Evolution Tomorrow and Beyond - Robin May

Tonight we're talking about the future of evolution. Um, and in a hundred years, a thousand years, you can definitely come back and tell me how wrong I was. But right now you can't prove it. So I can say anything I like over the next 45 minutes, um, and no one can prove me wrong. So what a great carte blanche to go. And that's exactly what I intend to do. So tonight we're talking about the future of evolution. Where it might go and what it might do. Will we ever be able to see beyond the current observable universe? Oh, it's much worse than that. The observable universe is shrinking. If you want to know what are my odds of winning the lottery, you come straight to probability. Yeah, because probability is all about how likely or not events are to happen. I think the chance of there being an undiscovered second species, very like humans out there in the world today is pretty slender. However, And these are the pictures, if you haven't seen them. I mean, New York was orange. The air was orange. They said one day out in that air was like smoking a pack of cigarettes. It had the same effect on the lungs as smoking a number of cigarettes. So people who'd never smoked in their life were suddenly going to suffer some of the same health effects. Any further questions is a brand new podcast from Gresham College, A place where we ask our speakers all of your questions that went unanswered following their lecture guests have included Ronald Hutton, Robin May, Chris Lin tot, Sarah Hart, and Maggie snowing. Any further questions? All episodes are available wherever you listen to your podcasts. Um, and uh, I really like this, this quote when we're talking about the future. This is Neil's boar who won the Nobel Prize, um, his rather famous quote about, uh, prediction being really quite difficult, especially about the future. Um, and I think that is definitely true of evolution as it is with many other things. But nonetheless, I'm gonna give it a whirl and see if we can predict, um, what might happen over the next decades, centuries, maybe even, uh, millennia going forwards. But before we do that, I think it's quite useful just to quickly recap on what evolution is, especially for those of you who are coming to this completely new. So what does evolution, um, and how does it work? And it's really quite straightforward. Evolution is all about, as you hopefully know, natural selection, uh, choosing things amongst a varied population. So here's my model organism, a little blue.here. Organisms reproduce. They have offspring. Those offspring are not identical to themselves either because of sexual recombination, so shuffling of genes or because of mutation, or a bit of both. So they have all, they have offspring. The offspring are all different. Those offspring compete for resources, food, habitat, whatever. And not all of them make it. So there is selective, uh, we knowing of that population. And so what you end up with is this variable population, um, gets narrowed down. Only the winners survive. Um, those winners are successful, they reproduce and they have their own offspring, which look a bit like themselves, um, and so on and so forth. That process iterates again and again over generations. And eventually what you end up with, um, is a kind of gloriously diverse population of the winners, essentially the winners during the period in which they were selected. Um, and so you end up with a, a tree that looks a bit like this, um, rather ancient one now, all these different species. And that a first approximation is how evolution works. It works by selecting amongst variation and only the winners survive. And I think one of the really important things to think about is there are actually only two ways in which evolution can do that. And people often talk about, you know, ask me questions about, you know, well, how, how will, how can we engineer evolution? And actually evolution is about two things. Um, and it's a bit like it's, it is the two things that sort of feature in a kind of, um, I don't know, like a holiday novel or something. It's all about sex and death, basically. Those are the only two ways you can evolve. Um, because if you take a varied population, like those of you listening here in the hall, and I want to select a way, um, to get a particular type of evolutionary thing. There are two options. One is that I can kill those of you that I think are not suitably fit for the environment. So you die, you don't reproduce your loss to evolution or, and, um, you selectively reproduce from those, um, who are very successful. So they get basically more mating opportunities than the rest of us. Or I have to say, this particular painting of Venus and Adonis, I don't see very much evolutionary success going on there. Um, but that is how evolution works. So the, the, the most successful offspring don't die and do reproduce, and that is how it has worked for three and a half billion years on this planet. Just in the last few decades, we as humans have entered a third opportunity, um, to evolution. And that is the option to actively engineer genes to change genes without either killing, uh, or selectively reproducing from things. So we have gained the ability to edit DNA, um, and to change things. So genetically modified organisms and indeed genetically modified, um, humans in the future potentially. And we'll talk a little bit about that towards, uh, the end of this lecture. But those really are the kind of the tools that the evolution uses and it uses those to shape populations in response to a changing environment. And uh, and really the key thing about evolution is that change is all important. If everything stays exactly the same, there's a little bit of evolution that goes on due to a process called genetic drift. There's random chance and these kinda things, but it's weak. What really drives strong evolution is big change, something that shifts the environment in a way that now starts to select for a different trait in the population. So when we think about the future of evolution, what we're thinking about is how might the planet change and therefore start to exert an evolutionary pressure, um, that drives it in a particular direction. And there are of course lots of ways that the planet is changing. Um, but I think it will come as no surprise to this audience, hopefully to any audience that one of the ways the planet is changing at a remarkable pace, unfortunately, is in terms of temperature. So this is a graph for the last couple of thousand years. Um, and, and my professional colleague Mars, Alan would explain this far better than I'm, but I think you don't have to be a climate scientist, uh, to see that the temperature has gone up really dramatically just in the last few decades, um, beyond anything that has happened, uh, in recent history. Uh, and unless you do something pretty drastic about it, and to be honest, even if we do do something drastic about it, this will still continue for some time due to accumulated carbon dioxide and methane. Um, the planet is gonna get warmer and that is going undoubtedly going to have an evolutionary impact on many species, particularly those species that currently inhabit the coldest parts of the planet. Because those are the parts that will obviously get warmer and those organisms will be less suited to that particular environment. So for instance, if you are a polar specialist like this polar bear, unfortunately your future is looking pretty bleak. And I guess there are sort of two potential roots outta that. So, uh, polar bears might just go completely extinct end of story, or they might evolve in a way that makes them better adapted to the changing environment they find themselves in. And actually the latter is not entirely unfeasible.'cause it turns out that polar bears are relatively recent species to evolve. If you do a genetic typing of polar bears, what you find is they share an ancestor, um, with brown bears. Uh, very recently in terms of evolutionary time, somewhere between 150,000 and 600,000 years ago. That's, that's a very brief period of time in terms of evolution. It's even shorter than the period of time that our own species has existed. Um, and so actually there are very recent offshoot, and in fact today we still have rare cases of hybridization between brown bears, um, and white polar bears. And so one possibility I think, as the planet warms, um, is that undoubtedly many polar bears will die and go extinct. Uh, but in terms of an evolutionary trajectory, they rate may remerge with, uh, brown bears. And ultimately in hundreds of years from now, we may only have brown bears that share a lineage from both of those ancestral populations, which is a slightly depressing thought, although I dunno if it's more depressing or less depressing than just going extinct. So climate change is clearly one way in which we as humans are shaping the world and shaping evolution. But it's not the only way. There are lots of ways that we are shaping, um, the planet around us and also therefore the evolution of the species that cohabit it, uh, with us. And one of the, um, things that we do do, of course, to the world around us is we build on it and we change its structure and we do things like this. We put roads in as a proportion of the entire world. Surface roads are absolutely tiny. Um, but in particular areas. And we are here having this lecture in Central London, that they're of course a very dominant feature of the, of the landscape. Even in areas where they are a tiny feature of the landscape, they actually exert quite a strong selective pressure on some species. Um, and there's some really fascinating work that's come out recently from the United States, which shows its impact on one particular species. And that's the swallow. So swallows as you know, birds that fly around quite fast, um, uh, they often swoop over roads 'cause they're catching insects. Insects, uh, tend to accumulate on these large warm surface, especially after rain. And that means unfortunately that they get hit by cars. Um, and so being able to swerve a car is quite a good strong selective pressure, uh, on a swallow. And it turns out that that is having a direct measurable evolutionary impact on that species right now. So if you look at swallows who have met a sticky end, uh, in a, in a collision with a car, what you see here, these are the black bars, is that dead swallows tend to have longer wings than the swallows that, uh, that than the swallows that survived. And that's because if you have a long wing, you are really good at gliding and swooping, but you are less maneuverable. Like if you think about airplanes, for example, big jumbo jets go a long distance, but they can't suddenly go upside down those planes that going do loop the loops and put smoke out and make you feel a bit sick, um, they have tiny short wings 'cause they're very maneuverable. Same thing for swallows, swallows with short wings, very maneuverable, less likely to get hit by a car and survive. Which means that over the last 50 years or so when we've been driving motorcars at speed on roads, we have been selecting for shorter winged swallows. Uh, and you can see that actually there's the white dots here. Um, this is a 40 year, uh, time sequence, more or less. And the average wing length of swallows, at least in the United States, has got shorter and shorter and shorter over time. Um, and so this is a, a kind of small but significant way in which we are shaping the evolution of a species indirectly, but quite rapidly actually. 40 years is really a very brief period of time, um, for evolution to, to take place. So we're warming the world and we're changing it for people. We are building roads, we're changing things. What else are we doing? Um, and this I think is one of the really, uh, neat observations that shows that sometimes the impacts of evolution are really, really quite unpredictable. Um, and this is work that's come out recently, largely led by Oxford and collaborating groups. Um, looking at a species that is pretty familiar to those of us, at least in, in Europe and and North America. This is the great tit as we call it in the UK United Kingdom. Um, a small, very common bird, I'm sure many of you have seen it. Um, and for many years there has been an intriguing observation about great, its, there are common species right across Europe. Um, but it turns out that if you look at the length of their bill, then the ones that live in the UK here in the UK have longer bills than all of the great tits we see in mainland Europe. Um, and so people have speculated for a long time, well, is this because, uh, is it actually kinda some kind of cryptic subspecies? Is it evolving in a different direction? Um, might it be what's called a founder effect? So maybe there was a very small population of great tits that started life in the uk, uh, with longer bills. And so we have 'em that way. But it turns out that's not true at all. It turns out that this is evolution in action because if you look at, uh, bill length over time, what you see is that in the United Kingdom, the bills are getting longer and longer over time, over quite a rapid period of time. Actually, this is only about 30 years. So something in the UK is selecting for longer bill length in great tits. Um, and what might lab be? And it turns out to be really quite fascinating. It's something that many of us do. It's this, we feed birds, um, and we often feed 'em in things like this. And if you've got a really short bill, it's very frustrating 'cause you can't get to your peanut. Um, and if you've got a long bill, you can, um, and it turns out, so then you say to you, well, why is this any happening in the uk? And it turns out, and I didn't know this until fairly recently, it turns out that we are pretty obsessive in the UK about feeding birds. In fact, we feed birds by weight, more wild bird food than the entire rest of Europe put together. Um, and Europe's quite a big place. Uh, so we are pretty keen on this, and this is why we're driving evolution because actually a wild bird feeding in domestic gardens is a pretty big selective pressure on great ts in the uk. Um, and I dunno whether that's good, bad or indifferent, but it is quite interesting. I think that something that many of us do is actually driving the evolution of a species. And who knows hundreds of years from now, if we keep feeding birds, maybe we will end up with two different populations, um, of great tits in these different locations. So we are shaping evolution in lots and lots of different ways. Okay? We are changing the animals around us, we're changing plants to, um, we are driving this kind of process of selection. But actually I think there is one species beyond all others, which is the one that is most likely to have to evolve rapidly in response to things that humans do. And the species that I think will evolve fastest as a result of humans, um, is this one here, uh, which is, uh, the human species itself. Um, the these two are now large teenagers and probably cringing if they're watching this on YouTube later on. Um, uh, but anyway, uh, so humans ourselves, I think are probably the species that is most likely to have to evolve as a result of our own activities. And why do I say that? I say that because many of the things that we do as humans that we have done to transform the world are having a really direct effect on our own lives. Many of them are good public transport, better healthcare, all these kinda things. Um, some of them not so much. And I think one of the things in particular that we have done, of course, is we have expanded our population enormously in terms of numbers, but also enormously in terms of density. Many, many, many of us live in cities or mega cities around the world of millions of people in very high density. I'm always slightly worried about talking about density when I'm in a crowded lecture theater. Uh, but we often come together in high density. Um, and as we have experienced, unfortunately, uh, very clearly in recent years, large populations closely crowded together are the perfect breeding ground, uh, for disease, uh, because disease can spread rapidly, um, between populations. That's true of all animals and plants. Um, but in a human case, of course, it's, it's also particularly prevalent when it's, uh, when it's a human disease. So we have created these large populations of people, um, and they're getting bigger, especially the city. The urban population is getting much, much bigger. And so, uh, so it is an ideal condition for, uh, a disease spread. And disease is of course one of the most dramatic ways in which evolution shapes natural selection. Uh, because we said a a few slides ago, uh, there are only two options really. You either die or you reproduce really well. And a disease that kills lots of people is a very powerful way to change the frequency of genes and therefore the evolution of a population. And we have seen that repeatedly over history. So if we look for example, in the historical record at the single biggest pandemics that we're aware of having just lived through one, um, uh, they are absolutely enormous. And actually, unfortunately, despite the huge human tragedy of COVID-19, it doesn't even scratch the surface in terms of previous pandemics. So this, for example, is influenza flu virus. This is the 1918 pandemic flu, uh, that arose at the end of the First World War in Spain, typically, and a spread across most of the world very rapidly within about 18 months. That pandemic flu, we estimate to have killed about 40 million people. That's about 2% of the human population at the time. And just to put that in perspective, that's about 20 times more as a proportion than COVID-19 killed. Um, so this was a pretty significant pandemic that wiped out a very large proportion of the human population. It though is much, much smaller than previous pandemics that we know of from history. This is another virus. This is smallpox, happily eradicated, still the only case of a human disease that we have successfully eradicated from the planet. Um, uh, hopefully the first of many. But nonetheless, this one. So smallpox is a disease that was endemic, uh, to Europe originally, um, and was not present in the Americas. And when European settlers first moved to America, some of them inadvertently brought smallpox with them because it was, it was carried in them or in their, their bedding and their materials, um, and exposed a completely naive American native population to this disease, for which they had no immunity at all. Um, and as a result of that, uh, during the sort of immediately subsequent to the discovery of the, what we call the new world, um, smallpox swept the native population. And we estimate, although we have obviously no really robust records, but it's estimated, um, that about 90% of the Native American population died of smallpox, um, in the decades following European discovery of the Americas, uh, about 50 million people at the time. And a huge, huge impact on that population. We, of course, have no genetic data demonstrating what that might have impacted on the, on the survivors, um, of that population. But nonetheless, a huge selective pressure. And if we go back even further, particularly into the Middle Ages, um, you will be familiar hopefully with this organism. This is Yesinia Pestis, the causative agent of the Bubonic Plague or the Black Death. Um, and the Black Death is a, a disease that originated in Asia. They're spread around the world. Um, and until relatively recently in history, actually, what you would have are waves of epi epidemics. Uh, a different variant of the bacteria might come, or, or different kind of population would come pr potentially on, uh, trade routes. The Silk Road in particular, um, it would enter a population and then it would sweep, it would cause large mortality, and then it would die out and then come back again later on. Um, and the worst, uh, historical record we have of this, or the best historical record of the worst event, um, is about 1346, uh, when the black deaths swept through, uh, Western Europe in particular, um, and led to many of the things that you read of in history, where entire cities, including London, um, sort of vacated out to try and avoid. The Black Death records are very difficult to come by. But if we look at things like graveyard records, the estimate is that across most of Europe, about 50% of the human population, uh, was wiped out by this disease in about six or seven years. Um, and I think, I mean, it's very difficult to get your head around that. Um, I don't even want to begin to think what that would be like. But the idea that half your population has gone well within a, a single generation is, is quite remarkable. That level of selective pressure, of course, leads to big evolutionary consequences. And we'll touch on some of those in in a second. These moments from history, though are unfortunately not consigned to history. There are other things we are doing, I think, that are likely to shape very strongly our evolutionary response going forwards due to disease. And of course, one of the things we're doing, unfortunately, inadvertently is selecting for organisms that are resistant to our own therapies, antibiotic resistant bacteria in particular. And, uh, this is a process that of course has only been going on since we started to use antibiotics about a hundred years, more or less, by adding antibiotics, um, particularly by using them inappropriately at low dose or in areas where they're not essential. Like in agriculture, for example, um, we have driven a very, very strong evolutionary process in pathogens to become resistant to them because only resistant organisms survive. Um, and as a result of that, what we now find ourselves in is a situation where many, many pathogens are resistant to 1, 2, 3, or almost all of the frontline antibiotics. And this is just a, a, a single graph showing that for two organisms, Escher, Coline, and Klebsiella, um, which are both infections of humans, and a snapshot in time looking at how many isolates, so how many bacteria that you sample from people out there are resistant to these different groups of antibiotics. And I think, um, you can see quite easily without reading the numbers, uh, that resistance is remarkably high, remembering that a hundred years ago or so, all of these WA bars will be zero. Um, so we have selected for a large amount of resistance very rapidly. There are, I'm delighted to say, lots of activities ongoing to try and reduce this problem. So better use of antibiotics, new antibiotics, more use of vaccination. Um, but nonetheless, without that process, I think what we see, uh, quite rapidly in front of us is a prospect where many common infections are now untreatable and once again, return to being essentially lethal infections. And I think, uh, you know, it's just outside of sort of living memory. But if you are 120, 130, you would easily remember a time when, uh, you know, stepping on a nail in a garden might have been a death sentence because you have no antibiotics to treat it. Um, and if we're not careful, we might return to that. And if we do, then antibiotic resistant pathogens may be an incredibly powerful force at evolving humans away, because now you can't rely on an antibiotic to get over your, uh, your infection. What you rely on is your own genetic predisposition, and therefore, evolution kicks back in. So there are outbreaks of things we know about, like black death, there are things that we can predict but haven't quite got there yet, like antibiotic resistance. Um, and then of course there is a third risk of major disease from stuff that we didn't see coming, or at least, um, we haven't immediately recognized. IE completely new pathogens arising from the environment. And we've had, uh, one of those quite recently. But, um, unfortunately it's not the only one out there. Um, so, and that's largely because humans are roaming into areas of the world doing things that we haven't done before, exposing ourselves to environments we haven't seen. And so, for example, entering areas of pristine rainforest with no previous human contact, there are many, many pathogens that are found in, uh, endemic animal populations, for example, to which humans have not been exposed. And rather, like the Native American smallpox situation, we have no intrinsic resistance. And so if one of those jumps from an animal to a human, we could end up with a new pandemic of, of fairly dramatic proportions. Um, and you might think that this chance is actually really, really quite low, um, disappointingly, I'm afraid it's actually not as low as you might like it to be. And so there was a program run outta the United States called Predict, um, between 2009 and 2019 in which they screened, uh, wildlife, particularly in the tropics for novel viruses, in particular things that might cause human disease. And in the 10 years this program at Ran, they identified 949 novel viruses with human potential. It's almost a thousand pathogens, um, that we didn't know about before that were out there discovered in a single project. So, um, so on this very gloomy note, uh, I guess what I'm saying is that I think this is really quite, um, a worryingly high probability that at some point in the foreseeable future, maybe not next year or 10 years or a hundred years, but in the, in the foreseeable evolutionary future, we will have a major lethal pandemic of humans that will shape our future evolution, will either go completely extinct or there'll be a, a, a dramatic selection for people who are intrinsically resistant to whatever that infection is. And that will shape the future of human evolution. So if that happens, um, what might we expect to come out the other side? Um, and we obviously don't know. Um, and that's the fun thing about this lecture. I can tell you whatever I like. Um, but there are some things we can learn from history that tell us a bit about that. So for example, we can look back at major pandemics of the past and we can say, what did they do to the human population? So this is the black death once again here. Um, and the black deaths, I said, swept through Europe, killed lots of people. And actually one of the places we have the most useful scientific resources right here in London, where at the time it swept through so many people died, uh, that the city of London dug plague pits and they threw people into them. Um, and then because, uh, then as now, uh, local authorities were very cautious about saving money, um, they realized that having dug a big plague pit, if it wasn't completely full, you could cover it with a bit of soil in the following year, you could use it again. Um, and so what you have in particular areas, especially Smithfield, just around the corner from here, are plague pits that are like little time capsules at the bottom. You've got lots and lots of people who died of the black death on top of them you have people who died a few years later of something else. So those people in the upper layer by definition, survive the black death and the people at the bottom didn't. So what you can do is you can rescue the DNA from those people, and you can compare genes present in those who died from those who didn't die. And Louis Rero in particular has done that, um, and has looked for genes that are significantly overrepresented in the survivors. So these are genes which we hypothesize had something to do with helping those people survive, even though they then died a few years later or something else. Um, and what you see are some genes, the ones that are colored in here, um, that are significantly overrepresented. And it comes as kind of no surprise that most of the genes that seem to be very strongly selected for are genes that have a role in the immune system, particularly in kind of hyping up the immune system, making it more aggressive. And that makes sense, right? If you're gonna, uh, uh, be struck down by a bacterial infection, what you want is an immune system that's geared up, ready to fight it off. And so those people survive better. There was a price to pay because if your immune system is always ramped up, ready for an infection, sometimes it gets it wrong and damages you instead. And so, um, if you have some of these genes, you're also more likely to suffer from autoimmune diseases like rheumatoid arthritis. Um, and so there's a trade off, you survive the black death, but unfortunately you have nobby knuckles when you've got older, which is probably a pretty good deal actually at the time. Um, but, uh, so one prediction I think I can make with some confidence is at some point in the future, there will be a major pandemic of humans. Lots of people will die, and the people who come out the other end will have better immune genes than the rest of us. Um, and they may well also therefore have to pay a price in terms of autoimmunity. So that feels like a relatively safe prediction. You are welcome to come back in 300 years and tell me I got it wrong. Um, uh, but I won't be here. Um, so, so that's my first prediction. However, surviving a pandemic is a part of surviving a pandemic is about having a really good immune system. But no, it's not the only answer. There are other things that you can do to avoid dying in a pandemic. Uh, and we've seen one of those demonstrated during the Covid pandemic because one of the most effective measures we had at controlling the disease was lockdown, much as it was pretty miserable. Keeping people away from each other is a pretty good way of reducing the spread of disease. So telling people to stay at home is quite a good state to measure to help that. But what about if we don't have a state measure? Are there genetic factors that might lead to this? And it turns out that there might be, because it turns out there are genes or genetic variants that are associated with your likelihood of being sociable or not sociable. Um, and so there's quite an interesting study fairly recently where people, uh, were screened or not screened. They were, they were questioned about their sociability. Are you the kind of person who likes going out and partying? Uh, do you prefer to stay at home and read a book? Um, do you ever feel socially anxious? Do you get worried if you haven't seen people or do you actually prefer your own company? And you can do an approach called a genome-wide association study, and you can look for genes, genetic variants that are associated, uh, with enjoying partying or enjoying your own company. And you can find genes essentially associated with whether you feel lonely or not. Um, and there are lots of them, okay? They're all very, very weak effects. There's no gene here that suddenly turns into a party animal. Um, but lots of these genes together mean you're more likely or less likely, uh, to be kind of very sociable. So one possibility in my future, rather bleak pandemic po you know, scenario, um, is that you will select for people who have good immunity. You will also select for people who are a bit anti-social, um, and hang around on their own. They don't go out and get mixed. And so maybe what we'd see is these genes are, are selected. And one of the most interesting things is that some of these genes actually turn out, um, to have roles in the nervous system. So for example, DPD two, I dunno which one it is. DPD two, which is a dopamine receptor. Dopamine is a neurotransmitter in the brain. Um, so it actually makes plausible sense, uh, that you have sort of slight subtleties in your brain that make you more or less likely to be sociable. Um, and if that turns out to be an advantage in terms of not catching the next pandemic, maybe those genetic variants, uh, will be selected for. So, so, so far we've got a group of people who are gonna have good immune systems, quite a bit of autoimmunity, uh, and be pretty anti-social, just to make it even more bleak. There is a third possibility here too, of course. So let's imagine this pandemic is roving through, uh, human populations. I think it's a reasonable bet to say that society will not continue in the way that we think of. If you had a pandemic that kills 50% of humanity, I don't think we're all gonna be sitting here reading our newspapers and being relaxed. I think there is likely to be quite a big societal breakdown. And of course there are thousands of science fiction novels and films written about this kind of Armageddon, uh, prospect. So let's imagine now lots of people died. Society's broken down, worlds falling apart, people are roaming around, um, in a sort of very bleak, apocalyptic kind of, uh, mechanism. There are certain things that are probably going to be beneficial to you as an individual in that fairly apocalyptic scenario. And unfortunately, one of them is you're probably gonna be not the kind of person to sit down and have a gentle chat with people. You are probably likely to be quite swift to violence, uh, because if everyone's fighting over food and short resources, um, if you are the guy who wants to settle everybody down and have a chat, you're not gonna make it. Um, and and so, uh, violence, particularly violence in response to a challenging situation might well, unfortunately be something that is selected for. So the question is, are the genetic markers, um, of violence, um, and rather disappointingly, it turns out there are, um, and in fact the biggest one we know of is this, uh, protein here. This is M-A-O-A-A mean oxidase, um, which is the product obviously of, of gene. And this gene was identified by a group who were working with a family in the Netherlands, um, which has a, a, a remarkable and very sad history of extreme violence in men. So in this family cohort, in this family tree, uh, men were highly likely to conduct violent crime and end up in prison, the women, not at all. Um, and that immediately suggests there is something going on here that is on the X chromosome because women, as you might recall from your GTSE biology, women carry two x chromosomes, the xx, and therefore, if there's a genetic mutation, they would need it on both of their chromosomes To show that phenotype, to show that, uh, trait men, uh, have an X and a Y, and the Y is a tiny chromosome that's largely empty, tells you something about men. Um, uh, and, and so we only need one copy, faulty copy on the X chromosome to show whatever is associated with that. So there are lots of what's called X-linked diseases that show themselves in men. So the fact that this family had all the boys were violent and the girls were perfectly normal, suggested there was a gene on the X chromosome that was somehow associated with violence, and it turns out to be this one here. Um, and in fact, uh, if you look at the, the, the men in that family who were in prison, essentially all of them carried this mutant form of, of MAOA. That's pretty extreme, being violent enough to end up in prison. But it turns out that this gene is actually quite variable and all of us have different, slightly different flavors of it. In particular, there's a variation that changes the amount of the protein you make. The more protein you make, essentially the less likely you are to be violent. You have a low level of this, uh, protein, you are more likely to respond violently, particularly to provocation. So if you're the kind of person who loses your temper in, in a bit of a road rage incident, you may have a low level of MAOA at the moment in society. I guess, if anything, there might be a mild evolutionary pressure against that trait because generally beating people up in a road rage and it's a bad idea. Um, and, and so there's no selective pressure, but in a scenario where the world has fallen apart, uh, and you are all fighting, literally fighting for supplies, actually having the variance that cause violence might be something selected for. Um, and so this I think is another gene, uh, that might end up, uh, shaping our future. Um, so that is a really bleak scenario there. So the world's gonna have a massive pandemic. Most of us are gonna die. Those of us are gonna survive, are gonna have, you know, arthritis be lonely and antisocial and also be very violent. Um, other than that, the world is gonna be great. So let's, let's, let's see if we can raise the tone a bit for, for the last part of the lecture. So, so this is all about natural evolution and those processes happen all the time. But I think there is also, and of course one of the most fascinating things over recent decades has been the fact that we now start to control to a minor extent, but to control the trajectory of evolution of all sorts of things around us. And we've talked earlier in this series about selecting, you know, livestock and domestic pets and things, but also of ourselves. Uh, and we've been doing this by and large, only really for about one generation out 40 or 50 years, where we have started to shape deliberately our own evolution. And of course, the place we've done that most is in terms of our reproduction. Um, IVF in vitro fertilization, originally, of course purely used as an ability to, to enable people to have children who couldn't otherwise have children these days. Also used as a very, um, powerful tool actually to help people avoid, uh, genetic disorders in, in their offspring. So typically, um, there are now something like 600 genetic disorders that can and often are screened in embryos prior to implantation. So you can check that your, your future baby will not have a whole range of diseases, um, before you implant it. And I think largely that has been a terrifically good thing. It's enabled people to, um, have children that don't have things like sickle cell anemia, for example, Huntington's disease, cystic fibrosis, lots and lots of serious diseases. It does though lead to an evolutionary consequence.'cause what you have done is you have taken a genetic variant that by definition you have and you have stopped it being passed onto your offspring even though you've reproduced. So that is something that has never happened before in evolution, because as I said, many times this lecture, the only options that were previously available were dying or reproducing. But now there's a third one you've edited, you've changed, uh, that offspring by selective processes. That has been a really, really minor thing despite the large number of IVF babies in terms of the overall genetic impact on, uh, society. But there's a lot more coming in particular the last 10 years, of course, we've had this transformation of our genetic tools, particularly with the discovery of crispr, this, um, technique by which you can very, very precisely edit DNA and change it, and something that is now done in labs all around the world on all sorts of different organisms. It is also being used now clinically in humans, and I would point out, but thus far, not in a way that is heritable. So people are doing CRISPR editing of DNA, but not in the cells that you will pass on to your offspring, not on your egg cells or your sperm cells. Um, and so what we're doing at the moment clinically is using it to treat things in tissues of someone who's already got a disease, but potentially there is no problem there, there's no barrier to using this to edit sperm and egg cells. Um, and therefore to create babies that have a different genetic compliment. Um, and of course, uh, this has happened despite a, a global moratorium on it. Um, one, uh, scientist in China who did this, um, ostensibly for, for positive reasons, to edit the genome of two baby girls who are due to be born to an HIV positive mother. Um, and to edit them in a way that made them resistant to HIV at face value, a kind of positive thing to do, uh, but ethically an absolute minefield and done with zero permission at all. And indeed he ended up in prison for it. But nonetheless, um, those two baby girls exist. They're out in, in the world somewhere, um, and are a new type of evolutionary step, if you like, for humanity. And the question I think remains, is that something that will never happen again? Or actually is that a sort of barrier that's now been broken and will, will start to happen that raises all sorts of interesting and challenging ethical questions? So for example, many of us in the room and certainly myself would say that this process, um, has huge benefits, particularly for what we call monogenic serious diseases. So genes, so, so disorders where a single gene is affected and the consequence on the, on the child is profound. So for example, cystic fibrosis, cystic fibrosis is called by a single faulty gene. It's relatively easy to correct. The consequence of having cystic fibrosis is pretty terrible. Um, so I suspect many of us in the room would say, actually, if there's an opportunity to edit our genes to make sure our children didn't have cystic fibrosis, that seems like a reasonable thing to do. There are lots of other diseases though, where actually it's a little bit less easy. So for example, there's a disease called y linked sperm genic failure. And in that process, um, boys, men are unable to reduce functional sperms. So they're sterile as a carrier of that gene. Even as a boy, you're not unhealthy, you're perfectly fit, uh, but you're sterile. Um, and so this is a disease and it's a single gene. So this is a disease where you could edit as a parent, you could say, I don't want my son to be sterile, I'm gonna edit this gene to print it. Um, and I can see a perfectly valid reason for doing that. But of course, you're doing it not for your child, but actually for your grandchildren, it's a kind of insurance policy. So make sure you could have grandchildren years to come and starts to get a little bit muddier. Monogenic diseases, single gene disorders are, uh, there are many, many of them, but they are typically quite rare. But what we have a lot more of are polygenic diseases. Diseases where lots and lots of genes interact often with the environment to cause common, uh, ailments. And so for example, atherosclerosis. So disease of of blood vessels, um, very, very common, particularly in Western Europe. Lots of this is about diet, smoking, poor health choices, but lots, it's also about genes. There are genetic variants that make you more or less likely to things like high cholesterol, um, and the impacts of atherosclerosis At the moment, we are a long way off from being able to tweak all of these genes, but I don't think it's impossible. I don't think it's gonna stay, you know, unfeasible for very long. We might find ourselves in the future where actually you could say, well, my baby has got a higher than average risk of having a heart attack when they're 63. Um, I'm gonna edit all these 27 genes to make sure we lower their risk. And there would be a good rational reason to that. Of course, what we don't know is whether editing those 27 genes might have some other effect. Maybe you're gonna reduce their risk of a heart attack, but you make them also, I dunno, less good as a global tiddlywinks player. Um, and actually maybe that was their future. You've just changed. We don't, we don't know that even trickier when you're dealing with, uh, genes that have very late effects. I think. So for example, Alzheimer's disease obviously absolutely devastating to people who suffer it. Um, with the exception of early onset Alzheimer's, typically a disease of old age. Again, a combination of chance, environmental factors, et cetera, et cetera. But also some genetic predisposition. We start to understand more about the genes there. What about if you were to be given the opportunity to edit your child, to reduce their risk of Alzheimer's, it's not a guarantee. They might still get it, but it would reduce their risk. But only when they're 60, 70, 80 years old, is that something that we as a society should accept, um, and therefore sort of evolve our species in a new direction? Or perhaps most controversially of all? What about old age itself? Uh, we know that there are genes associated with better health in old age longevity, um, or poor health. At old age, you could immediately easily envisage a future in which people are offered the choice to crisper edit their embryo, to extend their lifespan by five or six years. Um, or perhaps their health spans the, the amount of time they spend healthily. And again, as a parent, I think many of us would say, well, that sounds like a good idea. I won't be there to see it, but great, let's have my child here, a hundred or 150, or, who knows what's possible? Um, but you would be fundamentally shape, shape changing the trajectory, uh, for the future of our species. And I think there's lots of really challenging questions for us, um, as, as humans. Uh, and, and I guess the biggest challenge is how we coordinate that globally, because it's no good one country deciding it's gonna do it or not if nobody else does, because you know, once the genie's outta the bottle, it's underway. And then what about the stuff that's got nothing at all to do with disease, but is still for some people at least quite important. So this protein structure in front of you is alpha actinin. It's a muscle protein and it comes in different flavors, in particular different variants in particular, there's one variant which is strongly associated with sprinting ability. And if you look at people who win gold medals with a hundred meter or 200 meters, the vast majority carry the sprint variant of this gene. It is entirely possible to edit your embryo if you wanted to, to make it much more likely to be a sprinter than a nons sprinter. Um, you know, for many of us, I think that's completely pointless. Why would you want to do that? But there are people out there who really, really want to see their child win a gold medal and maybe they'll start to apply pressure to bring this kind of skill into it. Or even really trivial things like height. We now, we've done lots of genome wide association studies for markers associated with height. It would be theoretically possible to engineer an embryo to have a far better chance of becoming a, a two meter giant than the rest of us. Um, or alternatively, if you want a really small char, 'cause you've got another very small house, um, maybe you could select them for that as well. Um, these things start to become achievable, uh, within, within the kind of grass of science. I guess there's one slight cautionary tale here though, is that the more genetics we do, the more powerful the tools get, the more we start to see how these, uh, genetic influences shape our lives. Uh, but the more caution comes with it and, and the cautionary tale I have is around this, is around music. You might think that music is a such a intrinsically kind of human cultural thing. It's got nothing to do with your genetics and you would unfortunately be wrong. Um, so there has been a study just a couple of years ago looking at musicality or more specifically people's ability to do things associated with music, like keep a rhythm or keep a tone. You can ask people whether they can keep rhythm or not, and you can test them and you can divide them into those who can keep rhythm and, and those like me who clearly can't. Um, and, and you can then do genetics on those and work out what genes are associated with an enhanced musical ability or a less enhanced one. And you find, just like those previous graphs I've shown you, where these are all different genes, the ones above the dotted line here are genes that are statistically, uh, overrepresented in the more musical amongst us. Okay? So if you carry lots, and you'll see there's loads and loads of them, as you might expect, it's not straightforward. You're not either musical or not, but there are lots of genes, um, that if you have these variants together, you are more likely to be a musical talent, um, than a complete non-musical person like myself. So, um, so you might say, aha, what I would really like to have is the next, you know, uh, I don't know, whatever, um, conductor of the Royal Albert Hall or the next Joe Stellar violinist or, um, something like that. Um, I'm gonna edit my child for all of these things here and I'm gonna make them super, super musical. And if you did that, you would be, uh, taking an enormous gamble. And we know that because of a really beautiful piece of very recent data, um, from this chap here. This is Ludwig van Beethoven, um, who you might have heard of. He's a musician, um, and, uh, he's one of the world's most successful musicians ever in history. And rather fortuitously, when Beethoven died, somebody had the good foresight to think this guy was really famous, gonna keep his hair, and they kept a lock of Beethoven's hair. Um, and it turns out that when you keep a lock of someone's hair, you keep their DNA with it. So very recently a group has sequenced Beethoven's genome. Uh, I don't think they got his permission, which is a bit worrying, but anyway, um, they've sequenced genome, so we now know what Beethoven's uh, genome was like. Um, and so you can compare Beethoven to that recent study and you say, this guy was a musical genius. Where does he fall on the spectrum? And it turns out that he was massively unmusical. He was only in the ninth percentile. He was far less musical by genetics than the rest of us, uh, which I think is a salutary lesson in relying too much, uh, on genetics. So finally then having projected this vision of the future in which we're all gonna die horribly, um, and even if you think you're gonna be musical, you're not gonna be musical. Um, there is one kind of straw left to grasp out maybe when it all gets too much when we've boiled the earth through climate change and released all sorts of horrible plagues. Um, and, and everything is falling around our ears. Maybe we just need to get out of here and we need to disappear off planet earth, um, and colonize some new location like Mars. So if we were gonna do that, is there likely to be an evolutionary impact for the colonists own Mars? And of course the answer is of course there's going to be an evolutionary impact and there are two options. It might be random, it might be the people who ended up there and the rest of us, us didn't. Or you might, if you're gonna invest billions of dollars setting up a colony in Mars, you might say, well, I don't want to take my chance on evolution. I'm going to, uh, stack the cards in my favor. I'm going to edit people who go to Mars with useful genes. So they're ready to go. And what might they be? They may maybe be like, so you might for example, edit this, uh, genius, the protein, uh, which has the really catchy name of SLC 24 A five, uh, trips off the tongue. And this is a gene that regulates skin pigmentation. If you're on planets don't have a thick atmosphere like the uk, you're gonna get a lot of uv, a lot of ultraviolet. Um, being pale and white skin is not a great choice. You are much more likely to get skin cancer, much better to have darker skin pigmentation. So you might edit your astronauts to have the version of this that's associated with darker skin. Simpler way obviously would be just to recruit astronauts who are already dark skinned in the first place. Um, but, but nonetheless as a genetic editing tool, you could, you could do this. You might also want to edit this one. This is EPAs one. This is a protein, um, that is associated with blood vessel thickness and oxygen use. And it turns out there is a variant of this gene that helps people survive in low oxygen at high altitude. It's very, very common in, in people, for example, on the Tibetan plateau at high altitude. Um, uh, uh, but very uncommon in the rest of us who live down here on, on more or less at sea level. Um, because you're gonna be in an environment with no oxygen, it's gonna be quite scarce. Um, I think it would be quite sensible thing to edit all your astronauts to have the version of this that lets them get by on lower oxygen so they don't all black out and have altitude sickness the entire time also there. So you might wanna edit that one there. Um, or how about this one? This is neuropeptide y It drives signaling in the brain. Um, and in particular, uh, it, it is correlated quite strongly. Different levels are correlated quite strongly with anxiety and depression. If you are gonna take six months closed in a spaceship to get to Mars, you really don't want someone who's gonna get a bit anxious and depressed on day one. And so you might edit all your astronauts to have the version of this that's associated with being really quite chilled out. Um, so they're quite mad. Of course there's a slight downside they might get to Mars and be so chilled out. They don't do anything when they get there. Um, but nonetheless, you might want to kind of edit all these sort of things here and, and there are more and more and more examples. So I think, you know, there is a real question about to what extent would you intervene in this going forward? And I guess my last cautionary tale would be you can do all of this and you still won't necessarily predict the future. And so perhaps the best lesson of all of this is if you want to ensure yourselves about whatever might be coming about the future evolution of humanity by far and away, the best way you can do that is to ensure you have lots and lots of diversity in your gene pool right now. And so the positive message to end this otherwise pretty apocalyptic kind of lecture on, um, is that all the things we do to increase equality, diversity, and the movement of people all around the world are actually pretty sound things to do evolutionarily. And on that minorly upbeat note, I will finish there. Thank you very much. I think the great hit referenced it very well. I mean, there is a lot of question about food. Oh no, <laugh>. Yeah, and bird feeders. See I told you, we all feed our birds. That's why<laugh>, um, I love that one. Um, are there good effects of high cholesterol genes and, uh, what would be negative consequences of removing such a variance? Yeah, so that's a good question. So, um, so high cholesterol is associated with heart disease and all sorts of negative problems. And actually there's a broader, broader question here is that lots of the things that are associated with poor health today are actually quite useful back in evolutionary time. So for example, gene variants that accumulate cholesterol, bad idea if you are in wealthy UK and with free access to chocolate. Um, pretty good idea. Maybe 50,000 years ago when food was scarce and you needed to get every last available bit of fat outta the dead wooly mammoth you were eating or something. Um, and so actually these, these kind of allude to that kind of suggestion that a lot of our modern health problems are about the fact that we're adapted to a kind of neolithic diet, but now we're subjecting ourselves to other things. So, so that's a long way of saying yes, there are right at the moment not so great in, in modern society. Good. Um, I'm going to ask another question related to food. Should a non GMO food be as desirable as some food packages claim it to be? Oh my goodness. That's a bit left field, right?<laugh> should, uh, should, should, well, I mean the desirability of food is quite tricky because that's, I mean, it's very personal, isn't it? I dunno, you know, um, I'm looking around the audience here, like Brussels sprouts, definitely not. Uh, I bet there some of you at least eat brussel sprouts. They're not edible, actually can't eat a brussel sprout. They're disgusting. Um, it, it, so, so I think there's a, you know, the, the desirability of thing is really tricky. I mean, I guess there's sort of evolutionary question there. If you're gonna go to Mars and you're all gonna be drinking stuff that's basically just toothpaste, um, uh, you know, might, would you want to select these people who are, you know, just don't care about food, for example, not the people like me who are obsessed with it. Um, and, uh, because actually, you know, if you're the kind of person who lives for a sort of fantastic meal out on a Friday night, you're not gonna do well in Mars. So maybe, maybe we'll select for that. If someone wanted to do any of this, could you stop them? Well, so the short answer is not really, I mean, you can obviously send 'em to prison. You can do all sorts of things. There are, there are, at, at the moment it still requires pretty advanced laboratory facilities to do most of these things. So I, I guess we would have an early indication if a billionaire started building a really fantastic lab and their apparent reason, um, we might get some, my early sickness signs. You might be able to intervene quite hard to do that.'cause they haven't committed a crime at that stage. Of course. Um, I mean in the case of the, of the two, uh, children in, in China, you know, the, the science went to prison. Um, and he's not gonna work again as a kind of scientist, I think. Uh, but those two children exist and so it's sort of answer the bottle. I do think there is a real kind of society dialogue we need to have about, not if this happens, but when it happens, how you deal with it. I mean, for example, if someone was to do a genetic change that was, we really felt was quite bad, would you do something different to those people? I mean it's, you know, would you treat those children differently somehow? I mean, that sounds awful, but, you know, how would you, how would you deal with that? So, so yeah, that's a, that depressingly the answer I think is no, you can't really stop it. You just have to hope that people's good sense prevail, which historically has not always happened. Actually. Some, someone is asking about editing genes and embryos or can you, so can you only edit genes and embryos or can you fully, can fully grown humans receive edited genes? Yeah, so, so, so both. So in, in fully grown humans, and that's already under clinical trial and number of conditions, you can change genes in, in some cells in some tissues, but not in the whole human. So for example, if you have a cystic fibrosis, which is a lung disease, obviously you can edit the DNA in their lungs, um, by inhaled, uh, processes. Um, but it wouldn't affect their genes particularly elsewhere, especially in, in their germ cells. So in the eggs and sperm that will be inherited. And that's one of the reasons why that is, um, essentially allowed, uh, all over the world now.'cause it's not, you're not changing the future resolution. If you want to edit in a way that is stable forever. The way you normally do that is editing at a single cell stage. So either spare more eggs, um, and then you, because essentially there's a hundred percent success then. And then you can kind of, um, you know, grow up that embryo from there. Um, and that's the way it's done kind of commercially at the moment. In theory, you could design a system that was so effective, it would change the DNA in every single cell of your body. Um, I, I think I, that's really very challenging and I, I guess you, the question would be why you would do that because it's easier just to edit the single cells. Alright. Um, yeah, this may be slightly tangential, but uh, when you were talking about Mars, you mentioned a gene for, um, oxygen, um, found in Tibet and so on. I read somewhere and I wonder if you can confirm it, that such a gene might have been in, uh, inherited from the de so branch is that You, you are very well read indeed and in indeed that's quite correct. So for those not familiar with the stories, Denis Saban are an extinct branch of, uh, of human evolutionary history, um, known only really from, uh, so Russia and, and Saur and that that part of the world, um, which despite the fact they're now extinct, we know nothing about them, have clearly contributed genes to modern humans. epa one, this genetic variant associated, the variant that is associated with high altitude living appears to be a Denis Aven gene. And so one model is that during the human migration into higher areas of Asia in particular, they met and interbred with Denis s those hybrid humans had a massive advantage 'cause they could live high in the altitude, um, the others couldn't. And so that gene has been selected for, so yes, it's another, it's another gene. We owe our dead relatives for those of us who have it. Good. We have a question on actually, um, global warming. What kind of evolutionary changes do you think global warming may have on humans? Have we started to understand how this might affect us? Yeah, yeah. So the impact of climate change on humans directly. So if you think about the way evolution works, which essentially is through death and, and reproduction, as I said, not withstanding genetic editing, what you'd be, I guess what you're thinking about are things where climate change will kill people with particular variation. I think at the moment, if you look at the world as a whole, unfortunately the people who are gonna be most affected by climate change, it's not about their genetics, it's about where they live and the kind of resource they have. Those of us in colder climates with good air conditioning will probably make it, um, those people in hotter parts of the world without access to that will not. Um, so a very bleak scenario is that it will essentially drive populations of humans to extinction who are in those parts of the world. Mm-hmm, <affirmative>, um, let's hope it doesn't get anywhere near that. Um, there are some sort of trivial things that might change. So for example, it's possible. So infant mortality, babies overheat quite easily. Um, and so infant mortality might go up in a very warm world. And so you might imagine that genetic variants associated with things like better sweating, less body hair, um, might be selected for, uh, you know, for that to be apparent in the gene pool, you'd have to have really quite high mortality. And that is a really bleak and depressing thought. Lots of dead babies. Um, but it is a possibility I think that, that, you know, well, let's, let's hope we never get there, but it's possible. Okay. With, uh, orangutans now applying medical bandages, is there evidence that primates are evolving more quickly, like swallows and tits? Yeah, so, so for the gray tapes like the ANGs, uh, unfortunately probably the single biggest evolution thing that's happened to them is us. Um, because, you know, most of the, most of the great eight populations are, are strongly threatened because of human activity. I'm not aware of any research done on kind of evolution of those species, but for instance, it might be possible that they, we have selected for great apes that are more wary of humans because that's quite a good survival trait. Um, I, I guess there's a slight, uh, sort of correlation there in terms, so generally evolution works fastest in organisms with very large populations and very short generation times like bacteria because your, your kind of, your clock is running really, really fast. Primates of course are big slow evolving because they're, they, they have long generation times. Um, uh, I guess one of the interesting sort of, uh, questions associated with that particular, that story you're just talking about there is what might select for intelligence. So is it possible, for example, um, that because of selective pressure on gray tapes, the most intelligent gray tapes, the ones that are surviving?'cause they're the ones that realize that the guy coming with a gun is a bad idea and you should run the other way. Um, and I don't, I don't know of any data on that, but it wouldn't it be quite an interesting thought experiment to roll the clock towards a million years and wonder if, you know, we're all extinct 'cause of that pandemic I keep talking about. Um, but actually other selective processes have driven evolution of intelligence in, for example, a primate that is now the dominant species on the, on the planet. Um, that that, you know, was it planet the apes is maybe not as farfetched as we thought. Um, you mentioned that, uh, there was effect of Bob Plague on, um, so basically survivors had more strong community system. Do you know anything about similar, well, any other effect of COVID-19 on traits in humans? And so another, sorry, another disease process that's driven it. I mean, those who survived COVID-19, uh, or those who died from COVID-19. Yes. Difference between them. Yes. So COVID-19. So yes, so there has been some work done on that. And indeed, um, even though, I mean I, you gotta be careful how you say this, you know, even so COVID-19 was a huge disaster in terms of statistical loss. One in a thousand people worldwide COVID-19. So on an evolutionary scale, that's a relatively small selective pressure. Despite that you can indeed see, um, genetic markers of survival. So particularly in patients who went into intensive care, who, who didn't. So there's been some studies done on, on populations who both got covid to 19, some end up in hospitals, some didn't. The ones who didn't have a number of genetic variants that are more common. And one of the most interesting things is that some of those genetic variants are, um, like the, like the bubonic plague example are associated with high immunity. Um, and some of this, this one or two that seem to be neandertal gene variants that are present in some members of the population and not others, um, and have conferred an advantage in fighting off the virus. Um, and so there's ironically many of us here today who have survived Covid to 19 owe that to these kind of neandertal variants there, uh, long term whether those will become, will be visible in the human population in a thousand years time, will we, will we see this genetic bottle? I don't know because one in a thousand is not a huge case, but yes, there is definitely, it has also selected particular genetic variants. Thank you very much. I had two statements and then end of a question. So firstly, there was a point raised around genetic changes to our children offsprings for the sake of competitive advantages. So I could say, you know, a person sitting next to me, we're at a sports day now I would love to say, oh, my son or my daughter wins that sprint race because of a, a genetic change. But within that, there is a a point for all of us, which is we each having a choice to make rather than something being forced upon us. However, at the same time there's a country in Central Asia. Now, I can't recall exactly what country is ends of astan, can't remember which one. However, what they've done is they've considered the science, they've considered the technology and they've said to themselves, we are gonna create the best Olympics set up possibly ever. And they're implementing it at a state level. Now geopolitics enters into the conversation. So it firstly started with me versus my neighbor here and our kids. But then it kind of extrapolates further out to countries versus countries that are competitive advantage. So my question for you, professor, is if you were to advise the government of the UK around a policy and a strategy in a, in a nutty, simple, hopefully in a witty way as well, what would you say to them about this? Uh, nice easy question there, right? What would I say? Uh, I'm not sure I can make it witty at all. Well, I mean basically what I would say is that's a really bad idea and it's a bad idea on lots of levels. Um, a because as I think we've shown you, you really can't guarantee anything with genetics. B uh, you know, even if you could absolutely guarantee that you're gonna have a population that's amazing at the Olympics or whatever else, how do you possibly know that's gonna be useful by the time those people become older? So for example, you know, a hundred years ago being able to do beautiful calligraphy was quite a strong selective advantage using a mobile phone. Not so much now quite a big difference in that kind of profile. So I think any attempt to kind of predict what will be useful going forward is, is pretty poor. Um, but the second thing I would say is absolutely your first point there is that, you know, fundamentally human choice is incredibly important here. And even if you are an absolute dictation, I think history tells us that, you know, absolute t chips ultimately always fail. Um, and so any attempt to sort of engineer a population in that way is always kind of doomed to failure, I hope, which is maybe a slightly more upbeat ending than some of the other ones, <laugh>. Well, thank you very much, professor me for this wonderful lecture. Thank you very much.