CJEU rules that mutated organisms are covered by the GMO Directive

Last week, the CJEU ruled that organisms obtained by mutagenesis are genetically modified organisms (GMOs) and are, in principle, subject to the obligations laid down by the GMO Directive. The implication of this decision is that products produced by gene-editing techniques, such as CRISPR/Cas-9, will be subject to the same regulations as transgenic organisms. The Agritech industry has met the CJEU decision with dismay, arguing that it will further stifle agribiotech innovation in the EU.

Gene editing and transgenics

IPKat followers will be familiar with the on-going patent disputes on both sides of the Atlantic concerning CRISPR/Cas-9 (IPKat post here). Gene editing technologies such as CRISPR/Cas-9 can be used to efficiently mutate the genome of plants and animals. Before the development of gene editing technologies, new plant products were produced by insertion of large sections of foreign DNA into an organism's genome (transgenics). For example, a pesticide resistant crop may be produced by insertion of a pesticide resistance gene from a naturally resistant plant into the genome of the crop plant. Conventional genetic mutation techniques were not suited for performing large alterations to the genome, but were used to produce random mutations, followed by screening and selection for a desirable phenotype. By contrast, gene editing technologies enable researchers to precisely change the genetic sequence by targeted mutation.

Transgenic Kat (Wongsrikeao et al.)
Non-human genetically modified organisms (transgenic or mutated) may be patented under the European Patent Convention, in contrast to organisms produced by "essentially biological processes" such as natural breeding methods (IPKat post here). Until the latest CJEU decision, gene edited plants were excluded from the EU's restrictive legislation relating to GMO's, and therefore possessed a clear commercial advantage over transgenic products.

The GMO Directive

The purpose of Directive 2001/18/EC on the deliberate release of GMOs into the environment (the "GMO Directive"), and Implementing Regulation (EU) No 503/2013, was to control the risk from GMOs to human health and the environment within the EU. Under the Directive, parties wishing to cultivate and sell GMO's must apply for authorization (See here for a helpful flowchart: "EU decision-making process explained").

The GMO Directive regulates the use and sale of GMO's within the EU. Organisms falling within the Directive can only be released into the environment or placed on the market following an environmental risk assessment and public consultation. Registration of GMO organisms and labeling of GMO products is also compulsory.

The GMO Directive also includes a "safeguard clause" (Article 23) allowing Member States to restrict the use and sale of GMOs previously approved by the EU (in line with Article 191(2) of the Treaty on the Functioning of the European Union (TFEU). Article 191(2) requires that, under the "precautionary principle", preventive action should be taken to avoid environmental damage. Consequently, even if a GMO product is authorised, Member States can opt-out and restrict or ban a GMO product. This opt-out provision has been widely used (full list of opt-outs by Member States here).

The GMO Directive excludes organisms obtained by mutagenesis from the definition of a GMO (Annex I B). The reasoning behind this exclusion was to prevent the stringent requirements of the Directive being applied to organisms produced by traditional, non-targeted mutagenesis techniques that had long been widely available.

Kat made from a plant product
Impact of the GMO Directive

The EU GMO authorization procedure represents one of the most stringent regulations on the cultivation of GMO foods in the world. Whilst many GMO foods and products have been approved in the EU for import and sale (GMO Register), Directive 2001/18/EC allows Member States to restrict or ban cultivation of EU authorized GMO products in their territories. Where Member States choose to ban cultivation of a GMO product, it appears the decision is often based on political motives, particularly given that the European Food Safety Authority (EFSA) will have already given the green-light to the product in question. It is widely recognized that the EU legislation on GMO Products (and that of particular Member States) has had a significant dampening effect on the agribiotech industry within the Union.

National proceedings

In France, the agricultural union Confédération paysanne, in conjunction with 8 other parties, sought annulment of the provision of the French Code de l’environnement (Environmental Code) corresponding to the mutagenesis exclusion of the GMO Directive (Article D. 531-2).  Confédération paysanne argued that:
"the use of herbicide resistant seed varieties obtained by mutagenesis carries a risk of significant harm to the environment and to human and animal health. It leads to an accumulation of carcinogenic molecules or endocrine disruptors in cultivated plants intended for human or animal consumption...moreover, to the risks of unintentional effects, such as undesired or off-target mutations on other parts of the genome".
Confédération paysanne thus sought revocation of Article D. 531-2 and the ban of herbicide resistant seeds produced by mutagenesis. Confédération paysanne further argued that the mutagenesis exclusion was at odds with Article 2 of the GMO Directive, which defines a GMO as "an organism, with the exception of human beings, in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination".

The Conseil d’État stayed proceedings and referred to the CJEU the question of whether organisms obtained by mutagenesis are covered by the Directive despite the exemption of Annex I B. The French court also asked the CJEU whether, according to the precautionary principle of Article 191(2) of the TFEU, member states have discretion to define the regime to be applied to organisms obtained by mutagenesis, regardless of Annex IB exclusion of the GMO Directive.

Preliminary ruling

In a preliminary ruling earlier this year, the Advocate General Michal Bobek was of the opinion that mutagenesis techniques meeting the criteria laid down in Article 2(2) are exempt from the obligations of the GMO Directive, provided that they do not introduce foreign DNA (i.e. that they satisfy the criteria of Annex I B). The Advocate General was also of the opinion that the GMO Directive does not prevent member states from introducing their own ban on organisms obtained by mutatagenesis according to the precautionary principle, given that the intention of the GMO Directive was not to stipulate that all mutated organisms are safe.

The preliminary ruling of the Advocate General was greeted with cautious optimism by many within the agritech industry.

CJEU Decision

In a dramatic turn-around, on 25th July 2018, the CJEU ruled that organisms obtained by mutagenesis are GMOs and are subject to the obligations laid down by the GMO Directive. The CJEU also particularly ruled that GMO Directive applies to organisms obtained by mutagenesis techniques that have been developed since adoption of the GMO Directive, reasoning that these techniques can now be used to produce organisms similar, from a risk perspective, to those that can be produced using transgenic methods.

In answer to the specific referred question as to whether organisms obtained by mutagenesis are excluded from the GMO Directive by Annex IB, the CJEU first noted that, under EU law, the GMO Directive should be interpreted by consideration of not only its wording "but also the context in which it occurs and the objectives". The Court noted that the objective of the wording of Annex IB was to exclude organisms that are "obtained through certain techniques of genetic modification which have conventionally been used in a number of applications and have a long safety record".

However, the CJEU reasoned, the GMO Directive should be interpreted as applying to organisms obtained by mutagenesis techniques that have been developed since adoption of the GMO Directive, given that these techniques can now be used to produce organisms similar (from a risk perspective) to those that can be produced using transgenic methods. The CJEU concluded that:
"excluding organisms obtained by new mutagenesis techniques from the scope of the GMO Directive would compromise the objective pursued by that directive, which is to avoid adverse effects on human health and the environment, and would fail to respect the precautionary principle which that directive seeks to implement. "

Surveying the new regulatory landscape
In view of its answer to the first question, the CJEU considered it unnecessary to answer whether Member States had the right to introduce their own ban on organisms obtained by mutagenesis according to the precautionary principle.

Perspective

Gene editing technologies are immensely valuable from a research perspective. The relatively permissive regulatory environment for the cultivation of gene edited organisms in the EU also provided a clear commercial advantage to the technologies over transgenics. The CJEU decision has been so far met with dismay by the industry, with the outcry that "classification of genome-edited organisms as falling under the GMO Directive could slam the door shut on this revolutionary technology" (source: Rothamsted Research). Are we likely to see a falling-off in European patent filings directed at gene edited organisms? At the very least, we may expect the urgency to specifically claim a gene edited form of GMO products to lessen. 


Following the EPO decision last year in Tomatoes II G 2/12 and Broccoli-II G 2/13, together with the latest CJEU decision, the agritech industry faces ongoing challenges to the development of new plant products in the EU. On the one hand, plants and plant products produced by "natural" breeding methods cannot be protected under the patent system, whilst plants and plant products produced by transgenic, and now gene editing, techniques, are subject to crippling legislation. The EPO and EU must of course balance the promotion of innovation with ethical concerns regarding genetic modification, but has the right balance been struck?
CJEU rules that mutated organisms are covered by the GMO Directive CJEU rules that mutated organisms are covered by the GMO Directive Reviewed by Rose Hughes on Friday, August 03, 2018 Rating: 5

5 comments:

Rather be safe than sorry said...

In those matters the precautionary principle should prevail, and I am inclined to find the decision very wise.

I have read some reports that the famous CRISPR/Cas-9 techniques are by far not as precise as it was made us to believe. In this respect, the decision is fully justified.

The safety of the methods themselves, be it for transgenic or mutagenetic modifications, and their impact on our environment has by no means be demonstrated.

The safety regulators are still too much influenced by large lobby groups, when they do not simply put their name on documents provided by industry.

People in Europe are not ready to swallow everything which is put in their dishes, and it is good so.

When looking at the latest blog published on Kluwer Patent blog,

http://patentblog.kluweriplaw.com/2018/08/01/international-investment-arbitration-extraordinary-remedy-concerning-decisions-european-patent-office-future-unified-patent-court/

I would not be surprised if firms engaged in these techniques will not end up with bringing States before arbitration chambers, the legality and usefulness of which has still to be demonstrated.

Millipede said...

This decision shows that food and the regulations thereof should be dealt with under th eheading 'psychology' and not under the heading 'science'.
It is completely ridiculous and not understandable from a scientific point of view that natural and thus untargeted mutation would be OK, while artificial, but targeted mutation would pose risks.
It is just the other way around: when a mutation occurs in nature, the kind of mutation, where it has taken place and which effects it causes on the rest of the genetic constituency of the plant (or animal) are unknown and thus, inherently, risky. Instead, if a targeted mutation is performed, it is crystal clear what the change has been and how this would affect the plant or animal.

It is time that scientists would uncover the myths that surround the production of food and the glorification of 'organic' foods. For instance, not using fungicides or insecticides would increase the risk of pathogens infecting the food crops, which would increase the ingestion of toxins produced by these pathogens. Doin things the way that our grandfathers have practiced would also mean that people would starve from famine (because of potato blight disease) or got sick (because of aflatoxin on their peanuts). Thank God but especially the scientists that have enabled safer ways to produce food.

Sunk Costs Fallacy said...

Re: Millipede

I'm sorry but this post is just hugely naive from a scientific perspective, despite the opening gambit which would have suggested otherwise. It simply reeks of a lack of basic understanding of genetics.

Natural "mutations", as you call it, do of course happen from time to time. However, you have to understand that natural genetic variation occur at a nucleotide level (hence the term SNPs - single nucleotide polymorphisms). These can of course still have significant effects, but the fact that a lot of research still looks into them shows that the effects are most of the time small. What you also overlook is that naturally, cell that acquire more significant mutations simply cannot survive and just die.

Genetic modification usually involves large-scale changes to genomes - entire genes or groups of genes being deleted or added. This just does not happen normally. This is simply not the same as natural variation.

Regarding risks, I would tend to agree that traditional forms of modification, using recombination techniques, are usually safe. This is more because it is a primarily in vitro technique and so there are further checks you can perform.

The problem with CRISPR is that many of the proposed therapies are in vivo, and CRISPR necessitates the use of an exogenous nuclease to carry out the modification. The initial research appeared to confirm that the nuclease is highly specific, but as has been mentioned, there have been some recent reports which show that modifications can occur elsewhere as a result.

I'm of course no all-out skeptic, but this is a significant issue for its potential as a therapy if you are actively providing a source of random mutagenesis into a live subject.

You cannot be so naive and just assume developments in technology are automatically safe. And please don't confuse artificial genetic modification with natural variation. That is literally fake news.

Do not pull my leg said...

Thanks to "Sunk Costs Fallacy" for the precise explanation of the differences between the various processes leading to mutations. Natural mutations even “helped” by seed breeders have nothing in common with provoked mutations as covered by the Directive 2001/18/EC and the present decision of the CJEU.

The gobbledygook of the big seed manipulators are not to be taken at face value. Contrary to what Millipede wants us to believe the genetic modifications he supports have not shown the safety level required.

When it comes to pesticide use, it has been shown that the level of pesticides required by GMO is ever increasing, as, probably through natural mutations, the weeds develop resistance to the pesticide. What a wonderful perspective. I do not think that by increasing the level of use of pesticides the world population will be fed correctly. To me the contrary is true!

And the mess left in nature is there for generations to come. This has nothing to do with psychology, but with hard facts. It might be fascinating from a scientific point of view to handle the genome, but history has shown us that not every scientific achievement has helped humanity. There again the contrary seems true.

Julian said...

CRISPR is not perfect as has recently been reported. More to the point, after the horrendous reaction to Monsanto's attempts decades ago to persuade the public that GMOs are 'good', is it unreasonable to see the Court veering towards caution rather than gung-ho, Frankenfood is ok? Even more to the point, how many readers of this blog are aware of the 5+ years attempt of the PR workers for agribusiness to convince the EU that NBT (new breeding techniques, such as CRISPR, Talen, etc) is squeaky clean? See Nina Hollander's article on the subject for CEO. New, efficient, profitable, etc. does not mean 'of course we want it'. The decision gives us the chance to debate it at length and to decide what we, the community, want. Me, I'm in favour with appropriate regulation.

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