Genome editing in EU law

The European Court of Justice recently produced a judgement (Case C-528/16) that means that genome edited organisms will be regarded as genetically modified and subject to the EU directive 2001/18 about genetically modified organisms, which is bad news for anyone who wants to use genome editing to do anything with plant or animal breeding in Europe.

The judgement is in legalese, but I actually found it more clear and readable than the press coverage about it. The court does not seem conceptually confused: it knows what genome editing is, and makes reasonable distinctions. It’s just that it’s bound by the 2001 directive, and if we want genome editing to be useful, we need something better than that.

First, let’s talk about what ‘genetic modification’, ‘transgenics’, ‘mutagenesis’, and ‘genome editing’ are. This is how I understand the terms.

  • A genetically modified organism, the directive says, is ‘an organism, with the exception of human beings, in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination’. The directive goes on to clarify with some examples that count as genetic modification, and some that don’t, including in vitro fertilisation as well as bacterial and viral processes of horizontal gene transfer. As far as I can tell, this is sensible. The definition isn’t unassailable, of course, because a lot hinges on what counts as a natural process, but no definition in biology ever is.
  • Transgenics are organisms that have had new DNA sequences introduced into them for example from a different species. As such, their DNA is different in a way that is very unlikely to happen by spontaneous mutation. For technical reasons, this kind of genetic modification, even if it may seem more dramatic than changing a few basepairs, is easier to achieve than genome editing. This the old, ‘classic’, genetic modification that the directive was written to deal with.
  • Mutagenesis is when you do something to an organism to change the rate of spontaneous mutation, e.g. treat it with some mutagenic chemical or radiation. With mutagenesis, you don’t control what change will happen (but you may be able to affect the probability of causing a certain type of mutation, because mutagens have different properties).
  • Finally, genome editing means changing a genetic variant into another. These are changes that could probably be introduced by mutagenesis or crossing, but they can be made more quickly and precisely with editing techniques. This is what people often envisage when we talk about using Crispr/Cas9 in breeding or medicine.

On these definitions, the Crispr/Cas9 (and related systems) can be used to do either transgenics, mutagenesis or editing. You could use it for mutagenesis to generate targeted cuts, and let the cell repair by non-homologous end joining, which introduces deletions or rearrangements. This is how Crispr/Cas9 is used in a lot of molecular biology research, to knock out genes by directing disruptive mutations to them. You could also use it to make transgenics by introducing a foreign DNA sequence. For example, this is what happens when Crispr/Cas9 is used to create artificial gene drive systems. Or, you could edit by replacing alleles with other naturally occurring alleles.

Looking back at what is in the directive, it defines genetically modified organisms, and then it goes on to make a few exceptions — means of genetic modification that are exempted from the directive because they’re considered safe and accepted. The top one is mutagenesis, which was already old hat in 2001. And that takes us to the main question that the judgment answers: Should genome editing methods be slotted in there, with chemical and radiation mutagenesis, which are exempt from the directive even if they’re actually a kind of genetic modification, or should they be subject to the full regulatory weight of the directive, like transgenics? Unfortunately, the court found the latter. They write:

[T]he precautionary principle was taken into account in the drafting of the directive and must also be taken into account in its implementation. … In those circumstances, Article 3(1) of Directive 2001/18, read in conjunction with point 1 of Annex I B to that directive [these passages are where the exemption happens — MJ], cannot be interpreted as excluding, from the scope of the directive, organisms obtained by means of new techniques/methods of mutagenesis which have appeared or have been mostly developed since Directive 2001/18 was adopted. Such an interpretation would fail to have regard to the intention of the EU legislature … to exclude from the scope of the directive only organisms obtained by means of techniques/methods which have conventionally been used in a number of applications and have a long safety record.

My opinion is this: Crispr/Cas9, whether used for genome editing, targeted mutagenesis, or even to make transgenics is genetic modification, but genetic modification can be just as safe as old mutagenesis methods. So what do we need instead of the current genetic modification directive?

First, one could include genome edited and targeted mutagenesis products among the exclusions to the directive. There is no reason to think they’d be any less safe than varieties developed by traditional mutagenesis or by crossing. In fact, the new techniques will give you fewer unexpected other variants as side effects. However, EU law does not seem to acknowledge that kind of argument. There would need to be a new law that isn’t based on the precautionary principle.

Second, one could reform the entire directive to something less draconian. It’s not obvious how to do that, though. On the one hand, the directive is based on perceived risks to human health and the environment of genetic modification itself that have little basis in fact. Maybe starting from the precautionary principle was a reasonable position when the directive was written, but now we know that transgenic organisms in themselves are not a threat to human health, and there is no reason to demand each product be individually evaluated to establish that. On the other hand, one can see the need for some risk assessment of transgenic systems. Say for instance that synthetic gene drives become a reality. We really would want to see some kind of environmental risk assessment before they were used outside of the lab.

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