Participatory Genomic Research: Ethical Issues from the Bottom Up to the Top Down.

Participatory approaches to genomic research manifest along a continuum from bottom-up citizen-science initiatives designed to liberate scientific inquiry from the constraints of traditional research institutional contexts and professional practices to top-down investigator-initiated studies designed to expose the public to scientific research processes and build its support and enthusiasm for genomic research. With foundations as varied as open science, crowdsourcing, patient advocacy, social media, the digitization of health, and the neoliberalization of academic research, a range of ethical frameworks inform the modes of participatory genomic research. Using illustrations from citizen genomic science, patient advocacy, and investigator-led and government-initiated genomic research efforts, we argue that as participatory genomic research pushes the conventional research boundaries toward a more democratizing ethos, it challenges scientific practices and the ethical conduct of genomic research both within and outside of the traditional sites of biomedical innovation.

Precisely Where Are We Going? Charting the New Terrain of Precision Prevention.

In addition to genetic data, precision medicine research gathers information about three factors that modulate gene expression: lifestyles, environments, and communities. The relevant research tools-epidemiology, environmental assessment, and socioeconomic analysis-are those of public health sciences rather than molecular biology. Because these methods are designed to support inferences and interventions addressing population health, the aspirations of this research are expanding from individualized treatment toward precision prevention in public health. The purpose of this review is to explore the emerging goals and challenges of such a shift to help ensure that the genomics community and public policy makers understand the ethical issues at stake in embracing and pursuing precision prevention. Two emerging goals bear special attention in this regard: (a) public health risk reduction strategies, such as screening, and (b) the application of genomic variation studies to understand and reduce health disparities among population groups.

Serving epigenetics before its time.

Society prizes the rapid translation of basic biological science into ways to prevent human illness. However, the premature rush to take murine epigenetic findings in these directions makes impossible demands on prospective parents and triggers serious social and ethical questions.

Tracking U.S. Professional Athletes: The Ethics of Biometric Technologies.

Professional sport in the United States has widely adopted biometric technologies, dramatically expanding the monitoring of players' biodata. These technologies have the potential to prevent injuries, improve performance, and extend athletes' careers; they also risk compromising players' privacy and autonomy, the confidentiality of their data, and their careers. The use of these technologies in professional sport and the consumer sector remains largely unregulated and unexamined. We seek to provide guidance for their adoption by examining five areas of concern: (1) validity and interpretation of data; (2) increased surveillance and threats to privacy; (3) risks to confidentiality and concerns regarding data security; (4) conflicts of interest; and (5) coercion. Our analysis uses professional sport as a case study; however, these concerns extend to other domains where their use is expanding, including the consumer sector, collegiate and high school sport, the military, and commercial sectors where monitoring employees is viewed as useful for safety or to maximize labor potential.

Citizen science or scientific citizenship? Disentangling the uses of public engagement rhetoric in national research initiatives.

BACKGROUND: The language of "participant-driven research," "crowdsourcing" and "citizen science" is increasingly being used to encourage the public to become involved in research ventures as both subjects and scientists. Originally, these labels were invoked by volunteer research efforts propelled by amateurs outside of traditional research institutions and aimed at appealing to those looking for more "democratic," "patient-centric," or "lay" alternatives to the professional science establishment. As mainstream translational biomedical research requires increasingly larger participant pools, however, corporate, academic and governmental research programs are embracing this populist rhetoric to encourage wider public participation. DISCUSSION: We examine the ethical and social implications of this recruitment strategy. We begin by surveying examples of "citizen science" outside of biomedicine, as paradigmatic of the aspirations this democratizing rhetoric was originally meant to embody. Next, we discuss the ways these aspirations become articulated in the biomedical context, with a view to drawing out the multiple and potentially conflicting meanings of "public engagement" when citizens are also the subjects of the science. We then illustrate two uses of public engagement rhetoric to gain public support for national biomedical research efforts: its post-hoc use in the "care.data" project of the National Health Service in England, and its proactive uses in the "Precision Medicine Initiative" of the United States White House. These examples will serve as the basis for a normative analysis, discussing the potential ethical and social ramifications of this rhetoric. We pay particular attention to the implications of government strategies that cultivate the idea that members of the public have a civic duty to participate in government-sponsored research initiatives. We argue that such initiatives should draw from policy frameworks that support normative analysis of the role of citizenry. And, we conclude it is imperative to make visible and clear the full spectrum of meanings of "citizen science," the contexts in which it is used, and its demands with respect to participation, engagement, and governance.

"Reflection and soul searching": Negotiating nursing identity at the fault lines of palliative care and medical assistance in dying.

Authorities within the field of palliative care frequently espouse that assisted death is - and must remain - separate from palliative care. This fault line, between palliative care and assisted death, has important implications for how we enact end-of-life care, particularly in jurisdictions where assisted death is legal. And yet little is known about how direct-care clinicians providing palliative care navigate this demarcation in everyday practice. This qualitative study reports on semi-structured interviews with 22 palliative care nurses from across Canada, where assisted death was legalized in 2016. Although a minority of participants did express categorical opinions around the (non) legitimacy of assisted death as an ethical end-of-life care option, most engaged in an ongoing and sometimes painful process of questioning and self-examination. Their ethical reflections were more nuanced than simply dismissing MAiD as incompatible with palliative care philosophy; yet this idea of incompatibility weighed heavily as they reasoned through their experiences and questioned their own perspectives. Nurses described grappling with the finality of assisted death, which contradicts their belief in the telos of palliative care; when adequately resourced, palliative care should be available to support people to live well before death. At the same time, commitment to important palliative care values such as the non-abandonment of dying people and respecting peoples' individual end-of-life choices reveal the possibility of overlap between the ethos of assisted death and that of palliative care nursing. Drawing on scholarship in feminist ethics, our study sheds light on the moral identity work that assisted dying catalyzes amongst palliative care nurses. We highlight what is at stake for them as they navigate a delicate tension in responding ethically to patients whose suffering motivates an interest in assisted death, from within a wider professional collective that upholds a master narrative about the incompatibility of assisted death and palliative care.

In the vanguard of biomedicine? The curious and contradictory case of anti-ageing medicine.

The rise of anti-ageing medicine is emblematic of the current conditions of American biomedicine. Through in-depth interviews with 31 anti-ageing practitioners, we examine how practitioners strive for-and justify-a model of care that runs counter to what they see as the 'assembly line' insurance-managed industry of healthcare. Their motivation, however, is not merely a reaction to conventional medicine. It is derived from what they see as a set of core beliefs about the role of the physician, the nature of the physician-patient relationship, and the function of biomedicine. We analyse this ideology to underscore how anti-ageing medicine is built on a 'technology of the self', a self in need of constant surveillance, intervention, and maintenance. The ultimate goal is to create an optimal self, not just a self free of illness. A fundamental irony is that, despite their self-presentation and the perception of the public, anti-ageing providers do not use practices that are especially 'high-tech' or unconventional. Instead, the management of ageing bodies rests on providers' perceived knowledge of their patients, tailored treatments, and a collaborative pact between the provider and patient.

Propranolol and the prevention of post-traumatic stress disorder: is it wrong to erase the "sting" of bad memories?

The National Institute of Mental Health (Bethesda, MD) reports that approximately 5.2 million Americans experience post-traumatic stress disorder (PTSD) each year. PTSD can be severely debilitating and diminish quality of life for patients and those who care for them. Studies have indicated that propranolol, a beta-blocker, reduces consolidation of emotional memory. When administered immediately after a psychic trauma, it is efficacious as a prophylactic for PTSD. Use of such memory-altering drugs raises important ethical concerns, including some futuristic dystopias put forth by the President's Council on Bioethics. We think that adequate informed consent should facilitate ethical research using propranolol and, if it proves efficacious, routine treatment. Clinical evidence from studies should certainly continue to evaluate realistic concerns about possible ill effects of diminishing memory. If memory-attenuating drugs prove effective, we believe that the most immediate social concern is the over-medicalization of bad memories, and its subsequent exploitation by the pharmaceutical industry.

Suffering and medicalization at the end of life: The case of physician-assisted dying.

'Suffering' is a central discursive trope for the right-to-die movement. In this article, we ask how proponents of physician-assisted dying (PAD) articulate suffering with the role of medicine at the end of life within the context of a decriminalization and legalization debate. We draw upon empirical data from our study of Carter v. Canada, the landmark court case that decriminalized PAD in Canada in 2015. We conducted in-depth interviews with 42 key participants of the case and collected over 4000 pages of legal documents generated by the case. In our analysis of the data, we show the different ways proponents construct relationships between suffering, mainstream curative medicine, palliative care, and assisted dying. Proponents see curative medicine as complicit in the production of suffering at the end of life; they lament a cultural context wherein life-prolongation is the moral imperative of physicians who are paternalistic and death-denying. Proponents further limit palliative care's ability to alleviate suffering at the end of life and even go so far as to claim that in some instances, palliative care produces suffering. Proponents' articulation of suffering with both mainstream medicine and palliative care might suggest an outright rejection of a place for medicine at the end of life. We further find, however, that proponents insist on the involvement of physicians in assisted dying. Proponents emphasize how a request for PAD can set in motion an interactive therapeutic process that alleviates suffering at the end of life. We argue that the proponents' articulation of suffering with the role of medicine at the end of life should be understood as a discourse through which one configuration of end-of-life care comes to be accepted and another rejected, a discourse that ultimately does not challenge, but makes productive use of the larger framework of the medicalization of dying.

From "Personalized" to "Precision" Medicine: The Ethical and Social Implications of Rhetorical Reform in Genomic Medicine.

Since the late 1980s, the human genetics and genomics research community has been promising to usher in a "new paradigm for health care"-one that uses molecular profiling to identify human genetic variants implicated in multifactorial health risks. After the completion of the Human Genome Project in 2003, a wide range of stakeholders became committed to this "paradigm shift," creating a confluence of investment, advocacy, and enthusiasm that bears all the marks of a "scientific/intellectual social movement" within biomedicine. Proponents of this movement usually offer four ways in which their approach to medical diagnosis and health care improves upon current practices, arguing that it is more "personalized," "predictive," "preventive," and "participatory" than the medical status quo. Initially, it was personalization that seemed to best sum up the movement's appeal. By 2012, however, powerful opinion leaders were abandoning "personalized medicine" in favor of a new label: "precision medicine." The new label received a decisive seal of approval when, in January 2015, President Obama unveiled plans for a national "precision medicine initiative" to promote the development and use of genomic tools in health care.

Bioidentical hormones, menopausal women, and the lure of the "natural" in U.S. anti-aging medicine.

In 2002, the Women's Health Initiative, a large-scale study of the safety of hormone replacement therapy (HRT) for women conducted in the United States, released results suggesting that use of postmenopausal HRT increased women's risks of stroke and breast cancer. In the years that followed, as rates of HRT prescription fell, another hormonal therapy rose in its wake: bioidentical hormone replacement therapy (BHRT). Anti-aging clinicians, the primary prescribers of BHRT, tout it as a safe and effective alternative to treat menopausal symptoms and, moreover, as a preventative therapy for age-related diseases and ailments. Through in-depth interviews with 31 U.S.-based anti-aging clinicians and 25 female anti-aging patients, we analyze attitudes towards BHRT. We illustrate how these attitudes reveal broader contemporary values, discourses, and discomforts with menopause, aging, and biomedicine. The attraction to and promise of BHRT is rooted in the idea that it is a "natural" therapy. BHRT is given both biomedical and embodied legitimacy by clinicians and patients because of its purported ability to become part of the body's "natural" processes. The normative assumption that "natural" is inherently "good" not only places BHRT beyond reproach, but transforms its use into a health benefit. The clinical approach of anti-aging providers also plays a role by validating patients' embodied experiences and offering a "holistic" solution to their symptoms, which anti-aging patients see as a striking contrast to their experiences with conventional biomedical health care. The perceived virtues of BHRT shed light on the rhetoric of anti-aging medicine and a deeply complicated relationship between conventional biomedicine, hormonal technologies, and women's bodies.

Physicians and euthanasia: a Canadian print-media discourse analysis of physician perspectives.

BACKGROUND: Recent events in Canada have mobilized public debate concerning the controversial issue of euthanasia. Physicians represent an essential stakeholder group with respect to the ethics and practice of euthanasia. Further, their opinions can hold sway with the public, and their public views about this issue may further reflect back upon the medical profession itself. METHODS: We conducted a discourse analysis of print media on physicians' perspectives about end-of-life care. Print media, in English and French, that appeared in Canadian newspapers from 2008 to 2012 were retrieved through a systematic database search. We analyzed the content of 285 articles either authored by a physician or directly referencing a physician's perspective. RESULTS: We identified 3 predominant discourses about physicians' public views toward euthanasia: 1) contentions about integrating euthanasia within the basic mission of medicine, 2) assertions about whether euthanasia can be distinguished from other end-of-life medical practices and 3) palliative care advocacy. INTERPRETATION: Our data showed that although some medical professional bodies appear to be supportive in the media of a movement toward the legalization of euthanasia, individual physicians are represented as mostly opposed. Professional physician organizations and the few physicians who have engaged with the media are de facto representing physicians in public contemporary debates on medical aid in dying, in general, and euthanasia, in particular. It is vital for physicians to be aware of this public debate, how they are being portrayed within it and its potential effects on impending changes to provincial and national policies.

Manufacturing desire: the commodification of female sexual dysfunction.

The process of bringing new drugs to market interweaves commercialism, science, clinical medicine, and governmental regulation. Through their authority and public persona as medical experts, academic clinical trial researchers studying these pharmaceuticals are integral to this process, serving as mediators between producers (the pharmaceutical companies) and consumers (clinicians and patients) of new drugs through a complex set of exchange networks. Using examples from my ethnographic research on the search for pharmaceuticals to treat what has become known as female sexual dysfunction, this paper explores the links academic researchers make with drug manufacturers and consumer markets. Academic researchers have become an integral aspect of drug development, not only by conducting clinical trial research, but also by participating in a number of other activities that assist pharmaceutical companies in identifying and creating new markets. In this paper, i examine how researchers attend professional meetings where they present clinical trial data, lecture at continuing medical education conferences, and offer themselves as ' experts' to raise awareness about disorders and their treatments. Modifying a sociology of technology approach, this paper focuses on the actors in the social network who mediate the junctions between technological producers and consumers. This extends work in this area through theorizing the linkages between exchange networks, commodification techniques, and technoscientific developments.

Big data, open science and the brain: lessons learned from genomics.

The BRAIN Initiative aims to break new ground in the scale and speed of data collection in neuroscience, requiring tools to handle data in the magnitude of yottabytes (10(24)). The scale, investment and organization of it are being compared to the Human Genome Project (HGP), which has exemplified "big science" for biology. In line with the trend towards Big Data in genomic research, the promise of the BRAIN Initiative, as well as the European Human Brain Project, rests on the possibility to amass vast quantities of data to model the complex interactions between the brain and behavior and inform the diagnosis and prevention of neurological disorders and psychiatric disease. Advocates of this "data driven" paradigm in neuroscience argue that harnessing the large quantities of data generated across laboratories worldwide has numerous methodological, ethical and economic advantages, but it requires the neuroscience community to adopt a culture of data sharing and open access to benefit from them. In this article, we examine the rationale for data sharing among advocates and briefly exemplify these in terms of new "open neuroscience" projects. Then, drawing on the frequently invoked model of data sharing in genomics, we go on to demonstrate the complexities of data sharing, shedding light on the sociological and ethical challenges within the realms of institutions, researchers and participants, namely dilemmas around public/private interests in data, (lack of) motivation to share in the academic community, and potential loss of participant anonymity. Our paper serves to highlight some foreseeable tensions around data sharing relevant to the emergent "open neuroscience" movement.

Gatekeepers or intermediaries? The role of clinicians in commercial genomic testing.

BACKGROUND: Many commentators on "direct-to-consumer" genetic risk information have raised concerns that giving results to individuals with insufficient knowledge and training in genomics may harm consumers, the health care system, and society. In response, several commercial laboratories offering genomic risk profiling have shifted to more traditional "direct-to-provider" (DTP) marketing strategies, repositioning clinicians as the intended recipients of advertising of laboratory services and as gatekeepers to personal genomic information. Increasing popularity of next generation sequencing puts a premium on ensuring that those who are charged with interpreting, translating, communicating and managing commercial genomic risk information are appropriately equipped for the job. To shed light on their gatekeeping role, we conducted a study to assess how and why early clinical users of genomic risk assessment incorporate these tools in their clinical practices and how they interpret genomic information for their patients. METHODS AND FINDINGS: We conducted qualitative in-depth interviews with 18 clinicians providing genomic risk assessment services to their patients in partnership with DNA Direct and Navigenics. Our findings suggest that clinicians learned most of what they knew about genomics directly from the commercial laboratories. Clinicians rely on the expertise of the commercial laboratories without the ability to critically evaluate the knowledge or assess risks. CONCLUSIONS: DTP service delivery model cannot guarantee that providers will have adequate expertise or sound clinical judgment. Even if clinicians want greater genomic knowledge, the current market structure is unlikely to build the independent substantive expertise of clinicians, but rather promote its continued outsourcing. Because commercial laboratories have the most "skin in the game" financially, genetics professionals and policymakers should scrutinize the scientific validity and clinical soundness of the process by which these laboratories interpret their findings to assess whether self-interested commercial sources are the most appropriate entities for gate-keeping genomic interpretation.

Integrating genomics into clinical oncology: ethical and social challenges from proponents of personalized medicine.

INTRODUCTION: The use of molecular tools to individualize health care, predict appropriate therapies, and prevent adverse health outcomes has gained significant traction in the field of oncology under the banner of "personalized medicine" (PM). Enthusiasm for PM in oncology has been fueled by success stories of targeted treatments for a variety of cancers based on their molecular profiles. Though these are clear indications of optimism for PM, little is known about the ethical and social implications of personalized approaches in clinical oncology. OBJECTIVE: The objective of this study is to assess how a range of stakeholders engaged in promoting, monitoring, and providing PM understand the challenges of integrating genomic testing and targeted therapies into clinical oncology. METHODS AND MATERIALS: The study involved the analysis of in-depth interviews with 117 stakeholders whose experiences and perspectives on PM span a wide variety of institutional and professional settings. RESULTS: Despite their considerable enthusiasm for this shift, promoters, monitors, and providers of PM identified 4 domains that provoke heightened ethical and social concerns: (1) informed consent for cancer genomic testing, (2) privacy, confidentiality, and disclosure of genomic test results, (3) access to genomic testing and targeted therapies in oncology, and (4) the costs of scaling up pharmacogenomic testing and targeted cancer therapies. CONCLUSIONS: These specific concerns are not unique to oncology, or even genomics. However, those most invested in the success of PM view oncologists' responses to these challenges as precedent setting because oncology is farther along the path of clinical integration of genomic technologies than other fields of medicine. This study illustrates that the rapid emergence of PM approaches in clinical oncology provides a crucial lens for identifying and managing potential frictions and pitfalls that emerge as health care paradigms shift in these directions.

Examining the ethical and social issues of health technology design through the public appraisal of prospective scenarios: a study protocol describing a multimedia-based deliberative method.

BACKGROUND: The design of health technologies relies on assumptions that affect how they will be implemented, such as intended use, complexity, impact on user autonomy, and appropriateness. Those who design and implement technologies make several ethical and social assumptions on behalf of users and society more broadly, but there are very few tools to examine prospectively whether such assumptions are warranted and how the public define and appraise the desirability of health innovations. This study protocol describes a three-year study that relies on a multimedia-based prospective method to support public deliberations that will enable a critical examination of the social and ethical issues of health technology design. METHODS: The first two steps of our mixed-method study were completed: relying on a literature review and the support of our multidisciplinary expert committee, we developed scenarios depicting social and technical changes that could unfold in three thematic areas within a 25-year timeframe; and for each thematic area, we created video clips to illustrate prospective technologies and short stories to describe their associated dilemmas. Using this multimedia material, we will: conduct four face-to-face deliberative workshops with members of the public (n=40) who will later join additional participants (n=25) through an asynchronous online forum; and analyze and integrate three data sources: observation, group deliberations, and a self-administered participant survey. DISCUSSION: This study protocol will be of interest to those who design and assess public involvement initiatives and to those who examine the implementation of health innovations. Our premise is that using user-friendly tools in a deliberative context that foster participants' creativity and reflexivity in pondering potential technoscientific futures will enable our team to analyze a range of normative claims, including some that may prove problematic and others that may shed light over potentially more valuable design options. This research will help fill an important knowledge gap; intervening earlier in technological development could help reduce undesirable effects and inform the design and implementation of more appropriate innovations.