Global Governance of Human Genome Editing: What Are the Rules?

Human gene editing, particularly using the new CRISPR/Cas9 technology, will greatly increase the capability to make precise changes to human genomes. Human gene editing can be broken into four major categories: somatic therapy, heritable gene editing, genetic enhancement, and basic and applied research. Somatic therapy is generally well governed by national regulatory systems, so the need for global governance is less urgent. All nations are in agreement that heritable gene editing should not proceed at this time, but there is likely to be divergence if and when such procedures are shown to be safe and effective. Gene editing for enhancement purposes is not feasible today but is more controversial with the public, and many nations do not have well-developed regulatory systems for addressing genetic enhancement. Finally, different nations treat research with human embryos very differently based on deeply embedded social, cultural, ethical, and legal traditions. Several international governance mechanisms are currently in operation for human gene editing, and several other governance mechanisms have been proposed. It is unlikely that any single mechanism will alone be effective for governing human gene editing; rather, a polycentric or ecosystem approach that includes several overlapping and interacting components is likely to be necessary.

What Are Best Practices for Ethical Use of Nanosensors for Worker Surveillance?

Many employers now offer workers wearable or implantable devices that can monitor their health, productivity, and wellness. Nanotechnology enables even more powerful and functional monitoring capacity for these devices. A history of workplace monitoring programs suggests that, despite nanosensors' potential benefits to employers and employees, they can only be successful and sustainable when a company's motivations for offering them are acceptable and transparent to workers. This article describes 5 best practices for motivating nano-enabled worker monitoring programs that are acceptable, effective, and ethical.

Physicians' duty to recontact and update genetic advice.

This perspective addresses whether physicians have a duty to recontact former or current patients to update clinical advice based on newly discovered genomic information. Genetic information is unique compared with other medical data in that the underlying data do not appreciably change during the patients' lifetime, but the clinical significance of that information will continue to evolve. Based on relevant case law and guidelines, there is no general, established legal duty for physicians to affirmatively recontact former or current patients to update clinical advice based on newly discovered genetic information. However, integration of genomics into clinical practice is advancing quickly, and there may be limited, specific situations where a physician may have a duty to provide updated genetic information.

Transgenerational epigenetics and environmental justice.

Human transmission to offspring and future generations of acquired epigenetic modifications has not been definitively established, although there are several environmental exposures with suggestive evidence. This article uses three examples of hazardous substances with greater exposures in vulnerable populations: pesticides, lead, and diesel exhaust. It then considers whether, if there were scientific evidence of transgenerational epigenetic inheritance, there would be greater attention given to concerns about environmental justice in environmental laws, regulations, and policies at all levels of government. To provide a broader perspective on environmental justice the article discusses two of the most commonly cited approaches to environmental justice. John Rawls's theory of justice as fairness, a form of egalitarianism, is frequently invoked for the principle that differential treatment of individuals is justified only if actions are designed to benefit those with the greatest need. Another theory, the capabilities approach of Amartya Sen and Martha Nussbaum, focuses on whether essential capabilities of society, such as life and health, are made available to all individuals. In applying principles of environmental justice the article considers whether there is a heightened societal obligation to protect the most vulnerable individuals from hazardous exposures that could adversely affect their offspring through epigenetic mechanisms. It concludes that unless there were compelling evidence of transgenerational epigenetic harms, it is unlikely that there would be a significant impetus to adopt new policies to prevent epigenetic harms by invoking principles of environmental justice.

Contrasting Medical and Legal Standards of Evidence: A Precision Medicine Case Study.

As the health care system transitions to a precision medicine approach that tailors clinical care to the genetic profile of the individual patient, there is a potential tension between the clinical uptake of new technologies by providers and the legal system's expectation of the standard of care in applying such technologies. We examine this tension by comparing the type of evidence that physicians and courts are likely to rely on in determining a duty to recommend pharmacogenetic testing of patients prescribed the oral anti-coagulant drug warfarin. There is a large body of inconsistent evidence and factors for and against such testing, but physicians and courts are likely to weigh this evidence differently. The potential implications for medical malpractice risk are evaluated and discussed.

A new window of opportunity to reject process-based biotechnology regulation.

The question of whether biotechnology regulation should be based on the process or the product has long been debated, with different jurisdictions adopting different approaches. The European Union has adopted a process-based approach, Canada has adopted a product-based approach, and the United States has implemented a hybrid system. With the recent proliferation of new methods of genetic modification, such as gene editing, process-based regulatory systems, which are premised on a binary system of transgenic and conventional approaches, will become increasingly obsolete and unsustainable. To avoid unreasonable, unfair and arbitrary results, nations that have adopted process-based approaches will need to migrate to a product-based approach that considers the novelty and risks of the individual trait, rather than the process by which that trait was produced. This commentary suggests some approaches for the design of such a product-based approach.

The value of multigene predictors of clinical outcome in breast cancer: an analysis of the evidence.

OBJECTIVE: Multigene predictors are being used increasingly in early-stage breast cancer patients for prediction and prognosis. However, one consequence of the increased use of multigene predictors, and the heightened efforts toward their incorporation into routine clinical practice, is the potential for future malpractice litigation. It is, therefore, important to ascertain the strength of the evidence for using the different commercially available multigene predictor assays clinically. We evaluated the literature for evidence of clinical validity of four currently available gene signatures and to assess the influence of the 21-gene-expression assay on changes in treatment recommendations. METHODS: A systematic search of the peer-reviewed literature from January 2002 to March 2014 for multigene predictor assays was carried out, and a meta-analysis was conducted. RESULTS: The adjusted Cox hazard ratio average for studies that met the eligibility criteria was 3.538 (95% CI: 1.513-8.469). The 21-gene signature showed the highest stability in the estimation of likelihood of distant risk of recurrence. Using the recurrence scores resulted in changes in treatment recommendations in 31.8% of all patients in the studies. CONCLUSION: This study may provide insight about the use of multigene predictors in clinical practice for prediction and prognosis of breast cancer.

Public perceptions of presymptomatic testing for Alzheimer disease.

OBJECTIVE: To explore the self-expressed desire for, envisioned reaction to, and basic understanding of presymptomatic Alzheimer disease (AD)-related genetic and biomarker tests. PATIENTS AND METHODS: The Alzheimer's Prevention Registry is an online community of people at least 18 years of age who are interested in AD prevention research for purely informational purposes or to be considered for possible research participation in future studies. Information about presymptomatic testing and an online multiple choice format survey were posted from November 1, 2012, through June 20, 2013, on the registry website. RESULTS: Of 4036 respondents, 80.8% (3195/3952) wanted genetic testing if paid by insurance and 58.7% (2261/3851) if it would cost them at least $100. A total of 80.2% (3112/3879) wanted biomarker testing. If at high risk for AD, 90.5% (3478/3841) endorsed that they would "pursue a healthier lifestyle," but 11.6% (427/3706) endorsed "seriously consider suicide." The implication of a positive genetic test result was incorrectly understood by 13.1% (500/3812) and 32.6% (1255/3848) failed to view a positive biomarker test result as evidence of increased risk for or the presence of AD. CONCLUSION: Despite efforts to increase public awareness of AD, our survey results suggest that greater education of the public is needed. Interested patients should probably undergo psychological screening to identify those at high risk of adverse psychological outcomes, and disclosure of presymptomatic test results should be anchored to tangible constructive action plans, such as healthy lifestyle changes, long-term care planning, and, when available and appropriate, participation in research trials.

The labeling debate in the United States.

The mandatory labeling of genetically modified (GM) food has become the predominant policy issue concerning biotechnology in the United States. The controversy over GM labeling is being debated at several different levels and branches of government. At the federal level, the Food and Drug Administration, which has primary jurisdiction over food safety and labeling, has steadfastly refused to require labeling of GM foods since 1992 based on its conclusion that GM foods as a category present no unique or higher risks than other foods. Proposed legislation has been repeatedly introduced in the US. Congress over the years to mandate GM labeling, but has made very little progress. With federal labeling requirements apparently stalled, the main activity has switched to the state level, where numerous individual states are considering mandatory GM labeling, either through legislation or proposition. The debate over GM labeling, at both the federal and state levels, has focused on five issues: (1) public opinion; (2) the legality of labeling requirements; (3) the risks and benefits of GM foods; (4) the costs and burdens of GM labeling; and (5) consumer choice. While the pro-labeling forces argue that all of these factors weigh in favor of mandatory GM labeling, a more careful evaluation of the evidence finds that all five factors weigh decisively against mandatory GM labeling requirements.

Regulatory and reimbursement innovation.

Coverage with evidence development and parallel review for molecular diagnostics aid regulation and reimbursement.

Prudent precaution in clinical trials of nanomedicines.

Clinical trials of nanotechnology medical products present complex risk management challenges that involve many uncertainties and important risk-risk trade-offs. This paper inquires whether the precautionary principle can help to inform risk management approaches to nanomedicine clinical trials. It concludes that prudent precaution may be appropriate for ensuring the safety of such trials, but that the precautionary principle itself, especially in its more extreme forms, does not provide useful guidance for specific safety measures.

The benefits and challenges of a voluntary occupational exposure database.

OBJECTIVE: This article describes the experience of creating and implementing an occupational exposure database for synthetic vitreous fibers (SVFs). The lessons learned and benefits achieved through this experience may be instructive to government and industry when assessing the need, utility, and design of an occupational exposure database for nanomaterials. METHODS: This article consists of an empirical account of the issues faced during the construction and maintenance of an occupational exposure database for SVFs. RESULTS: The occupation exposure database for SVF proved to be beneficial and successful but encountered several challenges relating to data consistency, data quality, and other problems. CONCLUSIONS: The SVF database provides a good case study to illustrate the potential benefits and challenges of creating and administering an occupational exposure database.