Comment submitted by Luke Alphey

Dear EPA, I have a long-term interest in the development of regulations around insect biotech products, including both public health (mosquitoes) and agriculture (plant pests) applications. In collaboration with various partners including USDA I led the early field trials with GM insects in several countries and helped develop regulatory and public engagement frameworks associated with these. I have several comments in respect of this application, some quite general, some more specific. I strongly support rational, science-based analysis of risks – and preferably also benefits, at least a comparison with a ‘no-action’ alternative – as the basis for regulation of biotech products. All credible, science-based pathways to harm need to be considered, conversely hypothetical negative outcomes lacking a credible pathway to harm should be excluded from serious consideration. New tools to manage invasive insects are urgently needed – the current crisis with New World screwworm highlights the relative lack of such. Ideally, these would include highly species-specific interventions capable of controlling the specific pest with minimal off-target effects on other insects or other elements of the ecosystem. This is valuable for all applications, but perhaps particularly so for controlling invasive pests in ecologically sensitive settings. Genetics-based systems, which rely on mating between a modified insect and the wild pest type, potentially provide a major source of such tools. While self-sustaining genetic systems which aim to homogeneously modify an entire species may be extremely valuable in specific circumstances – New World screwworm, perhaps, or Anopheles gambiae, there are far more cases where a targeted, local intervention is required. These also tend to be more readily reversible; in many cases, as with RIDL/fsRIDL and here with pgSIT, simply by ceasing to release more of them. Taking these considerations together, it is crucial that a clear, science-based regulatory pathway be established for current and future genetic biocontrol technologies where the control agent is a modified pest insect. A visible and predictable pathway through to full commercial registration, at a burden (cost, time) clearly and predictably manageable for SMEs, is crucial for innovation in this area. Lack of this has been a significant obstacle; though companies not founded and products not developed may not be easily measured, it is clear to those of us with direct experience in this field. Specifically in respect of pgSIT, this technology produces a control agent that is functionally very similar to the irradiated sterile insects that have been used for decades in the Sterile Insect Technique. Specifically, the released males – automated genetics-based sex separation is one of the features of this technology – mate with wild females, but no viable offspring arise from such matings. As with irradiation, which is rarely at such a high dose as to give zero fertility, and with the initial RIDL mosquito strains, which also had a small proportion of surviving progeny, incomplete penetrance of sterility is not a significant hazard, though in fact pgSIT can have very good performance in this regard. In short, though the molecular biology of this system is innovative, the resulting control agent is rather familiar. Based on the available scientific evidence and the biological characteristics of this self-limiting technology, I conclude that there is no scientifically credible basis to expect significant adverse effects on the environment from the proposed use. I therefore support EPA granting the requested registration. Yours faithfully Luke Alphey Professor of Genetics, University of York