Agricultural insect pest control: combining genetics, resistance management and dynamics

The public and consumers increasingly want to see more sustainable methods used to control pests and there is general concern to promote sustainability and biodiversity in agricultural ecosystems.
Diamondback moth (DBM) is a major worldwide pest of brassicas (e.g. broccoli, cabbage) causing economic losses of $4-5bn annually through management costs and crop damage. DBM has evolved resistance to all known classes of synthetic chemical insecticides and to at least two bio-pesticides based on Bt, Bacillus thuringiensis. Bt toxins typically have specific action against particular insect Orders (e.g. Lepidoptera), have unparalleled environmental safety and have been widely engineered into transgenic crops. The evolution of resistance to Bt toxins is a real challenge to the sustainable exploitation of this key bio-pesticide. DBM has not only evolved resistance to Bt many times in the field, but is also a proven laboratory system for testing evolutionary theory.
Our industry partner, Oxitec Ltd (an Oxford spin-out), is pioneering genetically engineered "sterile" insects to suppress populations of agricultural or public health pests. Released "RIDL" male insects find mates in the wild and their offspring inherit a genetic construct that prevents them developing to adulthood. Our theoretical work predicts that a female-specific version will not only reduce insect numbers (daughters die so there are fewer females to lay eggs) but also help dilute any resistance in the population (sons inherit Bt-susceptible alleles from released males).
Our cross-disciplinary research project brings together experts in ecology and evolution of the DBM-Bt system and world-leading biotechnologists to explore the management of insect resistance to bio-pesticides and the interplay with genetic insect control.
Novel RIDL strains of DBM will be developed, in addition to Oxitec's prototypes, and a phased series of experiments will be conducted on their biology, genetic traits, and performance for suppressing DBM populations and managing resistance to Bt. Key performance traits include male mating competitiveness, sperm competition with wild-type males, longevity, dispersal, the ability to find mates and suitability for mass-rearing. These will be analysed at increasing levels of detail and realism, from small laboratory cage experiments to experiments in simulated (field cage) and actual field conditions, progressively identifying and prioritizing the most suitable strains.
We will perform a series of experiments involving competition and selection to explore the effect of RIDL male releases on the evolution of DBM resistance to Bt bio-pesticides. The experiments will incorporate key features of existing resistance management strategies, such as Bt-free refuges to provide a source of Bt-susceptible genes alongside Bt diet (this is a key feature of current measures to manage resistance to Bt crops), populations with non-homogeneous spatial structure and various ecological conditions, and mixtures of different toxins (multiple toxins are used in spray treatments and engineered into some plants). These experiments will provide direct tests of theoretical predictions about the evolution of resistance and provide information about the system's dynamics to inform the formulation and parameterization of further mathematical models.
Our empirical experiments will be supported by a range of novel mathematical models to gain a fuller understanding of the bio-economics of integrated pest management approaches combining bio-pesticides with genetic pest control. We will explore the potential cost-effectiveness and policy options for integrated biologically-based management of agricultural pests such as DBM.

This is a cross-disciplinary collaborative LINK project, with commercial partner Oxitec Ltd, with the objective of optimizing a biotechnological solution for the management of insect resistance to bio-pesticides. We will combine genetic technological developments with mathematical models, laboratory and field experiments to develop an integrated research approach for novel methods of insect pest management.
Oxitec pioneered the development of RIDL - Release of Insects carrying a Dominant Lethal genetic system - a novel approach to insect pest management based on the sterile insect technique.
Oxitec has recently developed transgenic RIDL DBM strains with female-specific lethality. Theoretical modelling has predicted that RIDL releases can mitigate resistance by reducing pest population size and driving pesticide-susceptible genes into a population through the male line.

Our project aims to build on these recent advances. We will test this novel theory using experimental evolution and competition assays to simulate existing resistance management strategies (work packages 1 and 2). We will extend testing to scenarios that are predicted to increase the impact of RIDL releases on resistance management. These scenarios will be increased spatial structure and exposure to multiple toxins. In work package 3 the fitness and field-suitability of new RIDL DBM strains will be investigated through fitness and mating competition assays. Performance of these strains will carefully evaluated in an experimental series that culminates in the field. This will be thoroughly supported by a range of novel mathematical models that will provide a detailed understanding of the evolution of resistance to Bt and its toxins in diverse and heterogeneous agro-ecosytems and also of the cost-effectiveness of genetic control methods for agricultural pests such as DBM (work package 4).

Pest insects cause enormous damage to agricultural crops. For example, the costs of managing the diamondback moth plus the residual crop losses amount to estimated US$4-5billion worldwide annually. The evolution of resistance to control methods threatens the sustainability and biodiversity of agricultural ecosystems. Better understanding of the evolution of resistance to biopesticides has great scope for impact on agriculture internationally, beyond any particular organisms on which our project focuses. Further evidence-based knowledge about the potential of a new genetic biotechnology to slow or reverse the spread of resistance will add to the tools available for integrated pest management approaches.

Who will benefit: Direct beneficiaries from this research will be academics with similar research interests and those interested in developing novel approaches for insect pest management. This is a collaborative LINK project, with industrial partner Oxitec Ltd. The company's significant contribution to the resources for this research clearly demonstrates significant user interest in the proposed research. Our project has direct benefits to those in the commercial sector in understanding the evolution and management of resistance in agricultural insect pests. Indirect beneficiaries of the collaborative research projects include groups and organizations with a focus on sustainable food and farming such as the Agriculture and Horticulture Development Board, ACRE (Advisory Committee on Releases to the Environment) and SACGM (Scientific Advisory Committee on Genetic Modification) and, more broadly EFSA (European Food Safety Authority). As our research project is focused on the empirical and theoretical aspects of pest control, this research will also be relevant to those with an interest in transgenic manipulations using gene-based and microbial-based biological control methods. The general public will benefit from this research by gaining an increased understanding of the biology of transgenic insects and modern methods for the management of pest insects.

How will they benefit: Our research has clear benefit to those interested in the control of pest insects. Any method of pest management (whether based on genetic or conventional techniques) requires an understanding of the potential issues associated with the evolution of resistance. Our research has potential to foster greater awareness amongst all direct and indirect beneficiaries (and consequently has economic implications) of the effects of resistance on undermining the use and release of novel pest control strategies. This project will deliver specific additional impact; our collaborative work will result in field-tested insect strains ready for commercial development and generate new bio-economic knowledge directly relevant to implementing this approach.

What will be done: We will use the standard routes of dissemination (e.g. conferences, seminars and publishing scientific papers) for informing our academic colleagues of the progress in our project. As outlined in our impact plan we have an established track record (e.g. our involvement with STEMNET, ACRE and the Royal Society) in disseminating our research findings more broadly amongst different stakeholder groups. In particular, we will use STEMNET and the BBSRC to engage with the wider public (particularly schools) to present our research findings in a non-technical and engaging way. Contacts within DEFRA (and particularly ACRE) will be used to ensure that this group of beneficiaries are fully informed our progress throughout the project and made aware of publications arising from the research after the lifetime of the grant. We will run a workshop with relevant stakeholders to convey the broad policy implications of our research on resistance management. The collaborative LINK project (with Oxitec Ltd) will allow us to ensure that the economic benefits of our work on insect pest management are fully realised.