Guidance framework for testing of genetically modified mosquitoes

Tags: Containment, Genetically modified mosquitoes, Policy, Regulation, Risk and safety, Risk assessment
WHO, WHO-TDR, 2014.

For more than two decades, scientists have been working to harness the promise of molecular biology to develop genetically modified mosquitoes (GMMs) for use as public health tools to prevent the transmission of these diseases. Several of these genetic technologies are now advancing to field testing. The introduction of molecular biology techniques represents the next step in a progression that builds on the widespread success of programmes employing release of radiation-sterilized insects to control the Mediterranean fruit fly (Med fly) and other insect pests affecting plants and animals, a process known as Sterile Insect Technique (Dyck, Hendrichs & Robinson, 2005). Radiation and chemo-sterilization methods also have been applied to mosquitoes (Dame et al., 2009), but they pose several difficulties that might be overcome using genetic modification technologies. Recent advances in the development of GMMs have raised hopes for the availability of new, potent and cost-effective tools to aid in the fight against malaria and dengue. Data on which to base evaluation of the protective potential of GMMs can only be collected through testing, including testing under the natural conditions in which the technology would be utilized. Without the ability to conduct careful and stepwise testing, no new technology can be brought to fruition for the public good. However, given the novelty of GMMs, concerns have been raised about the need for thorough, thoughtful and transparent preparation for and conduct of field trials (Reeves et al., 2012) and frameworks for environmental risk assessment (RA) have been produced at various levels (examples are provided in Section 3. Biosafety, and in David et al., 2013).
Since 2001, scientists involved in this research have, with the support of TDR, the Special Programme for Research and Training in Tropical Diseases (WHO-TDR) and other funders, gathered periodically to consider issues relevant to testing and implementation of genetically modified vectors. Through such discussions, broad agreement has been reached within the scientific community on two tenets, which thus far have been observed.
• First, field-testing should begin with release of sterile or otherwise self-limiting modified male mosquitoes in order to gain experience with the technology under circumstances where its effects can be controlled by halting releases (Benedict & Robinson, 2003). Field releases of GMMs carried out to date have focused on the testing of non-replicating, functionally sterile, males (which do not bite).
• Second, testing of modified mosquitoes incorporating gene drive should begin under physical confinement (Alphey et al., 2002; Benedict et al., 2008). No GMMs designed to replicate and spread the modification to wild-type mosquitoes have yet been tested outside of the laboratory.

As the research progresses, a need has been expressed both within the scientific community and by the public for additional standards and guidance. WHO-TDR and the Foundation for the National Institutes of Health (FNIH) co-sponsored a technical consultation meeting in 2009 to assess current progress and future development of genetically modified mosquito technologies. The meeting was attended by participants from around the world with expertise in molecular biology, medical entomology, ecology, regulatory requirements, ethical, social and cultural issues, as well as staff from WHO, FNIH and other research funders WHO-TDR, 2010). Participants recommended the establishment by WHO and FNIH of a working group to develop a comprehensive guidance framework to provide quality standards for assessing the safety and efficacy of genetically modified xv mosquitoes and addressing legal, ethical, social and cultural issues that arise during their development and deployment. A multidisciplinary effort was subsequently commissioned and over 40 experts recruited to contribute at various stages of development. In accordance with the recommendations, the group included many members who possessed a broad knowledge in their topic areas but were not involved directly in research on GMMs. A draft guidance framework was produced and opened for public comment in late 2012. Responses to public comment have been incorporated into this current version.