Since the 1960s, Genetically Modified Organisms (GMOs) have been developed through diverse scientific techniques and the EU has endeavoured to regulate their use and cultivation. While the EU has established a legal framework to ensure that genetically modified products obtained through modern biotechnology are safe, the regulatory status of organisms resulting from directed mutagenesis techniques, and in particular CRISPR/Cas9, is still unclear. This legal status is important - if products obtained by these methods fall outside Directive 2001/18, they are not subject to the obligations laid down in the Directive such as the case-by-case environmental risk assessment, traceability and labelling before entering into the EU market or being released into the environment.

The seed industry considers that plants resulting from these new breeding techniques cannot be considered as GMOs because no trace of such genetic modification is detectable in the end product and no foreign DNA is added to their genes by using some of these techniques. Their opponents, however, argue that it is another attempt by producers of new GMOs to escape EU regulation. In that regard, a French agricultural union joined by eight other associations initiated legal action against an article of the French Environmental Code which partly implements Directive 2001/18. They argued before the national court that herbicide tolerant varieties of rapeseed and sunflower resulting from directed mutagenesis could be seen as ‘hidden GMOs’ and should not be eligible for the exemption provided for in Directive 2001/18. Following these legal proceedings, the French Conseil d’Etat made a request for a preliminary ruling before the Court of Justice of the European Union (CJEU).

On 25 July 2018, the CJEU issued its decision in Case C-528/16, confirming that organisms developed by directed mutagenesis techniques are GMOs within the meaning of Directive 2001/18 and are regulated under it. Considered as a significant milestone in the interpretation of Directive 2001/18, this decision clarifies the scope of the Directive and more precisely, the ambit, the rationale and the effects of the exemption enshrined in Article 3 and its Annex IB (the mutagenesis exemption). With regard to the far-reaching consequences that could arise from the non-regulation of these organisms, and given that products issued from these techniques are close to commercialisation on the EU market, this blog aims to look more closely at the legal examination of the material scope of this exemption. For this purpose it will consider certain scientific explanations. Since ‘mutagenesis’ is the only term mentioned in the exemption, the question is whether this exemption encompasses all kinds of mutagenesis and even those which were unknown at the time of the adoption of the Directive? Or does it only encompass the mutagenesis techniques that were known in 2001 including the random mutagenesis technique?

In considering these questions, this blog will first explain the different mutagenesis techniques. Random mutagenesis enables only the change of one base pair in random sites by using chemical compounds or irradiation application. It is characterised by a rather limited efficiency since the probability to achieve the desired characteristic is very low. Directed mutagenesis techniques - developed after 2001 - allow the introduction of precise changes into the genome by adding, removing, changing or replacing DNA sequences or entire genes at specific locations into the genome. In addition, these new techniques allow selection of the genetic modifications introduced and, therefore, achieve an estimated probability of successful genetic changes of nearly 100% for each application. This is even more so with CRISPR/Cas9 which enables faster, cheaper and easier genetic modifications compared to random mutagenesis and even the directed mutagenesis techniques.

Organisms modified genetically by directed mutagenesis techniques are GMOs because they meet the conditions contained in Article 2 of Directive 2001/18. Indeed, since the directed mutagenesis techniques alter the genetic material of the genome ‘in a way that does not occur naturally by mating and/or recombination’, they are classified as GMOs.

I believe that organisms developed by directed mutagenesis techniques should not fall within the scope of the mutagenesis exemption notwithstanding the exemption expressly mentioned. Four arguments support this statement.

First, the directed mutagenesis techniques should be interpreted in the light of the conditions existing in 2001 when Directive 2001/18 was adopted. Since the random mutagenesis technique was the only technique known and used at the time of the adoption of the Directive, one could argue that the legislature aimed to exempt solely this technique in 2001. This position is upheld by the historical origin of the Directive. In fact, the aim of the legislature was to regulate the deliberate release of GMOs developed by a new technique that carried a higher risk compared to the one related to random mutagenesis. As regards directed mutagenesis techniques, it is exactly the same issue since those techniques carry a higher risk than the random mutagenesis technique. Therefore, any other technique and, a fortiori, the directed mutagenesis techniques that were unknown, or in any case not used in breeding techniques in the EU or worldwide in 2001, should not be exempted from the scope of the mutagenesis exemption.

Second, since Recital 17 of Directive 2001/18 mentions explicitly that it should not apply to organisms obtained through certain techniques of genetic modification ‘which have conventionally been used in a number of applications and have a long safety record’, organisms obtained by directed mutagenesis techniques should be regulated under Directive 2001/18. In addition, with regard to the difference of accuracy in the genetic changes, the economic and industrial potential that result from the ease, rapidity and lower cost of the directed mutagenesis techniques and the unexpected applications that these techniques enable today, the term ‘mutagenesis’ must be interpreted as exempting only organisms developed by random mutagenesis technique.

Third, the precautionary principle, which must be seen as one of the leading principles of Directive 2001/18, can be triggered as regards the scientific uncertainty concerning the impact of the directed mutagenesis techniques and the potential risks that may result to both the environment and human health. Indeed, looking at Article 1 in particular, it shows that both the drafting and the implementation of Directive 2001/18 must be carried out following a precautionary approach. As a result, it is doubtful that the EU legislature aimed not to apply the precautionary principle to mutagenesis that will be developed in the future, being aware that any new techniques of mutagenesis would fall within the scope of the exemption and, therefore, extend the scope of the exemption infinitely.

Fourth, while the Preamble of Directive 2001/18 indicates that the Directive is adopted on the basis of Article 114 of the Treaty on the Functioning of the European Union, it is clear that the intention of the legislature was to strengthen both human health and the environment protection by ensuring maximal harmonisation of the provisions of EU Member States on the deliberate release of GMOs into the environment. Besides, even Article 1 of Directive 2001/18 expressly states that a high level of environmental protection must be pursued in order to avoid different national legislations undermining the functioning of the internal market.

To conclude, since the legislature aims to ensure a high level of protection of human health and the environment, one could claim that all organisms obtained by directed mutagenesis techniques should be regulated under Directive 2001/18. Consequently, they should be subject to the obligations laid down in the Directive, namely the case-by-case environmental risk assessment, traceability and mandatory food labelling before entering the EU market or being released into the environment. Otherwise, the absence of regulation concerning these organisms could generate significant risks both for human health and the environment. This could lead to the legal circumvention of Directive 2001/18 and the emergence of non-tariff barriers to trade. It could furthermore undermine the confidence of European consumers who will be unable to know how their food is produced, even though they massively reject genetically modified products.