July 20, 2019, by Brigitte Nerlich

Inspecting Pandora’s box: Promises and perils of gene drives

This is a guest post by Aleksandra Stelmach, University of Nottingham, Institute for Science and Society.

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Some years ago the sociologist Alan Petersen noted that metaphors of new biotechnologies not only express hopes and fears about their use and misuse, but that they also set the agenda for debate and action. Thus, metaphors not only convey meanings, but also tell us what to hope for and what to be afraid of in the context of emerging biotechnologies.

I thought about Petersen’s article when I read the latest Nature news feature about gene drives. This piece, entitled ‘Hijacking evolution’, is all about hopes and fears related to this new genetic engineering technology (for a good video explanation see here). While, it is hoped, gene drives could soon be used to help control pests or insect-borne diseases such as malaria, the Nature article explores the fears, or the ‘unknowns’ of this new technology, especially its potentially negative unintended consequences. The article is well worth reading in full, but in what follows I will first highlight some key points, and then focus on metaphors and stories of risk that are used to communicate about gene drives.

Gene drives: what they do and what they’re for

So, what are the hopes and fears related to gene drives? They are laid bare already in the opening sentence of the Nature story: ‘Self-destructing mosquitoes and sterilized rodents: the promise of gene drives. Altering the genomes of entire animal populations could help to defeat disease and control pests, but researchers worry about the consequences of unleashing this new technology.’

It seems that both promises and perils of the new technology lie in how it works and what it attempts to achieve. The Nature article describes it by recounting the story of two scientists from Imperial College London who, in 2011, first engineered gene drives in mosquitoes. ‘Austin Burt and Andrea Crisanti had been trying for eight years to hijack the mosquito genome. They wanted to bypass natural selection and plug in a gene that would mushroom through the population faster than a mutation handed down by the usual process of inheritance. In the back of their minds was a way to prevent malaria by spreading a gene to knock out mosquito populations so that they cannot transmit the disease’.

Since then, the article explains, ‘Gene drives have rapidly become a routine technology in some laboratories; scientists can now whip up a drive in months. (…) scientists have engineered CRISPR-based gene-drive systems in mosquitoes, fruit flies and fungi, and are currently developing them in mice. But that’s just the beginning of the story. Questions about whether a gene drive is possible have been supplanted by other unknowns: how well they will work, how to test them and who should regulate the technology.’

The article suggests that technical challenges surrounding gene drives are less daunting than the social ones, as, according to Kevin Esvelt, a prominent gene drive expert from MIT, ‘Technologies like this have real-world consequences for people’s lives that can be nearly immediate’. So what are the main concerns about gene drives?

The challenge of mutations

The first issue revolves around the question whether gene drives will work as intended.  Since genes drive have been tested only in laboratories, and have not yet been released in the wild, it is not certain that they can be effective in helping control diseases and pests. According to Nature, ‘As soon as researchers began to make gene drives regularly in labs, animals developed resistance against them – accumulating mutations that prevented the drives from spreading’ in subsequent generations.

To avoid such a scenario, scientists are now trying to target genes that are resistant to mutations, for examples those linked to reproduction. So far the task has proved difficult in mammals, such as mice which could potentially be targeted with gene drive technology (see a previous post by Brigitte Nerlich on this topic). But last autumn the group led by Andrea Crisanti from Imperial College London succeeded in engineering a self-destruct mosquito by making a gene drive that disrupts its fertility gene called doublesex: ‘With the drive in place, female mosquitoes cannot bite and do not lay eggs; within 8–12 generations, the caged populations produced no eggs at all. And because it is crucial for procreation, doublesex is resistant to mutations, including those that would confer resistance to a drive construct.’

Back in the autumn this research was hailed by the media as a success and even dubbed as ‘giving malaria a deadline’. Crisanti, who is now working on improving the safety of this technology, is quoted in Nature as saying: ‘I want to make sure that the likelihood of developing resistance is very, very remote before saying the technology is ready for the field’.

The issue of control

The second question is about other potential applications of gene drives. They could be used, for example, to help conserve fragile ecosystems on islands by eliminating invasive rodents.

Researchers working on prevention of insect-borne diseases, such as dengue fever, are also trying to develop tools that are ‘more subtle than completely wiping out insect populations’. According to Nature, ‘Omar Akbari and his colleagues at UCSD engineered Aedes aegypti mosquitoes to express an antibody that protected the insects against all four major strains of dengue. They are now attaching that antibody to a drive to see whether it will spread. Akbari is also building an all-purpose gene drive that activates a toxin when any virus, not just dengue, infects A. aegypti. “We want to build a Trojan horse in the mosquito,” says Akbari. “When a mosquito is infected by a virus — whether it’s dengue, Zika, chikungunya, yellow fever, whatever — it activates our system, which kills the mosquito.”

Another major concern is whether gene drives can be controlled and how their potentially adverse effects could be mitigated. As Nature reports, scientists in the field are developing ‘gene drives with built-in controls, external overrides or both’. For example, Esvelt has built a ‘self-exhausting drive’ called, metaphorically, a daisy drive. ‘The drive is engineered to lose a link at a time, like plucking one flower from a chain linked head to stem, until it runs out over several generations’.

Even if these built-in controls are effective, it is not clear how the modified organisms would behave in the wild. The article quotes the biologist and bioethicist Natalie Kofler from the Editing Nature group at Yale University. Kofler warns that since gene drives could potentially change entire populations, they ‘could also, in theory, negatively affect human health by causing the malaria parasite to evolve to be more virulent or to be carried by another host’.

Governing the unknown

The complexities and concerns related to gene drive research mean that scientists will need more time to develop and trial this technology. There remains, of course, the issue of governance, and the Nature story asks: ‘Who decides when to use a gene drive?’

Fredros Okumu, director of science at the Ifakara Health Institute in Dar es Salaam in Tanzania, stresses that interested countries should be able to make such decisions themselves. Okumu argues that gene drive technology would be perceived as more trustworthy in Africa – the country which could benefit from applying gene drives to control the spread of malaria or dengue – if African researchers could develop it locally. Kofler, who, in the past, argued for a collective oversight of gene drives, thinks that historically marginalised groups should be involved in the decision-making process.

Interestingly, the focus of the Nature story seems to be on who should decide on when to use gene drives, rather than questioning whether this technology should be used at all. Reacting to this publication Matthew Cobb, a zoologist from Manchester University, tweeted: ‘Outlines the key issues, but why no reference to the need for **international** regulation, or highlighting the apparent lack of interest in this issue from leading scientific organisations?’ . Cobb advocates the need for a global regulatory framework of gene drives and has written about benefits and risks of this technology (see for example here).

Metaphors and stories

This brings me to the question: what are the risks related to gene drives and how are they conveyed through metaphors and stories? Although the Nature article offers only a snapshot of the ongoing debate, it may provide some initial ideas about the metaphorical and narrative framings at work.

Hijacking

Judging only by the title of the Nature feature, gene drives present considerable risks to the natural world. The article opens with the striking metaphor of ‘hijacking evolution’, and points to the dangers of messing with the genetic make-up of wild organisms, as ‘researchers worry about the consequences of unleashing this new technology’. The theme of fear of unintended consequences of emerging technologies has roots in the story of Pandora’s box, a well-rehearsed trope in the field of science studies and science communication. As the article explains, gene drives could ‘in theory, negatively affect human health by causing the malaria parasite to evolve to be more virulent or to be carried by another host’.

But as I read on, I found fewer framings of risks to environment, and – instead – more metaphors of risks posed by gene drives to the targeted organisms, such as mosquitoes or mice. For example, the metaphor of hijacking also refers to ‘hijacking the mosquito genome’, but here it has rather positive connotations, as it provides ‘a way to prevent malaria’.

Similar framings were previously used in gene drives debates, as the hijacking metaphor was deployed to highlight both advantages  and potentially negative consequences of this new technology. It seems then that the hijacking metaphor might not only evoke dangers, but also that hijacking evolution or mosquito genes might be considered a risk worth taking.

Engineering and control

Although gene drives rely on the gene-editing tool CRISPR, ‘editing’ metaphors associated with CRISPR don’t seem to dominate the Nature article. Instead, numerous engineering metaphors are used, well-known from synthetic biology: gene drives are made, built, engineered, developed, designed and devised. Scientists can ‘insert’ or ‘plug them in’, or even ‘’whip them up’ in a short space of time. Gene drives are also presented as a ‘routine technology’, with ‘built-in controls, external overrides or both’. Safety is being improved, as scientists are ‘studying how to control, counter and reverse gene drives’.

In addition, engineering metaphors convey the image of a rational technology (as discussed here by Victor de Lorenzo) that can be controlled and reversed. On the other hand, the gene drive technology promises control over nature, as it has been proposed as ‘a way to reduce or eliminate insect-borne diseases, control invasive species and even reverse insecticide resistance in pests’.

An overall impression is that the gene drive technology is being developed with safety and ethical issues in mind. This contrasts with earlier and more alarming media stories which drew attention to the unpredictability of this technology and highlighted ‘Sorcerer’s Apprentice’ lab fears’, referring to the worry that researchers will not be able to control the technology they have created.

War and destruction

When potential applications of gene drives are discussed, the language is reminiscent of ‘control of disease’ discourse permeated by war and plague metaphors. Such discourse was used in the past, for example in the context of ‘war on invasive species’ or ‘war on cancer’, and it relies heavily on aggressive, militaristic language. The tactics used in gene drive research are described with the help of metaphors of deception: there is talk of scientists ‘bypassing natural selection’, ‘hijacking genes’ and ‘building a Trojan horse in the mosquito’. The overall impression is that with the help of gene-drives it might be possible to wage guerrilla style warfare on pathogens.

The aim is to design gene drives that can ‘manipulate or eradicate’, ‘knock out’ or even ‘completely wipe out’ insect populations. While being used against disease and pest, gene drives behave like bioagents: they can ‘spread by themselves’, ‘radiate’ or ‘mushroom through the population’, metaphors that also evoke nuclear warfare. Their application results in ‘self-destructing mosquitoes and sterilized rodents’.

While these metaphors draw attention to risks posed by gene drives to mosquitoes and pests, they don’t highlight other risks and concerns that have been debated elsewhere (see here for example), namely that gene drives can be weaponised and used by unauthorised groups or individuals. This could even amount to what has been termed ‘entomological warfare’ in which gene drives are used to sabotage crops and spread diseases.

Another issue is whether war and destruction metaphors should be used more cautiously or even at all when talking about gene drives. The use of militaristic framing in biomedical discourses has significant drawbacks and has been criticised by social scientists (for example in the context of Zika, here and here), who pointed out that militaristic language and thinking put an excessive focus on the issue of gaining control, even at great cost, and make it easier to ‘sacrifice people and their rights’ in the pursuit of new cures and technologies. 

Messengers of risks

Coming back to Petersen and his article on risk metaphors, the Nature article nicely illustrates the point that metaphors, though powerful, are also partial. While they alert us to some risks and opportunities, they obscure other potential benefits and dangers of new technologies. This might include questions about how they can be misused, what kinds of risks they bring and to whom, which ethical issues are deemed important, and also who should be involved in governance and decision-making.

This means that in order to get a more nuanced understanding of the field and debates about risks, it’s important to analyse a plurality of different metaphors (see this article by Brendon Larson; and previous blog posts on gene drive metaphors here and here). It also means that it’s important to keep an eye on how metaphors behave in different contexts and how they change over time.

As Petersen notes, metaphors tend to evolve with the field and the changing scientific and political agendas. Given that gene drives are seen as the next big thing in science and society, there will surely be more metaphors to study.

Image: Creative Commons

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