This dissertation investigates and describes the concept of precision medicine from historical, conceptual, capital investment, industry strategic, regulatory oversight, and medicalization perspectives. The study examines the various current and ongoing challenges, impacts, assimilations, and actual adaptive measures occurring within each of these areas as a result of the emergence and continued evolution of precision medicine as a medical discipline, as well as the technosocial advancements characteristic of precision medical products, such as companion diagnostics and targeted therapeutics, seeking market entry in the United States. The dissertation argues that there is a disjunction between precision medicine and historical governance, oversight, and medical practice mechanisms. Through case studies of two case products, Foundation Medicine’s F1CDx companion diagnostic and Novartis’ Kymriah CAR-T Cell therapeutic, the dissertation illustrates the impacts, destabilization and destandardization effects, and re-standardization efforts around a precision medicine diagnostic and therapy. As a central contribution, this dissertation demonstrates and illustrates the impact(s) that precision medicinal technologies are having on the technoscientific network involved in the creation, development, evaluation, governance, and implementation of medical products in the United States. Results revealed an emerging precision medical innovation model between and among member components of a precision medical ecosystem comprised of the above-mentioned focal areas and that, to fully understand the emerging precision medical innovation model, it is critical to understand not only the impacts of precision medical technologies on the individual components of the precision medicine ecosystem, but also the impacts, adaptations, assimilations, and occlusions inherent to the ecological relations within and across the ecosystem itself. Findings include the destabilization of the traditional drug development process across all stakeholder areas, characterized by the development of non-linear adaptive processes at both the premarket and post-market phases. Although the findings from this study are significant, it is likely that they are temporary in nature and will continue to evolve in accordance with the further advancement of precision medicine, ultimately re-stabilizing the precision medical development ecosystem.

Atrial fibrillation (AF) is the most common abnormal heart rhythm, affecting

nearly 2% of the world’s population at a cost of $26 Billion in the United States annually, and incalculable costs worldwide. AF causes no symptoms for some people. However, others with AF experience uncomfortable symptoms including palpitations, breathlessness, dizziness, and fatigue. AF can severely diminish quality of life for both AF sufferers and their loved ones. Beyond uncomfortable symptoms, AF is also linked to congestive heart failure and stroke, both of which can cause premature death. Medications often fail to control AF, leading patients and healthcare providers to seek other cures, including catheter ablation. To date, catheter ablation has yielded uneven results, but garners much attention in research and innovation in pursuit of a cure for AF. This dissertation examines the historical development and contemporary practices of AF ablation to identify opportunities to improve the innovation system for the disease. First, I trace the history of AF and AF ablation knowledge from the 2nd century B.C.E. through the present. This historical look identifies patterns of knowledge co-development between science, technology, and technique, as well as publication patterns impacting knowledge dissemination. Second, I examine the current practices of AF ablation knowledge translation from the perspective of clinical practitioners to characterize the demand-side of knowledge translation in real-world practice. Demand-side knowledge translation occurs in nested patterns, and requires data, experience, and trust in order to incorporate knowledge into a practice paradigm. Third, I use social network mapping and analysis to represent the full AF ablation knowledge-practice system and identify

opportunities to modify research and innovation practice in AF ablation based on i

measures of centrality and power. Finally, I outline six linked recommendations using raw data capture during ablation procedures and open big data analytics, coupled with multi-stakeholder social networking approaches, to maximize innovation potential in AF ablation research and practice.

Neuroimaging has appeared in the courtroom as a type of `evidence' to support claims about whether or not criminals should be held accountable for their crimes. Yet the ability to abstract notions of culpability and criminal behavior with confidence from these imagines is unclear. As there remains much to be discovered in the relationship between personal responsibility, criminal behavior, and neurological abnormalities, questions have been raised toward neuroimaging as an appropriate means to validate these claims.

This project explores the limits and legitimacy of neuroimaging as a means of understanding behavior and culpability in determining appropriate criminal sentencing. It highlights key philosophical issues surrounding the ability to use neuroimaging to support this process, and proposes a method of ensuring their proper use. By engaging case studies and a thought experiment, this project illustrates the circumstances in which neuroimaging may assist in identifying particular characteristics relevant for criminal sentencing.

I argue that it is not a question of whether or not neuroimaging itself holds validity in determining a criminals guilt or motives, but rather a proper application of the issue is to focus on the way in which information regarding these images is communicated from the `expert' scientists to the `non-expert' making decisions about the sentence that are most important. Those who are considering this information's relevance, a judge or jury, are typically not well versed in criminal neuroscience and interpreting the significance of different images. I advocate the way in which this information is communicated from the scientist-informer to the decision-maker parallels in importance to its actual meaning.

As a solution, I engage Roger Pielke's model of honest brokering as a solution to ensure the appropriate use of neuroimaging in determining criminal responsibility and sentencing. A thought experiment follows to highlight the limits of science, engage philosophical repercussions, and illustrate honest brokering as a means of resolution. To achieve this, a hypothetical dialogue reminiscent of Kenneth Schaffner's `tools for talking' with behavioral geneticists and courtroom professionals will exemplify these ideas.

Leo Kanner first described autism in his 1943 article in Nervous Child titled "Autistic Disturbances of Affective Contact". Throughout, he describes the eleven children with autism in exacting detail. In the closing paragraphs, the parents of autistic children are described as emotionally cold. Yet, he concludes that the condition as he described it was innate. Since its publication, his observations about parents have been a source of controversy surrounding the original definition of autism.

Thus far, histories about autism have pointed to descriptions of parents of autistic children with the claim that Kanner abstained from assigning them causal significance. Understanding the theoretical context in which Kanner's practice was embedded is essential to sorting out how he could have held such seemingly contrary views simultaneously.

This thesis illustrates that Kanner held an explicitly descriptive frame of reference toward his eleven child patients, their parents, and autism. Adolf Meyer, his mentor at Johns Hopkins, trained him to make detailed life-charts under a clinical framework called psychobiology. By understanding that Kanner was a psychobiologist by training, I revisit the original definition of autism as a category of mental disorder and restate its terms. This history illuminates the theoretical context of autism's discovery and has important implications for the first definition of autism amidst shifting theories of childhood mental disorders and the place of the natural sciences in defining them.

In the past century, a number of technological projects have been undertaken as grand solutions to social problems. In the so called century of biology, this technological world view focuses on biomedical advances. The President of the United States, who once called for nuclear weapons and space exploration, now calls for new biotechnologies, such as genomics, individualized medicine, and nanotechnology, which will improve the world by improving our biological lives. Portrayed as the Manhattan Project of the late 20th Century, the Human Genome Project (HGP) not only undertook the science of sequencing the human genome but also the ethics of it. For this thesis I ask how the HGP did this; what was the range of possibilities of goods and evils imagined by the HGP; and what, if anything, was left out. I show that the Ethical, Legal, and Social Implications (ELSI) research program of the HGP was inscribed with the competencies of the professional field of bioethics, which had lent itself useful for governing biomedical science and technology earlier in the 20th century. Drawing on a sociological framework for understanding the development of professional bioethics, I describe the development of ELSI, and I note how the given-in-advance boundaries between authorized/unauthorized questions shaped its formation and biased technologically based conceptualizations of social problems and potential solutions. In this sense, the HGP and ELSI served both as the ends of policy and as instruments of self-legitimation, thus re-inscribing and enacting the structures for these powerful sociotechnical imaginaries. I engage the HGP and ELSI through historical, sociological, and political philosophical analysis, by examining their immediate context of the NIH, the meso level of professional/disciplinary bioethics, and the larger context of American democracy and modernity. My argument is simultaneously a claim about how questions are asked and how knowledge and expertise are made, exposing the relationship between the HGP and ELSI as a mutually constitutive and reciprocally related form of coproduction of knowledge and social structures. I finish by arguing that ELSI is in a better position than bioethics to carry out the original project of that field, i.e., to provide a space to elucidate certain institutionally authorized questions about science and technology. Finally, I venture into making a prophecy about the future of ELSI and bioethics: that the former will replace the latter as a locus for only formally rational and thin ethical debates.

Corporations in biomedicine hold significant power and influence, in both political and personal spheres. The decisions these companies make about ethics are critically important, as they help determine what products are developed, how they are developed, how they are promoted, and potentially even how they are regulated. In the last fifteen years, for-profit private companies have been assembling bioethics committees to help resolve dilemmas that require informed deliberation about ethical, legal, scientific, and economic considerations. Private sector bioethics committees represent an important innovation in the governance of emerging technologies, with corporations taking a lead role in deciding what is ethically appropriate or problematic. And yet, we know very little about these committees, including their structures, memberships, mandates, authority, and impact. Drawing on an extensive literature review and qualitative analysis of semi-structured interviews with executives, scientists and board members, this dissertation provides an in-depth analysis of the Ethics and Public Policy Board at SmithKline Beecham, the Ethics Advisory Board at Advanced Cell Technology, and the Bioethics Committee at Eli Lilly and offers insights about how ideas of bioethics and governance are currently imagined and enacted within corporations. The SmithKline Beecham board was the first private sector bioethics committee; its mandate was to explore, in a comprehensive and balanced analysis, the ethics of macro trends in science and technology. The Advanced Cell Technology board was created to be like a watchdog for the company, to prevent them from making major errors. The Eli Lilly board is different than the others in that it is made up mostly of internal employees and does research ethics consultations within the company. These private sector bioethics committees evaluate and construct new boundaries between their private interests and the public values they claim to promote. Findings from this dissertation show that criticisms of private sector bioethics that focus narrowly on financial conflicts of interest and a lack of transparency obscure analysis of the ideas about governance (about expertise, credibility and authority) that emerge from these structures and hamper serious debate about the possible impacts of moving ethical deliberation from the public to the private sector.