An Introduction to Containment Recommendations for Gene Drive Mosquitoes and the Laboratory Rearing of Genetically Engineered Mosquitoes in Africa

One of the rewards of having been the editor of Vector-Borne and Zoonotic Diseases (VBZ) has been the ability to provide timely and accurate information that keeps those in the field well informed. It was a privilege in 2003 to publish the landmark first public version of the “Arthropod Containment Guidelines” (ACGs; Benedict et al. 2003), which were produced by the American Committee for Medical Entomology (ACME)—a subgroup of the American Society of Tropical Medicine and Hygiene (ASTMH). Since then, additional articles related to the ACGs and methods to work safely with vectors have been published in VBZ, for example, the “Guidance for contained field trials of vector mosquitoes engineered to contain a gene drive system: Recommendations of a scientific working group” (Benedict et al. 2008) and “Considerations for the use of human participants in vector biology research” (Achee et al. 2015), and in 2019 an updated revision of the ACGs (ACME 2019, Higgs 2019).

The prospect of using genetically engineered arthropods to reduce the incidence of vector-borne diseases either indirectly by suppressing vector populations or directly by replacing wild-type vector species with less competent ones has long been discussed; however, only in the past few years has this become feasible. The advent of CRISPR/Cas9-based gene drive and its application to mosquitoes have been a critical factor in bringing the dream to reality, but with opportunity also comes responsibility. Safe and secure handling of genetically engineered arthropods under laboratory/insectary conditions was considered in the original and revised ACGs, and under field conditions by Benedict et al. (2008). Although not discussed in these ACGs, hence the need for this addendum, Benedict et al. (2018) discussed containment and management of gene drive arthropods as distinct from genetically modified mosquitoes under laboratory conditions. A prerequisite for the application of engineered mosquitoes for mosquito-borne disease control is the rearing of these mosquitoes in countries where releases will ultimately occur. In 2018, three companion articles were published in VBZ that discussed this very issue (Mumford et al. 2018, Quinlan et al. 2018a, 2018b), with James et al. (2020) discussing efficacy and safety criteria for advancing gene drive-modified mosquitoes to field testing.

In this issue of VBZ, we publish two highly relevant articles that coincidentally, although submitted independently, are complementary.

The first article by members of ACME is an addendum to the ACGs, entitled “Containment practices for arthropods modified with engineered transgenes capable of gene drive.” This is a very comprehensive and insightful document that like the ACGs provides researchers in this field with invaluable and practical advice. This addendum was prepared over a period of ∼7 months after a vote by the ACME council to develop the document. The peer-reviewed document in this issue of VBZ has been approved by the ACME council and with the goal of providing recommendations for investigators working in this quickly evolving field of research. As advocated in the latest version of the WHO Laboratory Biosafety Manual (https://www.who.int/publications/i/item/9789240011311), the ACME recommendations take a risk-based approach to determining containment requirements. Therefore, although most envisioned work with gene drive arthropods is covered in the addendum, it is acknowledged that the so-called split gene drive work, or research where risk assessment suggests low probability of spread, may be covered by the current ACGs (Adelman, personal communications). Importantly, the addendum considers how research on gene drive-modified arthropods can be safely conducted in regions where the same species currently exists or that would be hospitable to establishment of the species. The recommendations also recognize the need for researchers to engage local communities and the public in the risk assessment process.

The second article in this issue (Guissou et al. 2021) reports on progress along the recommended stepwise approach established in the previous publications on the safe and secure rearing and research of engineered mosquitoes in endemic countries, describing the successful development, management, and operation of a transgenic insectary facility in Burkina Faso. This includes a description of permitting to import engineered Anopheles gambiae s.l., the design and construction of the facility, procedures used for maintaining the mosquitoes, and requirements for conducting a regulated study. This study provides inspiration to all of us in fields related to medical entomology and vector biology by showing what can be accomplished with strong institutional and staff commitment, solid collaborations, and commitment to technology transfer. The years of work reported in this article were aimed at building a strong foundation before moving on responsibly with future strains. This is a significant step in bringing the dream of using engineered mosquitoes to control malaria to reality.