Developing insect population models to support the design of GM control strategies
Lead Research Organisation:
The Pirbright Institute
Department Name: Vector-borne Viral Diseases
Abstract
The stable fly is a major nuisance insect with a global distribution and is capable of mechanically transmitting a range of important livestock and human pathogens. The stress and injury caused by its biting activity are estimated to cost the US cattle industry around $1billion/year. Its impact is projected to increase in regions including Brazil and Australia as a consequence of recent changes to the management of sugar cane and other vegetable waste. Better control methods for stable flies would therefore benefit animal welfare, bioenergy production and food production.
The industrial host of this project, Oxitec, is a world leader in developing methods for manipulating insect populations through the development and release of genetically modified strains. For mosquitoes, this typically involves the release of very large numbers of modified male insects to outcompete wild-type males. This has minimal impact because male mosquitoes do not blood-feed. To use similar approaches to control stable fly populations, there is a greater need for tools to design optimally efficient release strategies because male and female stable flies both blood-feed.
The proposed project will develop process-based models of stable fly populations and use modern statistical approaches to fit them to data. Process-based models explicitly model biological processes such as birth and death rates rather than simply modelling abundance. They are relatively complex and the difficulty of fitting them has historically been a limitation, but they are better for exploring the responses of populations to unusual circumstances such as climate change or control strategies. Recently, better statistical approaches to fitting complex models to data have been developed, such as Approximate Bayesian Computation (ABC).
The Mathematical Biology group at Pirbright has a history of successfully using cutting-edge statistical approaches to fit complex biological models to data. During the recent outbreak of Schmallenberg virus in northern Europe, the group used Approximate Bayesian Computation to fit a complex disease transmission model to the early stages of the outbreak, allowing inferences to be made about key disease transmission parameters which were provided to the European Commission to make outbreak management decisions. The conclusions of the model were later validated experimentally. The group also has a history of facilitating the acceptance of modelling outputs for policy decisions. For example, disease spread simulations provided by the group were recently used to help make the case for licensing a novel bluetongue vaccine product, and during the BTV outbreak in the UK in 2007 the group provided simulation outputs in real-time in response to queries from policymakers.
Process-based insect population modelling is a logical next step for the group's research into the spread of vector-borne diseases, as it will allow the effects of climate change and novel control strategies on insect vector populations to be predicted with greater certainty. The stable fly is an ideal species to begin with for several reasons. Firstly, as outlined above, the species is associated with a substantial and growing direct impact in many areas of the world and represents a large potential market. Secondly, an opportunity exists to develop the model in parallel with a GM control product and then use the project outputs to design optimal release strategies of the new strains, supporting its uptake. The academic partner maintains the only colony of stable flies in the UK and is able to support the project via materials and know-how. Colleagues at EMBRAPA have recently begun collecting a large dataset of population observations that they are willing to share for the project, and an outline population model was already developed during previous research activities.
The industrial host of this project, Oxitec, is a world leader in developing methods for manipulating insect populations through the development and release of genetically modified strains. For mosquitoes, this typically involves the release of very large numbers of modified male insects to outcompete wild-type males. This has minimal impact because male mosquitoes do not blood-feed. To use similar approaches to control stable fly populations, there is a greater need for tools to design optimally efficient release strategies because male and female stable flies both blood-feed.
The proposed project will develop process-based models of stable fly populations and use modern statistical approaches to fit them to data. Process-based models explicitly model biological processes such as birth and death rates rather than simply modelling abundance. They are relatively complex and the difficulty of fitting them has historically been a limitation, but they are better for exploring the responses of populations to unusual circumstances such as climate change or control strategies. Recently, better statistical approaches to fitting complex models to data have been developed, such as Approximate Bayesian Computation (ABC).
The Mathematical Biology group at Pirbright has a history of successfully using cutting-edge statistical approaches to fit complex biological models to data. During the recent outbreak of Schmallenberg virus in northern Europe, the group used Approximate Bayesian Computation to fit a complex disease transmission model to the early stages of the outbreak, allowing inferences to be made about key disease transmission parameters which were provided to the European Commission to make outbreak management decisions. The conclusions of the model were later validated experimentally. The group also has a history of facilitating the acceptance of modelling outputs for policy decisions. For example, disease spread simulations provided by the group were recently used to help make the case for licensing a novel bluetongue vaccine product, and during the BTV outbreak in the UK in 2007 the group provided simulation outputs in real-time in response to queries from policymakers.
Process-based insect population modelling is a logical next step for the group's research into the spread of vector-borne diseases, as it will allow the effects of climate change and novel control strategies on insect vector populations to be predicted with greater certainty. The stable fly is an ideal species to begin with for several reasons. Firstly, as outlined above, the species is associated with a substantial and growing direct impact in many areas of the world and represents a large potential market. Secondly, an opportunity exists to develop the model in parallel with a GM control product and then use the project outputs to design optimal release strategies of the new strains, supporting its uptake. The academic partner maintains the only colony of stable flies in the UK and is able to support the project via materials and know-how. Colleagues at EMBRAPA have recently begun collecting a large dataset of population observations that they are willing to share for the project, and an outline population model was already developed during previous research activities.
Technical Summary
Not applicable for FLIP applications.
Planned Impact
The proposed research will develop process-driven population models of Stomoxys calcitrans, the common stable fly, and Bayesian methods for fitting these models to field data. The general methodology is also likely to be useful for modelling the population dynamics of a range of insect species. The principal advantage of process-based models over statistical models is that they are more capable of exploring responses to change. Because of this, the principal potential beneficiaries of this research include organisations interested in knowing the responses of S. calcitrans populations to novel conditions, specifically environmental change and control strategies.
The first major group of beneficiaries is that of industrial companies developing GM solutions to insect population control and modification. The use of genetic modification to control insect populations is still a novel technology, although small-scale field releases have been used successfully. Reducing the costs associated with the mass-rearing and release of modified insects will reduce the direct costs of these activities and increase their profitability. Oxitec, a UK company, is the global leader in this area.
The second group is that of policy-makers. The legislative and regulatory framework pertaining to the use of GM releases for insect population control in the UK and EU is still developing. This project represents an opportunity to apply lessons learned during the process of integrating mathematical modelling into infectious disease policy decisions to accelerate the integration of mathematical modelling outputs into the policy decision-masking process related to GM insect releases.
The third major group of beneficiaries is farmers, both in the UK and elsewhere. S. calcitrans is a major nuisance insect with a global distribution and is capable of mechanically transmitting a range of important livestock and human pathogens. The stress and injury caused to animals and people by its biting activity are substantial in many parts of the world, and it is a common species on British cattle farms. The model developed during this project will include climatic drivers and so will allow the regional effects of seasonal and longer-term environmental changes, and of control strategies such as the removal of larval haitats, to be better understood. Furthermore, the impact of Stomoxys activity is believed to be increasing in some parts of the world because of changes to the management of agricultural waste, particularly that generated during the production of bioethanol from sugar cane, in an attempt to reduce the environmental impact of these processes. By supporting the development of a product which has the potential to reduce S. calcitrans populations, this research could resolve the conflict between bioethanol production and livestock production in some parts of the world.
Effective control methods for stable flies would benefit animal welfare, bioenergy production and food production. Oxitec is about to begin exploring the potential for using GM control strategies for controlling Stomoxys. The planned project is perfectly timed to exploit this opportunity to integrate mathematical modelling in the development and licensing process for new GM insect products by helping a UK company that leads the world in this field to develop a method of controlling a major and emerging insect problem.
The first major group of beneficiaries is that of industrial companies developing GM solutions to insect population control and modification. The use of genetic modification to control insect populations is still a novel technology, although small-scale field releases have been used successfully. Reducing the costs associated with the mass-rearing and release of modified insects will reduce the direct costs of these activities and increase their profitability. Oxitec, a UK company, is the global leader in this area.
The second group is that of policy-makers. The legislative and regulatory framework pertaining to the use of GM releases for insect population control in the UK and EU is still developing. This project represents an opportunity to apply lessons learned during the process of integrating mathematical modelling into infectious disease policy decisions to accelerate the integration of mathematical modelling outputs into the policy decision-masking process related to GM insect releases.
The third major group of beneficiaries is farmers, both in the UK and elsewhere. S. calcitrans is a major nuisance insect with a global distribution and is capable of mechanically transmitting a range of important livestock and human pathogens. The stress and injury caused to animals and people by its biting activity are substantial in many parts of the world, and it is a common species on British cattle farms. The model developed during this project will include climatic drivers and so will allow the regional effects of seasonal and longer-term environmental changes, and of control strategies such as the removal of larval haitats, to be better understood. Furthermore, the impact of Stomoxys activity is believed to be increasing in some parts of the world because of changes to the management of agricultural waste, particularly that generated during the production of bioethanol from sugar cane, in an attempt to reduce the environmental impact of these processes. By supporting the development of a product which has the potential to reduce S. calcitrans populations, this research could resolve the conflict between bioethanol production and livestock production in some parts of the world.
Effective control methods for stable flies would benefit animal welfare, bioenergy production and food production. Oxitec is about to begin exploring the potential for using GM control strategies for controlling Stomoxys. The planned project is perfectly timed to exploit this opportunity to integrate mathematical modelling in the development and licensing process for new GM insect products by helping a UK company that leads the world in this field to develop a method of controlling a major and emerging insect problem.
Publications
Panjwani A
(2016)
What Is Stopping the Use of Genetically Modified Insects for Disease Control?
in PLoS pathogens
Description | As for all FLexible Interchange Programme (FLIP) projects, a primary objective of the activities funded under this grant was to improve the interchanger's connections with, and understanding of, industrial and stakeholder processes and how they can be integrated with BBSRC's strategic priorities. This has been achieved; I have established or strengthened links with industrial and policy collaborators in the UK, Brazil, the US and Australia and received invitations to discuss or present research findings and advisories in this area. In addition, during this grant I have developed code for modelling insect populations, and by analogy other populations with similar life-histories. A publication describing these models, the process of fitting them, and how the results can assist industrial partners and policymakers in making informed decisions about control strategies is currently in preparation, and once this is accepted the fully-commented code and sample data for test runs will be made available via the award holder's Github repository. The research identified further areas requiring research, including the development of a general framework for agent-based models to understand insect populations and insect-pathogen interactions, and this insight will result in the preparation of new proposals on this topic. |
Exploitation Route | As described above, once the publication describing this application of the model has been accepted the code permitting others to develop and fit models of similar populations will be freely shared via the award holder's Github repository. The author is also planning to share lessons learned on this project on engagement with industry and policy users of modelling outputs via his role within the Brish Ecological Society, and to provide advice to policy-makers on using models via his connections with Defra. |
Sectors | Agriculture, Food and Drink,Education,Environment,Manufacturing, including Industrial Biotechology |
Description | General discussion of potential uses of models with industrial partner and potential governmental sponsors has allowed stakeholders to identify additional questions that are a policy/industry priority for mechanistic population model frameworks to address. Future work on this grant will result in specific actionable conclusions about the possible outcomes of different releases strategies or population suppression. |
First Year Of Impact | 2016 |
Sector | Government, Democracy and Justice,Manufacturing, including Industrial Biotechology |
Impact Types | Economic,Policy & public services |
Description | Participation in a House of Lords Breakfast Briefing event, 10th February 2015 |
Geographic Reach | National |
Policy Influence Type | Contribution to a national consultation/review |
Impact | The event led to a national consultation on the use of genetically modified insects for disease control, the outcome of which was a recommendation for field trials in this area and a recognition of the need for reform of regulations. |
URL | http://www.parliament.uk/genetically-modified-insects |
Description | Vectorbite workshop 2016 participation award |
Amount | $360 (USD) |
Funding ID | 1R01AI122284-01 |
Organisation | National Institutes of Health (NIH) |
Sector | Public |
Country | United States |
Start | 03/2016 |
End | 03/2016 |
Title | basic Stomoxys model |
Description | To do |
Type Of Material | Computer model/algorithm |
Year Produced | 2017 |
Provided To Others? | No |
Impact | To do |
URL | https://github.com/arboviral/stomoxys |
Description | Evaluation of the potential for suppression of Stomoxys calcitrans populations via the release of genetically modified insects |
Organisation | Oxitec Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | We have provided know-how and materials to enable Oxitec to establish colonies of Stomoxys calcitrans. |
Collaborator Contribution | Oxitec has agreed to share confidential data on the performance of the resulting genetically modified strains developed from our wild-type materials to permit the use of Stomoxys calcitrans population models under development at Pirbright to project the outcomes of different GM insect release strategies. |
Impact | Collaboration/MTA signed; colony established, preliminary (non-spatial deterministic) model completed. |
Start Year | 2014 |
Description | Mechanistic population modelling network |
Organisation | University of Oxford |
Department | Department of Zoology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | To increase critical mass for research discussions relating to mechanistic population modelling, I and Professor Michael Bonsall (head of the Mathematical Ecology Research Group within the Zoology Department) have initiated a collaboration in this area by agreeing for a postdoc within MB's group to be hoested by Pirbright for two days a week beginning in March 2016. |
Collaborator Contribution | We are subsidising bench fees for the cost of hosting a part-time mathematical biology postdoc from MERG (Dr Nina Alphey) at Pirbright for twelve months. |
Impact | Hosting only began this week. |
Start Year | 2016 |
Description | Mechanistic population modelling of mosquito vectors |
Organisation | University of Oxford |
Department | Department of Zoology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | To increase critical mass for research discussions relating to mechanistic population modelling, my group has become the industrial sponsor for a NERC DTP studentship project to jointly develop (with Professor Michael Bonsall of the Mathematical Ecology Research Group within the Zoology Department) mechanistic population models for Aedes mosquitoes. |
Collaborator Contribution | The student will spend a minimium of twelve months continuously based at Pirbright utilising our Aedes mosquito resources to conduct experimental ecology experiments to parameterise and validate mechanistic population models developed jointly by both partners. Achieving the same outcomes via a joint doctoral studentship between Pirbright and an academic partner would cost us £50k over four years instead of the £4k required by operating as a NERC CASE sponsor. |
Impact | Collaboration began this month (March 2016). |
Start Year | 2016 |
Description | Cafe Scientifique, Bradfield School, West Berkshire: "How insects spread viruses" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Cafe Scientifique is a public forum for exploring the latest ideas in science and technology. Meetings take place in cafes, bars, restaurants and even theatres, but always outside a traditional academic context. I presented to an audience of the general public and answered questions. |
Year(s) Of Engagement Activity | 2017 |
Description | Cafe Scientifique, Reading: "How insects spread viruses" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Cafe Scientifique is a public forum for exploring the latest ideas in science and technology. Meetings take place in cafes, bars, restaurants and even theatres, but always outside a traditional academic context. I presented to an audience of the general public and answered questions. |
Year(s) Of Engagement Activity | 2007,2017 |
Description | Careers evening at Gordon's School in Surrey |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | I and other colleagues ran a stand advertising the Institute and explained scientific careers, pathways to employment in academia and opportunities for apprenticeships etc to school pupils and their parents. |
Year(s) Of Engagement Activity | 2017 |
Description | GM insects public discussion |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | I and a postdoc at Pirbright organised a public discussion event in February 2015 in central London on the use of genetically modified insects for disease control. The event provided members of the general public with an opportunity to meet scientists, policymakers and stakeholders involved in this area to discuss the potential risks and benefits of using GM insects as a disease control measure and debate how future policy decisions about it should be made. The questionnaire responses indicated that the event succeeded at: • increasing the audience's level of understanding of the core technologies which make the production of GM insects possible; • increasing the audience's level of understanding of how GM insects could help to control animal and human disease; • encouraging participants develop an opinion on whether GM insects should be used to control animal and human diseases; • improving the audience's understanding of the current UK regulatory system. We also recorded information about the audience's level of concern about GM and organisations involved in GM as well as their trust in regulatory systems designed to regulate research in GM. |
Year(s) Of Engagement Activity | 2015 |
URL | https://dx.doi.org/10.6084/m9.figshare.2064354.v1 |
Description | Insect Festival 2017 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Ran a stand on blood-sucking arthropods and their role in the transmission of disease at the Royal Entomological Society's Insect Festival. Talked to public, answered questions. Lots of enquiries about ticks, midges, mosquitoes and large biting flies (particularly horseflies). |
Year(s) Of Engagement Activity | 2017 |
URL | https://www.yorkmuseumstrust.org.uk/whats-on/events/insect-festival-2017/ |
Description | Invited participant, Improving the Use of Evidence in Policymaking in the UK Government (Parliamentary Office of Science and Technology) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Invited to attend meeting to launch POST report "Improving the Use of Evidence in Policymaking in the UK Government" as a result of previous collaboration. |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.sciencecampaign.org.uk/resource/casereportimprovingtheuseofevidence2017.html |