A recent ruling by the Court of Justice of the European Union (CJEU) has increased the difficulty of developing plants modified through mutagenic breeding. This blog post presents two perspectives on the judgment, one from Kathleen Garnett and another from Felix Beck.
Confédération Paysanne & Others, Case C-528/16: GMO cabbage or plain old cabbage?
Kathleen Garnett, Consultant and writer on EU government and law
In 2016, Stefan Jansson, a plant biology professor at Umeå University in Sweden, consumed a meal of cabbage he had cultivated in his garden using seeds modified with CRISPR Cas-9 technology. Jansson believed this to be the first time anyone had eaten a CRISPR-modified cabbage.
Two years later, the CJEU issued a ruling on mutagenic plants that disappointed Jansson and many other scientists. The ruling effectively classified his CRISPR Cas-9 cabbage as a GMO.
The scientific community has criticized the CJEU’s ruling in the Confédération Paysanne & Others case, with some calling it disastrous. This piece will explain the legal reasoning behind the judgment. Since the case revolves around “mutagenesis,” a specific plant breeding technique, a brief explanation of this technique will provide context.
Background on transgenesis and mutagenesis
Transgenesis and mutagenesis are the two most common artificial methods scientists use to modify the DNA of plants.
Transgenesis involves transferring a gene from one species to the genome of another. This is accomplished through sophisticated techniques like gene guns or soil bacteria.
Cross-breeding between different species does not occur naturally. However, transgenesis allows bioengineers to overcome this species barrier. Annex I A of Directive 2001/18, the EU law on genetically modified foods, describes transgenic techniques.
In the United States, many crops such as maize, soybeans, corn, and cotton are grown using this technology. In contrast, the EU only cultivates one commercial transgenic crop, approved in 1998.
Mutagenesis, on the other hand, alters the genetic makeup of an organism without transferring foreign DNA. This process, involving stable changes to an organism’s genetic information, can occur randomly and spontaneously in nature. Since the 1960s, scientists have been inducing rapid, unnatural mutations in plants to enhance certain characteristics, such as making citrus fruits sweeter and thinner-skinned.
It’s important to note that the term “mutant” plant is the scientific term for these novel plants and is not meant to be alarmist. Even the FAO/IAEA, the international organization responsible for cataloging these plants, uses the term “mutant” in its database.
Conventional mutagenesis
In 2001, mutagenesis primarily relied on mutagenic chemicals or ionizing radiation to induce rapid mutations in plants. These two technologies will be referred to as “conventional” mutagenesis in this piece.
The EU chose to exempt conventional plant mutagenesis from Directive 2001/18/EC, likely because it was a well-established technology with a long safety record. Conventional mutagenesis creates numerous mutant plants, most of which are not viable or have undesirable traits. Only a small fraction exhibit enhanced traits, and it is these plants that were exempt from the GMO Directive in 2001. Over the past 17 years, over 46 varieties of mutant herbicide-resistant sunflower and six varieties of mutant herbicide-resistant rape seeds have been added to the EU’s common plant variety catalog without undergoing the GMO Directive’s risk assessment procedures.
Novel mutagenesis
In the last decade, advancements in mutagenesis have moved away from mutagenic chemicals and ionizing radiation. New, precise technologies have emerged, including:
site-directed nucleases (SDN) (including ZFN-1/2/3 and CRISPR systems);
oligonucleotide directed mutagenesis (ODM);
cisgenesis;
RNA-dependent DNA methylation (RdDM);
Grafting (non-GM scion on GM rootstock);
reverse breeding; and
agro-infiltration.
Unlike traditional cross-breeding, creating novel seeds using these methods necessitates sophisticated scientific techniques and equipment. While growing plants from these seeds can be done conventionally, producing the seeds is not.
Questions referred to the CJEU
In 2015, Confédération Paysanne, a non-profit organization, and eight other groups concerned about the environment and GMOs, petitioned the French Prime Minister to prohibit the cultivation and sale of herbicide-resistant rapeseed created using traditional mutagenic techniques. They argued that these varieties posed a risk to the environment and human and animal health.
When their request was denied, the applicants appealed to the French Conseil d’État, which referred the case to the CJEU for interpretation of EU law. The Conseil d’État sought to determine whether plants created using new, directed mutagenesis techniques:
meet the definition of a GMO as per Article 2 of Directive 2001/18/EC;
are exempt from the GMO Directive’s impact assessment and traceability requirements;
qualify as GMOs according to Article 4 of Directive 2002/53/EC, which establishes a European common catalog of agricultural plant varieties;
are subject to harmonizing measures that restrict member states’ ability to regulate them; and
fall under the precautionary principle of Article 191(2) of the Treaty on the Functioning of the European Union (TFEU).
Advocate General Bobek’s Opinion
In January 2018, Advocate General Bobek interpreted the GMO Directive narrowly. He agreed that new, directed mutagenesis techniques fall under the definition of a GMO but are exempt from the precautionary principle and other requirements due to the Annex I B exemption.
Bobek argued that the EU intended to exempt all forms of mutagenesis from the GMO Directive, regardless of when they were developed. He reasoned that the GMO Directive only addressed transgenic GMOs, as described in Annex I A. Had the intention been to include all new breeding techniques, the Annex I B exemption for mutagenesis would not have been necessary. Consequently, all mutagenic plants are exempt from the GMO Directive’s stringent requirements. Bobek concluded that the GMO Directive allows member states to implement their own regulations on mutagenesis, as long as they adhere to overarching EU law obligations.
CJEU Findings
The CJEU’s judgment differed significantly from Advocate General Bobek’s opinion.
The CJEU ruled that organisms developed using mutagenesis techniques are considered GMOs under Directive 2001/18.
The court stated that both transgenic and mutagenic techniques modify an organism’s genetic material in a way that does not occur naturally.
Furthermore, the CJEU determined that the use of “inter alia” in Annex I A implies that the list of genetic modification techniques is not exhaustive. Therefore, techniques not specifically listed are not automatically excluded.
The court concluded that only organisms created using mutagenesis techniques with a long history of safe use are exempt from the directive.
The CJEU emphasized the need for a strict interpretation of the Article 3(1) exemptions listed in Annex I B, citing its ruling in the Białowieża Forest case, which drew on precedents related to the Habitats Directive. The CJEU stated that the wording of Article 3(1), along with the Annex, does not offer clear guidance on the specific techniques the EU intended to exclude.
Therefore, the CJEU opted for a contextual examination of the exemption. Recital 17 clarifies that the Directive does not apply to techniques with a history of conventional use and a long safety record. Consequently, the exemption does not extend to newer techniques whose risks to the environment and human health remain uncertain.
The court highlighted that the ability to directly modify an organism’s genetic material through mutagenesis can achieve results comparable to introducing a foreign gene. It also noted that these new techniques allow for significantly faster and larger-scale production of genetically modified varieties compared to conventional mutagenesis methods.
This is where the precautionary principle becomes relevant. The court cited recitals from the Directive, emphasizing the potential for irreversible environmental effects from the release of living organisms, regardless of the quantity. It stressed the need to manage risks to human health and the environment.
The court reiterated that the precautionary principle was considered when drafting the Directive and should be applied during its implementation. It further emphasized the importance of monitoring the development and use of GMOs.
The court concluded that recital 17 justifies the exemption for conventional mutagenesis due to its established safety record. However, the precautionary principle, as highlighted in Article 4(1), does not support exempting new mutagenesis techniques developed after the adoption of Directive 2001/18.
The impact of the Judgment
This ruling is significant because the Directive’s scope is no longer limited to transgenesis techniques. Any artificial modification of a plant using new, directed mutagenesis techniques must adhere to the requirements outlined in Directive 2001/18.
Furthermore, the judgment’s language raises numerous unanswered legal questions. The reasoning could potentially extend to all new plant breeding techniques, not just transgenic and mutagenic ones.
The CJEU repeatedly emphasizes terms like “naturally occurring,” “conventional use,” “at a rate and in quantities quite unlike those resulting from the application of conventional methods,” and “long safety record.” These terms are central to the Directive’s distinction between conventional and novel, artificial techniques.
Some argue that the use of mutagenic chemicals and ionizing radiation in conventional mutagenesis, though considered conventional in 2001, is not “naturally occurring” and should also be regulated. This raises questions about the definition of “conventional use” and its temporal implications. If “naturally occurring” has a legal definition, can terms like “artificial,” “induced,” and “forced” also be defined? These considerations could impact the EU’s biotechnology policy in the future.
Unlike Advocate General Bobek’s narrow interpretation of the Annex I B exemption, the CJEU adopted a broader approach. The court prioritized the Directive’s objective of safeguarding human health and the environment. By focusing on the potential irreversible effects of releasing mutant plants into the environment, the CJEU aligns mutagenic plants, and possibly all new plant breeding techniques, with the Directive’s original intent of protecting human health and the environment from unforeseen consequences of GMO technology through the precautionary principle.
Comments
This ruling does not prevent researchers from continuing their work on new plant breeding techniques. However, it mandates that they operate in regulated environments. The risk assessment obligations outlined in the Directive necessitate objective and transparent scientific analysis. Prof. Jansson and his team can continue their research, but it will likely need to be conducted in a controlled laboratory setting rather than a garden.
The ruling does, however, make it more difficult for companies to commercialize new, mutagenic plants in the EU. It’s important to reiterate that the ruling does not ban the cultivation of these plants in the EU. However, due to the stringent obligations, very few GMO varieties are grown in the EU.
To illustrate the challenges of commercializing mutagenic plants in Europe, consider Prof. Jansson’s CRISPR Cas-9 cabbage. Under the new ruling, it would be subject to notification, authorization procedures, environmental risk assessments, risk management measures, and regular inspections. Maintaining the anonymity of the seed supplier would also be impossible.
While this ruling is a setback for those seeking to commercialize new plant breeding techniques without restrictions, its immediate effects on EU consumers, who already enjoy a diverse selection of fresh produce, seem less significant.
To be or not to be… a regulated GMO: The CJEU’s verdict on genome editing
Felix Beck, Doctoral candidate, University of Freiburg/Germany
The CJEU’s recent judgment concerning the regulation of genome-edited crops has sparked debate across the EU. Scientists and plant breeders have criticized it as regressive, while GMO skeptics praise it for upholding the precautionary principle. This piece will examine the legal reasoning behind the Court’s decision.
The French Conseil d’Ètat asked the CJEU to clarify whether crops modified using “genome editing” techniques are subject to the EU’s GMO Directive (2001/18/EC). Genome editing refers to techniques like CRISPR that enable precise modifications to the DNA of various organisms, allowing for the activation or deactivation of specific genes. Unlike traditional genetic engineering, genome editing is more precise and does not always involve introducing foreign DNA. Whether organisms modified using these techniques should be subject to the EU’s GMO regulations has been a point of contention.
The court readily concluded that genome-edited organisms meet the definition of GMOs under Article 2(2) of Directive 2001/18/EC. It avoided addressing whether the phrase “altered in a way that does not occur naturally,” used to define GMOs, pertains to the genetic modification technique or its outcome. This suggests the Court leans toward a process-oriented interpretation, where any in vitro genome modification would be considered a GMO under Directive 2001/18/EC.
The more complex issue was whether genome-edited organisms qualify for exemption from regulation as products of “mutagenesis.” Traditional mutagenesis exposes organisms to chemicals or radiation to increase genetic mutations, with breeders selecting for desired traits. Article 3 and Annex I B of Directive 2001/18/EC exempt organisms bred through “mutagenesis” from the directive’s scope. However, the term is not clearly defined, leaving room for interpretation regarding its application to new mutagenesis techniques.
The CJEU based its decision on recital 17, which states that the Directive should not apply to techniques with a history of conventional use and a proven safety record. The Court reasoned that targeted mutagenesis lacks such a safety record and is therefore not exempt.
This reasoning is sound. A distinction exists between the general definition of mutagenesis (any method inducing genetic mutations) and its legal meaning within Directive 2001/18/EC. Recital 17 suggests that only techniques known and commonly used when the Directive was adopted in 2001, such as those using chemicals or radiation, should be exempt. Otherwise, any change in scientific terminology could alter the scope of regulations.
The Directive does not address whether targeted mutagenesis is as safe as or safer than conventional mutagenesis; it simply lacks a comparable safety record. Therefore, rejecting a dynamic interpretation of “mutagenesis,” as Advocate General Bobek proposed, was reasonable.
However, the CJEU also relied on general claims about the risks of genome editing being similar to those of conventional GM techniques and that genome editing could accelerate the development of modified organisms. These claims, disputed by many scientists, might make it difficult for them to accept the legal validity of the judgment.
Ultimately, the CJEU is not the appropriate body to assess the risks of genome editing or determine its regulation. This is a policy matter for the European Union legislature. The court should not be faulted for its interpretation of the Directive but rather for the European Union legislature’s inaction. When proposing and revising the Deliberate Release Directive, the European Commission pledged to update it regularly to reflect scientific and technological advancements. It is time for them to fulfill this promise.
Art credit: John Byrne and Terry Austin, Marvel Comics