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Matthew Cobb

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2022-11-30
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2022-11-30
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  1. About what this means for the next generations and so on. And from that point of view, I can see absolutely no reason to do this. And it should be banned internationally. And yeah, there should be no more talk of it, really.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  2. Well, I think it's very simple. We say that editing the germline should be banned. It should be forbidden. Editing that is forever that will change not only will change the next generation, it's not going to change the individual who you do it to because it's going to be in your experim or in the embryo that you've created, that should be forbidden. And I think one of the reasons it's very moral. If you just think about it, okay, nobody has to be born, but those children in China did not ask to have their genes edited. They did not give permission to anybody to do that. And so people who dream of, you know, making us being able to go and live on Mars, just think about what that would involve. And, you know, the individuals who that would be done to who would then grow up, what if they didn't like that? What if they didn't want that to happen? They've effectively become a kind of slave to your collective fantasy. And that is outrageous. And it's, you know, it's a degradation of humanity. And I think we need to get a bit more angry about these kind of fantasies and to think them through.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  3. Can stop you doing this. But I think there has been a shift to people asking the question they should have asked first, why are we doing this? Now, I heard John Qui's case, I think it was pretty clear he wanted to be the first and he thought he was going to literally thought he was going to get a Nobel Prize for this as it happens. He's become an unperson and is name is Mud, to say the least.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  4. Going on living on Mars because that is just not going to happen. But even to change single letters of DNA in a known genetic disease, that in an embryo is really not necessary. Only a few hundred people. And remember, you're not curing a disease here. What you're actually doing is allowing a particular human to be born. In other words, you are treating the desire of people to have their own biologically related healthy child. Now, there's no right to have such a child. And I think the potential dangers of this approach are so strong that it should be banned. There's no way at the moment of stopping this, in particular in the USA. There's no law against, in the UK, if you do this, you'll have the law down on your ton of bricks. In the US, if you've got your own money or you're a privately funded institution, there's no federal law that...

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  5. But nobody ever asked well which genetic diseases and why can't they be dealt with with the current techniques, which is IVF and pre-implantation selection? How many people are going to be able to have a healthy child with gene editing that would not be able to do it with pre-implantation selection and IVF? And now people who ask that question, it turns out to nobody actually knows the number, but it's perhaps a few hundred couples around the world. That's it. Because having the right combination of genes that means you can't benefit from the current technique approach, which is basically have lots of fertilized embryos and then you find the ones that have not got the genetic defect, the number of couples in such a situation is vanishingly small. So I think once you ask the question, which they should have asked at the beginning, why do we want to do this? And we leave that kind of techno-fantasies about, you know, editing people.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  6. Is astonishingly delicate, and you can, according to the titles of some of the papers, lose whole chromosomes. So gene editing of an embryo, which is supposed to be kind of molecular scissors, can be more like a chainsaw and it could have catastrophic consequences. So the consequence of all this work, I mean, this terrible, terrible experiment went horribly wrong. I mean, he was sent to jail for three years. He's out now. I've been banned from ever working on assisted reproduction again. The girls, who knows, hope they're okay. That's all we can do. There's been a shift in the, I think, in the scientific community. Before this, from kind of 2015 to 2018, there was lots of meetings and lots of articles written with the vast majority of people saying, oh, we should be on what they called a prudent path to having genome editing. The argument being we can get rid of genetic disease.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  7. Genes edited forever, right? There are very practical ways of doing that. And so there was no unmedical need. The experiment went horribly wrong. The changes he introduced were not in every cell. So the girls are what are called mosaic. So we don't know whether that will have an effect. Some of the changes that he introduced have never been seen in anybody else. So we don't know what will happen. And with a bit of luck, they'll be absolutely fine, okay? But we don't know that. And the Chinese government rightly not turning them into a circus. We don't actually know what happened to the rest of their genes because I think the really chilling thing is that we now know at around about the time he was doing that experiment and since then there have been lots of papers come out that show that it's all to do with the state of the cell when you start doing this chopping up. And as I indicated earlier on, it's very delicate, in fact. And in embryos in primates in particular and in humans in particular,

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  8. Okay, so what happened is in 2018, Her John Cuy, who was a Chinese researcher, he edited two, and now we know three, or he brought to term three embryos. Who knows how many embryos he edited and how many are maybe sitting in freezers in China somewhere. He edited these baby girls who were normal. So you've got to remember these are normal embryos, healthy. There's nothing wrong with them. He introduced genes or changes, which he said would enable them to resist getting HIV, trying to copy a naturally occurring genetic variant, which does indeed mean that some people don't get HIV, or they're much less likely to get it. But as it happens, those people are also much more likely to get other diseases. So even if everything had gone to plan, it wouldn't have been a win-win. But above all, there was no unmet medical need. These children, there's plenty of ways that everybody knows of not getting HIV, and it does not involve having your

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  9. We weren't particularly interested in it. And indeed, buying seeds every year is the basis, has been largely the basis of the explosion in our food production since the Second World War, because this is what you do. You get two strains. They produce a hybrid, which is infertile, but which is incredibly productive. And so you buy the seeds every year. And this is what farmers of all over the world have been doing. And it's been okay. But then when it was suggested that Monsanto are kind of surreptitiously trying to introduce this idea, that again added to the general kind of suspicion. So the result was Monsanto, overall, I think, some pretty good reasons, got a very bad press.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  10. To keep the seed from year to year, and they prosecuted small farmers in quite scandalously kind of aggressive examples of trials in particular in Canada, but all over the world. And this led to them becoming the bad boys and even their CEO accepted this and went online and spoke by video conference to a Greenpeace meeting, say, yeah, we haven't been listening properly and kind of did a Maya Culpa, but it was too late. And there was even this mythology, it wasn't a mythology. Monsanto came up with the idea or they bought a company that had the idea of making a plant seed that would not grow, that would die after one generation. So you couldn't keep the seeds because they'd be infertile. This is called the Terminator gene by the opponents. In fact, it never existed. They never made it. They bought a company that had it.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  11. Food security concerns, and there was the development of globalization and the World Trade Organization was set up, which basically said, okay, you won't be able to stop anybody importing goods to your country. You've got to accept this going to be this free exchange of goods all over the world. And so older listeners might remember there were lots of demonstrations in Seattle and all over the world as people who didn't like this idea fought back against it. And there was this kind of conjunction of fears about big business, very sensible, fears about globalization, probably sensible too, concerns about food security, and then genetically modified plants got mixed up. And Monsanto in particular started getting very bullish about its genes because when you buy Monsanto seeds, you don't own the genes. They do. And so you're only hiring them. And you're not allowed.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  12. Into the water courses. It's terrible. I saw a bloke using glyphosate the other day, and it was rainy. I thought, why this is illegal. You shouldn't be doing this. It gets into watercourses. It's really bad for amphibians. Plus, there's arguments about whether it's bad for humans as well. So they did that, which is kind of kind of, I mean, other companies thought of that and they said, no, there'll be a public outrage if we're producing our own herbicide and then giving you the means to resist it. People won't like that. Monsanto went ahead. So that was bad. What really happened was that as GM crops became a reality in the late 90s, it coincided with a period of intense suspicion about food security in the UK. We had a completely unrelated mad cow disease panic, which wasn't really a panic because 130 people died of variant CJD, which is almost certainly caused by eating contaminated beef. So there's great...

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  13. The public. Well, yeah, they did two things which weren't quite so clever. Firstly, they came up with the idea of producing their own pesticide. This is now marketed as Roundup glyphosate, which will kill plants, fine. But finding a mutation that would enable plants to resist theirbicide. So they eventually found a bacterium that could do this in the waste pipe of one of their plants that was producing glyphosate. And some bacterium had evolved the way of resisting it and could survive. So they got that gene. They put it into their plant. And what that does is it means that if you're a farmer, you can now grow your plants closer together because the weeds, you're not just going to get rid of the weeds, just spray the place with your herbicide. And so you don't have any weeds anymore and your plants are resisting it. Now this has all sorts of consequences, in particular runoff.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  14. Of whatever kind. So they thought, okay, what if we get the gene from this BT as it's called bacterium and put it into a plant? Then the plant will produce its own organic, natural insecticide. And that's what they did. I mean, it took a bit of time. Genetic engineering plants was quite complicated, but they succeeded. And that has led to a reduction of about, it's estimated of about three quarters of a billion tons less of insecticide because these plants are producing this very specific substance which will only affect caterpillars that try and eat the particular plant. And that is a success story and there's no point in denying it. And it is great. I think I've got nothing bad to say about that.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  15. The jungles of Vietnam during the war. So they did everything, you know, it's everything that was bad. And their CEO was remarkably far-seeing. At the end of the 60s, he said, look, we've got to get out of chemicals. These are the words you said, this is not sustainable. We cannot carry on chucking this stuff all over the planet. We've got to change. We can't carry on producing insecticides. And so they came up with this very clever plan in order to get out of chemicals. That is why not get a gene from, as it happened, a bacterium that naturally produces by accident in a way a chemical that will inhibit the growth of caterpillars. It kills caterpillars. Now, caterpillars don't eat bacteria, so it's kind of a chance, but they knew that the organic food industry in the US allowed organic farmers to spray their fields with this bacterium because that meant that the caterpillars couldn't eat their cotton or their

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  16. Where I was Tell us a little bit about that. Yeah, so Monsanto in the 60s was a chemical company. And so they made AstroTurf, you know, plastic grass. They made DDT. They made Asian Orange, which defoliated

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  17. But the thing that struck me. Not disease is actually Strangely enough, there's virtually no genetic engineered crops resistant to diseases. They either resist insects or they resist.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  18. Kevin said that he was really excited for the first day, thinking I can cure malaria. And then he thought, well, he woke up the day after and thought, wait a minute, this could all go horribly wrong. How do we stop it? How can we stop one of these things if it's not right? And similarly, the researchers in California who made this introsophila, they initially, once they were very happy with their result and they got more of the flies they were interested in, they realized the potential and thought, well, should we even publish this? Because it is very dangerous. And indeed, the US DARPA, the kind of shadowy defense research agency, is very interested in this technology. It's the main funder of gene drive technology because clearly you can imagine that you could not get rid of malaria, but you could create an insect.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  19. It was spreading really, really quickly, very quickly. Yeah. And the first one of these to be actually made using CRISPR was actually made by a bunch of scientists who they didn't know anything about this debate. I don't know where they've been, but they haven't been paying attention. And it was a PhD student who needed more copies of a particular gene that he was studying, which changed the bristles on his flies or something like that. I can't remember. And so he came up with the idea separately, completely independently, and they built this thing and it spread. They started off with yellow eyes, a kind of classic Drosophila. They work in Drosophila, the fruit fly. Classic Drosophila I mutant, and it spread through the population just with start with one gene, and then it doubles in every individual that it occurs. And so it just spreads exponentially through the population. And they, like Kevin Asfelt, who realized theoretically how you could do it with CRISPR, make one of these things.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  20. Population, if you're producing sterility, and this works in the laboratory big laboratory cages of mosquitoes, the population just will disappear in about 10 months. So it will work. That's absolutely clear.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  21. It will produce an enzyme which is looking for the site on the other chromosome where there is no gene. It will then cut the DNA. It's a nuclease, so it cuts DNA. The cell then goes, oh, I've got a gap in my DNA. What's on the other chromosome? Oh, there's a sequence there. I'll copy it over. Hey, Presto, you've got two copies of this gene. And so what Bert was just interested in this is a theoretical possibility. And he immediately thought, well, wait a minute, what if we attach to this homing endonuclease, as it's called, this thing which attacks its own location? What happens if we attach to that, we include in that sequence, say a gene making of female sterile or a gene making a mosquito immune to malaria? Then you would very, very rapidly spread through the population this gene. So this would either crash the population.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  22. That's not a word that will be familiar to many. Yeah, so a gene drive, it's a cunning way of increasing the number of copies of a gene in a population. So it goes back a bit to what I was talking about earlier on about how if a piece of DNA is cut, it can use the other cell, the other chromosome rather, to repair the DNA. So this was dreamt up by a researcher at Imperial College called Austin Burt at the beginning of the century. And he imagined, well, if we, in fact, you find these things naturally occurring in funguses, they don't exist in animals. If you've got a gene that encodes a nuclease, so an enzyme that cuts DNA, but it recognizes its own site, so it's targeted to cut on the other chromosome where there is no gene. What will happen then is you've got, you start off with one copy of this thing, this gene.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  23. Yeah, I mean, so in Burkina Faso, I mean, they did lots of very good things, but journalists and consulting before, no gene drives have been released, must be absolutely clear. People do use sterile mosquitoes in various places to reduce the population. They reduce lots and lots of sterile males that mate with females and stop the population.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  24. Decide for the region, for the country, for the whole continent, for the whole world. So one of the people who devised gene drives, Kevin Asfelt, said, well, a release somewhere is going to be a release everywhere. In other words, you need to think about this on a global scale. And really what we need is not only local understanding, prior informed consent and a veto if they don't want to do it, then they stop it. But actually some form of international regulation of this technology, just like we have international regulation of civil aviation or of nuclear power.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  25. They need to understand the villagers, the people in the locality, they need to understand what could happen, in particular with the ecosystem, what might be the fragile balances that are upset. And how do you explain that to a population which is largely non-literate and in which there is no word for gene? So this is one of the issues that's been dealt with by target malaria, which is a nonprofit organization that encompasses partly Bill Gates and Foundation, but also lots of academic groups, for example, at Imperial College in London. And one of the ingenious ways that they've dealt with this in Burkina Faso, where they're consulting with the government and with the locals on this, is to use theatre to explain to the local villages what they want to do and what could be the consequences. And I think that's a very sensible and serious way of doing it. But then immediately you think, well, okay, the problem we've got here is that these things can spread because, you know, mosquitoes don't just live in a village. Mosquitoes fly. And the genes are designed to spread themselves very, very rapidly. So why should a village?

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  26. Development or the potential development of gene drives that is these ways of manipulating the ecosystem. And I think any discussion of this, because it all sounds kind of scary, you have to start from the brute fact that 600,000 people died last year of malaria. The vast majority of them were children under five. And that's with all the insecticides, all the bed nets and all the rest that we're providing. And that's entirely due to malaria being transmitted by mosquitoes. So if we could find a way of stopping that, that would be a good thing. And one of the issues is, okay, you can be pretty certain that any village that has a high level of malaria is going to want to do whatever it can to save its children.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  27. Really don't get it. But we now know that the Russians who were there had already lobbied Brezhnev, the Russian premier, to start building a program to make genetic weapons, to make new bioweapons using genetic engineering. And indeed, they eventually succeeded in the 1980s. So this wasn't just something that was a fantasy. It was actually happening at the same time as the people at a cinema were focusing primarily on how can we contain any microbes in the laboratory and ensure they don't escape. So at the beginning, they missed a boat, missed a trick. They should have been discussing those possibilities. I think more recently there has been a growing recognition in the scientific community that this is of particular importance to the public. And I think this has been seen in particular in the

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  28. Scientists have a meeting at Asilamar, and as I've indicated, they are really concerned about how to do the experiment safely. And they rule off the agenda of this big meeting of about 200 people. They rule off the agenda, any discussion about ethics, about editing humans, about the environment, or about the possibility of producing genetic weapons, even though they all recognize David Baltimore, who is one of the organizers, then a very young scientist, he says, yes, this is the most dangerous potential use of this technology, but we're not going to discuss it. We now know that Ada Silamar in 1975, there was a Russian delegation composed of worthy members of the Academy of Sciences who were kind of ridiculed by the young Americans researchers because these were all people who are even older than me, you know, in their late 60s, early 70s. And the American scientists said, oh, those old Russians, they don't understand anything.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  29. Well, it's a bit surprising in a way. So, and sometimes they really miss the boat. So many geneticists, students who study genetics will learn about this meeting that took place in California in 1975 at a place called Asilamar. And that was when after the beginning of genetic engineering became a reality and you could pretty much move DNA not as precisely as with CRISPR, but you could move bits of DNA from one organism to another in pretty much any kind of organism. And this very quickly, within a matter of a few years, led, for example, to the ability to produce insulin. So everybody who's listening who takes insulin or has a family member who uses insulin, that is produced in a genetically engineered microbe which traces its ancestry back to experiments that were done in the mid-1970s.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  30. Absolutely. They don't often think, well, you know, should we be doing this? They generally think, yes, this is going to be very exciting because it will either lead to new processes for producing drugs or it can cure disease or whatever. But they get concerned about the potential for danger and they have called for moratoriums. They've stopped doing the experiments. And there's no other branch of science that has done that. Even the scientists working on the Manhattan Project during the war to build a nuclear bomb, they had arguments about it, but they didn't actually stop working. So geneticists are quite proud of that. And I think they're right to be because it's actually a very important kind of tradition that they are thinking, many of them are thinking very hard about what could go wrong and trying to put in place steps that could prevent that before it does.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  31. Always happens after the accident. But in the case of genetics, that could be too late. If something is a bad idea and turns out to have bad consequences, then the thing will actually be replicating itself because, well, that's the magic of life. It grows and it reproduces and it spreads. So everybody has been concerned, I think right from the very beginning. And that's what's striking is that genetics has this unique history in that unlike any other science that I've come across, four times scientists themselves have said, look, this is really dangerous. We should not do this. We should wait and think about how, well, what's interesting is they've always thought, think about how we can do it safely.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  32. Cracked, he's the first person to crack the genetic code, he said look, by the time we're going to be able to do this soon and we need to think about it now. So he was very prescient and he made a, I mean, it's a principle which I know a lot of the genetic engineers who I've spoken to and whose work I've studied are very aware that they need to think about the risks before the technology becomes available because as Sidney Brenner, who's one of the leading molecular geneticists of the second half of the 20th century, when he was asked about this in the 1970s, he said, well, the difference between a genetic accident and a road accident is that road accidents generally aren't self-replicating. So, you know, something bad can happen on a railway and you realize, okay, well, we've got to change the signaling, whatever, because security and health and safety is always lagging behind.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  33. Well, pretty much as soon as everybody became confident that DNA was the genetic material and there was a genetic code, which wasn't quite as instantaneous, I found even as late as 1961, so Crick and Watson using data from Franklin and Wilkins discovered the double helix in 1953. But as late as 1961, some people were saying, well, maybe it's DNA, maybe it's proteins that encode the genetic material. So it did take quite some time. But basically by kind of 1961 when the genetic code was cracked, everybody accepts that DNA is the genetic material and people start to think about how we could, in particular use it to deal with genetic diseases. And this starts to become a real possibility because various enzymes are developed by the middle of the 1960s. And in 1967, Marshall Nirenberg, who was about to win the Nobel Prize and was one of the people.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  34. Enzymes to find a particular piece of DNA. But basically, if you've got 18 letters in a protein encoding sequence, they're going to be pretty much unique in your DNA. And so they should guide the relevant enzymes to cut in a particular part in that sequence. So though it sounds, I mean, it's 18 letters out of 3 billion, you just leave it to the enzymes to work out how to do it. That's the kind of amazing thing.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  35. The crisper molecules that you put into the cell to try and fix things is they've got to unravel, in human being, they've got to check through 23 chromosome pairs to find the sequence that they're really, really interested in. They've got to unravel the DNA, read it, find the bit that fits, and then start mobilizing the enzymes to snip it up. So it's an amazing process that takes, I mean, you have an awful lot of molecules in there. only got one set of DNA molecules in the cell, but you've got, you put in lots and lots of these CRISPR sequences and enzymes that can then go and find the right bit of DNA home in. And it's this precision which led Fyodor Ernoff to coin the term gene editing. This was in fact before CRISPR appeared on the scene. So this was in about 2005 when there were much more complicated ways of programming your

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  36. Well, if you're a human, you've got around about 3 billion letters of DNA, right? So 3 billion base pairs, because there's two strands to the DNA molecule and they're complementary. If you've got an A on one strand, you've got a T on the other because that's the way it holds itself together. And so you've got to find a sequence out of three billion letters. And that sounds kind of crazy. In fact, because of the, that's the way the genetic code works, you've got an incredibly varied set of letters corresponding to either just nothing, kind of junk DNA, remnants of old viral infections, including in human beings, bits of DNA that copy themselves and the key bits are the bits of DNA that either encode proteins or regulate how other genes are going to function. So the challenge for the

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  37. That you've put in there, so the bacterial sequences and the enzymes will just be dissolved and disappear. So you end up with a change that is purely genetic, is simply the genetic information has been altered in the way you want it to happen. Is that okay? Is that clear enough?

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  38. To try and fix the DNA that it's lacking. And normally it gets this from the other chromosome because you're a diploid organism, you've got two pairs. So if one chromosome is damaged, it looks to the other one and says, okay, that's the sequence. I'll copy it over. And if you're clever, you can persuade it not to use the other chromosome, but instead the DNA that you've introduced. So the end result of this, if you can introduce the various CRISPR components, which originally from bacteria into a cell, it will target the DNA that you've kind of programmed it to chop up and then repair that using some additional DNA that you've introduced into the cell. The advantage of this compared to previous methods of genetic modification, for example, in GM plants, is that the changes very, very precise, or it should be, because you programmed it where it should go. And secondly, the cell will very quickly metabolize all the stuff.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  39. If bacteria can use this system to mobilize these enzymes, we could do the same for any gene that we're interested in. We'd replace a viral kind of guide, which is what the bacteria has with a piece of DNA that we're interested in. It will target the nucleases, these enzymes, to a particular location in a DNA sequence. And what it relies upon is the way that the cell repairs DNA that's broken because cells don't like having their DNA broken. It happens a lot through radiation or chemicals or whatever. So if you break the DNA, the cell will then try and fix it. And one of the ways, if the cell's in the right state, and this is really quite important in terms of what happens when things don't quite work right, if the cell's in the right state, it will use another piece of DNA to

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  40. Change the genes of any organism pretty much to a particular genetic sequence that we want to introduce. So if you know the DNA of an organism that you want to change and you know what you want to change it to, and that's going to be a sequence of bases or letters ATC, there are just four letters in the genetic code. We can now change them in any way we want. The way CRISPR works, it was first discovered as a kind of natural immune system in bacteria. And what the bacterium does is if it's infected by a virus and it can beat off the virus, it stores some of the viral DNA in its own DNA, which it can then, or its descendants, can then use to mobilize what are called nucleases, which are enzymes which will chop up.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  41. Well, there's lots of ways of changing genes, which I mean, the books about genetic engineering and our ability to change the genes of other organisms. And we've been doing this inadvertently since we appeared on the planet because we're predators. So we've been eating stuff. And that's changed the genes of the stuff we've been eating, whether it's been plants or animals. The big change came first with agriculture when we started selecting animals and plants to eat and drink, eat, and consume, but also we did biotechnology. We harnessed without knowing it the power of microbes to make beer and bread and so on. The big change came in the 1970s when we could precisely introduce the genes from one type of organism into another. Initially, this was involving bacteria and viruses. Now we can...

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  42. Since it became a viable technique. And yet those worries have turned out to be not unfounded, but they haven't, none of the fears have been realized. So I wanted to kind of test my fears today to see whether I'm kind of making a fuss about nothing or whether they're exactly the same as worries in the past, where people write to be worried in the past and should we be worried now. So it was a bit of kind of self-exploration and therapy in a way, except it didn't quite work out that way.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  43. It's something that I've been doing. People have been doing. I know COVID-19 was not a genetically engineered disease. But we have the capacity to do that. And scientists are trying to make diseases more dangerous in order to predict the potential development of future pandemics. And the final thing that I'm worried about is, again, an extremely well-meaning approach, which is to perhaps rid the world of malaria mosquitoes, but the technique that this requires involves is basically like a genetic atom bomb. You would release one of these genetic structures and it would just drive its way. They're called gene drives, drive its way through a natural population. And I'm very concerned about all three, but I know that people have been very worried about genetic engineering in the past for the last 50 years.

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT

  44. It's really three things. The recent developments in new genetic engineering people have probably heard of this. It's called CRISPR. It's incredibly cheap. It's much simpler than previous techniques. And it has already transformed science. So I have been interested in this since it appeared as a technique in about 2013. It has enabled us to do some astonishing things, which I hope we're going to talk about some great things. But it has also raised three prospects that I am particularly worried about. And those are, on the one hand, the ability to edit the human germline. So that means genes that will be changed and will go down the generations. And that has happened. It's the possibility of editing viruses to become more dangerous. This doesn't in fact need CRISPR, but it...

    2022-11-30 · Intelligence Squared · The Perilous Quest Towards Gene Editing, with Matthew Cobb · IDENTIFIED FROM THE TRANSCRIPT