Genome editing designates new methods that allow targeted interventions to be carried out in the genetic material, the genome of a cell (1). The CRISPR/Cas method (2) is a molecular biological method to specifically cut and modify DNA ("genome editing" or "gene scissors"). Genes can be inserted with the CRISPR/Cas9 method or used only remotely or switched off (3). This method was discovered in 2012, originally as a defence mechanism of bacteria against viruses. Soon, researchers around the world were using it to modify the DNA of a wide variety of organisms.
The CRISPR/Cas9 method works in protozoa, fungi, plants, animals and humans (4).
It provides a fast, cost-effective and easy-to-use system for making precise genetic changes. This has made it easier to investigate the function of genes. For example, CRISPR/Cas9 is used to modify model organisms in basic research, in cancer research or in research on infectious diseases (5). Especially in agriculture, this targeted mutation or alteration of crops plays a major role. The plants could be improved by this change in their genes, becoming more resistant to fungi, pests, drought and so on (6). These changes can also be triggered by classical breeding, e.g. using chemicals or irradiation. However, this method is unspecific and takes several generations. With CRISPR/Cas9 it is more precise, faster and cheaper (7).
The decisive question for the possible future commercial application of CRISPR plants in agriculture is whether they are legally regarded as genetically modified plants if only something has been removed from the genome (mutagenesis) and no transgene has been inserted (transgenesis). This is because genetically modified plants are very strictly regulated, especially in the EU (8). The ECJ answered this question in 2018.
Decision of the ECJ
Following a preliminary ruling procedure initiated by the French Council of State, the ECJ had to clarify whether the new breeding methods for plants (mutagenesis methods for producing herbicide-resistant plant varieties) are to be subsumed under the term "genetically modified organisms" within the meaning of Article 2(2) of the GMO Directive (9).
In its judgment of 25 July 2018 (10), the ECJ ruled that Article 2(2) of the Directive on GMOs is to be interpreted as meaning that organisms obtained by new targeted mutagenesis methods/procedures are "genetically modified organisms" (GMOs) within the meaning of this provision. Article 3(1) of the Directive on GMOs (the exception to the scope of the Directive on GMOs), in conjunction with Annex IB No 1 and recital 17, must be interpreted as meaning that only those organisms which have been traditionally used in a number of applications by mutagenesis processes/methods and which have long been regarded as safe (i.e. conventional) are excluded from the scope of the Directive on GMOs (11, 12).
The consequence of this judgment is that organisms which have not yet been produced with new mutagenesis processes/methods in a number of applications (such as the CRISPR method) are subject to the authorisation and labelling requirements of the GMO Directive.
The ECJ justified its decision by citing the protection of human health, the precautionary principle and the potential adverse effects on the agricultural market (in the sense of an uncontrolled spread across national borders with possibly irreversible effects) (13).
According to the Austrian Ministry of Social Affairs, which is responsible for the enforcement and further development of genetic engineering law in Austria, the ruling of the ECJ confirms the Austrian legal position, because according to Section 2 para 2 subpara 4 of the Genetic Engineering Act only the procedures of undirected (conventional) mutagenesis are excluded from the scope of the Austrian Genetic Engineering Act (14).
In Austria, the CRISPR/Cas9 method is used in basic research, particularly in the fields of molecular, cell and developmental biology, microbiology, biomedical research, population genomics research on model organisms and basic plant genome research (15). According to the Federal Ministry of Education, Science and Research, the decision of the ECJ has no direct consequences for Austria, because in Austria work with GMOs is only carried out in a closed system. There is therefore no release and no placing on the market of GMOs under the Austrian Genetic Engineering Act (16).
Nevertheless, as far as plant breeding is concerned, the ECJ ruling was praised by environmentalists. In science and industry in the field of plant breeding, however, this judgment is disappointing. From an objective point of view, the judgment means objectively baseless unequal treatment of biotechnological methods (17). This is because DNA can also be removed by "classical", albeit more time-consuming, methods of breeding such as radioactive radiation or using genetically modified chemicals. But these products are not classified as genetically modified organisms pursuant to the GMO Directive, because they have long been considered safe. Still, these classical methods are based on the random principle, which is not without risk, and this would not be the case with the targeted CRISPR method (18).
Other countries, such as the USA, Canada, Argentina, Brazil, Australia, Japan or Israel, take a case-by-case approach. The authorities check whether newly edited plants are to be regarded as normal breeding or fall under the respective genetic engineering regulations. In fact, it remains unclear how agricultural imports from such countries are to be kept "genome editing-free", because there is no way of proving whether the genetic modification was carried out by CRISPR/Cas (19).
(1) Ministry of Social Affairs, AQs on New Breeding Techniques and the ECJ Judgment of 6 August 2018 (3); (available at: www.sozialministerium.at/site/Gesundheit/Gentechnik/FAQs_zu_den_Neuen_Zuechtungstechniken_und_dem_EuGH_Urteil).
(2) Engl "Clustered Regularly Interspaced Short Palindromic Repeats" and "CRISPR-associated proteins 9" (see Ministry of Social Affairs, AQs on New Breeding Techniques and the ECJ Judgment 6 August 2018 (4)).
(6) Gärtner, EuGH aktuell: Neue Züchtungsformen der Gentechnik, IUR-Newsletter 4/2019.
(7) See Ministry of Social Affairs, AQs on New Breeding Techniques and the ECJ Judgment of 6 August 2018 (3).
(9) Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC.
(10) ECJ 25 July 2018, C-528/16.
(11) ECJ 25 July 2018, C-528/16, Rn 30, 38, 51, 77f, 86.
(12) The Union legislator has not made any provision for organisms excluded from the scope of the GMO Directive. The Member States are therefore empowered to adopt a legal regulation for them and to subject them (in compliance with Union law, in particular the rules on the free movement of goods laid down in Articles 34 to 35 TFEU), to the obligations provided for in the directive on GMOs or to other obligations (ECJ 25 July 2018, C-528/16, Rn 79).
(13) ECJ 25 July 2018, C-528/16, Rn 49.
(14) See Ministry of Social Affairs, AQs on New Breeding Techniques and the ECJ Judgment of 6 August 2018 (8)
(15) Query response by Dr Faßmann, Federal Minister for Education, Science and Research, 20 November 2018, on written question 1722/J by deputy Gamon, Msc, ad question 1 (available at: www.parlament.gv.at/PAKT/VHG/XXVI/AB/AB_01728/index.shtml).
(16) Query response by Dr Faßmann, Federal Minister for Education, Science and Research, 20 November 2018, on written question 1722/J by deputy Gamon, Msc, ad question 2.
(17) Reiter, Mit Mutagenese gewonnene Organismen sind GVO, RdU 2018/152 (209).
as well as: www.transgen.de/forschung/2564.crispr-genome-editing-pflanzen.html.
(19) www.transgen.de/forschung/2564.crispr-genome-editing-pflanzen.html; sowie: Gärtner, EuGH aktuell: Neue Züchtungsformen der Gentechnik, IUR-Newsletter 4/2019.