Date Published: June 21, 2017
Publisher: Blackwell Publishing Ltd
Author(s): Nina Alphey, Michael B. Bonsall.
The sterile insect technique is an area‐wide pest control method that reduces agricultural pest populations by releasing mass‐reared sterile insects, which then compete for mates with wild insects. Contemporary genetics‐based technologies use insects that are homozygous for a repressible dominant lethal genetic construct rather than being sterilized by irradiation.Engineered strains of agricultural pest species, including moths such as the diamondback moth Plutella xylostella and fruit flies such as the Mediterranean fruit fly Ceratitis capitata, have been developed with lethality that only operates on females.Transgenic crops expressing insecticidal toxins are widely used; the economic benefits of these crops would be lost if toxin resistance spread through the pest population. The primary resistance management method is a high‐dose/refuge strategy, requiring toxin‐free crops as refuges near the insecticidal crops, as well as toxin doses sufficiently high to kill wild‐type insects and insects heterozygous for a resistance allele.Mass‐release of toxin‐sensitive engineered males (carrying female‐lethal genes), as well as suppressing populations, could substantially delay or reverse the spread of resistance. These transgenic insect technologies could form an effective resistance management strategy.We outline some policy considerations for taking genetic insect control systems through to field implementation.
Many insects in agro‐ecosystems are considered to be major global pests causing significant economic harm. For example, the pink bollworm Pectinophora gossypiella (Saunders), a specialist pest of cotton, originated in Asia and spread to America, Australasia and Africa in the 20th Century (Naranjo et al., 2002). It is now present in almost all cotton‐growing countries, and is a key pest in many of them. The Mediterranean fruit fly (‘Medfly’) Ceratitis capitata (Wiedemann) is a highly invasive generalist attacking more than 250 host plants, and is one of the world’s most economically important pests (CABI, 2016). Diamondback moth Plutella xylostella (L.), a pest of brassicas (including a number of vegetable and oilseed crops), has evolved resistance to all classes of synthetic insecticides, as well as to some biopesticides; it was the first insect observed to evolve field resistance to dichlorodiphenyltrichloroethane and to Bt (a biopesticide derived from a bacterium Bacillus thuringiensis). Diamondback moth costs the global economy an estimated US$4–5 billion per year through a combination of lost yield and costs of management (Zalucki et al., 2012; Furlong et al., 2013).
The idea of releasing sterile insects into wild populations as a pest management intervention was independently conceived in the 1930s and 1940s by geneticist A. S. Serebrowskii in Moscow; tsetse field researcher F. L. Van der Planck in what is now Tanzania; and E. F. Knipling at the U.S. Department of Agriculture (USDA) (Klassen & Curtis, 2005). Van der Planck and Serebrowskii focussed on sterility resulting from hybrid crosses between different species or different genetic strains. Knipling (1955) pursued the use of ionizing radiation to induce dominant lethal mutations causing sterility.
Starting with the USDA in the 1950s (Knipling, 1955), mathematical modelling has long been used to understand the potential effect of sterile insect methods on an insect population (Alphey & Bonsall, 2014b). Models can address research questions relevant to a particular context, whether the target insect is a plant pest that causes damage when ovipositing, through feeding or by transmitting plant pathogens, or is a vector of human, livestock or wildlife diseases. Those research questions can serve a range of purposes, including helping to understand underlying biological processes, designing appropriate traits, predicting the impact of fitness costs, informing the design and evaluation of experiments, or exploring potential benefits.
Genetic insect control methods need not be directly aimed at population suppression. The female‐lethal, or male‐selecting, versions could in principle be used to help manage resistance to other control methods. First, consider an example of another plant pest control method using GM technology: insecticidal crops.
We can take this concept of using transgenic insects to manage resistance a step further. What if heritable resistance were to arise to the lethality of the genetic construct itself? Such resistance has not been reported in any species of engineered insects, whether in trials or at an earlier stage of technology development, although a hypothetical resistant gene can be described and modelled (Alphey et al., 2011b). Key features of a putative resistance allele (R) are: the effectiveness of the resistance (what fraction of RR individuals bearing a lethal allele can survive to maturity?); the dominance of resistance (the lethal‐surviving proportion of SR genotypes, relative to RR homozygotes); and the magnitude and dominance of any fitness costs of the R allele in individuals that do not carry the lethal construct. With good quality control, released males can be assumed homozygous susceptible to the lethality of the genetic construct (S alleles) and do not carry any mutation or variant conferring resistance (R) that might be present in the wild population. In a similar vein to the Bt resistance management described above (Alphey et al., 2007, 2009), any progeny of released males will inherit one copy of the susceptible S allele, as well as one copy of the lethal genetic construct, which provides resistance dilution. The S alleles of released males are inherited through their male progeny where the construct is female‐specific, and are also passed on via any progeny that survive the lethal effect (i.e. resistant phenotype). So, if resistance is not recessive (some SR individuals can survive), a bisex‐lethal mechanism will also have this inherent resistance dilution potential (Alphey et al., 2011b).
Heritable genetic ‘sterility’ is not the only genetics‐based method being developed to control insect populations (Alphey, 2014; Burt, 2014). Recent advances in genetic modification have focussed on techniques of gene and genome editing. Molecular methods, including CRISPR (‘clustered regularly interspaced short palindromic repeats’) approaches, have been developed with the aim of precisely modifying genes (Esvelt et al., 2014; Kim & Kim, 2014). These techniques have the potential to drive genetic constructs through a population, incorporating ‘gene drive’ mechanisms that confer greater‐than‐Mendelian inheritance even if the construct has fitness costs.
Developing genetic approaches to insect control through to field applications is an interdisciplinary endeavour. Theoretical analyses such as those described in the present review are part of a much bigger picture, a composite of varied elements that must work together to achieve real change. Laboratory science is crucial for the creation of appropriate strains, particularly molecular biology and insect genetics. Applying this technique successfully to populations in nature is largely an exercise in applied ecology. For example, how many insects are in the target population? This is hard to measure, although it is a key element of the effective release ratios that will be achieved, and so influences the impact, duration and cost of a control programme. How might the effects of identified fitness costs scale up to population level? Insect behaviour is important; where do they mate and lay their eggs, and how far can they disperse? Released engineered males must be able to reach a significant proportion of females in the target population and be reasonably competitive for mates when they find them. Evolutionary biology and behavioural ecology must be understood, for example, to ensure that mass‐reared insects retain appropriate mating behaviours, and to inform future resistance management strategies for self‐sustaining genetic traits that will be designed to persist in the environment.
Policy and regulations surrounding genetic insect control have developed and expanded in the last few years and continue to receive attention (e.g. House of Lords Science and Technology Committee, 2015). Based on existing environmental risk legislation, in most jurisdictions that have regulatory frameworks for these, the deliberate release of genetically modified insects requires proportionate assessment to ensure that wider biodiversity and/or human health is not adversely affected. Simultaneously, the benefits of suppressing agricultural pests, reducing harm and improving plant yields impinge on cost–benefit analysis in using particular control technologies.
The need for new innovations to deal with emerging agricultural pests and diseases has never been greater, and this is an interesting time for the science and research of genetic control of insects. Some of the GM technologies described in the present review are already being proven in the field. The next wave of molecular methods is being applied to disease‐transmitting mosquitoes and this is beginning to reach over to agriculturally important species. Attention is being given to regulatory aspects to enable the safe and appropriate implementation of these biological, genetics‐based strategies. Collectively, these developments advance the prospects for realizing tremendous agricultural and socio‐economic benefits.
This review is part of a larger project. Further information on our research and science policy work on genetic insect control can be found on the Mathematical Ecology Research Group website: https://merg.zoo.ox.ac.uk/projects/genetic-insect-control. Our outreach activities, including a mosquito control computer game are available at: https://merg.zoo.ox.ac.uk/outreach. Our science policy work can be seen at: https://merg.zoo.ox.ac.uk/science-policy.