The controversial decision by the European courts in 2018 to regulate gene-edited organisms as GMOs has had a damaging effect on biotech companies working in this area.
The current GMO regulations were established in Europe in 2001 and were designed to strictly regulate the introduction of DNA from other species into animals and plants. These regulations do not cover mutagenesis techniques, such as exposure to radiation, where mutations are artificially induced without inserting 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 as another version of mutagenesis.
In 2016, the French government requested the current GMO directive to be re-interpreted after the arrival of new gene editing techniques. The resulting decision in 2018 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 request from the French government, Michal Bobek, Advocate General of the Court of Justice of the European Union, released a statement in early 2018 with 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 meant that any technique developed since the regulations originally 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 reached with this particular decision is ironic, because the directive specifically exempts from regulation those 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.
“Compared to what is still allowed – for example, artificial mutagenesis via radiation – CRISPR-Cas9 is so precise,” said 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. “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-Cas9, it’s like using a shotgun to shoot something versus using a really precise rifle.”
Managing the fallout
Since the ruling came out in July 2018, it has had a negative impact on academic researchers and biotech companies based in Europe. Johnathan Napier, a senior plant scientist at Rothamsted Research in the UK, was in the unique situation of being halfway through a field trial of camelina oilseed plants that were 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 changed while the plants were in the ground,” Napier told me.
He pointed out that the GMO regulations are not really set up to regulate plants that have undergone gene editing. “The risk-assessment process is based a lot on asking questions such as ‘what foreign DNA have you got in your plant?’ None of those questions are actually relevant because there is no foreign DNA in our gene-edited crop.”
While the regulations are largely aimed at commercial crops, Napier believes they will also impact funding for basic research. “The argument will go like this: ‘there’s no point in funding this basic research because ultimately this technology will never be adopted in Europe.”
Phytowelt also felt the pinch. Assenmacher explained that since the regulations were updated, a lot of customers have been asking if they can use artificial mutagenesis with radiation, an older and less precise technique, rather than more precise technology such as CRISPR. Customers see 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-Cas9 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 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 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 specializing 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 biotech companies 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 specializing in intellectual property and innovation at the University of Copenhagen.
The experts seem in agreement that a solution for a lot of companies 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. “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 Holger 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 research is regulated in Europe. The situation has mobilized researchers and businesses working in this space to work together to promote positive change in previously unseen ways.
A few months after the EU decision, 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 research centers and organizations have called on European policymakers 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 biotech companies wanting to use gene editing techniques in Europe remains murky, it seems that many are hopeful that the debate around it may be the first signs of a brighter future.
“There is an urgent need for a public-facing inquiry at a European level that, in the most transparent way, permits an analysis of what the law needs to do,” commented Hitchcock, who believes the case brought by the French government “was an indicator of the state of the law [that revealed] the law does not work and it needs to be changed.”
This article was originally published in February 2019 and has since been updated to reflect the latest advances in gene editing regulations. Cover illustration by Elena Resko. Images via Shutterstock.