What if a new method of genetic engineering could eliminate life-threatening diseases like malaria? What if we could increase crop yields and combat world hunger with the help of this new method? But what if the same technique could also be used as a weapon of mass destruction? 

This new method of genetic engineering, known as gene drives, is being increasingly discussed not only in the genetics research community, but also in the political and legal realm. It may even be the most dangerous genetic engineering method that has been developed to date. In short, gene drives are genetic elements that change the inheritance pattern of a trait. The primary aim of the gene drive technology is to use special mechanisms to ensure that a trait is passed on to as many of an organism's offspring as possible. Gene drives are being considered as a new approach to address several intractable global problems, including controlling disease transmission (e.g. malaria), pests and invasive species, reducing crop loss, and preserving biodiversity. But they also raise many environmental, safety, social, ethical, political and economic questions and present enormous challenges, particularly for legislators. 

Inheritance of up to 100 percent of genetic material possible 

Gene drives are genetic elements that are inserted into the genetic material of an organism at a specific location to modify a genetic trait. A special mechanism ensures that the inheritance rate of a modified trait is increased in sexually reproducing organisms, thereby accelerating its spread. The genetic trait modified in the laboratory is thus given a kind of ‘turbo’ that ensures that it is more likely to be passed on to the offspring than in nature. In natural reproduction, the offspring inherit approximately 50% of a genetic trait. Gene drive technology bypasses conventional rules of inheritance, allowing up to 100% inheritance of that genetic trait. This means all individuals will have a desired genetic trait after a few generations. Another breakthrough in the field of genetic engineering has been the discovery of the CRISPR/Cas9 gene scissors, which can also be used in the field of gene drives.

However, gene drives are currently still in the development stage and practical applications are limited to insects and laboratory experiments. Nevertheless, the potential applications of gene drives are very diverse, and great hopes are being pinned on this technology. There is hope that gene drives could be used to combat deadly diseases such as malaria, yellow fever, and dengue fever. With an integrated gene drive construct, disease-carrying mosquitoes could be deprived of their ability to transmit certain pathogens, such as malaria, and their population could be reduced or even eradicated. In agriculture and nature conservation, gene drives could also be used to control invasive species.

Gene drives are subject to strict international regulations

Gene drive organisms contain at least one foreign gene and are therefore considered to be genetically modified organisms (GMOs). As such, they are subject to national and international gene-editing legislation. At the international level, the European requirements for gene drives are complemented by the requirements of the Convention on Biological Diversity (CBD), the Cartagena Protocol on Biosafety, and the Nagoya Protocol on Access and Benefit Sharing (ABS).

Overall, the EU gene-editing legislation is rather strict. In the EU, Directive 2009/41/EC on the contained use of genetically modified micro-organisms and Directive 2001/18/EC on the deliberate release into the environment of GMO (the ‘Release Directive’) form the basis of the European gene-editing legislation. While the Directive on the contained use regulates the use of GMOs in genetic engineering facilities, such as laboratories, and applies to the development of GMOs in enclosed spaces, the Release Directive regulates the use of GMOs outside enclosed systems in the context of a deliberate release. Deliberate release refers to the intentional introduction of a GMO into the environment. The key element of the Release Directive is the step-by-step approach. This stipulates that a GMO must be tested step-by-step, first in an enclosed system, for example in a laboratory, and proven to be safe. In a second step, the GMO is released like in a field study, which is carried out for a certain period at a specific location. If a GMO proves to be safe in the first two steps, it can be approved for commercial use in the third step. 

While decisions on the release of GMOs in field studies are taken at national level, i.e. in Germany in accordance with the German Genetic Engineering Act, decisions on the commercialized approval take place at European level. However, the release of GMOs in the second step is only approved if an accompanying risk assessment shows that the risks of the release can be classified as negligible. This risk assessment records, analyzes, weighs, and evaluates the uncertainties and risks associated with gene drives.

Legal barriers complicate the assessment of potential risks

The main regulatory challenge related to gene drives concern the risk assessment of the deliberate release. To date, there are no uniform standards or tangible criteria for such a risk assessment at European or international level. This is largely due to the actual risks posed by releasing a gene drive. Once released into the wild, gene drive organisms can spread uncontrollably in the environment. This could lead to considerable consequences for the safety of the environment, such as irreversible damage to an entire ecosystem. In addition, resistance to a gene drive could develop over time, resulting in the failure of the gene drive to achieve its intended goal. There is also a constant risk that a gene drive system could be misused to transmit deadly bacterial toxins to humans or to target crops.

As ecosystems do not respect national borders, releasing gene drives could lead to unavoidable border crossings of GMOs, which could lead to unpredictable political or diplomatic conflicts, as the countries involved may have different standards for dealing with GMOs and the consequences of their release. The fact that gene drives are being developed and researched in countries other than those in which they will be released raises the issue of how to ensure fair access to this new technology and how to share the benefits and risks of gene drives between the countries developing gene drives and those affected by their impacts.

Gene drive opponents are also concerned about potential ethical issues, as gene drives raise the question of whether the irreversible genetic modification of wild and protected species is permissible under nature conservation law, and whether the use of genetic engineering in nature contradicts the goals of nature conservation.

Overall, there are currently several legal and practical hurdles that need to be assessed as to the potential risks that may arise from the release of gene drives. 

What should be considered in the future regulation of gene drives?

To date, gene drives have not been released due to the considerable risks and uncertainties involved. Comprehensive regulation of gene drives including uniform standards for risk assessment is essential to evaluate the potential risks. There is a strict European legal framework for GMOs, but it needs to be adapted to the specificities and risks of gene drives. 

Therefore, there is a need for internationally applicable guidelines with standards for a case-by-case risk assessment, particularly in the context of releasing gene drives. Before using gene drive organisms, consideration should be given to whether other measures to control certain disease vectors, pests, or invasive species pose fewer risks. Defining specific protection objectives and identifying potential adverse impacts on these protection objectives should also be considered in future legislation. Legislation should also provide for requirements for a comprehensive monitoring plan for the release of gene drive organisms to identify, monitor and, if necessary, intervene in the potential environmental impacts. 

At the same time, it should be ensured that establishing new regulatory requirements for gene drive organisms does not lead to an ‘overregulation’, which could hinder the development of new technologies and jeopardize their benefits for society. 

Beneficial use of gene drives requires controlled use 

A first step towards an international regulation of gene drives was agreed at the negotiations on the Convention on Biological Diversity (COP15) in December 2022. At the conference, an Ad Hoc Technical Expert Group on Synthetic Biology was established to support the process for horizon scanning, monitoring and technology assessment of synthetic biology. In parallel, an Ad Hoc Technical Expert Group (AHTEG) on Risk Assessment was established at the tenth meeting of the Conference of the Parties to the Cartagena Protocol on Biosafety to develop guidelines for the risk assessment and management of gene drive organisms. These ad hoc expert groups could help advance international regulation of gene drive organisms and their release. In support of the work of these expert groups, governments, their institutions, local communities, and civil society organizations can submit information for consideration by the expert groups. 

It remains to be seen whether the first results of the expert groups can already be assessed at the next Conference of the Parties to the Convention on Biological Diversity (COP16) in October/November 2024 and whether the benefits of gene drive can be appropriately exploited in the future through controlled use.