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Making the Breast Cancer Gene: an Archaeology of the Translational Clinic

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Making the Breast Cancer Gene: an Archaeology of the Translational Clinic Making the Breast Cancer Gene: An Archaeology of the Translational Clinic by Candace Massey B.A., University of British Columbia, 2013 Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Arts in the Department of Sociology and Anthropology Faculty of Arts and Social Sciences Candace Massey 2017 SIMON FRASER UNIVERSITY Summer 2017 Approval Name: Candace Massey Degree: Master of Arts Title: Making the Breast Cancer Gene: An Archaeology of the Translational Clinic Examining Committee: Chair: Dara Culhane Professor Cindy Patton Senior Supervisor Professor Michael Hathaway Supervisor Associate Professor Coleman Nye External Examiner Associate Professor Department of Gender, Sexuality, and Women's Studies Date Defended/Approved: May 16th, 2017 ii Abstract Between 1994 and 1995, the discovery of two gene mutations—BRCA1 and BRCA2, combined with a genetic test, led to the creation of a clinical practice centered on diagnosing and managing genetic risk for breast cancer. The discovery of the BRCA genes is framed as a model of how genetic knowledge and technologies can be swiftly “translated” into improved health outcomes for patients, despite the fact that the role of genes in common diseases has come under scrutiny following the completion of the Human Genome Project in 2003. Examining what Michel Foucault terms as the “conditions of emergence” for a genetic theory of breast cancer, this project employs close textual analysis of newspapers, press releases, and scientific research articles to critically examine the link between the discovery of the BRCA genes and translational research. Tracing the shifting relationship between genes and cancer, this project explores the impact of public criticisms on post-genomic research, describing emergent research norms, values, and epistemic commitments for translational actors, including scientists and patient advocacy groups. Keywords: BRCA; Post-Genomics; Translational Research; History of Science, Technology, and Medicine; Thought Style; Molecularization iii Dedication For my mother— In the eclipse of your life, I continue to learn from you. iv Acknowledgements I wish to thank my supervisor, Dr. Cindy Patton, for her time, encouragement, and critical insight throughout all stages of this project. Her academic guidance has challenged me to meticulously question, just as much as to justify my own, and others theoretical perspectives. Her supervision has helped me to develop my reading, writing, and analytic capabilities at a graduate level. My thanks and appreciation extends to my committee member, Dr. Michael Hathaway, for his support, insight, and direction. I want to acknowledge Dr. Dany Lacombe and Dr. Sonja Luehrmann, for their teaching and encouragement. I also want to recognize Isabelle Maurice-Hammond, Geoffrey Morrow, and Brianna Dines for their support, humour, and creativity. Our impromptu adventures and energizing conversations are the glue that holds this thesis together. v Table of Contents Approval .......................................................................................................................... ii Abstract .......................................................................................................................... iii Dedication ...................................................................................................................... iv Acknowledgements ......................................................................................................... v Table of Contents .............................................................................................................vi Chapter 1. Introduction ............................................................................................. 1 1.1. Assembling Hereditary Breast and Ovarian Cancer ................................................ 1 1.1.1. Strata X: The New Genetics ...................................................................... 5 1.1.1.2. Sequencing the Genome ............................................................................ 5 1.1.2.3. Criticisms of Gene-Centered Research ...................................................... 8 1.1.2. Strata Y: Re-Imagining the Genome ........................................................ 13 1.1.2.1. Post-Genomics ...................................................................................... 13 1.1.2.2. Translational Research .......................................................................... 14 1.1.3. Social Studies of the New Genetics ......................................................... 16 1.1.3.1. Geneticization Thesis ................................................................................ 16 1.1.3.2. Molecularization Thesis ............................................................................ 19 1.1.3.3. Case Study: The Breast Cancer Gene ..................................................... 22 Chapter 2. Analytical Framework ............................................................................ 26 2.1. Constructivist Works Approaching Scientific Practice and Innovation ................... 26 2.1.1. Capital ‘D’ Discovery: the Kuhnian Paradigm-Shifts of Normal Science ................................................................................................... 26 2.1.2. Situated Logics: Fleck’s Thought Style and Polanyi’s Tacit Knowledge ............................................................................................... 30 2.1.3. The Foucauldian Statement and Theories of Object Formation ............... 34 2.1.4. Epistemic Things ..................................................................................... 36 Chapter 3. Discovering the Breast Cancer Gene ................................................... 38 3.1. Dr. Mary-Claire King and the Genetic Thought Style ............................................ 38 3.2. The Molecular Turn in Oncology ........................................................................... 42 3.3. Making a Problem: Genetic Thought Style and Tacit Knowledge .......................... 47 3.4. Making the Gene: Stylized Knowledge and the Construction of Boundary Objects ................................................................................................................. 53 3.5. Finding the Skeleton Key ...................................................................................... 57 Chapter 4. Genes, Genes Everywhere, and Not a Disease to Treat? ................... 60 4.1. Genes, Genes, Everywhere, and Not a Disease to Treat? .................................... 60 4.1.1. Locating Translational Research as a Discursive Formation .................... 63 vi 4.1.2. The Epistemic Things of Translational Research: Forging a New Pathway .................................................................................................. 68 4.1.3. The Mutation of a Scientific Fact-Object: Splitting the BRCA Pair ............ 71 4.2. The Epistemic Value of Rare Genes ..................................................................... 75 4.2.1. Rewriting a Mendelian Disease Etiology: The Anna Karenina Hypothesis ............................................................................................... 78 4.2.2. From Gene-as-Risk to Gene-as-Function: Making Mutations with “Biological Relevance” ............................................................................. 80 Chapter 5. Translational Ontologies: Re-Assembling Disease Entities and the Breast Cancer Patient ..................................................................... 86 5.1. A Cultural Reading of Disease: Between an Anatomical and Molecular Atlas of the Body ........................................................................................................... 86 5.1.1. Unfixing the Disease Proper .................................................................... 92 5.2. Patient Advocacy Groups in the Era of Translational Genetic Medicine: Stand up to Cancer (SU2C) .................................................................................. 95 5.2.1. Presencing Things, Futures ................................................................... 102 5.2.2. Un-tying, Re-tying, Throwing Out the Ribbons of Anatomical Disease? ............................................................................................... 110 Chapter 6. Conclusion: The Present-Futures of Genetic Cancer Research ...... 113 6.1. Discursive Formation, Stylized Thought .............................................................. 115 6.2. Hope, Hype, Expectations—Disappointment?: Affective Assemblages of Translational Research ....................................................................................... 117 References…. ............................................................................................................ 120 vii Chapter 1. Introduction 1.1. Assembling Hereditary Breast and Ovarian Cancer In 1994, US researchers linked the discovery of an inherited susceptibility gene, BRCA1, with a documented pattern of familial breast cancer.1 Four months before a research team headed by geneticists Dr. Yoshi Miki and Dr. Mark Skolnick cloned and patented BRCA1, competing scientists in the field remarked that the discovery was long overdue, and that the gene would be sure to surface “any day, any week, any month now.”2 Building on seventeen years of research in her laboratory at UC Berkeley, geneticist Dr. Mary-Claire King led an earlier study that provided researchers with
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