August 3, 2018, by Brigitte Nerlich
Genome editing in the news: Trying to keep up
Gene/genome editing has been much in the news recently and it is becoming increasingly difficult to stay on top of new developments. The last two weeks alone have seen major announcements, which I shall briefly list in this blog post.
This leads me to a question that has been troubling me: How does one do public engagement, let alone Responsible Research and Innovation in such a fast-moving context?
Gene editing and off-target effects
On 16 July the journal Nature published a paper in which scientists from the Wellcome Sanger Institute (Cambridge) reported that they had “discovered that CRISPR/Cas9 gene editing can cause greater genetic damage in cells than was previously thought. These results create safety implications for gene therapies using CRISPR/Cas9 in the future as the unexpected damage could lead to dangerous changes in some cells.”
This caused some discussion and concern, but the jury is still out about the wider implications for CRISPR research. Whatever the eventual outcome of more research into this, the paper became a backdrop for other gene/genome editing stuff that happened in July.
Gene editing and human reproduction
On 17 July the Nuffield Council on Bioethics published a report on genome editing in the context of human reproduction. This provoked a lot of, in my view, unnecessary, speculation about ‘designer babies’ and some counter-arguments against such speculations, by Kenan Malik, David Aaronovitch and Sarah Chan, for example.
These speculations happened despite the report itself never speculating about designer babies and focusing instead on recommending very sensible actions in the context of genome editing and human reproduction. Interestingly, it presciently stated that designer babies “constitute a background of cultural memory, informal knowledge and expertise that could easily be mobilised in relation to heritable genome editing interventions”. But what were the, in my view, sensible recommendations? Here are some of them:
- “We recommend that social research should be carried out to develop greater understanding of the implications of genome editing for the welfare of the future person. […]
- We recommend that before any move is made to amend UK legislation to permit heritable genome editing interventions, there should be sufficient opportunity for broad and inclusive societal
- We recommend the establishment of an independent UK body to promote public debate on the use of genomic and related technologies to respond to societal challenges; to help to identify and understand the public interests at stake; and to monitor social, cultural, legal, and health impacts.
- We recommend that governments in the UK and elsewhere should work with international human rights institutions, such as the Council of Europe and UNESCO, to promote international dialogue and to develop a framework for international governance of heritable genome editing interventions.
- We recommend that heritable genome editing interventions should only be licensed on a case-by-case basis subject to: assessment of the risks of adverse clinical outcomes for the future person by a national competent authority (in the UK, the HFEA); and strict regulation and oversight, including long-term monitoring of the effects on individuals and social impacts.”
Gene editing and GM crops
On 25 July the European Court of Justice made a long-awaited ruling on genetic modification of crops, specifically about gene editing – a judgement that took several years to make and was prompted by concerns of what one might call interested groups. This judgement too provoked some discussion and raised some eyebrows. I quote Ottoline Leyser whose piece for The Conversation encapsulates my own feelings on this:
“The European Court of Justice has made an important ruling on genetically modified crops. Since 2003, new crop varieties produced by genetic modification have had to be assessed for their risks to the environment and human and animal health before they can be farmed in the European Union. The court has now decided that genetic modification includes any technique that induces genetic changes ‘in a way that does not occur naturally’. This includes new genome editing techniques such as CRISPR/Cas9, but also approaches that have been used in plant breeding since the 1960s.”
Older approaches to genetically modifying crops are seen as more ‘natural’ and are therefore supported by the court, while newer ones, like gene editing, which are arguably safer, are not. The issue at stake is nicely encapsulated by this chart. And there are other issues, well summarised by Leyser. (For a critique of the trait vs process issue, see Royal Society here.)
Leyser and other experts have come to the conclusion that the judgement is logically flawed and doesn’t even ask the right questions. A similar view was expressed in an editorial for The Guardian. For more information you can also read this article in Nature, but there are many more, including a nuanced blog post on the PLOS synbio blog.
It is interesting that another, more critical, Guardian article on this topic evokes the Nature article with which I started this post and which put a real dampener on CRISPR enthusiasm: “A study published in the journal Nature last week found that the gene-editing technology Crispr-Cas9 can cause significantly greater genetic distortions than expected, with potential ‘pathogenic consequences’”.
[I have just come across this German reflection on this issue and how science communication could be done better: unfortunately it’s in German, but it’s really good!]
Gene drives
At the same time as we got new insights into the more difficult aspects of CRISPR, grappled with problems that gene editing my pose in the distant future for technologies of human reproduction, got a strange ruling on gene editing crops, there were also various advances in the field of ‘gene drives’ (which made its debut in mammals), but I don’t want to go into those, as this post is already getting too long.
Gene editing and public engagement
My question is: How can ordinary people, the ones so fervently evoked in the Nuffield and other reports on gene/genome editing, deal with all this and how can public engagement activities keep up with these ever-new developments and ever wider and deeper moral, ethical, legal and political questions? Some insights can come from public surveys, but, of course, they only provide a small snapshot of what should be a global ‘debate’.
At present, genome editing, including germline editing, seems to evoke more hopes than fears in the public sphere, both in the United States and the United Kingdom. A 2017 US survey “found that people really only drew a line when editing, especially germline editing, was for ‘enhancement [of human abilities] rather than treating disease”, and this seems to continue in 2018. A Royal Society report found that the UK public is cautiously optimistic about genetic technologies, including genome editing.
I wonder what a survey on European attitudes to the EU ruling on gene editing in crops would bring to light…., including, at the moment at least, UK attitudes… Oh, and what will all this mean after Brexit…? And what does it all mean for ‘responsible innovation’? Answers on a postcard, please!
Image: Max Pixel
I am a bioscientist and I am a little surprised by the outcry of my scientific peers. Contrary to Prof Leyser, I don’t see a logical flaw in the ruling from a purely legal standpoint. Her quote above “The court has now decided […] ‘in a way that does not occur naturally'[…]” Is wrong in that this decision was already made in Directive 2001/18, thus was decided much earlier and a new ruling has to take this legal definition into account. This is not to say that such a directive cannot be changed in the future and I will elaborate on that below.
Also from a scientific point of view the ruling seems logical to me. The use of CRISPR/Cas9 as a means of introducing genetic alteration cannot be called anything else but genetic engineering, which by the very definition must result in a Genetically Modified Organism (GMO). I have discussed this with peers and am open to be corrected on this argument. The argument that it is safer than traditional genetic engineering methods does not change that fact, in my opinion. Furthermore, as the Nature article shows that you quote above: CRISPR is not without flaw and off-target events were recorded.
So far to explain why I am surprised in the reaction of the scientific community that usually reacts level-headed and logical. Now I want to add a big BUT: I absolutely agree with the scientific community that the legislation on genetic engineering should be revised. Not only for CRISPR derived organisms, but for any method which can arguably make safer strains than so called “traditional” methods (random mutagenesis). In my opinion this should not happen through one court ruling, but rather through a democratic process changing the current legislation based on current scientific understanding. A court ruling in July in favour of novel techniques would have been a short-cut to using certain techniques but it would not have addressed the bigger issue of genetical modification and how to handle GMO’s in Europe. This could have led to more insecurity of the wider population of what makes a GMO and what does not. Personally I would have difficulties explaining why a CRISPR derived strain is not a GMO. Furthermore, the fact that CRISPR has off-target effects could have given an argumentative stance to anti-GMO groups, since it was praised as a tool without unknown consequences which it turned out not to be.
To summarise, I am pro-GMO but agree with the European Court ruling from a legal and scientific point of view, which does not mean that the GMO debate should end here. The EU should allow GMO’s for consumers, but let’s get it right from the basics without short-cuts.
You make a really good argument. I suppose the role of the ECJ is to interpret the law, not to make policy. However, European etc. societies need to have some debates I think about what’s natural and what’s artificial and what that distinction actually means, if anything. And of course also about the technology/product distinction etc. Have you seen this? https://blogs.royalsociety.org/in-verba/2018/07/26/when-is-genetic-modification-not-genetic-modification/ which is quite interesting…
That is a very interesting read indeed. I guess I look(ed) at the subject from a technological perspective as well. (I hope I am excused to do so since I am a user of the technology and spend most of my time introducing non-natural changes in the genomes of bacteria) It was eye-opening for me to look at it differently, as the article suggests as “[…] a product-based approach that focuses on the genetic change that has been made.” rather than how it was made. Therefore, distinguishing between genetic changes that could occur naturally, even if they were reached by genetic engineering, and changes that would never occur naturally (eg transgenesis).
This should definitely build the cornerstone of future policy. And I absolutely agree with you that the discussion needs to be had and regulations need to change. Thank you for an interesting insight!
And thanks for an interesting discussion!