Kathleen Garnett

On 25^th of July the Grand Chamber of Judges at the European Court of Justice will deliver their judgement on the Conféderation Paysanne & Others case. Many refer to this case as the “New Plant Breeding Technique” (NPBT) case. In reality the case is about a very specific form of plant breeding called  “mutagenesis” but the implications are such that the Court’s findings will undoubtedly have an impact on all forms of new plant breeding techniques, which is why this case is very important to those following the GMO debate.

Many will have heard of GMO’s. Few of mutagenesis.  Mutagenesis is the quiet, unassuming sister-technology of GMO science; mentioned in the EU’s 2001 GMO Directive and falling under the definition of a GMO but exempted from the stringent requirements on the deliberate release into the environment of genetically modified organisms.

The technology and application of mutagenesis has been around since the 1960’s, which may explain why in 2001 the EU decided to exempt this particular technology from the Directive’s application given that it has been “conventionally used” and has a “long safety record” (recital 17, 2001/18/EC). For the past 17 years those working on mutagenesis have succeeded in placing over 46 varieties of mutant herbicide resistant sunflower and six varieties of mutant herbicide resistant rape seeds on the EU Common Catalogue of Plant Varieties without having to undergo the stringent risk assessment procedures set out in the GMO Directive.  Outside of the EU mutagenesis is a fast evolving, fast growing technology as can be evidenced by the increasing number of plant varieties being listed internationally as mutants. The IAEA Mutant Variety Database lists no less than 3240 mutant variety of plants. One example of a mutant plant is a mandarin called KinnowLS developed by researchers at the University of California Riverside to be sweeter, with less seeds and a thinner skin. As the IAEA home-page states,

“The widespread use of mutation techniques in plant breeding programmes throughout the world has generated thousands of novel crop varieties in hundreds of crop species, and billions of dollars in additional revenue.”

Mutation is generally defined as, “a process by which the genetic information of an organism is changed in a stable manner, resulting in a mutation.” or more simply put, “having the ability to cause a permanent change in an organism’s genes”. Mutations, as some of us may remember from our school biology classes, can occur spontaneously and randomly in nature every few generations or so. In 2001, when the GMO Directive was approved by the EU institutions, the technology of mutagenesis relied on two primary methods to induce rapid, unnatural, mutation; either through the use of mutagenic chemicals or through the application of ionising radiation. This method creates thousands of mutant plants the vast majority of which are useless in that they either show undesirable product defects or are simply non-viable.  Only a few new plants bred out of mutagenesis show enhanced traits.  It is the latter group of mutant plants which in the EU are deemed “safe” and have been registered on the catalogue of common plant varieties without any basic risk assessment.

In the past decade, however, technological advancements in mutagenesis have ensured that the technology no longer relies on either mutagenic chemicals or ionising radiation to affect artificial mutation. A number of new, precision technologies have emerged in the field of mutagenesis which include:

• 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.

Many may agree that “oligonucleotide directed mutagenesis” technology sounds less like a benign, prize-winning new plant ready to be shown at the Chelsea Flower Show’s “Fruit & Veg stand” and more and more like some hard-core bio-tech, well, mutants. Which is essentially what they are. Dr Sarah Agapito-Tenfen, who specializes in CRISPR or gene editing technology explains,

Trait improvement through classic breeding in crops can be accelerated by CRISPR-based genome engineering. CRISPR has been tested in commercial crops to increase yield, improve drought tolerance, and increase growth in limited-nutrient conditions to breed crops with improved nutritional properties and to combat plant pathogens.

Modern mutagenic technology is so novel no one could claim that it has been “conventionally used” nor could anyone in all honesty claim that novel mutagenic technology as listed above has a “long safety record”.

Dr Agapito-Tenfen goes on to clarify that,

“The opportunity to do this genome editing also raises various safety and ethical issues that have to be considered. One of the safety concerns relates to the possibility to generate permanent DNA breaks at other, unintended sites in the genome. The rules governing off-target activity of CRISPR are just beginning to be understood in more detail. In addition, CRISPR ability to edit small bits of DNA sequences generates minimal modifications, and it also makes it more difficult for regulators and farmers to identify a modified organism once it has been released. Lack of detection of CRISPR modified crops would raise concerns over labeling and consumer’s rights, as well as risk monitoring issues.”

Mutagenic applications have objectively speaking clearly moved on since 2001, which is why the Conféderation Paysanne, a French agricultural union defending the interests of small-scale farmers sought to have the novel, new mutagenic plant varieties that simply did not exist in 2001 bought under the GMO Directive and subject to the stringent risk assessment criteria spelt out in the Directive.

There is little dispute that plants developed by novel mutagenesis fall firmly under the definition of a GMO.  Advocate General Bobek’s opinion on 18 January 2018 confirms this,

“In my view, provided that they meet the substantive conditions of Article 2 (2) of the GMO Directive, organisms obtained by mutagenesis are GMO’s within the meaning of the GMO Directive.”

The Advocate General is correct to say so. Like GMO’s, mutagenic plants are biological entities that occur not through natural mating or recombination. Once created artificially  they are capable of replication and of transferring genetic material (Article 2 “Definition” Directive 2001/18/EC). Nor, importantly and not to be over-looked  mutant plants, like GMO’s are initially unable to exchange genetic material through “traditional breeding techniques”.  In short, amateur gardeners would be incapable of spending a happy Sunday afternoon in the garden-shed with a paint brush swapping pumpkin pollen grown from seed to create a fabulous, new prize-winning pumpkin for Halloween. The only way to make mutant plants is through the use of professional scientists using professional equipment in a laboratory.

Having acknowledged that mutagenic plants fall under the definition of a GMO as set out in the Directive Advocate General Bobek then, unfortunately, goes down the rabbit hole of trying to use scientific terms to match legal principle. The Advocate General had a wonderful opportunity to pull back from the internecine squabbles over scientific terminology and create clarity and legal certainty. Instead the reader ends up with convoluted sentences such as,

“However, as long as the process of mutagenesis does not involve the use of recombinant nucleic acid molecules or GMOs other than those produced by one or more of the techniques listed in Annex IB, those organisms are exempt from the obligations laid down by the GMO Directive by virtue of Article 3 (1) of the GMO Directive, read in conjunction with its Annex I (B).”

Now was the moment for the Advocate General to think out of the box to try and understand how the law can deliver legal certainty on the use of cutting-edge, state-of-the-art novel produce since this case although referring to mutagenic plants per se encapsulates all of these highly important and very pertinent issues facing innovative products be it a mutagenic plant, a GMO plant, novel food, pesticides, herbicides, cosmetics, paints, chemicals  etc. The inter-play between innovation, novelty, safety, risk assessment, traditional, conventional, artificial is encapsulated in this case. Anyone who has been following the debate on regulating novel innovations has seen how the EU institutions are playing hot-potato amongst each other throwing the potato into each other’s hands with none of the institution wanting to be left carrying the steaming hot mutant spud  – hence perhaps such a convoluted judicial opinion.

According to Kai Purnhagen and co-authors, Bobek,

“… clarifies that it is either the EU’s or member states’ task- not that of the CJEU – to adjust Directive 2001/18/EC to technology advancement. Both notions have important policy implications and put the ball back in the court of policymakers.”

Bobek is right to suggest that it is either the EU institutions or the member states who should regulate on this matter but given there is stale-mate on this issue between the Commission, the member states and the European Parliament it would have been a good opportunity for the AG to offer more judicial clarity.  In other words all Bobek has achieved if the ECJ apply his opinion is to pass the ball back to the regulator, who will pass the buck back to the member states, who will dither amongst themselves, sit on it and pass the buck back to the Commission, who will seek an opinion from the Parliament until another NGO or industry decides to bring yet another case to court in the hope that the ECJ will make the complex issues clearer ….

“Naturally occurring”, “traditional breeding techniques”, “conventional use”, “long-standing safety record”, “precautionary principle” are all vital terminologies intentionally and deliberately woven into the text of the Directive in 2001 with the express, written intention “…to protect human health and the environment.” Yet this over-arching, Article 1 (thus number 1 objective) of the GMO Directive has been regrettably brushed aside by Advocate General Bobek as if of little or no consequence.  There is a very strong argument to be had than in 2001 the EU institutions passed a Directive with safety at the very heart of its intention based on the precautionary principle, yet Bobek proposes that the EU intended nothing more than “to draft something that exempts mutagenesis techniques from the GMO Directive unless they fall under Annex 1 B caveat.”

Thoughts that could have have been addressed in Bobek’s opinion but which are completely absent include: what does the Directive mean when it specifies “naturally occurring”? How can natural be distinguished from artificial?  What does “traditional breeding technique” imply and how can it be distinguished from novel, modern technique? Why did recital 17 talk about “conventional use” and “long safety record” and how can this be compared to novel, patented technology in light of the strict prior art requirements applied by EU patent law? Can anything that clearly is novel and untested be so safe as to be placed on the market without any risk assessment?

In Bobek’s opinion the precautionary principle, which is core to the whole rationale of the 2001 GMO Directive,  is a mere side-show to the more important exemptions of Article 3 and the caveat of Annex 1 (B).

Bobek states,

“Further to their argument as to what the EU legislature meant in 2001, the Applicants  essentially claim that in 2018, the mutagenesis exemption should be interpreted in the light of the factual conditions that existed in 2001. Therefore, only those safe techniques that were routinely used at the time of the adoption of the GMO Directive fall under the mutagenesis exemption. The stated reason for such an interpretation is the precautionary principle.

I disagree.”

It has already been established that mutagenic plants require the express intervention of mankind working in a professional laboratory, using artificial techniques before they are created. They are so novel there is no history of their safety record because there is simply no long-established, conventional track record of their use. This is not to say that their use should not be considered – but their use must certainly be examined in greater detail rather than dismissed as “they were exempted” without a closer examination of the context in which the Directive was written.

Advocate General Bobek’s opinion may please some but its overall reasoning is disappointing. It could have offered so much more but falls short on many, many fronts leaving questions unanswered that urgently need to be resolved. It will be interesting to see next week if the Grand Chamber concurs with his views or decides to address some of the fundamental issue of safety, novelty, risk assessment, new, natural, traditional in a more comprehensive, contextual and holistic manner. Failure to do so could drag this on-going and unresolved issue into the future for decades to come.