Opinion of the Advocate General — ECLI:EU:C:2022:841
Date: 2022-10-27
Language of the case: French
Subject matter: Environment;Approximation of laws
Procedure: Reference for a preliminary ruling
Origin: France

Summary C-688/21 – 1 
Case C-688/21 
Summary of the request for a preliminary ruling pursuant to Article 98(1) of 
the Rules of Procedure of the Court of Justice 
Date lodged: 
17 November 2021 
Referring court: 
Conseil d’État (France) 
Date of the decision to refer: 
8 November 2021 
Applicants: 
Confédération paysanne and Others 
Defendants: 
Premier ministre 
Ministre de l’Agriculture et de l’Alimentation 
Intervener: 
Fédération française des producteurs d’oléagineux et de 
protéagineux 
  
1. Subject matter and facts of the main proceedings: 
1 The proceedings concern the rules on genetically modified organisms (also 
‘GMOs’) and in particular the rules on GMOs obtained by mutagenesis. The 
legislation, and first and foremost 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, exclude such GMOs from their 
scope. 
2 A genetically modified organism is a living organism the genetic heritage of 
which has been modified by human intervention. Transgenesis, which is a genetic 
engineering technique referred to in Part 1 of Annex I A to the Directive of 
12 March 2001 and is subject to the obligations laid down in that directive, 
EN 
SUMMARY OF THE REQUEST FOR A PRELIMINARY RULING – CASE C-688/21 
 
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consists in inserting into the genome one or more new genes from close or 
separate species. Conventional or random mutagenesis, which is referred to in 
Annex I B to the Directive of 12 March 2001 and is not required to fulfil the 
obligations laid down in that directive, consists, on the other hand, in causing 
random mutations in a DNA sequence by the action of chemical or physical 
mutageneous agents (ionising radiation). This technique was applied in vivo to 
whole plants or parts of plants, which were then subjected to selection and 
crossing procedures in order to select the mutations of interest from an agronomic 
viewpoint. Following the adoption of the Directive of 12 March 2001, new genetic 
modification methods were developed. These methods first of all consisted in 
applying random mutagenesis procedures in vitro, by subjecting plant cells to 
chemical or physical mutageneous agents. New techniques, known as targeted or 
genome editing mutagenesis, now consist, thanks to genetic engineering, in 
causing a precise mutation in a target gene without introducing a foreign gene. 
Thus, in particular, oligonucleotide-directed mutagenesis (ODM), which consists 
in introducing into cells a short DNA sequence which will cause a mutation in the 
cell identical to the cell carrying the oligonucleotide, is distinguished from 
directed nuclease mutagenesis (SDN1), which uses different types of proteins 
(zinc finger nucleases, TALEN, CRISPR-Case9) capable of cutting or editing the 
DNA. Cells thus modified are then subjected to in vitro cultivation techniques in 
order to regenerate entire plants. 
3 By application of 12 March 2015, the applicants in the main proceedings, a 
French agricultural union and eight associations concerned with the protection of 
the environment and the dissemination of information on the dangers of GMOs, 
asked the referring court to annul the implied decision of the Prime Minister 
refusing their request that, inter alia, he revoke Article D. 531-2 of the code de 
l’environnement (Environmental Code), transposing Directive 2001/18, which 
excludes mutagenesis from the definition of techniques giving rise to genetic 
modification within the meaning of Article L. 531-1 of the code, and ban the 
cultivation and marketing of herbicide-tolerant rape varieties obtained by 
mutagenesis, and to order the Prime Minister, subject to a periodic penalty, to take 
all steps to introduce a moratorium on herbicide-tolerant plant varieties obtained 
by mutagenesis. 
4 The applicants in the main proceedings submitted before the referring court, inter 
alia, that mutagenesis techniques have evolved and now make it possible to 
produce, as with transgenesis techniques, herbicide-resistant varieties. However, 
they submit, the obligations laid down in Directive 2001/18 do not apply to those 
varieties, even though they present risks for the environment or health arising in 
particular from the release of genetic material of those varieties leading to the 
appearance of weeds which have acquired the herbicide-resistant gene, from the 
ensuing need to increase the quantities and vary the types of herbicides used and 
the resulting pollution of the environment, or from unintentional effects, such as 
undesired or off-target mutations on other parts of the genome and the 
accumulation of carcinogenic molecules or endocrine disruptors in cultivated 
plants intended for human or animal consumption. 
CONFÉDÉRATION PAYSANNE AND OTHERS 
 
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5 By judgment of 25 July 2018, Confédération paysanne and Others (C-528/16, 
EU:C:2018:583), the Court of Justice clarified the scope of the exemption 
concerning mutagenesis, stating, in the light of recital 17 of Directive 2001/18, 
that Directive 2001/18 excludes from its scope only ‘organisms obtained by 
means of techniques/methods of mutagenesis which have conventionally been 
used in a number of applications and have a long safety record’. In addition, the 
Court of Justice stated in paragraph 51 of its judgment that ‘Article 3(1) of 
Directive 2001/18, read in conjunction with point 1 of Annex I B to that directive, 
cannot be interpreted as excluding, from the scope of the directive, organisms 
obtained by means of new techniques/methods of mutagenesis which have 
appeared or have been mostly developed since Directive 2001/18 was adopted’. 
6 Following that judgment of 25 July 2018, Confédération paysanne and Others 
(C-528/16, EU:C:2018:583), the Conseil d’État (Council of State, France), by a 
new decision of 7 February 2020, ordered the Prime Minister to determine by 
decree the restrictive list of techniques or methods of mutagenesis which have 
conventionally been used in a number of applications and have a long safety 
record. 
7 A draft decree was drawn up on that basis which treated ‘random mutagenesis, 
with the exception of in vitro random mutagenesis consisting in subjecting plant 
cells cultivated in vitro to chemical or physical mutageneous agents’ as a 
‘[conventional use] without any noted drawbacks with regard to public health or 
the environment’. 
8 In the meantime, that draft has been notified, pursuant to Directive 2015/1535 
laying down a procedure for the provision of information in the field of technical 
regulations and of rules on Information Society services, to the Commission, 
which issued a detailed opinion on 28 May 2021. 
9 In that opinion, the Commission states, in particular, that the distinction drawn 
between in vivo mutagenesis and in vitro mutagenesis is not supported by the 
judgment of the Court of Justice of 25 July 2018, by EU legislation or by the 
scientific advances in such techniques. In its view, there is no distinction between 
the two techniques, but rather a continuum in the genomic changes triggered by in 
vivo and in vitro random mutagenesis, as well as in the regeneration of the 
resulting plants. The European Commission relies, in that regard, on a preliminary 
report of 19 May 2020 by the European Food Safety Authority (EFSA), in which 
that authority concludes that the processes and the repair mechanisms that are 
triggered by the mutagen act at the cellular level, and that there is thus no 
difference in the way the mutagen affects the DNA, regardless of whether the 
mutagen is applied in vivo or in vitro, and that the type of mutations induced by a 
specific mutagen are expected to be the same regardless of whether that mutagen 
is applied in vivo or in vitro. In its view, random mutagenesis as a whole should be 
regarded as one and the same technique of genetic modification within the 
meaning of Article 3(1) of Directive 2001/18. It infers from the foregoing that the 
SUMMARY OF THE REQUEST FOR A PRELIMINARY RULING – CASE C-688/21 
 
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draft decree infringes that directive because it includes in vitro random 
mutagenesis within the scope of the legislation on genetically modified organisms. 
10 It is true that, in its opinion on the draft decree, 1 the Comité scientifique 
(Scientific Committee) of the Haut Conseil des biotechnologies (High Council for 
Biotechnology, ‘the HCB’) does state that the DNA repair mechanisms activated 
by alterations induced by a mutagen and/or the cultivation conditions are identical, 
whether the cells are cultivated in vitro or in vivo. However, the HCB also sets out 
the specific effects of in vitro cultivation, referred to as ‘somaclonal variations’, 
which are defined as genetic and epigenetic variations resulting from the impact of 
in vitro cultivation on plant material, the frequency of which is greater than that of 
spontaneous mutations. Thus, according to the HCB, in vitro cultivation is a 
source of metabolic changes and stress exerted on the cells and tissues, on account 
of the particular lighting, growth medium and humidity conditions of such 
cultivation, and a number of studies show how those conditions trigger a series of 
changes in how the functioning of the genome is regulated. 
11 By pleadings lodged on 16 June and 17 September 2021, the Fédération française 
des producteurs d’oléagineux et de protéagineux (French Federation of Oilseed 
and Protein Crop Producers) asks the Conseil d’État, (i) to recognise that the 
[French] State implemented the decision of 7 February 2020 by notifying the 
Commission, as required by Directive 2015/1535, of a draft decree clarifying the 
list of techniques of mutagenesis exempted from the legislation on genetically 
modified organisms and that the adoption of that decree was prevented by the 
primacy of EU law, in the light of, in particular, the detailed opinions of the 
Commission and of five Member States, as well as by the Commission’s study on 
new genomic techniques and the preliminary report of the European Food Safety 
Authority (EFSA), which constitute changes in factual and legal circumstances, 
and, (ii)  to clarify the meaning and the scope of the decision of 7 February 2020, 
so that in vitro random mutagenesis continues to be exempted from the legislation 
on genetically modified organisms and that, at the very least, effect may be given 
to potential directions in a manner consistent with EU law. In the alternative, the 
French Federation of Oilseed and Protein Crop Producers asks the Conseil d’État 
to refer a question to the Court of Justice for a preliminary ruling. 
2. Assessment by the Conseil d’État 
12 There are two opposing approaches to determining the techniques of mutagenesis 
which have conventionally been used in a number of applications and have a long 
safety record within the meaning of the judgment of the Court of Justice of 
25 July 2018. 
 
1 High Council for Biotechnology (2020). Opinion of the Scientific Committee in response to the 
referral of 2 July 2020 concerning the draft decree amending Article D.531-2 of the 
Environmental Code (ref. HCB-2020.07.07-1). (Paris, HCB), 44 p. Available at 
http://www.hautconseildesbiotechnologies.fr. 
CONFÉDÉRATION PAYSANNE AND OTHERS 
 
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13 Under the first approach, which is the approach adopted by the European 
Commission and the EFSA, account is to be taken, to that end, only of the process 
by which the genetic material is modified, whereas, under the second approach, 
which is the approach used by the Conseil d’État in its decision of 7 February 
2020, account should be taken of all the effects on the organism of the process 
used where they are capable of affecting human health or the environment, 
regardless of whether those effects stem from the mutageneous agent or from the 
method used, as the case may be, to reconstitute the plant. 
14 In that connection, the Conseil d’État will refer the first question set out below. 
15 If the Court of Justice answers that question to the effect that, in order to 
distinguish from amongst techniques/methods of mutagenesis those techniques 
which have conventionally been used in a number of applications and have a long 
safety record, account must be taken of all the variations in the organism induced 
by the process used, including somaclonal variations, which may affect human 
health and the environment, it will be necessary to determine which factors are to 
be taken into account with a view to establishing whether a technique/method of 
mutagenesis has a long safety record within the meaning of the judgment of the 
Court of Justice of 25 July 2018. 
16 In that connection, whilst it is clear from the documents in the case file that 
considerable research has been conducted into in vitro random mutagenesis since 
the 1980s and that different varieties thus obtained were registered in the 1980s 
and 1990s, that is to say before the adoption of Directive 2001/18/EC of 12 March 
2001, there is very little evidence of the use of those varieties in farming over that 
period, even though only open field use appears relevant to ensure the safe release 
into the environment of genetically modified organisms. 
17 In that connection, the Conseil d’État will refer the second question set out below. 
3. Request for the expedited procedure 
18 In addition to the particular risks which are at stake for human health and the 
environment, the present case raises a major point of controversy involving the 
European Commission and a significant number of Member States and, 
furthermore, is of concern to all Member States. Although none of those factors, 
taken in isolation, would be decisive in and of itself to justify the Court of Justice 
agreeing to the use of the expedited procedure provided for in Article 105 of its 
Rules of Procedure, taken as a whole those factors appear to justify the use of that 
expedited procedure. In the alternative, in the event that the Court of Justice were 
to reject that request, a request would have to be made that it adjudicate on the 
present case as a matter of priority, in accordance with Article 53(3) of the Rules 
of Procedure. 
SUMMARY OF THE REQUEST FOR A PRELIMINARY RULING – CASE C-688/21 
 
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4. Questions referred for a preliminary ruling 
19 The Conseil d’État refers the following questions: 
1. Is Article 3(1) of 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, read 
in conjunction with point 1 of Annex I B to that directive and in the light of 
recital 17 of the Directive, to be interpreted as meaning that, in order to 
distinguish from amongst techniques/methods of mutagenesis those 
techniques/methods which have conventionally been used in a number of 
applications and have a long safety record, within the meaning of the judgment of 
the Court of Justice of 25 July 2018, consideration need be given only to the 
methods by which the mutageneous agent modifies the genetic material of the 
organism, or must account be taken of all the variations in the organism induced 
by the process used, including somaclonal variations, which may affect human 
health and the environment? 
2. Is Article 3(1) of Directive 2001/18/EC of 12 March 2001, read in 
conjunction with point 1 of Annex I B to that directive and in the light of 
recital 17 of the Directive, to be interpreted as meaning that, in order to determine 
whether a technique/method of mutagenesis has conventionally been used in a 
number of applications and has a long safety record, within the meaning of the 
judgment of the Court of Justice of 25 July 2018, account need be taken only of 
open field cultivation of the organisms obtained using that method/technique, or 
may account also be taken of research work and publications that do not relate to 
such cultivation and, in relation to that work and those publications, is 
consideration to be given only to work and publications relating to risks for 
human health or the environment?