In vitro random mutagenesis is confirmed as not within scope of GMO regulation; gene editing remains within scope. Report: Claire Robinson

Plants produced using in vitro random mutagenesis do not fall within the scope of the EU's GMO regulation, Directive 2001/18, according to a ruling last week by the European Court of Justice.

In vitro random mutagenesis involves subjecting plant cells to chemical or physical agents (e.g. radiation) that cause damage (mutations) to the DNA, in the hope that a resulting mutation may produce a desirable effect in the plant. This kind of mutation breeding has been used for decades but only affects a minority of the plants on the market.

The ruling has been widely misreported, including in a Reuters piece headlined, "In-vitro plant gene editing technique excluded from GMO rules, EU court says". In fact the new ruling does not remove gene editing, such as that performed using the CRISPR/Cas method, from the GMO regulation or strip any regulatory safeguards from gene-edited plants. These plants continue to fall under the GMO regulations, as ruled by the Court of Justice in 2018.

Gene editing is sometimes called directed mutagenesis, in contrast with random mutagenesis. It is the latter technique that the ruling is concerned with.

The new ruling effectively affirms the status quo in the EU and changes nothing regarding "new GMOs". While the GMO regulation has always recognised random chemical- and radiation-induced mutagenesis techniques as GMOs, these techniques have been exempted from the requirements of the regulation due to an assumed decades-long history of safe use alongside conventional breeding. That remains the case with the new ruling.

The new ruling also states that it makes no difference whether the mutagenesis is performed on whole plants or plant parts (in vivo) or on plant cells in a Petri dish (in vitro). The court views both these techniques equally, as exempted from the requirements of the GMO regulation.

Debate in France

The ruling comes as a result of a debate in France over how plants produced with random mutagenesis techniques are regulated. The French farmers' union Confédération Paysanne and other associations had asked the French government to subject organisms produced with random mutagenesis techniques to the GMO regulations – which would have meant subjecting them to risk assessment and labelling.

In 2020 the Conseil d'Etat, France's apex court, ruled that organisms produced using in vitro mutagenesis techniques should be subject to the EU GMO regulation. However, the French government didn't implement the ruling. So Confédération Paysanne and the other associations brought another case before the Conseil, seeking a ruling to force the implementation of the 2020 decision. The Conseil asked the European Court of Justice to rule on whether in vitro random mutagenesis should fall under the GMO regulation.

Importantly, the Court of Justice emphasises that its ruling is supported by the dual criterion:
(i) conventional use in a number of [breeding] applications and
(ii) with a long safety record.

This criterion, the Court says, is "closely linked to the very objective of that legislation, namely, in accordance with the precautionary principle laid down by EU law, to protect human health and the environment".

It's crucial to note that the Court does not suggest that newer techniques such as gene editing are exempt from the regulation and in GMWatch's view there is nothing in the ruling that would justify that interpretation, or that suggests that the Court is headed in that direction.

On the contrary, the ruling shows that the Court is aware that certain GM techniques can lead to modifications of the organism which differ, in their nature or by the rate at which they occur, from the techniques exempted from the GMO regulation due to a long history of safe use alongside conventional breeding. These types of GMO, the Court states, are not exempted from the requirements of the regulation as this "would not respect the intention of the EU legislature".

Reactions

The farmer union ECVC is very concerned by the ruling. In a press release it said the judgment "has opened the door to a massive flood of unlabelled and unassessed GMOs in farmers’ fields and on European citizens’ plates, whilst at the same time allowing a handful of multinational organisations to use patents to appropriate and control cultivated biodiversity".

ECVC said, "These techniques [in vitro mutagenesis] are all patentable and are therefore neither natural nor traditional. They were developed shortly before 2001 at the same time as transgenesis (even though most products arrived on the market well after 2001), and generate the same health and environmental risks that justify the current regulatory obligations of risk assessment, labelling and traceability."

ECVC explained the implications of the ruling: "Seeds resulting from these 'in vitro mutagenesis' techniques will now only be regulated by the EU seeds catalogue of varieties. These techniques leave identifiable traces in the organisms they are used on. But unlike the GMO regulation, the catalogue does not require any breeding techniques to be indicated, nor is it mandatory to disclose the processes that allow the identification of the genetic and epigenetic 'signatures' that the techniques leave. It will thus become impossible for farmers and consumers to distinguish these GMOs from any other non-GMO conventionally bred plant. Seed companies will be able to market GMOs by claiming to have used these in vitro mutagenesis techniques and directly registering their new varieties in the catalogue, even for GMOs that in reality result from one of the new genetic modification techniques still regulated today."

GMWatch adds that while the ruling was not a surprise and in our view is consistent with our own understanding of the EU GMO regulation, in vitro mutagenesis plants undoubtedly pose a higher risk than in vivo mutagenesis plants. That's because in vitro tissue cultures induce huge numbers of mutations and these will be added to the mutations caused by the radiation or chemicals. Some of these mutations could result in the plant becoming unexpectedly toxic or allergenic. In vivo mutagenesis doesn't use tissue culture, so that source of mutations would be avoided, though the mutations induced by the chemicals or radiation would still be present. It is likely that in vitro mutagenesis plants have been in the food supply for some time.

Nevertheless, it is a positive result that gene editing is not deregulated under this ruling and that its language does not (in our view) leave space for that to happen.