Ethical, Legal, and Social Implications of Personalized Genomic Medicine Research: Current Literature and Suggestions for the Future.

PURPOSE: This review identifies the prominent topics in the literature pertaining to the ethical, legal, and social issues (ELSI) raised by research investigating personalized genomic medicine (PGM). METHODS: The abstracts of 953 articles extracted from scholarly databases and published during a 5-year period (2008-2012) were reviewed. A total of 299 articles met our research criteria and were organized thematically to assess the representation of ELSI issues for stakeholders, health specialties, journals, and empirical studies. RESULTS: ELSI analyses were published in both scientific and ethics journals. Investigational research comprised 45% of the literature reviewed (135 articles) and the remaining 55% (164 articles) comprised normative analyses. Traditional ELSI concerns dominated the discourse including discussions about disclosure of research results. In fact, there was a dramatic increase in the number of articles focused on the disclosure of research results and incidental findings to research participants. Few papers focused on particular disorders, the use of racial categories in research, international communities, or special populations (e.g., adolescents, elderly patients, or ethnic groups). CONCLUSION: Considering that strategies in personalized medicine increasingly target individuals' unique health conditions, environments, and ancestries, further analysis is needed on how ELSI scholarship can better serve the increasingly global, interdisciplinary, and diverse PGM research community.

Governing nonconventional genetic experimentation.

A large and highly heterogeneous group of individuals conducts genetic and genomic research outside of traditional corporate and academic settings. They can be an important source of innovation, but their activities largely take place beyond the purview of existing regulatory systems for promoting safe and ethical practices. Historically the gene-targeting technology available for non-traditional genomic research has been limited, and therefore these activities have attracted little regulatory attention. New technologies such as CRISPR/Cas9, however, give nonconventional experimenters more extensive gene editing abilities at an unprecedented level of accessibility. The affordability and accessibility of these powerful technologies are raising questions about whether the current largely laissez-faire governance approach is adequate. This article recommends steps to enhance self-governance, including establishing umbrella organizations to represent community interests, creating a community IRB modelled on the DIYBio Ask a Safety Expert Service, and adopting an ethical obligation to report rogue experiments.

Predictive Genetic Testing by the U.S. Military: Legal and Ethical Issues.

INTRODUCTION: Precision medicine is a significant component of the military medical vanguard. One area of growing interest involves predictive genetic testing (PGT)-which can be used for both medical evaluation and operational planning. Predictive genetic testing is likely to play an increasingly important role in the military, in terms of both medically related testing to predict the risk of disease or injury and testing for non-medical traits that may be relevant to military performance. MATERIALS AND METHODS: This article describes predictive tests that currently are in use by the military or that might be of interest to the military. The article also explores the risks and benefits associated with PGTs, describes the ambiguities in the current laws and directives governing the military use of PGT, and proposes a set of guidelines for the use of PGTs by the military. RESULTS: There is no publicly available law or DoD policy that prevents the military from conducting PGT before or after accession. Currently, the only genetic testing routinely employed by the U.S. military is for medical purposes. In addition to non-routine genetic testing to diagnose genetic diseases and conditions, the military also uses targeted testing for predictive purposes. As additional predictive genetic tests are developed and become widely used, the military can be expected to employ those that are of relevance. Predictive military genetic testing of active duty service members could reduce their risk of illness and injury, improve their physical and mental fitness, enhance the health and well-being of the unit, make mission accomplishment more certain and efficient, and reduce medical and other costs for the military and veterans. Moreover, individuals with genetic variants that might enhance the likelihood of successfully completing a military mission could be preferred for certain positions or assignments, such as special operations. At the same time, there are risks that genetic information may be used for improper purposes or may stigmatize service members. CONCLUSIONS: Predictive genetic testing is likely to play an increasingly important role in the military, in terms of both medically related testing to predict the risk of disease or injury and testing for non-medical traits that may be relevant to military performance. In instances where PGT meets standard scientific measures of validity and utility, test results can be used to promote the health and welfare of individual service members, units, and military missions. In cases where PGT does not rise to the level of meeting standard scientific criteria, officials should proceed cautiously in incorporating the information into clinical care and military decision-making. There needs to be an appropriate method of collectively calculating risks and benefits. Moreover, although military directives prohibit "unlawful discrimination," this term has received no elaboration in any publicly available military pronouncements. This lacuna should be rectified to provide proper guidance to service members, medical personnel, and the public. Although the promise of PGT may compel military officials to consider ways to maximize the use of test results, the risk of undermining military goals with unverified uses also should be considered appropriately.

Compulsory Immunization Protects Against Infection: What Law and Society Can Do.

Since their broad implementation, immunizations have decreased morbidity and mortality due to a number of serious infectious diseases. In recent years, exaggerated concerns about the safety of immunizations have resulted in decreased immunization coverage in many regions and epidemic outbreaks of serious transmissible diseases - most particularly measles. This commentary reviews the legal justification for compulsory immunization and the ethical justification for civil incentives to assure compliance with immunization practices.

Making all the children above average: ethical and regulatory concerns for pediatricians in pediatric enhancement research.

Building on the knowledge generated by the long history of disease-oriented research, the next few decades will witness an explosion of biomedical enhancements to make people faster, stronger, smarter, less forgetful, happier, prettier, and live longer. Growing interest in pediatric enhancements is likely to stimulate the conduct of enhancement research involving children. However, guidelines for the protection of human subjects were developed for investigations of therapeutic modalities. To date, virtually no attention has been paid to whether these rules would be appropriate for investigations to establish the safety and efficacy of technologies intended for enhancement rather than therapeutic uses and, if not, whether ethically acceptable rules could be designed. This article discusses whether the current guidelines for pediatric research provide appropriate protections for pediatric subjects in enhancement research and considers what additional protections might be necessary.

The Haves, the Have-nots, and the Will-nots.

What if science enabled us to live an extended lifespan? Well, not us, but people in the future, and perhaps not everybody in the future, at least not at first. Should we allow and encourage science to develop this capability, or should we try to prevent or inhibit it? John Davis's book New Methuselahs: The Ethics of Life Extension is a thorough exploration of these questions. He presents the arguments for and against developing this capacity, and he considers three perspectives: those of individuals who will be able to extend their lives (the Haves), individuals who will not because they can't afford to (the Have-nots), and individuals who will not extend their lives because they are opposed to doing so (the Will-nots). Davis is a philosopher, and the bulk of this book is for the cognoscenti.

Human subjects protections in biomedical enhancement research: assessing risk and benefit and obtaining informed consent.

The protection of human subjects in biomedical research relies on two principal mechanisms: assessing and comparing the risks and potential benefits of proposed research, and obtaining potential subjects' informed consent. While these have been discussed extensively in the literature, no attention has been paid to whether the processes should be different when the objective of an experimental biomedical intervention is to improve individual appearance, performance, or capability ("enhancement research") rather than to prevent, cure, or mitigate disease ("health-oriented research"). This essay examines this question in order to ensure that subjects in biomedical enhancement research receive adequate protection.

Who Do You Trust?

The ability of patients to trust physicians to act in their best interests is a critical aspect of a welfare-maximizing relationship. This commentary discusses physician trustworthiness within the framework of the Affordable Care Act and considers steps to reinforce trustworthy behavior.

Malpractice reforms: are they fair?

In the debate over medical malpractice reform, the dimension of fairness often is invoked but is poorly understood. This article describes the factors that promote fairness in public policy and then examines whether proposed or enacted tort reforms would be fair. It finds that many of the reforms that are being promoted by perinatologists would be unfair; however, some reforms, including one broad-ranging proposal that was put forward by the Institute of Medicine, could satisfy fairness criteria depending on how they were implemented.

Genetic enhancement: plan now to act later.

All three main articles in the issues of the Kennedy Institute of Ethics Journal endorse the view that genetic enhancement should be permitted, including human germ-line genetic enhancement. However, unregulated, wealth-based access to genetic enhancement in general, and germ-line enhancement in particular, would create intolerable risks for society. Although there are a number of practical problems raised by proposals to regulate or restrict access to genetic enhancement, which will make it difficult if not impossible to muster support for any effective restrictions until we begin to experience the societal problems that genetic enhancement will create, it is important to consider now what restrictions would be appropriate, how they would be imposed, and what changes would be needed in existing laws and institutions to facilitate them. Without this type of groundwork, there is no way society will be in a position to act in time.

Reproductive Information and Reproductive Decision-Making.

Opponents of reproductive choice are attempting to limit reproductive decisions based on certain underlying reasons. This commentary explores the rationales for these limitations and the objections to them. It concludes that reasoned-based limitations are unsupportable and unenforceable.

Anti-aging medicine: can consumers be better protected?

The use of interventions claiming to prevent, retard, or reverse aging is proliferating. Some of these interventions can seriously harm older persons and aging baby boomers who consume them. Others that are merely ineffective may divert patients from participating in beneficial regimens and also cause them economic harm. "Free market regulation" does not seem to weed out risky, ineffective, and fraudulent anti-aging treatments and products. Public health messages, apparently, are having little effect. What more can be done to achieve better protection for older consumers? An analysis of the potential for federal and state action reveals many barriers to effective governmental regulation of anti-aging interventions. In view of dim prospects for stronger public regulation, physicians and other professionals--especially geriatricians and gerontologists--will need to be more aggressive in protecting older consumers. In particular, The Gerontological Society of America and the American Geriatrics Society should undertake a sustained program of specific educational efforts, directed at health professionals and the general public, in which they sort out as best they can the helpful, the harmful, the fraudulent, and the harmless anti-aging practices and products.

Ethical, legal, social, and policy issues in the use of genomic technology by the U.S. Military.

Advances in genomic science are attracting the interest of the U.S. military for their potential to improve medical care for members of the military and to aid in military recruitment, training, specialization, and mission accomplishment. While researchers have explored the ethical, legal, and social issues raised by the use of genomic science in a wide variety of contexts, there has been virtually no examination of these issues in connection with the use of genomics by the military. This article identifies potential uses of genomic science by the military, proposes an applicable ethical and legal framework, and applies the framework to provide ethical and legal guidance for military decision-makers.

Genetic enhancement in sport: just another form of doping?

Patented genetic technologies such as the ACTN3 genetic test are adding a new dimension to the types of performance enhancement available to elite athletes. Organized sports organizations and governments are seeking to prevent athletes' use of biomedical enhancements. This paper discusses how these interdiction efforts will affect the use and availability of genetic technologies that can enhance athletic performance. The paper provides a working definition of enhancement, and in light of that definition and the concerns of the sports community, reviews genetic enhancement as a result of varied technologies, including, genetic testing to identify innate athletic ability, performance-enhancing drugs developed with genetic science and technology, pharmacogenetics, enhancement through reproductive technologies, somatic gene transfer, and germ line gene transfer.

Medical practice guidelines as malpractice safe harbors: illusion or deceit?

American medicine has long sought to control the standard of care that physicians are expected to provide to their patients. One effort to insulate the standard of care from external interference, called a "safe harbors" approach, would enable physicians to avoid liability for malpractice if they adhered to medical practice guidelines. The idea is to eliminate the "battle of experts" and reduce defensive medicine by requiring judges and juries to accept guidelines as conclusive evidence of the standard of care. Yet current efforts to improve the guideline development process, including the use of evidence-based guidelines, are unlikely to be able to overcome the shortcomings that led a similar safe harbors initiative to fail in the early 1990s. Moreover, there is no adequate justification for conferring this degree of self-regulatory power on the medical profession.