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Genomic Designation: New Kinds of People at the Intersection of Genetics, Medicine and Social Action

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Genomic Designation: New Kinds of People at the Intersection of Genetics, Medicine and Social Action Genomic Designation: New kinds of people at the intersection of genetics, medicine and social action Daniel Navon Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2013 © 2013 Daniel Navon All rights reserved ABSTRACT Genomic Designation: New kinds of people at the intersection of genetics, medicine and social action Daniel Navon Genetics can do more than predict, explain or help treat medical conditions – it can create new ones. The social sciences have assumed that genetics must work in and through existing categories of human difference in order to inform clinical practice or social mobilization. By contrast, I go beyond the specter of reductionism and examine the emergence of new kinds of people at the intersection of genetics research, clinical practice and social action. For over fifty years, conditions like the XXX, Edwards, Fragile X and 22q11.2 Deletion Syndromes have been discovered, delineated and diagnosed strictly according to abnormalities in the genome, even in the absence of phenotypic coherence – a practice which I call ‘genomic designation’. This dissertation uses comparative historical methods, fieldwork and citation analysis to examine the history of genomic designation, its variable impact on practice and its implications for our understanding of the biosciences, medicine and social mobilization. I argue that genomic designation represents an important and growing practice that extends and challenges existing formulations of key concepts like ‘biosociality’, geneticization and the rise of a ‘molecular gaze’ in contemporary medicine. Furthermore, I show how it offers an opportunity to develop a typology of ways in which genetics can radically reconfigure medical classification. However, over the course of its fifty-year history, genomic designation has varied enormously as a clinical and social phenomenon and therefore in the way it impacts lived experience. I show how, during the first few decades after genomically designated syndromes began to be delineated in the human genetics literature in 1959, they gave rise to very little by way of clinical protocols, practices or specialist centers and virtually no social or advocacy organizations. And yet, in recent decades, genomically designated conditions have emerged as bona fide categories of clinical practice and social mobilization. Drawing on Fleck, Foucault and Haydu, I propose a framework of ‘reiterative facticity’ that aims to combine work from the sociology of science and medicine with a comparative-historical approach by analyzing the way that the very same genetic mutations take on divergent meanings and implications according to contrasting conditions of possibility, repertoires of collective action and the networks of research and advocacy organized around genomically designated conditions. I discuss the way that genomically designated syndromes are often ‘leveraged’ as models in biomedical research, and how this can turn them into privileged sites of knowledge production, commercial investment and social mobilization. In particular, I analyze the intersection of genetic disorders and autism in order to understand the nosological conditions for genomic designation and the ‘trading zones’ in which genetic and psychiatric systems of classification can achieve a productive interface. Finally, I use historical and fieldwork material to examine the conditions and repertoires of collective action through which a complex network has been assembled around 22q11.2 Deletion Syndrome, turning it into what Hacking would call a new kind of person that can realign clinical judgment, treatment and care. In this way, a comparative study of genomic designation shows how biological abnormality must be mediated by historical conditions and prevailing modes of understanding and acting on human difference, but also mobilized by heterogeneous networks of actors working to interface with but also transform existing structures. By way of conclusion, I discuss the possible impact of new non-invasive prenatal genetic testing on genomic designation, summarize my findings and suggest fruitful lines of future research. ! Table of Contents List of tables and figures ii Acknowledgements iv Introduction 1 Part I 1. From mutations to new medical conditions 21 2. The varieties of genomic designation: 52 Multiple pathways and an ideal-typical typology of syndromes Part II Introduction 85 3. Immobile mutations: 106 Nowhere to go in the 1960s and 70s and the exception that proves the rule 4. Of elves, warriors and autistics: 162 Leveraging abnormality in genetics research and advocacy 5. The trading zone of autism genetics: 217 Looping and the intersection of genomic and psychiatric classification 6. Assembling a new kind of person: 277 Mobilizing mutations and realigning illness Conclusion 362 References 395 ! i! ! List of tables and figures Introduction Figure 1: FISH test indicating a 22q11.2 microdeletion 2 Chapter 1 Figure 1: Clinical Syndrome Referent 44 Figure 2: Genomically-Designated Syndrome Referent 44 Table 1: Genotype-phenotype relations in four medical conditions 45 Table 2: Preliminary list of genomically designated conditions 47 Chapter 2 Figure 1: Modularity analysis of research literature 65 Figure 2: Modularity analysis with and without 22q11-related papers 66 Figure 3: Citation networks for four key moments 68 Figure 4: Citation network and communities in 1992-1995 71 excluding articles about 22q11. Figure 5: Citation networks and communities in 1998-2002 and 2003-2009 73 Figure 6: Frequency of syndrome names in paper titles, 1996-2012 74 Chapter 3 Figure 1: The standardization of human chromosome numbers 107 agreed upon in Denver, 1960 Figure 2: New York Times, April 21 1968, p. 1 126 Figure 3: Articles published by year with XYY in their titles 141 Figure 4: KS&A Brochure from XYY Syndrome 157 ! ii! ! Chapter 4 Table 1: Leveraging, alliances and resources in 207 MAOA, Williams and Fragile X Syndrome research Chapter 5 Table 1: Disease genes reported in people diagnosed with 232 autism spectrum disorders Table 2: Recurrent genomic disorders/chromosomal abnormalities 232 associated with autism Figure 1: Articles on chromosomal disorders associated with autism 239 and rates of MR and ASD keywords, 1991-2002 Figure 2: Articles on chromosomal disorders associated with autism 240 and rates of ASD and Fragile X keywords, 1991-2012 Figure 3: Papers on chromosomal disorders associated with autism 241 and ASD, Fragile X titles by year, 1982-2012 Table 3: Histories of autism association in 10 genomically designated conditions 243 ! iii! ! Acknowledgements The first note of thanks has to go to all the families, advocates and biomedical experts who have taken the time to talk to a sociologist prying into their research, practice and lives. I look forward to more over the coming years. The Binational Science Foundation, Mellon Foundation and Columbia’s Lindt and Lazarsfeld Fellowships, its Institute for Social and Economic Research and Policy and the Department of Sociology all provided crucial support while I was formulating, researching and writing the dissertation. A number of scholars at Columbia and elsewhere have taken the time to read and comment on my work and provide sage advice over the last few years. I am especially grateful to Sarah Franklin, Herbert Gans, Dani Lainer-Vos, Shamus Khan, Bill McAllister, Aaron Panofsky, Nikolas Rose, Chuck Tilly, Stefan Timmermans and Diane Vaughan. Special thanks are due to John Chalcraft and Laleh Khalili, who generously took a disenchanted philosophy student under their wings in Edinburgh and helped him make the transition to the social sciences and humanities. Brendan Hart, Anne Montgomery, Roz Redd, Aurora Fredriksen, Mattias Smångs, Hrag Balian, Jen Kondo, Des Fitzgerald, Nancy Davenport and Onur Ozgode blurred the lines between friend and colleague in a way that made the whole experience more interesting and more fun. Matt Spooner and Dan Herbert were simply incredible friends throughout. Sara Shostak and Alberto Cambrosio embraced me as a colleague as I took my first steps in a new subfield and wound up being fabulous external committee members. Uri Shwed has been a wonderful friend, colleague and collaborator over the last few years, and ! iv! ! Chapter 2 of this dissertation can be traced back one of many cherished nights spent drinking beer in his Riverside Drive apartment. I had already completed my graduate coursework when I decided to write my dissertation about genetics, medicine and advocacy, and Nadia Abu El-Haj’s ‘Science and Society’ course was an invaluable introduction to my new field. More importantly, her expertise in science studies and genetics as well as her sage advice about my work as well as some of the trickier decisions of the last few years were invaluable. Peter Bearman helped a recovering philosophy undergraduate to begin to think like a sociologist, if an unconventional one. I try to not hold that against him. In his workshops and in our meetings he always helped me think though innovative research designs, including ones focused on the outliers and oddities, which could get at big questions. He helped me navigate grad school, the transition out of it and made a spirited case for the move towards this dissertation topic, for which I am very grateful. I owe a truly extraordinary debt of gratitude to my advisor, Gil Eyal. Beginning with the two classes I took in my first year at Columbia,
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