‘Genomes Do Not Respect National Boundaries’: In Conversation with Anjana Ahuja and Ultan McDermott
After the Genetic Modification Debate at the Cambridge Union, I sat down with a member of the proposition and the opposition to put them in close conversation with each other and try to unpack some of the complex issues that had been raised in the debate. The motion was This House Believes Genetic Modification of Humans is the Future of Healthcare, and in proposition was Ultan McDermott, who is a consultant oncologist at Addenbrooke’s Hospital, Cambridge and as of last year the debate’s sponsor company AstraZeneca’s chief scientist in oncology. In opposition was Anjana Ahuja, a science columnist at the Financial Times who holds a PhD in space physics from Imperial College London.
My main question is, thinking about the kind of science that we’ve heard about tonight, increasing in viability as time goes on – is it possible for debates like this to maintain their currency in a field which is constantly changing, constantly evolving?
AA: I write for a global audience on the science that matters – science that has ethical, political, social, cultural impact and genetic modification of humans is definitely in that bag….and we don’t have enough debates like this, but it’s better to have the debate late than not at all. And I do think that the more we discuss with general audiences what the impact of scientific progress can be, then the more informed we can be as we move forward, because as we’ve seen with the genome-editing of the two babies in China there is the legal and regulatory framework issue but there is also a moral dimension to what’s been done. With some of these things we’re talking about the future of humanity and the way that we want our species to evolve, and I think those are conversations that scientists can’t have amongst themselves.
UM: I agree with all of that – I think with CRISPR and artificial intelligence…arguably these are the things that our government should be discussing at present, whereas there is another topic that is sucking the oxygen out of the room. These are hugely important topics, and I think it’s important as well in this setting as well as more broadly across the UK to begin to educate individuals that as scientists, we also consider the societal impact; we think about the ethics; we think about the long-term ramifications; the effect it will have on our patients. I’m not sure if, in the UK, there is a sense that scientifically there are individuals who are beginning to consider all of these issues together. I think there’s a huge education need in the UK, even very early in schools…we were discussing earlier about the importance of critical thinking and this is a part of that, and [debates] like this are part of that. More broadly, there is a responsibility to educate the public on the impact that science will have – I think to most people on the street science is an abstract concept, but these issues are going to have a very profound impact in the next ten to twenty years.
AA: In some ways they’re having an impact now – with what happened last year with the gene-edited babies, there were two notable things that came out of that. One was that the scientists didn’t know this had happened – which is really an awful indictment of self-regulation. And the second thing was the shock in the public at what happened, and this idea that we were caught woefully underprepared and we hadn’t begun to think about it, because when you think about CRISPR it’s only really been in the market since 2011/12 and I don’t think anyone thought about producing germline-edited humans just yet. So I think that does remind us that there is a rogue element and that we do need to think more broadly than self-regulation, and we do need to include everyone in that conversation. That was a real shock to me…I mean I’d heard rumours but…in some ways I was quite disappointed by the response of the scientific community, because actually if you look at the post-mortum of that [situation] it turned out that quite a few people had an inkling of what was going on but nobody had stepped in, really. I mean, the guy who did it was under the radar but he wasn’t flying so low that he couldn’t have been spotted. Because the danger of it is if you get off on the wrong footing, as we saw with the genetic modification of food, it can be very, very hard to row back, and the problem is that you’re then stuck in the public eye with all the negative baggage which can overwhelm the positives of it.
UM: There are huge positives too…it’s important to [distinguish] somatic and germ-line editing: the risks of somatic are considerably less, so arguably the advances there will be much more rapid or are happening already. But I think like it or not, last year was hopefully as a wakeup call to the scientific, medical, ethical and political communities, I think it needs a number of the relevant stake-holders. Hopefully it will be a catalyst for those individuals and parties coming together – I think we do need a set of international standards with appropriate sanctions. There will always be rogue elements, that’s always going to happen, but the modifications are going to happen and we either regulate or we don’t – we must regulate them, and I think if we apply strictures as to when they can be used they will modify over time…I think what I would be concerned about is if individual countries start deciding on their own [boundaries] for doing this, because that’s a recipe for disaster.
AA: I think that’s a really important point, because…when the Chinese work was announced, or rather revealed at that Hong Kong conference, even the other scientists from China were unclear as to whether the law had been broken. And even now there isn’t a great deal of clarity on that, what kind of sanctions the scientist involved is going to face. And that’s just within one country! And we do know that elsewhere in China, there are trials going on where patients who have had some gene editing have not necessarily been tracked, so I think there are real questions to ask about how we do this, especially as this technology crosses borders – like you say, the piecemeal regulation and laws that we have may not be fit for purpose, so we do need to bang heads together probably…
I spoke to someone who put forward a view that the invention and popularisation of genetic modification techniques is in many ways similar to the invention of the atomic bomb – you can’t un-invent that technology; once it’s been brought to the table it can’t then be taken away again. How do you think our knowledge about these techniques is impacting on our progress forward?
AA: I will just say that there is a distinction, in that you need the raw materials for an atomic bomb, whereas CRISPR is cheap and dirty I suppose. It’s easy to use and you have the raw materials in every country.
UM: That’s the danger of CRISPR I suppose, is it is by far the most accurate way to modify DNA, and it’s also quite easy to do…It’s very powerful, and usually in the past very powerful tools have been technically quite complicated, so therefore only a few labs could do it – CRISPR unfortunately has broken that mould. It is amply accessible…the genie is out of the bottle, and we have to regulate. People may roll their eyes and say that it will be difficult to reach a consensus, but if we don’t then last year is gonna be just the beginning. Last year has to be a wakeup call. One would imagine that if the US, China and the EU got together and starting putting a set of regulatory standards [in place] then that would begin to carry quite a lot of weight. You won’t carry every country with you, that’s just impossible, but unfortunately genomes do not respect national boundaries. It is true, and the reality is that there will unfortunately be germ-line edited kids for various reasons that will happen off the grid, but I think that ties into the idea of a national consensus which covers what sanctions they can apply and rigorously enforce those. And arguably if you get the big hitters together then you begin to get momentum.
There was a statement from one of the speakers [on the proposition] during the debate who said “I trust that you are all sensible” in reference to self-regulation – I wondered how you both felt about that?
AA: I thought it was very naive.
I feel like we’ve seen too much history to believe that.
UM: I don’t trust people to be sensible…I think for that reason, to my mind that’s why it can’t be left to individuals, that’s why we need to get a group of scientists, doctors, lawyers, ethicists, families with disabilities; the entire breadth of stakeholders involved in putting together a regulatory framework. It cannot be “we’ll be sensible” because history shows people are not sensible.
AA: We already have it now…
UM: It only takes one person not ‘being sensible’…it is a good point that that forever tarnishes the reputation [of the technology]. Because the reality is that genetic modifications will play a role in healthcare – it’s quite right that there are lots of other things we should be doing – but it will be hugely beneficial, there’s no doubt about that. They’re not going to be the panacea for every single illness, that’s not realistic, but my big concern that people get so focused on the germ-line – which is the riskier part – and we end not doing the somatic side, which is less risky but with stuff like cancer is going to have a huge impact.
AA: I think the somatic side is really uncontroversial, because the only risk is to the patient…
UM: Well, the only risk is to give someone big muscles or make them green, if they’re silly enough to do that.
AA: …or the risk is that you cure the cancer.
UM: That’s right, certainly at AstraZeneca on the somatic side, we are looking at therapeutic editing for genetic diseases of high un-met need. I think our big focus is the safety, even on the somatic side. It’s like any drug, you want to make sure that it’s safe.
AA: It is a different kettle of fish though, than germ-line editing, because with germ-line editing if you get it wrong, in some ways you’re condemning a whole family line. That’s the distinction.
UM: Exactly – who takes over the long-term follow up? Who takes responsibility for that? So, Robin [Lovell-Badge, another proposition speaker from AstraZeneca] was part of the committee who drew up the first set of guidelines in 2016 at the first international summit on human gene editing. That’s where I stole the ‘compelling medical need’ and ‘absence of real alternatives’ terminology, but the additional things that they had are ‘strict independent oversight’, ‘assessment of societal impact’, and ‘long-term follow-up’. So if you add those, as a basis, that’s not unreasonable and if you apply those to most things people would want to do in a germ-line setting, most of the [problems] you’d knock off straight away. Because obviously [with the gene edited babies in China] there was no compelling medical need and plenty of reasonable alternatives [with the issue of HIV]. I think it’ll be ‘watch this space’ with international consensus…I think there’ll be a meeting of minds, or I hope there will be. There needs to be.
AA: I think the other thing to say is that the UK is a real leader in biotech legislation.
UM: I was at a summit in London and the director of the Human Fertilisation and Embryology Authority was there…they’ve been doing this for twenty, thirty years now. I think the UK has a really special role to play in this…we shouldn’t stand back at all. We have decades of experience bringing together complex, innovative genetic therapies with a ‘sensible’ but effective regulatory framework. We have done that for thirty years and the HFEA has real expertise in this area. Mitochondrial DNA replacement? Who would have thought of that ten years ago? And the UK was the first place it was ever done. So we should be leading the way. There’s lots of other things we’re not doing so well on, but here we really could lead the way.