In a case with wide-reaching implications for the European Union’s (EU) regulation of products developed using CRISPR/Cas9 and other targeted genome-editing techniques, the European Court of Justice (ECJ) released an advisory opinion by an Advocate General last month suggesting that products developed using new mutagenesis techniques should be exempt from risk assessment and other requirements applicable to genetically modified organisms (GMOs). Subsequent adoption of the Advocate General’s conclusions by the ECJ would mean that products developed using directed nuclease mutagenesis methods such as CRISPR/Cas9, TALEN, and zinc-finger nucleases will not be subject to regulation as GMOs under the EU’s 2001 GMO Directive (2001/18/EC).
The case (C-528/16) asks the ECJ to consider whether organisms developed using novel, directed mutagenesis techniques that involve genetic engineering processes are eligible for the long-established exemption for GMOs developed using mutagenesis techniques under EU law. According to the Advocate General, although organisms developed using mutagenesis are “GMOs” within the meaning of the GMO Directive, as long as the associated mutagenesis processes do not involve the use of recombinant nucleic acid molecules or other GMOs, those organisms are exempt from the GMO Directive’s requirements. The Advocate General’s opinion is not binding but will be considered by the ECJ in crafting its decision, which is anticipated later this year.
In 2015, a French agricultural union argued in national court that the mutagenesis exemption should apply only to conventional techniques in routine use at the time of the GMO Directive’s adoption in 2001, and therefore products such as herbicide-resistant seeds developed with newer, targeted mutagenesis techniques are not eligible for the GMO Directive’s exemption. In 2016, the court referred a series of questions related to this case to the ECJ.
As explained by the Advocate General, mutagenesis involves an alteration of a living organism’s genome, but it does not entail the insertion of foreign DNA into the organism. When the GMO Directive was adopted in 2001, conventional mutagenesis techniques involving in vivo application to entire plants had already been in use for decades to produce random genetic mutations. More recently, however, new mutagenesis techniques such as in vitro application to plant cells, as well as targeted mutagenesis techniques that apply new genetic engineering techniques (including oligonucleotide-directed mutagenesis and directed nuclease mutagenesis like CRISPR/Cas9), have allowed developers to target precise mutations within a gene.
In his opinion, the Advocate General emphasized the need for courts to interpret the GMO Directive’s provisions dynamically. In rejecting the argument that the mutagenesis exemption should be interpreted “in light of the factual circumstances that existed in 2001,” the Advocate General closely evaluated the GMO Directive’s text and legislative history and intent, while cautioning that placing additional limits on the mutagenesis exemption would improperly require the Court to rewrite the underlying legislative text. However, the Advocate General also recognized that the mutagenesis exemption only reflects the EU legislature’s intent not to regulate such products at the EU level, suggesting that individual Member States are not precluded from regulating mutagenesis techniques consistent with their own legal obligations.
Significantly, in the absence of a risk assessment or other scientifically verified evidence indicating that additional protective measures would be necessary, the Advocate General declined to apply the “precautionary principle” to concerns raised about the potential safety of new mutagenesis techniques. Noting that “[a] fear of a risk, or risk of a risk, is not enough,” the Advocate General stated that the precautionary principle should be applied only when concrete risks to human health or the environment have been identified and are supported by a “minimum amount of serious and independent scientific research.”