When uncertainty exists about the occurrence of potentially serious risks in innovative products, precaution must be applied. This is how the precautionary principle is put into practice. But what does the application of precaution mean for innovation? In this series of articles on the precautionary principle, we provide insight into what is involved in applying the precautionary principle. In this article, we look at the role of the precautionary principle in gene drive technology.
- Gene drive technology provides a way to rapidly, and permanently, genetically modify wild animals or plants.
- This technology may have the potential to solve major societal problems in the fields of ecology, health and agriculture. It also comes with new, uncertain and unfamiliar risks.
- Applying the precautionary principle in the development of gene drives is important. It can ensure that the interests of all stakeholders and future generations are taken into account.
Generally, it takes a long time for a genetic change in a plant or animal to spread through an entire population, because a gene is only inherited by half of the offspring. A gene drive increases the odds of inheriting a trait to nearly 100%. It is a genetic element that influences the probability of inheritance to its own advantage. In this way, the genetic characteristics of a population can change rapidly and permanently. A gene drive is a phenomenon that occurs in nature. The introduction of the cheap and fast genome modification technique CRISPR-cas9 has made it considerably easier to make synthetic gene drives.
Gene drive technology offers new and unprecedented possibilities to modify nature. Gene drive researchers and developers regard gene drives as the solution to pressing problems in the fields of public health, ecology and agriculture. Opponents, however, speak of an extinction technology, of which the development should be stopped. The possibilities and risks of a gene drive become apparent in one of its most cited applications: in the fight against malaria.
Gene drives can only be applied efficiently in organisms that reproduce sexually and have a short generation time. For example, mosquitoes (1 week) or mice (10 weeks). In this way, a genetic variation can spread quickly through a population. Humans or other animals with a long generation time are not suitable. It would take centuries for a gene to spread through the entire population. Additionally, viruses or bacteria cannot be modified with a gene drive because they do not reproduce sexually.
Several developers and researchers around the world are working on this technology. These include Target Malaria (sponsored by the Bill & Melinda Gates Foundation), DARPA (a research institute of the US Department of Defense), and international non-governmental organisations whose mission is nature and species conservation. Such as Island Conservation.
Applications of gene drives
By means of a gene drive, it may be possible to genetically modify mosquitoes so that they can no longer act as a host for the malaria parasite, thus preventing its transmission to humans. Another possibility that is researched is the creation of a drive that makes female mosquitoes infertile. The mosquito population responsible for transmitting the malaria parasite could then eventually die out. There is great benefit to be gained from the application of a gene drive. It could lead to the elimination of one of the most common infectious diseases that still claims many lives each year. On the other hand, the technology could potentially wipe out an entire species. There are large differences in how acceptable people find it to use a gene drive to achieve such a goal.
Other possible applications of gene drives are: the eradication of exotic species that pose a threat to local biodiversity, and increasing the resilience of animals or plant to climate change.
It is not certain whether using gene drives is the best method to tackle the aforementioned challenges. There are doubts among both scientists and critics about the technical feasibility of gene drives. Scientists question the ability of gene drives to overcome the complexity of our ecosystem. Amongst others, questions have arisen concerning the stability of modified organisms in the wild. In addition, there is much uncertainty about the dangers, risks and consequences of deploying a gene drive.
The effects of a gene drive are not easily confined to a particular country, as animals or plants can cross borders without hindrance. This creates an additional layer of complexity. It makes regulation and decision-making on the application of the technology difficult, and it could even lead to political conflicts. What if one country agrees to deploy a gene drive, but the neighbouring country does not? At this moment, it is not possible to keep modified organisms within a national boundary. There are several unresolved issues, including: who should be involved in deciding whether or not to use gene drives? In which cases should the technology be applied? And which interests should be taken into account, and to what extent?
In earlier articles we wrote that, in the case of uncertainty about serious risks of new technologies, precaution must be exercised. This is also important in the case of gene drives.
This article is based on one of the ten case studies in the RECIPES project. The purpose of these case studies is to gain more insight into the controversies and complexities involved in applying the precautionary principle to various innovations
The results of the RECIPES project will allow the EU to remain at the forefront of science by re-examining the precautionary principle in relation to innovation and major societal challenges. The project started in January 2019 and will last for three years, with an extension of six months. Eleven organisations from seven European countries are working together on the RECIPES project. The initiator of this consortium is the Faculty of Law at Maastricht University.
The risk of gene drives
The risks of gene drives depend on the animal or plant that is modified, the environment and the genetic alteration that is made. This makes it difficult to assess and estimate the risks. Roughly speaking there are risks in the fields of environment, health and regulation. Gene drives have the ability to spread independently through a wild animal or plant population, and to cause a lasting change. This is the greatest risk of the technology. It is also the reason why some see the technology as a game changer in genetic modification techniques.
One concern expressed by critics is that, despite good intentions, an irreversible change is made to the ecosystem while this technology is not yet fully understood. A worry is that the gene drive will mutate. This could then lead to a change in the DNA of the organism in other places as well. The consequences of this are unpredictable.
Another risk is that, if this technique is used to eradicate a (non-native) species in a specific location, there is a chance that the genetically modified species will spread around the world.. In doing so, other populations, and even entire species, could be wiped out. Currently, it is not possible to halt or reverse the negative effects of a gene drive. It is unknown what happens in the ecosystem when a species disappears. What species will take over that niche? And what impact will that have? If the malaria parasite is eradicated, will it be replaced by another, even more virulent parasite?
A final risk regarding genetic modification is the wide availability and accessibility of the CRISPR-Cas9 technique. When more known about how gene drives can be developed, the technique could be used for less beneficial applications. If the development and use of the technology cannot be controlled and regulated, the technique could be misused. Insects have been used for biological warfare in the past. Gene drive technology could be used by terrorists in a similar way to inflict great damage.
Application of gene drives may involve major risks. However, there is scientific uncertainty about the likelihood of these risks, which is caused by several factors.
Because gene drives are released into nature, they have an effect on various ecosystems. Not enough is known about ecosystems to properly determine what the consequences of altering or eradicating a species will be. This makes it difficult to determine the risks of using gene drives, and the chance of these risks occurring.
In addition, the complex interplay between the animal and its environment in nature cannot easily be replicated in a laboratory. The ecological, economic and social consequences are difficult to capture in predictive computer models. Moreover, it is difficult to make correct models because there is currently little data on (the consequences of) releasing a gene drive. This kind of data cannot be obtained without actually releasing a gene drive. And that brings with it the same uncertainties and risks mentioned earlier. It is also questionable whether more data will lead to better predictions at all. There are many variables that play a role, and it only takes one change in variables for the prediction to be different. The current COVID-19 pandemic, for example, demonstrates how a small (unforeseen) mutation can have major consequences.
Finally, researchers and other stakeholders that are involved interpret the risks of gene drives differently. There is disagreement about whether gene drives should be seen as synthetic biology (which we wrote about earlier in the report Leven maken). This has consequences for the way gene drives should be regulated. In addition, there are individual, cultural and religious differences in views on nature and to what extent humans are responsible for it. This creates different perspectives on the permissibility of gene drives. Someone who is convinced that humans should not intervene in nature and that the eradication of species is inadmissible under any circumstances, will find even the smallest possible risk of this occurring too great.
Applying the precautionary principle in gene drive research
How should we deal with precaution in relation to the development and application of gene drives? Researchers, policymakers and other parties involved do not disagree on whether precaution should be exercised. However, there are various ways in which those involved (wish to) implement the precautionary principle. For example, there are opponents of gene drives. These include the approximately 170 civil society organisations that, a few years ago, collectively called for a total ban (moratorium) on further development of the technology because they consider its dangers too great.
This strict interpretation of precaution is met with resistance from some researchers and stakeholders of the technology. They argue that it is unethical not to research gene drives, given their social promise. They advocate a broader interpretation of the precautionary principle. They propose a modified risk assessment, in which research into gene drives is allowed under certain conditions. Ultimately, the request for a moratorium at the UN Convention for Biodiversity in 2018 was not granted. However, it was decided that an extensive risk assessment is necessary, in which the risks for humans, animals and the environment are examined for each application.
The importance of further dialogue
Presently, the application of the precautionary principle has not led to a ban on the development of gene drives. Since the technology alters a shared environment, consequences of the deployment affect everyone. It is important that researchers, policymakers and representatives of society enter into dialogue, and discuss how the development of gene drives can be guided by values that are important to society. The precautionary principle can play a role in this, as we suggested in an earlier article. Its application can help to determine where the boundaries lie for the use of this technology. Who decides on those, and who bears the responsibility for the application of precautionary principle and the consequences of the technology? Are there alternatives to gene drives and how do they relate to this technology? Applying the precautionary principle can also help to take into account the interests of future generations. In this respect, it is important that the focus of applying precaution is not on the final assessment of the risks, but that the application of precaution is considered early on in the research process.
Gene drive researchers are already doing this to some extent. Recently, researchers from various disciplines published a document with rules they adhere to regarding safety measures for lab and field studies. The document also contains suggestions for regulation of the technology. Given that gene drives can have large-scale effects, it is important that the application of precaution is not left solely to the developers of the technology, but that the discussion about it is broadened.
Gene drives offer new and unprecedented opportunities to intervene in nature. An earlier case study for the RECIPES project demonstrated that it is important to discuss the desirability of a technology in parallel with its development. By applying the precautionary principle early on, it can steer innovation in the right direction. In this way, the principle does not become a barrier to technological progress. But it serves as a compass to steer innovation in the direction of society's interests and needs.