In theory, genetic modifications that are linked to underdominance (heterozygotes are less fit than either homozygote) can be introduced and maintained by natural selection in a wild population, even if they come at some fitness cost. This is stable in the sense that the effector gene is maintained indefinitely without any further intervention; however, in a different sense the system is completely reversible back to a wild-type state if desired (underdominance results in an evolutionary bi-stable switch). There is also the added beneficial property of geographic stability—the genetic modifications “stick where you put them.” Early attempts at engineering underdominant systems with translocations (in the 1970s and '80s) were not successful. We have revisited the problem and engineered single-locus underdominance, with gene expression knock-down/rescue of haploinsifficient ribosomal proteins, in the highly tractable model organism Drosophila melanogaster as proof of principle. This system has a very robust fitness configuration and is designed to be portable to a wide range of species. Currently we are focused on a species conservation application with non-native Culex quinquefasciatus mosquitoes that vector avian malaria (Plasmodium relictum), which is expanding its range in Hawai'i and is a major threat to the survival of several endemic Hawaiian honeycreeper bird species.