr Akio Morishima for the design and production of this volume; the indexer Ms Cath Topliff; Mrs Sarah Beanland and Ms Fiona Plowman for proofreading; Mrs Debra Gee for transcribing the seminar; Ms Caroline Overy for assisting with running the seminar and Mr Adam Wilkinson who assisted in the organization and managing of the meeting. Finally, we thank the Wellcome Trust for supporting the Witness Seminar programme. Tilli Tansey Apostolos Zarros School of History, Queen Mary University of London vii ILLUSTRATIONS AND CREDITS* Figure A Professor Jon Cohen; provided with permission xvi Figure 1 Professor Fran Balkwill 3 Figure 2 Professor Tilli Tansey 3 Figure 3 Professor Sir Ravinder Nath (Tiny) Maini 7 Figure 4 Professor Joachim Kalden 10 Figure 5 Professor Sir Marc Feldmann 13 Figure 6 Associate Professor Richard Williams 16 Figure 7 Professor Jeremy Saklatvala 18 Figure 8 Professor Yuti Chernajovsky 28 Figure 9 Dr James (Jim) Woody; provided with permission 31 Figure 10 Professor Henning Walczak 33 Figure 11 Professor Sir Ravinder Nath (Tiny) Maini and Professor Henning Walczak 42 Figure 12 Associate Professor Richard Williams and Professor Sir Marc Feldmann 49 Figure 13 Dr Marcos Vidal and Professor Joachim Kalden 61 Table 1 Witness Seminar outline programme 5 Appendix 1 Timeline of important events in the history of TNF; illustration devised by Dr Apostolos Zarros based on data from Balkwill (2009) and Dayer (2002) 73 * Unless otherwise stated, all photographs were taken by Mr Wilde Fry, Wellcome Trust, and reproduced courtesy of the Wellcome Library, London. ix Appendix 2 Simplified overview of the main biological actions of TNF in rheumatoid arthritis; illustration devised by Dr Apostolos Zarros based on data from Feldmann (2009) and Dayer (2002) 75 Appendix 3 Overview of TNF inhibitors mentioned in the current Witness Seminar transcript; table devised by Dr Apostolos Zarros based on data from Shealy and Visvanathan (2008) and Kalliolias and Ivashkiv (2016) 77 x ABBREVIATIONS ASS argininosuccinate synthase BCG British Cytokine Group CAR chimeric antigen receptor CAT Cambridge Antibody Technology CD4 cluster of differentiation 4 CD95 cluster of differentiation 95 cDNA complementary DNA CTLA4 cytotoxic T lymphocyte-associated protein 4 DKFZ Deutsches Krebsforschungszentrum (German Cancer Research Center) DMBA 7,12-dimethylbenz[a]-anthracene EMA European Medicines Agency ERC European Research Council EULAR European League Against Rheumatism Fc fragment crystallizable FDA Food and Drug Administration (USA) GM-CSF granulocyte-macrophage colony-stimulating factor GSK GlaxoSmithKline HLA-DR human leukocyte antigen – antigen D-related ICRF Imperial Cancer Research Fund (UK) IFN interferon IFN-β IFN beta IFN-γ IFN gamma IgG immunoglobulin G IgM immunoglobulin M xi IL-1 interleukin-1 IL-1α IL-1 alpha IL-1β IL-1 beta IL1B human gene for IL-1β IL-2 interleukin-2 IL-6 interleukin-6 IL-8 interleukin-8