Wellcome Trust – Written evidence (GMI0025)

Key messages

• Insect-borne diseases continue to pose a significant risk to human and animal health globally.  Over half the world’s population are at risk of debilitating infectious diseases such as malaria, dengue, chikungunya, West Nile fever and others.  Diseases affecting livestock such as bluetongue and Schmallenberg have spread to various parts of Europe.
• Due to the burden posed by insect-borne diseases, all avenues of intervention to treat or prevent insect-borne diseases should be supported if found safe to do so, within a robust regulatory environment which maintains the confidence of the public.
• The Wellcome Trust believes that Genetically Modified Insects (GMIs) potentially offer a more targeted and less environmentally harmful approach to insect-borne disease control than non-GM techniques and insecticides.
• However, the most effective way to control a vector-borne disease is through a combination of approaches and we envisage GMIs will play a complementary role alongside existing Integrated Pest Management (IPM) programmes.
• The regulatory framework for GMI technologies needs to assess both the risks and benefits of the technology.
• Increased funding and alternative funding models are required for the continued development and application of such technologies, due to the lack of market forces to drive development.
• Effective public engagement to raise awareness of GMI technologies will be essential. This is particularly important given the lack of public confidence in GM crops due to poor public engagement prior to and upon their release. Engagement with communities in which GMIs are to be released for vector control is critical. 

Introduction

1. The Wellcome Trust is a global charitable foundation dedicated to improving health. This year, we are planning to invest £750 million in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health.

2. As a funder of research addressing the burden of insect-borne diseases, including insect control strategies such as GMIs, we are pleased to respond to this consultation.

Our interest in GMIs

3. Insect-borne diseases continue to pose a significant risk to human and animal health globally.  Over half the world’s population are at risk of debilitating infectious diseases such as malaria, dengue, chikungunya, West Nile fever and others.  Dengue fever is the fasted growing vector-borne disease in the world, with a 30-fold increase of incidents over the last fifty years. About half of the world’s population are now at risk to the disease, with the most serious illnesses and deaths being amongst children in some Asian, African and Latin American countries[1].

4. Although low- and middle-income countries (LMIC) have the greatest burden of insect-borne diseases, there is also a growing threat to Europe and the UK[2],[3]. Invasive mosquitoes have become widely established across Europe, with subsequent transmission and outbreaks of dengue and chikungunya virus. Malaria has re-emerged in Greece, West Nile virus has emerged throughout parts of eastern Europe and the prevalence of tick-borne diseases, such as Lyme disease, continue to increase. In animal health, Bluetongue and Schmallenberg viruses have emerged in northern Europe proving it to be equally susceptible to transmission of vector-borne disease.

5. Changes in vector distribution are due to a number of factors: increased global travel creating new opportunities for invasive vectors and pathogens; climatic changes and changes in land use, infrastructure, and the environment. Such changes represent a significant risk to the UK. Lessons from the outbreaks of West Nile virus in North America and chikungunya in the Caribbean emphasise the need to assess future vector-borne disease risks and prepare contingencies for future outbreaks[4],[5].

6. The Wellcome Trust has supported a range of research into treatments, vaccines and vector-control techniques to control mosquito-borne diseases such as malaria, West Nile virus, chikungunya and dengue fever, however no successful vaccines have been developed to date. Given the increasing risk of vector-borne diseases – and because the most effective way to reduce transmission remains  control of disease-carrying mosquitoes[6] – the Trust supports the development of safe and effective new technologies that have the ability to reduce the transmission of insect-borne disease to humans, livestock and agricultural crops, within robust and appropriate regulatory frameworks.

7. We have funded £846,000 towards the development of RIDL (Release of Insects carrying a Dominant Lethal), an innovative gene drive technique developed by Oxford based company Oxitec Ltd. Their approach uses advanced genetics to modify male insects to be 'sterile'. Oxitec has created RIDL strains of Aedes aegypti, the principal mosquito species responsible for spreading dengue fever. These genetically modified male mosquitoes, which do not bite or spread disease, are then released to mate with wild females. No viable offspring can result from these matings and as a result, the mosquito population is ultimately reduced below the threshold level that is required to transmit the disease.

Advantages of GMIs over other approaches             

8. Releasing sterile insects has been used as an effective control method against agricultural pests for over 50 years. But it has not until now been applied to mosquitoes because of the limitations of conventional non-GM sterilisation techniques, such as radiation.

9. The Wellcome Trust believes that GMIs offer significant opportunities. Aedes aegypti are easier to manipulate in labs than other types of mosquito, which is a major reason why this technology has been able to develop. Therefore if the technique is successful, it may have the potential to reduce the transmission of more Aedes aegypti mosquito-borne diseases (not just dengue) making GMIs a powerful mechanism to improving health.

10. Secondly, GMIs can target specific diseases and species very precisely. Field trials by Oxitec have seen a >90% reduction in the population of the target species in the Cayman Islands and a 96% reduction in Brazil. Researchers believe that this level of effectiveness would be enough to prevent endemic dengue fever in any setting globally[7]. The approach leaves non-target insect species unharmed and reduces the amount of chemicals used, unlike non-specific chemical insecticides, which may have a significantly negative impact on the environment and local ecology.

11. However, it is important to note that the most effective way to control vector-borne diseases is through a combination of approaches (e.g., for malaria, a vaccine when available, plus vector control, bed nets and anti-malarials).  We envisage GMIs will play a complementary role alongside existing Integrated Pest Management (IPM) programmes and we encourage this approach.

Regulation of GMIs

12. In Europe, the regulation of GMIs currently falls within the scope of the EU Directive for the Deliberate Release of Genetically Modified Organisms (GMOs) (2001/18/EC).  This Directive rightly requires that all GMOs undergo an extensive risk assessment prior to any release into the environment.  However, the Directive only approves organisms for release into the environment based on the risks of GMOs to human health and the environment as opposed to focusing on the purpose of the organism. Given the potential benefits of GMIs for both human and animal health, the Wellcome Trust encourages the development of a regulatory framework that assess both the risks and the benefits of GMI technologies, similar to legislative frameworks in the U.S, Australia, New Zealand and Brazil[8].

Limitations, risk and resistance in GMIs

13. There are limitations to the current technologies used to develop GMIs for insect-borne disease control.  For example, not all species of mosquito can be mass bred in laboratories and such approaches are only likely to work where there is only one main pathogen-carrying species[9].

14. Another risk is the development of resistance in target vector populations. As might be expected in any intervention which drives down a population or exerts any other selective pressure, resistance would be expected to build up over time and should be monitored. Resistance would be expected to evolve both to the drive mechanism (e.g., mutations in the genomic region you were targeting making the drive mechanism ineffective) and towards any genetic trait you were modifying (e.g., the ability to resist a particular pathogen). In developing such technologies, it will be important to learn from the development of resistance in other pathogens. This could be done through mathematically modelling the expected speed and spread of resistance before planning and implementing any intervention, to make any successful interventions last as long as possible (e.g., by using them in combination or in a co-ordinated way).

15. Companies developing GMI technologies, such as Oxitec, are required to make in-depth assessments of the impact GMIs may have on the local ecology and food chains, based on controlled studies. Monitoring must be undertaken before, during and for years after release of GMIs to prove its safety and efficacy, including ensuring that the environmental impact is minimal.  Further research and longer-term studies are required to ensure new GMIs have no adverse effect or unintended impacts on the environment and other organisms.

Funding the development of GMIs

16. GMI technologies have struggled to attract funding for development and commercialisation due to the uncertainty of return on investment. It seems that this is partly a result of target markets being in LMICs but also the uncertainty surrounding public acceptance and government approval of release of GMIs.  Large amounts of capital are needed to establish and scale up GMI technology.  Current funding for such technologies rests with charitable and public funders.  Given the significant potential benefits to populations at risk of vector-borne diseases, we would welcome alternative financial incentives and business models to support development and commercialisation.

How could the UK benefit economically from both developing GMI technology and its use within the UK?

17. The UK currently spends millions per year in aid to countries with significant vector-borne disease burden and in research for interventions to prevent such diseases.  Contributing to reducing this burden could help reduce aid spend.  Further, development of such cutting edge technologies enhances the UK science base.

18. The use of GMIs to control vector-borne diseases in livestock, and the potential wider use of GMIs in agriculture in the UK is further reason to support development. The most important economic problems to be addressed using GMIs may well be crop pathogens and pests since current use of insecticide is much greater in agriculture than in human and animal vector-borne disease control. The additional economic benefits resulting from agricultural use should also be taken into account when assessing the potential benefit of GMI technologies.

What are the critical factors in effective public engagement from lab to final release?

19. We believe that effective public engagement with communities in which GMIs are to be released for vector control is essential.  The introduction of GM crops provides a salutary lesson about the dangers of not engaging effectively. Companies and academics proposing release of GMIs need to engage regulatory authorities, citizen groups and the Government from an early stage, ensuring dialogue with all groups in the community. We strongly believe that people need to understand both the risks and the benefits of GMI technologies so that they can come to an independent and well-informed view regarding such technologies.

20. Public engagement will be necessary both in the LMICs where most of these technologies will be deployed but also in the countries where these technologies are being developed, to help build up trust and ensure there is an environment conducive to research and investment in this technology.

September 2015