Scientists have studied what are now called gene drives for more than 50 years. But the development of a powerful genome editing tool in 2012, CRISPR/Cas9, led to the recent breakthroughs in gene drive research that build on that half century’s worth of knowledge. Just prior to the beginning of this study and since the committee was first convened, scientists have published four proofs of concept—one yeast—one in fruit flies, and two in different species of mosquitoes—that demonstrate gene drives can be developed in the laboratory, at least in these organisms. Proposed applications for gene-drive modified organisms for basic research, conservation, agriculture, public health and other purposes will likely continue to expand as genome editing tools such as CRISPR become more refined. Gene-drive modified organisms are on the horizon.
Proof-of-concept in a few laboratory studies, however, does not lead to the immediate release of gene-drive modified organisms into the environment. Gene-drive modified organisms could bring very significant benefits, but to make sure that release does not cause more harm than good, more work remains to be done. Laboratory and field research is needed to refine CRISPR/Cas9 and other gene drive mechanisms, and to understand how gene drives might work under different environmental conditions and in a wide variety of other organisms. The considerable gaps in knowledge about potential off-target and non-target effects necessitate collaborative, multidisciplinary approaches to gene drive research, risk assessment, and public policy decisions for each proposed application of a gene-drive modified organism. Systems to share data and new knowledge will be needed as future gene-drive modified organisms are developed and prepared for release in confined field trials and into the environment.
There is insufficient evidence available at this time to support the release of gene-drive modified organisms into the environment. However, the potential of gene drives for basic and applied research are significant and justify proceeding with laboratory research and highly controlled field trials.
Recommendation 9-1: Funders of gene drive research should coordinate, and if feasible collaborate, to reduce gaps in knowledge not only about the molecular biology of gene drives, but also in other areas of fundamental and applied research that will be crucial to the responsible development and application of gene drive technology, including population genetics, evolutionary biology, ecosystem dynamics, modeling, ecological risk assessment, and public engagement.
Recommendation 9-2: Funders of gene drive research should establish open access, online repositories of data on gene drives as well as standard operating procedures for gene drive research to share knowledge, improve frameworks for ecological risk assessment, and guide research design and monitoring standards around the world.
The nature of gene drives—which are intended to spread select genetic elements into populations of living organisms—raises many ethical questions and presents a challenge for existing governance paradigms to identify and assess environmental and public health risks. In the United States and many other countries, governance of biotechnology, especially genetically modified organisms, is predicated on the management of risk through confinement and containment. Gene drives do not fit well within the existing regulatory logic of confinement and containment be-
cause they are designed to spread a genotype through a population, making confinement and containment much more difficult (or even irrelevant) and the environmental changes introduced by release potentially irreversible. A phased testing pathway and robust ecological risk assessments are essential for navigating uncertainty and informing decisions around the development and application of gene-drive modified organisms.
Recommendation 9-3: The distinguishing characteristics of gene drives—including their intentional spread and the potential irreversibility of their environmental effects—should be used to frame the societal appraisal of the technology, and they should be considered in ecological risk assessment, public engagement, regulatory reform, and decision making.
Recommendation 9-4: Proposed field tests or environmental releases of gene-drive modified organisms should be subject to an ecological risk assessment and structured decision making processes. These processes should include modeling of off-target and non-target effects from the genome level through ecosystem level. When possible, empirical estimates of such variables as gene flow, population change, trophic interactions, and community dynamics should be developed as part of the models.
Public engagement can help to frame and define the risks of gene-drive modified organisms and provide input into practical decision making and policy development, but there are few avenues for such participation and insufficient guidance on how communities can and should take part. Without a defined process for public engagement and clear role for the public in assessment of gene drive technology, government accountability for related policy making may be compromised, reducing the effectiveness of available governance mechanisms. Moreover, the goals of public engagement need to be clear, both to inform communities and stakeholders about gene drive research and to ensure their meaningful input into policy decisions. Ongoing and iterative public engagement can help to frame and define the relevant harms and benefits of gene-drive modified organisms, provide input into risk assessment and practical decision making, and align research and policy with public values. It will be particularly important for ecological risk assessment to reflect the values of relevant publics, and for the assessments to inform public policy decisions about emerging gene drive technologies, including comparisons with alternative strategies.
Recommendation 9-5: Governing authorities, including research institutions, funders, and regulators, should develop and maintain clear policies and mechanisms for how public engagement will factor into research, ecological risk assessments, and public policy decisions about gene drives. Defined mechanisms and avenues for such engagement should be built into the risk assessment and decision-making processes from the beginning.
Among the complex questions that arise for governance from gene drive research are how to select sites for field testing or environmental releases of gene-drive modified organisms, and who should be involved in making such decisions. Scientific and technical factors, including the presence of the target species and methods for confinement and containment, will need to be considered together with the values of the relevant publics that may be affected and their understanding of the risks, and the presence and capabilities of local governance bodies. Researchers will need to be able to engage with local communities, which may be particularly challenging in systems where democratic processes are not well established and power differentials may preclude some members of the public from such participation.
Recommendation 9-6: In selecting sites for field testing and environmental releases, researchers and funders should be guided by their professional judgement, the feasibility of risk assessment and community engagement, and the community’s values and understanding of the balance of benefits and harms. In site selection, preference should be given to
locations in countries with the existing scientific capacity and governance frameworks to conduct and oversee the safe investigation of gene drives and development of gene-drive modified organisms.
A comprehensive approach to the development and governance of gene-drive modified organisms will need to go beyond considerations of public health and the environment, such as, but not limited to, the benefits of technological innovation, the implications of intellectual property, public engagement, and economics.
Gene editing is not a new endeavor. There are experts in the science and governance of gene editing whose experience could be applied to gene drive research with the aim of facilitating the exchange of knowledge.
Guidelines established by the World Health Organization (WHO) for research on genetically modified mosquitoes provide a useful foundation for the establishment of guidelines for gene-drive modified organisms. As the WHO emphasizes for genetically modified mosquitoes, for example, the path for developing a gene-drive modified organism includes not only proof of efficacy, but also proof of acceptability and deliverability. Fundamental, applied, and translational laboratory and field research contribute to the proof of efficacy. Risk assessment, public engagement, and regulatory approval contribute to proof of acceptability. The cost-effectiveness of the technology versus alternative technologies may influence both acceptability and deliverability. In order to augment the deliverability of a gene-drive modified organism, a commitment to ongoing, long-term public engagement, and appropriate financing to support the monitoring of environmental releases are imperative.