Instant Genius - Is gene editing inspiring or terrifying? – Nessa Carey

Episode Date: April 25, 2019

In 2012, scientists developed a method to edit any part of the human genome, and the implications were astounding. Now, we’re starting to see the technology’s potential; we will soon cure previously untreatable diseases, but at the same time, rogue scientists are experimenting in ways considered unethical by the wider medical community. So where does gene editing go from here? In this week's Science Focus Podcast, Nessa Carey, author of the book Hacking the Code Of Life: How gene editing will rewrite our futures (£12.99, Icon) explains how gene editing was developed, how it works, and why it holds so much promise for medical science. We talked to her about the potential ways this technology could be mishandled, and how we should go about making ethical decisions around when and for whom gene editing is used. What does a future like where we can manipulate the human genome to any end? Should we be inspired, or terrified? She speaks to BBC Science Focus editorial assistant Helen Glenny. If you like what you hear, then please rate, review, and share with anybody you think might enjoy our podcast. You can also subscribe and leave us a review on your favourite podcast apps. Also, if there is anybody you’d like us to speak to, or a topic you want us to cover, then let us know on Twitter at @sciencefocus. Listen to more episodes of the Science Focus Podcast: Eating for your genes - Giles Yeo Can we slow down the ageing process? What makes me 'me'? - Aoife McLysaght The genetic hunt for the Loch Ness Monster - Neil Gemmell Everything that’s wrong with the human body - Nathan Lents Transhumanism: using technology to live forever - Mark O’Connell Follow Science Focus on Twitter, Facebook, Instagram and Flipboard Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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delivering digital precision with analogue warmth. So you can experience exceptional sound at home. Music just as the artist intended. Visit name audio. com to learn more. Everybody, pretty much everybody, had been working together. There had been ethical reports, there was good collaboration. Everyone accepted that we needed to move in a very stepwise way and then suddenly a scientist in China announced that he had gene edited to baby girls and had done it in such a way that they would be germline modified. So they

will pass on this change to their children. And it's just caused carnage. Because now it's so much hard to build this consensus, it's just been the most extraordinarily unhelpful development. It really is one of those situations where you just put your head in your hands and you think, thank you for making us all look like crazy people. You're listening to the Science Focus podcast from the BBC Science Focus magazine team. With the UK's best-selling science and technology monthly, available in print and in several digital formats throughout the world.

Find out more at sciencefocus.com or look out for us in your app store. Hello and welcome to the Science Focus podcast. I'm Jason Goodyear, commissioning editor at BBC Focus magazine. In 2012, scientists developed a method to edit any part of the human genome, and the implications are astounding. And now, seven years on, we're really starting to see the technology's potential. Soon, we'll be able to cure previously untreatable diseases, but at the same time, rogue scientists are experimenting in ways considered unethical by the wider. medical community. So where does gene editing go from here? Mercer Kerry is here to explain how gene editing was developed, how it works, and why it holds so much promise for the future of medical science. We talk to her about the potential ways this technology could be mishandled and how we should

go about making ethical decisions around when and for whom gene editing is used. What does the future look like when we can manipulate the human genome to any end? Should we be inspired or terrified? Here's editorial assistant Helen Glennie talking to Nessa Kerry. Okay, so Nessa, your new book is called Hacking the Code of Life, how gene editing will rewrite our futures. Why are you interested in writing about this topic? Because it's the biggest thing that's happened in biology for decades, really, in terms of how it's going to change what we can do as scientists, as researchers,

and as what we can do that will change the world around us really quite dramatically. there just basically isn't a bigger story. It's quite remarkable. And what is your background? So my background is I used to be an academic scientist. I was a senior lecturer at Imperial College and I'm a visiting professor there. And in 2001, I moved to industry. So I worked in the biotech and the pharmaceutical sectors for over a decade. Now I work for myself training people and also when I have the time writing popular science books. A lot of things could come under the umbrella of genealded. or genetic modification.

Can you tell me a bit about what we've done in the past and how that's led up to the technology that we've got now? Yeah, so we've been able to do genetic modification of one form or another since the 1970s. And it was a very valuable technology in terms of the kind of questions that scientists could answer, but it had major limitations. It was quite cumbersome. It was very difficult to do really high precision work.

What's happened since 2012, actually, is this new form which is called gene editing, which uses a very different technology. It's sometimes called CRISPRC-Cast-9. And this new technology is quite extraordinary. It's incredibly easy to use. And you can use it in any species that you want to target, and you can use it to create absolutely exquisite changes in genes.

So, for example, in humans, we have about 3 billion base pairs, the basic letters of our genetic alphabet, And you can use gene editing to change just one of them. And we've never had a technology like it. We've never had one that can work with such precision. And we've never had one that's so easy to use. And I think that's where the fabulous strengths of gene editing lie, but also the things that are most concerning for us lie,

because actually you don't need to be much of a specialist to be able to get this technology to work. Yeah, so can you give us a quick gene editing lesson? How does CRISPR KS9 work? Basically, all you know is you put into cells a short stretch of nucleic acid, so a little bit like our genes, and it will find a matching sequence in our genes, and it will bind to it. And you can do this for any organism. You just need to design this short stretch of genetic material.

At the same time, you also add an enzyme. It's basically a protein that acts like a pair of scissors. So when the stretch of gene that you've put in finds its matching sequence in the DNA of whatever organism you're targeting, it will bind and then this enzyme, these molecular scissors, they'll also bind and they'll cut the DNA, but only where this introduced genetic piece of material has bound. So what you get is targeting of a very, very precise cutting mechanism. That's then been refined slightly since 2012 so that not only can you cut the DNA and repair the DNA, you can actually just say change one letter of our genetic alphabet. So it's basically been made more focused and more precise, but the basic technology is just finding the right bit of DNA and then cutting it.

Okay. And you mentioned that it's not particularly hard. And we've seen a few home gene editing kits and things like that crop up onto the market. Are people actually doing this to themselves? So there's certainly been at least one person who claims to have done this to himself. He got himself filmed while he was injecting gene editing material into his muscle. He injected gene editing material that was basically to make his muscles grow bigger, and they didn't. But he's your kind of classic garage biohacker.

And yeah, there is no reason why more and more people won't do this. and it would be incredibly difficult to control. And did anything go wrong for him when he tried to inject his muscles with this stuff? No, it didn't. Nothing went wrong. You know, he didn't start developing second arms or anything like that, but nothing went right either. It's that classic problem where you can't base anything on an N of one. We have no idea what dose of the gene editing reagents he used.

We've no idea if they were functioning. If he had developed bad reactions, it could easily have been because the stuff had been contaminated. It was scientifically completely meaningless. In PR terms, it was genius, but scientifically tells us nothing. Now, there's a distinction that we need to make when we're talking about CRISPR interventions, and that's somatic gene editing versus germline gene editing. Can you explain the difference between those two processes? Yeah, sure. So somatic is by far the less contentious of the two versions. Somatic means we would use gene editing to try and create changes in the body's tissues. So, for example, you might try and prevent somebody's muscles from wasting

by giving them gene editing that increases muscle growth, or you might try and repair something in the liver. The treatment is just for that person that you're treating. It won't affect their children. However, germline gene editing is very different. In germline gene editing, we would be creating individuals whose DNA was changed throughout their body, including in the cells that create either sperm or eggs, depending on whether they're male or female. If you create a change that way, that change will be passed on to all of their offspring, should they have children. And that's incredibly different from anything we've ever done before. That is changing the DNA of future generations in humans. And nothing like that had ever been done or even imagined until very

recently. Right. And so you do that by changing the DNA of an embryo at a very early stage. Is that Correct? Yeah. Basically, what you would do is you'd use the same technology as test tube babies, so in vitro fertilization, and you would treat very early embryo when it's only really a few cells, and you would want every cell in that embryo to carry exactly the same change. That's very different from, say, treating a child or treating an adult. So we'll come back to germline editing, but right now, what's going on in semantic gene editing? What have we been able to do? So no one's actually been treated yet using this technology, but it's going to be very close. There are a number of companies who are already getting regulatory approval from drug authorities in Europe and in the US to carry out gene editing.

And the very first disease that we're likely to see treated through this is probably going to be either sickle cell disease or the closely related disease thalcemia. And this is a condition where patients have mutations in their hemoglobin and they become anemic, they can get severe joint pain, they can become very prone to infections. And that's almost inevitably going to be the first set of diseases that we see treated with this technology. And there are a number of reasons why they're the perfect test bed for gene editing. Yeah, what are those reasons? Why do those ones work so well? They work so well partly because we can identify those patients really well. we know what mutations to look for, so that helps. Also, there's a lot of people who have sickle cell disease or thalassemia. So that means, A, that you have a large potential patient population for

trials, but B, it also makes it commercially much more viable to do this, because these clinical trials are going to cost tens or probably hundreds of millions of dollars to develop this. The other reason why sickle cell disease is such a great one to treat is what you can do is you can take the bone marrow cells out of the patients. You can treat the bone marrow cells in laboratory culture with the gene editing, select the ones where the gene editing's gone right, and then put them back in the patients to repopulate the bone marrow and start creating healthy red blood cells, which are the ones affected in this disease. So sickle cell disease, it's almost like the universe has given us the perfect test case, which is a terrible way of

describing it because it's an awful disease for people who have it. But it is the perfect one for gene editing. So what are we expecting from these trials? Is this the sort of thing where you think that everyone who is treated should be cured or is it less of a success right there expecting than that? No, I mean the first stage of the trials will be, I would imagine, because this is usually how it works for safety. So you check that nothing goes wrong. You don't re-inject these cells into the bone marrow and find catastrophic consequences. And no one's expecting to see bad safety outcomes from this because repopulating bone marrow is a very well-established procedure. What you would actually hope to see with sickle cell disease is actually that you can cure

the disease. And that would be extraordinary because we can't cure sickle cell disease at the moment. We give patients drugs and they're not very good and they have to take them all their lives. Because when you repopulate the bone marrow, those cells that are edited will produce more cells that are also edited, this will become a basically self-sustaining therapeutic system within the patient's body. It's probable, though, that we may not get the doses, et cetera, right the first time round. So one of the things that we'll be looking at in clinical trials, scientists will be

examining things like how many cells do you have to edit, how many of them need to repopulate the bone marrow, what level of gene expression you need to get of the normal hemoglobin gene in order to see a good clinical outcome. So there's a lot of questions that need to be addressed, but most of them are quite logical stepwise questions. After we've done trials for sickle cell anemia and thalcemia and stuff like that, presumably that technology will then be applied to other conditions. What do you expect to see in the future?

What kind of conditions do you think we can use this treatment for? I think it's inevitable that the first treatments that we see will be for very clearly defined genetic disorders. So conditions where there's one gene that's gone wrong and we know exactly what happens when that gene goes wrong. So it could be for conditions such as ones where patients have extraordinarily high cholesterol levels, for example. Or it could be for conditions where patients can't metabolize certain ordinary food stuffs so that those build up to toxic levels in the brain and cause brain down. damage. So I think we'll probably see it for things like that. We might see it for there's a condition in children called spinal muscular atrophy where again we know exactly what the genetic defect is. So I think it's inevitable that the first applications of this technology are going to be for these

conditions where there is a really severe clinical outcome and they are driven by really well-defined mutations in single genes. So that's where this technology will inevitably have its greatest impact in treatment of human conditions. Now there's this view of CRISPR that it's sort of a magic treatment that will end up being able to fix everything, but what can't we treat with it? Well, we can't treat most of the conditions that are actually crippling most healthcare systems and that most of us develop. We can't at the moment foresee terribly well how we'd use it to treat the diseases of aging.

So things like Alzheimer's disease, we can't imagine how we could use it for that. We can't imagine how we could use it for mental health disorders. And that's because actually we don't understand enough about these conditions. We wouldn't know what to start changing in order to reverse these conditions or even to stabilize them. So the conditions that are absolutely the ones that are hitting the aging population are the ones that are going to be most difficult to treat. And that remains true even with CRISPR in our toolbox. Germline editing has been slightly more contentious. And we recently saw news hit the headlines of a Chinese scientist who edited the DNA of embryos of a set of twins.

And those changes would be passed on to the DNA of all the cells in their body and passed on to any children they had. So can you explain why this is quite a contentious project for the scientists to undertake? So changing the germline, changing the DNA of future generations, that's an enormous step. That's one we've never really deliberately taken before. And we know from lots of developments in the past that when there's something this dramatic that researchers can do, it's incredibly important that the scientific community moves in step with general public understanding of what the possibilities are. And also that we have a really strong ethical framework and a good regulatory framework for this kind of work, because this is a really dramatic change.

So everybody, pretty much everybody, had been working together. There had been ethical reports, there was good collaboration. Everyone accepted that we needed to move in a very stepwise way. And then suddenly a scientist in China announced that he had gene edited to baby girls and had done it in such a way that they would be germline modified. So they will pass on this change to their children. And it's just caused carnage. now it's so much hard to build this consensus.

And it's just been the most extraordinarily unhelpful development. It really is one of those situations where you just put your head in your hands and you think, thank you for making us all look like crazy people. Because it's just been the most appallingly premature act. And I think everybody's in despair about it. And what's the worst case scenario for germline editing? Well, the worst case scenario is that the germline editing could cause changes that we can't predict.

So one of the concerns about the work that's been conducted in China is that it hasn't even been done very well. And we're not yet sure how precise the editing was. So there's a risk that this may have introduced other mutations into the DNA that will be passed on to the offspring. The other big thing that I think is a broader concern is that we will use germline editing to start changing future generations for character. characteristics that we like at the moment or characteristics that actually advantage some groups over others.

Now, I think the whole fear of we're going to create these super bright, super fast, super strong and super gorgeous humans who will be massively advantaged by gene editing, that's extremely unlikely. We wouldn't have a clue how to begin to do any of that. but that is, I think, the bigger background concern for people is what happens once this becomes a fully commoditized technology. How do we stop, in particular, the parental generation making decisions for their offspring that their offspring had no say in whatsoever? It starts to challenge the whole concept of what do we mean by consent in terms of medical procedures? And that's a very thorny issue. Yeah, and I guess along with that is the question of where do you draw the line? What is a condition that desperately needs fixing?

What is something that's just a nice to have? Yeah, absolutely. I mean, a classic example of that is, I think, if you think of a condition where children are born in pain and spend their entire lives in excruciating pain with very little quality of life, I don't think many people would have too many concerns about gene editing to prevent that. But if you think about something like deafness, some parents would consider having a deaf child an absolute disaster. Other parents wouldn't see it as that big a deal and deaf parents may

actually prefer to have a child who is deaf. How do we decide where the line is drawn there and who should make that decision? That's a really difficult one. Yes, is there any regulatory body at the moment that's set up to make those decisions? So the UK, for example, has a very good regulatory system when it comes to working on embryos and what you can and can't do. But one of the problems is that globally, there is no overarching regulatory framework. And that means we could end up with situations where in the future as gene editing becomes more established, we start finding people essentially acting as gene editing tourists. If they can't get the edit done on an embryo that they want in Europe or in the US, they may take the decision to go to other states where there

won't be such strong regulatory frameworks and to have the editing done there. And that's going to be extraordinarily difficult to control. There must be people out there who are looking forward to cures for diseases that are well-established as being caused by, you know, a problem in DNA. Are there conditions out there that we know will definitely be able to fix with germline editing if we, you know, advance the technology enough? Yeah, absolutely. Huntington's disease would definitely be able to be completely removed from a family tree by doing gene editing.

There are, however, of course, other ways of doing it. You could actually just continue with prenatal testing, for example, and then aborting fetuses who are carrying a mutation. So there are other ways of making sure that diseases are not passed on in a family. But there may be good reasons why a family doesn't want to use those other roots. But I think we can imagine that there will be significant pressure from families where they have seen what happens as a consequence of this mutation in their family. And they don't want other family members to keep going through this. And it's going to be very difficult to balance that pressure against a very stepwise desire to build regulatory frameworks that work for the long term. In theory, we could use this technology, not just to fix problems, but to make improvements like,

using gene editing to make us, I guess, versions of more intelligent, faster, fit are stronger. Are there any genetic changes that have been identified that would be easy to make in terms of making us sort of better rather than fixing a problem? There are some, it depends how you define better. So, for example, if what you wanted was your kids to be extremely mussely, we know what change you were. do there. You would get exceptionally musseled children. It would be a bit freaky, but we'd know how to do that. So there are a few things like that. But in terms of things like how people look or how fast they can run, and particularly in terms of things like intelligence, where it's incredibly difficult even to define what we mean by that, those are characteristics which are such a

complex interplay of multiple genetic influences and the environment. And particularly, you environment in terms of wealth, that actually the idea that we'll be able to edit for those, at the moment it's massively beyond anything of which we're capable. Yeah, so the wealth issue seems to be something that comes up a lot. Do you know about any cases where you have people who are willing to pay a lot of money in order to get some sort of experimental CRISPR treatment for a condition that they're suffering from? So we haven't seen any examples of that that I can think of in the West. We certainly know that all the press coverage says that in China there have been at least

100 people who have been given gene editing as a treatment for their disease, not germline gene editing, but somatic gene editing. We have no data whatsoever on what that change has actually been, possibly because European and American journals might not be willing to publish the data. data if they felt the work hadn't been done ethically. It may also be because the Chinese experimenters may not wish to declare it publicly because then they might find themselves getting sued for inappropriate use of the CRISPR technology by the organizations that own the patents. And we have to remember that China is a very privatized healthcare system. We always

have this vision that China, because it's a communist state, has massive nationalist health systems. it doesn't. People absolutely have different access to different levels of healthcare depending on their income. So I would think it's pretty likely that in China at least we're seeing somatic gene editing as a consequence of access because of wealth. Yeah, it's kind of easy to imagine a situation where a sort of underground semantic gene editing lab is earning quite a lot of money because they could promise people, you know, treatments to diseases which at the moment don't have treatments. Do you think there's a chance of that? Oh, I think unfortunately there's every chance of that. And what we'll see is a lot of charlatan organisations making money out of people who are desperate. We're already seeing that with, say, stem cell therapy clinics who offer treatments that have absolutely no

regulatory control and no real hope of working. And they're basically just ripping off. desperate people. And I think we will absolutely see that. So how do you think we should go forward from where we are now? I think one of the things that's going to be absolutely key is that every person working in biology who's even vaguely interested in gene editing should be doing everything they can to engage with the wider public and also with policymakers and with anybody else who has an interest in healthcare. And in other aspects of this as well, such as in things like creation of genetically edited crops or creation of genetically modified farm animals, there are all sorts of implications of this technology. And I think it's incredibly important that all scientists are

engaged in a genuine dialogue with the wider population. And it should absolutely be a dialogue. It needs to be a case of scientists listening to the concerns of the wider population, not just trying to transmit information and trying to say, this is how it's going to go, this is how it will be. We are as a community of scientists actually getting better at engaging with the public. And I think this is such an important technology. We need to make sure that we move with public approval and public support and so that we can start forming. if not global, at least regional agreements on how this technology will be used and what we do and don't think is acceptable. And how do we balance the potential safety problems with wanting to reap the benefits of this technology as quickly as possible? So that's actually a really difficult question.

And it's not difficult because of the science. It's difficult because as people, we're really, really rubbish at understanding risk as individuals. We're just notoriously bad at it. So small new risks frighten us much more than big old risks because we're used to the big old risks. I think what we have to understand as society is that nothing is absolutely risk-free. What we can expect of this technology is that it should not be any riskier than any existing approach that we use. I don't think we can expect it to be entirely risk-free because nothing else is.

But we again have to build consensus around that. And I think that's a really hard one to do. Also because bad exciting science that taps into people's fears tends to survive much more vividly in the public imagination than the good, boring science that actually shows the bad exciting stuff is wrong. So we have a real dialogue that we have to build. We know from the history of various controversies,

in science that actually sometimes all it takes is one really bad paper that taps into fears. And you can't get rid of the influence of that for a really long time. So we have to find better ways of communicating. And we have to find better ways of working with colleagues in the media so that the wider population gets actually a very balanced view of what's going on, not just the disaster versus the triumphs, but actually understanding the spectrum in between. Yeah, we don't want to repeat the vaccination's autism debacle. Oh, dear God, no, anything but that.

And that is the concern that we will end up with another of those absolute nightmare scenarios. So we have to be pragmatic about this. This technology has the potential to make the world a massively better place. It does, of course, also have the potential to be misdemeanor. used. But you don't deal with that by saying, okay, it's completely banned or it's completely free for everyone to use however they feel like it. We have to find ways of agreeing what we all believe are the acceptable uses. I think the thing that's really exciting for a geek like me about this technology is it just means you can do much more fun science than we were ever able to do before.

because all the old genetic modification technologies, you really had to be working in just one of a handful of species, everyone had worked, such as mice or a particular microscopic worm or fruit flies. With this technology, if you're interested in an obscure grasshopper gene, you can actually go and you can investigate what happens to that grasshopper gene using gene editing. If you really, really wanted to and you had the money, you could do something in hippos. I'm not suggesting anyone's going to do anything in hippos, but you can't. could. We've never had a technology like that before. It is so cool. It allows us to do the really curiosity-driven thing that sometimes is just the most fun in science, where we just discover weird and wonderful stuff about how the world around us works that we never envisaged before. And actually, in my kind of Uber geek phase, that's the bit I'm most excited about.

That was Nessa Kerry talking about how gene editing might change our future. Her book, Hacking the Code of Life is available from ICON Books Now. Thanks for listening to the Science Focus podcast. In the latest issue of BBC Science Focus magazine, we find out what came before the Big Bang. We also interview Sir David Attenborough, who tells us how we can save the planet. Plus, we find out if addiction is on the rise,

whether anti-vaxes are putting us all at risk and why testosterone doesn't give casta semenia an advantage. And as always, there's much, much more inside. Thank you for listening to the Science Focus podcast from the BBC Science Focus magazine team. With the UK's best-selling sites and technology monthly, available in print and in several digital formats throughout the world. Find out more at sciencefocus.com or look out for us in your app store. This podcast is sponsored by Name, Audio and Focal. The texture and emotional depth of music can be lost through digital sources or poor signal.

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