Why We Should Reexamine the "Golden Age" of Antibiotics in Social Context.

Economics is the primary discipline used to understand supply chain design, scale-up, and management. For example, antibiotics can be compared to other forms of "tragedy of the commons," whereby a common good (effective treatment of infections) is jeopardized by individual consumption and lack of community oversight and stewardship. While economic analysis can explain innovation decline in terms of market failure, one pitfall of an early-stage focus on research and development is a failure to challenge the discovery narrative. Ethics also has a distinct place in helping us envision alternatives to what markets can produce. This article advances a more contextualized view of how science and technology policy has shaped antibiotic supply chains over many years, emphasizing how shifting the story we tell about past successes is central to securing a reliable antibiotic supply chain in the future.

Can One Health Policy Help Us Expand an Ethics of Interconnection and Interdependence?

One Health-a holistic approach to health that brings the moral status of animals and environments into consideration-is understood as a "professional imperative," a value-laden obligation that flows from the scope and objectives of professional roles. In this article, antimicrobial resistance provides a case study to demonstrate the fruitfulness of public health and bioethics collaborations by applying One Health key concepts of interconnection and interdependence. Moving toward an ethics of One Health requires a more nuanced analysis of ecological relationships, including humans' connections to other species as hosts, vectors, domestic companions, meat-eaters' food, and farmers' livelihood.

The New Precision Stewards?

The precision health era is likely to reduce and respond to antimicrobial resistance (AMR). Our stewardship and precision efforts share terminology, seeking to deliver the "right drug, at the right dose, at the right time." Already, rapid diagnostic testing, phylogenetic surveillance, and real-time outbreak response provide just a few examples of molecular advances we dub "precision stewardship." However, the AMR causal factors range from the molecular to that of global health policy. Mirroring the cross-sectoral nature of AMR science, the research addressing the ethical, legal and social implications (ELSI) of AMR ranges across academic scholarship. As the rise of AMR is accompanied by an escalating sense of its moral and social significance, what is needed is a parallel field of study. In this paper, we offer a gap analysis of this terrain, or an agenda for "the ELSI of precision stewardship." In the first section, we discuss the accomplishments of a multi-decade U.S. national investment in ELSI research attending to the advances in human genetics. In the next section, we provide an overview of distinct ELSI topics pertinent to AMR. The distinctiveness of an ELSI agenda for precision stewardship suggests new opportunities for collaboration to build the stewardship teams of the future.

Lay understandings of drug-gene interactions: The right medication, the right dose, at the right time, but what are the right words?

As pharmacogenomic (PGx) testing increases in popularity, lay concepts of drug-gene interactions set the stage for shared decision making in precision medicine. Few studies explore what recipients of PGx results think is happening in their bodies when a drug-gene interaction is discovered. To characterize biobank participants' understanding of PGx research results, we conducted a focus group study, which took place after PGx variants conferring increased risk of dihydropyrimidine dehydrogenase (DPD) deficiency were disclosed to biobank contributors. DPD deficiency confers an increased risk of adverse reaction to commonly used cancer chemotherapeutics. Ten focus groups were conducted, ranging from two to eight participants. Fifty-four individuals participated in focus groups. A framework approach was used for descriptive and explanatory analysis. Descriptive themes included participants' efforts to make sense of PGx findings as they related to: (1) health implications, (2) drugs, and (3) genetics. Explanatory analysis supplied a functional framework of how participant word choices can perform different purposes in PGx communication. Results bear three main implications for PGx research-related disclosure. First, participants' use of various terms suggest participants generally understanding their PGx results, including how positive PGx results differ from positive disease susceptibility genetic results. Second, PGx disclosure in biobanking can involve participant conflation of drug-gene interactions with allergies or other types of medical reactions. Third, the functional framework suggests a need to move beyond a deficit model of genetic literacy in PGx communication. Together, findings provide an initial evidence base for supporting bidirectional expert-recipient PGx results communication.

Ethical Challenges in COVID-19 Biospecimen Research: Perspectives From Institutional Review Board Members and Bioethicists.

Biospecimen research is a prominent investigative strategy that aims to provide novel insights into coronavirus disease 2019 (COVID-19), inform clinical trials, and develop effective, life-saving treatments. However, COVID-19 biospecimen research raises accompanying ethical concerns and practical challenges for investigators and participants. In this special article, we discuss the ethical issues that are associated with autonomy, beneficence, and justice in COVID-19 biospecimen research and describe strategies to manage the practical challenges, with an emphasis on protecting the rights and welfare of human research participants during a pandemic response. Appropriate institutional review board oversight and bioethics guidance for COVID-19 biospecimen research must maintain their focus on protecting the rights and welfare of research participants, despite the urgent need for more knowledge about the virus and the threat it poses to communities and nations.

Communicating unexpected pharmacogenomic results to biobank contributors: A focus group study.

OBJECTIVES: The goals of this study were to explore 1) the impact of returning unexpected pharmacogenomic (PGx) results to biobank contributors, and 2) participant views about improving communication. METHODS: We conducted a qualitative focus group study with biobank participants (N = 54) who were notified by mail of an individual research result indicating increased risk for adverse events associated with the common cancer drug 5-fluorouracil (5-FU). We employed a framework approach for analysis. RESULTS: Our results revealed three themes illustrating participants' questions and uncertainty, especially regarding how to share results with health providers and family members, and remember them over time. Participants valued results for themselves and others, and for the future of medicine. Risk perception was framed by health identity. "Toxicity narratives," or familiarity with another's adverse reaction to chemotherapy, increased the sense of importance participants reported. CONCLUSION: These focus group results highlight research participant remaining questions and high valuation of PGx results, even when unexpected. PRACTICE IMPLICATIONS: We identify PGx research participants' needs for clear clinical translation messaging that attends to health identity, pragmatics of sharing information with family members, and patient perceptions of barriers to transferring research results to a clinical context.

At a Moment's Notice: Community Advisory Board Perspectives on Biobank Communication to Supplement Broad Consent.

INTRODUCTION: To address ethical concerns about the of future research authorization, biobanks employing a broad model of consent can design ongoing communication with contributors. Notifying contributors at the time of sample distribution provides one form of communication to supplement broad consent. However, little is known about how community-informed governance might anticipate contributor responses and inform communication efforts. OBJECTIVE: We explored the attitudes of members of a three-site Community Advisory Board (CAB) network. CAB members responded to a hypothetical proposal for notifying biobank contributors at the time of sample distribution to researchers utilizing the biobank. METHODS: We used regularly scheduled CAB meetings to facilitate 3 large-group and 6 small-group discussions. Discussions were audio-recorded, transcribed, and analyzed for thematic content using descriptive thematic analysis. RESULTS: The results challenged our expectation of general support for the proposed communications. While CAB members identified some advantages, they were concerned about several potential harms to biobank contributors and the biobank. The CABs understood biobank communication in terms of an ongoing relationship with the biobank and a personal contribution to research. CONCLUSION: Our findings contribute to the emerging literature on community engagement in biobanking. Additional communication with biobank contributors can serve a variety of value-based objectives to supplement broad consent. Design of communication efforts by biobanks can be improved by CAB members' anticipation of the unintended consequences of additional contact with contributors. CAB members' holistic interpretation of communication efforts suggests that biobank leadership considers all communication options as part of a more comprehensive communications strategy.

Assessing the implications of positive genomic screening results.

Aim: Before population screening of 'healthy' individuals is widely adopted, it is important to consider the harms and benefits of receiving positive results and how harms and benefits may differ by age. Subjects & methods: Participants in a preventive genomic screening study were screened for 17 genes associated with 11 conditions. We interviewed 11 participants who received positive results. Results: Interviewees expressed little concern about their positive results in light of their older age, the risk condition for which they tested positive, or other pressing health concerns. Conclusion: Researchers and clinicians should recognize that returning positive results may not have the impact they presume given the diversity of the conditions screened and those who choose to undergo screening.

Reexamining the Ethics of Human Germline Editing in the Wake of Scandal.

In November 2018, the announcement that genetically edited human embryos had been used for reproductive purposes caused international uproar; many observers argued that editing the human germline was unethical, particularly given the early stage of the science and the absence of appropriate oversight. We provide an overview of the implications of these events, focusing on the relevant ethical considerations for physicians addressing patient questions and concerns. The editing of the human germline for reproductive purposes should be understood against an historic backdrop of clinical research in assisted reproduction, as well as other exemplars of translational investigation. An important question raised by our growing capacity to genetically alter human embryos is how to understand the implicit social contract between science and society. To ensure that translational research continues to enjoy the historic trust placed in scientists and research organizations, it is critical that scientific and health care institutions proactively engage governments, patient advocacy organizations, and the general public in the formation of policies that guide gene editing.

A New Governance Approach to Regulating Human Genome Editing.

For years, genomic medicine-medicine based on the growing understanding of the genetic contribution to many diseases and conditions-has been hailed as the future of medical treatment, but it has thus far had limited effect on day-to-day medical practice. The ultimate goal of genomic medicine has always been the ability not just to identify dangerous gene mutations, but to fix them. Now CRISPR and related genome-editing technologies may have the potential to provide a safe and effective way to repair dangerous mutations. In the wake of ethically dubious experiments with human embryos in China, the international governance of human genome editing is emerging as an urgent topic for scientists, regulators, and the public. Efforts to develop a governance model are underway at national and international levels. These efforts are the subject of multiple initiatives by national and international health and science organizations and are topics of discussion at scientific conferences, summits, and meetings. This Article reports on the Authors' multi-year, interdisciplinary project to identify and investigate the practical, ethical, and policy considerations that are emerging as the greatest concerns about human genome editing, and ultimately to develop policy options. The project involves monitoring the discussions of groups, both government-sponsored and private, that are considering how genome editing should be governed; observing conferences where the topic is discussed; analyzing emerging policy reports by national and international bodies; and interviewing a wide range of stakeholders, including scientists, ethicists, and those who make and comment on public policy. The Article identifies several stakeholder concerns that are especially prominent in the research to date and begins to explore the implications of these concerns for alternative models of governance. There are current indications that, for practical purposes, a focus on "soft," hybrid forms of governance based on networks of multiple public and private stakeholders may turn out to be the most promising course to pursue. The "new governance" paradigm developed in the corporate and financial sectors offers a useful model for understanding the dynamics of this approach.

Fostering a prevention mindset for responsible gene editing.

In this special issue, we solicited three commentators to discuss issues specific to the responsible conduct of research as it relates to the birth of gene-edited children. We explore the ethics of prevention and its ties to the responsible conduct of gene-editing research to introduce three commentaries addressing: (1) the relevance of cultural and regulatory context in China, (2) how to actualize calls for greater public engagement, and (3) where we might improve graduate education of genomic researchers.

Is Enhancement the Price of Prevention in Human Gene Editing?

New gene-editing tools challenge conventional policy proscriptions of research aimed at either human germline gene editing or human enhancement by potentially lowering technical barriers to both kinds of intervention. Some recent gene-editing reports have begun to take up the prospect of germline editing, but most experts are in broad agreement that research should prioritize medical applications over attempts to enhance human traits. However, there is little consensus about what counts as human enhancement in this context, or how to deal with the issues it flags. Moreover, several influential reports interpret medical applications to include disease prevention as well as treatment as a goal for gene-editing research. This challenges the current policy consensus because using gene editing to prevent disease would incidentally facilitate human enhancement applications in a variety of ways. If such research efforts are penalized by policy concerns about enhancement, then their preventive health benefits could be lost. To avoid being caught off guard by such challenges, science policy makers will need to think more carefully about what "prevention" might mean in the gene-editing context, and develop research governance that can anticipate and address the human enhancement concerns it will raise. To accomplish the latter, the scope of policy making will need to expand from its narrow focus on human clinical trials to engage with basic researchers driving the translational pipeline toward preventive gene editing and the science policy makers who have to address its "off-label" uses.