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Stories in Isolation the Impact of Gene Discovery on Families And Stories in Isolation The impact of gene discovery on families and professionals Catherine Sampson Submitted to Cardiff University in fulfilment of the requirements for the degree of Doctor of Philosophy September 2009 UMI Number: U585292 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Dissertation Publishing UMI U585292 Published by ProQuest LLC 2013. Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 DECLARATION This work has not previously been accepted in substance for any degree and is not concurrently submitted in candidature for any degree. Signed.O?Jf^4*^ft< . ..(candidate) Date .•3?.:3:.as3.............. STATEMENT 1 This thesis is being submitted in partial fulfilment of the requirements for the degree of PhD. Signed. .. .(candidate) Date a o * 3 : ..2 s S f ll............ STATEMENT 2 This thesis is the result of my own independent work/investigation, except where otherwise stated. Other sources are acknowledged by explicit references. A bibliography is appended. Signed Q)fr*&r?r.. .. .(candidate) Date... ....2Q.-3.:.2sP%............ STATEMENT 3 I hereby give consent for my thesis, if accepted, to be available for photocopying and for inter-library loan, and for the title and summary to be made available to outside organisations. Signed. .. .(candidate) Date.............3P :.53r.. Z & t 1 ..... Acknowledgements Thanks are due firstly to the families for their time, energy and generosity in giving very personal interviews, and the scientists at the Institute who shared personal and professional memories of their endeavour. My own family have been unstintingly generous in their support. Special thanks to Katie for proving that star charts work for mature students as well as toddlers, Ciara for pep talks at crucial times, and Julian for astute comments and mastering beans on toast when time was short. My dad and sisters Oma, Hilda and Anne have, as always, been a source of comfort and diversion when it was needed. Mum, though absent, is constant. Thanks to my supervisors; Paul Atkinson at the Cardiff School of Social Science (SOCSI) whose insights guided not just the research but me as a researcher; and Angus Clarke at the Institute of Medical Genetics and the ESRC Centre for Economic and Social Aspects of Genomics (Cesagen), for his optimism and support. Mel Evans at Cesagen averted several technology related crises and the library staff, especially at the Bute, were always helpful. Thanks to Jamie Lewis, Sara Delamont, Maggie Gregory and Richard Taulke-Johnson for perceptive advice, and to Katie Featherstone and Hannah Lister for ensuring that the last few steps were taken. Liz Renton at the SOCSI Post-Graduate office has been patient and kind, no matter what the enquiry. It would not have been the same experience without the friendship and support of Rebecca Dimond, Amy Lloyd and Jackie Needs. To my old friends, especially Lee- Anne, Caroline, Carol, Maria, Loma, Pauline and Jo, thanks for not giving up on me when I was preoccupied, and to Sian for neighbourly help. Thanks to Peter Harper whose help was always given kindly and to Lindsay Prior who gave me an unexpected opportunity. This research was supported by ESRC/MRC studentship PTA-037-2005-00015 Summary This thesis examines the impact of the 1992 myotonic dystrophy gene discovery on families, clinicians, and a team of scientists who played a key role in the successful international research collaboration. The gene isolation resulted in a diagnostic test but not, as yet, treatment or cure. The scientific team, now dispersed, and families attending the myotonic dystrophy clinic were interviewed, and the myotonic dystrophy medical record archive was examined. Reflexive practice enabled the research strategy to adapt to emergent themes. A broad repertoire of qualitative methods was used to explore the data from these varied sources. Documentary traces in the archive captured research and service trajectories, from the grounding of scientific success in relationships between home, clinic and laboratory, to the contemporary management of myotonic dystrophy where bureaucracy and technology are visible but clinical expertise predominates. Through vivid recollections and use of narrative devices the scientists reconstructed a unique era in clinical genetic research. An emotional register, privileging relationships and the grounding of scientific advance in everyday laboratory work, distinguished their accounts. This language revealed subtle differences between narratives, where there was universal recognition of the importance of the discovery for a scientific career, but ambivalence regarding its personal meaning for some key actors. For families, gene discovery represented hope for future generations while personal meaning was located in the maintenance of valued roles of everyday life. The accounts narrated the challenges of adapting to an uncertain prognosis despite definitive diagnosis. Vocabularies of strength were at variance with physical weakness highlighting the significance of narrative analysis as both method and representation of meaning. Analysis of gene discovery revealed complex interpretations of meaning for the scientists, multiple representations of myotonic dystrophy across the data sources, and the gene test, rather than gene isolation, as a key turning point for families. Contents Introduction and Structure 1 Chapter one Stories in Isolation Introduction 5 Beginnings 8 Transient presences 9 Archiving the past and illuminating the present 9 Interpretations of progress 10 The story of myotonic dystrophy 14 Medical representation of DM 15 Classification 16 Ideology 19 From genes to proteins 23 Chapter two Bodies of Work: Literature, Context and Background Introduction 25 Social Science: Scientific discourse 27 Meaning in practice 28 The social life of an idea 31 Family cooperation 32 Gene Talk: Meaning in context 34 Meaning and metaphor 36 Patient People Defining issues 38 Body, Story, Self 41 The DM archive: Context 46 Function 48 History 50 Meaning 51 The DM clinic: Classification and Uncertainty 52 Technology 56 Relative Risk 57 Summary 61 Chapter three Characterising DM: Methods and Process Introduction 63 Resources: Outline 63 The DM archive and DM register 64 The researcher 65 v Research design: Epistemology 66 Documents as research topic 67 Narrative 69 Memory 73 Interviewing 74 The semi-structured interview 76 The life story interview 77 The email interview 77 Research protocol 79 Ethics 80 Recruitment 82 The Real World: 82 Home visits 83 Gene discovery interviews 87 Accessing the medical record 89 Data analysis 90 The DM archive 91 Single case analysis 93 Gene discovery analysis 95 Family interviews 98 Summary 99 Chapter four Molecular Detectives Introduction 101 Laboratory Cultures: Creative Accounting 102 Being Grounded 106 Chemistry lessons 108 Gender 112 Solutions through Problems 113 Turning Points: 114 Patronage 114 Funding 116 Technology 117 Social Scientists: The Conference 118 Ideal types 119 Competition and collaboration 120 Luck and judgement 123 The moment of discovery 125 Boundaries: 126 Moral tales 126 Hope and Hype 128 Lags and Phases 130 Personal meaning: Biography 131 Ethics 133 The Aftermath 135 Registering emotion 137 vi The impact of gene discovery 139 Summary 141 Chapter five Bound Together: Research and Service in the DM medical record Introduction 144 DM, the Clinic and the Family: Relationships 147 Risk 153 Classification 156 The punctuated chronology of DM: Intersections of everyday life and work 163 Introduction 163 Constructions of reality 164 Rhetoric in research 165 The case of a life and the life of a case 168 Life stories 171 Summary 174 Chapter six Gripping Stories: Narratives of DM and everyday life Introduction 178 “Oh God, here we go”: Accounts of diagnosis 180 An agent of change: Defining DM 185 Searching for knowledge 188 Researching knowledge 192 Agency and Isolation 194 Disclosure 195 Reconfiguration 198 Interpretive repertoires and Performance 201 Searching for meaning 202 Biography 205 Summary 209 Chapter seven Everyday lives, Genetic tomorrows Introduction 212 Expression 213 Emotivation: Motive and Emotion 219 Anticipation 223 Epiphany 229 Bibliography 230 Appendices One: Interview question 274 Two: Research protocol 276 Three: DM archive data collection sheet 282 Four: Family trees for DM family interviews 284 vii Introduction and Structure The discovery of the gene for myotonic dystrophy (DM) by an international research collaboration in 1992 represented a major scientific advance. A small team of scientists, based at a local Institute of medical genetics and led by a clinical geneticist, made a significant contribution to DM gene discovery through a combination of clinical and scientific expertise and cooperation with an extensive network of families with DM. A tendency towards earlier onset and increased severity of DM in successive generations had been observed clinically but the biological basis of this phenomenon, known as anticipation, had been fiercely contested in the decades before the “era of
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