The current GMO regulations were established in Europe in 2001 and were designed to strictly regulate genetically modified animals and plants into which DNA from other species had been inserted. They did not cover ‘mutagenesis’ breeding techniques, such as exposure to radiation, where mutations are artificially induced without insertion of foreign DNA.
In the last few years, fast and precise gene editing techniques such as CRISPR-Cas9 have become available. This has triggered much debate about whether gene editing should count as ‘genetic modification’ or simply another version of ‘mutagenesis’.
Last summer’s decision was initiated by a request from the French government in 2016 to ‘re-interpret’ the current GMO directive based on new plant editing techniques that have arisen since 2001. The resulting decision to apply stricter regulation to organisms that have undergone gene editing has had far reaching outcomes and according to many has conclusively demonstrated that the EU’s GMO directive is ‘no longer fit for purpose.’
Following the earlier request from the French government, Advocat General Michal Bobek, who lead the Court of Justice of the European Union case, released a statement in early 2018 regarding the proposed changes to the regulations. He suggested that while crops that have undergone gene editing should be considered GMOs, they could be exempted from strict regulation if no foreign DNA was inserted.
Despite this, and contrary to scientific advice, the court ruled that only techniques that have“conventionally been used in a number of applications and have a long safety record” should be exempt from GMO regulations. This means that any technique developed since the regulation came into being, including CRISPR gene editing, is now subject to the same regulations as GMOs. In contrast, older and less precise techniques, such as exposing plants to radiation to trigger random mutations that might be useful, are not.
“The position we reach with this particular decision is ironic, because the directive specifically exempts from regulation organisms produced by an entirely random process, but it regulates those which are actually produced by a very precise process,” Julian Hitchcock, a lawyer specializing in life sciences at Bristows Law Firm in London, told me.
Nicolai Assenmacher, Product Manager at Phytowelt GreenTechnologies, a German industrial biotech that carries out genetic engineering and gene editing in bacteria and plants for customers.
“Compared to what is still allowed – for example, artificial mutagenesis via radiation – CRISPR/Cas is so precise… It’s still not really clear how many off-target effects you get, but they are way less compared to artificial mutagenesis via radiation…Compared to CRISPR/Cas, it’s like using a shotgun to shoot something versus using a really precise rifle,” he commented.
Managing the fallout
Although the ruling only came out in July 2018, it has already had a negative impact on academic researchers and biotech companies based in Europe. Johnathan Napier is a senior plant scientist at Rothamsted Research in the UK. He was in the unique situation of being halfway through a field trial of Camelina oilseed plants, edited using CRISPR to produce high levels of Omega 3 oils, when the ruling came through.
“It was, I really hope, a once in a lifetime experience where the regulatory status of your field trial changes while the plants are in the ground.”
Despite the negative ruling, Napier is planning to apply to grow more gene edited crops this year. He pointed out that the current GMO regulations are not set up to regulate plants that have undergone gene editing. “The risk-assessment process is based a lot on asking questions about: ‘What foreign DNA have you got in your plant? What size is the element? What vectors did you use?’ Well, none of those questions are actually relevant because there is no foreign DNA in our gene-edited crop.”
While the new regulations are largely aimed at commercial crops, Napier believes it will also impact funding for basic research. “The argument will go like this: ‘Well, there’s no point in funding this basic research because ultimately, the research will never be translated because this technology will never be adopted in Europe. Therefore, what’s the point?’”
The European biotech industry is already feeling the impact of the updated regulations. Indeed, a Belgian startup working on CRISPR edited bananas allegedly lost its funding a few months after the ruling.
Phytowelt has also felt the pinch. Assenmacher explained that since the regulations have been updated, a lot of their customers have been asking them if they can use artificial mutagenesis with radiation, an older and less precise technique, rather than newer more precise technology such as CRISPR. He says the customers this as their only option to produce new genetic strains for their breeding projects.
The company has also lost business due to the ruling. “Before this decision, we had five customers who were close to signing contracts with us in genome editing projects with CRISPR/Cas and due to the decision of the European Court, they’ve decided not to do it since they would not have been able to use the product itself in Europe,” said Assenmacher.
“Since we have also other incomes, we managed to get over it… but I’m really sure that a lot of startups have been influenced by this so extremely that they had to stop.”
Why Europe is the biggest loser
In contrast to the European ruling, many other countries have decided to adopt Michal Bobek’s view and exempt gene edited organisms from GMO regulation, as long as they do not contain foreign DNA. This includes the US and Canada as well as a number of South American and Asian countries.
“I know that several large biotech companies have pulled out of research programs in Europe altogether following the ruling; in the US, by contrast, field tests are underway as we speak,” Jacob Sherkow, a professor at New York Law School specialising in life sciences, told me.
“I think there’s a more complicated story here about European attitudes to science, industry, and food culture than ‘progress.’ This is a case where, I think, European attitudes to ‘big science’ and food purity have trumped any form of scientific realism.”
While big biotechs have been affected, it is likely that smaller companies will bear the brunt of the change in legislation.
“The increased regulatory costs for such uses might be a problem that can be addressed by the big agricultural companies, but not necessarily by small and medium-sized enterprises. Hence, this decision is pushing technology back into the hands of the big market players in Europe,” said Timo Minssen, a professor specialising in intellectual property and innovation at the University of Copenhagen.
The experts seem in agreement that a solution for a lot of companies following the regulation change will be to move either partly or wholly out of Europe to somewhere with more favorable legislation.
“If the law is no good, then you have to go somewhere else,” said Hitchcock. “The lack of an appropriate regime that’s facilitative and looks at the dangers of not adopting such technologies is economically bad for Europe and they really need to pull their finger out.”
Europe will also lose access to products, crops and technology from other countries, as it will become difficult for a company developing products somewhere with less strict regulation to sell to companies or organizations situated in Europe.
“Excessive regulation of new agriculture technologies – that neither improve the safety nor quality of crop products – will discourage investment and innovation, and may preclude or limit the use of innovative techniques in the development of new varieties by both the public and private sector,”commented Holge Elfes, a spokesperson for Bayer’s crop science division in Germany.
While the nature of EU law makes it unlikely that the ruling will be overturned any time soon, it has highlighted that there are big problems with the way such research is regulated in Europe. It has mobilized researchers and businesses working in this space to work together to promote positive change in previously unseen ways.
Indeed, in November last year the chief scientific advisors to the European Commission issued a statement concluding that “new scientific knowledge and recent technical developments have
made the GMO Directive no longer fit for purpose.”
In addition, over 85 European plant and life sciences research centers and organizations have called on European policy makers in a position paper to safeguard innovation in plant science and agriculture and prevent what amounts to a ban on developing crops that are climate resistant or more nutritious than currently available varieties.
Although the way ahead for plant scientists and biotechs wanting to use gene editing techniques in Europe remains murky, it seems that many are hopeful that the increased discussion that has been initiated may be the first signs of a brighter future.
“There is an urgent need for a public-facing enquiry at a European level that, in the most transparent way, permits for an analysis of what the law needs to do,” commented Hitchcock.
He believes that the case brought by the French government was a litmus test. “It was an indicator of the state of the law. It’s in fact more a ruling on the law than on the particular case in question and that test said, ‘The law does not work and it needs to be changed.’”