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.

Governing new technologies that stop biological time: Preparing for prolonged biopreservation of human organs in transplantation.

Time limits on organ viability from retrieval to implantation shape the US system for human organ transplantation. Preclinical research has demonstrated that emerging biopreservation technologies can prolong organ viability, perhaps indefinitely. These technologies could transform transplantation into a scheduled procedure without geographic or time constraints, permitting organ assessment and potential preconditioning of the recipients. However, the safety and efficacy of advanced biopreservation with prolonged storage of vascularized organs followed by reanimation will require new regulatory oversight, as clinicians and transplant centers are not trained in the engineering techniques involved or equipped to assess the manipulated organs. Although the Food and Drug Administration is best situated to provide that process oversight, the agency has until now declined to oversee organ quality and has excluded vascularized organs from the oversight framework of human cells, tissues, and cellular-based and tissue-based products. Integration of advanced biopreservation technologies will require new facilities for organ preservation, storage, and reanimation plus ethical guidance on immediate organ use versus preservation, national allocation, and governance of centralized organ banks. Realization of the long-term benefit of advanced biopreservation requires anticipation of the necessary legal and ethical oversight tools and that process should begin now.

The problems with forbidding science.

Scientific research is subject to a number of regulations which impose incidental (time, place), rather than substantive (type of research), restrictions on scientific research and the knowledge created through such research. In recent years, however, the premise that scientific research and knowledge should be free from substantive regulation has increasingly been called into question. Some have suggested that the law should be used as a tool to substantively restrict research which is dual-use in nature or which raises moral objections. There are, however, some problems with using law to restrict or prohibit certain types of scientific research, including (i) the inherent imprecision of law for regulating complex and rapidly evolving scientific research; (ii) the difficulties of enforcing legal restrictions on an activity that is international in scope; (iii) the limited predictability of the consequences of restricting specific branches of scientific research; (iv) inertia in the legislative process; and (v) the susceptibility of legislators and regulators to inappropriate factors and influence. Rather than using law to restrict scientific research, it may be more appropriate and effective to use a combination of non-traditional legal tools including norms, codes of conduct, restrictions on publication, and scientist-developed voluntary standards to regulate problematic scientific research.

The ghost in our genes: legal and ethical implications of epigenetics.

Epigenetics is one of the most scientifically important, and legally and ethically significant, cutting-edge subjects of scientific discovery. Epigenetics link environmental and genetic influences on the traits and characteristics of an individual, and new discoveries reveal that a large range of environmental, dietary, behavioral, and medical experiences can significantly affect the future development and health of an individual and their offspring. This article describes and analyzes the ethical and legal implications of these new scientific findings.

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.

Hormesis and toxic torts.

Policy implementation of hormesis has to date focused on regulatory applications. Toxic-tort litigation may provide an alternative policy venue for real-world applications of hormesis. Businesses and government entities, who are sued by individuals claiming to have been injured by exposure to very low levels of toxic substances may defend those cases by deploying hormesis to argue that such exposures were unlikely to be harmful. The threshold issue in using hormesis in toxic-tort defense is whether such evidence will be admissible under applicable standards for scientific evidence, which will likely turn on whether hormesis is deemed to be ;generally accepted' in the relevant scientific community. Given the relatively novel status of hormesis, its admissibility will likely be a close call, but is likely to be held admissible in favorable circumstances. If admissible, hormesis is likely to receive a fairer and more even-handed consideration than in regulatory decisions, where regulatory agencies are bound by policy-based default assumptions that limit their receptivity to new concepts such as hormesis. The perception of hormesis by juries will likely be the critical factor for determining the utility of hormesis in toxic-tort litigation, and this perception is likely to be affected by the presentation and circumstances in the individual case.

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.

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.

Transnational models for regulation of nanotechnology.

Like all technologies, nanotechnology will inevitably present risks, whether they result from unintentional effects of otherwise beneficial applications, or from the malevolent misuse of technology. Increasingly, risks from new and emerging technologies are being regulated at the international level, although governments and private experts are only beginning to consider the appropriate international responses to nanotechnology. In this paper, we explore both the potential risks posed by nanotechnology and potential regulatory frameworks that law may impose. In so doing, we also explore the various rationales for international regulation including the potential for cross-boundary harms, sharing of regulatory expertise and resources, controlling protectionism and trade conflicts, avoiding a "race to the bottom" in which governments seek economic advantage through lax regulation, and limiting the "nano divide" between North and South. Finally, we examine some models for international regulation and offer tentative thoughts on the prospects for each.

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.