TYPE Original Research PUBLISHED 16 March 2023 DOI 10.3389/fpls.2023.1141455 Possible EU futures for OPEN ACCESS CRISPR-edited plants: Little EDITED BY Neil E. Hoffman, Animal and Plant Health Inspection Service margin for optimism? (USDA), United States REVIEWED BY Leire Escajedo San-Epifanio 1*, Igor Filibi 1, Ainhoa Lasa López 1, Johannes Rath, University of Vienna, Austria Pere Puigdomènech 2 and Javier Uncetabarrenechea Larrabe 1 Claus Krogh Madsen, Aarhus University, Denmark 1 Department of Public Law, Historical-Legal Sciences and History of Political Thought, University of the Basque Country, Bilbao, Spain, 2 Centre for Research in Agricultural Genomics - CRAG, *CORRESPONDENCE Spanish National Research Center (CSIC) - Institut of Agro-food Research and Technology (IRTA) - Leire Escajedo San-Epifanio Autonomous University of Barcelona (UAB) - University of Barcelona (UB), Barcelona, Spain leire.escajedo@ehu.eus SPECIALTY SECTION This article was submitted to Plant Biotechnology, This article addresses the scenarios that may be encountered by the first a section of the journal Frontiers in Plant Science application for pre-market approval of a CRISPR-edited plant in the EU. Two alternative scenarios are considered in the short and medium term. One of these RECEIVED 10 January 2023 ACCEPTED 22 February 2023 possible EU futures depends on the final drafting and approval of EU legislation PUBLISHED 16 March 2023 on certain New Genomic Techniques, which was started in 2021 and is due to be CITATION quite advanced before the next European Parliament elections in 2024. Since the Escajedo San-Epifanio L, Filibi I, proposed legislation excludes plants with foreign DNA, two different approval Lasa López A, Puigdomènech P and processes for CRISPR-edited plants will coexist if the legislation enters into force: Uncetabarrenechea Larrabe J (2023) Possible EU futures for CRISPR-edited one for plants whose genome has been altered, resulting in mutagenesis, plants: Little margin for optimism?. cisgenesis and intragenesis; and the second for plants whose alterations result Front. Plant Sci. 14:1141455. doi: 10.3389/fpls.2023.1141455 in transgenesis in general. In the event that this legislative process does not succeed, CRISPR-edited plants in the EU could face a regulatory scenario whose COPYRIGHT © 2023 Escajedo San-Epifanio, Filibi, Lasa foundations were laid in the 1990s: the regulatory framework that applies to GM López, Puigdomènech and crops, food and feed. In this review, an ad hoc analytical framework has been Uncetabarrenechea Larrabe. This is an open- access article distributed under the terms of built that considers in depth the two possible futures for CRISPR-edited plants in the Creative Commons Attribution License the EU. This framework emphasises the way in which the European Union and (CC BY). The use, distribution or the Member States (MS), with their respective national interests, have historically reproduction in other forums is permitted, provided the original author(s) and the shaped the regulatory framework for plant breeding in the EU. On the basis of the copyright owner(s) are credited and that analyses carried out on the two possible futures for CRISPR-edited plants and of the original publication in this journal is cited, in accordance with accepted their potential with respect to plant breeding, the main conclusions are the academic practice. No use, distribution or following. Firstly, that the regulatory review that started in 2021 is not in itself reproduction is permitted which does not “good enough” for plant breeding and CRISPR-edited plants. Secondly, that comply with these terms. compared to its alternative, the regulatory review currently underway contains at least some promising improvements in the short term. Hence, thirdly, in addition to adopting the current regulation, the MS need to continue to work towards a substantial improvement in the legal status of plant breeding in the EU in the medium term. KEYWORDS European integration, EU regulatory framework for plant breeding, EU legislation on new genomic techniques, premarket approval of CRISPR-edited plants, EU status of CRISPR-edited plants Frontiers in Plant Science 01 frontiersin.org Escajedo San-Epifanio et al. 10.3389/fpls.2023.1141455 1 Introduction present, so MS are frequently forced to rewrite new consensuses on the palimpsest of older agreements, whether they were good or bad, The Scottish journalist Allan Little is often quoted as saying that and on a background of prior crises and disagreements. in Europe ‘history is the unseen guest at every table’ (Little, 2012), The need to be mindful of this institutional peculiarity of the irrespective of the agenda. This has been the case since the period European Union, as well as the presence of historical precedents, immediately following the end of Second World War, when becomes especially relevant when the object of analysis is a political countries that had been using coal and steel to make weapons to and regulatory scenario as dysfunctional as the one experienced by kill each other (see list 1) tried to build the European Coal and Steel European plant biotechnology. Although negotiation of EU Community. One of the main objectives of that initiative was clear: regulations for CRISPR-edited plants for the 2020s seems “the solidarity in production thus established will make it plain that superficially to be a technical issue, there are significant historical any war between France and Germany becomes not merely roots. It is important to make this context visible. It is possible to unthinkable, but materially impossible” (Schuman, 1950). Of group these issues into three main blocks: course, preventing war is not the main element that holds the EU together nowadays, but for the countries of the region there is still a) The first block of issues arises from the peculiarity of something inevitable about EU membership. From a geostrategic integration of agriculture into the EU. The six funding MS point of view, countries of the region cannot afford to remain (see below list 1) agreed that agriculture could not be left out outside the EU. Although it has not been easy, integration offers of the European project, even if there was still no clear numerous synergies and economies of scale to MS, as well as a much consensus on how to realise its integration (McMahon, greater political reach than they would achieve individually. 2007). Among other things, the MS debated at the time the Therefore, France has described the EU as a power multiplier or favouring of national production over third counties and multiplicateur de la puissance (Verluise, 2017). mechanisms to stabilise prices (Tracy, 1993). Nowadays, However, this is not synonymous with the fact that all Member related concerns are still alive in the European arena, States (hereinafter MS) on all occasions and in all contexts embodied in expressions such as ‘preservation of participate in the EU with the same level of conviction and independence in food access’, as declared by French commitment. At least in the short term, some countries tend to ministers after the COVID-19 crisis. Those are some of the accept decisions that entail sacrificing some of their more factors that explain why successive versions of the Common immediate interests, negotiating trade-offs in areas that have little Agricultural Policy (CAP), which is updated every 5 years, or nothing to do with each other. The EU is at essence a common have been so contentious. However, in addition to them, we market, although this is not its exclusive function. Once the 27 have to consider that the CAP accounted for 66% of the heads of governments of the MS and the European Commission Community Budget in the early 1980s and currently absorbs (hereinafter the EC) have established a possible ‘common interest’ a third of the bloc’s entire budget. This underlying in the Council of the EU or Consilium (hereinafter EU Council), the background is reflected in many decisions that intersect EC is responsible for fulfilling commitments and their legislative with agriculture. For example, in 2015, when the approval implementation, whether in the sphere of the Community of the agricultural GMO opt-out was being debated (EP Legal institutions or in other international scenarios, with a view Observatory, 2015), the Committee of the Regions warned towards the global market (Bradford, 2020). The role of the that the attitudes of some MS in the GMO decision-making European Court of Justice (hereinafter ECJ), is no less relevant: it process were not so much related to GMOs as to the is the ultimate guarantor of these Community commitments, positions they advocated on the CAP (CoR, 2015). supervising the correct implementation and application of EU b) Another block of issues concerning negotiations on Law within the constitutional framework defined by the CRISPR-edited plants is the chronic disagreement of MS EU Treaties. on plant biotechnology in particular. The EU was one of the Seventy-five years after the Declaration of Rome that gave birth first regions in the world to adopt a GMO regulation in the to this unique union, the EU is the product of many concrete 1990s (Escajedo San-Epifanio, 2008; 2010), but its achievements and numerous lessons learned from complex implementation has been very disappointing. In an situations (such as the introduction of a single currency, the failed official document, the EC acknowledged that decision- attempt to draft a federal constitution or, recently, Brexit). The EU’s making in this area has turned out to be “largely the governance model combines federal, quasi-federal and confederal exception to the usual functioning of the EU comitology elements, and it accommodates the institutional and political procedure as a whole” (EC, 2015). In an attempt to address diversity of the MS while avoiding disruption of the integration the situation, the European Parliament (hereinafter EP) process. This results in a complex multi-scale federalism (Filibi, voted separately in 2015 for the recognition of an opt-out 2013). Admittedly, from time to time analysts speak of integration prerogative for GMO cultivation on the one hand, and an fatigue, but the EU continues to expand into new areas and generate opt-out prerogative for GM food and feed trade on the innovative policies (Lasa Ló pez, 2011; Bradford, 2020) and is other hand (EC, 2015). The former was adopted as radically redefining the classical concept of state sovereignty Directive 2015/412; the latter was rejected by a strong (Uncetabarrenechea and Filibi, 2022). However, history is always majority of the members of the EP (Escajedo San- Frontiers in Plant Science 02 frontiersin.org Escajedo San-Epifanio et al. 10.3389/fpls.2023.1141455 Epifanio, 2017). The disagreement, however, is not only below). The perception of disagreement and ambiguity related “to issues associated with the safety of GMOs for grew even stronger in 1999 when the EU Council, with health or the environment” (EC, 2015), but is also the result many other issues on the table, chose to relegate the status of the intersection of competing views about the of GM crops, food and feed pending a stronger consensus. management of domestic agricultural interests, the Selecting the most urgent matters and postponing the work allocation of funds related to agricultural and plant of negotiating others is not unusual in the EU. More than science research, commercial interests, and the 20 years have passed since the adoption of Directive 2001/ management of plant variety rights (80% of them 18/EC, and in that time the EU has expanded from 15 MS dominated by just three countries: the Netherlands, (see list 3) to 27 MS, even with the loss of the UK. However, France and Germany). Moreover, it should be noted that the difficulty of adequately confronting political tensions far from the improvement in the first model of GMO remains unresolved, although some studies suggest that decision-making processes they agreed upon in the 1990s, public opinion is evolving (Evanega et al., 2022). the obsession of some MS to maintain some political room for manoeuvre has incorporated later reforms that would According to the EC, the issues raised by MS around GMOs allow de facto blockages of GM crop authorisations (see “reflect national concerns which do not only relate to issues below 3.2). associated with the safety of GMOs for health or the environment” c) A third and final set of concerns is the limited way in which (EC, 2015) and now that we are facing the regulatory future for mechanisms of democratic political confrontation have CRISPR-edited plants, it is reasonable to ask whether MS are really been used in the EU to manage the ideological diversity in a position to commit to a “sufficiently good” legislation. As around GMOs. On the one hand, MS have not reflected Robert Schuman said, a united Europe is not built all at once, but together on some forms of anti-GMO attitudes and actions “through concrete achievements that generate de facto solidarity” that took place in the late 1990s and the 2000s. All (Schuman, 1950). Each collective achievement relies on the democracies face situations of political conflict where expression of a strong political will by the MS (EC, 1993). What (major) effort is needed to redirect political confrontation kind of political will have the MS expressed regarding CRISPR- over conflicting ideas into the legitimate, constitutionally edited plants and what achievements might the EU build from it? established spaces and channels set up for this purpose. Capturing and interpreting that political will is one of the objectives While political disagreement is considered essential and of this research. At least two EU futures may emerge for CRISPR- natural to all democracies, violent expressions of edited plants in the short term (see 2). The first of these futures is disagreement are to be avoided. Nevertheless, the latter dependent on the approval of an ad hoc regulation (2.2). The second was not factored in when the EU faced anti-GMO attitudes future for CRISPR-edited plants involves accommodating CRISPR- and actions in the late 1990s and 2000s. Indeed, some anti- edited plants within the regulatory framework that was created in GMO activists in France, the UK, Germany and 1990 and reformed in 2001 for GM crops, food and feed (2.3). Both Switzerland carried out almost synchronously violent future scenarios - including some possible derivations thereof - are actions against crop-research fields whose institutions had discussed in depth in this paper from political and legal perspectives been complying rigorously with regulatory standards (see sections 3 and 4), with consideration of how they are affected by (Kuntz, 2012; 2020). Further, governments and courts “historical issues” (see a, b, c above). Methodologically, the research failed to protect those who were complying with the law. undertaken has involved tracing three decades of EU regulatory and Moreover, a debate on ideas has systematically been non-regulatory decisions, as well as failed attempts at regulation avoided and some political scientists have found it and disagreements about plant biotechnology. This work has been striking the way that some politicians adopt parts of anti- carried out with a close eye on the institutional particularities of the GMO discourse and suggest that it is a common sentiment EU from the origins of the Common Agricultural Policy to the of the majority of European public opinion (Shurman and present day, both in its structural and dynamic dimensions, i.e. the Munro, 2006; Hayes, 2007; Seifert, 2017; Seifert, 2020). As is geopolitical and historical evolutionary dimensions. often the case, excerpts from political opinion lose meaning when placed out of context. Some forms of rejection to GMOs were and continue to be linked to a deep and 2 Two possible near-term regulatory legitimate rejection of the dominant model of futures for CRISPR-edited plants in globalisation and its overriding environmental ethics. Yet, the EU without delving into these positions as a whole, some governments have found it easy to adopt and exploit In 2019, the EU Council launched a process aimed at providing specific allegations of the anti-GMO movement. Finally, a “clearer, more evidence-based, applicable, proportionate and the literature also draws attention to the lack of EC reaction sufficiently flexible regulatory framework” for plants obtained by to MS that were notoriously non-compliant with the GMO means of New Genomic Techniques (NGTs), in order to “cope with Directive 90/220/EEC (Lee, 2008) and the permissiveness of advances in science and technology in this area” (Council Decision the EC in face of the de facto moratorium (see details 2019/1904). The EC commissioned a study on how this task should Frontiers in Plant Science 03 frontiersin.org Escajedo San-Epifanio et al. 10.3389/fpls.2023.1141455 be undertaken, with April 2021 as a deadline for submission. Given at that time specific research programs to stimulate the that 2024 is the date set for the next European Parliament elections development of biotechnology, as manifested in the (and thus the appointment of a new EC with a new political Biotechnology Action Program (1985-1989) and later initiatives agenda), it was estimated that if the deadlines were met, a (e.g. BRIDGE). revision draft of the regulation is estimated to be ready within As described by the OECD, since 1980 biotechnology has this parliamentary term (EC, 2022). The EC met the deadlines and evolved “from a scientific curiosity towards commercial in Autumn 2021 opened a time period to develop specific legislation applications” (OECD, 1999) and, as a consequence, regulation at for NGT-derived plants (2.1). Depending on whether the envisaged the national and international levels of some of its aspects was reform is achieved, CRISPR-edited plants will have one of the considered imperative. In the European region, the MS of the then following two futures in the EU (2.2. and 2.3). EEC took an important decision at that time because there was a lack of national-level policies on the use of biotechnology, so they embarked together on this new and common regulatory path. Three 2.1 New times are here decades later, we can affirm that the result of that decision has both light and shadows, depending on the biotechnology sector in In their document “Neue Zeiten, Neue Antworten” – New question. This common path has yielded very good results in Times, New Answers- the German Greens (Bündnis 90/Die some biotechnology sectors -especially the health sector-, but Grünen, 2018), in contrast to earlier times, reflected on the European agri-biotechnologies collapsed due to a regulatory advisability of analysing whether certain new biotechnologies framework with many shortcomings (Escajedo San-Epifanio, 2017). could help to meet the challenges posed by climate change. It is difficult to know whether the outcome would have been Similarly, many other political, scientific and/or governmental different for agri-biotechnologies if the MS had agreed on voices at European or national levels have recently alluded to the harmonisation in two stages: a first stage of national regulatory contributions that new genomic techniques could make to the frameworks in the 1990s, followed by a second stage as a prelude to ambitious sustainability goals of the European Green Deal (COM harmonisation at the EU level. We are not aware of any discussion 2018/640), the Farm to Fork Strategy (COM 2020/381) and the at that time on the possibility of each MS regulating agri- Long-Term vision for rural areas (COM 2021/345). In addition, biotechnologies separately, as an alternative to an EU framework. some governments are investing in scientific research programmes However, it is known that between 2010 and 2015 the possibility of in the belief that an agreement will be reached sooner rather some devolution of agricultural competence with respect to GMOs than later. was discussed (Escajedo San-Epifanio, 2017). Although it did not go Nonetheless, a political context favourable to an agreement does as far as a devolution, Directive 2015/412/EC, which recognises an not always guarantee a good consensus. The starting point of the opt-out prerogative for MS (see Box 1), can be read along these EU’s plant biotechnology policy was a period with many factors that lines. Given the difficulty of reaching tangible agreements on were conducive to a good agreement. It was the late 1980s and the GMOs, and as a more efficient alternative to an opt-out MS of the (then) EEC (see list 2) were still in the process of prerogative, some experts discussed why it would have been completing their internal market. Among the concerns on the table, preferable to regulate an opt-in prerogative rather than an opt- the White Paper entitled Completing the internal market (EC, 1985) out prerogative (Escajedo San-Epifanio et al., 2019; Eriksson et al., stressed the necessity of leaving behind the economic crisis of 1973. 2020; 2021). That is, some kind of mechanism that would protect Integration required, among other things, a closer approximation of the rights of those MS that wish to use specific GMOs once those strategic regulations, more agility and efficiency in decision-making GMO crops had been favourably assessed at the EU level. processes and a strengthening of the socio-economic cohesion of The current situation is not comparable to that of the 1980s: the region. A goal of strengthening the scientific foundations of the The 27 MS know that all possible futures for CRISPR-edited plants economic community also took on special relevance (EC, 1985). should be EU futures; a devolution of powers to each of the MS This period of integration coincided with the socio-political seems to be unthinkable. Additionally, the foundation stone of any emergence of biotechnology. The European institutions launched regulatory future for CRISPR-edited plants must be placed now, BOX 1 Evolution of MS’ policy discretion in GMO decision-making (1990-2015). The decision to create a common regulatory framework for GMOs emerged from consensus by the MS in the late 1980s. At that time, there were no previous state frameworks in the MS on this issue, so harmonisation was not necessary. The immediate task was the creation ex novo of a minimum set of rules on the commercial and agricultural use of GMOs, which was expected to move towards further convergence in the future. The tendency to start by agreeing on minimum standards and gradually move towards greater policy convergence has been a constant in many areas of European integration. This is nothing new. But it is striking that, in the specific case of GMOs, there has been a drift over time towards a less united EU. Thus, while scientific assessment and decision-making have been progressively centralised, at the same time there has been a progressive increase in the margin of political discretion surrounding decision-making within the MS. In the 1990s, the first regulatory framework for GMO crops opted for a system characterised by two elements: decentralisation of scientific assessment complemented by mutual recognition, and final administrative decision-making at the EU level with little room for individual political decision making. Since 2001, important changes have taken place in this respect. On the one hand, there has been centralisation of scientific assessment in the European Food Safety Authority (EFSA), created in 2002. On the other hand, two important actions of political discretion have been granted to the MS -see list 3-: a veto power incorporated in Directive 2001/18/EC, and an opt-out prerogative enacted in Directive 2015/412 (Escajedo San-Epifanio, 2017; Gonzá lez-Vaqué , 2017). These margins of discretion have important implications for the decision-making system (see Box 4) and its blocking facility (3.3.1). Frontiers in Plant Science 04 frontiersin.org Escajedo San-Epifanio et al. 10.3389/fpls.2023.1141455 before the 2024 elections to the EP. At this point in time in early To some extent, the legislative failure would be an unfortunate 2023, there are only two possible options: the approval of some legal consequence of MS being unable to take on the effort of adopting text in the context of the legislative initiative on NGTs (2.2) or the the new legislation. postponement of the decision to the next parliamentary period, What would be the situation for CRISPR-edited plants if the which would place CRISPR-edited plants in a by-default legal legislation currently being drafted is not adopted? Applying Article situation until at least 2025 or 2026 (2.3). Let us now compare 2.2 of Directive 2001/18/EC, CRISPR techniques give rise to GMOs the main elements of these two possible EU futures concerning (see details in 2.3.1). Therefore, by default, the same legal status CRISPR-edited plants in the EU, leaving the more detailed applies to them as to transgenic plants with regard to market access development of both for Sections 3 and 4. or food use, irrespective of whether the CRISPR technique has led to mutagenesis, cisgenesis, intragenesis or transgenesis. Consequently, the default pre-market approval that will remain for CRISPR-edited 2.2 First possible future: Specific legislation plants is composed of two elements: for plants obtained by means of CRISPR? - As far as agricultural use is concerned, Directive 2001/18/EC As indicated in the introduction, the most promising future for on the deliberate release of GMOs would apply. CRISPR-edited plants is linked to the legislative process launched - In the case that CRISPR-edited plants or products obtained by the EC in Autumn 2021. That is the so-called initiative for the from them were to be used as food or feed, Regulations creation of legislation for plants produced by certain new genomic 1829 and 1830/2003 would also apply. These regulations techniques, including their food and feed products (EC, 2022). This establish the premarket approval procedure for food uses of initiative has already passed the institutional and stakeholder GMOs, as well as their labelling and traceability feedback period, as well as the public consultation period. requirements. Since the end of the consultations, there have been three EU actions that point to the possibility of the new regulation being Regarding the possible application of this regulatory framework adopted. The first action was the publication of the Factual to CRISPR-edited plants, we must make two observations: 1) the Summary Report, which indicated that the results of the particular political use that this regulation makes of some scientific consultation had been “quite favourable” to the legislative concepts (2.3.1); 2) the veiled criticism that the EU Council has amendment. Secondly, the preparatory work being carried out by made of this regulation, indicating in 2019 (see above) that NGTs EFSA on possible risk assessment criteria for plants derived from need a more proportionate, applicable and science-based targeted mutagenesis and cisgenesis was made public in October regulation (2.3.2). 2022 (EFSA, 2022). Finally, as recently as November 2022, the preparation of this legislation on NGTs appeared on the list of tasks that the current EC, led by Ursula von der Leyen, plans to complete 2.3.1 An observation on the dividing lines used by before the next European elections. this old regulatory framework In section 4 we will examine in more detail what is currently The establishment of any regulation usually has among its known about the legislation that is in the pipeline. Prior to that, components a section delimiting the scope of the regulation. This however, let us look at what the future might hold for CRISPR- is a material decision about the substance of a regulation, but it also edited plants if the legislative process does not succeed (2.3). needs to be expressed in the text. In the particular case of the EU’s GMO regulatory framework of the 1990s and the 2000s, delimitation was necessary for determining which GM crops and 2.3 Second possible future for CRISPR- food fall under the EU’s legal capacity and which do not. In order to edited plants: A future by default carry out this delimitation in a very synthetic way, the MS visualised an imaginary subdivision of plant varieties, granting them a Rational choice theory highlighted at least two major different legal status depending on the technique used to obtain explanatory factors that are often overlooked in political analysis them. Accordingly, as we will see below, the EU included a (Huntington, 1997): first, that politicians are endlessly description of dividing lines that separate some subgroups from opportunistic; and second, that all decisions take place in some others as part of the Directive on the deliberate release of GMOs type of institutional setting. These factors must also be weighed (Directive 220/90/EEC). Let us see how this was done in the legal when the choice made by policy-makers is a decision “to do texts (listed in Box 1) applicable to this case. nothing”. In particular circumstances, doing nothing could be As far as GM crops are concerned, Directive 220/90/EEC was considered a good option or at least an option (Cantekin, 2016), created primarily with consideration of techniques involving the use and there are many cases in which policymakers opt for this choice of rDNAs, but in the absence of more specific prior legislation, the if they consider that for some reason a dispute may be intractable. following was done: firstly, the concept of GMOs in general was Applied to the case of CRISPR-edited plants, a hypothetical failure defined in the text of the Directive; and secondly, it was specified to of the EU to reach a consensus in 2023-2024 on plants derived from which GMOs the legislation applied and which were exempted. certain NTGs cannot be interpreted as a lack of awareness of the Thus, a GMO was defined as any “organism, with the exception of potential of these techniques for current European plant breeding. human beings, in which the genetic material has been altered in a Frontiers in Plant Science 05 frontiersin.org Escajedo San-Epifanio et al. 10.3389/fpls.2023.1141455 way that does not occur naturally by mating and/or natural CRISPR feed imported from third countries and presumably recombination” (art.2.2.). Additionally, a list was included in the difficulties in correctly identifying them as such (see below). This annexes defining which techniques were exempted from the does not seem to be the situation desired by MS. Indeed, when in provisions of the Directive even though such techniques give rise the aforementioned 2019 decision the EU Council called on the EC to GMOs (e.g. classical mutagenesis). Directive 2001/18/EC for “more evidence-based, enforceable and proportionate” maintained this approach for the delimitation of GMOs that were regulation (Council, 2019), a veiled criticism of the current subject to and exempted from its application. Consequently, this regulatory framework was revealed. Although not stated directly, defined three types of pre-market approval applicable to crops, the EU Council’s opinion is in line with those expressed by major depending on whether a new plant variety can firstly, be considered European scientific institutions, such as ALLEA/EUSAGE, EASAC, GMO or not; and secondly, whether the breeding technique used is Leopoldina or COSCE. All of them suggested that the emergence of an exempted technique or a technique under Directive 2001/18/EC NGTs seems a good opportunity to comprehensively review (and (see summary in Box 2). improve) the pre-existing plant breeding framework. In other words, a rigorous scientific assessment could conclude The reference to scientific evidence and the idea of that the risk associated with a particular GM food or feed would be proportionality point to the legal need to properly situate NGT- equivalent to that of a conventional counterpart (e.g. a food or feed derived plants in relation to the whole range of breeding techniques. derived from a mutant plant). However, GM food and feed were A holistic regulatory framework, i.e. one that does not pre-classify removed from the novel food category in the 2000s, when specific risks according to the techniques used (see 2.3.1), would allow MS regulations for genetically modified food and feed were enacted (see to control more effectively and proportionately the actual risks of above Box 1). As some parts of the literature argue, from that point each plant whose genome has been modified. Thus, the report onwards, GM crops, food and feed were given a legal status in the prepared for the STOA (Custers and Dima, 2022: 13) states that EU that recognises them as distinct from their parent crops new genome editing techniques are “highly precise”, and that in (Davison and Ammann, 2017). See summary in Box 2. relative terms their risks and uncertainties are “lower than the risks and uncertainties of conventional random mutagenesis, which 2.3.2 A “not sufficiently evidence-based nor makes use of radiation or chemicals to induce genetic changes” proportionate” regulation (Custers and Dima, 2022: 16). However, the current regulation of The default position of GMO rules applying to CRISPR-edited GMOs, which by default includes CRISPR-engineered plants, does plants is not good news. As widely recognised, decision-making on not analyse the risks in this holistic framework. On the contrary, it GMOs has been stalled for decades in the EU and it is highly pre-classifies potential risks according to the technique used to doubtful whether any operator would venture to process a pre- obtain the modified plant and, consequently, a plant obtained by market approval application for CRISPR-crops under the current random mutagenesis is considered to be of lower risk than a plant regulatory scenario. At most, stakeholders would only consider modified by CRISPR, regardless of the specific modification that has submitting applications for authorisation of CRISPR feed crops that been carried out. In fact, only the latter technique is currently possess high commercial interest, but little else would be judged subject to authorisation requirements prior to its deliberate release viable. This situation is similar to the experience with GMOs. for cultivation (see Box 3). According to data published by the EC, the absence of GM crops We agree with those who have taken a position on the and food in the EU contrasts with the situation for GM feed: desirability of a holistic review of the regulatory framework for soybeans used in animal feed come from countries where more than plant breeding (see above), although such a legislative option is not 90% of soybean production is GM (COM 2015, 176 final). European currently on the table. In other words, if the legislative process feed producers cannot compete on a level playing field. described in point 2.2 does not succeed, the default future for Projecting this situation to the case at hand, this second possible CRISPR-edited plants will be exactly the same as the one in which future would be an EU without CRISPR crops and food, but with transgenic plants have existed since the adoption of Directive 2001/ BOX 2 Classification of plant varieties according to the premarket approval process foreseen for crops, and the food and feed derived from them in the EU. Applying the provisions of Directive 2001/18/EC and other rules on pre-market approval of new plant varieties and their food uses, we can distinguish three groups of plant varieties: 1) Plant varieties that cannot be considered GMOs according to Directive 2001/18/EC, and to which, consequently, Directive 2001/18/EC does not apply. The Regulation. EU 2015/2283 on novel food would only apply in the case that their derived products can be considered novel food. 2) Plant varieties that are GMOs but do not require premarket approval due to the techniques used for their breeding as defined by Directive 2001/18/EC. Their use as food and feed may require authorisation in the context of the EU 2015/2283 Regulation on novel food. 3) Plant varieties that are GMOs and whose premarket approval is subject to the above-mentioned Directive 2001/18/EC. Where applicable, food and feed obtained from these varieties require authorisation under Regulation 1829/2003, as well as compliance with the labelling and traceability rules provided for in Regulation 1830/ 2003. Frontiers in Plant Science 06 frontiersin.org Escajedo San-Epifanio et al. 10.3389/fpls.2023.1141455 BOX 3 The advantages of a holistic encompassing regulatory framework: the example of random and targeted mutagenesis. Gamma rays are the most widely used mutagenic radiation in plant mutation breeding (Li et al., 2019), and ethyl methanesulfonate or EMA is among the most widely used chemical mutagens. These are two examples of classical mutagenesis. The first results of mutation induction in crop plants were published in the late 1920s and their use became widespread from the 1960s onwards. At the time of GMO regulation in the 1990s, the MS declared the following: first, that mutants obtained by radiation or chemical mutagens are GMOs; second, that pre-market approval is not required for their use in agriculture because they were considered to have a sufficient history of safe use. In contrast to what has been agreed at the EU level, French national legislation states, that random mutagenesis "does not give rise to GMOs" (art. L-531, Code de l'environnement). Today, it is possible that in some cases food and feed derived from mutant plants may require authorisation under the Novel Food Regulation 2015 as novel food; but these products are not subject to traceability or labelling procedures comparable to those that apply to GM food and feed (see Box 2). Nevertheless, in this future-by-default, a CRISPR-mutated plant would be treated as a transgenic. This situation does not seem consistent with the comparative sequencing results of conventionally mutated and CRISPR-mutated plants. Today's technology, which did not exist in the 1960s, allows us to test case-by-case impacts on genomes, and it would make sense to have a regulatory framework in which risk assessment focuses on the actual changes made to genomes, rather than being biased or pre-classified by groups of techniques. 18/EC. However, the implementation of this rule will not be easy. basis of the ‘factual or social circumstances prevailing when that rule Under current regulations, pre-market approval for agricultural or was adopted’. AG Bobek, as detailed in Box 4, argued why such a food use of genome-edited plants sourced from the EU will go frozen interpretation should not be accepted. However, the ECJ in through the processes mentioned in Box 2. But in the case of its judgment in this case C-528/16, held that in the specific case of genome-edited plants and their products arriving from third GMOs there are reasons that justify limiting the interpretation to countries, the EU is likely to encounter problems in enforcing the the date of adoption of the Directive, which is an exception to the labelling and traceability requirements that Regulation 1830/2003 established path of European case law. imposes on genetically modified food and feed (Van der Meer et. al., At the end of the 1980s, the then MS were facing the socio- 2023). The information necessary to implement or develop an economic effects of the 1973 crisis and the previously mentioned appropriate detection method for product identification may not White Paper of 1985 encouraged them to speed up the process of be readily available to EU authorities (Ribarits et al., 2021). completing the internal market. Since strengthening the scientific and technological bases of the economic community was identified as one of the pillars of this process, it was unthinkable that biotechnology policy would remain excluded from this new 3 The second possible future European era. But building a good regulatory framework for agri- for CRISPR-edited plants: “frozen” biotechnologies was not an easy task. Moreover, the EU did not yet since 2001 have a sufficiently solid institutional structure or experience. By contrast, in the US, representatives from more than 18 federal With regard to this regulatory framework-by-default for agencies and executive offices spent two years working on the design CRISPR-edited plants, it is also important to note that the of a specific and coordinated regulatory framework for agri- legislative approach employed seemed to have “frozen” the biotechnologies. In 1986, the federal government published the framework at the time when Directive 2001/18/EC entered into Coordinated Framework for the Regulation of Biotechnology force. Such a ‘freeze’ would imply, as AG Bobek describes (AG (Farquhar and Meyer, 2007), which, as far as crops, food and feed Bobek, 2018) in his opinion on case C-528/16, that twenty years are concerned, has relied on the coordinated action of the FDA, later we would be required to interpret Directive 2001/18/EC on the USDA and EPA (US Government, 1986). BOX 4 A scientific-technical regulatory framework that became ‘frozen’ in 2001. In the mid-2010s there was some debate in the EU, given that the wording of Directive 2001/18/EC indicates that "mutagenesis", without further precision, gives rise to GMOs that are exempt from the application of the Directive (see Box 2). A court case initiated in France led to a request to the ECJ to clarify whether targeted mutagenesis should (or should not) be considered as an exempted technique, in application of the literal provision of the Directive. AG Bobek, in his non-binding conclusion (AG Bobek, 2018), and the ECJ (ECJ, 2018) adopted a different position on the issue (Casacuberta & Puigdomènech, 2018). AG Bobek said that while the EU does not have to act on all matters for which it has competence, once the MS decide to legislate on something, there is a constitutional obligation to keep that legislation up to date. Given that some aspects of Directive 2001/18/EC were reformed in 2008 and 2015, AG Bobek said there seems to be no basis for considering that what was not reformed in 2008 and 2015 was frozen in 2001. He also expressed his opinion on the legal argument that New Plant Breeding Techniques resulting in mutagenesis should be understood to be covered by the exemption that the Directive has provided with regard to mutagenesis, as long as they do not involve the use of rDNA. Consistent with that understanding, the AG interpreted the exemption that Directive 2001/18/EC applies to "mutagenesis techniques not involving the use of rDNA" (see Box 2) as follows. Any plant obtained by mutagenesis, whether classical or directed mutagenesis, shall be understood to be covered by the regulatory exemption as long as it does not involve the use of rDNA (Bobek, 2018: para 60 and 62; Purnhagen & Wesseler, 2018: 18). The ECJ, however, made a particular use of self-restraint, as it has been especially criticised for its poor scientific basis (Casacuberta and Puigdomènech, 2018; Escajedo San-Epifanio, 2022). According to the court, mutant plants had been declared exempt from the GMO Directive in 2001 because of their long safety record, and after that date there had been no declaration on plants obtained by directed mutagenesis. For that reason, and applying the precautionary principle, the court considered that it was more appropriate to apply the transgenic regime to edited genome plants than to other mutant plants. However, this understanding ignores the fact that targeted mutagenesis did exist in 2015, the date of the last reform of the Directive. At the same time, it seems that the court recognizes the concept of "long history of safety" as a new criterion or dividing line; that is, as an additional criterion to the dividing lines that the Directive uses to distinguish between GMOs exempted by and subject to its regulatory regime. It so happens, however, that this term (long safety use) does not appear in the text. Moreover, there is no record that the MS reached any explicit agreement (regulatory or political) during the drafting of the standard that specified what is to be understood by the term "long safety record". Frontiers in Plant Science 07 frontiersin.org Escajedo San-Epifanio et al. 10.3389/fpls.2023.1141455 The US will not need to pre-classify plant breeding techniques obstacle to adequately accommodate the legal treatment of new in the same terms as the EEC (vid supra), because the competence plant breeding techniques (Abbot, 2015; Callaway, 2018). Former over plant breeding, whether GMO or non-GM crops, will be the EU Ombudsman Diamandouros (Diamandouros, 2018) explained responsibility of a single institutional structure as a wholeIn the EU, in 2018 that although the matter to be regulated was the use of a on the other hand, a whole narrative will be built on the scientific technological advance, some other policy issues made the aforementioned dividing lines. In essence, the dividing lines that regulation of GMOs a “deeply political matter” that needed to be were created to establish who has the legislative capacity for each addressed at political level and could not be exclusively confined to plant variety (see above) will condition the future of the regulatory an administrative ruling. This is not so much an attribute of the framework. This is because the dividing lines embodied two technical content, but is related to the unsatisfactory European immovable premises. The first premise is that plant breeding decision-making structure for plant biotechnology and the fact that techniques, including those yet to come, have been ordered this structure has been in place since the 1990s (Daviter, 2012). chronologically, and from the simplicity of the discourse it seems We argue that there are at least three deep policy issues, all of that any new plant breeding technology is bound to have more them strategic, that had to be addressed at the political level in the impact and potentially more risk than the pre-existing ones. The late 1980s, when the EEC was designing what would become second premise, in line with this, is that the European regulatory Directive 90/220/EEC on the deliberate release of GMOs: the framework does not need a clause or mechanism to revise its choice of the type of regulatory framework; the specification of approach in the light of scientific and technological developments. GMOs under and exempted from Directive 2001/18/EC; and the In an interesting non-binding opinion on case C-528/16, AG decision-making model for authorisation. Bobek (see Box 4) explained in 2018 that the principles of European The decisions on the regulatory approach (by sectoral or Community law prevented the GMO regulation from being horizontal uses), as well as the delimitation of the EU’s sphere of considered frozen in 2001. It is also interesting to note that the competence (see 2.3.1) were also decisions with an important discussion on whether and to what extent NBTs result in GMOs (or a political dimension. It is understood that we face a political use of similar regulatory term) has been ongoing since the mid-2000s in scientific terms beyond the technical delimitation. The dividing line, many jurisdictions around the world, as detailed in the 2021 paper by described in detail in 2.3.1, determined in the early 1990s which Van der Meer et al. However, the ECJ in its judgment on case C-528/ GMOs were to be “EEC business”, regulated on the basis of a 16 ruled the opposite way. The ruling did not explicitly refer to common consensus, and which were not. And the very existence of whether the interpretation of Directive 2001/18/EC should be this dividing line, which was kept in Directive 2001/18/EC, would understood as “frozen” at its date of creation. Nevertheless, the ECJ also have two important consequences. First, any decision on the did advocate an originalist interpretation or an interpretation in line dividing line (to leave a future GMO technique to one side or the with the time of the creation of the legislation. Namely, the ECJ stated other) would inevitably have a political component associated with that the consensus of the MS on certain elements of Directive 2001/18/ it. In other words, effectively it would mean determining the pre- EC had not been renewed since its drafting and, on that basis, argued market approval of a technique, but also defining which level of that the precautionary principle recommends an interpretation of the decision-making (Community or national) would be responsible for Directive in line with its date of creationSee it detailed in Box 4. taking decisions. The second consequence would be a tendency to reinforce this dividing line, given that the MS would only maintain an important sovereign decision-making capacity over GMOs 3.1 The evolution of this frozen exempted from the Directive on deliberate release (currently regulatory framework Directive 2001/18/EC). These decisions predictably led to another question: whether Freezing, as is well known, is a preservation technique that, the EEC would use a product-based or process-based evaluation among other things, protects certain objects from the effects of the process (Sprink et al., 2016). Since the EEC would not have a holistic passage of time. Symbolically, it is used in this case to refer to the competence on plant breeding in general or even on GMOs as a regulatory framework for GMOs, because the framework seems to whole (transgenic or not), a product-based evaluation model was have remained impervious to the passage of time. Why then are we very difficult to organise institutionally. Not impossible, but now talking about the evolution of this regulatory framework? It is difficult. Nevertheless, it is not conclusively clear that Directive the case that while the content of the framework will not be revised 2001/18/EC opted for a purely process- based regulation (Tagliabue, except in specific areas, the practical application or, as it were, the 2017). In fact, it has been discussed among different institutions and way the regulatory framework functions will be affected by the in the literature whether the interpretation and application has been passage of time. focussed on the resulting GMO organisms, the techniques used to The evolution of this fragmented regulatory model over time, obtain them or a combination of both (Van der Meer et al., 2023). together with some problematic elements it already contained from Let us now look at a key element of the regulatory framework the beginning, will significantly affect the development of agri- that the EU applies to GMOs under the Directive: the decision- biotechnologies in the EU, and because of the freeze, will be an making process. Frontiers in Plant Science 08 frontiersin.org Escajedo San-Epifanio et al. 10.3389/fpls.2023.1141455 3.2 The decision-making model or Achilles’ applications that were subsequently processed after 2002, the MS heel of the EU regulatory framework to be systematically opted for an extraordinary combination of decisions. applied by default to CRISPR-edited plants A non-decision was agreed in the committee (see Box 1), but then external pressure was exerted on the EC not to formalise the draft The decision-making process on the premarket approval of GM for authorisation. One of the most striking cases was the one that crops food and feed has always been the Achilles’ heel of the EU reached the ECJ as case T-164/10, Pioneer Hi Breed Int. (Escajedo regulatory framework for GMOs. A two-fold need for authorisation San-Epifanio, 2017). In view of the EFSA report, the Commission decisions had to be addressed when the EEC first regulated the prepared an authorisation draft in which the MS expressed a non- deliberate release of GMOs in the 1990’s. Firstly, there was a need to decision. Subsequently, both the MS and the European Parliament articulate at the European level some way to address the scientific pressured the Commission, recommending it not to formalise the assessment of risks associated with GM food and feed. Unlike the authorisation of the crop. Without mentioning the attitude of the FDA in the US, created in 1906, The European Food Safety MS and the Parliament’s resolution, the CJEU judgment in the Authority (EFSA) did not exist in the 90s. Secondly, an Pioneer case condemned the Commission for its inaction, appropriate panel or committee had to be selected or established reminding it that it was obliged to comply with its obligations to make the final decision on the authorization of a GMO in the under Directive 2001/18/EC. light of the scientific assessment. Uncomfortable with this situation, the Barroso Commission The initially established model provided, firstly, for a scientific initiated a process to increase the discretion of the MS in exchange evaluation that could be carried out in any MS under common for the decision to be taken on a more scientific basis - see above criteria and, secondly, for final decision-making involving all the Box 1 -; an arrangement that, as we have already seen, has been MS at the level of the EEC (see Box 1). The model initially widely criticised (Paskalev, 2012). This gave rise to the opt-out established provided for a scientific evaluation that could be prerogative, which allows any MS to partially withdraw from carried out in any MS under common criteria, and subsequently something that other MS have decided at the EU level. While a final decision-making process involving all the MS at the EEC there have been major disagreements in other EU areas, there is no level. Several factors, however, mostly of a political nature, hindered other area in the EU where a similar prerogative is allowed (Salvi, the proper functioning of this scheme from the outset (see Box 1). 2016; Poli, 2015) and it has been considered that the opt out seems Between 1998 and 2004, no applications for authorisation of GMOs to be more of a trade-off and temporary solution than a long-term under Directive 90/220/EC reached the end of the decision-making solution (Escajedo San-Epifanio, 2017). process (Lee, 2008, 2-3), and some of the 15 MS (see list 3) introduced measures into their national legal systems that aimed to prohibit or hinder national market access for GMOs that had 4 The first (and only truly) possible already been authorised at the EU level. EU future for CRISPR-edited plants: This situation was called “de facto moratorium” (Liebermann A new regulation and Gray, 2006) and was formalised in 1999, when the MS expressed that since a major revision of the regulatory framework Let us consider the information available to date on the was underway - leading to the creation of Directive 2001/18/EC - it legislation that is being drafted on plants obtained by means of did not make sense to continue making authorisation decisions. certain NGTs. The main novelty is the creation of a fourth subgroup Nevertheless, the new Directive and the creation of EFSA (in 2002) of plants within the pre-market approval categories of crops, food were not sufficient to unblock the situation. According to the new and feed seen in Box 2 (see Box 5). regulation, when EFSA issues an opinion in favour of the Seen from the political perspective and the EC’s effort to authorisation of a GM crop, the EC prepares a favourable draft generate a consensus among the MS on plants obtained through decision. The MS then meet and analyse the draft; a favourable draft NGTs, the decision to reference its legal framework with respect to means that the application meets all the requirements set out in the GM plants and those obtained through classical mutagenesis has a regulations. The MS have then the political possibility to vote for or certain logic. When complex issues intersect, it is common for against the draft. However, in the event that the MS do not issue any international agreements to apply what is known as the technique of decision, after a period of time, the regulations stated that the EC compartmentalisation and specialisation of decisions. Narrowing must formalise the draft decision. Nevertheless, in the few and specifying the margins of agreements tends to allow existing BOX 5 Placing plants obtained by means of NGTs between GMOs exempted from the Directive and GMOs “under Directive”. In addition to the status applicable to conventional plants (see Box 2), three different statuses for genetically modified plants will coexist in the EU if the current legislation is approved: (1) plants modified by techniques included in the list of exempted techniques in Directive 2001/18/EC; (2) plants obtained by techniques that remain under Directive 2001/18/EC; (3) and plants that, if applicable, would fall under the new legislation on plants obtained by means of certain NGTs. Regarding food and feed: (a) the GM food and feed regulations would apply to the agri-food use of plants in group 2; (b) Regulation 2015/2883 on novel food would apply to exempted plants (group 1) if they give rise to novel foods; and (c) it remains to be seen what new regulations are envisaged for group 3. Some of the elements of the Roadmap and the fact that DG Health is in charge of proposing the Draft (EC, 2021 IIA) suggest that there will be a specific regulation on the food safety assessment of food and feed derived from plants obtained by NGTs. Frontiers in Plant Science 09 frontiersin.org Escajedo San-Epifanio et al. 10.3389/fpls.2023.1141455 consensus to flourish, thus avoiding the lack of consensus on related Along these lines, the EFSA published a document in October issues. In this sense, compartmentalisation can be positive, but it 2022 entitled “Criteria for risk assessment of plants produced by may also have disadvantages, which, as will be seen below, seem to targeted mutagenesis, cisgenesis and intragenesis”, at the request of have occurred in this case. the EC (EFSA, 2022). In this proposal, it is assumed that “where the Before going into this, it is worth referring to the legislative history of safe use of genomically edited plants cannot be sufficiently instrument and the DG in charge of developing it. The regulation of demonstrated, the function and structure of the introduced allele GM plants is currently contained in different instruments, most should be carefully assessed” (EFSA, 2022), in an approach that notably Directive 2001/18/EC and Regulations 1829 and 1830 of suggests the following elements. Firstly, the way in which the 2003. The Directives allow MS a certain margin of self-regulation regulation establishes the concept of “history of safe use” when transposing them into their respective legal systems, but this is (hereafter HoSU) will be key, not only in its definition, but not the case with the Regulations, which are applied homogeneously especially in terms of allowing the evolution of scientific throughout the EU. At the current stage of the development of knowledge to be a reference for adjusting its concrete application. legislation on plants obtained via NGTs, it is unknown whether Otherwise, this regulation will remain the same as the GMO plants obtained through certain NGTs would be regulated by a regulations: frozen in relation to the time of its formulation. Directive or a Regulation, but everything suggests that the legislative Secondly, it seems that in the case of plants without HoSU, there instrument will be only one of these two possible instruments. In any is a tendency to apply a risk assessment system very similar to the case, considering that food is involved, it is likely to be a Regulation. one established for transgenics in Directive 2001/18/EC. This is The political leadership in drafting the legislation seems to have been despite the fact that both the report submitted to the STOA in 2022 entrusted to DG Health, without prejudice to the possibility of (Custers and Dima, 2022) and EFSA itself (EFSA, 2022) have coordinating with other bodies on certain elements. acknowledged that, in some cases, plants obtained by directed Let us now see how the decision has been compartmentalised and mutagenesis or cisgenesis do not pose new risks compared to specified in this case. Within the roadmap (EC, 2021, IIA), plants those produced by mutant plants or even those obtained by derived from certain NGTS have already been described as requiring conventional breeding techniques. regulation with reference to existing legislation (i.e. Directive 2001/ There are some inconsistencies associated with the above- 18/EC and Regulations 1829 and 1830/2003). Since this reference mentioned EU Council objective of providing a “clearer, evidence- regulatory framework established groups of organisms, drawing based, enforceable, proportionate and sufficiently flexible regulatory dividing lines according to their breeding processes (2.3.1), it was framework” for plants obtained by new genomic techniques, in foreseeable that the technique would also serve as a reference for the order to “cope with advances in science and technology in this field” delimitation between this prior regulation and the one applicable to (Council Decision 2019/1904). NGTS. And, of course, some reference should be made to previous It seems that we are unlikely to achieve these objectives in this EU experience in assessing: 1) genetically modified plants (as mutants way. In terms of clarity, it does not seem a good decision to place are not assessed stricto sensu at the EU level); 2) risks associated with such importance in a concept like HoSU, which is a legally food and feed derived from genetically modified plants (referred to in indeterminate concept. Nor does it seem to achieve the objective the legislation as genetically modified food and feed); and 3) risks of of proportionality, given the difference between plants obtained food and feed derived from mutants falling within the scope of the through NGTs on the one hand, and mutants and conventionally novel food legislation (see Box 2). bred plants on the other. For the latter, HoSU is not required to However, the extent to which these inescapable references decide on their agricultural use, and at the same time, ad hoc should or should not limit the freedom of legislators to define an assessment will only be used in relation to their food use if it is appropriate ad hoc framework for GM-derived plants is open to considered that substantial equivalence cannot be determined with debate. The MS and stakeholders are currently reflecting on this respect to the homologous (conventional or classical mutants). issue. Two things seem to have been neglected from the outset: 1) However, contrary to the scientific opinions provided by the the scientific-technical assessment of plants derived from certain EFSA on NGT-derived plants, the possibility that some of them NTNs would not be the same as that of mutated plants, because can be considered as equivalent to conventional or mutant plants in only food risks are assessed for the latter and not agricultural risks terms of agricultural or food use seems to be generally excluded. (see Box 2); 2) nor would the assessment of crops, food and feed These difficulties, however, are not only due to the criteria obtained in this way have the status of transgenic. But this way of proposed for scientific assessment, but are the consequence of very thinking, which has always been referenced with regard to mutant different governance models for the risks associated with crops, and transgenic plants, is guiding the legislative process towards the food and feed in the EU and the US. The current institutional model common assumption that the associated risks of an edited plant in the EU is far from providing the regulatory flexibility that exists must necessarily be presumed to be higher than those of a mutant in the US through the FDA, USDA and environmental authorities, plant and lower than those of a transgenic plant. acting separately and/or jointly. Frontiers in Plant Science 10 frontiersin.org Escajedo San-Epifanio et al. 10.3389/fpls.2023.1141455 5 Conclusion: A milestone in the must therefore start working now for the post-2024 future. Let us hope that the MS do not close this legislation but that work history of EU plant breeding is continues in the medium term to ensure a regulatory framework approaching, but it is not the end of for European plant breeding that, while adequately protecting the the journey environment and human health, offers plant breeders legal certainty to remain and develop in the EU. The years 2021 to 2024 will be reported in the political history of European plant breeding as the first time the EU tried to provide CRISPR-edited plants with a regulatory framework, but it will not 6 Legal provisions cited in the text be the last. Of the two possible futures that have been described, only one of them is somewhat promising for CRISPR-edited plants, Directive (EU) 2015/412 of the European Parliament and of the but only somewhat. In our opinion, a legislation whose risk Council amending Directive 2001/18/EC as regards the possibility assessment gives more weight to obtained products and their for the MS to restrict or prohibit the cultivation of genetically specific uses than to processes alone would be closer to the modified organisms (GMOs) in their territory, OJ L 68, 13.3.2015, objectives expressed by the EU Council, namely, to achieve a p. 1–8. “clearer, evidence-based, enforceable, proportionate and sufficiently Directive 2001/18/EC of the European Parliament and of the flexible regulatory framework”. Council on the deliberate release into the environment of Nevertheless, the legislation in the pipeline remains promising genetically modified organisms. Current consolidated version, because it seems that the EU has come to this point with some after EU Regulation 2019/1381 of 20 June 2019: 27/03/2021. lessons learned. The GMO regulatory space has proven to be Regulation (EC) No 1829/2003 of the European Parliament and dysfunctional in many respects and the MS today continue to of the Council on genetically modified food and feed, OJ L 268, express conflicting views. History, as an invisible guest, is very 18.10.2003, p. 1–23. much present in this scenario, and as explained above, a holistic Regulation (EC) No 1830/2003 of the European Parliament and review of all rules applying to plant breeding would have been of the Council concerning the traceability and labelling of unthinkable. As an alternative, the EC has made a very important genetically modified organisms and the traceability of food and effort to put on the table what should be on the table and exclude feed products produced from genetically modified: Official Journal what should not. The goal has been to avoid competing interests L 268, 18/10/2003. that, while part of the long journey from farm to fork, can only be Regulation (EU) 2015/2283 of the European Parliament and of extrinsically related to plant breeding decisions. Seen in comparison the Council on novel foods: OJ L 327, 11.12.2015, p. 1–22. to how the regulatory framework for GMOs has evolved, the merit of the EC in finding its own space for genome-edited plants should not be minimised. 7 EU MS lists, by date This short-term future is, however, only promising to a certain extent, because in our opinion the proposed legislation will not be the best possible, even if it is passed. In terms of comparison with the List 1. EEC founding Members. France, West Germany, Italy, other possible futures (or future by default, see above 2 and 3) it is the Netherlands, Belgium and Luxembourg. certainly an acceptable option. But it should not be overlooked that in List 2. EEC members, late 1980s: Belgium, Denmark, France, itself, the legislation underway pays the price of being overly Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, referenced to or constrained by the influence of the GMO Portugal, Spain and United Kingdom. regulatory framework. This being the case, it is virtually impossible List 3. EU members 2001. Austria, Belgium, Denmark, Finland, to shield the regulation of genome edited plants from the deep issues France, Germany, Greece, Ireland, Italy, Luxembourg, that have surrounded GMOs (see 1, especially a, b and c). This is Netherlands, Portugal, Spain, Sweden, and the United particularly evident in the approach to risk assessment (see 5), Kingdom. although it is likely to be felt in other aspects of regulation. The best approach for this specific legislation would have been to act as if there were a holistic framework for plant breeding and as if we had to fit genome-edited plants into that puzzle. In that way, Data availability statement flaws in other pieces of the puzzle, in particular transgenics, would not have unduly influenced this legislative development. The original contributions presented in the study are included In any case, with the end of the current parliamentary term in the article/supplementary material. Further inquiries can be imminent, it is unlikely that the approach will be redirected. We directed to the corresponding author. Frontiers in Plant Science 11 frontiersin.org Escajedo San-Epifanio et al. 10.3389/fpls.2023.1141455 Author contributions Conflict of interest LE, IF, AL, and JU conceived and designed the study and the The authors declare that the research was conducted in the structure of the manuscript, as well as the basis for each of its absence of any commercial or financial relationships that could be sections. LE wrote the first draft of the manuscript. LE, IF, AL, and construed as a potential conflict of interest. JU wrote sections of the advanced manuscript. PP reviewed in particular the technical sections of the manuscript. All authors contributed to the article and approved the submitted version. Publisher’s note Funding All claims expressed in this article are solely those of the authors This work has been supported by the Spanish Ministry of Science and do not necessarily represent those of their affiliated and Innovation, VegEquity Project – Plant Breeding and European organizations, or those of the publisher, the editors and the Integration (PID2021-123796OB-C21 DER), PR. LE; and Basque reviewers. Any product that may be evaluated in this article, or Government Grant for Research Groups of the Basque University claim that may be made by its manufacturer, is not guaranteed or System, IT1733-22 Multilevel Governance and EU Law (2022-2025). endorsed by the publisher. References Abbott, A. (2015). Europe’s genetically edited plants stuck in legal limbo. 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