Pharmacology & Drug Discovery

PHARMACOLOGY & DRUG DISCOVERY Compilation of edited interviews conducted by the History of Modern Biomedicine Research Group, Queen Mary University of London Edited by E M Tansey and A Zarros Volume 3 2017 ©The Trustee of the Wellcome Trust, London, 2017 First published by Queen Mary University of London, 2017 The History of Modern Biomedicine Research Group is funded by the Wellcome Trust, which is a registered charity, no. 210183. ISBN 978 1 91019 5260 All volumes are freely available online at www.histmodbiomed.org Please cite as: Tansey E M, Zarros A. (eds) (2017) Pharmacology & Drug Discovery. Voices of Modern Biomedicine, vol. 3. London: Queen Mary University of London. CONTENTS The History of Modern Biomedicine Interviews (Digital Collection) and the current volume; acknowledgments v Illustrations and credits vii Abbreviations ix Introduction Professor David Webb xi Compilation of edited interviews 1 1: Arendt, Josephine 2 2: Aronson, Jeffrey 22 3: Bakhle, Mick 44 4: Blackburn, Tom 60 5: Flower, Roderick 80 6: Green, Richard 100 7: Humphrey, Patrick 118 8: Marsden, Charles 136 9: Miner, Wesley 156 10: Sanger, Gareth 174 Related resources 193 Index 199 THE HISTORY OF MODERN BIOMEDICINE INTERVIEWS (DIGITAL COLLECTION) AND THE CURRENT VOLUME The History of Modern Biomedicine Research Group originated in 1990 as the Wellcome Trust’s History of Twentieth Century Medicine Group, which in October 2000 became a part of the Wellcome Trust’s Centre for the History of Medicine at UCL. From October 2010 until June 2017 it was a part of the School of History, Queen Mary University of London, principally funded by a Strategic Award from the Wellcome Trust. Throughout that period, the remit of the Group has been to develop and strengthen links between medical historians, and medical scientists, and practitioners, and to stimulate and expedite the historical study of contemporary biomedicine, especially by creating material resources to inform such studies. These have included the famous Witness Seminar series, widely available freely online and in print,1 and more recently a series of in-depth individual interviews. The History of Modern Biomedicine Interviews (Digital Collection), curated by Professor Tilli Tansey, Mr Adam Wilkinson, Mr Alan Yabsley, and Dr Apostolos Zarros, comprises these interviews.2 The Collection has been deposited in Queen Mary Research Online (QMRO), the online repository of Queen Mary University of London.3 The material has been linked to Digital Object Identifiers (DOIs) and can be cited. The History of Modern Biomedicine Interviews (Digital Collection) contains approximately 700 items including audio and video interview transcripts (as .pdf files), and video interview media files (as .mp4 files; video clips corresponding to the video interview transcripts archived). In addition, each interview entry includes a ‘How to cite’ file (.docx file) that acts as a guide on how to cite each item. Readers should note that video interview transcripts deposited there are edited for clarity and factual accuracy, following the principles of oral history methodology. However, the Collection’s audio interview transcripts are in most 1 See http://www.histmodbiomed.org/article/wellcome-witnesses-volumes (accessed 28 March 2017). 2 Tansey E M, Wilkinson A, Yabsley A, Zarros A. (curators) History of Modern Biomedicine Interviews (Digital Collection). Queen Mary Research Online. Queen Mary University of London, London, 2016– 2017; https://qmro.qmul.ac.uk/xmlui/handle/123456789/12359 (accessed 28 March 2017). 3 For more details, visit the QMRO website at https://qmro.qmul.ac.uk/xmlui/ (accessed 28 March 2017). v cases subject to enrichment by the interviewee and further editing. Related material has been deposited in the Wellcome Library. We now present a further edited selection from that Collection. This, the third of a three volume series of ‘Voices of Modern Biomedicine’, focusses on pharmacology and drug discovery. Sections have been selected and edited to highlight the broad features of each interviewee’s career and contributions, and much detail has been omitted. Readers wanting to learn more are encouraged to read the full interview and other material listed in the ‘Related resources’ section at the end of the volume. Moreover, we should note that some readers might consider that the interview of Josephine Arendt is of less relevance to the thematic core of drug discovery and pharmacology; we, the editors, do not share this view. We believe that her work and her experiences – as highlighted within the included edited interview – offer an interesting account of the discoveries that led to the understanding of the crucial role that melatonin and other metabolites play in the regulation of circadian rhythmicity, which is a major (patho)physiological regulator in health and disease. ACKNOWLEDGEMENTS We are grateful to Professor David Webb for writing an introduction to this volume, and also to the Wellcome Library, London, for permission to use photographs. We would like to thank Ms Lynda Finn for conducting a number of these interviews; Ms Emma M Jones, Ms Caroline Overy, Mrs Sarah Beanland, and Ms Fiona Plowman for their editorial assistance; Mr Alan Yabsley for his editorial and technical support (including filming and production of several of the original interviews); and Mr Adam Wilkinson for his excellent project management. We are grateful to Mr Jeremey Claridge, Dr Stephen Welburn, and Mrs Sarah Molloy for their time and assistance in setting up the History of Modern Biomedicine Interviews (Digital Collection), assigning DOIs to the interview transcripts, and making sure this Digital Collection is well integrated in QMRO. We are also grateful to Mr Akio Morishima for the design and production of this volume; the indexer Ms Cath Topliff; and Mrs Debra Gee for transcribing the original interviews. Finally, we thank the Wellcome Trust for their financial support. vi ILLUSTRATIONS AND CREDITS* Figure 1 Professor Josephine Arendt 2 Figure 2 Dr Jeffrey Aronson 22 Figure 3 Dr Mick Bakhle 44 Figure 4 Dr Tom Blackburn 60 Figure 5 Professor Roderick Flower 80 Figure 6 Professor Richard Green 100 Figure 7 Professor Patrick Humphrey 118 Figure 8 Professor Charles Marsden 136 Figure 9 Mr Wesley Miner 156 Figure 10 Professor Gareth Sanger 174 * All photographs were taken by Thomas Farnetti, Wellcome Trust, and reproduced courtesy of the Wellcome Library, London. vii ABBREVIATIONS 5-HT 5-hydroxytryptamine; serotonin 6-keto-PGF1α 6-keto-prostaglandin F1 alpha AFRC Agricultural and Food Research Council ATP adenosine triphosphate ATPase adenosine triphosphatase BAP British Association of Psychopharmacology BBSRC Biotechnology and Biological Sciences Research Council B J Clin Pharm British Journal of Clinical Pharmacology BJP British Journal of Pharmacology BMJ British Medical Journal BNA British Neuroscience Association BPS British Pharmacological Society; Pharm Soc BRA Brain Research Association CASE Collaborative Awards in Science and Engineering CNS central nervous system COMT catechol-O-methyltransferase CWC Chemical Weapons Convention DMU De Montfort University DMPK drug metabolism and pharmacokinetics ECT electroconvulsive therapy EEG electroencephalography FDA Food and Drug Administration (US) fMRI functional MRI GABA gamma aminobutyric acid GI gastrointestinal GM gastric motility GP General Practitioner GSK GlaxoSmithKline ix HPLC high pressure liquid chromatography IBS irritable bowel syndrome ICI ICI Pharmaceuticals IUPHAR International Union of Pharmacology J Physiol The Journal of Physiology KCL King’s College London MAO monoamine oxidase MDMA 3,4-methylenedioxy-methamphetamine MIMS Monthly Index of Medical Specialities MRC Medical Research Council MRI magnetic resonance imaging Na+,K+-ATPase sodium/potassium ATPase NIH National Institutes of Health NIMH National Institute of Mental Health NHS National Health Service OUP Oxford University Press Pharm Soc British Pharmacological Society; BPS Phys Soc The Physiological Society PTSD post-traumatic stress disorder QMUL Queen Mary University of London R&D Research and Development RCS Royal College of Surgeons RS Royal Society SAD Seasonal Affective Disorder SB SmithKline Beecham SHO Senior House Officer SSRI selective serotonin reuptake inhibitor SWOT Strengths, Weaknesses, Opportunities, Threats (analysis) TAT Therapeutic Area Team x INTRODUCTION The science of pharmacology has made outstanding contributions to the discovery and development of medicines over the last 50 years, and at the same time supported the health and wealth of the United Kingdom. This fascinating volume, which complements the highly successful Witness Seminar programme, brings together edited interviews with a range of individuals with different fields of expertise and perspectives. It takes us through the careers and life journeys of eminent pharmacologists, and reminds us how research completed in academic institutions, the pharmaceutical industry and the National Health Service has had major effects to extend life, and improve the quality of life, in those of us born in recent times. The pharmacologists and clinical pharmacologists who have contributed first- hand accounts are highly-regarded for the leading roles that they have played in advancing our vibrant field of science. We must be grateful to the participants for the generosity with which they have given their time to this project, and for their openness in discussion. We all gain from ‘standing on the shoulders of giants’ and it is essential

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