Science, Regulation, and Precedent for Genetically Modified Insects

Questions have been raised about the transparency and scientific quality of regulatory processes applied in the first open field releases of genetically modified (GM) insects, and there is concern that inappropriate precedents have been set [1], particularly through generic risk assessments covering multiple species and technologies [2]. The GM insects tested in the field so far are intended for sterile insect release programs against a major pest of cotton (pink bollworm, Pectinophora gossypiella) in the United States [3] and against Aedes aegypti, the mosquito vector of dengue fever, in the Cayman Islands [4], Malaysia [5], and Brazil [6]. In the pink bollworm release, the GM insects were sterilised by radiation and the GM trait was a heritable red marker colour that allowed discrimination from wild types. In the Aedes aegypti releases, the mosquitoes carried an inserted inherited dominant lethality trait that causes late larval stage mortality in offspring of homozygous and heterozygous individuals, as well as the colour marker trait to provide an essential discrimination from wild types. For control programs, insects with new genetic properties could be introduced either in large numbers in self-limiting populations or in smaller numbers in self-replicating populations for a specific beneficial purpose [7,8], but releases have so far only involved the self-limiting category. The release of GM insects into the environment poses two broad risk issues. There are potential environmental risks associated with the introduction of large numbers of any selected mass-reared population, in many cases of an alien species, that can interact with both the wild population of that species and other, non-target organisms, including humans. There are also specific risks related to the GM technologies introduced into the process, which may also interact with the broader environment through particular expressed traits, such as metabolic products, or through fitness differences compared to untransformed insects. In terms of mass release risks, we should expect GM insects to be regulated in a way that is similar to that applied to the widespread release of conventional beneficial insects, for which there are already international guidelines [9]. Given the potential for natural or assisted spread from insect releases, for both the intended organisms and any secondary pathogens, parasites, etc., this may need regional or international decisions (an example was the beneficial parasite of the cassava mealybug in Africa [10]). While such assessments should be carried out on a case-by-case basis, this process can build on the vast experience of new organism introductions that have already been made. National regulations, while not consistent in operation across all countries, determine the conditions under which non-GM insects can be released, and examples of such releases are common from all continents. The release of GM insects is, in principle, a similar activity. There is not yet any widely accepted specific guidance for GM insect releases. There is a regional standard in North America for the movement and confined field release of transgenic insects [11], while international guidance is still in preparation on open field release of GM mosquitoes [12]. The Cartagena Protocol on Biosafety offers broad principles on risk assessment for GM organisms [13], but no specific guidance for GM insects. Billions of mass-reared insects, which are not GM, are released into the wild each week around the world. Many are non-native pest species reared, irradiated, and distributed in sterile insect release programs [14]. In addition to sterile releases, fertile biological control agents, including insects, have also been released, so far in over 7,000 cases [15]. They are released in large numbers in continuous augmentative control programs and in smaller numbers for long-term self-replication to suppress pest species. Using a similar approach, mosquitoes infected with strains of Wolbachia bacteria intended to reduce their ability to transmit dengue have been released in the wild to establish self-replicating populations of infected mosquitoes [16]. Millions of pollinators are released on a regular basis in both protected and field crops, often imported from abroad [17]. The majority of these releases have been widely accepted as beneficial, although some have failed and some risks are recognised as constraints for these uses [14,15,17,18]. As in the case of GM insect technologies, biological control scientists are calling for proper adherence to national regulations and international standards as they continue to search for and release new agents [15]. Pollination with imported pollinators is under review [17] due to declines in native pollinators in many countries. Some sterile insect procedures have begun to be standardised to assure quality and reduce risks [19]. A common standard for risk