Gene-Editing Mosquitoes at The European Youth Event 2018

By Jonathan Pugh

 

The below is a slightly extended version of my two 5min presentations at the European Youth Event 2018, at the European Parliament in Strasbourg. I was asked to present on the following questions:

 

  1. What are the ethical issues surrounding gene-editing, particularly with respect to eradicating mosquitoes?

 

  1. Should the EU legislate on gene-editing mosquitoes?

 

 

What are the ethical issues surrounding gene-editing, particularly with respect to eradicating mosquitoes?

 

We humans have been grappling with moral questions regarding genetic modification for many years now. However, the rise of the CRISPR/cAS9 gene-editing system has brought these questions back into the public sphere with a vengeance. The reason for this is that the CRISPR system is more precise, easier to use, and cheaper than preceding methods of genetic modification. It has hugely enhanced our ability to exert control over the genomes of various different organisms.

Naturally, there has been a great deal of interest in the potential for editing the human genome, particularly following the publication of the first study successfully changing DNA sequences in human embryos. This study has prompted ethical reflection on the sorts of influence that we should be able to exert over future generations. Could it be permissible to use gene-editing to cure serious genetic diseases like Huntingdon’s Disease and cystic fibrosis? Could it also be permissible to use the technology to change non-disease traits, like eye-colour, looks, or even intelligence? Could such a technology be used without violating fundamental moral principles of justice and equality?

These are undoubtedly profound questions. However, they are perhaps not the most pressing ethical questions that gene-editing raises. One reason for this is that the technology cannot yet be used to reliably and safely target the genes we want to target in human embryos without significant risks of off-target mutation. As such, clinical uses are still a very long way off. In contrast, studies have suggested that gene-editing can, and is already being used in other ways that raise a different set of ethical questions that are no less profound.

For one example, consider the use of gene-editing in the fight against mosquito-borne diseases. Such diseases represent a significant global disease burden; according to WHO, there were 214 million cases of malaria in 2015, resulting in 438 000 deaths. Using pre-CRISPR techniques of genetic modification, scientists in the EU have already edited genes in the Aedes aegypti species of mosquito (responsible for spreading the Zika virus, Malaria and dengue amongst others) so that the offspring of the mosquito cannot reproduce. These gene-edited mosquitoes are already being field tested in South America, with the modification leading to significant reductions in the mosquito population in the local area, and human disease.

The CRISPR system opens up new opportunities for gene-editing strategies. It might be used to target other genes in other species. For example, some teams have explored the use of CRISPR to modify the Anopheles stephensi mosquito so that it becomes resistant to the plasmodium parasite that causes malaria in humans. More significantly, these researchers, and others investigating the use of CRISPR in this context, have harnessed the CRISPR system to develop gene drive systems for their genetic modifications. Such gene drive systems could potentially enable researchers to spread a chosen genetic mutation throughout an entire species, by stimulating preferential inheritance of the affected gene. As well as being deployed in the fight against vector borne diseases, gene drive systems might also be employed for environmental causes, such as suppressing the population of an invasive and destructive species.

This is not in the realm of science fiction; the technology is here, detailed in respected scientific journals. As such, it is hugely important to assess the ethical implications of how we should use this technology.

Some commentators have criticized the technology as being contrary to the principle of the sanctity of life, or by arguing that it amounts to ‘playing God’. In my research, I have suggested that these objections are problematic for a number of reasons, and that they obscure what is really at stake in this debate. One problem they both face is that both allegations could have similarly been made against our choice to eradicate the variola virus responsible for smallpox in the 1970s, through an extensive vaccination program. Yet this was one of modern medicine’s greatest triumphs.

The real ethical questions that the prospect of gene-editing mosquitoes raises are grounded by our scientific uncertainty about the technology; will the modification work? Would eradicating a species of mosquito adversely affect the ecosystem? Will the modification spread to other species? These are empirical questions about which there is significant debate, and we clearly need more data to answer them. However, these empirical questions must be the starting point for what is really the fundamental ethical question here, which is ‘How should we make decisions about whether or not to deploy a technology, when we have only a limited understanding of its potential risks and benefits? Who should decide? Do we have the right to deploy a technology that could plausibly change the global ecosystem, if others object to its use?

The easy answer here is to say that we should not take any risks, and that in the light of any uncertainty, we should simply maintain the status quo situation; perhaps it is better the devil you know. Of course, that is not the approach that we have taken with other sorts of novel technology, such as IVF and the internet. But more importantly, in this case the status quo is one in which many hundreds of thousands of people are dying from diseases that this new technology could potentially prevent. As such, we need have to have very strong moral reasons to maintain this situation. Rather than avoid the ethical questions by simply adverting to the possibility of risk, we have an obligation to engage in moral reasoning about how to weigh the relevant risks and benefits here, grounded in the best scientific evidence available to us.

 

Should the EU legislate on gene-editing mosquitoes?

 

There are two different questions here. The first is whether this technology is a legitimate target of EU legislation. The second is whether there is any existing EU legislation that already sufficiently regulates this technology. I shall discuss each question in turn.

It might be argued that this technology is not a legitimate target of EU regulation simply because mosquito-borne disease is not primarily a European problem; after all, there are comparatively few incidents of mosquito-borne diseases in Europe, and the technology is primarily intended for use in countries outside of the EU. However, I want to urge against this view for three reasons.

First, the prevalence of mosquito-borne disease might plausibly increase in Europe as the effects of climate change take hold. Second, native animal that could be targeted with gene drives might become vectors for new pandemics; indeed the most devastating pandemic in European history, the great plague of 1347-1351, was caused by a bacterium that was carried to Europe by fleas on the backs of rats. With this in mind, it is notable that scientists have now developed a population suppressant gene drive that works in rodents. Further research in this area might allow us to develop gene drives in the future that could limit the spread of future pandemics.

Finally, much of the research into the genetic modification of disease vectors is being carried out in the EU, whilst field trials of the products of this research are being performed in other parts of the world. If the EU stands to benefit from this research, it also has a moral responsibility to make sure this research is being performed responsibly.

In fact, I suggest that gene-drive technology is in fact a paradigm example of a case in which there is a clear need to develop international agreement about a new technology. Mosquitoes do not respect national boundaries; accordingly, the consequences of nationally isolated decisions to employ gene drives would not simply be restricted to those nations. We all have a stake in getting the answers right. By the same token, the EU should have a global outlook here, by making its decision on potential regulation of this technology in consultation with nations outside of the bloc. As a leader in the research for this technology, the EU has an opportunity to set an example of global moral leadership, by taking steps towards developing much-needed trans-national agreement on the specific regulation of gene-drive technologies.

So genetic modification and gene drives are a legitimate target of European legislation. Is any existing EU legislation that already sufficiently regulates this technology? The EU already has a directive concerning the release of genetically modified non-human organisms (GMOs) into the environment. This is an important piece of legislation, but I believe that there are at least two ways in which the existing directive needs to be modified in order to appropriately regulate disease vectors that might be modified using the CRISPR system and gene drives.

 

Too Lax? Community Consultation or Community Consent?

 

I believe that the existing directive is too lax in one important respect. Article 9 of the directive requires that member states shall consult the public prior to the deliberate release of GMOs and disseminate relevant information about the trial.

This sort of community consultation and information disclosure is of course important, and perhaps even sufficient for the experimental release of agricultural GMOs. However, there is a strong case for claiming that the public should have greater moral protection in field trials of gene drive systems mosquitoes. The reason for this is that such trials would include elements of both an environmental experiment and a public health clinical trial. After all, in order to assess the impact of the mosquitoes, it is likely that field trials will need to obtain public health data, and perhaps even data from individuals (for more on this, see David Resnik’s excellent discussions here and here)

In the case of public health trials though, there are far more stringent consent protections for communities, as evidenced in the clinical trials directive (and the clinical trials regulation that will succeed it) than mere consultation. Whilst the informed consent of every individual is often not possible for public health interventions, adequate regulation is this area should aim for democratic procedures that can capture broad community consent to the intervention, rather than consultation and information dissemination alone. Indeed, researchers themselves have been promoting this model of “responsive science”, which champions not only transparency, but gives affected people the final say on whether a trial goes ahead.

Accordingly, I recommend that the EU stipulate clear guidelines on the model of community consent required for permissible field trials of genetically modified disease vectors, and more broadly, how the GMO directive should be understood to interact with the clinical trials regulations in this context.

Of course, there are also broader challenges for democratic procedures in such trials. Following a 2015 revision to the initial directive, if an EU member state objects to the use of an approved GMO, other member states must establish ‘coexistence regulations’, to avoid cross-border GMO contamination. However, it is unclear how successful such co-existence measures can be in the case of genetically modified mosquitoes, particularly if a gene-drive is employed. Accordingly, rather than relying on a simple model of majority rule, the EU may have to reconsider how to navigate fundamental democratic issues in deciding whether to implement field trials that may put even abstaining states at unavoidable risk.

 

Too Restrictive? The Perils of Precaution

 

In other ways though, the GMO directive is overly restrictive.

Under the existing directive, GMOs are subject to a risk assessment performed by the European Food Safety Authority. One problem with this is that many of the risks and benefits of GM mosquitoes arguably go beyond the scope of the EFSA’s expertise. I recommend that the risk assessments of GMO mosquitoes should instead be performed by a collaborative body, consisting of members of both the EFSA and the European Centre for Disease Prevention and Control. Such a collaborative body is necessary to adequately assess the diverse risks and benefits at stake with gene-drive technology in epidemiology, public health and bio-diversity. Indeed, these bodies have already produced a collaborative publication on combatting vector-borne disease.

The more significant problem though is that under the existing directive, these risk assessments must be performed under the guidance of the precautionary principle. This principle places priority on the avoidance of risk, and places the burden of proof firmly on proponents of GMOs to prove that they are safe. Accordingly, risk assessments prioritise information pertaining to the potential risks posed by GMOs over information pertaining to their potential benefits.

The precautionary principle is often criticised amongst philosophers, because it plays into a number of cognitive biases that humans are prone to exhibit, including loss aversion and an assumption that nature is benign. More importantly though, the precautionary principle offers only limited help in making adequate risk assessments in this context. The reason for this is that if vector-borne disease becomes more prevalent, or we face new pandemics, then a decision to maintain the status quo is itself failing to take precautions against a very serious, and foreseeable risk. Furthermore, the principle may also put gene-drive research into a catch 22 regarding the principle’s burden of proof; the onus is on researchers to prove such organisms are safe before they can be released into the environment, but there will be some scope for doubt about the safety of the organisms until we conduct field tests by releasing the organisms into the environment.

Accordingly, my final recommendation is that the European Parliament should reconsider the role of the precautionary principle in the directive, and closely attend to the potential benefits, as well as the risks associated with different courses of action available. In this regard, I echo the spirit, if not the precise letter, or the House of Lords recommendation on genetically modified insects.

This is not to say that we should ignore the risks of the technology and carry out field tests regardless of the risks of gene-drive. Rather, given the high stakes involved, we should base our assessment on all of the available morally relevant information. This includes both information about the benefits and risks of the technology. It may be that such analysis leads to the conclusion that we should not deploy GM mosquitoes in the EU, depending on the decision principles we employ in weighing the relevant facts. Rather the point is that we have a moral responsibility to reach this conclusion on the basis of sound, scientifically grounded moral reasoning informed by all the morally relevant facts at our disposal.

 

Post –Script

 

I was invited to speak in a panel discussion alongside Louison Charmoillaux (a volunteer for Greenpeace Lyon) and Adrien Pasquier (PhD student, Telethon Institute of Genetics and Medicine [TIGEM]). The panel was moderated byJonathan Hendrickx, (Freelance journalist). You can find a video of the panel here (be sure to change the language settings to English to hear translations of the French speakers).

 

 

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