Integrating gene drives with established pest controls to mitigate spillover risk

Gene drives—artificial genetic constructs that can rapidly spread in a population due to biased inheritance—are a promising tool for controlling disease vectors and invasive species. While gene drives can eradicate target populations within several generations, their unintended spillover into non-target populations poses serious ecological concerns. Here, we examine how integrating gene drives with established pest control methods, such as pesticide application and sterile-male release, can mitigate spillover risk. We develop optimal control models to identify cost-effective treatment strategies that minimize total eradication costs, accounting for actual investments and potential damage from spillover. We show that pesticides are most cost-effective at the intermediate stage of eradication when gene drives have already slowed population growth but do not yet substantially suppress the population. For sterile-male release, however, we observe two distinct types of optimal strategies, the choice of which depends on parameter values: intensive early-stage releases, or mild later-stage releases. Using established pest controls also relaxes requirements to gene drive design, favoring milder suppressive effects as the treatment intensifies.