Systematic identification of plausible pathways to potential harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa

Abstract Background Population suppression gene drive has been proposed as a strategy for malaria vector control. A CRISPR-Cas9-based transgene homing at the doublesex locus ( dsxF CRISPRh ) recently shown to increase rapidly in frequency in, and suppress, caged laboratory populations of mosquito Anopheles gambiae . Here, problem formulation, an initial step environmental risk assessment (ERA), was performed simulated field releases West Africa. Methods Building on consultative workshops Africa that previously identified relevant health protection goals ERA control, 8 potentially harmful effects from these were identified. These stratified into 46 plausible pathways describing causal chain events would be required potential harms occur. Risk hypotheses interrogate critical steps each pathway, analysis plan involving experiments, modelling literature review test those hypotheses, developed. Results Most involved increased human (n = 13) or animal disease transmission, emphasizing importance subsequent stages data vectorial capacity comparing transgenics non-transgenics. Although some 14) based known anatomical alterations homozygotes, many could also applicable range other transgenic strains 18). In addition population target organisms being accepted outcome existing control programmes, investigations revealed efficacy caused by should itself directly affect most 35). Conclusions Modelling will play essential role clarifying dynamics this relationship between reduction exposure specific harms. This represents comprehensive identification harm using formulation organism, transparent communication tool inform future regulatory studies, guide ERA, stimulate further, broader engagement use vectors