17 December 2015

GMO Bugs

The House of Lords Science and Technology Committee has released its upbeat report on Genetically Modified Insects, stating
The problems caused by infectious disease and agricultural pests are real. Genetically modified (GM) insects have the potential to address both these problems. The UK is a world leader in the development of this technology. The European Union’s regulatory process, however, is likely to hold back progress. There is a moral duty to test the potential of the technology. We therefore support further research and call for action to test the efficiency of the EU process via a trial which should also be used to drive public engagement.
The world’s fastest growing insect-borne disease is dengue. The global incidence of dengue has grown dramatically in recent decades and about half of the world’s population is now at risk. Dengue can be found in tropical and sub-tropical climates across the world. The possibility of an outbreak of dengue, however, now exists in Europe. This mosquito-borne viral infection causes a flu-like illness, and can develop into a potentially lethal complication named severe dengue. Severe dengue is a leading cause of hospitalization and death among children in many Asian and Latin American countries. A recent study estimated there to be 390 million dengue infections per year.
In 2015 there have been approximately 214 million cases of malaria and 438,000 deaths. Sub-Saharan Africa is particularly affected; so far this year, the region has been home to 89% of malaria cases and 91% of malaria deaths. Malaria is both preventable and curable, and increased efforts have seen significant reductions in malaria incidence (the rate of new cases) and deaths. Nevertheless, about 3.2 billion people, nearly half of the world’s population, live in countries, territories and areas where malaria is endemic.
By 2050 the world’s population will likely increase by more than a third to over 9 billion people. World food production will be required to increase by 70% to feed this larger, more urban and richer population. Insect pests affect all aspects of food production, storage, transport and waste. Agricultural losses due to insect damage are high. For example, insect pests cause an average annual loss of 7.7% in production in Brazil, a reduction of approximately 25 million tons of food, fibre and biofuels, with total annual economic losses reaching around US$ 17.7 billion. Insect-borne diseases also have a heavy impact on livestock. Research conducted at the Pirbright Institute in the UK prevented Bluetongue disease becoming endemic in UK sheep and cattle, an estimated saving to the UK economy of £480 million in 2008 alone.
The development and use of GM insects offers significant potential for both the control of infectious diseases and the management of agricultural pests. It is possible to manipulate an insect’s DNA in order to alter its function or reduce its fitness. In this way, insects which transmit diseases or damage crops can be modified. GM insect technologies are a potential form of biological control, in contrast to the use of chemical controls, such as insecticides, which can be harmful to people and the environment.
GM insect technology has already been trialled for dengue transmitting mosquitoes. Developed by the UK company Oxitec Ltd., field evaluations have seen a >90% reduction in numbers of the target species in the Cayman Islands and a 96% reduction in Brazil, which is argued to be sufficient to prevent endemic dengue fever anywhere in the world. From the evidence we heard, it may be the case that GM insect technology is more suited to tackling dengue than malaria.
In November 2015, scientists announced that they had successfully used GM insect technology so that a modified mosquito passes on genes conferring resistance to a pathogen (an organism that causes disease) to almost all of its offspring, not just half, as would normally be expected. This offers the possibility of a gene resistant to the parasite that causes malaria being able to spread quickly through a wild population of mosquitoes. In early December 2015, scientists, including Professor Austin Burt who gave oral evidence to our inquiry, announced findings that could speed up the development of techniques to suppress mosquito populations to levels that would not support malaria transmission.
The potential of GM insect technologies, however, should not be over-stated; an arsenal of strategies is required to tackle insect-borne diseases and crop pests. GM insect technologies do not represent a panacea. They are one of a number of experimental techniques being investigated in order to control insect-borne diseases and reduce agricultural pests.
Nevertheless, despite inevitable uncertainties, we conclude that GM insect technologies should be afforded an opportunity to play a complementary role in helping to meet the global challenges of disease control and food security. The UK, moreover, is a world leader in this area and hosts the only company in the world producing and distributing GM insects (Oxitec Ltd.). Unfortunately, we are very concerned that the benefits offered by GM insects may not be realised. The EU regulatory regime for genetically modified organisms (GMOs) is not functioning effectively. Although no EU-level GM insect applications have been received to date, the regime has seen many applications for GM crops. In these cases, the regime is failing lamentably. The prescribed process is not being followed and the system is gridlocked. Strenuous efforts must be made to ensure that the system operates more efficiently and that future GM insect applications are not stymied unnecessarily. To this end, the UK Government must bring pressure to bear on the European Commission to ensure that the current regime works as intended.
However, ensuring that the current system works as intended is not sufficient. The EU regulatory regime does not take into account the benefits of a technology; regulation is entirely on the basis of risk. Any rational approach to deciding whether or not to pursue a given technology should include an assessment of its net benefits. At the moment, moreover, no consideration is given to the risks of alternatives to the GM application. A potential new GM insect technology to reduce an agricultural pest population, for example, would not be compared alongside the insecticide currently used to tackle the pest. As such, GMOs are effectively considered against an idealised, risk-free alternative. For many GM insect technologies, the alternative may present a number of risks and problems, and, in many cases, such risks and problems (the use of insecticides for instance) may be the imperative behind the development of the GM insect technology in the first place. Consideration of the benefits of a technology, and acknowledgment of the control methods currently in use, should be incorporated into the regulatory regime in order to address this illogical situation.
In order to attempt to break the current impasse, we recommend that the Government invests in a GM insect field trial to test fully the science of GM insects, regulatory processes and policies. This stimulus is required in order to move beyond the current stasis induced by the failings of the EU regulatory regime. Moreover, the pursuit of such a trial should be the catalyst for a public engagement exercise. It is imperative that the public is given the opportunity to understand the development of GM insect technologies in a transparent way so that the polarised debate which has enveloped GM crop technologies is avoided.
GM insect strategies for agricultural use are likely to have greater scope for application within the EU, though there may be future uses for public health purposes that could be applicable in Europe. In all likelihood, however, the main uses of GM insect technologies, particularly for public health purposes, will occur outside the EU. In this regard, we are concerned that the application of GM insect technologies in the countries whose need is greatest may be affected by a lack of international guidance and leadership on the governance and regulation of these technologies. We therefore recommend that the Government, in light of its strong commitment to international development, actively considers how these challenges of international guidance and leadership can be fully achieved.
The application of GM insect technology, together with advances in the broad area of biotechnology, has the potential to provide additional tools for the control of insect-borne diseases and crop pests. The conceivable prize is enormous and the opportunity must not be squandered. Our concern is that unless there is change, and an injection of momentum and urgency, it will be.
The report goes on to refer to "a bleak picture", stating
The process for GM crops is clearly failing lamentably. It is not working as intended. The new national derogations for commercial cultivation of GM crops, referred to by the Minister, are to be broadly welcomed as a potential means of breaking the gridlock, but only time will tell if they can have any effect.
Concerns expressed about the regulatory regime were voluminous, and extended beyond poor implementation, and the vagaries outlined by the Minister, to fundamental misgivings about the design of the regime. We heard repeatedly, from nearly all parties involved, that the system does not work as intended and is subject to excessive political interference once the scientific risk assessment has been completed by EFSA. Policy-makers should not ignore the scientific evidence base.
Further concerns highlighted to us also included: regulation was not designed with GM insect technologies in mind, but is rather an extension of the legislation for GM crops; regulation is entirely on the basis of risk, and benefits are not considered; the process is regulated rather than the product generated; and self-limiting population replacement strategies are considered in the same way as self-perpetuating population replacement strategies.
In the paragraphs that follow, we briefly catalogue the litany of criticism that was directed towards the regulatory regime. As Dr Jack Stilgoe, Senior Lecturer at the Department of Science and Technology Studies, University College London, put it to us: “I am afraid it is one of those situations where you could say ‘you wouldn’t start from here’.” We agree, but we have, of course, no choice, and if the potential of GM insects is to be realised, then urgent actions are required.
As we have noted, the regulatory regime covers all GMOs including both GM crops and GM insects. Although it does remain to be seen if GM insect applications would be subject to regulatory difficulties resulting from part C of directive 2001/18/EC, all the experience of GM crops would seem to point to it. Professor Rosemary Hails, Chair, Advisory Committee on Releases to the Environment (ACRE), stated: “in the EU we do not have a functioning system for GM crops.”83 Camilla Beech, Head of Regulatory Affairs at Oxitec Ltd., gave a clear view from the commercial sector: “As an applicant we believe that the European system does not work because it is just not predictable. You put an application in and you can never predict when you are going to receive a response. That is bad for innovation and it is bad for companies.”84 100.Innovate UK stressed that the deliberate release directive had not been designed with GM insect technologies in mind, but was rather an extension of the legislation for GM crops: “The current regulations pre-date the existence of GM insects and do not seem to effectively accommodate this technology.”85 George Eustice MP, however, disputed the view that the currently regulatory regime could not effectively accommodate GM insect technologies: “from a regulatory point of view, we do not see any reason why the GM process that exists for crops in the EU should not equally be applied to GM insects.”86 101.We heard repeatedly that there is currently no means to consider the potential benefits of GMOs within the regulatory regime. As such, decisions are made entirely on the basis of risk alone. The National Institutes of Bioscience (NIB) stated: “Without considering benefits, one is implicitly comparing the proposed action with a non-existent risk-free alternative—a Utopian fallacy. Benefits, and therefore risk-benefit, could be considered explicitly.”
Furthermore, we were surprised to learn that new technologies are not evaluated alongside alternative means to address the problem. For example, a potential new GM insect technology to reduce an agricultural pest population would not be compared alongside the insecticide currently used to tackle the pest.
The current EU regime operates via a system of process-based regulation. That is to say, the trigger is the process by which a product is made rather than the nature of the product itself. In this regard, Camilla Beech, Head of Regulatory Affairs at Oxitec Ltd., offered the following analogy: “It is like reviewing a book as to whether it has been written on a typewriter or a computer and not on its content.”
This process-based system would consider population replacement and population suppression GM insect strategies in the same way. John Mumford, Professor of Natural Resource Management, Centre for Environmental Policy, Imperial College London, highlighted a fundamental conflict within the current framework when population replacement strategies were considered: “there are seven large areas of technical concern within the deliberate release directive, and persistence is one of those seven. Obviously, with the self-sustaining mode of action for some of these methods, you are starting from an assumption that the whole mode of action is a concern. That is an inherent conflict within the regulation.”  In this way, the deliberate release directive is fundamentally not designed to consider self-perpetuating population replacement strategies.
The criticism directed towards the regulatory regime raises the question of whether the focus should be on making the current system work better, or seeking to overhaul it entirely. Professor Rosemary Hails argued that there would be merit in trying to make the existing system work as it should: “We ought to be proactive on trying to make the current system work more effectively. In essence, we have the evidence that it works more effectively in other countries.”
The current system is framed around the implementation of the Precautionary Principle. On the use of this Principle, Professor Rosemary Hails stated: “the Precautionary Principle properly applied would also take into account the risks of not developing a particular technology and the benefits forgone. It is a misuse of the Precautionary Principle that has led us to this place.”
The Government maintains that the best course of action is to ensure that the regulatory environment works as it is written. George Eustice MP said: “All the EU has to do is not necessarily rewrite its process but just gain some credibility by sticking to the process that it has written down.”
George Freeman MP put it in the following terms: “GM technology is taking off across the world. The question is not whether we are going to stop it; the question is whether we are going to help contribute to leading it and getting the right regulatory framework in place.”
We welcome the Government’s endorsement of the potential of GM technologies and its recognition of the importance of a functioning regulatory environment. We are concerned, however, by its view that the most appropriate course of action is only to ensure that the current system proceeds as it is written. This is not sufficient.
GM insects have the potential to help in the control of both insect-borne diseases and agricultural pests, bringing both public health and economic benefits. The UK is a world leader in the development of GM insect technologies and the public good and the commercial opportunities are tangible. However the current EU regulatory regime for GMOs risks this opportunity being squandered. The regime is failing as applied to GM crops and the full potential of GM insects will not be realised if it continues to fail to function adequately.
We accept that there is some practical merit in the Government’s decision to work to ensure that the existing regulatory regime for GMOs at least functions as written. We ask the Government to set out clearly how it intends to do so and to publish annual updates on progress made in improving the operation of the system, starting in the summer of 2016. However, we do not accept that this is sufficient and we advocate a more radical review of the regulatory framework later in this Chapter.
International regimes
By way of comparison, we explored a number of international (non-EU) regulatory frameworks for GMOs in order to ascertain the characteristics of alternative regulatory regimes. Norway was cited as a notable example. Although a non-EU country, Norway is a member of the European Economic Area (EEA). As a member of the EEA, it has incorporated EU-based regulation but has also included an additional component. Professor Rosemary Hails told us: “Norway has some additional legislation—the Gene Technology Act 1993—where it considers the benefits also of a particular element to the community and the contribution to sustainable development, but that is in addition to the other regulations.”
Outside Europe, we were told that Canada has adopted a regime of trait-based regulation. This is effectively the reverse of the system in the EU whereby process-based regulation is used. Dr Jeremy Sweet, an Environmental Consultant with Sweet Environmental Consultants and member of the EFSA GMO panel, said of the Canadian system: “they do not discriminate GMOs from other types of engineering or manipulation or technologies. They look at the novelty of a product and say, ‘Are we concerned about this and do we need to look at it and regulate it?’”
Oxitec Ltd. highlighted the regulatory environment in Brazil. This regulatory system has been tested, unlike that in the EU, and the Brazilian authorities accepted a trial release of Oxitec GM mosquitoes. Oxitec suggested that this successful release in Brazil was due to “a clear regulatory framework based on plausible scientific pathways to harm and subsequent evaluation allowed the assessment of the dossier for commercial release in approximately 9 months from submission to approval.” From what we heard of the EU regulatory system, such efficiency would seem highly unlikely were a similar application to be received.
Oxitec also highlighted the regulatory environment in the USA where, under the National Environmental Policy Act, agencies are required to issue an Environmental Assessment that takes into consideration the alternatives available alongside the GMO application. Thus, GM insects are not considered against an idealised ‘risk-free’ alternative.
The joint submission received from a grouping of eminent Brazilian scientists—Dr Amaro de Castro Lira Neto, Dr Marcia Almeida de Melo and Professor Paulo Paes de Andrade—also highlighted the US system of regulation. They suggested that the main point of success of the US system is: “the full independence of the risk assessment procedure against the other risk analysis steps, i.e., risk management and risk communication, and ultimately against political decisions.” Furthermore they stressed that: “No political interference is allowed, at least under normal circumstances.”
This independence of the risk assessment procedure from political decision-making presents a stark contrast to the picture painted for us of the EU regulatory system. This group of Brazilian scientists also suggested that this independence is the cause of rapid adoption of biotechnology in Brazil and, to a certain extent, in Argentina, Australia and Canada as well.
Alternative regulatory protocols
We were presented with a number of alternative regulatory models that may allow for more effective incorporation of GM insects into the general GMO regulations. A number of these have been touched on above. Warnings were issued, however, about the pursuit of a new regulatory regime. George Eustice MP stressed to us: “with any European process you always have to be conscious that by taking the lid off things and trying to play around with the wiring, you might end up with something worse. It is a terrible thing to say, but I am afraid there is a track record of trying to tamper with things in Europe that are not quite right, and they end up worse than ever.”
.Although a radical overhaul of the current regulatory process may be unlikely or undesirable at this time, a number of potential alterations to the regulatory process were highlighted to us.
A trait-based approach
A trait-based approach to regulation was raised as a sensible, scientifically-sound alternative to the current process-based regulatory system. In this case, the product, rather than the means by which it has been formed, is considered. This system is in operation in Canada. Professor Rosemary Hails indicated that ACRE would deem this approach to be more scientifically defensible and “more scientifically rational now.” Dr Jeremy Sweet also highlighted that trait-based regulation is a “science-based approach”.
.A move to a trait-based system would allow separate consideration of GM insects created via population suppression and population replacement strategies. It would also result in population suppression approaches such as Oxitec’s genetic-equivalent of the SIT being considered in the same way as traditional irradiation-based SIT approaches. This may be more rational as the nature and implications of the end products are arguably the same; it is simply that the process to create them is different.
Not all the evidence we heard suggested that trait-based regulation is superior to process-based regulation. Dr Jack Stilgoe warned us that there may be good reasons for a process-based system: “They are to do with the uncertainties that we might be unable to predict in terms of the products, whether those are the products themselves or the products of that particular innovation in terms of the consequences and ramifications of those traits, and actually paying attention to the processes might better take you into a precautionary approach to governing those uncertainties.”
New technological developments may be captured within a system of trait-based regulation. For example, both transgenic and cisgenic GMOs would be included. Dr Jeremy Sweet indicated that it is becoming increasingly difficult to draw a distinction between “GM” and “non-GM”. He emphasised to us that: “We are getting into a bigger and bigger mess by basing the regulation around the technology.”
Government Ministers also highlighted to us that new emerging technologies are serving to blur the boundaries between GM and non-GM. However, on the prospect that trait-based regulation could incorporate new (cisgenic) technologies and remove the need for such arbitrary classifications, George Eustice MP stated: “We would not want those [emerging technologies] to be treated as GM, otherwise you are going to hold back the development of a very exciting new area.” He continued: “Once you start talking about trait-based approaches to this, I think there is a danger that you start to tip some of those other novel techniques too closely to the GM regulatory regime, which is the worst of all worlds, because then you have other exciting new technologies that we hope to protect from this and to maintain an understanding that they are not GM, and get muddled up in this unsatisfactory regime as well.”
At present, cisgenic organisms, such as those created using gene-editing techniques, including CRISPR, are not considered within 2001/18/EC. We consider this to be correct. We heed the warning that a move to trait-based regulation would alter this situation. However, while we agree with the Minister that new emerging technologies should not be stifled by a failing regulatory system, we do not think it appropriate to ignore the deficiencies of the regulatory regime for other developing (transgenic) technologies.
We urge the Government to monitor the development of new genetic technologies, including GM insects, in order to ensure that the regulatory regime is fit-for-purpose. We recognise that a move to a trait-based system may not currently be appropriate. We see the risk that a move to a trait-based system may be counter-productive in the short term. We acknowledge, however, that trait-based regulation may be a valid long-term aim in order to develop a more scientifically robust, overarching regime once current regulatory barriers within 2001/18/EC have been addressed. Monitoring and surveillance of persisting GMOs
.Persistence is not currently accounted for within the directive 2001/18/EC. The Institute for Science, Innovation and Society at the University of Oxford highlighted that ‘future-proofing’ would be needed in light of the development of self-sustaining, persistent gene-drive techniques: “These ‘second generation’ varieties will present a radical challenge to existing regulatory frameworks. For one, they will likely require forms of pre-release testing and post-release monitoring yet to be developed.”
.Mechanisms will be required in order to allow for effective post-release monitoring and tracking of new genetic material promoted via gene drives, and designed to persist in the environment, particularly as these may not be included within 2001/18/EC. This could include means to implement both ecological monitoring and GM screening. The Institute for Science, Innovation and Society continued: “We need better tools for the monitoring of GM insects in the environment, and the development of these tools needs to be addressed in a public and straightforward manner by the relevant scientific and regulatory institutions.” We are persuaded by these arguments.
The ecological impact of GMOs designed to persist in the environment presents a new regulatory challenge. In light of the advances in gene-drive research, we conclude that underpinning research is required in order to allow effective monitoring and tracking of this new generation of genetic modifications. The regulatory framework should take persistence into account and stipulate appropriate monitoring requirements. Consideration of benefits and evaluation alongside alternatives
We heard a number of times that taking into account the benefits of a technology could be a desirable addition to the current regulatory process. ACRE has given thought to how this could work within the existing framework. Professor Rosemary Hails explained to us that: “For example, in the whole risk assessment process, the very last question is to characterise the overall risk of a GM organism. Additional information could be provided on context under that question and that context could include benefits also. The reason why that does not happen routinely is the questions leading up to that final question do not put in the building blocks for benefits in the same way as they do for risks.”
Although any rational approach to deciding whether or not to pursue a given technology would include an assessment of its net benefits, the key element must first be sound scientific risk assessment. Professor John Mumford stated: “the risk assessment stage should be independent of values such as benefits. Those may enter at a later stage at the risk management stage, where a decision is made, but not at the assessment stage. Assessment should be objective and management should focus on performance and benefits.”
We heard different views on how benefits might be considered. Benefits and risk are often considered as opposites. However, Sir Roland Jackson, Executive Chair, Sciencewise, questioned this linkage and stressed that benefit is not the opposite of risk. He urged that benefits and dis-benefits be considered alongside each other. Risks and dis-benefits must not be conflated. He provided us with the following clarification: “Questions of benefits encompass a much wider range of issues than the question of science-defined risk. If you are to have a system that looks at benefits as well as risk, you have to look at wider dis-benefits—things like impacts on employment, ways of farming or landscapes, which are not dealt with in a risk assessment.”
Benefits must be considered at an appropriate stage of the regulatory process and not confused with scientific risk assessment. We consider that benefits and dis-benefits should be considered after the process of scientific risk assessment has taken place, at the risk management stage.
As well as confusion surrounding benefits and dis-benefits, more clarity is needed in considering hazard, exposure, risk, and vulnerability. In the Government Chief Scientific Advisor’s 2014 annual report Innovation: managing risk, not avoiding it, Sir Mark Walport argued that it is vital that these terms are understood.
Hazard is frequently equated or confused with risk, and this leads to poor debate, confused communication and flawed decision-making.
.Professor Austin Burt highlighted the potential perversity in not including consideration of the benefits of a GM insect strategy. He stated: “I would not go to a Government in sub-Saharan Africa with this idea of a genetically modified mosquito and not talk about malaria. That does not make sense.”
Professor Luke Alphey reiterated this view: “If you are not talking about the benefits and the reasons why you are doing it, how will you persuade anybody it is worth doing? At that level it does not make any sense.”
The Government do not think that considering benefits should be pursued, despite appreciating the logic behind these arguments. George Eustice MP suggested that such a move would be unlikely to make a significant change in ameliorating the current major problems at the EU level: “My argument would be if the problem is a political barrier and an overly cautious political culture, to say that we are just going to balance the risk against benefits does not do much to reassure that problem.”
Dr Ladislav Miko, Deputy Director-General in the DG for Health and Food Safety at the European Commission, corroborated this perspective: “In my view, all the experience we have shows that the position of member states which are not supporting the GMs will not be dramatically changed by any socio-economic analysis.”
Benefits were not the only additional consideration that we were told ought to be incorporated into the regulatory regime. As previously highlighted, in the current regime GMOs are effectively considered against an idealised, risk-free alternative. Obviously such an alternative does not exist. Furthermore, for many GM insect technologies, the alternative presents a number of risks and problems. In many cases, this is the imperative behind the development of the GM insect technology in the first place. A clear example is insecticides.
The Institute for Science, Innovation and Society called for evaluation of GM insects alongside alternative approaches to the problem in question. They stated that: “Application of genetic methods of insect control should be evaluated alongside alternative courses of action.” While the existing plausible pathways to harm requirements go some way towards acknowledging this, we perceive it to be vital that, on a case-by-case basis, appropriate comparators are used.
We consider the argument for including the benefits of a technology within the regulatory process to be entirely valid. Furthermore, we do not agree with the stance of the Government and the European Commission that there would be little to gain in modifying the current framework to include consideration of benefits. We recommend that consideration of benefits and dis-benefits be incorporated into the regulatory regime once the scientific risk assessment has taken place, during the risk management stage.
Furthermore it is inappropriate that new GMO technologies are considered in relation to an unrealistic, risk-free alternative. We recommend that the regulatory process should acknowledge control methods currently in use, such as insecticides, which a new technology may replace.
It is clear to us that the regulatory regime is failing as it is currently applied to GM crops. Furthermore, we envisage that these failings would likely affect GM insect applications. Views on how the regime could be improved are numerous. Action, as we recommended earlier in this chapter, needs to be taken to try and improve the current system, but this is only sufficient as a first step.
We are concerned that a situation has arisen whereby applications are not received due to concerns over the regulatory framework, yet the regulatory framework cannot be tested nor improved until such an application materialises. There are concerns that GM insect applications would likely be subjected to the considerable delays experienced by crop applications. The Minister, George Eustice MP, described such applications to us as being “stuck in limboland.”
Action needs to be taken to try and breathe new life into this policy area and provide some momentum and a focus for activity. It is with this in mind that we think the Government should initiate an insect trial akin to the Farm Scale Evaluations of new GM crop technologies. In our view, this would represent a positive means of trying to break the regulatory deadlock.