Should We Genetically Edit Human Life? - Matthew Cobb

1. 0:00 – 1:29

   Intro

   1. MCMatthew Cobb0:00

      ... Soviet researcher stabbed himself with a syringe containing one of the most dangerous and horrible viruses called Marburg virus, which is a bit like Ebola, but much more dangerous. Uh, he died horribly, but of course, you never let anything go to waste. And whilst he was dying horribly, the virus in his body was changing, was mutating. So they took blood samples and hey, presto, they ended up with a new, even more dangerous version of the virus.

   2. CWChris Williamson0:22

      (laughs)

   3. MCMatthew Cobb0:22

      So that was good.

   4. CWChris Williamson0:25

      Matthew Cobb, welcome to the show.

   5. MCMatthew Cobb0:27

      Thank you very much. Good to be here.

   6. CWChris Williamson0:29

      How do you describe what you do for work when someone comes up to you and says, "What do you, what do you do on a daily basis, Matthew?"

   7. MCMatthew Cobb0:35

      (laughs) Well, it-

   8. CWChris Williamson0:35

      What's your answer?

   9. MCMatthew Cobb0:36

      ... depends on, on, uh, who they are (laughs) and what I've been doing recently. Uh, technically I'm a, I'm a lecturer, so I'll say I teach at the university. Uh, but I also write, I research, I do all sorts of things.

   10. CWChris Williamson0:51

       Recently, your fascination has been with The Genetic Age. You've called it a perilous quest to edit life. Why perilous?

   11. MCMatthew Cobb1:00

       Uh, because, uh, lots of things can and indeed have gone wrong. Uh, and part of the point of the book is to highlight three areas in particular of, uh, the application of genetic technology that I think are particularly concerning and I think the public needs to be aware of. And political regulatory solutions need to be found to respond to those dangers.

2. 1:29 – 8:05

   Will Gene Editing be a Net-Positive?

   1. MCMatthew Cobb1:29

   2. CWChris Williamson1:29

      I had Rob Reed on the show a little while ago. You familiar with Rob?

   3. MCMatthew Cobb1:32

      Nope.

   4. CWChris Williamson1:33

      So he did a, a four-part series with Sam Harris about two or three years ago about the dangers of biotechnology, uh, bioweapons. Specifically, he was looking at, uh, is it BSG certified labs? Is that the... What's the acronym?

   5. MCMatthew Cobb1:47

      Don't know.

   6. CWChris Williamson1:47

      Uh, it's the something, something, something level of, uh, accreditation-

   7. MCMatthew Cobb1:50

      Yeah.

   8. CWChris Williamson1:50

      ... that different labs have in terms of their security.

   9. MCMatthew Cobb1:52

      Yeah.

   10. CWChris Williamson1:52

       Uh, and he did this four-part series, and it was absolutely terrifying. He was talking about, you know, desktop, um, weapon creators basically, where you can synthesize particular sequences and it all goes up to a cloud. And I mean, that, that worried me quite a lot. So I was, uh, relatively prepared, I think, for more concern about it. And given the research that you've done, do you see gene editing as a net positive at this stage? Is it a dream or is it a nightmare?

   11. MCMatthew Cobb2:22

       Oh, well, in terms of what it can do, both for science and medicine, it's quite extraordinary. Uh, I mean, for the last 50 years, we've had the ability to precisely edit genes. I mean, humans have been altering, uh, genes primarily inadvertently, uh, simply by our presence o- on the planet and our actions as, uh, hunter-gatherers, as predators. We've changed the genes in animals and plants. Uh, and then later on with the development of agriculture and finally, uh, selective breeding, then we've deliberately changed characters, though we didn't actually know what we were doing. So, uh, genetic engineering develops 50 years ago this autumn, and involves the precise alteration of genes in a desired way. And that has been absolutely transformational. However, uh, there are these concerns and that's... They've been perpetual throughout the history of genetic engineering. That's what particularly interested me. So as I say, there are areas that I'm very concerned about and, uh, not, not so much bioweapons as more generally gain of function research, as it's called, which we can discuss later on, uh, of dangerous pathogens. That's one thing that particularly concerns me. But I'm aware that my worries are very similar to those that have been repeatedly raised over the last half century and have turned out to be unfounded. So it's partly to explore, uh, this consistent, uh, kind of promises and then fears and then dissipation of the fears, uh, that we can see over the last five decades and that I recognized in my own concerns today. That's one of the reasons why I wrote the book.

   12. CWChris Williamson4:06

       It's a permanent Cassandra complex around the genetic development.

   13. MCMatthew Cobb4:10

       Yeah, yeah. And you've got to remember that, uh, when Cassandra has opened, uh, the box, there's something left at the bottom, and that thing is hope. Uh, so, you know, Cassandra doesn't just release all the, the horrors on the world. There is always hope. And I think that is, that is true as well. Because, you know, to, to clearly answer your question, the, the net is a net positive, what genetic engineering has enabled us to do. Uh, if, uh, any listeners use insulin or any of their familin- family members use insulin, then that insulin has been produced, uh, in a genetically engineered microbe. Now, insulin prices have not plummeted as was promised, uh, when this was first developed 45 years ago, but that's for a rather different reason. In terms of the economies of scale and the safety of what people put into their bodies now with the insulin that is produced through genetic engineering, that is far safer than the previous versions which were all derived from animals and weren't identical to the human version.

   14. CWChris Williamson5:12

       Is that what people were using? Before we had, we could synthesize insulin, people were taking animal insulin?

   15. MCMatthew Cobb5:18

       Yeah. You take pancreas from, uh-

   16. CWChris Williamson5:19

       No way.

   17. MCMatthew Cobb5:20

       ... either cow... Well, (laughs) where else can you get it from? (laughs)

   18. CWChris Williamson5:22

       I didn't know how long we were able to, to do this for.

   19. MCMatthew Cobb5:25

       Well, it's been... Insulin was developed as a drug in the early years of the 20th century. Uh, and for decades, therefore, you were relying on the supply of drugs, uh, supply of insulin as a, as a byproduct of the, um-

   20. CWChris Williamson5:39

       The supply of animals.

   21. MCMatthew Cobb5:39

       ... as a byproduct of, uh, of the, uh, the slaughter of animals. So you'd extract the pancreas and then you could get the insulin from that. But that was a very long process and above all, the insulin that is produced in pigs or in cows, uh, has a slightly different structure. It's got one extra amino acid compared to the human version and-... as a consequence, people eventually developed a kind of an allergic response to it. Eventually caused problems when this was the only form of insulin they had. So when the genetic engineers in one of the earliest applications of this technology in 1978, they made human insulin, or they produced, they produced human insulin with exactly the same molecular structure in a microbe. This was a res- remarkable breakthrough because, in fact, it was actually better than what you could get, uh, on the market. It was better than the previous solution. So just to take that one example, in terms of medicine, then, you know, genetic engineering, the production of drugs, there's a new paper just came out literally last week with, describing a new way of synthesizing an anti-cancer drug which is a thousand times more productive, uh, than the traditional way, which involves lots and lots of different plants. They put the plant genes, uh, into a yeast, and then they're able to virtually produce the whole drug. They've got one final stage to make. Uh, but effectively this will transform the production of anti-cancer drugs. So in terms of medicine, this has been really, really transformational. In terms of science, then it's hard to think of a branch of biology which does not in one way or another, uh, rely upon genetic engineering as a tool to understand how organisms function. So it has been absolutely fantastic. But it's not sim- you know, it is a tool. It's a technology. Technologies get applied. They don't simply sit in the lab. They get turned into plants in fields. Uh, and as we know there's been huge controversy, uh, over genetically modified, uh, plants as to whether they're safe. They are. They're quite safe to eat. Uh, but there has been... You know, people aren't happy about them for all sorts of reasons, and this has led to the, as I said, these cycles of fears and, uh, excitement that carry on down today. I mean, the repeated, uh, excitement

3. 8:05 – 12:10

   Can We De-Extinct Animals?

   1. MCMatthew Cobb8:05

      about the possibility of de-extincting mammoths or, um, thylacines, which are a marsupial, uh, that lived i- in Australia and went extinct, uh, about 100-odd years ago. Uh, I mean, these are actually fantasies. They're nonsense. I don't think you can-

   2. CWChris Williamson8:22

      You can't... We c- we can't do a Jurassic Park and get some-

   3. MCMatthew Cobb8:26

      No.

   4. CWChris Williamson8:26

      blood from a mosquito in some amber and re- recreate animals?

   5. MCMatthew Cobb8:28

      No. No. Indeed, my... A few years ago, my colleagues from the University of Manchester, uh, studied, uh, mosquitoes in modern amber that was only a few decades old, and the DNA had all gone. So, uh, you can't-

   6. CWChris Williamson8:42

      Who'd have known, who'd have known that Steven Spielberg was lying to us this whole time-

   7. MCMatthew Cobb8:45

      Well-

   8. CWChris Williamson8:45

      ... about genetics?

   9. MCMatthew Cobb8:46

      Spielberg just wrote the book, uh, just, uh, just, uh, made the film. The book was written by Michael Crichton, who, who had form, uh, on, uh, underst- trying to use, uh... or exploring the, the worries about, uh, you know, diseases and genetic engineering. And what's very striking is that, uh, I mean, Crichton's book came out in 1991. The film came out in 1993. But since then, in s- this century, there's been a kind of cultural acceptance of, uh, genetic engineering, and it doesn't seem to be something that people are concerned about. So there's no films made this century. There's no books written this... Not even kind of, you know, techno thrillers like, uh, Jurassic Park that have explored this. There's nothing about GM crops, for example. You might have imagined that this would be a source of, uh, excitation for thriller writers, for filmmakers, but it hasn't happened. And, uh, it strikes me that you can generally tell what a society is concerned about through the cultural products that explore it. Uh, if you think of, I don't know, the steam engine in the tw- in the 19th century, then the steam engine featured not only in paintings, but also in novels. And it was, it was seen as this, this transformational force, which indeed it was. Or the, uh, the threat of atomic war in the, in the second half of the 20th century. And since the end of the 20th century, there really hasn't been much of any caliber, uh, exploring these dangers. And it seems to me that indicates that our, our eyes kind of gone off the ball. We, we're not paying attention anymore to, to what's going on because these things are extremely significant, and yet we don't seem to be preoccupied with them. I mean, just the Jurassic Park franchise tells you this because it moved away from being the, the, the danger, the potential of carrying out this genetic manipulation. They say in the film but not in the book, uh, you know, your scientists were so busy thinking about whether they could, they didn't think about whether they should. And that moral dilemma, which is at the heart of the film, the first film, very rapidly dissipates, and a- all, all we've got now is... And the whole thing is scary CGI monsters on the rampage, and we know it's gonna happen. And, you know, the ethics of it is neither here nor there. It's just turned into a, a CGI fest. So there's something happening in the, in the global consciousness, in our global awareness, that is... indicates, uh, a lack of concern, and that might be... Well, that's fine, I mean, you don't get, you don't get many thrillers, uh, about railway engines anymore, though I... There was just a film just came out recently. So, you know, maybe, uh, may- may- maybe there is still that lurking concern about, uh, about trains. Atomic power, atomic war, we... despite recent events, doesn't seem to be particularly concerning anymore. So maybe people are just accepting this. But as I say, there are these three areas of recent development which are both very exciting but also very alarming that I think, uh, suggest that we should be alarmed, and we should be concerned.

   10. CWChris Williamson12:03

       The difference between could and should is a very interesting distinction. I think for almost all of human history......

4. 12:10 – 22:51

   Addressing Concerns about Bioweapons

   1. CWChris Williamson12:10

      our capacity to do things has always been lower than our desire to do things, right? Like technology has lagged behind the things that we've wanted to be able to create, and it's only recently that we've got to the stage where technology has perhaps surpassed our wisdom. It's a Eric Weinstein co-quote where he says, um, "We're gods, we're just shitty gods," which is the same as saying, "We're gods-"

   2. MCMatthew Cobb12:31

      (laughs)

   3. CWChris Williamson12:31

      "... we're gods, but for the wisdom." The fact that you have the opportunity to create something on a desktop synthesizer which could have some pretty big ramifications, up until the point at which you could create it, your could is below your should. And now it's the other way around, you can create things that you maybe shouldn't do.

   4. MCMatthew Cobb12:49

      Well, yeah, I mean, I'm not quite so worried about, um, basement hackers and biohackers. That, that's something that everybody got very excited about about 10, 15 years ago. Uh, and in particular, the security services when, uh, they feared that people would be creating, uh-

   5. CWChris Williamson13:06

      Smallpox in mom's kitchen or something.

   6. MCMatthew Cobb13:08

      Yeah, whatever. And it is incredibly complicated. I'm not wa- I, you know, the, I mean, for a start, the biohacker movement has largely kind of faded away and people aren't anywhere near as excited about it, uh, as they used to be. But one of the reasons being is that it's very, very hard. So for example, when scientists develop, you know, they, they synthesize the poliovirus from scratch, that was on the basis of a laboratory's decades-long experience of working with these tools. So even if you can imagine a DNA sequence that, uh, could do something terrible and you can get it synthesized, then what do you do? You've gotta introduce it into some organism which then has to express that, uh, particular protein in, in, in some way, and then it has to be turned into a vehicle, turned into a, a way of actually transmitting this stuff. So even if you had, you know, very strong malicious intent, it's not something that is easy to do. Uh, and I'm much more concerned about established laboratories, uh, carrying out research under conditions that may not be optimal or about, uh, governments carrying out, you know, clandestine military research which then goes awry. I think that's much more worrying in terms of, of bioweapons. I'm not terribly concerned about biohackers. But it, it, it is the case that, uh, in fact the, the, the West's security obsessions about this, which grew enormously after 9/11, 9/11 is really the kind of hinge around which a lot of this research developed. The Soviet Union had been carrying out, uh, bioweapons research from the mid-1970s onwards, uh, without anybody knowing, uh, what was going on. This became apparent in, towards the end of the 1980s when a series of defectors revealed to the West what had been going on. Uh, with the collapse of the Soviet Union there was great concern that this might get into the hands of rogue states and terrorists and all the rest of it. But after 9/11, which coincided with a series of breakthroughs being made by researchers, for example, some Australian researchers, uh, who were trying to deal with the problem of wild mice, uh, in Australia, which are devastating to the local, uh, marsupial animals that live there. So they were researchers who, you know, they're, they're ecologists. Uh, they were trying to find a way of getting rid of the mice, uh, and they inadvertently made mousepox, which is a disease very similar to smallpox but it only affects mice, they inadvertently made mousepox immune to vaccination. And it was very obvious that if this worked with mousepox, the same procedure could make smallpox immune to vaccination, and that is incredibly alarming. Um, and the researchers were so disturbed by what they found that for 18 months they discussed and debated, and the Australian Defense Ministry got involved, as to whether they should even publish, uh, this, this study. So when all this happened and coincided with 9/11 and the terrible, uh, catastrophe there, and ter- and fears all around the West about terrorists and so on, uh, there was this big... I- it also coincided with the, uh, the SARS outbreaks in China in 2002 and 2004, so it was the development of an understanding that there would be spillover events from, uh, natural diseases in animal populations, just as had happened in 1918 with the Spanish flu. And repeated concerns in the West about, "Oh, this technology is incredibly easy to use, we should really be worried about it 'cause, you know, any old fool can do it." And eventually, the very people you might imagine (laughs) would pay attention to that did indeed, because after the fall of Al-Qaeda in Afghanistan, uh, US forces discovered, uh, documents written by some of their leaders saying, uh, that, "The enemy kept on telling us that this was such an amazing, easy technology, so we decided to try." Now they failed, I'm glad to say, uh, but they failed primarily because it is in fact much harder than the very simple descriptions that are made in, in the media and by security agencies and so on. It's very hard, first to master the genetics, and secondly to then weaponize the particular thing that you may have created.

   7. CWChris Williamson17:40

      Is there not a concern moving forward that as technology becomes more developed and these systems inevitably have more of the kinks worked out, that that will democratize this danger a little bit more? That someone may be able to, in 50 years, have a desktop synthesizer which is as easy as the push of a button to microwave a me- a meal to be able to create smallpox?

   8. MCMatthew Cobb18:01

      Um, well, that is indeed possible and there are various solutions to this because you can't, you know, you can't unlearn (laughs) what we know. You can't, uh-... part of the- this is the contradiction, uh, that science thrives on, uh, being open and sharing resources and information, and yet there are things that we can do that are extremely dangerous. Uh, now you can't make a, uh, a nuclear reactor or a nuclear bomb in your back garden, um, but you could, I mean, in, I can, you know, you, I can- I'll accept your fantasy that in 50 or maybe 100, maybe 200, doesn't matter how far in the future, that such a device, uh, might be possible. So then the question comes of how you regulate access to such things. When, uh, there was this kind of panic in the beginning of the century, then there was all sorts of discussion, uh, about whether you should, um, limit the access to, uh, DNA synthesizers because now, uh, you can actually, you, you simply give the, give the machine instructions and it will produce a, a sequence of DNA, uh, corresponding to that. As I say, the issue is not actually sequencing the DNA, and all sorts of journalists have, you know, (laughs) sent off for bits of smallpox from, uh, various laboratories, which then send the DNA sample through the post, but, you know, DNA is inert. It doesn't actually do anything on its own. It's gotta be put into a cell, which then has to understand the instructions it's being given, and that step is remarkably difficult, and it requires not just abstract scientific knowledge, which you can indeed gain from a, a textbook. You can understand what- how to do it, but actually doing it (laughs) and carrying out the procedures, uh, in an effective way, that is really, really hard. And any scientist... So we, we all know about PCR, for example, uh, polymys- polymerase chain reaction. We've all had PCR tests during the COVID pandemic, but any researcher (laughs) who starts working on PCR, the first thing they learn is that it never works. And even if you've got the whole protocol set out and you know exactly what to do, you carry it out and then nothing happens. It is very, very complicated, very subtle, and you need to acquire, uh, very good laboratory skills. Now, you could acquire those skills and turn evil, or you could be recruited by somebody who is evil, so I'm not disputing that this is, uh, possible, but it is not at the moment any... I mean, it is- it's very striking that despite, uh, bioweapons being as old as genetic engineering itself, so 50 years, as soon as the technology became, in fact even before the technology was a reality, when it was still a hypothesis, uh, the Soviet Union agreed to start building and in- investing in such things. Um, none of these bioweapons have ever been deployed, either by a state or by, uh, terrorists. So it is clearly a bit trickier than it would appear on paper.

   9. CWChris Williamson21:09

      Yes.

   10. MCMatthew Cobb21:09

       But that doesn't mean to say that we shouldn't be worried about it because all these things are held in laboratories, just like there are two stocks of smallpox or maybe more. Uh, you know, last November, a laboratory, um, somewhere in the Midwest of America suddenly discovered in its freezer a whole load of smallpox samples that were supposed to have been destroyed decades earlier.

   11. CWChris Williamson21:27

       I read about that.

   12. MCMatthew Cobb21:28

       Uh, it's absolutely terrifying. Uh, and, you know, it's, they've, people have tried to reactivate smallpox using either body parts preserved in formalin or corpses that were buried in the tundra during, uh-

   13. CWChris Williamson21:45

       I also read about that as well, yeah.

   14. MCMatthew Cobb21:46

       You know, and so this is rather alarming that you might be able to... Well, for a start, global warming might lead to, you know, zombie-

   15. CWChris Williamson21:56

       Smallpox corpses-

   16. MCMatthew Cobb21:58

       ... smallpox particles, yep.

   17. CWChris Williamson21:58

       ... floating down the street.

   18. MCMatthew Cobb21:59

       You know, emerge, well, you've just gotta get the smallpox emerging from the, from the ground. I mean, I, I think this is very unlikely, but it is not impossible. I mean, it's something, (laughs) not another thing to worry about. I don't think people should-

   19. CWChris Williamson22:10

       Add it to the list.

   20. MCMatthew Cobb22:11

       ... like take it- Right. But, yeah.

   21. CWChris Williamson22:11

       We'll add it to the list.

   22. MCMatthew Cobb22:12

       But it sh- it shows the kind of problems, uh, that there are. But the technology, I, I'd emphasize, the technology is, one, very simple to describe and to understand, but extremely difficult to actually apply. There's a, an aspect to the, of, uh, what, what, what, what French sociologists of science who study this to see how, how people in the laboratory actually do the experiments. It's the, the ability to manipulate, what the French call la gestuelle, the, the gestures, the, the skills that you need to acquire, to make the experiment work, are often really, really quite complicated and can take years and years to acquire.

5. 22:51 – 30:11

   The Biggest Close Calls in Gene Editing

   1. MCMatthew Cobb22:51

   2. CWChris Williamson22:51

      What are some of the biggest close calls that the world's had with dangerous gene editing that you discovered during your research, then?

   3. MCMatthew Cobb23:00

      Well, I don't think there's been... (sighs) The, the, the main thing that has been worrying has been the, uh, gain-of-function research. I, I think the starting point is that, um, genetics is different from every other science, uh, in that on four occasions, scientists have been so concerned by what they're doing, by the research they're carrying out, by the implications of what they've discovered, that they have called for a pause, a moratorium on research, and that's been applied. And no other science has ever done that. I mean, science has done some amazingly destructive things, most notably atomic power. So when the scientists were making the, uh, nuclear bomb in the Manhattan Project, after the fall of Nazi Germany, uh, there was a big discussion about whether they should carry on because the worry was that the Nazis were gonna get a bomb, and they'd kill everybody and so on. But with the fall of Nazi Germany, it was obvious that, no, the Ja- Japanese were not, uh, able to emulate that, and so there was a big debate about whether they should continue. And although there was an open letter, uh, written to President Roosevelt, it was never actually developed, never actually delivered.... and the scientists carried on. So there, there was some debate. They never stopped work. Whereas, as I say, four times, geneticists have actually stopped work. First at the very, very beginning in 1971 then again in 1974 when they were concerned that this might lead to, for example, uh, the, an epidemic of cancer-causing genes, uh, because the viruses that they were manipulating were potentially, uh, cancerogenic. That turned out not to be the case, and almost certainly the viruses, in fact, don't cause cancer, uh, in humans. But those concerns were the ones that led to the current, uh, levels of biosecurity which still hold today. And as long as you follow them to the strict letter, then all should be well. But things can go wrong. Um, in 2012, Ron Fouchier, who is a virologist, who'd been carrying out what's called gain-of-function research... Just as I mentioned earlier, this became very fashionable after, uh, in the early years of this century when both the, the prospect of future pandemics and the fear that bioterrorists or rogue states might start using this technology led to the US, in particular, funding research where dangerous pathogens were rendered more dangerous. Now, this wasn't military research. This was all funded, for example, by the National Institutes of Health in the USA, and the idea was, okay, we're gonna have a pandemic. Once that virus arrives, it will mutate. We've seen this with the coronavirus, with COVID-19. Once that virus arrives, it will mutate. If we can predict how it is going to become, if it, how it could become more dangerous, then we'll be forewarned and forearmed. That's the argument. So, for example, in 2011, Ron Fouchier, this, uh, scientist working in Rotterdam, uh, he went to a conference in Cyprus, and he got up on the platform, and he said, um, "I've, uh, done something really, really stupid." Those were his terms. Um, he had, I, and I quote, "Mutated the hell out of H5N1," and that's bird flu virus. Bird flu virus is about 100 times more dangerous than COVID-19. The reason we haven't had a terrifying pandemic of bird flu virus, uh, of bird flu is because it's only transmitted by touch. So when it has spilled over from bird populations, then it's been relatively straightforward to deal with, with strict, uh, kind of public health measures. But what Fouchier had done by mutating the hell out of it was to make it now transmissible through the air, just like COVID-19. And he was so alarmed by what he'd done, he predicted what could happen. He'd mutated the virus. He thought, "Well, if I fiddle around with this part of it, maybe it will, you know, start to float through the air," and indeed it did. Other researchers very soon did the same thing. He was so terrified by what he was doing that together with his colleagues, they published an open letter saying, "Right, we're gonna stop doing this." (laughs) They said for, uh, eh, eh, eight weeks, it turned out to be for about eight months, while new biosafety protocols were implemented. But that was very clearly a... You know, that was a bullet we dodged. If that had, disease had got out, then we would be in a terr- would've been in a terrible, terrible mess. Now, there were a whole series of, uh, leaks from various US laboratories, from ordinary laboratories manipulating bird flu in, in other ways, that led to a suspension of funding of gain of research, gain-of-function research, uh, in the US. But eventually, even that was rescinded, and now there are two or three such projects. Now, those seem to me to be really foolhardy. The argument, as I've said, is this will enable us to predict the course of future pandemics. Well, (laughs) I think we can see that the way the world responded to COVID-19 was not in any way, shape, or form informed by that research. It was of no help whatsoever. Other routes had to be taken to understanding and eventually to coming up with a vaccine, and in a handful of cases, uh, to ways of ameliorating the infection. So, I think the justification for that kind of research, and this is a big debate in the scientific community about this, uh, I think the justification is, is nonexistent, and I think that research should be stopped because even the safest laboratory can have laboratory leaks. I should mention in passing that there is no evidence that COVID-19 was fabricated in a laboratory. There's not even any evidence that it escaped from, uh, a laboratory that had, say, been cultivating it to understand it better or whatever. All the evidence we have at the moment, and this might change in the future, all the evidence we have at the moment is that this was a natural spillover event from a wild population of animals, just as ha- as had happened with SARS, uh, in the early years of the century. It must be said that identifying the SARS source as pangolins took 15 years, so it's very complicated to identify the exact source of such a spillover event. And the event that produced the, uh, spillover that caused the 1918 flu pandemic is still debated but was almost certainly from cattle, but even that hasn't been actually demonstrated.

   4. CWChris Williamson29:34

      I wonder which is more difficult to try and work out, where the genesis of a 100-year-old pandemic came from or to try and work out the genesis of a three-year-old pandemic that happens to be in China controlled by the CCP.

   5. MCMatthew Cobb29:49

      (laughs)

   6. CWChris Williamson29:49

      I think that they probably end up evening out at around about the same level of difficulty.

   7. MCMatthew Cobb29:53

      Yeah, indeed, and, uh, a whole s- I mean, the Chinese bureaucracy's got an enormous appetite for secrecy, uh, and there have been a lot of missteps, uh, by funders and researchers in the West which has led to a lot of suspicion. And it's quite possible, uh, that we'll never, we'll never know,

6. 30:11 – 36:04

   How to Make Labs More Secure

   1. MCMatthew Cobb30:11

      uh, where, where-

   2. CWChris Williamson30:11

      Oh, yeah, there was talk a- t- talk about the US contributing to funding of this particular lab out in Wuhan and-

   3. MCMatthew Cobb30:18

      Yeah. Yeah.

   4. CWChris Williamson30:18

      ... that, yeah.

   5. MCMatthew Cobb30:19

      I mean, they, they fund all sorts of research. There's nothing, nothing... It's not a conspiracy anymore. You know, they funded Ron Fouchier's laboratory in Rotterdam. That didn't make Rotterdam the center of some, you know-... Highness project to do what? It's hard to know.

   6. CWChris Williamson30:33

      Well, I mean, yeah, you, you, the, the interesting thing that I learned from speaking to Rob Reed a few years ago was the number of different ways, especially when you're talking about, uh, gain-of-function research, uh, genetically engineered or genetically modified viruses, bacteria, et cetera, the number of ways that it can escape from a lab, even the highest-

   7. MCMatthew Cobb30:53

      Mm-hmm.

   8. CWChris Williamson30:53

      ... security lab. There was one story he told me about, which you might be familiar with, where the air conditioning stopped working and backed up, and it meant that one of the particular vents which is supposed to be shut didn't end up being shut, and a bunch of people in a nearby town were infected with some virus that, a- anthrax or something, that we thought we'd previously gotten rid of. There are so many way- there's stories of, uh, like the, the classic Hollywood version of the guy in the rubber gloves and he cuts himself and something, he ends up being infected in that sort of a way. People putting it in their pockets and walking out of the lab without realizing. These are at BSCG-4, like the highest level that you can get to, and it seems very much perhaps similar in the way that the development of AI is behind the control mechanisms to make sure that the-

   9. MCMatthew Cobb31:41

      Yeah.

   10. CWChris Williamson31:41

       ... alignment problem gets sorted. It seems to me that the level of security within these labs is inferior to the lethality of what they're synthesizing within them.

   11. MCMatthew Cobb31:50

       Yeah, and I think the, the, the fundamental issue here is one of regulation and control. Now, there is a structure that could and should oversee all this, and it's called the Biological Weapons Convention. And this was signed in 1972, so at the very same moment that genetic engineering became a reality, and it, uh, came into function in 1975. And apart from the fact that both, say, the Soviet Union, South Africa, which had very well developed biological weapons programs, signed up to it, and, you know, there's complete disparity between what they were doing in, uh, private and what they said in public. The fundamental issue with the Biological Weapons Convention is that it's toothless. Uh, it has no power of inspection, no power of sanction, so if anybody were to, uh, go out with its rules, so what? Uh, and when there was the recent, uh, proposal, about eight years ago, I think, to ha- to, to give the Biological Weapons Convention teeth, a bit like the International Atomic Energy Agency, which is currently, uh, in, in Ukraine. They can send in inspectors. They can, you know, everybody has to accept-

   12. CWChris Williamson33:03

       Sanction shit and do stuff.

   13. MCMatthew Cobb33:03

       ... that they can go, and then they can sanction stuff. It's-

   14. CWChris Williamson33:05

       Yeah.

   15. MCMatthew Cobb33:05

       ... you know, it's been the cause of a huge diplomatic rouse, uh, with Iran, for example, because of the powers of the IAEA. If the, when there was a proposal to give the Biological Weapons Convention similar inspection and sanction powers, the USA put a veto on it because that would involve having inspectors in US labs, and they said, "If you come into our commercial labs or into our military labs, then you will threaten either our commercial secrets or our military secrets." And therefore it's not happening. So there is a, a, I mean, I, I think this issue of global regulation, uh, which is very unfashionable, but it's absolutely necessary, as we can see with the IAEA, uh, is one that actually underpins all three, uh, examples of, uh, the current dangers that are lurking within potentially advantageous genetical engineering research. We need to have ways of actually controlling it that are not simply, uh, on paper, but they also involve, uh, people in hazmat suits going into laboratories and measuring, uh, air pressure and the circulation and the safety procedures and what exactly, you know, going through computers, seeing what genes are being manipulated and actually having a, a, a s- right of control over that. And I, I think without that, then there will, in the end, be, uh, a problem. And out of the two examples you just gave, both took place in the, in the Soviet Union. There was an outbreak of anthrax in, uh, Sverdlovsk, uh, which the Soviet Union insisted came from, uh, people eating contaminated meat, uh, but which research has very, uh, going into the, going into the Soviet Union, uh, afterwards showed, in fact, the air, the, the, the wind, uh, passage showed very clearly that this could only have come from a nearby, uh, biological laboratory and there was some kind of leak. Uh, in the second example, a Soviet researcher stabbed himself with a syringe containing one of the most dangerous and horrible viruses called Marburg virus, which is a bit like Ebola but much more dangerous. Uh, he died horribly, but of course you never let anything going to- go to waste, uh, and whilst he was dying horribly, uh, the virus in his body was changing, was mutating, just like coronavirus can mutate within, uh, people today. And so they took blood samples and hey, presto, the, they ended up with a, a new even more dangerous version of the virus.

   16. CWChris Williamson35:34

       (laughs)

   17. MCMatthew Cobb35:34

       So that was sort of good. It's all true. It's terrifying, but all true.

   18. CWChris Williamson35:39

       (laughs) Oh my God. So, uh, Comrade Friedman over the far side is in terrible pain-

   19. MCMatthew Cobb35:46

       (laughs)

   20. CWChris Williamson35:46

       ... but while he's there, let's use him. He, he, he died as he would have wanted to live-

   21. MCMatthew Cobb35:51

       Yeah, there you go.

   22. CWChris Williamson35:51

       ... creating new viruses.

   23. MCMatthew Cobb35:52

       There you go. That was pretty much what happened. And he, I mean, this was not just some hapless lab researcher as well. I forgot his name now. It was one of the head researchers. I mean, it's absolutely awful. I mean, and he would have died in, in a horrible,

7. 36:04 – 50:33

   When the Research Community Fear Discoveries

   1. MCMatthew Cobb36:04

      horrible way.

   2. CWChris Williamson36:05

      What was the fourth m- pause. We've done the first three.

   3. MCMatthew Cobb36:09

      Okay. Yeah.

   4. CWChris Williamson36:09

      Two in the '70s, one with you gentlemen up on stage who-

   5. MCMatthew Cobb36:14

      Yeah, Ron Fouchier.

   6. CWChris Williamson36:14

      ... modified the heck out of it. What was the fourth one?

   7. MCMatthew Cobb36:17

      Yeah. Oh, the fourth one, the fourth one, uh, was in 2019, and (sighs) sadly it's not been as successful. So in 2018, uh, in November, a Chinese researcher called He Jiankui, uh, went to a conference on, uh, human gene editing...... and he announced to... Well, by then, it wasn't everybody's surprise because it had all leaked in the few days before. But, uh, he announced that he had carried out a, an experiment, he called it gene surgery, uh, on two human embryos, and he had altered their genes, uh, in, as it turned out, a quite most catastrophic way, in that what he had intended to do did not happen. So this is using the, the technique called CRISPR, which is often portrayed as a, a pair of scissors, both meta- you know, both in words but also in pictures, you see a pair of scissors cutting DNA. Uh, and these are molecular scissors and enzymes that will very precisely, uh, cut DNA, and you can persuade the cell's, uh, DNA repair mechanism to repair it in a particular way. So you can alter genes very precisely, and this has proved a... since its development in 2012, this has proved quite remarkable in terms of developing new scientific understanding, uh, but also, uh, new therapies, uh, potential therapies for existing people. What He Jiankui had done was rather different. Rather than say, changing the DNA in somebody's blood cells to cure them of sickle cell disease, as has been done experimentally, um, what he did was to mutate the embryos. So these were when there was just a single cell, he injected these, uh, CRISPR constructs into the cells, and eventually those, uh, two baby girls were born, he announced in November 2017... 2018, sorry. And then, uh, a year later, uh, it turned out that there was yet another baby. So there's three baby girls ... in Borden.

   8. CWChris Williamson38:16

      So just, just that, hearing that from you, about the fact that not only had he done this completely pirated, massively lambasted, completely unethical research, but that there was a third child in this.

   9. MCMatthew Cobb38:29

      Yeah, that's only, that's only just been revealed. There was rumors of it, and now, uh, it's been confirmed. Well, it's probably worse than that. I mean, anybody who's gone through IVF knows that you have an awful lot of embryos. You don't implant them all. So who knows what's lurking in liquid nitrogen, uh, in Chinese labs.

   10. CWChris Williamson38:48

       Huh.

   11. MCMatthew Cobb38:49

       Um, now, there's two issues to this. Firstly, uh, I think the starting point is that there was no reason to do it. What he was trying to do, he said, was to enable the girls to, uh, resist HIV, because, uh, there's a naturally occurring, uh, form of gene in some populations of humans that means that people are much less likely to get HIV. Now, uh, that particular mutation, that alteration is what he was wanting to introduce. But if you've got that alteration, one, it's not a guarantee. Uh, you know what? There are plenty of ways of making sure you don't get HIV, and they're well known, and they've been well known for about 30 years now. You know, don't use IV, don't share your needles, have protected sex, and that's probably gonna be okay. You'll be all right. Um, so there was no actual need to go down this route of genetic engineering. Secondly, the mutation that he was introducing actually makes it more likely that you'll die of other diseases. I mean, there's very little that's free in biology. If you gain one way, you, you lose in another. And finally, most importantly, what he said he had done, he had not done. So he was trying to introduce one particular, uh, change. That didn't happen. The change he introduced was still in the same gene, but it was to produce a change that has never been seen in any other human being. Finally, the, uh, the girls, or the two girls we kn- have details, some details of, um, not all their cells are the same. So because you inject this stuff into a single cell embryo, you think, "Okay, that's great. Then surely all the genes must be altered, yeah?" But the, j- th- th- this CRISPR stuff, they've gotta find this sequence out of three billion base pairs, they've gotta find where it is, and then they've got to chop up the, uh, the, the DNA and get this new piece of DNA put in. In the meanwhile, the s- the embryo is growing. That's what an embryo wants to do. It's, it's turning into a, a, a multiple-cell organism, and as a result, these girls are what are called mosaic. The CRISPR didn't work in every cell that the girls, uh, are made up of. So we have no idea what's gonna happen. It may be they're fine. Uh, we don't know what the mutation does. We don't know the que- what the consequences of being mosaic are. Uh, so anyway, He Jiankui announced this, uh, very rapidly to, uh, a horrific response.

   12. CWChris Williamson41:20

       Yeah, well, he, he's at a confere- I mean, w- was, did people lynch him?

   13. MCMatthew Cobb41:25

       Um, there was kind of a stunned silence. I mean, it, it was fascinating, the, uh, well, there were, there were questions. People knew what he was gonna say because, um, uh, Antonio Regalado, who's a, a journalist with, uh, uh, MIT Technology Review, he had written, he'd spotted, uh, a... in, in a Chinese database, he'd spot... he'd interviewed He Jiankui, would talk to him, and he'd picked up there was something going on, and he found in a Chinese database of clinical trials evidence that this was going to take place. So a few days before the conference, uh, it was all over the internet. So when the conference took place, everybody knew what he was going to announce. What they didn't know was quite how bad it was. Everybody knew it was gonna be bad, but then when the actual results were demonstrated, and despite his claims that, "Oh, it's all fine, and we just made this particular change," it was clear from the limited data that he presented, uh, and the main commentary on this went on on Twitter, in fact. Uh, you know, the... it was the #CRISPRbabies. Uh, it was literally what it was called. And you could see, you know, eminent scientists who weren't at the conference around the world watching the live stream, you know, taking screen grabs of the images he was projecting, and then trying to understand what on earth had gone wrong and getting absolutely furious. In the meeting itself, there was... it wasn't quite so, uh...... uh, there was no anger, although, uh, uh, a Chinese, uh, uh, a re- and a US researcher called David Liu, uh, he kind of (laughs) punctured the whole thing by saying, "What was the unmet medical need?" Because in any medical procedure, the first thing you've got to say is, "Well, I'm doing this because there's no other way of doing it." You know, you're not gonna, I don't know, chop a- chop your leg off because you've, you've pulled a muscle, right? I mean, that would cure you if you pulled a muscle, but it's absolutely crazy. So that question, what was the unmet medical need that those em- normal, healthy embryos had, there was no answer to that. Um, and He Jiankui didn't, didn't give one. It's- there were some researchers, who I won't name, who initially said, "Well, it's not so bad." And it must be said that around 50 people knew what he'd done before it was announced. So these were people he'd talked to, in particular in America, researchers in America who he'd gone round and explained what he was planning to do. Uh, and then sometimes h- he said, "Well, I've implanted the embryos." And so they knew, but they all... Nobody said a word. I mean, a few people said, "Oh, that's really cool." Um, other people, uh, in their responses to him, uh, said, "Well, uh, uh, why are you doing this? I don't wanna know any more about it." But they still didn't, you know, they didn't blow the whistle. Nobody went public before this had been announced. Um, but eventually, within a f- matter of days, everybody realized that this was a really bad thing and even the Chinese press, which had initially said, "This is a huge step forward for Chinese research," 'cause China has a, uh, a, a deep, uh, eugenic tradition, as indeed does the USA, um, and Sweden, and many other countries. Um, and... Or an i- an interest in eugenics. So their initial response of the official governmental response was very positive, but within 12 hours, uh, all those web pages had mysteriously disappeared and, uh, He Jiankui, uh, was put under house arrest, he was then tried, he was sentenced to three years in jail. Uh, he's now been released, but he's been forbidden from ever working, uh, on, uh, assisted procreation ever again. So this happened in 2018 and the response of many, but not all scientists, uh, working in this field was to call for a five-year moratorium and in February 2019 they published a, a call for this five-year moratorium on, uh, heritable genome editing. So this is, as I say, this is, this is editing of genes that will be passed onto the next generation. So ideally, every cell in your body shares the same mutation, including your eggs or your sperm, depending whether you're a boy or a girl, and therefore those genes will be carried onto the next generation. So you gotta be sure you've got it right. Um, and, uh, but not everybody agreed with this. So, uh, including one of the co-, uh, inventors, uh, of CRISPR, Jennifer Doudna. She refused to sign this call saying, "Look, it's too late. You know, research has got to carry on." But what's striking is that... I mean, He Jiankui was a, a foolish, vain man, but he was actually really doing what most of the scientific community had been accepting since 2015 'cause in 2015 once it became obvious that CRISPR could work, uh, in human embryos, that it worked in primates and therefore it was clearly gonna work in human embryos, um, the- there was a big meeting in Washington in December 2015 at which they said, "Okay, well we clearly need to have global consensus on this, but," uh, y'know, eye, "everybody's got to agree that this is editing human, uh... the heritable part of the human genome is, is what we should be doing. But, um, nonetheless, we think we should establish..." what they called a prudent path, "a prudent path to the development of, uh, the application of gene editing." And, um, that was the, that was the accepted phrase. "We're on a prudent path." Couple of years later, in the beginning of 2017, as He Jiankui was developing his ideas there was a big report, uh, by a bioethicist in the US which said... which actually junked the whole talk of consensus. So consensus doesn't appear anywhere in the document and it was just the prudent path, and there was never any, uh, measurement or sense of the importance of safety. So all the, the dangerous stuff we've been talking about, the, uh, gain-of-function research, I mean those researchers are, you know, really, really aware (laughs) of what safety is. But safety was never, uh, was never centered, was never even mentioned as being in any way definable as to, you know... What measure, what- how many errors are you, would you find acceptable in editing the human genome? None? 1,000? A million? We got, as I say, three and a half billion bits of, letters of DNA. How many are you prepared to see go wrong? Uh, there was never any mention of that. Um, so when this report came out in 2017, the scientific press described it as being an amber light to gene editing. So amber, proceed with caution. And that was what He Jiankui took. I mean, he, he was a bad man. He was working what was already described as the Wild East of gene editing at the time because regulations were difficult to understand or were unclear in China, plus there was a lot of kind of, uh, turning a blind eye, uh, to regulations if progress could be made. There's great appetite for scientific progress. So in fact, it was the whole of the scientific community, I think... Well, virtually. Not everybody. Some people did say very clearly, "Do not do this." And they put their finger on the reason why you shouldn't. Why would you want to do it? Now the answer that everybody gives is, "Oh, well, you wanna get rid of genetic diseases." But you don't get rid of genetic diseases by editing an embryo. What editing an embryo does is to allow a certain human being to be born. It doesn't actually alt- you know, until you start fiddling around, there's n- there is no human. So it allows that human to be born.... and at the moment, if you have a genetic disease, then you go through IVF and you then do what's called pre-implantation selection. In other words, you test the embryo when it's, uh, a few cells old and you take one of those cells and you look at its DNA and you see does this have the mutation that causes the disease or not. If it does-

   14. CWChris Williamson49:18

       What would be an example of one of those diseases?

   15. MCMatthew Cobb49:20

       Um, well, you, I mean, this is the kind of thing that, uh, you carry a, uh, you, you could do this, um, for example, with, um... Put me, put me, uh, (laughs) put me on the spot here.

   16. CWChris Williamson49:31

       Is Huntington's, is Huntington's one?

   17. MCMatthew Cobb49:32

       Uh, well, yeah. Hun- yeah, absolutely. Huntington's disease. I mean, Huntington's disease is absolutely awful. So Hunting's disease is what's called a dominant disease. You just need one copy of the gene. You've got two copies of every gene, you just need one copy. Uh, and if you've got that gene, then you are basi- basically it's a death sentence. You're gonna die almost certainly in your late 30s, early 40s of a horrible neurodegenerative disease. Now people often know that there's Huntingdon's disease in their family. So even if they are affected, they can have a healthy child if they only have one copy of the gene. The vast majority of people only have one copy of the gene. They can have a healthy child by doing this pre-implantation selection. So couples who want to have a healthy child or a non-affected child, um, can do this at the moment through this technique and you've gotta go through, I mean, the horrible bit of this is IVF, as anybody who's done IVF knows.

8. 50:33 – 57:11

   Concerns about IVF

   1. MCMatthew Cobb50:33

      (laughs)

   2. CWChris Williamson50:33

      What? Sorry, you just, uh, I'm not familiar with IVF and why it's horrible. What- what's horrible about IVF?

   3. MCMatthew Cobb50:39

      Okay. Well, uh, basically, so, uh, IVF is in vitro fertilization, so they make a test tube baby. So you've got to, I mean... So a- as a bloke, uh, yeah, you producing the, uh, the genetic contribution, that's not particularly problematic. Whereas if you're a woman, you'd know, yeah? So you've gotta, as they put it, harvest the eggs. Now normally, a woman will produce just one egg, maybe two, but generally just one egg a month. You need hundreds of them, so basically you have to be filled full of hormones and then they have to stimulate the release of those eggs, they have to collect them, all this is incredibly invasive. It's stressful because, uh, depending on where you live, I mean, if you're incredibly rich, then you can carry on doing it as long as you can stand it. Uh, in the UK for example, then you will get three goes at this, three rounds of IVF. Um, uh, and if it doesn't work, then the, the National Health Service won't pay for you, uh, to do that anymore. You have to go private and it is very, very expensive. So, uh, it is extremely stressful and unpleasant for the woman and despite the, my jovial remark, it's very stressful for the, uh, the, the, the partner, the male partner as well because you want to have a baby, so it's that desire that in fact is being treated here. Because, as I said, normally you would go through IVF and pre-implanta- if you ha- know you've got a genetic disease, you go through IVF, have pre-implantation selection, find the right, uh, eggs, put them into the mother and if all being well, you'll produce a non-affected baby. Now the only people who could have their desires to have a non-affected child met by genetic engineering would be those couples either where you've got a recessive disease like cystic fibrosis where both couples have two copies of the gene, so they can't give a healthy copy that you might find in an embryo 'cause, uh, they, that's all they've got. Or if you've got somebody with, um, somebody with, uh, Huntingdon's disease, say, a dominant disease, where they have two copies of the gene and so all they can pass on is an affected copy which will then mean that the offspring is gonna be affected. So the question then comes, well, okay, so we're meeting the desires of these people to have a non-affected baby. We're not curing anybody of anything. We're responding to that understandable desire. Lots of people want to have children, all sorts of people want to overcome fertility for all sorts of reasons. It's absolutely legitimate. But how many people, how many such couples are there around the world? Now the short answer is we don't know, but, uh, the people who work in this field doing genetic counseling virtually never meet people in either of those categories. They are incredibly rare. I think there are two or three couples in the USA where both people are homozygous for cystic fibrosis and that's one of the most common, uh, genetic diseases. So we're talking about maybe a couple of hundred pairs of people around the world and this procedure would be adopted in order not to cure anybody of anything but to meet their desire to have a healthy baby. And there's no right to have a healthy baby. That's, you know, it, it, it doesn't work that way. So it seems to me and i- indeed even the bioethicists who five, six years ago were saying, "Well, maybe it's not so bad," have actually gone, "Oh, wait a minute, why would we want to do this?" In fact, the only people who could be helped by this are, you know, very, very few people and we're not actually... We're just helping them to meet their desires, not actually doing anything more fundamental than that. So I think for all those reasons, coupled with the fundamental problems of safety because we now know that this pair of scissors, CRISPR, is in fact much more complicated, or rather, the way that the cell responds to it can cause all sorts of strange things to happen. So cells go through a cycle of quiescence and then divi- division and so on, and depend on where there are, they are in the cycle, they will respond in different ways to having these molecular scissors shoved into them and bits of their DNA being chopped up which they've then got to fix. And we now know that in mammals in particular, this is very, very sensitive and, uh, in some cases, uh, so in human cell lines, so not in embryos but in s- human cells...... performing CRISPR at particular points in the cell cycle can lead to the loss of a whole chromosome. Right? You've got 23 pairs of chromosomes, so roughly, (laughs) you know, 5% of your DNA just disappears. It gets chewed up by something that isn't quite a pair of scissors and is a bit more like a chainsaw gone amok. So people are beginning to realize that the, the metaphors, the precise, exciting, you know, seductive metaphors are in fact, uh, hiding a really complex reality. And so for all those reasons, uh, I, I agree. I don't think there's any reason why we should do this and the dangers, uh, are so extreme. Finally, which you may or may not consider it to be significant, the question is, how is this technology gonna be, uh, distributed? Is it going to be equitably distributed? Well, I think we know the answer to that. (laughs) So, you know, it's not gonna be, uh, a- a- a couple in an African village who have a genetic disease who are gonna benefit from this. It's primarily going to be, uh, rich Americans where this is legal. It's illegal, I would point out, uh, in many countries, but not in the USA.

   4. CWChris Williamson56:17

      No way.

   5. MCMatthew Cobb56:18

      Yeah, you can do it. If- if you're in the USA and you've got a load of money, you can do what you want.

   6. CWChris Williamson56:23

      Wow.

   7. MCMatthew Cobb56:24

      So state funding, federal funding will stop you doing it because, um, their concern about stem cells, which is primarily based from the religious right, uh, considering that a stem cell is a, a, a, a human being with a soul and all the rest of it. You can't... State funding cannot... Federal funding cannot be used for, um, stem cell research, so that extends to any manipulation of embryos. But if you don't need to ask the National Institutes of Health for money-

   8. CWChris Williamson56:50

      Got the cash in your back pocket, you can.

   9. MCMatthew Cobb56:52

      And that there are institutions that are like that and exist, and indeed, they have carried out some of the key steps towards human gene editing or heritable gene editing, uh, in private universities and hospitals in the USA.

   10. CWChris Williamson57:07

       How close? I mean, CRISPR, I

9. 57:11 – 1:05:09

   How Close We Are to Human Gene Selection

   1. CWChris Williamson57:11

      took on board the pair of scissors that might also be a scalpel.

   2. MCMatthew Cobb57:15

      (laughs)

   3. CWChris Williamson57:15

      You know, it's laser precision.

   4. MCMatthew Cobb57:16

      Yeah.

   5. CWChris Williamson57:17

      We can go in and do the thing. I was also aware that genes i- i- it's not like this is the eye gene, and this is the hair gene, and this is the penis size gene. You don't just go in and fiddle around with an individual thing. It's often huge, huge numbers of them that, that all are sort of codependent in very interesting and different ways. How far away are we from people being able to select, uh, an embryo that's got a higher IQ or to edit an embryo so that it's got blue eyes and blonde hair if they want to have the Fourth Reich come back around?

   6. MCMatthew Cobb57:50

      Okay, right. Just deal with the eyes, right? So you learn at school that, um, blue eyes are recessive and brown eyes are dominant. So if that means that if you've got two brown-eyed parents, they could have a blue-eyed child because the gene that encodes for blue eyes is, you know, hidden by the, by the brown... Uh, potentially hidden by a brown gene. And this, at, uh, school, you know, genetics courses sometimes causes some eyebrow-raising because the opposite conclusion could be made. If you've got two blue-eyed parents, then having a brown-eyed pa- child will be impossible because there's no brown gene there. The blue-eyed parents, by definition, according to this view, would both have two blue genes, so all they can pass on to their offspring are blue genes, so you should have a blue-eyed baby. And on occasion where this isn't the case, then children have and can be quite traumatized by that because it suggests various things have gone on.

   7. CWChris Williamson58:52

      Male parental uncertainty going on there.

   8. MCMatthew Cobb58:54

      There you go. Now, uh, most recent st- uh, thankfully, uh, that is rubbish. (laughs) Uh, well, stuff may have been going on, but you can't tell from eye color. So basically, more or less, eye color is so complicated that with any, uh, two eye color parents, you can have any eye color baby. The reason being that the latest estimate is that there are s- over 60 genes involved in producing eye color. So they're all interacting. And a gene isn't just doing one thing, it's got lots of... You know, it's, it's a structure. It's got... Different bits of it are enabling or shaping the protein it produces in a particular way, or meaning it's expressed at a particular moment. And all those differences in those 60 different genes are all interacting to produce the color of eyes, uh, that you have. And you've got two copies of those 60 genes. (laughs) So if you wanted to have a blue-eyed baby, that would be very, very difficult. You could not guarantee it under current technology. So there are some companies in America, and again, this is illegal in the UK, but in the USA, uh, you can go to companies that say they will screen your embryos. So they do exactly what I was saying earlier on, pre-implantation screening, not... Or you can screen the eggs and sperm if you wish, but it's better to do it on the embryo. And they will look for genes that supposedly encode for intelligence or blue eyes or stature or whatever. But in virtu- I mean, the, the, the point about diseases is that they are very remarkable, some of them, because they have, they can have, very, very simple genetic bases. Like Huntington's disease, which is just because you've got an extra set of three letters of DNA that is repeated, that tags onto, uh, the end of the gene and that makes the protein go all wonky. But most characters we have, like eye color, certainly like intelligence, the genetic component of whatever intelligence is, is composed of thousands and thousands of genes. So, uh, you know, if people, listeners wanna give their money to one of these companies, okay, but, you know, I think you'd be better off, if you want your child to be smart, then, you know, have the baby in whatever way you can and then give them lots of books to read and encourage them to be curious, and that'll do the trick, I think.

   9. CWChris Williamson1:01:16

      Yes. One of the interesting things since learning about behavioral genetics last year was that a lot of people, I think, try to, uh, retrofit their child to be somebody that they wanted it to be-

   10. MCMatthew Cobb1:01:28

       (laughs)

   11. CWChris Williamson1:01:28

       ... whilst not realizing that 50% of that child is made up of that person there that stood across, that's sleeping in the bed on the other side from you. And yeah, I mean, that's, that was one of the interesting things. You mentioned the word eugenics earlier on. I, I find any, uh, accusation around eugenics, especially when it comes to conversations of behavioral genetics, completely laughable because you go, "Well, hang on. Why do you think you chose your partner?"

   12. MCMatthew Cobb1:01:52

       (laughs)

   13. CWChris Williamson1:01:53

       What are the physical cues of fitness that you were... Why is it that you think smooth skin and good hair and nails and teeth and all of that, what, what are those cues of? Even bad breath, bad breath's something that we associate with poor dental hygiene. Well, kind of, but it's also something else that suggests that there's something wrong with your immune system perhaps or that all of these things that we pick is a, a visual form. Beauty is eugenics. That's what you're choosing. You're choosing an outward f- version of fitness. But okay, so we've got gain-of-function, bad. We've got gene editing, bad.

   14. MCMatthew Cobb1:02:26

       Well, gene... Uh, hu- heritable genome editing I think is wrong-

   15. CWChris Williamson1:02:30

       Yes.

   16. MCMatthew Cobb1:02:30

       ... uh, and dangerous, uh, and ineffective. Uh, but editing of, uh, say blood cells is going to be, is already experimentally and, uh, will be clinically extraordinary. And if it can be rolled out cheaply and to scale, could, for example, uh, resolve problems of sickle cell disease, which is an enormous problem, uh, for the Afro-Caribbean community in the UK and for, uh, Black Americans and indeed for, uh, people in Africa. This has got a very simple genetic basis, single letter of DNA, uh, that is altered. And so altering that in your blood cells where the, the hemoglobin is, uh, i- i- is present and determines the shape of those blood cells, that is something that can be done. So there are... I mean, you know, it's the heritable, it's the passing onto the next generation that raises the, the, the, the really problematic ethical problems. E- even that having been said, gene therapy, uh, on say, you know, an existing cells in your body has to be safe. And that is, we're still a long way from demonstrating partly for the reasons that I explained earlier about these perhaps unrecognized changes. I- Sorry. Yeah.

   17. CWChris Williamson1:03:45

       I have a friend who recently went to a undisclosed Central American country, uh, to get gene therapy for myostatin inhibition done.

   18. MCMatthew Cobb1:03:59

       Mm-hmm.

   19. CWChris Williamson1:04:00

       So this is the Belgian Blue Bulls, I think, have this. This is the way that they're able to grow such insane muscle. These blues, these bulls look like Arnold Schwarzenegger. Uh, I think it's a country which has autonomous zones within it where medical ethics basically don't exist. There's a friend of mine that flew down from somewhere near where I live and got this procedure done. He's going back for a couple more of these and he's getting, um, uh, body fat analysis, a ton of blood work done, he's going in for, to, to get his labs pretty much every single week. So yes, the, the talk of elective procedures around this now for the super soldier serum from Captain America, uh, I think... I, I actually do think that Captain America has contributed to an awful lot of what people-

   20. MCMatthew Cobb1:04:47

       (laughs)

   21. CWChris Williamson1:04:47

       I'm being genuine. You know, you-

   22. MCMatthew Cobb1:04:48

       No, no, no, indeed, indeed. There is-

   23. CWChris Williamson1:04:49

       That is, the gene editing thing, I guess that's the closest one we've had, you know? You have the super soldier serum.

   24. MCMatthew Cobb1:04:54

       Yeah.

   25. CWChris Williamson1:04:54

       That's how they made him.

   26. MCMatthew Cobb1:04:55

       Yeah, absolutely. Um, well, I hope your friend's okay. Uh, and I hope-

   27. CWChris Williamson1:04:59

       Nothing's happened. Nothing's happening, happened so far. So what was-

   28. MCMatthew Cobb1:05:02

       And I hope he got a big balance, big bank balance. (laughs)

   29. CWChris Williamson1:05:04

       He does, he does indeed. Yes.

   30. MCMatthew Cobb1:05:05

       Then, you know, okay, fooling his money and all that. (laughs)

10. 1:05:09 – 1:20:33

    The Ability to Manipulate Eco-Systems

    1. MCMatthew Cobb1:05:09

    2. CWChris Williamson1:05:09

       What, what were the other things that you were concerned about?

    3. MCMatthew Cobb1:05:11

       Okay, the third, the third thing that I'm concerned about is something which is, again, being pursued with the very best of intentions. And I really want to emphasize this, that in virtually all cases, the scientists doing this work are well-intentioned. They are not Dr. Strangelove. They are not Victor Frankenstein. They are not trying to create something awful. The concern is, and this is a concern that they generally share, that things could go wrong. So this third area is our ability to manipulate ecosystems. So you could... People always say, "Okay, well, you know..." Let's say malaria, half a million people a year currently die of malaria. So with all the DDT we spread around the planet, with all the bed nets that protect people at night from mosquitoes, half a million people die of malaria, and, you know, other mosquito-transmitted diseases are available, but that's the big killer, and most of those half million are infants, children under five. So why don't we alter the mosquitoes so either that they're sterile so they go, they disappear, or say that they're immune to malaria? They can't carry the malaria parasite which sits in them, not doing them any harm but not doing them any good until they inadvertently inject it into us with their saliva, uh, as an anticoagulant whilst the females are biting us. So if you do this... I mean, you can imagine all sorts of ways of doing this and really... I mean, let's, let's say there is a gene, single gene, you can change a single letter of DNA, and now the mosquitoes are immune or they're going to become sterile. So if you release, you produce lots and lots of mosquitoes like this, even if the mosquito has two copies of the gene you've manipulated, when you release it into the wild, that gene is almost certainly going to disappear, even if you produce bazillions of the damn things, because there are even more mosquitoes that don't carry that gene in the wild population. And very simple population genetics shows that over relatively few generations, it disappears. So what, uh, what people realized at the beginning of this century was, well, okay, we're going back to the, what I was saying earlier on about cell repair mechanisms.In certain microbes, there exists a, a kind of parasitic bit of DNA that, uh, produces an enzyme that will cut very precisely at a location of, uh, the genome. And that location is where the DNA is. (laughs) So what happens is that you've got, uh, one copy of this, uh, gene. Uh, it's expressed, it produces an enzyme, which a pair of scissors, and it chops the DNA on the other chromosome. The cell looks at this gap in its DNA, it doesn't like that. Cells don't like having gaps in their DNA. And it goes, "Okay, I'll use this sequence over here on the other chromosome as a model, and I'll copy that over. And now, hey, presto, I've got two copies." And this is called a gene drive because now what you had a single copy, you've now got two. In the next generation, that individual mates with, uh, an ordinary individual. In the embryo, you've just got one copy initially. It copies over and that, when it hatches that offspring, that mosquito has now got two copies. And you imagine that on a population scale, and basically you've got exponential growth. So this gene drive, as you've called, as, as it's called, was hypothesized by a chap called, uh, Bert at Imperial College in, uh, in London at the beginning of the century. And he was, he was just thinking about, "Well, you could do that." This was before CRISPR was invented, before gene editing was, uh, even been given a name. But he saw that this thing existed in microbes and he thought, "Well, okay, maybe we could harness this in some way, if we could find a way." With CRISPR, that became a possibility, and virtually as soon as CRISPR became a, uh, a technology, so at the beg- in multicellular organisms, so at the beginning of 2013, researchers started to apply it, to think about how it could be done, and they were terrified. Um, so they realized that, okay, yes, it just goes off. As, as, as two researchers who actually published an article on this, they discovered it again by mistake. They were just trying to think, "We need more copies of this gene we're interested in." Right? They were interested in, I can't remember, the shape of a, a fly's wing or something, and they wanted more, more copy, more flies with that particular defect. And one of the students, a PhD student thought, "Okay, well maybe I could use this way of kind of copying it over and okay, yeah, and we can produce loads and loads of flies like this." And then they realized what they'd done, they basically created, uh, what they called at the title of the, uh, of the, um, article, a genetic chain reaction. This is a genetic bomb. It goes off. If you, if one of these things were to get out, then the, even a single individual, assuming it survived and mated, after one or two generations, once you got up to several dozen copies of this gene in the wild, this would then go haywire. There'd be no way of stopping it. So something that started off as an incredibly well-intentioned solution to half a million people dying a year, to eradicate mosquitoes in a particular area, um, or to render them, uh, immune to, uh, malaria, that contains within it quite clearly the potential for catastrophe. 'Cause you might say, "Well, who cares about mosquitoes?" Uh, and the answer is, well, an awful lot of animals, (laughs) uh, eat mosquitoes either as flies or as larvae in water. And although all the ecological studies that have been done show that there's no single predator that relies upon the mosquito- any of these mosquitoes, so, you know, there's no- nobody's gonna die, no whole population of other animals gonna wi- get wiped out, lots and lots and lots and lots of animals in, throughout the animal kingdom will eat these things. And if some of those animals go even a little bit hungry because the mosquitoes they normally have now gone, then you end up potentially with ecological disequilibrium, at the very least. We don't know, 'cause we know and u- understand so little about ecology. So we've got this potentially life-saving transformative technology, incredible power, and you've also got the great conce- and you've also got the great concerns from the scientists themselves, again, who've raised the alarm about this and said, "We need either to find ways of, uh, ensuring that this will dissipate," so there's a way of cl- all sorts of clever ideas have been come up with, uh, so that after several generations this will stop. And that will mean the mosquitoes will eventually come back because they'll spread back into the local area, but it will mean that it will be limited in space.

    4. CWChris Williamson1:12:08

       It's like being able to run an experiment.

    5. MCMatthew Cobb1:12:10

       Yeah. I mean, you know, you do it and then stop. It would no longer carry on. The- it would require a certain combination of genes and that would eventually become disaggregated, uh, by the exchange of genes during sexual reproduction. That's one of the ideas. Um, th- th- this actually works. This works to produce sterility, and it works in the laboratory, and you can make a whole cage of mosquitoes disappear in about eight generations. It also works in slightly more naturalistic circumstances, in, you know, cages that are held on a lab site but with access to air. They can't get out, but they can, they can breathe, you know? I mean, it's- (laughs) so it's a bit more realistic. So we know it will work. I don't think there's any reason to think it, it won't work. So the question then comes, who should decide? And then you've got all sorts of problems 'cause you clearly, you think, "Well, okay, the people who are most affected, they should just- should have a, a say in this." So the local community, so there's a group called Target Malaria, which is kind of consortium of lots of, uh, researchers, uh, for the more paranoid amongst your listeners, uh, it's partly funded by the Gates Foundation with perfectly good intentions 'cause they wanna get rid of malaria, you know? And it's better to use this perhaps than, uh, a load of DDT which kills all sorts of insects.... and, uh, in Burkina Faso, they have been discussing with local villagers, who've got a very high level of malaria, lots of their children are dying, how can, you know, can... would you agree to this in principle to this ex- you know, a local release taking place? To which their reply was, "Well, we don't have a word for gene in our local language." Most of the population is illiterate. So how are you going to explain to local people what you want to do? 'Cause you want them to have informed consent, what's called prior informed consent, that they understand what's gonna happen. So one of the things they've done, very clever, has been using theater. So they-

    6. CWChris Williamson1:14:09

       My god, they've done interpretive dance to explain what a gene is.

    7. MCMatthew Cobb1:14:12

       Well, nearly, nearly. (laughs) And what a g- even worse, what a gene drive is. I mean, that still doesn't mean to say that people understand even after going through the theater and the explanations. People are saying, "Well, how can a, a mosquito be half human and half, half, uh, mosquito and, uh, how are they gonna grow as big as airplanes?" So there's still some problem. And even then after they've done all this when journalists... And they discussed with the local leaders and all the rest of it. When journalists went in and talked to the local community, for example, they talked to the women doing the washing, and they said, "What do you think about this?" And the women said, "Well, nobody talks to us about anything. It's the men that decide everything." So, you know, communities are structured. They're not simple, you know, constantly talk to the leaders and it's all okay. So you've got a problem about ensuring the whole community understands. Does everybody have to agree or can you have a simple majority? Uh, and then you've got the problem, well, okay, they might agree, the government might agree, but in deciding this, you could be deciding something that's gonna affect the region, country, continent, the whole planet. You, you may remember that, uh, during the Rio Olympics, there was a big scare about Zika virus. So, Zika virus is transmitted, uh, by, uh, mosquitoes and causes, uh, terrible fetal abnormalities, and it's still a problem. I mean, we only heard about it in the West because they were saying to athletes, "Don't, you know, go there if you are pregnant or you're planning on getting pregnant because, uh, it can cause terrible, uh, problems." It's still ongoing, uh, in South America. But the key point is Zika lives in a mosquito that shouldn't be in South America. It used to live... it used to be confined to Africa where the m- mosquito and the virus didn't cause any problems 'cause the virus wasn't exactly the same. The mosquito traveled over the Atlantic 'cause, you know, they lay their eggs in any kind of stagnant water, old car tires put on ships for all sorts of reasons, traveled across the Atlantic, and then the mosquito changed and Zika changed. So even if you say, okay, the village all understand, they understand gene drives and all the rest of it, should they decide for potentially the whole planet? So, these are real problems and this is what happens when you get a technology. I mean, we're not talking about scientific discovery. We're talking about applying it in the real world in the most complicated thing we know, which is the planet's ecosystem. And although it's quite possible that any such release would be fine and not cause, uh, any danger, it might also cause catastrophe, and we don't know. We really don't know. All I can do is emphasize that the scientists involved take this very, very seriously indeed, the security protocols, they're coming up with plans that can establish kind of up to 60 checkpoints before you might do this. Nothing's been done yet where, you know, you could say, right, you know, a bit like with the launch of the, the, the rocket the other day, you got a no go, no... a go, no go decision point. And at any one of those 60 odd points, you can say, "Okay, no, we stop. We... this isn't safe." And I think that kind of approach with far deeper, uh, ecological understanding, full local community engagement, and above all, international regulation. We're back there again, yeah? Uh, and part of the problem is, you know, people have been discussing this and saying, "God, this is amazing." It's also very alarming. And American, uh, researchers in particular have written an awful lot about it, you know, very clever sociologists and political theorists. But they've got a major problem because what they, they end up wanting to write about is the need for international regulation, like with the AIAEA as I mentioned earlier on. But the US government won't sign up to that. They will not accept it. They don't even sign up to the International Criminal Court. And as I said, they've opposed the Biological Weapons Convention being strengthened. So I cannot see the US government signing up to an international structure that would regulate the application of gene drives, even though I think that is what is absolutely necessary. So in every one of these cases, we've got really complicated science rendered more complicated by taking it out of the lab and putting it in the real world, uh, and then even more complicated issues to do with human society and politics and how we understand who should decide these things. And my point of view is that all this stuff is far too important to be left to the scientists. People need to understand it, the benefits, the potential benefits, especially in terms of the, uh, the kind of more safe applications I've been talking about. But even the potential benefits, say, uh, of gene drives. My, my position on dreve- drives at the moment is that I'm very, very concerned about them. On the other hand, I do understand that if this... we could be so certain that this would be safe or that we could stop the multiplication of these genes with great confidence, uh, then yeah, you would save thousands and thousands of lives. And I don't think that's a negligible weight in the balance that we've got to come up with. But I don't think I should be deciding. I think listeners should be deciding, public around the world, politicians need to engage with this and so on.

    8. CWChris Williamson1:19:15

       We are gods but for the wisdom. It's a very-

    9. MCMatthew Cobb1:19:17

       Indeed. Indeed.

    10. CWChris Williamson1:19:18

        ... very terrifyingly potentially apocalyptic view of the future depending on how much wisdom and how much technology we have.

    11. MCMatthew Cobb1:19:24

        Yeah, absolutely. And indeed that is the... uh, that is the title of the, um, uh, the US edition of, of my book. In the UK it's called The Genetic Age. In the US, uh, they took a rather grander title, uh, because I, I quote Stewart Brand, who's the guy who, uh, set up The Whole Earth Catalog and who is behind, uh, or ins- inspired many of the projects for de-extincting for example. And in, uh, the second, I think, issue of The Whole Earth Catalog in 1968 or 1969, uh, he said, uh, "We are to become as gods and we better get used... we better get good at it." Uh, and so they've called, uh, the US edition of the book, which is coming out in November is called As Gods: A Moral History of the Genetic Age. Now, I'm not really comfortable with the word moral, uh, but I get what they're getting at, and it's really... it's a... the real word is a critical history and I'm being critical, but that doesn't play well on book covers. So (laughs) they put the word moral. I'm no great moral arbiter, uh, and I'm probably much better at finding problems than I am at finding solutions. But if I can highlight some of the problems, then cleverer, smarter people, uh, can come up with some solutions that we can all, uh, engage with.

    12. CWChris Williamson1:20:32

        Matthew

11. 1:20:33 – 1:21:05

    Where to Find Matthew

    1. CWChris Williamson1:20:33

       Cobb, ladies and gentlemen. If people want to keep up to date with the stuff that you're doing online and check out your work, where should they go?

    2. MCMatthew Cobb1:20:39

       Um, oh, probably best thing to do is follow me on Twitter @matthewcobb.

    3. CWChris Williamson1:20:43

       I love it. Matthew, I appreciate you. Thank you.

    4. MCMatthew Cobb1:20:45

       Thank you very much. It's been great.

    5. CWChris Williamson1:20:46

       Well, that's happening people. Thank you very much for tuning in. If you enjoyed that episode, then press here for a selection of the best clips from the podcast over the last few weeks. And don't forget to subscribe. Peace.

Episode duration: 1:21:06