Regulating Genetic Research and Applications
A DISCUSSION OFThe Legal and Regulatory Context for Human Gene Editing
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R. Alta Charo’s “The Legal and Regulatory Context for Human Gene Editing” (Issues, Spring 2016) provides an excellent broad overview of the current status and challenges surrounding biotechnology governance around the globe. The article also touches, if briefly, on the current oversight issues in biosecurity, mentioning self-governance models of the National Scientific Advisory Board on Biosecurity (NSABB) that emerged from recommendations in the 2003 National Academies’ report Biotechnology Research in an Age of Terrorism.
When thinking about biotechnology from a security governance perspective, it will be necessary to anticipate the types of security threats that may emerge as science and technology advance, the potential consequences of those threats, the probability that adversaries will obtain or pursue them, adversarial intent, and the potential effect on strategic stability.
The CRISPR/Cas9 system, and emerging variants on the system, enable unprecedented control and ease when editing the genome. It’s somewhat analogous to remote “command and control” of the genome and is what makes the tools novel and different from earlier gene editing methods. Potential impacts on biomedicine and human health are vast, including beneficial applications for enabling gene and cell replacement therapies, drug discovery through functional genomic screens, and simplifying the production of disease models that permit validated therapy targets and increased efficiency for testing drug efficacy. But the future challenges and pitfalls associated with CRISPR/Cas9, especially pitfalls with implications for international security, are still to be determined. Governance to address uncertainties, while not hindering research, is tough.
The broader biosecurity and nonproliferation communities (as well as congressional committee findings) have recognized that in the twenty-first century biological weapons are sometimes (but not always) cheaper, easier to produce, more widely available, within the capabilities of an increasingly large number of people with access to minimal technical skills and equipment, more concealable, and inherently exploitive of more dual-use technologies. The potential synergies between biotechnology and other emerging technologies, such as nanotechnology, big data analytics, and the cognitive neurosciences, not only suggest tremendous potential promise for advancement in technology for consumers and defense applications, but also raise new concerns. A driving concern is that within this century, both nation-states and non-state actors may have access to new and potentially devastating dual-use technology.
Reducing the risk from state-based misuse of biotechnology for biological proliferation will mean consideration of the highly transnational nature of biotechnology research and development. Traditional and innovative new approaches to nonproliferation and counterproliferation are important policy elements to reduce the risk of malfeasant application of technology. Robust international agreements lower the risk of terrorist applications by eliminating legal routes for states and terrorists to obtain agents, precursors, or weaponization materials, and by minimizing possible transfers from state to non-state actors through theft, deception, or other means. Efforts to strengthen the international regime to control transfers of dual-use materials and equipment are also important. The highly transnational nature of biotechnology research and development is a major consideration in reducing the risk of misuse of biotechnology for weapons.
Margaret E. Kosal
In R. Alta Charo’s article about human gene editing regulation, she gestures toward a regulatory model that has a lot in common with the “learning health system,” a recently described model in which a health care system is constantly engaged in a process of policy monitoring, rapid feedback, and quality improvement. Analogously, as new technologies emerge, a “learning regulatory agency” would apply the assessment methods and standards that it knows well, but would always be on the lookout for systematic biases, flaws, or new domains of innovation that are poorly served by its current tools. The agency would then adapt, developing new methods and standards accordingly.
We think that as policy makers contemplate the promise and potential pitfalls of gene editing technologies, it will be valuable for a “learning agency” to take some lessons from another recent innovation in biotechnology—genomics and precision medicine. Following on the success of the Human Genome Project, precision medicine initiatives arrived with the potential to read patients’ health and response to therapy off their genetic profiles. In that spirit, biotechnology companies raced forward, searching for meaningful genetic associations and then developing diagnostic technologies to detect these genes. But lacking a structured system for market entry, companies began offering tests for sale directly to consumers, without having to demonstrate that these associations were clinically meaningful predictors of patient outcomes. Unfortunately, an insufficient evidence base about how to use and interpret genetic tests—as would be demanded by stricter regulation—often left both clinicians and patients confused. In part as a result, precision medicine has failed, thus far, to live up to its high expectations.
In response to this problem, the Food and Drug Administration is now proposing to oversee more closely certain aspects of clinical diagnostics. However, we think that one lesson for a learning agency to draw from the precision medicine case is to be more proactive in requiring evidence of clinical utility for new biotechnologies. Applying this lesson to gene editing could mean that developers will need to go beyond merely showing that their technologies can successfully edit their targets in controlled conditions—they must also show that this intervention translates into reliable, cost-effective, and clinically meaningful benefit.
This experience also calls into question the regulatory policy narrative that policy makers must choose between protecting the public through strict regulation and promoting innovation through loose regulation. Indeed, the loose regulatory environment surrounding diagnostic technologies in precision medicine seems to have failed by both measures: There have been few genuine therapeutic breakthroughs emerging from this space, and the public has been made more vulnerable to scientifically dubious claims surrounding the utility of genetic testing. Both of these outcomes can erode public trust in science and regulation. Thus, although the ideal of an adaptive learning agency is a good one, it is critical to be clear about what should be driving this adaptation. An ideal learning agency would adapt and evolve alongside the science (with all of its messy uncertainty), not to the perception of what the science could be.
Spencer Phillips Hey
Harvard Center for Bioethics
Aaron S. Kesselheim
There is currently a three-speed Europe for the biotechnology industry, with each of its three applications—health care, industrial, and agricultural—operating under different regulatory approval processes.
From 2012 to 2017, it is estimated that the annual growth rate for biotechnology products in the health care field (medicines and diagnostics) will be 5.5%, and 80% will be due to small- and medium-size enterprises. Europe has seen a greater number of approvals of biosimilar products (22 over the past 10 years) than in the United States, and more than 40 monoclonal antibodies active in different therapeutic areas, but especially cancer therapy, have received regulatory approval. This has been helped by several imaginative European Early Access Approval schemes that are hedged around by the requirement for strictly enforced post-marketing safety studies. These are monitored by new safety regulations introduced in 2013, including the establishment of a new European safety committee, the Pharmacovigilance Risk Assessment Committee. Health technology assessments, more highly developed in Europe than in the United States, and pressure on health care budgets by cash-strapped payers limit the availability of costly biotechnology products, even after regulatory approval.
Other new European regulatory initiatives relevant to health care biotechnology products include introducing in 2014 improved regulations for approving clinical trials; replacing the inconsistent implementation of the previous European Clinical Trials directive; developing in 2007 a new product classification called Advanced Therapy Medicinal Products, which incorporated gene therapy, cell therapy, and tissue engineered products; and creating a new office within the European Medicines Agency to provide regulatory advice to small- and medium-size enterprises at a favorable financial rate.