In this two-part article, we delve into the complexities of gene editing in plants and the ongoing EU legislative debates, followed by an exploration of gene drives and their regulatory challenges. Part 1 examines the legal status of gene-edited plants under EU law and the European Commission’s recent proposal for a new regulation, while Part 2 focuses on the broader implications of gene drives, highlighting both national and international legislative frameworks and future regulatory considerations.

Part 1: Gene editing use in plants

Some 9,000 to 11,000 years ago, humans began to cultivate plants, selecting those with desirable characteristics and using their seeds for future harvests. Today, so called New Genomic Techniques (NGTs), a term used to describe innovative gene editing techniques developed within the last two decades, are increasingly recognized as a scientific silver bullet with the potential to ensure food security in a changing global climate and to contribute to a more sustainable agricultural economy. 

Gene editing in plants can be utilised in various ways to achieve diverse outcomes, such as increasing yields, enhancing nutritional value (e.g., boosting vitamin content or eliminating allergens), improving resistance to extreme weather conditions, and reducing the need for pesticides and fungicides. Outside of Europe, several NGT products are already available or in the process of becoming available on the market. In the Philippines, for example, they have bananas that do not brown – combating food waste and CO2 emissions.

Conventional plant breeding techniques would typically involve crossing plants with specific characteristics and selecting the offspring with the favoured traits over the course of several generations. Although successful results can be achieved using conventional methods, the major disadvantage of conventional breeding is the high time requirement (the time taken to develop a new plant variety to reach market can often exceed ten years). NGTs on the other hand promise faster, cheaper, more precise and more predictable results. 

How does gene editing work, and what scientific principles make it possible? 

In short, gene editing techniques such as the genetic scissors known as CRISPR are methods for creating targeted mutations (mutagenesis) that can fundamentally alter an organism’s genetic make-up. By cutting DNA at specific locations and adding, removing or rearranging the genetic material, it’s possible to create very precise changes of the genetic code. Unlike Genetically Modified Organisms (GMOs) created through transgenesis, NGTs work without the introduction of exogenous DNA or RNA sequences (meaning no foreign genetic material from different non-crossable species is introduced into an organism’s genome). Instead, they work with the existing genes of the organism, its species or naturally compatible plants and thereby – in theory – some of the produced changes might also occur in nature or through conventional breeding. For more information on the science behind CRISPR and other gene editing tools, please refer to the opening article of our genomics series “From crisp packets to CRISPR, and beyond” by Rebecca Lawrence.

The current EU legal framework – an outdated set of rules?

NGT products are currently subject to the same regulatory standards as GMOs under the current EU gene editing legislation – one of the strictest in the world.

EU Directive 2001/18/EC on the deliberate release of GMOs into the environment (the “Release Directive”) has been in force since 2001 and the fundamental structure and objectives have changed little since then. Based on the precautionary principle, its primary objective is to protect human and animal health and the environment. Strict procedures are in place for the safety and risk assessments and the authorization of GMOs before they can be placed on the market, involving the EU Commission and the European Food Safety Authority (EFSA). Additionally, the legislation requires labelling and traceability, enabling consumers and professionals to make an informed choice. Individual EU Member States also have the right to exclude GMOs from their markets even if they are approved at the EU level. Member states can restrict or prohibit the cultivation of GMOs on their territory based on various grounds, including environmental and agricultural policy objectives, socio-economic impacts, and public policy reasons. Some critics argue that the requirements of the Release Directive are so stringent that they effectively act as a ban on GMOs. Currently, there is only one genetically modified crop, the insect-resistant GM maize MON810, that is commercially cultivated in the EU. This rather strict regulatory framework reflects the EU’s cautious approach to GMOs. 

In 2018, the European Court of Justice (ECJ) has classified organisms obtained through new mutagenesis techniques such as CRISPR, as GMOs within the definition of the current Release Directive – making them subject to the same strict regulatory standards as GMOs “conventionally” achieved through transgenesis (ECJ Judgement in Case C-528/16). According to Art. 2 Sec. 2 of the Release Directive, a GMO is defined as "any organism, other than a human being, in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination", referring both to the characteristics of the resulting organism and to the techniques that were used to produce the organism. The ECJ clarified that, although organisms that have been genetically modified by mutagenesis are explicitly excluded from the scope of the Release Directive under Art. 3 Sec. 1 in conjunction with Annex I B, this exclusion does not apply to products obtained through new genomic technologies. The ECJ ruled that, in accordance with recital 17 of the Release Directive, the exemption shall be interpreted narrowly and only applied to certain genetic modification techniques that have conventionally been used in a number of applications and have a long safety record (e.g. conventional random mutagenesis). 

Considering the (in part highly criticized) ECJ ruling, the Commission published a study on the legal status of NGT products in April 2021, confirming that organisms developed through NGTs are indeed subject to the existing GMO legislation. At the same time, however, the study concluded that the current legislation does not adequately account for recent research and advances in genetic engineering and that it needs to be adapted to scientific and technological progress. The study also highlighted that applying the same standards for the variety of potential plant products obtained by NGTs may be disproportionate or inadequate in certain cases – suggesting that a more nuanced approach could be beneficial. This development led way to the ongoing process of a proposal for a new regulation. 

The European Commission’s proposal for a new regulation

In July 2023, the European Commission has published a proposal for a new regulation on plants produced by NGTs, that aims to create a balanced regulatory framework, facilitating innovation in plant breeding while protecting human and animal health, the environment and ensuring transparency. 

The proposal distinguishes between simpler modifications in plants which are comparable to conventional plants (NGT1) and other more complex combinations of mutations (NGT2), applying different regulatory requirements to reach the market, considering their different characteristics and risk profiles. NGT plant applications will be subject to a verification procedure, based on a defined list of science-based criteria (NGT1 criteria) covering the type and extent of genetic modifications that can be observed in nature or with conventional breeding techniques. The criteria for equivalence to conventional plants include, for example, the substitution or insertion of no more than 20 nucleotides. If the products meet the NGT1 criteria, they will be treated like conventional plants and therefore be exempted from the requirements of the GMO legislation. For NGT1 plants no risk assessment will have to be made, and they can be labelled in the same way as conventional plants. At the consumer level, information on NGT1 plants will be provided through the labelling of seeds, in a public database and through the relevant catalogues on plant varieties. Only in organic farming, NGT1 plants would remain banned. The Commission also intends to create a principle of free movement for NGT1 plants. Consequently, NGT1 plants will be excluded from the scope of the 'safeguard clauses' that individual EU Member States may adopt to prohibit the use of a GMO in their territories. 

NGT2 plants on the other hand will continue to be subject to existing GMO regulations and require a full risk assessment and labelling before being placed on the market. However, some regulatory incentives such as accelerated procedures will be offered to applicants for NGT2 plants which contain traits potentially contributing to a more sustainable agri-food system.

Deregulation: an essential step or an incalculable risk?

Rapporteur Jessica Polfjärd emphasized: “NGTs are crucial to strengthen Europe's food security and to green our agricultural production.”[1] But while there seems to be a broad consensus on the need for legislative reform to avoid hampering the potential of NGTs for the development of a sustainable agriculture, disagreement remains on how much deregulation is appropriate. This is all the more so given that, according to the German Federal Agency for Nature Conservation (BfN), an estimated 94% of NGT plant applications are expected to fall into the NGT1 category and would therefore be subject to very little regulation compared to the current Release Directive.

Environmental organizations as well as some Member States’ regulatory authorities have raised significant concerns about the potential risks of such deregulation of NGTs. They warn that even small changes of genetic information could lead to unpredictable effects on the organism and on the environment, for example on bees and other pollinators.  Critics such as the French Food Safety Agency (ANSES) or the German Federal Agency for Nature Conservation (BfN) have also expressed doubts about the scientific justification of the proposed NGT1 criteria. They argue that the number of genetic modifications alone would not allow conclusions to be drawn about the risk potential of these plants. Rather, they favour that the risks of NGT plants should be assessed on a case-by-case basis as part of an authorization process (as is currently the case). 

In response, the European Food Safety Authority (EFSA) has issued a contradictory scientific opinion, dismissing the concerns of the national authorities. EFSA and other proponents point to the precision and efficiency of gene editing and assert that if only small genetic changes are made and no foreign DNA is introduced, genome-edited plants should be considered equivalent to conventionally bred plants in terms of potential risks. Some prominent scientific organizations, such as the German Academy of Sciences Leopoldina and the Max Planck Institute for Plant Breeding Research, support this view, arguing that there is no scientific basis for different regulations for NGT plants because it is only the production method that is different, not the plant. 

To sum up: there is no doubt that gene editing remains a controversial issue in society, politics and law.

What is the current status regarding the European Commission’s proposal?

The European Parliament largely approved the European Commission’s proposal in February 2024 (the vote passed with 307 votes in favour, 263 against, and 41 abstentions). However, there is one significant amendment by the Parliament: banning patent protection for both NGT1 and NGT2 plants to avoid legal uncertainties, increased costs, and new dependencies for farmers and breeders. The Council on the other hand has not yet reached the required qualified majority. EU countries remain divided on a number of controversial issues. These include the patenting of NGTs, the proposed division of NGT plants into two categories and the labelling requirements for each. Several compromise proposals, e.g. from Spain and Belgium, also failed to secure a majority. 

For the proposal to enter into force, a decision must be adopted by all three EU institutions – the Parliament, the Council and the Commission – through a trialogue process. Interinstitutional negotiations have yet to start, possibly due to the legislative process occurring during a turbulent European election year, with a new EU Parliament elected in June and a new Commission in September. In July, Hungary also took over the Council presidency from Belgium. As a result, to the chagrin of some, and the delight of others, the proposal currently seems stuck in limbo, making it difficult to predict how negotiations will proceed, when the proposal will be enacted, and what its final form will be.

Part 2: Gene drives: Genetic engineering without risk?

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. 

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, as mentioned in part 1 of our article, 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, analyses, 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), taking place from 21^st of October until the 1^st of November 2024, and whether the benefits of gene drive can be appropriately exploited in the future through controlled use.

[1] EU Parliament press release: “New Genomic Techniques: MEPs back rules to support green transition of farmers”, 07-02-2024.