The Ethics of Genetically Modified Mosquitoes and Gene-Drive Technology

Written by Jonathan Pugh

This is an unedited version of a paper by Dr Pugh which was originally published on The Conversation:

please see here to read the original article

In a startling development in ‘gene-drive’ technology, a team of researchers at the University of California have succeeded in creating hundreds of genetically modified mosquitoes that are incapable of spreading the malaria parasite to humans, and which could potentially spread this trait rapidly throughout mosquito populations in the wild. This success has the potential to be translated into a huge global health benefit. Although global malarial deaths have been in decline over the past decade or so, WHO estimates that malaria has been responsible for over 400’000 deaths this year alone. The Anopheles genus of mosquito acts as the vector for malaria, as infected Anopheles mosquitoes transmit Plasmodium parasites to humans via their bites, and it is these parasites that cause malaria.

It is possible to cure malaria (often through artemisinin-based combination therapy) if it is diagnosed early enough. Moreover, there are preventative measures that can be used to limit the spread of the disease, such as insecticide-treated mosquito nets and indoor residual spreading. However, not all such treatments and preventative measures are readily available, particularly in the sub-Saharan African countries where malaria is most prevalent, and opportunities for early diagnosis and treatment are often missed. As such, although the development of treatments and more powerful preventative measures have both played a large part in the decline in global malaria deaths, the fact remains that nearly half of the world’s population remains at risk of contracting this potentially fatal disease. By preventing the transmission of malaria, we would be saving hundreds of thousands of lives a year.

Gene-drive technology amounts to creating genetically modified organisms to stimulate the biased inheritance of certain genes throughout the entire population of that type of organism. The idea of using ‘gene-drive’ technology to combat the vectors of malaria is not new. Last year, a team at Imperial College London reported that they had successfully genetically modified Anopheles gambiae mosquitos to produce 95% male offspring, a reproductive tendency that was inherited by the modified mosquitoes’ offspring. Since only females of the species bite humans (and thereby transmit the Plasmodium parasite), it was hoped that this modification would have some limited short-term effect in reducing malaria transmission. More importantly though, the long-term effect of the modification would be the eradication of this species of mosquito.

The Californian team have reported the success of a different kind of genetic modification of Anopheles stephensi mosquitoes. Rather than modifying the species to alter the sex of the mosquitoes’ offspring, the Californian team modified the mosquitoes to carry genes for antibodies that target the Plasmodium parasite that causes malaria, and which mosquitoes transmit to humans in their bite. The results of early tests are highly promising. In the laboratory, the anti-malarial gene was inherited by 99.5% of the modified mosquitoes’ offspring. The hope is that mosquitoes modified in this way would breed with non-modified mosquitoes in the wild and pass the anti-malarial genes on to their offspring. Ideally, this would eventually lead to all members of the future generations being resistant to the malaria parasite.

For those who believe that there is something morally problematic about eradicating an entire species of mosquito, the Californian team’s gene-drive strategy is morally preferable to the Imperial team’s strategy. The former strategy does not aim to eradicate the Anopheles stephensi, but rather to prevent them from carrying the malaria-causing parasites. However, this is an important difference even for those who don’t believe that mosquitoes have no moral status. A number of scientists have raised concerns about hybridization between closely related animal species, and that in the case of gene-drive technology this could lead to a modified gene ‘hopping’ to an unintended species. In the case of gene-drive aimed at species eradication, this could lead to the unintended extinction of the ‘wrong’ species. In contrast, the possibility of such ‘gene-hopping’ in anti-malarial genes could be useful for malaria control, since a modified gene in one parasite-carrying mosquito species could spread it to the other seven that carry the Plasmodium parasite.

Yet, the recent announcement has been met with a degree of moral concern. In part, this is perhaps due to the use of the same Crispr-Cas9 gene-editing procedure that was controversially used to edit genes in human embryos this year. Naturally, many of the criticisms levelled against the use of Crispr-Cas9 to edit genes in human embryos are less readily applied to using the procedure to modify mosquitoes. For instance, one prominent objection to using Crispr-Cas9 in human embryos is that the procedure is unsafe and can lead to off-target mutations that would harm the embryo if it were brought to term. Whist this is a salient concern in the case of human embryos, it is less clear that we should be concerned that the procedure might harm an individual mosquito in so far as we believe that mosquitoes lack significant moral status.

However, many of the concerns raised in the context of using Crispr-Cas9 to edit genes in human embryos might plausibly be raised against the use of the same technology in mosquitoes. For example, a common objection is that to edit genes in either case amounts to ‘playing God’, to displaying the same sort of hubristic attitude of mastery over nature that Victor Frankenstein displayed in creating his monster in Mary Shelley’s famous novel. However, that the objection is commonly raised does not entail that it is persuasive. Indeed, the ‘playing God’ objection is familiar from the GM food debate. The standard response to the objection in this context is that humans have been selectively breeding both plants and animals for hundreds of years, and this can be viewed as an indirect form of genetic modification that we do not find morally problematic. Moreover, in seeking to find solutions to world hunger by genetically modifying crops, it is misguided to claim that we as a society are displaying the hubris of Frankenstein in seeking to develop this technology. Similarly, we might wonder whether our eradicating the variola virus responsible for smallpox through the development of vaccinations amounted to ‘playing God’ in a manner that displayed a morally deplorable form of hubris. Indeed, even if we this accusation could be weighed against us, would the moral wrong done in displaying such an attitude be sufficient to outweigh the moral value of the lives that could be saved by developing such technology? This hardly seems a compelling line of argument.

However, although the ‘playing God’ objection itself is unpersuasive, it does point towards a morally relevant consideration. Unlike the Gods, humans are not omniscient, and a pertinent worry in this context is that we might overlook the possibility of devastating unintended and unforeseen consequences of gene-editing technology. There are a number of such potential consequences that have been mooted. First, it might be claimed that releasing genetically modified organisms on the environment could potentially have dramatic effects on the ecosystem. There is, however, room for some degree of scepticism here. This objection was widely voiced against the Imperial team’s strategy of aiming to eradicate the Anopheles gambiae mosquito. However, although this criticism was widely voiced in media coverage, many scientists who research mosquito biology and ecology are sceptical that the eradication of mosquitoes would have particularly bad ecological consequences. In 2010, Nature ran a feature asking researchers in this area what would happen if mosquitoes were eradicated, and the following quote from the entomologist Joe Conlon of the American Mosquito Control Association in Jacksonville Florida captures a common thought amongst the featured researchers:

Mosquitoes don’t occupy an assailable niche in the environment. If we eradicated them tomorrow, the ecosystems where they are active will hiccup and then get on with life. Something better or worse would take over.

With regard to the recent development, if scientists doubt that the eradication of mosquitoes would have bad effects on the ecosystem then it is unclear why removing their capacity to transmit malaria would. This does not rule out the possibility of bad ecological effects; the scientific consensus on this issue might be wrong, or perhaps gene-drive technology might lead mosquitoes to develop other catastrophic capacities. Moreover, this possibility is made all the more worrisome by the irreversibility of the rapid changes evinced by gene-drive technology. However, we should bear in mind that in order to provide an adequate moral analysis of ‘worst case scenario’ consequence-based objections to novel technologies such as gene-drive technology, we should attend not only to the badness of the consequences, but also to the likelihood of their occurring.

Second, although gene-driven technology could be used to combat disease, it could also plausibly be developed into a bio-weapon if it fell into the wrong hands. Of course, gene-drive technology is not alone in being a so-called ‘dual-use’ scientific output that could be used for nefarious as well as honourable ends; for instance, similar concerns have been raised against the development of synthetic biology, and scientific findings pertaining to H5N1 flu transmission studies, amongst many others. However, the potential for a malign group to use gene-drive technology to develop bio-weapons raises a legitimate consequentialist concern.

Conversely, it might be argued that gene-drive technology might not even be effective in preventing transmission. For instance, it has not yet been established that a CRISPR-Cas9 gene-driven modification will be passed down over multiple generations; yet this would be required if the modification was to lead to the elimination of malaria as a global threat.

The prevalence of these consequentialist objections to gene-drive technology highlights the fact that we face a great deal of uncertainty when we consider the implementation of these technologies: Will the technology work or will it lead to unforeseen catastrophe? However, this does not mean that we must prohibit the future use of technologies, even for morally weighty goals. For one thing, it seems that we can take steps to minimize the risks of the sorts of bad consequences considered above, as well as increasing the likelihood that the technology will bring about its intended good effects. For instance, we should do the research that will enable us not only to increase the likelihood that releasing the modified mosquitoes will lead to the prevention of malaria, but also to develop as sophisticated models as possible to increase the reliability of our predictions about what else will happen if we were to release such organism into the wild. Similarly, that a scientific technology is ‘dual use’ does not alone entail that it should be prohibited. Rather the question that such technology raises is whether we can implement safeguards that are strong enough to minimize the risk of the output being used by malign groups to a morally acceptable degree. In the context of gene-drive technology, this is very much a hot debate, with some researchers arguing that precise information about generating gene-drives should be classified, whilst others argue that researchers should be transparent about such information.

With any novel technology, it seems that at some point we as a society must make a decision about whether or not to continue developing it to the point of use on the basis of a belief that the expected value doing so is greater than that of refraining from doing so. This is the same sort of leap that we have historically made in releasing GM crops into the ecosystem, in developing other dual-use scientific outputs, and deploying other novel technologies that could have had unintended and unforeseen consequences, such as IVF, and information technologies like the internet and mobile phones. Now is the time for cool, honest, rational reflection on the expected harms and benefits of gene-drive technology so that we can make an informed choice on this matter, rather than scaremongering claims about playing God and ‘Franken-mozzies’.

Yet we also need to think further into the future, and turn our attention to the moral questions that the successful use of this technology might raise. Suppose that in the future gene-drive technology is successfully developed, and that we could use it to rapidly and effectively prevent the transmission of malaria. Not only that, suppose further that gene-drive technology has also been successfully developed to combat other devastating diseases in both crops and humans. This, of course, is the dream scenario. However, whilst we should continue to pursue this dream, we should also not be blind to the effects that its realization will have. For instance, whilst we should of course celebrate the prevention of lethal diseases and famine, we must also begin to think about how we should make adequate preparations for implementing the infrastructure that will need to be in place in order to cope with the ensuing population increase that this will lead to, and doing so will require answering important moral questions about global distributive justice. To be clear, this is not an argument against developing gene-drive technologies; rather, it is to point out that their success is likely to raise new moral challenges. Given the potentially rapid effect of such technologies in eliminating diseases, it is incumbent upon us to consider these questions now, in addition to the ethical question raised by the deployment of gene-drive technology in itself, so that we are adequately prepared for the day when we can use the technology to rapidly bring about the end of devastating lethal diseases.