Regulatory aspects of gene-edited crops: A Q&A with Jim Dunwell
Posted 22nd June 2018 by Jane Williams
On January 2018, Michal Bobek, in a preliminary judgement in a case at the European Court of Justice, advised that “organisms obtained by mutagenesis” should not be seen as genetically modified, unless they contained recombinant nuclear acid molecules or other GM organisms. 
This preliminary opinion has left plant scientists around the world concerned about the future of gene editing technologies in the EU. The gene editing technology market is expected to grow to $10.55 billion by 2027 and it is expected to see considerable growth in Europe alone with new partnerships formed by companies such as Merck KGaA and Evotech AG.  But should the court, in its final judgement, decide that CRISPR falls under the EU’s GM legislation, CRISPR startups will be subject to the costly regulation process.
At the 6th Plant Genomics and Gene Editing Congress: Europe, Professor Jim Dunwell, University of Reading, discussed this issue in more detail, focusing on the regulatory aspects of gene-edited crops, specifically future commercialisation, the process of the legal regulatory case, and its possible outcomes in the context of European agricultural production and global trade post-Brexit.
We asked Jim about the protracted decision on regulation and what this will mean for the future of gene editing in crops.
What can plant gene editing do for agriculture and global food security?
Plant breeding in the past has, to some extent, relied upon the generation of mutations to generate variation. This was a random process and was achieved through chemical or irradiation induced mutation.
You combine any beneficial traits you’ve got and cross them into other backgrounds and test to confirm that they are better than your existing variety. The big advantage with genome editing is that you can create variation much more precisely, so it’s a much more efficient way of adding variation to a breeding program because you don’t have to get rid of all the deleterious changes that you sometimes get with randomised mutation breeding.
It’s to do with identifying a target gene and changing the DNA sequence of that target gene directly or using genome editing to change the expression of the gene. In other words, it’s not just possible to change the sequence of the gene or other parts of the genome, but it’s also possible to alter how that gene is switched on or off, because sometimes that dictates the specific performance of the plant.
It has already been applied commercially in a handful of important crops, which are the easiest ones to work with. The hope is that the technology now being developed can be used for even more species. However, we’re still in the very, very early stages of seeing how the technology can be applied and what impact it will have on global agriculture.
Commercial development is more highly advanced in the US because the regulatory position there is much clearer and more precise. People in larger businesses and commercial investors need to be sure that the products of their research can get to the market as quickly as possible. But in Europe, unfortunately, people can’t see how to get to the marketplace quickly, because of regulatory complexity and the interaction with the political system.
What will the recent judicial opinion mean for scientists?
The original judgement from the Advocate General on this European Court of Justice ruling is simply a preliminary ruling and will offer some guidance as to how the judges themselves will reach a final decision. I estimate that the final judgement won’t come out until the summer.
The reaction to the interim advice from the Advocate General is quite mixed because it’s obviously a long, complex thirty-page legal document. The main conclusions were that some of the mutation processes could be excluded from the “GM regulations” There’s already an existing system in legislation made in 2001 that says that mutagenesis is a named exclusion to the GM regulations.
What the judgement of this preliminary legislation didn’t say exactly was whether new genome editing methods would fit within the mutagenesis exception or not. Instead, it focused on whether there was evidence of recombinant DNA and final product or not. Although early judgement addressed some legal conclusions, it really didn’t give the precision that people working in the area would like to see.
On the other hand, the Advocate General also said that even if the new technologies go into the excluded category, countries are also free to take an independent judgement to decide if they would like to take national regulation authority over those new technologies. That doesn’t make the global European situation any clearer because different countries can pick and choose.
When the judgement is released late in the summer, it going to be considered quite differently in different countries. There’s a specific paragraph in Germany’s agreement to form a new coalition that they wanted to retain some independence on regulation. It said when the judgement comes out, Germany would take the approach to allow freedom of choice. If you read between the lines, that suggests they might impose regulation on these new techniques, regardless of what the European Court of Justice says. That makes the future market position very uncertain. In comparison, just 2 or 3 weeks ago, the USDA made a precise and clear judgement that they are not going to regulate these processes in most cases with regards to future breeding of crops in the US. The commercial investment environment there is much more straightforward.
Do you think that’s a better approach?
I think it gives clarity, and it’s the reason why commercial investment in this type of work in the EU is being effectively withdrawn. So the large companies are still doing the work, but they’re not doing it in Europe. They do in the US or in Southeast Asia, China in particular, where clearly the market size is larger, which leaves Europe behind in a way. If you want to get to the marketplace, you have to make the path to the market completely clear before any company will invest in your 5- or 10-year program to develop a commercial product. That’s the discouraging element of having this uncertainty within the regulatory approach.
Will regulation present financial obstacles?
Yes, any regulation certainly increases the cost. First you must apply for regulation, then you put your product forward to the regulatory systems. In the EU, if you go through this 27-or 28-nation system and if it is regulated as being GM, history says that some countries may be in favour and some against, and then if you go down to the independent country level, then you have to apply to different countries to see whether or not they will approve it.
There will be a certain disadvantage and that kind of uncertainty will mean that Europe will lose economically. I think it is unfortunate.
How could gene-edited crops be considered to be products of mutagenesis?
One argument is that the genetic change that we induce by using genome editing could have occurred spontaneously and naturally. The fact is, in most cases, they could because mutations occur all the time at a certain rate. What you can’t predict is how long it would take to identify those mutations, so you could search for decades in germplasm to try to find this optimum mutation.
If you know that you can induce a specific DNA change directly, then clearly researchers will do that, but they’ll end up with a genome edited variety. However, you can’t identify how such a variety was derived. It may contain single base changes, or a small deletion in the DNA, but it’s not possible by looking at the DNA sequence to say how you found a specific mutation. If you can’t identify the origin, then that makes bad legislation because objectively, regulation should not focus on the means by which a product was generated.
The final product should be considered since spontaneous mutations are not regulated and never have been. We consider this traditional inbreeding. It’s sort of ironic that those spontaneous mutations should be considered okay; the one that you produce in the lab, which is more precise… people say it’s not okay. It should not be subject to a different level of scrutiny.
If you can’t identify an origin, how can you biologically and fairly regulate something? If this mutation could occur naturally, many people and many regulators say they should not fall inside any regulatory boundaries and should just be considered something that could have occurred naturally without human intervention.
Why do you think there’s an argument for regulating genetic changes that haven’t occurred naturally?
In scientific terms, chemical or irradiation-induced mutation is random, so that it can mutate lots of genes as well as the one you’re interested. In contrast, in genome editing the off-target effects, which may occur, are likely to be much fewer.
I think as the technology improves, its precision will increase and any off-target effects will be minimal. That’s what’s happening in the animal cell culture world where this technology is even more advanced than it is in crops, as the really significant investment is in medical and animal genetics and potentially in modifying human cells in the future.
Stay tuned for more insights from Jim Dunwell in the next article, where we will be discussing GMOs, public perception of gene edited crops, and the principles that should be put in place to gain the consumer’s trust in gene editing technology.
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