Developing GM insects for sustainable pest control in agriculture and human health

With increasing demand for effective control of insect pests coupled with environmental sustainability, farmers and disease vector control authorities are facing enormous challenges to, respectively, maintain food production and protect human health. Pest control has long relied upon insecticides, which can be very effective, but continued reliance is hampered by several factors. Concerns over their potential impacts on the environment and human health have led to implementation of restrictions on residues on food, the number of sprays per season, implementation of spray-free pre-harvest periods, and withdrawal from the market of some modes of action. Insect populations develop resistance to insecticides, and there are a limited range of modes of action available. These issues have driven the development of diverse other pest control tools such as mating disruption using sex pheromones, release of natural predators, spraying biopesticides (e.g. Bt) and cultivation of insect-resistant transgenic crops which can be employed together to form integrated pest management (IPM) strategies. We propose a new pest control approach, called RIDL (Release of Insects carrying a Dominant Lethal) [1], as a potentially valuable new IPM component for agriculture and public health. RIDL utilises transgenic technology to engineer novel traits in pest insects, for application against the wild pest population. We have generated RIDL strains in several insect species: in the dengue vector mosquito Aedes aegypti [2], for example, when larvae are reared in restrictive conditions, male and female offspring do not survive to adulthood due to over-expression of a lethal effector gene, tTA. Permissible conditions are provided by adding tetracycline to the larval medium: the ‘Tet-off’ genetic system, and therefore expression of tTA, is suppressed and the insects survive as normal. Releasing these insects into the wild over a sustained period leads to mating between released males and wild females, resulting in population suppression as their progeny do not survive in the absence of tetracycline. In the factory, however, the RIDL strain can be reared as normal with tetracycline. These transgenic insect strains also express a fluorescent protein marker, which is heritable, easily screened under specialised filters and robust in field conditions. This approach is similar in effect to another matingbased pest control strategy, the Sterile Insect Technique (SIT), in which mass-reared insects are sterilised by radiation prior to release into the field. SIT (and RIDL) offers pest control that is highly species-specific, with consequently minimal ecological impact; and as it relies upon the mate-seeking instincts of male insects, it is highly effective against low-density or difficult-to-reach pest populations, and can provide highly effective local pest eradication and a barrier to reinvasion. SIT has been used with success against a number of important pest insects, notably in eradicating the New World Screwworm (Cochliomyia hominivorax) from North and Central America. Despite its success, wider SIT implementation is constrained by several inherent limitations. The use of radiation to sterilise the insects also compromises their performance in the field, and the requirement to invest in costly radiation sources and facilities generally restricts SIT application to large-scale programmes that justify the investment. Release of both sexes of sterile insects reduces SIT efficiency with Mediterranean fruit fly (Medfly, Ceratitis capitata), male-only releases are 3-5 × more efficient per male than are bi-sex releases [3]and generating sexing strains that permit efficient, large-scale sex-sorting is technically challenging by conventional chromosomal translocation methods. Rearing and releasing large numbers of a pest insect requires a reliable method of marking the methods, to distinguish between wild and sterile, and