Ethical Issues in Genetics and Infectious Diseases Research: An Interdisciplinary Expert Review.

PURPOSE: Research in genetics and infectious diseases (ID) presents novel configurations of ethical, legal, and social issues (ELSIs) related to the intersection of genetics with public health regulations and the control of transmissible diseases. Such research includes work both in pathogen genetics and on the ways that human genetics affect responses to ID. This paper identifies and systematizes the unique issues at this intersection, based on an interdisciplinary expert review. BASIC PROCEDURES: This paper presents results of a formal issue-spotting exercise among twenty experts in public health, law and genomics, biobanking, genetic epidemiology, ID medicine and public health, philosophy, ethics and ID, ethics and genomics, and law and ID. The focus of the exercise was on the collection, storage, and sharing of genetic information relating to ID. MAIN FINDINGS: The issue-spotting exercise highlighted the following ELSIs: risks in reporting to government authorities, return of individual research results, and resource allocation - each taking on specific configurations based on the balance between public health and individual privacy/protection. PRINCIPAL CONCLUSIONS: The public health implications of interactions between genomics and ID frame considerations for equity and justice. In the context of the COVID-19 pandemic, these issues are especially pressing.

Genomics in Patient Care and Workforce Decisions in High-Level Isolation Units: A Survey of Healthcare Workers.

The impact of host genomics on an individual's susceptibility, immune response, and risk of severe outcomes for a given infectious pathogen is increasingly recognized. As we uncover the links between host genomics and infectious disease, a number of ethical, legal, and social issues need to be considered when using that information in clinical practice or workforce decisions. We conducted a survey of the clinical staff at 10 federally funded Regional Ebola and Other Special Pathogen Treatment Centers to understand their views regarding the ethical, legal, and social issues related to host genomics and the administrative and clinical functions of high-level isolation units. Respondents overwhelmingly agreed that genomics could provide valuable information to identify patients and employees at higher risk for poor outcomes from highly infectious diseases. However, there was considerable disagreement about whether such data should inform the allocation of scarce resources or determine treatment decisions. While most respondents supported a confidential employer-based genomic testing system to inform individual employees about risk, respondents disagreed about whether such information should be used in staffing models. Respondents who thought genomic information would be valuable for patient treatment were more willing to undergo genetic testing for staffing purposes. Most respondents felt they would benefit from additional training to better interpret results from genetic testing. Although this study was completed before the COVID-19 pandemic, the responses provide a baseline assessment of provider attitudes that can inform policy during the current pandemic and in future infectious disease outbreaks.

The Ethics of Precision Rationing: Human Genetics and the Need for Debate on Stratifying Access to Medication.

Rising prices for new, transformative therapies are challenging health systems around the world, leading many payers and providers to begin rationing access to treatments, even in the countries that have been most resistant to doing so. This is the case for direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV). However, little attention has been paid to the increasing role that human genetics might play in rationing decisions. Researchers have already proposed that genetic markers associated with spontaneous HCV clearance could be used to restrict DAA access for some patients, although treatment would be medically beneficial for those patients. Would such forms of rationing present a form of genetic discrimination? And what of the public health implications of these approaches? Here we present an ethical analysis of such proposals for "precision rationing" and raise 4 key areas of concern. We argue that ethical issues arising in this area are not substantively different from the pressing ethical issues regarding rationing and discrimination more broadly, but provide important impetus for motivating broad public debate to find ethically sound ways of managing genomics and new expensive medications.

Genomics and Infectious Diseases: Expert Perspectives on Public Health Considerations regarding Actionability and Privacy.

There is growing evidence that human genetics plays a significant role in shaping human responses to infectious diseases. For instance, individuals' genetic susceptibility or resistance to infectious disease is likely to affect disease transmission. Yet little attention has been paid to the ethical, legal, and social implications of research in genomics and infectious disease, despite the unique ethical issues that arise in this arena. This article presents results from a pilot study exploring ethics in research on human genetics and response to HIV and other infectious diseases and is focused on perspectives from expert stakeholders. Whereas chairs of institutional review boards, biobank directors, and researchers in genomics and infectious disease expressed similar views about research privacy in the context of a public health emergency, they expressed different perspectives about the role that public health considerations ought to play in the return of individual results to research participants. These perspectives highlight the need to emphasize the importance of broad dialogue for helping various parties navigate the ethically complex current and future challenges of genomics and infectious disease research.

What If the Influenza Vaccine Did Not Offer Such Variable Protection?

BACKGROUND: The protection that an influenza vaccine offers can vary significantly from person to person due to differences in immune systems, body types, and other factors. The question, then, is what is the value of efforts to reduce this variability such as making vaccines more personalized and tailored to individuals. METHODS: We developed a compartment model of the United States to simulate different influenza seasons and the impact of reducing the variability in responses to the influenza vaccine across the population. RESULTS: Going from a vaccine that varied in efficacy (0-30%) to one that had a uniform 30% efficacy for everyone averted 16.0-31.2 million cases, $1.9-$3.6 billion in direct medical costs, and $16.1-$42.7 billion in productivity losses. Going from 0-50% in efficacy to just 50% for everyone averted 27.7-38.6 million cases, $3.3-$4.6 billion in direct medical costs, and $28.8-$57.4 billion in productivity losses. Going from 0-70% to 70% averted 33.6-54.1 million cases, $4.0-$6.5 billion in direct medical costs, and $44.8-$64.7 billion in productivity losses. CONCLUSIONS: This study quantifies for policy makers, funders, and vaccine developers and manufacturers the potential impact of efforts to reduce variability in the protection that influenza vaccines offer (eg, developing vaccines that are more personalized to different individual factors).

Personal Genetic Information about HIV: Research Participants' Views of Ethical, Social, and Behavioral Implications.

BACKGROUND: Personal genetic information (PGI) about HIV is produced in research and entering the clinic and direct-to-consumer market, but little consideration has been given to ethical and social issues, public perspectives, and potential behavioral implications. OBJECTIVES: This research queried the views of research participants at risk for or infected with HIV, exploring their perspectives on HIV-related PGI and its ethical, social, and behavioral implications. METHODS: We used focus groups to collect rich information about participants' perspectives on the ethical, social, and behavioral implications of PGI about HIV and host genetic research. We evaluated their reactions to three different types of genetic variants: those that made them more susceptible to HIV, more protected from or resistant to HIV, or more likely to transmit HIV to others. RESULTS: Overall, participants wanted PGI about HIV. Their reasons included a mix of personal or family health benefit and benefit to others, which varied in emphasis depending on variant type. While susceptibility variant information was seen primarily in terms of personal or family health benefit, for transmissibility and protective variant information, benefit to others emerged as a major reason for wanting PGI about HIV. Participants thought transmissibility variant information would help them prevent others from becoming infected, and protective variant information would allow them to volunteer for targeted research to help treat, cure, or prevent HIV. Possible harms were raised regarding the tendencies among some individuals to increase risky behavior with modulations in perceived risk. Potential behavioral implications were seen as significant, though complex, reflecting multifaceted risk perceptions. CONCLUSIONS: Our study adds to the evidence that participants in genetic research, across disease type, have a strong desire for PGI. For participants in research on the genetics of HIV, and potentially other infectious diseases, their desire for PGI is grounded in a perceived duty not to infect others, where they feel a moral responsibility regarding research participation and behavior change. Wider dissemination of HIV-related PGI may well increase research participation, but could have mixed effects on risk behavior. More research is needed on the implications of different variant types of PGI beyond susceptibility factors, especially protective variants or resistance factors.

Genomics and High-Consequence Infectious Diseases: A Scoping Review of Emerging Science and Potential Ethical Issues.

Host genomic research on high-consequence infectious diseases is a growing area, but the ethical, legal, and social implications of such findings related to potential applications of the research have not yet been identified. While there is a robust ethical debate about the ethical, legal, and social implications of research during an emergency, there has been less consideration of issues facing research conducted outside of the scope of emergency response. Addressing the implications of research at an early stage (anticipatory ethics) helps define the issue space, facilitates preparedness, and promotes ethically and socially responsible practices. To lay the groundwork for more comprehensive anticipatory ethics work, this article provides a preliminary assessment of the state of the field with a scoping review of host genomic research on a subset of high-consequence infectious diseases of relevance to high-level isolation units, focusing on its ethically relevant features and identifying several ethical, legal, and social implications raised by the literature. We discuss the challenges of genomic studies of low-frequency, high-risk events and applications of the science, including identifying targets to guide the development of new therapeutics, improving vaccine development, finding biomarkers to predict disease outcome, and guiding decisions about repurposing existing drugs and genetic screening. Some ethical, legal, and social implications identified in the literature included the rise of systems biology and paradigm shifts in medical countermeasure development; controversies over repurposing of existing drugs; genetic privacy and discrimination; and benefit-sharing and global inequity as part of the broader ecosystem surrounding high-level isolation units. Future anticipatory ethics work should forecast the science and its applications; identify a more comprehensive list of ethical, legal, and social implications; and facilitate evaluation by multiple stakeholders to inform the integration of ethical concerns into high-level isolation unit policy and practice.

The medicalization of obesity, bariatric surgery, and population health.

This article examines how the medicalization of obesity validates the use of bariatric surgery to treat obesity in the United States and how expansions in access to bariatric surgery normalize surgical procedures as disease treatment and prevention tools. Building on this discussion, the article poses two questions for population health regarding health technology: (1) to what extent does bariatric surgery treat obesity in the United States while diverting attention away from the ultimate drivers of the epidemic and (2) to what extent does bariatric surgery improve outcomes for some groups in the US population while simultaneously generating disparities? We conduct a brief, historical analysis of the American Medical Association's decision to reclassify obesity as a disease through internal documents, peer-reviewed expert reports, and major media coverage. We use medicalization theory to show how this decision by the American Medical Association channels increased focus on obesity into the realm of medical intervention, particularly bariatric surgery, and use this evidence to review research trends on bariatric surgery. We propose research questions that investigate the population health dimensions of bariatric surgery in the United States and note key areas of future research. Our objective is to generate a discourse that considers bariatric surgery beyond the medical realm to better understand how technological interventions might work collectively with population-level obesity prevention efforts and how, in turn, population health approaches may improve bariatric surgery outcomes.

"When Does It Stop Being Peanut Butter?": FDA Food Standards of Identity, Ruth Desmond, and the Shifting Politics of Consumer Activism, 1960s-1970s.

This article uses a historical controversy over the U.S. Food and Drug Administration's standard of identity for peanut butter as a site for investigating three topics of high importance for historians of technology, consumption, and food activism: how new industrial food-processing technologies have become regulatory problems; how government, industry, and consumer actors negotiate standards development; and how laypeople try to shape technological artifacts in spaces dominated by experts. It examines the trajectory of consumer activist Ruth Desmond, co-founder of the organization the Federation of Homemakers. By following Desmond's evolving strategies, the article shows how the broader currents of the 1960s-70s consumer movement played out in a particular case. Initially Desmond used a traditional style that heavily emphasized her gendered identity, working within a grassroots organization to promote legislative and regulatory reforms. Later, she moved to a more modern advocacy approach, using adversarial legal methods to fight for consumer protections.

"What is the FDA Going to Think?": Negotiating Values through Reflective and Strategic Category Work in Microbiome Science.

The US National Institute of Health's Human Microbiome Project aims to use genomic techniques to understand the microbial communities that live on the human body. The emergent field of microbiome science brought together diverse disciplinary perspectives and technologies, thus facilitating the negotiation of differing values. Here, we describe how values are conceptualized and negotiated within microbiome research. Analyzing discussions from a series of interdisciplinary workshops conducted with microbiome researchers, we argue that negotiations of epistemic, social, and institutional values were inextricable from the reflective and strategic category work (i.e., the work of anticipating and strategizing around divergent sets of institutional categories) that defined and organized the microbiome as an object of study and a potential future site of biomedical intervention. Negotiating the divergence or tension between emerging scientific and regulatory classifications also activated "values levers" and opened up reflective discussions of how classifications embody values and how these values might differ across domains. These data suggest that scholars at the intersections of science and technology studies, ethics, and policy could leverage such openings to identify and intervene in the ways that ethical/regulatory and scientific/technical practices are coproduced within unfolding research.

Barriers to Considering Ethical and Societal Implications of Research: Perceptions of Life Scientists.

BACKGROUND: As part of an empirical study investigating how life scientists think about ethical and societal implications of their work, and about life science research in general, we sought to elucidate barriers that scientists might face in considering such implications. METHOD: Between 2005 and 2007, we conducted a study consisting of phone interviews, focus groups, and a national survey of life scientists at biomedical research institutions. The study population included graduate students, postdoctoral fellows, faculty, clinical instructors, and research staff. We analyzed data through qualitative and quantitative methods. RESULTS: In analyzing the data, we found that life scientists do, in fact, face barriers to considering ethical and societal implications of research. We categorized these barriers as falling into four broad domains: (1) lack of awareness of ethical and societal implications; (2) lack of relevance of such concerns to their specific research; (3) self-confidence in their ability to resolve such concerns; and (4) aspects of the daily practice of science itself. CONCLUSIONS: Life science researchers experience elements inherent in their training and in the conduct of science as barriers to thinking about ethical and societal implications related to their work. These findings suggest areas in which research ethics educators, bioethicists, and the scientific community can focus their efforts to improve social and ethical accountability in research.

Biomedical scientists' perceptions of ethical and social implications: is there a role for research ethics consultation?

BACKGROUND: Research ethics consultation programs are being established with a goal of addressing the ethical, societal, and policy considerations associated with biomedical research. A number of these programs are modelled after clinical ethics consultation services that began to be institutionalized in the 1980s. Our objective was to determine biomedical science researchers' perceived need for and utility of research ethics consultation, through examination of their perceptions of whether they and their institutions faced ethical, social or policy issues (outside those mandated by regulation) and examination of willingness to seek advice in addressing these issues. We conducted telephone interviews and focus groups in 2006 with researchers from Stanford University and a mailed survey in December 2006 to 7 research universities in the U.S. FINDINGS: A total of 16 researchers were interviewed (75% response rate), 29 participated in focus groups, and 856 responded to the survey (50% response rate). Approximately half of researchers surveyed (51%) reported that they would find a research ethics consultation service at their institution moderately, very or extremely useful, while over a third (36%) reported that such a service would be useful to them personally. Respondents conducting human subjects research were more likely to find such a service very to extremely useful to them personally than respondents not conducting human subjects research (20% vs 10%; chi(2) p<0.001). CONCLUSION: Our findings indicate that biomedical researchers do encounter and anticipate encountering ethical and societal questions and concerns and a substantial proportion, especially clinical researchers, would likely use a consultation service if they were aware of it. These findings provide data to inform the development of such consultation programs in general.

Strangers at the benchside: research ethics consultation.

Institutional ethics consultation services for biomedical scientists have begun to proliferate, especially for clinical researchers. We discuss several models of ethics consultation and describe a team-based approach used at Stanford University in the context of these models. As research ethics consultation services expand, there are many unresolved questions that need to be addressed, including what the scope, composition, and purpose of such services should be, whether core competencies for consultants can and should be defined, and how conflicts of interest should be mitigated. We make preliminary recommendations for the structure and process of research ethics consultation, based on our initial experiences in a pilot program.