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Q&A: Recommendations outline pathway for deploying gene drives
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New recommendations published in The American Journal of Tropical Medicine and Hygiene outline a pathway for the safe and ethical testing of gene drive technology on mosquitoes to reduce malaria transmission in Africa.
The recommendations were compiled by an international group that included experts in mosquito research, ethics, regulatory science and policy, assembled by the Foundation for the National Institutes of Health (FNIH).
Despite concerns regarding the ethics of gene drive technology, Stephanie James, PhD, senior vice president of science at FNIH, and colleagues said gene drive products, such as CRISPR/Cas 9, hold the promise for controlling mosquito-borne illnesses in a high-impact, cost-effective way. Currently, no gene drive mosquito products are ready for field testing, but several investigational products are in laboratory development.
“Given the rapid pace of advances in the science, more can be expected to appear shortly,” James and colleagues wrote.
As gene drive technology continues to emerge, it is “imperative” that scientists, funders, regulators and policymakers be informed by the best practices for research, development and testing, according to the researchers. Therefore, James and colleagues developed recommendations for the safe and ethical testing of gene drive products. The recommendations are specifically for products that aim to reduce malaria transmission by Anopheles gambiae mosquitoes in Africa. They build on existing recommendations from WHO and the National Academies of Science, Engineering and Medicine (NASEM) addressing the potential impact of genetically modified (GM) mosquitoes on public health and conservation, as well as principles for sponsors and supporters of gene drive research.
To learn more, Infectious Disease News spoke with James about current challenges related to gene drive technology, key recommendations for safe and ethical testing of gene drive products and what the future holds for this research. – by Stephanie Viguers
What are some major issues with gene drive technology?
A major issue is determining whether and how these technologies can safely be tested for efficacy, and this is what we cover in the recommendations paper. Concerns that often are raised with gene drive technologies are that the gene drive construct would be capable of establishing itself within the population of target organisms (in this case, mosquito species that transmit malaria) from very low-level introductions, and that the modification could persist in the environment indefinitely and spread across national borders. These characteristics make the gene drive products different from GM products that have been developed thus far. Of course, these characteristics are exactly what makes gene drive such a promising option for control of malaria transmission in Africa. The possibility that self-sustaining gene drive would establish and spread from a low initial release frequency could provide for simple, infrequent delivery that would translate to cost-effective and durable protection that would be effective over vast areas without the need for human behavior change.
What are the most important recommendations in this article that scientists involved in gene drive research should consider?
The recommendations document represents an in-depth look at the entire developmental pathway for gene drive-modified mosquitoes as a tool for malaria control in Africa. This allows for examination of specific risks and benefits of gene drive research in the context of overall planning for malaria elimination. It is important to bring the gene drive conversation down to the level of discussing specific types of products for a specific use rather than discussing the technology at a generic level as it is usually presented in the media, because this helps respond to many questions that often are raised. For example, the working group recommended that, if implemented, gene drive products should be considered, at least at first, as complementary to other malaria control measures in an integrated strategy that will provide the best protection against malaria resurgence. It noted that gene drive products could provide a durable tool for sustaining elimination and preventing reintroduction of disease in areas where malaria has been eliminated and could be particularly important for malaria elimination in conflict areas or under other conditions where conventional tools cannot be delivered effectively.
The working group concluded that self-sustaining gene drive products can be tested in a safe and ethical manner but recommended that several resources be put in place to prepare for field testing. These are detailed in the report.
The working group also clarified that although there are no specific regulations for gene drive products in any country at present, there are important precedents from regulation of biocontrol agents, GM crops and clinical trials that address most of the concerns that have been raised. To address transboundary movement of gene drive-modified mosquito products, the working group recommended support to develop mechanisms for regional regulatory coordination and decision-making within the regional economic communities existing in Africa.
The report recommended an extensive list of safety considerations that should be examined under physical confinement (containment) before an investigational gene drive mosquito product is moved to field testing. The working group recommended that the standard for making the decision that an investigational product is safe enough to move to field testing is that it will do no more harm to human health than the wild-type mosquitoes on which it is based and no more harm to the ecosystem than other standard vector control interventions.
The working group emphasized the critical role of in-country scientists and institutions in the product development process, and the importance of co-ownership and codevelopment of the gene drive-modified mosquito product in a manner that promotes leadership of the in-country partners.
The report stresses the need for testing to be conducted incrementally, increasing the level of human and environmental exposure only after the investigational product has fulfilled agreed-upon safety, efficacy and acceptability criteria in the prior phase. It provides specific recommendations for these criteria at each testing phase.
The recommendations discuss ethical obligations of researchers and funders of gene drive research. Researchers are responsible for obtaining fair and legitimate authorization for field testing gene drive mosquitoes. Once a decision has been made to proceed from laboratory studies to field testing, both researchers and funders incur a responsibility for the safety of participants and must commit to abide by requirements imposed by regulators as well as ethical obligations to the community. Field testing must not begin until adequate funding is available to fulfill these responsibilities.
The recommendations place the need for ongoing monitoring in the context of current and planned mechanisms for monitoring for vector and malaria control and explain that many of the monitoring issues will be the same regardless of the nature of the tools used for malaria elimination. The working group members recommend that if continued ecosystem monitoring is required, this should be case specific, keeping plausibility and feasibility in mind and choosing endpoints for biological relevance specifically related to the potential to cause harm. They stress the need for the parties involved to reach agreement on monitoring requirements well in advance of each phase of the development pathway.
How do you see the future of gene drive research?
I believe gene drive products have great promise to play an important role in public health, conservation and food security, and agree with the finding of the NASEM panel that the potential benefits justify proceeding with safe and ethical research. I am hopeful that the comprehensive recommendations provided in this report will contribute to a standard for best practices in gene drive research that will ensure that development of these products is conducted responsibly, ethically and safely. As the recommendations conclude, “The ability of proponents of gene drive technology to demonstrate convincingly a thoughtful and prudent approach to their work may be a key determinant of whether it achieves sufficient public acceptance to allow its potential to be tested.”
References:
James S, et al. Am J Trop Med Hyg. 2018;doi:10.4269/ajtmh.18-0083.
National Academies of Sciences Engineering and Medicine. Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty and Aligning Research with Public Values. 2016. https://www.gene-drives.com/gene-drives.pdf. Accessed June 27, 2018.
Disclosures: James reports being employed by an organization that provides financial support for gene drive research. Please see the guidelines for all other authors’ relevant financial disclosures.