- 6 June 2023
- Posted by: inmentor
- Category: blog
In 2011 Emmanuelle Charpentier a French professor and researcher in microbiology, genetics, and biochemistry, and Jennifer Doudna an American biochemist began their collaboration giving rise to the discovery and development of one of the most popular and innovative technique for genome editing tool, the CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeat).
Conventional genetic mutation techniques were not suited for performing large alterations to the genome but were used to produce random mutations. By contrast, this gene editing technology enabled researchers to precisely change the genetic sequence by targeted mutation for example, to correct genetic errors in individuals, or to improve the characteristics of our crops, adapting them to climate change or making them healthier.
In sum, it consists of a quick, precise, and cheap-to-use gene-editing technique, described as ‘genetic scissors’.
So innovative was this discovery that in 2020 these scientists were awarded the Nobel Prize in Chemistry for a technology that, in the words of the committee “can change the DNA of animals, plants and microorganisms with extremely high precision. This technology has had a revolutionary impact on the life sciences”.
Although ground-breaking, it has not all gone smoothly and has had a few hiccups along the way as it is the subject of multiple and highly contentious patent battles in the US and before the EPO (European Patent Office) who, for legislation differences in the priority claim between the US and the European system, in January 2020 revoked this patent for lack of novelty.
In addition, its implication in the modification of plants and organisms has been a source of concern.
In France in 2015, the agricultural union Confédération paysanne sought annulment of provision D.531-2 of the French Code de l’environnement (Environmental Code). According to their petition, this article should include as organisms obtained by mutagenesis (GMOs), those modified with this CRISPR-Cas9 technique.
In the preliminary ruling referred to the Court of Justice of the European Union (CJUE), Advocate General Michal Bobek was of the opinion that genetically modified organisms (GMOs) obtained by mutagenesis, including those developed by novel genome editing techniques (NGTs) such as CRISPR-Cas9, are in principle exempted from the obligations of the European GMO Directive.
To state it more clearly, the controversy lies in in the way in which the genetic material has been modified, whether naturally, meaning according to Advocate Michal Bobek, by mating or natural recombination, or artificially.
In this regard, it is necessary to differentiate between transgenesis and mutagenesis.
Transgenesis is a genetic engineering technique that involves inserting one or more genes from one species into the genome of another species, resulting in a transgene. For example, a tomato plant that has a blueberry gene inserted into it to make it more antioxidant-rich and thus healthier.
Mutagenesis, on the other hand, does not involve inserting foreign DNA into an organism, but it does involve altering the genome of a species. Traditional mutagenesis, which has been used for decades, allows changes to be made to DNA by applying ionising radiation or chemical agents to a living being. This practice causes errors in its genome, which makes it possible to generate genetically modified organisms without introducing DNA from other species.
The remarkable feature of CRISPR-Cas is its precision, as it can cut both strands of an organism’s DNA. The cells have two possible mechanisms for repairing this incision.
The first, or non-homologous end joining, is based on “attaching” the severed pieces together, as if they were a wound. This can cause scarring of the DNA, and thus introduce mutations when repairing the wound.
The second is homologous recombination, whereby a sort of band-aid in the form of a DNA sequence is applied to close the wound. In this way, the genome incorporates a new fragment in the place where the previously cut sequence was.
In view of the above, genetically modified organisms (GMOs), i.e. transgenics, are currently regulated by European Directive 2001/18/EC, which imposes a very restrictive approval protocol for their use and commercialisation, based on the supposed negative effects on human health and the environment that these techniques produce.
To add fuel to the fire, on 25 July 2018, the Court of Justice of the European Union (CJEU) issued its judgment awaited by breeders concerning these new genomic techniques (NGTs). However, it did not bring good news to plant breeders and the agricultural sector as it classified genome-edited plants as genetically modified organisms (GMOs) and thus subjects them to prohibitive premarket risk evaluations.
The immediate consequence of this ruling is that prior to this 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.
According to the CJEU, the aim of the regulatory framework on GMOs is to “avoid negative effects on human health and the environment”, in violation of the precautionary principle. Although, according to the scientific community, such adverse effects on health have not been demonstrated by scientific evidence, EU legislation has been extremely restrictive with regard to genetic engineering, in contrast to other jurisdictions such as United States, Japan, China, Brazil and Australia.
This decision has been highly criticised by scientists and institutions all over for not being based on proven scientific evidence. Scientists are currently unable to reliably distinguish gene-edited plant products from natural products. The EU is therefore incapable of enforcing the GMO Directive as applied to gene-edited products imported from outside the EU, putting its own agri-tech industry at an even greater disadvantage.
A campaign has been launched against this decision involving up to 120 research centres from around Europe, releasing a statement, to bring the directive into line with new scientific developments, or at least to exempt genetically modified organisms from the disproportionate risk assessment protocols used for GMOs arguing that EU regulations no longer correctly reflect the current state of scientific knowledge.
It seems that the pleas have been heard and on 29 April 2021, the European Commission presented a study on the status of new genomic techniques (NGTs) under EU law in the context of the 2018 CJUE’s judgment and the practical questions that it raised.
According to the Commission, there are strong indications that the current GMO legislation is not fit for purpose for some NGTs and their products, and that it needs to be adapted to scientific and technological progress. It also states that NGT products have the potential to contribute to sustainable agri-food systems for example, in reducing dependency on pesticides, developing plants that are more resistant to climatic conditions, as well as contributing to food security and a more sustainable food chain.
The latest episode in this odyssey, for the moment, is the public consultation launched by the European Commission on the future EU legislation for plants produced by certain new genomic techniques that took place between 29 April – 22 July 2022.
The result shows that almost 80% of the 2200 participants consisting of citizens, academia and research institutions, companies and business associations, public authorities consider the current provisions of the GMO legislation as inadequate.
Mutagenesis techniques are highly versatile and can be used in the development of a wide range of different plant products while the existing EU rules largely date back to the 1990s and are based on the scientific knowledge of that time.
Outside Europe, the regulation of gene editing is taking very different directions from our own. The US, Australia, South Korea, Japan, Argentina and others have already taken the position that CRISPR regulation cannot be as restrictive as GM regulation. The US and Japan have mushroom and tomato varieties developed with this technique coming to market.
New products with new characteristics, better adapted to the environment, more resistant to pests or drought, will gradually be incorporated.
The European Commission has announced that it will shortly make a proposal for a new regulation for plants produced by certain new genomic techniques whose exact content is still unknown. Fears and expectations are high in the world of breeders. For many, this would be the last opportunity for the EU to correct course, avoiding once again losing the train of plant innovation.
