Key Examples
Post-Release Environmental Safety Monitoring of Gene Drive-modified Mosquitoes
Approval for field release of gene drive-modified mosquitoes at any phase of development is expected to require an accompanying plan for post-release monitoring to assess efficacy as well as safety for human health and the environment. Monitoring results will inform decision making about continued testing and implementation of the product, and its ongoing use and management. This workshop began to address practical questions around monitoring and surveillance planning for early small-scale releases of self-sustaining, low threshold, gene drive mosquitoes developed to control and eliminate malaria in Africa. Discussions focused on planning for monitoring of effects on biodiversity and ecosystem services.
June 11-13, 2024, Reston, VA
Purpose: To discuss the essential elements of a monitoring plan to detect the presence and environmental impact of gene drive-modified mosquitoes over time.
Guidance Framework for Testing of Genetically Modified Mosquitoes, 2nd Edition
World Health Organization, 2021. ISBN 978-92-4-002523-3 (electronic version); ISBN 978-92-4-002524-0 (print version)
The FNIH once again collaborated with WHO to produce an updated version of the original 2014 Guidance Framework, taking into account the substantial technical progress and lessons learned in the intervening 7 years. The new Guidance Framework will foster quality and consistency among processes for testing and regulating GM mosquito technologies intended to reduce transmission of diseases such as malaria and dengue. It recommends standards of efficacy and safety testing comparable to those used for trials of other new public health tools. It discusses ethical obligations, including the importance of co-development with a range of partners and communities. Relevant regulatory frameworks also are reviewed and recommendations are made for adapting and updating these to cover new GM mosquito technologies.
The Lancet Microbe covered the launch here.
Toward the definition of efficacy and safety criteria for advancing gene drive-modified mosquitoes to field testing
2020. Vector-borne and Zoonotic Diseases 20(4): 237
An essential part of the preparation process is the development of a Target Product Profile (TPP) that defines the characteristics of a candidate gene drive-modified mosquito product that would make it suitable for field testing.
Given that gene drive-modified mosquitoes are anticipated to persist for some time in the environment, defining the preferred efficacy and safety characteristics of the product is fundamental to considerations of potential benefits vs. risks. The FNIH held two workshops to convene a wide range of experts to speak to the various considerations for TPP development, and a third workshop is planned. A summary of the perspectives from the first two workshops was published.
February 25-26, 2019, London, UK
Purpose: To discuss efficacy characteristics that a gene-drive-modified mosquito (to be used for malaria control and elimination in an African setting) should meet before moving forward to field testing.
May 6-7, 2019, Irvine California
Purpose: To discuss consensus recommendations on data required to support an application for field testing of a gene drive mosquito in Africa and design of laboratory and insectary studies needed to obtain the required data.
Gene Drive-Mosquito Monitoring and Surveillance: A Scenario-Driven Workshop
The FNIH convened an expert meeting in 2019 to explore the monitoring and surveillance needs associated with various phases of open-field testing of gene drive-containing mosquitoes in Africa.
The goals of this meeting were to assess the level of readiness to respond to entomological monitoring requirements associated with housing and release of gene-drive-containing Anopheles mosquitoes in Africa, and to identify and define knowledge and technology gaps. The meeting revealed that as the scope and scale of trials increases, there will be a need to employ rapid, inexpensive “point of care”-like technologies to meet the volume of sampling anticipated. While there is some current research and development specifically on simple and rapid mosquito genotyping technologies, additional efforts will be necessary to meet the needs of gene drive mosquito programs. Simultaneous consideration of trial design and entomological monitoring requirements will be essential. The FNIH plans to continue to explore gene drive mosquito monitoring and surveillance needs through future meetings by using multiple specific and realistic scenarios that will be explored in much greater detail.
Guidance on stakeholder engagement practices to inform the development of area-wide vector control methods
2019. PLoS Negl Trop Dis 13(4): e0007286. doi: 10. 1371/journal.pntd.0007286.
The FNIH sponsored a three-day workshop in November 2017 in Reston, VA that brought together bioethicists and stakeholder engagement practitioners to discuss recommendations for stakeholder engagement and informed consent for interventions intended to operate at the community level, as is the case for many vector control tools, including gene drive.
The workshop resulted in a publication offering recommendations on how to design community and stakeholder engagement programs as part of the product development pathway.
Pathway to deployment of gene drive mosquitoes as a potential biocontrol tool for elimination of malaria in sub-Saharan Africa: Recommendations of a scientific working group
Am. J. Trop. Med. Hyg., 98(Suppl 6), 2018. doi: 10.4269/ajtmh.18-0083
The FNIH organized a multi-disciplinary international working group of experts to develop consensus recommendations for the safe and ethical testing of gene drive technology on mosquitoes as tools to reduce the burden of malaria transmission in Africa.
The authors propose a pathway for the responsible development of gene drive products, from initial discovery research to implementation, to inform researchers, funders, regulators and other government authorities, policy makers and international organizations.
- Using Gene Drive Technologies to Control Vector-Borne Infectious Diseases. Sustainability 10(12), 4789. 2018. doi: 10.3390/su10124789
- Symposium: Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination in Sub-Saharan Africa, ASTMH Annual Meeting, October 30, 2018 in New Orleans, LA USA.
Planning the First Releases of Gene Drive Mosquito Products: Site Preparation
In 2018, the FNIH convened a meeting of researchers developing mosquito gene drive products, vector biologists, regulatory experts and ethicists/social scientists. The attendees discussed the criteria for deciding on the site of the first open release of a mosquito gene drive product. These criteria represented the results of a survey of experts asked to assess the relative importance of various scientific, regulatory and social/ethical/community criteria for site selection, as well as current outstanding needs that should be met before such a release would be feasible.
The meeting outcomes included:
- recognition of the need for additional consideration of monitoring and surveillance needs and requirements (entomological, environmental and epidemiological);
- recognition of the need to further explore the issue of liability and accountability associated with gene drive trials in Africa and whether trial insurance will be feasible;
- identification of a need for gene drive mosquito containment guidelines that could form the basis of a facility certification process in Africa. The FNIH is pursuing follow-up activities in each of these three areas.
Insect Containment Accreditation Workshop
The FNIH convened a meeting in 2018 of international experts to consider the state of current regulations, guidelines and recommendations for the containment of genetically modified insects, as well as the value and feasibility of establishing a third-party accreditation entity that could support institutions making risk assessments and containment decisions.
The major outcomes of the meeting were recognition that:
- Development of genetically modified (GM) insect technologies demand careful consideration of containment requirements to avoid premature or unplanned releases;
- Technology has outpaced some regulations and guidance documents relevant to GM insect risk assessment and containment. A joint effort by multiple respected professional entomological societies might be well equipped to create expanded guidelines that have broad applicability;
- A neutral third-party entity for accreditation of insectaries and insectary management programs analogous to the institutional animal care and use accreditation entity could have value to institutions. Moving forward, the FNIH plans to engage with several organizations to explore their interest in participating in the creation of a broad set of GM insect containment guidelines that can enhance the ability of institutions and investigators to make good decisions and demonstrate their commitment to conducting research involving genetic technologies safely and responsibly.
Principles for gene drive research
2017. Science 358(6367):1135-1136 doi: 10.1126/science.aap9026.
(FNIH Announcement, Nov. 30, 2017)
One of the most important accomplishments of the Gene Drive Research Forum was the development of Principles for gene drive research, which were published in 2017. Sixteen organizations are signatories to the principles, which commit them to supporting efforts of the highest scientific and ethical quality, inspiring a transparent approach and backing biosafety measures. We maintain the principles as a living document: Contact us if your organization would like to become a signatory. To view the principles in brief and the signatories,
Principles
- Advance quality science to promote the public good
- Promote stewardship, safety and good governance
- Demonstrate transparency and accountability
- Engage thoughtfully with affected communities, stakeholders and publics
- Foster opportunities to strengthen capacity and education
Founding Signatories (in alphabetical order)
- Bill & Melinda Gates Foundation, Trevor Mundel
- Canadian Institutes of Health Research (CIHR), Paul Lasko
- Commonwealth Scientific and Industrial Research Organization (CSIRO), Jack Steele
- Foundation for the National Institutes of Health (FNIH), Maria Freire
- Fundação Oswaldo Cruz (Fiocruz), Marco Aurélio Krieger
- Health Research Council of New Zealand, Kathryn McPherson
- Indian Council of Medical Research (ICMR), Soumya Swaminathan
- Institut National de la Santé et de la Recherche Médicale (Inserm), Yves Lévy
- Institut Pasteur, Christian Bréchot
- National Health and Medical Research Council of Australia, Anne Kelso
- Open Philanthropy Project, Nick Beckstead and Alexander Berger
- Tata Trusts, R. Venkataramanan
- Wellcome Trust, Jeremy Farrar
Additional Signatories (in alphabetical order)
- Genome Canada, Cindy L. Bell
- National Institute of Food and Agriculture, Sonny Ramaswamy
- Revive & Restore, Ryan Phelan
Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values
National Academies of Sciences, Engineering, and Medicine, 2016. doi: 10.17226/23405
The FNIH co-commissioned with the National Institutes of Health this report, which provides recommendations for the conduct of responsible research on applications of gene drive technologies for public health, ecosystem conservation and agriculture, as well as for basic research uses.
Guidance Framework for Testing of Genetically Modified Mosquitoes
World Health Organization, 2014. ISBN 978 92 4 150748 6.
(Updated in 2021)
The FNIH collaborated with the World Health Organization to develop this guidance framework, which aims to foster quality and consistency among processes for testing and regulating new genetic technologies by proposing standards of efficacy and safety testing comparable to those used for trials of other new public health tools.
Guidance for contained field trials of vector mosquitoes engineered to contain a gene drive system: Recommendations of a scientific working group
Vector-Borne and Zoonotic Diseases, 8:127, 2008. doi: 10.1089/vbz.2007.0273
The FNIH organized a scientific working group of experts to create guidance that aims to aid researchers, government authorities and community leaders as they consider the design and implementation of field trials to assess the safety and efficacy of genetic strate