{"version":"1.0.0","segments":[{"startTime":5.425,"endTime":10.305,"body":"So I think everyone pretty much at school these days learns about evolution by natural"},{"startTime":10.305,"endTime":13.885,"body":"selection, survival of the fittest, all of those kind of concepts."},{"startTime":14.265,"endTime":17.949,"body":"Um, and today I want to turn that a bit on its head and think"},{"startTime":17.949,"endTime":20.405,"body":"about what happens when we start to mess with evolution."},{"startTime":21.635,"endTime":25.98,"body":"The Gresham College lecture that you're listening to right now is giving you knowledge and"},{"startTime":25.98,"endTime":30.325,"body":"insight from one of the world's leading academic experts, making it takes a lot of"},{"startTime":30.325,"endTime":30.615,"body":"time."},{"startTime":31.115,"endTime":34.208,"body":"But because we want to encourage a love of learning, we think it's well worth"},{"startTime":34.208,"endTime":34.415,"body":"it."},{"startTime":35.315,"endTime":38.695,"body":"We never make you pay for lectures, although donations are needed."},{"startTime":39.195,"endTime":40.535,"body":"All we ask in return is this."},{"startTime":41.045,"endTime":43.335,"body":"Send a link to this lecture to someone you think would benefit."},{"startTime":43.715,"endTime":47.631,"body":"And if you haven't already, click the follow or subscribe button from wherever you are"},{"startTime":47.631,"endTime":48.415,"body":"listening right now."},{"startTime":49.475,"endTime":51.055,"body":"Now let's get back to the lecture."},{"startTime":53.335,"endTime":57.243,"body":"And I want to take us right through things that have happened for thousands of"},{"startTime":57.243,"endTime":61.152,"body":"years and maybe nudge us towards the end in the direction of what might be"},{"startTime":61.152,"endTime":62.195,"body":"coming around the corner."},{"startTime":62.615,"endTime":65.824,"body":"Um, and it's a bit of a spoiler alert, ready for, uh, my next and"},{"startTime":65.824,"endTime":69.034,"body":"my final lecture, uh, which is in a couple of months time where we're gonna"},{"startTime":69.034,"endTime":72.243,"body":"think about, uh, wild speculation about the future of evolution, uh, which is essentially a"},{"startTime":72.243,"endTime":75.453,"body":"way of me saying, if you find tonight's boring, definitely don't come back in a"},{"startTime":75.453,"endTime":78.235,"body":"couple of months time, 'cause that'd be a real waste of your time."},{"startTime":78.815,"endTime":81.275,"body":"Um, so I wanna talk about artificial selection."},{"startTime":81.855,"endTime":87.207,"body":"And what I mean by that is the ability of some organisms to influence the"},{"startTime":87.207,"endTime":88.635,"body":"evolution of other organisms."},{"startTime":88.635,"endTime":91.635,"body":"So if you think about evolution, classical evolution, right?"},{"startTime":91.945,"endTime":96.315,"body":"It's based on the principle that most organisms over reproduce."},{"startTime":96.495,"endTime":98.435,"body":"We have more offspring than one."},{"startTime":99.135,"endTime":101.235,"body":"And that those offspring are diverse."},{"startTime":101.235,"endTime":107.515,"body":"They're not identical to their parents, they are genetically different either because of sexual recombination."},{"startTime":107.535,"endTime":111.728,"body":"So for humans, the fact that you have to have a partner and so your"},{"startTime":111.728,"endTime":115.922,"body":"kids are some blend of genes from both of you, or even if you're an"},{"startTime":115.922,"endTime":120.116,"body":"organism like a bacterium and you do clone yourself, you are still introducing variation through"},{"startTime":120.116,"endTime":120.955,"body":"things like mutation."},{"startTime":122.255,"endTime":125.755,"body":"So the basic principle is all organisms produce lots and lots of offspring."},{"startTime":125.755,"endTime":127.075,"body":"Those offspring are all a bit different."},{"startTime":127.265,"endTime":128.555,"body":"They compete for resource."},{"startTime":128.854,"endTime":132.804,"body":"And the ones that are best placed to maximize their use of that resource, they"},{"startTime":132.804,"endTime":133.595,"body":"are the fittest."},{"startTime":133.945,"endTime":137.079,"body":"They will survive and pass on the genes, uh, and the rest of us die"},{"startTime":137.079,"endTime":137.915,"body":"out and don't contribute."},{"startTime":138.135,"endTime":142.751,"body":"And that is the basic principle of evolution for all living organisms forever, as far"},{"startTime":142.751,"endTime":143.675,"body":"as we're aware."},{"startTime":144.895,"endTime":149.882,"body":"But what has happened, particularly in, in sort of recent, uh, evolutionary history, although possibly"},{"startTime":149.882,"endTime":152.875,"body":"before that too, is that organisms influence each other."},{"startTime":153.015,"endTime":154.955,"body":"So part of that selection is, is obvious."},{"startTime":155.455,"endTime":158.92,"body":"If you are a cheetah and you eat an antelope, you've done quite a good"},{"startTime":158.92,"endTime":160.075,"body":"selective process on that antelope."},{"startTime":160.335,"endTime":163.435,"body":"Um, but there are more subtle ways in which you can influence evolution."},{"startTime":163.435,"endTime":167.564,"body":"And of course, the kinda master species are doing that for good or for ill"},{"startTime":167.564,"endTime":168.115,"body":"is ourselves."},{"startTime":169.055,"endTime":172.635,"body":"Humans have been messing with the world essentially ever since we came into it."},{"startTime":172.735,"endTime":176.435,"body":"And in particular, messing with the evolution of other species and the species."},{"startTime":176.915,"endTime":180.685,"body":"I want to think about first this evening when we think about how humans influence."},{"startTime":180.685,"endTime":184.285,"body":"Evolution is one that many of you, uh, may interact with very regularly."},{"startTime":184.395,"endTime":185.125,"body":"It's this one."},{"startTime":185.345,"endTime":187.245,"body":"Our best friend, the domestic dog."},{"startTime":188.585,"endTime":192.765,"body":"And domestic dogs, as you all know, come in all sorts of shapes and sizes."},{"startTime":193.065,"endTime":196.285,"body":"Um, they are all though the same species pretty much."},{"startTime":196.585,"endTime":199.79,"body":"So they can all reproduce with each other, practically speaking can be a bit tricky"},{"startTime":199.79,"endTime":200.645,"body":"for some of them."},{"startTime":200.745,"endTime":204.365,"body":"But in theory, they're able to reproduce with each other because they're one species."},{"startTime":204.505,"endTime":206.885,"body":"But they are remarkably diverse."},{"startTime":207.835,"endTime":210.845,"body":"They are not remarkably diverse because of natural evolution."},{"startTime":211.065,"endTime":214.017,"body":"It is not that these things have been out there in the Savannah and they've"},{"startTime":214.017,"endTime":214.805,"body":"specialized in different ways."},{"startTime":214.805,"endTime":220.225,"body":"They are that way because we have created 'em, we have shaped them in that"},{"startTime":220.225,"endTime":225.285,"body":"way through a very, very aggressive process of evolution through an artificial selective process."},{"startTime":226.785,"endTime":230.446,"body":"And there's been a huge amount of work on this, which I think is really"},{"startTime":230.446,"endTime":234.108,"body":"reflective of, of our kind of current understanding of evolution, uh, particularly on the back"},{"startTime":234.108,"endTime":235.085,"body":"of advances in genetics."},{"startTime":235.625,"endTime":240.813,"body":"So what we now know is that the origin of domestic dog is probably about"},{"startTime":240.813,"endTime":244.965,"body":"30 or 40,000 years ago, uh, from, uh, from the gray wolf."},{"startTime":244.995,"endTime":245.285,"body":"Okay?"},{"startTime":245.285,"endTime":246.245,"body":"So up here in the top corner."},{"startTime":246.905,"endTime":248.245,"body":"And that is sort of undisputed."},{"startTime":248.745,"endTime":254.267,"body":"One of the interesting things about that date, I think, is that it predates humans,"},{"startTime":254.267,"endTime":256.845,"body":"uh, switch to a sedentary agricultural lifestyle."},{"startTime":257.065,"endTime":260.045,"body":"So this is before the date when we started living in villages."},{"startTime":260.394,"endTime":263.325,"body":"It's before the date when we started, uh, having crops and farming."},{"startTime":263.345,"endTime":264.525,"body":"We were still hunter gatherers."},{"startTime":264.545,"endTime":268.085,"body":"And people can speculate wildly about how we domesticated dogs."},{"startTime":268.265,"endTime":272.735,"body":"Um, but one kind of plausible hypothesis is that wolves are likely to have congregated"},{"startTime":272.735,"endTime":277.206,"body":"around early human tribes 'cause we were hunting, uh, and there would've been waste, there"},{"startTime":277.206,"endTime":280.485,"body":"would've been bones and carcasses and stuff for them to scavenge."},{"startTime":280.745,"endTime":282.365,"body":"Uh, and wolf puppies are quite cute."},{"startTime":282.585,"endTime":285.9,"body":"Uh, and so maybe early humans, uh, had those puppies kind of close to 'em,"},{"startTime":285.9,"endTime":287.005,"body":"might've fed them a bit."},{"startTime":287.005,"endTime":289.205,"body":"And so you get this kind of process of domestication."},{"startTime":290.585,"endTime":294.845,"body":"So 30 or 40,000 years ago, this lineage broke off from gray wolves."},{"startTime":295.415,"endTime":299.245,"body":"Prior to that, wolves themselves obviously had evolved from common ancestors."},{"startTime":299.305,"endTime":301.991,"body":"And what you can see here down the side are lots and lots of things"},{"startTime":301.991,"endTime":303.245,"body":"that are sort of related to dogs."},{"startTime":303.425,"endTime":307.285,"body":"And actually what you notice is they're all pretty much look like dogs, right?"},{"startTime":307.715,"endTime":309.765,"body":"Jackals, uh, foxes even."},{"startTime":310.035,"endTime":314.049,"body":"They all more or less look like dogs, even though their common ancestor goes back"},{"startTime":314.049,"endTime":316.725,"body":"millions of years, perhaps a couple of millions of years."},{"startTime":317.185,"endTime":319.805,"body":"Um, but largely speaking, they haven't changed that much."},{"startTime":320.675,"endTime":327.321,"body":"Whereas the domestic dog domestication in the last 30 or 40,000 years now looks incredibly"},{"startTime":327.321,"endTime":327.765,"body":"diverse."},{"startTime":327.945,"endTime":331.095,"body":"And I think if you were an alien suddenly beamed down onto the planet, you"},{"startTime":331.095,"endTime":334.245,"body":"wouldn't immediately look at all these and go, oh yeah, they're all the same species."},{"startTime":334.705,"endTime":338.055,"body":"Um, but you probably would look at most of these and think they might be"},{"startTime":338.055,"endTime":338.725,"body":"the same species."},{"startTime":339.705,"endTime":344.125,"body":"So domestic dogs have evolved far faster than any of their natural, uh, relatives."},{"startTime":344.125,"endTime":346.285,"body":"And that is because we have selected them."},{"startTime":346.945,"endTime":350.365,"body":"And actually the pace at which this has happened is quite extraordinary."},{"startTime":351.385,"endTime":356.119,"body":"So for the most part of that 30 or 40,000 years of history, we think"},{"startTime":356.119,"endTime":358.645,"body":"that domestic dogs looked pretty much like wolves."},{"startTime":358.645,"endTime":359.765,"body":"They were all pretty much the same."},{"startTime":360.835,"endTime":365.404,"body":"It's only actually in terms of, uh, Romans, the Roman Empire, that we start to"},{"startTime":365.404,"endTime":369.365,"body":"see documentary evidence of breeds of dog and then only one or two."},{"startTime":369.505,"endTime":373.205,"body":"So in Roman literature, you can see people talking about big dogs and small dogs,"},{"startTime":373.205,"endTime":376.165,"body":"um, but certainly not the diverse breeds of dogs we have now."},{"startTime":376.185,"endTime":381.139,"body":"And in fact, if you look at the, uh, several hundred breeds of dogs that"},{"startTime":381.139,"endTime":386.094,"body":"are recognized by, uh, breeding associations today, the vast majority only go back about two"},{"startTime":386.094,"endTime":387.085,"body":"or 300 years."},{"startTime":387.705,"endTime":392.283,"body":"So that diversity of dogs has largely cropped up just within a, a blink of"},{"startTime":392.283,"endTime":394.725,"body":"an evolutionary eye in the last few centuries."},{"startTime":395.505,"endTime":397.205,"body":"And that is, I think, quite remarkable."},{"startTime":397.705,"endTime":402.186,"body":"And it, it gives us a great power, particularly when we combine that with advanced"},{"startTime":402.186,"endTime":402.485,"body":"genetics."},{"startTime":402.485,"endTime":406.518,"body":"And there's a lot of interest now in using whole genome sequencing to try and"},{"startTime":406.518,"endTime":407.325,"body":"understand this process."},{"startTime":407.585,"endTime":411.542,"body":"Not because we are necessarily interested in dogs, although of course we are, but also"},{"startTime":411.542,"endTime":413.125,"body":"because they are a fantastic model."},{"startTime":413.145,"endTime":414.885,"body":"And they're a fantastic model for two reasons."},{"startTime":416.015,"endTime":419.905,"body":"First of all, there's a huge amount of diversity, a great Dane and a little"},{"startTime":419.905,"endTime":420.165,"body":"chihuahua."},{"startTime":420.165,"endTime":420.965,"body":"They're really quite different."},{"startTime":420.965,"endTime":424.285,"body":"So there's a lot of variation, which must be genetically programmed, right?"},{"startTime":424.285,"endTime":425.925,"body":"You don't have two chihuahuas."},{"startTime":426.145,"endTime":428.485,"body":"Uh, and the puppy of a chihuahua grows up to be a great Dane."},{"startTime":428.485,"endTime":431.045,"body":"It grows up to be a chihuahua because they're genetically programmed."},{"startTime":431.045,"endTime":437.189,"body":"So there are genetic programs that cause that body shape, but within a breed, actually"},{"startTime":437.189,"endTime":442.925,"body":"the genetic diversity is very, very restricted because breeders deliberately breed chihuahuas with chihuahuas."},{"startTime":442.925,"endTime":444.685,"body":"And so you get a very, very tight funneling."},{"startTime":444.685,"endTime":449.035,"body":"So what you end up with are groups of dogs that are very d very"},{"startTime":449.035,"endTime":451.645,"body":"different between them, but incredibly similar within the group."},{"startTime":451.785,"endTime":453.885,"body":"And that gives you a very powerful genetic tool."},{"startTime":453.985,"endTime":454.885,"body":"And that's what you see here."},{"startTime":454.905,"endTime":457.005,"body":"So this is a, a whole genome tree."},{"startTime":457.105,"endTime":461.636,"body":"So imagine it's kinda branched out as a tree, but coils around of uh, many,"},{"startTime":461.636,"endTime":462.845,"body":"many major dog breeds."},{"startTime":463.625,"endTime":467.37,"body":"Uh, and what it turns out to be is that actually, if you do all"},{"startTime":467.37,"endTime":471.115,"body":"the dog breeds of the world, there are roughly speaking about 23 groups, clades of"},{"startTime":471.115,"endTime":471.365,"body":"dogs."},{"startTime":471.365,"endTime":472.525,"body":"Those are the colors you see here."},{"startTime":472.865,"endTime":475.648,"body":"So you can bunch dogs together and those people in the audience who own dogs"},{"startTime":475.648,"endTime":476.205,"body":"know that, right?"},{"startTime":476.205,"endTime":480.205,"body":"So a Yorkshire Terrier and a West Highland terrier, you know, they're different, but they're"},{"startTime":480.205,"endTime":481.005,"body":"kind of similar."},{"startTime":481.455,"endTime":483.725,"body":"Great Dane and a bit different, Illation different again."},{"startTime":483.725,"endTime":488.375,"body":"And so you have these 23 big clusters where you have dogs within them that"},{"startTime":488.375,"endTime":489.925,"body":"are kind of similar, okay?"},{"startTime":490.325,"endTime":492.685,"body":"Terriers, pointers, spaniels, et cetera, et cetera."},{"startTime":493.585,"endTime":497.557,"body":"And then within those 23 groups, you have of course the great diversity of all"},{"startTime":497.557,"endTime":500.205,"body":"the different terrier breeds and all the different spaniel breeds."},{"startTime":500.745,"endTime":504.645,"body":"And, and that turns out to be a really, really powerful tool for understanding how"},{"startTime":504.645,"endTime":506.205,"body":"genes do all sorts of things."},{"startTime":506.385,"endTime":511.557,"body":"And one of the things that we have used that for is the ability to"},{"startTime":511.557,"endTime":516.73,"body":"combine that genetic information with all the information that dog owners themselves know about how"},{"startTime":516.73,"endTime":517.765,"body":"particular breeds perform."},{"startTime":518.585,"endTime":521.174,"body":"So if you think about that, we all know that even if you don't have"},{"startTime":521.174,"endTime":523.764,"body":"a dog, right, there are certain dog breeds that, you know, if you're walking past"},{"startTime":523.764,"endTime":526.354,"body":"'em in the street, you might take a step to one side 'cause they're a"},{"startTime":526.354,"endTime":527.045,"body":"bit, you know, dodgy."},{"startTime":527.305,"endTime":529.976,"body":"Um, there are certain dog breeds that you wouldn't leave at home with your carpets"},{"startTime":529.976,"endTime":531.045,"body":"'cause they're gonna chew it up."},{"startTime":531.305,"endTime":533.77,"body":"Um, there are some dog breeds that just sort of sleep in the corner all"},{"startTime":533.77,"endTime":535.085,"body":"day long and you're there, it boring really."},{"startTime":535.425,"endTime":540.845,"body":"Um, and these behavioral traits are breed associated, so they must be genetically associated."},{"startTime":541.305,"endTime":546.121,"body":"Um, and so this kind of genetic analysis gives you an ability to ask how"},{"startTime":546.121,"endTime":547.085,"body":"genes control behavior."},{"startTime":547.145,"endTime":548.965,"body":"And that is, um, exactly what has been done."},{"startTime":550.385,"endTime":555.022,"body":"And I think just to kind of think about this diversity, uh, in scale, it's"},{"startTime":555.022,"endTime":557.805,"body":"quite astronomical how much things can change over time."},{"startTime":558.225,"endTime":561.137,"body":"So here we have, I think he's deceased now, unfortunately, but this was the previous"},{"startTime":561.137,"endTime":562.885,"body":"record holder for the biggest dog in the world."},{"startTime":563.185,"endTime":564.365,"body":"Uh, this, I think he's called Zeus."},{"startTime":564.505,"endTime":567.525,"body":"So Zeus, uh, was just over a meter at tall at his shoulder."},{"startTime":567.585,"endTime":568.485,"body":"So he's up here somewhere."},{"startTime":568.485,"endTime":569.325,"body":"He's a great Dane obviously."},{"startTime":569.905,"endTime":573.79,"body":"Um, and here on the other side, uh, you have the smallest record holder, maybe"},{"startTime":573.79,"endTime":577.675,"body":"Schwab here, who I think is nine, just over nine centimeters the shoulder, which is"},{"startTime":577.675,"endTime":580.525,"body":"quite, you can put all in your pocket if you want."},{"startTime":581.385,"endTime":583.325,"body":"Um, so the, but they're both dogs, right?"},{"startTime":583.545,"endTime":588.148,"body":"So the genetic diversity that has, uh, been driven over the last few thousand years"},{"startTime":588.148,"endTime":591.525,"body":"has created these, um, these individuals that are so wildly different."},{"startTime":591.525,"endTime":592.725,"body":"And let's just put that in context."},{"startTime":593.745,"endTime":597.902,"body":"So around, uh, the time of the Roman empires is the first time you see"},{"startTime":597.902,"endTime":599.565,"body":"evidence of, uh, significant breed differences."},{"startTime":599.625,"endTime":602.405,"body":"Not as significant as this, but deep breed differences."},{"startTime":602.545,"endTime":604.525,"body":"So, so let's imagine, let's go back a little bit before that."},{"startTime":604.525,"endTime":605.925,"body":"Let's go back to the time the ancient Greeks."},{"startTime":605.985,"endTime":607.885,"body":"So two and a half thousand years BC for example."},{"startTime":608.545,"endTime":609.645,"body":"And you think about that."},{"startTime":610.465,"endTime":612.645,"body":"Um, and we take an individual human here."},{"startTime":612.915,"endTime":613.205,"body":"Oops."},{"startTime":613.345,"endTime":614.925,"body":"Uh, so this is Socrates."},{"startTime":615.025,"endTime":619.042,"body":"Um, so, uh, I don't actually know how tall Socrates was, but let's assume that"},{"startTime":619.042,"endTime":622.525,"body":"Socrates was roughly, uh, kind of miso size, maybe a little bit smaller."},{"startTime":623.665,"endTime":628.189,"body":"If humans had evolved at the same rate as domestic dogs since Socrates was alive,"},{"startTime":628.189,"endTime":631.205,"body":"then I would be looking at this audience out here."},{"startTime":631.625,"endTime":634.805,"body":"And some of you would be about the size of a European hair."},{"startTime":634.905,"endTime":638.64,"body":"So you'd be down here somewhere, um, and others of you would be the size,"},{"startTime":638.64,"endTime":639.885,"body":"uh, of an African giraffe."},{"startTime":639.885,"endTime":642.485,"body":"And your head would just about be scraping the ceiling of this rather lovely hall."},{"startTime":643.625,"endTime":647.918,"body":"So in the same period of time, we have evolved nowhere near as fast domestic"},{"startTime":647.918,"endTime":648.205,"body":"dogs."},{"startTime":648.205,"endTime":654.325,"body":"And that is because this process of artificial selection accelerates evolution at a remarkable rate."},{"startTime":655.825,"endTime":659.875,"body":"So we can then use that information and we can say, okay, over this period"},{"startTime":659.875,"endTime":663.925,"body":"of time, genes have changed and they've changed in ways that have influenced, uh, dog"},{"startTime":663.925,"endTime":667.165,"body":"size and shape, but also in ways that have influenced their behavior."},{"startTime":667.225,"endTime":669.005,"body":"And you can map those two things onto each other."},{"startTime":669.025,"endTime":674.587,"body":"And so, um, here we see that, so this is, if you like, a two"},{"startTime":674.587,"endTime":677.925,"body":"dimensional representation of how similar genetically particular dogs are."},{"startTime":678.545,"endTime":683.392,"body":"And what you see is exactly what I was just mentioning, that there's a huge"},{"startTime":683.392,"endTime":684.685,"body":"variation between particular lineages."},{"startTime":684.685,"endTime":689.17,"body":"So for example, here, Spaniels and ascent homes, very, very different from each other, but"},{"startTime":689.17,"endTime":690.965,"body":"within the group, very, very similar."},{"startTime":691.435,"endTime":691.725,"body":"Okay?"},{"startTime":692.545,"endTime":695.245,"body":"So now you can use this kind of map and map onto it."},{"startTime":695.245,"endTime":698.645,"body":"Things that we know are behavioral associated with breeds."},{"startTime":698.825,"endTime":703.641,"body":"So for example, excitability and people own dogs know some dog breeds terrier spaniels, they"},{"startTime":703.641,"endTime":704.605,"body":"get soup used."},{"startTime":704.665,"endTime":707.259,"body":"You don't have to say the word walkies, and they're up and they're racing around"},{"startTime":707.259,"endTime":707.605,"body":"going nuts."},{"startTime":708.135,"endTime":711.129,"body":"Other dog breeds from the African and Middle Eastern ones pretty mellow, you know, you"},{"startTime":711.129,"endTime":713.925,"body":"have to say walkies 17 times and they still look at you like really?"},{"startTime":714.265,"endTime":717.805,"body":"Um, and so that excitability is somehow genetically predetermined."},{"startTime":718.545,"endTime":722.428,"body":"And, and you can see that mapped out here in terms of an independent quantitative"},{"startTime":722.428,"endTime":723.205,"body":"score of excitability."},{"startTime":723.265,"endTime":727.48,"body":"So now we have a trait, a behavioral trait, how excitable you are and genetic"},{"startTime":727.48,"endTime":728.885,"body":"data to go with it."},{"startTime":728.885,"endTime":733.985,"body":"So you can start to ask questions about what are the genes that control these"},{"startTime":733.985,"endTime":735.005,"body":"behaviors like excitability."},{"startTime":736.065,"endTime":738.525,"body":"Uh, and there's an absolutely fabulous example here, which I wanted to show you."},{"startTime":738.585,"endTime":743.013,"body":"So here, this is work from Elaine Oanda, uh, where they have looked at a"},{"startTime":743.013,"endTime":745.965,"body":"trait that is particularly striking, which is working with livestock."},{"startTime":746.145,"endTime":749.463,"body":"So if you think about Coley dogs and herding sheep in this country, for example,"},{"startTime":749.463,"endTime":752.781,"body":"but also some of the livestock guardian dogs that are, that are used up in"},{"startTime":752.781,"endTime":756.099,"body":"the mountains to sort of sit and guard, um, you know, sheep or goats for"},{"startTime":756.099,"endTime":757.205,"body":"a long period of time."},{"startTime":757.755,"endTime":760.565,"body":"They're extremely good at working with livestock."},{"startTime":760.595,"endTime":761.845,"body":"They are very trainable."},{"startTime":761.845,"endTime":764.695,"body":"They have all these kind of traits that are not necessarily shared with with other"},{"startTime":764.695,"endTime":764.885,"body":"dogs."},{"startTime":764.985,"endTime":766.485,"body":"Uh, so, you know, we have a small terrier at home."},{"startTime":766.485,"endTime":768.845,"body":"There is no way I could train her to herd sheep ever."},{"startTime":769.225,"endTime":772.285,"body":"Um, so there is something about, uh, the trainability of these dogs."},{"startTime":772.345,"endTime":777.721,"body":"So now if we assume all those dogs have some shared characteristic, which is the"},{"startTime":777.721,"endTime":783.098,"body":"trainability around livestock, other dogs don't, you can ask using that genetic information, what genes"},{"startTime":783.098,"endTime":786.325,"body":"are shared by all these colored types of dog."},{"startTime":786.705,"endTime":789.934,"body":"Um, and absent from all the other ones, what are the genes that might contribute"},{"startTime":789.934,"endTime":790.365,"body":"to this?"},{"startTime":790.945,"endTime":794.164,"body":"Um, and when that was done, one of the fascinating things was that it came"},{"startTime":794.164,"endTime":796.525,"body":"up with a relatively small number of genes, including this one."},{"startTime":796.765,"endTime":801.482,"body":"EPH five and EPHA five is a very interesting gene 'cause we already know a"},{"startTime":801.482,"endTime":805.885,"body":"bit about that and we know that it's function is to control neural plasticity."},{"startTime":806.665,"endTime":811.412,"body":"So this is the ability of neurons in the brain to make and break and"},{"startTime":811.412,"endTime":812.045,"body":"remake connections."},{"startTime":812.145,"endTime":815.965,"body":"And this is the process by which you un you, you create memories essentially."},{"startTime":815.965,"endTime":819.64,"body":"So when you create a new memory, your neurons are breaking connections and making new"},{"startTime":819.64,"endTime":821.845,"body":"ones to, to cement that learning in your brain."},{"startTime":822.835,"endTime":825.525,"body":"This gene controls how readily they're able to do that."},{"startTime":825.785,"endTime":829.733,"body":"And what we see in these herding dogs is they have a version of this"},{"startTime":829.733,"endTime":832.365,"body":"gene, which seems to increase neuroplasticity and that fits right."},{"startTime":832.475,"endTime":833.765,"body":"Coly dogs are highly trainable."},{"startTime":833.955,"endTime":836.605,"body":"They need that plasticity to be able to learn."},{"startTime":836.945,"endTime":841.098,"body":"And so what humans have inadvertently done is we have selected for a variant of"},{"startTime":841.098,"endTime":845.251,"body":"the gene that confers a particular ability, which is the ability to learn and then"},{"startTime":845.251,"endTime":845.805,"body":"herd livestock."},{"startTime":846.225,"endTime":850.263,"body":"And what turns out to be enormously useful, not just for dog owners, but for"},{"startTime":850.263,"endTime":854.301,"body":"all the rest of us, is that this gene is also in humans and has"},{"startTime":854.301,"endTime":856.725,"body":"actually been previously associated with attention conditions in humans."},{"startTime":856.865,"endTime":861.696,"body":"So things like a DHD, um, and some of the autism spectrum disorders where people"},{"startTime":861.696,"endTime":866.205,"body":"are particularly focused or particularly dis focused, are associated with mutations in this gene."},{"startTime":866.665,"endTime":869.805,"body":"And, uh, although it's not yet proven, it's kind of a nice hypothesis, right?"},{"startTime":869.805,"endTime":874.438,"body":"You have things like thinking about coly dog, an ability to learn to be incredibly"},{"startTime":874.438,"endTime":875.365,"body":"hyperfocused on sheep."},{"startTime":875.665,"endTime":878.776,"body":"But anyone who's had a coly dog and doesn't trade into the sheep knows if"},{"startTime":878.776,"endTime":881.888,"body":"you leave them alone for too long, they start to use that kind of hyperfocus"},{"startTime":881.888,"endTime":884.999,"body":"for all sorts of ills and tear up the bedroom carpet and do all sorts"},{"startTime":884.999,"endTime":888.111,"body":"of terrible things, um, in a way that is not a hundred million miles away"},{"startTime":888.111,"endTime":891.222,"body":"from some of the attention disorders that we see in humans, uh, with the same"},{"startTime":891.222,"endTime":891.845,"body":"sort of mutations."},{"startTime":891.845,"endTime":896.535,"body":"And so we can learn from that, uh, deep study of dogs, perhaps things that"},{"startTime":896.535,"endTime":898.725,"body":"are relevant, uh, to human conditions too."},{"startTime":901.225,"endTime":904.645,"body":"So that process of selecting dogs has been very, very directional."},{"startTime":904.745,"endTime":908.748,"body":"So early on, maybe not so much, but certainly the last few hundred years, people"},{"startTime":908.748,"endTime":911.685,"body":"have been deliberately choosing particular dogs to breed with each other."},{"startTime":911.795,"endTime":914.925,"body":"It's a very deliberate process of selection."},{"startTime":916.225,"endTime":920.35,"body":"But over the time we've existed on the planet, humans have done a lot more"},{"startTime":920.35,"endTime":923.925,"body":"selection that is much more inadvertent, but nonetheless equally if not more influential."},{"startTime":923.925,"endTime":926.925,"body":"So I wanna talk a little bit about some of these inadvertent, um, changes that"},{"startTime":926.925,"endTime":927.325,"body":"we've done."},{"startTime":927.325,"endTime":931.037,"body":"And I'm gonna start by the innovative ones that have turned out to be incredibly"},{"startTime":931.037,"endTime":931.285,"body":"useful."},{"startTime":931.945,"endTime":935.92,"body":"Uh, and the place we see this most, I think is in our adoption of"},{"startTime":935.92,"endTime":937.245,"body":"what we now call agriculture."},{"startTime":937.985,"endTime":942.274,"body":"Uh, and so in an early lecture we talked a bit about how humans started"},{"startTime":942.274,"endTime":946.563,"body":"to, uh, start a farm essentially about 10,000 years ago, actually in many different locations"},{"startTime":946.563,"endTime":948.565,"body":"around the world at the same time."},{"startTime":949.025,"endTime":952.957,"body":"But the area where this has been most intensely studied is what we call the"},{"startTime":952.957,"endTime":956.365,"body":"fertile crescent around what is now the Mediterranean and sort of Middle East."},{"startTime":957.145,"endTime":961.502,"body":"And what we believe happened was that um, people who previously had been hunter gatherers,"},{"startTime":961.502,"endTime":963.245,"body":"uh, started gathering seeds to eat."},{"startTime":963.245,"endTime":966.335,"body":"Obviously they wouldn't, they might have come back to a camp, they might have s"},{"startTime":966.335,"endTime":967.365,"body":"spilled some of that seed."},{"startTime":967.365,"endTime":970.396,"body":"And then if came back in the following year, they find the thing they'd gathered"},{"startTime":970.396,"endTime":971.205,"body":"is now growing there."},{"startTime":971.425,"endTime":974.553,"body":"Uh, and cotton onto the fact that actually it's a lot less work to kind"},{"startTime":974.553,"endTime":977.682,"body":"of grow stuff here than to go and gather it and bit by bit start"},{"startTime":977.682,"endTime":978.725,"body":"to create agriculture and farming."},{"startTime":980.345,"endTime":984.17,"body":"Now of course, when hunter gatherers went out to gather what they gathered was not"},{"startTime":984.17,"endTime":987.485,"body":"a random sample, um, of, of what is out there in the right."},{"startTime":987.485,"endTime":991.295,"body":"I dunno if who, who cares to admit to having been bramble picking your blackberry"},{"startTime":991.295,"endTime":992.565,"body":"picking or scavenging the wild?"},{"startTime":992.565,"endTime":994.005,"body":"If you've done that, yes, definitely me."},{"startTime":994.585,"endTime":997.485,"body":"Do you, do you pick a random selection of blackberries?"},{"startTime":997.825,"endTime":998.045,"body":"No."},{"startTime":998.045,"endTime":998.245,"body":"Right?"},{"startTime":998.245,"endTime":1000.805,"body":"You pick the big juicy ones, not the horrible, seedy little ones."},{"startTime":1001.145,"endTime":1004.686,"body":"So what you bring back is not a random sample of what's out there in"},{"startTime":1004.686,"endTime":1008.228,"body":"the population, what you bring back, the ones that you are most interested in, the"},{"startTime":1008.228,"endTime":1009.645,"body":"big fat ones, the juicy ones."},{"startTime":1010.995,"endTime":1012.325,"body":"That is an evolutionary process."},{"startTime":1012.505,"endTime":1014.725,"body":"We are selecting something that we like better."},{"startTime":1015.025,"endTime":1020.269,"body":"And so what you see during the early days of, of, uh, agricultural development by"},{"startTime":1020.269,"endTime":1023.765,"body":"humans, um, is that process of accelerated evolution, uh, happening."},{"startTime":1024.145,"endTime":1028.953,"body":"So for example, if we look at grains and cereals, which are one of the"},{"startTime":1028.953,"endTime":1033.761,"body":"earliest crops for which we have evidence of domestication, we see a very rapid evolution,"},{"startTime":1033.761,"endTime":1035.685,"body":"uh, between about 10,008,000 years ago."},{"startTime":1035.785,"endTime":1040.483,"body":"So for example, here we have some data on grain size of barley."},{"startTime":1041.305,"endTime":1045.49,"body":"And what you can just about see here is if you look at an early"},{"startTime":1045.49,"endTime":1049.675,"body":"site, a site, an archeological site, which was a very recent, uh, after the beginning"},{"startTime":1049.675,"endTime":1053.86,"body":"of agriculture about 10,000 years ago, in the white dots, the barley grains we can"},{"startTime":1053.86,"endTime":1058.046,"body":"find in the archeological record are quite small, but very rapidly, a slightly later site"},{"startTime":1058.046,"endTime":1062.231,"body":"up here in the black dots, all the barley grains are much bigger because that"},{"startTime":1062.231,"endTime":1066.416,"body":"accelerated process of evolution, people have picked bigger grains, they've grown them, and they're bigger"},{"startTime":1066.416,"endTime":1069.765,"body":"the next generation, and they do it again and again and again."},{"startTime":1070.025,"endTime":1076.337,"body":"And we are accelerating this move to a larger grain size, very rapidly, a process"},{"startTime":1076.337,"endTime":1080.125,"body":"of accelerated evolution that's quite straightforward for grain size."},{"startTime":1080.145,"endTime":1083.085,"body":"Uh, but it turns out to be true also of lots of other interesting traits."},{"startTime":1083.345,"endTime":1088.008,"body":"Um, so for example, as we've moved towards these larger grain sizes, we've also thought"},{"startTime":1088.008,"endTime":1092.672,"body":"about or not thought about, we have inadvertently selected for things that are beneficial in"},{"startTime":1092.672,"endTime":1093.605,"body":"terms of yield."},{"startTime":1094.305,"endTime":1098.188,"body":"And, and the time we see this happening most dramatically is with the use of"},{"startTime":1098.188,"endTime":1098.965,"body":"tools in agriculture."},{"startTime":1098.965,"endTime":1102.388,"body":"And by tools I don't mean tractors, I mean very, very straightforward things, uh, like"},{"startTime":1102.388,"endTime":1102.845,"body":"the sickle."},{"startTime":1104.225,"endTime":1108.458,"body":"So it wasn't very long after the start of agriculture that we start to see"},{"startTime":1108.458,"endTime":1111.845,"body":"evidence for tool use in agriculture and in particular things like sickle."},{"startTime":1111.905,"endTime":1113.045,"body":"If you think about it, that makes sense."},{"startTime":1113.045,"endTime":1116.245,"body":"If you go out and gather grains by picking individual wheat grains, that's gonna take"},{"startTime":1116.245,"endTime":1118.165,"body":"you quite a long time to get a meal."},{"startTime":1118.985,"endTime":1121.395,"body":"If you go out with a sharp influence and you cut a big sheath, then"},{"startTime":1121.395,"endTime":1123.645,"body":"you might have enough for a meal in, you know, a couple of minutes."},{"startTime":1123.865,"endTime":1127.445,"body":"Um, so these, these tools provide a benefit except there's a problem."},{"startTime":1128.705,"endTime":1133.309,"body":"The problem is that plants, including cereals, they produce seeds because they want to reproduce,"},{"startTime":1133.309,"endTime":1135.765,"body":"not because they want to feed people, right?"},{"startTime":1136.305,"endTime":1140.055,"body":"So, uh, plants grow seeds and seeds are there to disperse those plants and to"},{"startTime":1140.055,"endTime":1140.805,"body":"grow new generations."},{"startTime":1140.805,"endTime":1144.245,"body":"So they are deliberate, designed to spread widely."},{"startTime":1144.785,"endTime":1149.845,"body":"And most wild relatives of cereals, um, have what's called shattering grain."},{"startTime":1150.225,"endTime":1153.78,"body":"So if you find a wild wheat and you tap it when it's ripe, the"},{"startTime":1153.78,"endTime":1154.965,"body":"seed goes and shoots everywhere."},{"startTime":1155.785,"endTime":1159.323,"body":"If you come into a field of wheat with your sickle and you start slicing"},{"startTime":1159.323,"endTime":1162.861,"body":"away, um, on wild wheat, what you will end up with a lot of sticks"},{"startTime":1162.861,"endTime":1163.805,"body":"and very few seeds."},{"startTime":1164.005,"endTime":1166.565,"body":"'cause as you're doing that, you're spreading seed all over the place."},{"startTime":1167.265,"endTime":1168.365,"body":"That's not very effective."},{"startTime":1169.395,"endTime":1175.179,"body":"However, there is a mutation that occurs, um, quite commonly actually in some cereals that"},{"startTime":1175.179,"endTime":1175.565,"body":"changes."},{"startTime":1175.565,"endTime":1179.952,"body":"This pheno changes this ability and you lose the ability to shatter you from non"},{"startTime":1179.952,"endTime":1180.245,"body":"shattering."},{"startTime":1180.545,"endTime":1184.798,"body":"And that's because instead of, uh, separating the seed from the seed head, uh, you,"},{"startTime":1184.798,"endTime":1188.485,"body":"the plant retains a kind of a stick that attaches the seed on."},{"startTime":1188.745,"endTime":1193.565,"body":"So then actually the seed is not, is not dispersed naturally."},{"startTime":1193.785,"endTime":1195.045,"body":"That's a really bad idea."},{"startTime":1195.045,"endTime":1197.652,"body":"If you're a natural weak plant, the last thing you wanna do is keep your"},{"startTime":1197.652,"endTime":1199.565,"body":"seeds stuck with you because you're not gonna disperse at all."},{"startTime":1199.985,"endTime":1203.685,"body":"But if you are out as a human gathering wheat and you're bringing it back"},{"startTime":1203.685,"endTime":1207.385,"body":"again, you will massively select for any mutants in which the seed is still attached"},{"startTime":1207.385,"endTime":1208.125,"body":"to the stalk."},{"startTime":1208.365,"endTime":1209.645,"body":"'cause they're the ones there when you come back."},{"startTime":1210.225,"endTime":1214.644,"body":"So what we see in the archeological record very rapidly is a switch from the,"},{"startTime":1214.644,"endTime":1217.885,"body":"so-called shattering type, the wire type to a non shattering variant."},{"startTime":1218.025,"endTime":1223.8,"body":"And very early on we see that the entire population essentially of serials shifts from"},{"startTime":1223.8,"endTime":1228.805,"body":"this natural process of shattering to being mutants that don't shatter at all."},{"startTime":1229.065,"endTime":1231.565,"body":"And it turns out that's because it's a very, very easy to do this."},{"startTime":1231.785,"endTime":1236.427,"body":"So there's a single, uh, letter change, DNA letter change that will change you from"},{"startTime":1236.427,"endTime":1238.285,"body":"this shattering type to non shattering."},{"startTime":1238.285,"endTime":1242.205,"body":"So the mutation happens commonly, it is very firmly selected."},{"startTime":1243.185,"endTime":1246.517,"body":"One of the most interesting things about this is that this has happened again and"},{"startTime":1246.517,"endTime":1249.405,"body":"again and again in different crops, in completely different parts of the world."},{"startTime":1249.945,"endTime":1254.261,"body":"So we see this switch from shattering to non shattering in wheat and barley in"},{"startTime":1254.261,"endTime":1255.125,"body":"the Middle East."},{"startTime":1255.745,"endTime":1259.984,"body":"And we see it in rice in the far east happening at the same time"},{"startTime":1259.984,"endTime":1264.223,"body":"because people are providing the same selective force and evolutionary force on all these different"},{"startTime":1264.223,"endTime":1266.485,"body":"crops by gathering it in all the time."},{"startTime":1267.305,"endTime":1272.805,"body":"And this is probably the first example we have ever in the history of the"},{"startTime":1272.805,"endTime":1277.205,"body":"planet of evolution, favoring a mutation that is actively disadvantageous the species."},{"startTime":1277.355,"endTime":1279.685,"body":"It's in right survival of the fittest."},{"startTime":1279.715,"endTime":1283.982,"body":"This is a very unfit phenotype in the wild, these plants would die out 'cause"},{"startTime":1283.982,"endTime":1285.405,"body":"they don't disperse their seeds."},{"startTime":1285.405,"endTime":1287.685,"body":"They're now dependent on humans for dispersal."},{"startTime":1288.385,"endTime":1290.645,"body":"But we are a very powerful evolutionary force."},{"startTime":1290.665,"endTime":1295.27,"body":"And so we have selected for this trait that is actively disadvantageous to the host"},{"startTime":1295.27,"endTime":1295.885,"body":"it's in."},{"startTime":1295.885,"endTime":1299.365,"body":"And we have driven that process of unnatural evolution, if you like."},{"startTime":1301.225,"endTime":1305.795,"body":"And we have course have done that again and again and again throughout agriculture, initially"},{"startTime":1305.795,"endTime":1310.365,"body":"by accident more recently, very deliberately, uh, by programs of crop breeding and livestock breeding."},{"startTime":1310.665,"endTime":1312.325,"body":"And we have all sorts of species."},{"startTime":1312.505,"endTime":1316.648,"body":"So for example, we have dairy cattle which produce far more milk than their carved"},{"startTime":1316.648,"endTime":1316.925,"body":"needs."},{"startTime":1317.265,"endTime":1321.885,"body":"Um, actually they're also selected for, um, sort of a lack of maternal instincts."},{"startTime":1321.885,"endTime":1325.026,"body":"Most modern dairy cattle, uh, you can take their calve away and they're actually not"},{"startTime":1325.026,"endTime":1325.445,"body":"that bothered."},{"startTime":1325.745,"endTime":1328.445,"body":"Um, you know, evolutionarily speaking, it's a very bad idea."},{"startTime":1328.665,"endTime":1331.87,"body":"Uh, but it's been selected for because farmers don't like fighting with their cows to"},{"startTime":1331.87,"endTime":1332.725,"body":"get their calves away."},{"startTime":1332.945,"endTime":1334.765,"body":"Um, and so we have selected these traits."},{"startTime":1335.105,"endTime":1337.285,"body":"We have chickens that lay sterile eggs every day."},{"startTime":1337.505,"endTime":1339.205,"body":"Not a very good trait out in the wild."},{"startTime":1339.515,"endTime":1340.805,"body":"Very useful if you're in farming."},{"startTime":1341.105,"endTime":1345.242,"body":"And so we have again, and again and again, selected species for traits that are"},{"startTime":1345.242,"endTime":1347.725,"body":"for the species itself, disadvantageous for us as humans."},{"startTime":1348.025,"endTime":1348.805,"body":"Hugely important."},{"startTime":1351.015,"endTime":1355.245,"body":"Those processes are, if you like, in the beginning, inadvertent."},{"startTime":1355.245,"endTime":1359.557,"body":"We didn't deliberately go out and select for, uh, non shattering grain, but it happened"},{"startTime":1359.557,"endTime":1359.845,"body":"automatically."},{"startTime":1359.875,"endTime":1364.398,"body":"More recently deliberate or have been beneficial to us, if not to the species, uh,"},{"startTime":1364.398,"endTime":1365.605,"body":"that it happens in."},{"startTime":1366.505,"endTime":1369.405,"body":"But not all of our evolutionary impact is beneficial."},{"startTime":1371.465,"endTime":1375.728,"body":"Um, during our history, we have also repeatedly done things by accident that have influenced"},{"startTime":1375.728,"endTime":1379.992,"body":"the evolution of other species in ways that are actually not that beneficial, at least"},{"startTime":1379.992,"endTime":1380.845,"body":"not to us."},{"startTime":1381.745,"endTime":1383.605,"body":"And there are lots and lots of examples of that."},{"startTime":1383.605,"endTime":1386.519,"body":"But one of the ones that I think is the most, um, uh, kind of"},{"startTime":1386.519,"endTime":1389.433,"body":"striking, uh, dates only from the last sort of 70 years or so, and it's"},{"startTime":1389.433,"endTime":1390.405,"body":"this one, this is warfarin."},{"startTime":1390.405,"endTime":1395.285,"body":"So warfarin, uh, is a drug, um, and it's a drug that stops clotting."},{"startTime":1395.345,"endTime":1397.165,"body":"So it's an inhibitor of blood clotting."},{"startTime":1397.625,"endTime":1399.654,"body":"And in fact, it might be used, but some of you in the audience might"},{"startTime":1399.654,"endTime":1399.925,"body":"use it."},{"startTime":1400.185,"endTime":1403.085,"body":"Um, it's prescribed for people in very low dose."},{"startTime":1403.465,"endTime":1405.885,"body":"If you have, um, a, a propensity to clot."},{"startTime":1405.885,"endTime":1409.053,"body":"So for example, if you've had a stroke, um, or you're at risk of heart"},{"startTime":1409.053,"endTime":1411.165,"body":"attack, you might be prescribed a low dose of warfarin."},{"startTime":1411.325,"endTime":1416.845,"body":"'cause it inhibits an enzyme that converts actually vitamin K, which you require for clotting."},{"startTime":1417.505,"endTime":1420.453,"body":"So if you're given a very low dose of warfarin, you slightly reduce the chance"},{"startTime":1420.453,"endTime":1423.205,"body":"of your blood clotting and therefore getting clots that might lead to a stroke."},{"startTime":1423.985,"endTime":1426.845,"body":"If you give a high dose of warfarin, it's a very bad idea."},{"startTime":1427.185,"endTime":1430.485,"body":"It totally inhibits the process and you start to bleed spontaneously."},{"startTime":1430.745,"endTime":1432.765,"body":"Um, and high dose of warfarin is lethal."},{"startTime":1433.475,"endTime":1437.245,"body":"It's lethal to humans, uh, but it's also lethal to lots of other mammals."},{"startTime":1437.245,"endTime":1441.463,"body":"And after warfarin was, uh, discovered in the 1950s, people clocked the fact that this"},{"startTime":1441.463,"endTime":1445.681,"body":"was a very useful drug if you wanted to control mammals that you don't like"},{"startTime":1445.681,"endTime":1446.525,"body":"in particular rodents."},{"startTime":1446.905,"endTime":1450.965,"body":"Uh, and so warfarin became used very rapidly in the 1950s as a rodent poison."},{"startTime":1451.425,"endTime":1453.045,"body":"Um, and it would be put in baits."},{"startTime":1453.145,"endTime":1457.453,"body":"Um, and indeed these unfortunate rats and m would eat the bait, uh, and they"},{"startTime":1457.453,"endTime":1461.762,"body":"would die, uh, swiftly, but pretty horribly from, um, hemorrhage seemed like a wonderful thing,"},{"startTime":1461.762,"endTime":1466.07,"body":"very useful, uh, used in particular in big cities in the us very rapid in"},{"startTime":1466.07,"endTime":1466.645,"body":"the 1950s."},{"startTime":1467.185,"endTime":1470.805,"body":"Um, but warfarin works by targeting a single enzyme."},{"startTime":1470.805,"endTime":1475.205,"body":"So there's an enzyme, which is the blobbing here that converts, uh, vitamin K into"},{"startTime":1475.205,"endTime":1476.965,"body":"the functional form to trigger clotting."},{"startTime":1477.605,"endTime":1482.165,"body":"Warfarin, which is a little molecule here, sits inside that protein and stops it working."},{"startTime":1483.715,"endTime":1488.355,"body":"That means that any tiny mutation that slightly changes the shape of the protein means"},{"startTime":1488.355,"endTime":1492.996,"body":"the protein doesn't stick to warfarin anymore, and it goes on doing its normal function"},{"startTime":1492.996,"endTime":1493.925,"body":"without being inhibited."},{"startTime":1494.355,"endTime":1497.885,"body":"It's a way of escaping from this, uh, this poisonous selective warfarin."},{"startTime":1498.465,"endTime":1502.609,"body":"And, uh, people might call me put two together and realize that actually those kind"},{"startTime":1502.609,"endTime":1505.925,"body":"of changes in evolution happen all the time because of spontaneous mutation."},{"startTime":1506.425,"endTime":1511.417,"body":"Um, normally there would not be selected for, but if you apply a strong selective"},{"startTime":1511.417,"endTime":1516.409,"body":"agent, like a poison that kills you, any rat that has a spontaneous mutation which"},{"startTime":1516.409,"endTime":1519.405,"body":"renders it insensitive to warfarin, has a massive advantage."},{"startTime":1519.825,"endTime":1524.434,"body":"And sure enough, we introduced warfarin in the 1950s by 1960, uh, in New York"},{"startTime":1524.434,"endTime":1529.043,"body":"in particular, pest controllers are reporting large populations of rats that seem to be totally"},{"startTime":1529.043,"endTime":1529.965,"body":"insensitive to Warfarin."},{"startTime":1530.225,"endTime":1534.646,"body":"Uh, and a couple of years later, actually, uh, even in Europe, people started to"},{"startTime":1534.646,"endTime":1537.005,"body":"report mouse populations that were also warfarin resistant."},{"startTime":1537.565,"endTime":1542.294,"body":"A process by which we have shaped the evolution of multiple species, actually within a"},{"startTime":1542.294,"endTime":1547.023,"body":"very brief period of time, uh, because of this intense period of, of evolutionary selection"},{"startTime":1547.023,"endTime":1548.285,"body":"we've placed on them."},{"startTime":1549.985,"endTime":1551.965,"body":"Now, warfarin is a pretty unique example, obviously."},{"startTime":1552.065,"endTime":1556.161,"body":"Um, it's very, very tightly focused around particular species, but this same process is something"},{"startTime":1556.161,"endTime":1560.258,"body":"which is driving a problem that is, should be at least close to all of"},{"startTime":1560.258,"endTime":1560.805,"body":"our hearts."},{"startTime":1560.865,"endTime":1564.285,"body":"And something we really worry about, uh, which is antimicrobial resistance."},{"startTime":1565.185,"endTime":1568.165,"body":"Um, so if you're not familiar with it, um, first of all, I'm horrified."},{"startTime":1568.185,"endTime":1572.976,"body":"Uh, but, but if you're not familiar with antimicrobial resistance is the, is the dramatic"},{"startTime":1572.976,"endTime":1577.768,"body":"rise in bacteria, but also increasingly fungi and viruses, uh, that are resistant to many"},{"startTime":1577.768,"endTime":1580.005,"body":"of our medications designed to target them."},{"startTime":1580.465,"endTime":1585.422,"body":"And the process that is driving this is the same sort of evolutionary selection that"},{"startTime":1585.422,"endTime":1587.405,"body":"has driven warfarin resistance in rats."},{"startTime":1588.025,"endTime":1592.78,"body":"Namely, if you apply a drug that is designed to kill something, any mutation in"},{"startTime":1592.78,"endTime":1597.536,"body":"the thing you're trying to kill that renders it insensitive will be very, very strongly"},{"startTime":1597.536,"endTime":1598.805,"body":"selected for very rapidly."},{"startTime":1599.305,"endTime":1603.885,"body":"And so you are, if you like, um, neutralizing your own weaponry very, very fast."},{"startTime":1604.465,"endTime":1606.725,"body":"And that is exactly what we see in the history of antibodies."},{"startTime":1606.725,"endTime":1610.725,"body":"So we've had antibiotics, broadly speaking, for, for under a hundred years."},{"startTime":1610.795,"endTime":1613.245,"body":"It's a brief snapshot of of civilization."},{"startTime":1613.465,"endTime":1615.005,"body":"Uh, we had sulfonamides quite early."},{"startTime":1615.225,"endTime":1619.875,"body":"But actually in terms of mainstream antibiotics, the biggest one obviously is penicillin introduced around"},{"startTime":1619.875,"endTime":1620.805,"body":"Second World War."},{"startTime":1621.785,"endTime":1626.826,"body":"Um, and actually every major class of antibiotic that we've introduced, which are on the"},{"startTime":1626.826,"endTime":1631.868,"body":"top line here, has been followed generally within 10 or 20 years by bacterial strains"},{"startTime":1631.868,"endTime":1633.885,"body":"that are resistant to that antibiotic."},{"startTime":1634.815,"endTime":1639.277,"body":"Early on in the sixties and seventies, what we started to see were bacteria that"},{"startTime":1639.277,"endTime":1640.765,"body":"were resistant to single drugs."},{"startTime":1641.065,"endTime":1645.041,"body":"So for example, you might introduce something like methicillin 1960 here, um, and then actually"},{"startTime":1645.041,"endTime":1649.018,"body":"only a couple years later, in this case, you start to find bacteria that are"},{"startTime":1649.018,"endTime":1651.405,"body":"resistant to methicillin and so on and so forth."},{"startTime":1652.785,"endTime":1655.685,"body":"By 1980s, this was apparent to most clinicians."},{"startTime":1655.685,"endTime":1659.711,"body":"And so clinicians being very smart and wanting to do well for their patients, realized"},{"startTime":1659.711,"endTime":1663.738,"body":"that treating the single drug is not such a great idea and started to use"},{"startTime":1663.738,"endTime":1667.765,"body":"combinations of drugs either together, uh, or sequentially in order to get over this problem."},{"startTime":1668.385,"endTime":1669.285,"body":"Worked for a while."},{"startTime":1669.345,"endTime":1673.956,"body":"But then what we start to see is the evolution of strains that are resistant"},{"startTime":1673.956,"endTime":1678.568,"body":"to multiple drugs, and in particular, uh, by the two thousands, these extensively drug resistant"},{"startTime":1678.568,"endTime":1682.565,"body":"strains that we're resistant to many, if not all of our frontline antibiotics."},{"startTime":1683.185,"endTime":1686.466,"body":"And this actually is one of the biggest risks, I think, to the future of"},{"startTime":1686.466,"endTime":1686.685,"body":"humanity."},{"startTime":1686.685,"endTime":1689.572,"body":"We talk a lot in these series about things that might bring humanity to an"},{"startTime":1689.572,"endTime":1689.765,"body":"end."},{"startTime":1689.905,"endTime":1693.336,"body":"Um, and there are, unfortunately, there are quite a lot of them, asteroid strikes, climate"},{"startTime":1693.336,"endTime":1693.565,"body":"change."},{"startTime":1694.425,"endTime":1696.085,"body":"Uh, this is one more to add to the list."},{"startTime":1696.205,"endTime":1700.822,"body":"I think, uh, we have to remember that essentially many, many of us in this"},{"startTime":1700.822,"endTime":1703.285,"body":"room are only alive because of these drugs."},{"startTime":1703.565,"endTime":1706.512,"body":"I think it's probably, I want a show of hands, but it's probably rare that"},{"startTime":1706.512,"endTime":1709.459,"body":"any of you in this room will have gone through your entire life, never taking"},{"startTime":1709.459,"endTime":1710.245,"body":"a course of antibiotics."},{"startTime":1710.785,"endTime":1715.597,"body":"And you assume completely that if you have a chest infection or a kind of"},{"startTime":1715.597,"endTime":1718.805,"body":"slightly dodgy wound, um, that you'll get better with antibiotics."},{"startTime":1719.225,"endTime":1722.496,"body":"But it was only a hundred years ago that that chest infection or that slightly"},{"startTime":1722.496,"endTime":1723.805,"body":"dodgy wound might have killed you."},{"startTime":1723.945,"endTime":1728.312,"body":"Uh, and if we're not careful, we'll go back to that, uh, process again, because"},{"startTime":1728.312,"endTime":1732.68,"body":"we have accelerated evolution in a way, uh, that has essentially rendered our own arsenal"},{"startTime":1732.68,"endTime":1733.845,"body":"of drugs are useless."},{"startTime":1734.545,"endTime":1739.205,"body":"And one of the reasons we've had that process is not just about medical intervention."},{"startTime":1739.865,"endTime":1743.587,"body":"So these are all medical antibiotics, um, but we have also used antibiotics for all"},{"startTime":1743.587,"endTime":1745.325,"body":"sorts of things that have driven this."},{"startTime":1745.345,"endTime":1749.805,"body":"So if you have antibiotics as a patient, you need those, you're selecting for bacteria."},{"startTime":1749.825,"endTime":1754.877,"body":"But actually the amount of antibiotics used in individual patients pales into insignificance historically versus"},{"startTime":1754.877,"endTime":1758.245,"body":"the amount that have been used in things like agriculture."},{"startTime":1758.665,"endTime":1762.96,"body":"Uh, and this is a process now that is largely, um, being phased out and"},{"startTime":1762.96,"endTime":1764.965,"body":"banned in many countries, including the uk."},{"startTime":1764.965,"endTime":1769.802,"body":"But until recently, people have applied large doses of antibiotics, particularly to livestock like intensively"},{"startTime":1769.802,"endTime":1774.64,"body":"reared chickens as a growth promoter, as a way to accelerate the growth, uh, of"},{"startTime":1774.64,"endTime":1775.285,"body":"these chickens."},{"startTime":1775.545,"endTime":1778.879,"body":"Um, because if you remove all the bacteria from a chicken, it actually grows a"},{"startTime":1778.879,"endTime":1781.325,"body":"bit faster, probably because it's scavenging more energy from its food."},{"startTime":1781.825,"endTime":1785.445,"body":"Um, but you are strongly, strongly selecting for antibiotic resistance."},{"startTime":1785.625,"endTime":1789.845,"body":"And a lot of this agricultural use has driven, um, the evolution of these strains."},{"startTime":1791.115,"endTime":1795.522,"body":"More recently, we're starting to see worrying trends that this is not just restricted to,"},{"startTime":1795.522,"endTime":1797.285,"body":"to antibiotics that are used clinically."},{"startTime":1797.985,"endTime":1802.995,"body":"So for example, if you look at fungicides that are used in agriculture, um, these"},{"startTime":1802.995,"endTime":1808.005,"body":"are not fungicides that are used in patients, but they are often chemically very similar."},{"startTime":1808.145,"endTime":1812.067,"body":"So here, for example, someone is spraying a field with a fungicide and many are"},{"startTime":1812.067,"endTime":1815.205,"body":"commercially available agricultural fungicides are based on a structure called an azel."},{"startTime":1816.175,"endTime":1820.537,"body":"These are not the same molecules that are used in individual humans, but they are"},{"startTime":1820.537,"endTime":1823.445,"body":"the same group of chemicals and they're structurally very similar."},{"startTime":1824.025,"endTime":1828.429,"body":"And we have started to see just in the last few years, patients with invasive"},{"startTime":1828.429,"endTime":1831.365,"body":"fungal infections that appear to be resistant to clinical azoles."},{"startTime":1831.545,"endTime":1836.54,"body":"And when you look at the mutations that those strains have, they're conferring resistance to"},{"startTime":1836.54,"endTime":1838.205,"body":"these agriculturally used azoles too."},{"startTime":1838.825,"endTime":1842.2,"body":"And if you think about it, that makes a lot of sense because many of"},{"startTime":1842.2,"endTime":1845.125,"body":"the pathogens we encounter that kill us are out there in the environment."},{"startTime":1845.145,"endTime":1846.525,"body":"We don't always get them from other people."},{"startTime":1846.545,"endTime":1848.445,"body":"And that's particularly true for fungi."},{"startTime":1848.445,"endTime":1852.016,"body":"So this is one, this is aspergillus, a fungus that's out there in the environment"},{"startTime":1852.016,"endTime":1853.445,"body":"we breathe in all the time."},{"startTime":1853.785,"endTime":1855.645,"body":"For most people, it's not a particular problem."},{"startTime":1855.785,"endTime":1860.953,"body":"But if your immune system is impaired, particularly following organ transplantation, this fungus can grow"},{"startTime":1860.953,"endTime":1863.365,"body":"within your lungs and ultimately kill you."},{"startTime":1864.235,"endTime":1866.165,"body":"It's treated with azoles."},{"startTime":1866.545,"endTime":1870.238,"body":"Um, but the problem is this fungus lives out in the environment, particularly in agricultural"},{"startTime":1870.238,"endTime":1870.485,"body":"places."},{"startTime":1870.485,"endTime":1871.965,"body":"It likes compost heaps, for example."},{"startTime":1872.665,"endTime":1876.658,"body":"So if you are spraying your fields with a fungus and then gathering in the"},{"startTime":1876.658,"endTime":1880.651,"body":"waste and making compost, you are essentially exposing your fungus to a low dose of"},{"startTime":1880.651,"endTime":1884.645,"body":"the thing that is supposed to kill it, perfect conditions for it to evolve resistance."},{"startTime":1884.645,"endTime":1888.357,"body":"And what we start to see, uh, and this is a structure of one of"},{"startTime":1888.357,"endTime":1892.07,"body":"the proteins here, what we start to see is that these fungi out in the"},{"startTime":1892.07,"endTime":1895.782,"body":"environment carry mutations that render them resistant to the fungus, uh, to the fungicide out"},{"startTime":1895.782,"endTime":1896.525,"body":"in the environment."},{"startTime":1896.945,"endTime":1901.045,"body":"The same mutations confer resistance to the fungicide that will be used in a clinic."},{"startTime":1901.465,"endTime":1905.485,"body":"And so you are essentially producing a population of fungi that are already already immune"},{"startTime":1905.485,"endTime":1908.165,"body":"to the drugs you might need to treat them with."},{"startTime":1908.505,"endTime":1912.183,"body":"And that I think is a really, really big concern and something that that needs"},{"startTime":1912.183,"endTime":1913.165,"body":"kind of rapid addressing."},{"startTime":1915.315,"endTime":1916.685,"body":"Okay, so that's a little bit of a depressing note."},{"startTime":1916.685,"endTime":1917.645,"body":"Let's, let's go a bit more upbeat."},{"startTime":1917.645,"endTime":1921.536,"body":"Let's think a little bit, um, uh, for the last, uh, quarter, an hour or"},{"startTime":1921.536,"endTime":1925.427,"body":"so about ourselves, we've talked a lot about our impact on selecting other species, cows"},{"startTime":1925.427,"endTime":1926.725,"body":"and we, thoughts and stuff."},{"startTime":1927.675,"endTime":1928.365,"body":"What about ourselves?"},{"startTime":1928.385,"endTime":1929.685,"body":"Do we select ourselves?"},{"startTime":1930.025,"endTime":1933.245,"body":"Um, and the short answer to that is we do select ourselves like all species."},{"startTime":1933.665,"endTime":1937.433,"body":"Uh, we are evolving all the time and we're evolving in all sorts of interesting"},{"startTime":1937.433,"endTime":1937.685,"body":"ways."},{"startTime":1938.665,"endTime":1941.965,"body":"So for example, um, this is a graph I've showed in earlier lecture too."},{"startTime":1941.965,"endTime":1946.254,"body":"This is a, a very interesting study where people have looked at the human genome,"},{"startTime":1946.254,"endTime":1950.543,"body":"the modern human genome, they've sequenced people like you in the room or you listening"},{"startTime":1950.543,"endTime":1954.833,"body":"online, and they have looked at the rate of diversity in all the 20,000 ish"},{"startTime":1954.833,"endTime":1955.405,"body":"human genes."},{"startTime":1955.405,"endTime":1957.245,"body":"If you imagine this is the whole human genome here."},{"startTime":1957.465,"endTime":1960.615,"body":"So chromosome 1, 2, 3, all the, the way to the end, every human gene"},{"startTime":1960.615,"endTime":1963.765,"body":"is mapped and what they say is, so let's look at a sample of, of"},{"startTime":1963.765,"endTime":1966.915,"body":"people in this room so that you know, all of you in this room here,"},{"startTime":1966.915,"endTime":1967.965,"body":"how different are those genes?"},{"startTime":1967.965,"endTime":1971.285,"body":"And what you see is that for most genes, there's not very much diversity, okay?"},{"startTime":1971.285,"endTime":1972.565,"body":"Most of us have genes that're very similar."},{"startTime":1972.735,"endTime":1977.842,"body":"There are some though that are evolving incredibly fast, that are really, really diverse because"},{"startTime":1977.842,"endTime":1979.885,"body":"they're under very strong evolutionary selection."},{"startTime":1980.665,"endTime":1983.815,"body":"Um, and actually the single gene in the human genome name that is evolving the"},{"startTime":1983.815,"endTime":1985.285,"body":"fastest is this one up here, LCT."},{"startTime":1985.665,"endTime":1989.696,"body":"Um, and this is the gene that confers the ability to digest milk as an"},{"startTime":1989.696,"endTime":1989.965,"body":"adult."},{"startTime":1990.545,"endTime":1993.845,"body":"So most mammals, all mammals, digest milk as, as infants."},{"startTime":1994.185,"endTime":1994.605,"body":"All of us."},{"startTime":1994.705,"endTime":1996.605,"body":"We know we don't digest milk as adults."},{"startTime":1996.635,"endTime":2001.06,"body":"Many humans, that's also still true, uh, but uniquely amongst mammals, most, um, at least"},{"startTime":2001.06,"endTime":2005.485,"body":"in Europe, most humans have the ability to continue to digest milk as an adult."},{"startTime":2005.485,"endTime":2007.845,"body":"And it's because this gene has stayed on."},{"startTime":2009.315,"endTime":2012.165,"body":"Most humans don't drink human milk as adults."},{"startTime":2012.175,"endTime":2013.405,"body":"Let's not even go there actually."},{"startTime":2013.705,"endTime":2016.165,"body":"Um, uh, but so, so why have we evolved this?"},{"startTime":2016.165,"endTime":2021.408,"body":"We've evolved this because we do drink the milk of other species as adults only"},{"startTime":2021.408,"endTime":2024.205,"body":"since though we've started agriculture, since domesticating livestock."},{"startTime":2024.745,"endTime":2029.134,"body":"So this gene has evolved incredibly fast in the last 10,000 years, less in fact,"},{"startTime":2029.134,"endTime":2033.524,"body":"um, because of our newly imposed selective pressure, which is that if you can drink"},{"startTime":2033.524,"endTime":2037.914,"body":"cow's milk in the middle of winter when no one else got anything to eat,"},{"startTime":2037.914,"endTime":2039.085,"body":"you are gonna survive."},{"startTime":2039.505,"endTime":2042.485,"body":"And if your neighbor can't digest that milk, they're going to die."},{"startTime":2042.985,"endTime":2047.709,"body":"And so we have selected ourselves because of agriculture to have a very rapidly mutating"},{"startTime":2047.709,"endTime":2049.284,"body":"gene that confers that benefit."},{"startTime":2051.625,"endTime":2052.804,"body":"That's very overt."},{"startTime":2052.804,"endTime":2053.165,"body":"Example."},{"startTime":2053.645,"endTime":2055.645,"body":"Drinking milk and surviving is quite an important advantage."},{"startTime":2055.905,"endTime":2057.485,"body":"Um, but there are much more subtle effects."},{"startTime":2057.505,"endTime":2061.308,"body":"And one of the things that has, uh, puzzled people for a long time is"},{"startTime":2061.308,"endTime":2064.605,"body":"whether we see evidence in humans of this process known as sexual selection."},{"startTime":2065.745,"endTime":2068.165,"body":"So most animals compete for mates."},{"startTime":2068.225,"endTime":2071.993,"body":"If you think about it, most animals have a courtship ritual, and it's not random,"},{"startTime":2071.993,"endTime":2072.245,"body":"right?"},{"startTime":2072.245,"endTime":2074.245,"body":"It's not, your chance of reproducing is not random."},{"startTime":2074.344,"endTime":2077.731,"body":"You have very successful individuals who reproduce a lot and unsuccessful ones sat in the"},{"startTime":2077.731,"endTime":2079.764,"body":"corner of the disco who don't reproduce at all."},{"startTime":2080.225,"endTime":2083.605,"body":"Um, and, and this has driven this process of sexual selection."},{"startTime":2083.605,"endTime":2087.655,"body":"So most animals, um, engage in these kind of courtship rituals and they choose their"},{"startTime":2087.655,"endTime":2087.925,"body":"partners."},{"startTime":2087.925,"endTime":2092.964,"body":"And perhaps this prime example here of the peacock where the peacock is displaying, uh,"},{"startTime":2092.964,"endTime":2096.324,"body":"to the p hen, um, essentially advertising his pross, right?"},{"startTime":2097.195,"endTime":2099.525,"body":"This tail is of no benefit at all."},{"startTime":2099.525,"endTime":2102.445,"body":"In fact, it's a handicap, it's a very disadvantageous to have a tail like this."},{"startTime":2102.745,"endTime":2106.733,"body":"Um, but it has evolved because it's a way for the peacock to signal to"},{"startTime":2106.733,"endTime":2109.925,"body":"the p hen despite the fact I'm carrying around this ridiculous tale."},{"startTime":2110.385,"endTime":2113.34,"body":"I'm still incredibly fit because I'm really tough and I eat really well and I"},{"startTime":2113.34,"endTime":2114.325,"body":"can fight other people off."},{"startTime":2115.045,"endTime":2117.005,"body":"I am the kind of mate you want to mate with."},{"startTime":2117.035,"endTime":2118.605,"body":"It's a sexual signal, okay?"},{"startTime":2119.175,"endTime":2121.045,"body":"These happen in all sorts of animals."},{"startTime":2121.045,"endTime":2124.927,"body":"Think about plumage and birds, think about courtship, rituals, red deer erupts, all these kind"},{"startTime":2124.927,"endTime":2125.445,"body":"of things."},{"startTime":2125.665,"endTime":2129.953,"body":"Now, the question is, and the question actually originally posed by Darwin, do humans do"},{"startTime":2129.953,"endTime":2130.525,"body":"this too?"},{"startTime":2131.305,"endTime":2134.825,"body":"Um, and actually we still don't really know the answer, but there are some interesting,"},{"startTime":2134.825,"endTime":2138.346,"body":"um, and maybe slightly controversial anecdotes that, that I wanna share with you that, that"},{"startTime":2138.346,"endTime":2139.285,"body":"suggest we might do."},{"startTime":2139.665,"endTime":2142.205,"body":"And, uh, with apologies for lowering the tone straight away."},{"startTime":2142.425,"endTime":2146.685,"body":"Um, the one I'm gonna choose to pick on tonight, um, is, uh, human breasts."},{"startTime":2147.265,"endTime":2152.554,"body":"Um, and the reason for picking on this is not just gratuitous, is because humans"},{"startTime":2152.554,"endTime":2153.965,"body":"are unique amongst primates."},{"startTime":2153.985,"endTime":2157.725,"body":"We are the only primate that has prominent breasts in females, okay?"},{"startTime":2158.105,"endTime":2161.262,"body":"If you go to the zoo and you look at gorillas or chimps or bonobos,"},{"startTime":2161.262,"endTime":2162.525,"body":"they, they, their breasts not visible."},{"startTime":2162.525,"endTime":2165.325,"body":"They're, they're kind of flat, but humans have prominent breasts."},{"startTime":2166.785,"endTime":2168.565,"body":"You might think that has a fitness advantage."},{"startTime":2168.565,"endTime":2171.445,"body":"Maybe they produce more milk, um, they're better at producing kids."},{"startTime":2171.665,"endTime":2173.525,"body":"All those things have been looked at and none of them are true."},{"startTime":2173.825,"endTime":2177.341,"body":"So there is no correlation between breast size, um, and the ability to produce kids"},{"startTime":2177.341,"endTime":2179.685,"body":"or to lactate or any of these kind of things."},{"startTime":2180.465,"endTime":2184.672,"body":"And in fact, the best evidence we have is that the driver of breast is"},{"startTime":2184.672,"endTime":2188.88,"body":"nothing to do with their function in producing milk, but they are a symbol of,"},{"startTime":2188.88,"endTime":2191.405,"body":"if you like, fitness, just like the peacock's tail."},{"startTime":2192.305,"endTime":2196.31,"body":"Um, and that is because one of the things that is a very good signal"},{"startTime":2196.31,"endTime":2197.645,"body":"of, of fitness is symmetry."},{"startTime":2198.065,"endTime":2201.445,"body":"So if you think about getting infections, largely infections are not symmetrical."},{"startTime":2201.445,"endTime":2204.078,"body":"If you get spots or wounds or whatever, they're on one side of the body,"},{"startTime":2204.078,"endTime":2204.605,"body":"not the other."},{"startTime":2205.225,"endTime":2207.965,"body":"And so humans, like most animals prefer symmetry."},{"startTime":2208.245,"endTime":2212.621,"body":"Symmetry is a sign that you are a fit individual, but you haven't had some"},{"startTime":2212.621,"endTime":2213.205,"body":"horrible infection."},{"startTime":2214.425,"endTime":2219.005,"body":"Two large prominent breasts, uh, with apologies are a very prominent way of advertising."},{"startTime":2219.005,"endTime":2221.205,"body":"You are symmetrical and you are therefore fit."},{"startTime":2221.385,"endTime":2225.145,"body":"And so one of the, uh, suggestions for the evolution of these is that they're"},{"startTime":2225.145,"endTime":2228.405,"body":"a way of advertising your fitness, nothing to do with their primary function."},{"startTime":2228.705,"endTime":2232.338,"body":"Um, and, and so the suggestion is that the rapid evolution of breast lives in"},{"startTime":2232.338,"endTime":2235.245,"body":"humans has been driven in the same way as the peacock's tail."},{"startTime":2236.105,"endTime":2238.525,"body":"That's a very visible signal of sexual selection."},{"startTime":2238.525,"endTime":2242.598,"body":"But one of the ones that I think is most interesting, and actually for which"},{"startTime":2242.598,"endTime":2246.672,"body":"there is now really quite robust evidence, is a completely invisible type of human evolution,"},{"startTime":2246.672,"endTime":2248.845,"body":"um, that relies on this, uh, protein here."},{"startTime":2249.915,"endTime":2251.525,"body":"This is a protein called MHC."},{"startTime":2252.545,"endTime":2254.285,"body":"Its function is in your immune system."},{"startTime":2254.685,"endTime":2260.151,"body":"Actually, it displays foreign proteins and tells your immune system, I've seen this foreign protein"},{"startTime":2260.151,"endTime":2261.245,"body":"from this bacteria."},{"startTime":2261.245,"endTime":2263.045,"body":"You should get, get busy and kill it, okay?"},{"startTime":2263.345,"endTime":2269.165,"body":"We all have MHC proteins on our cells, and they are highly diverse."},{"startTime":2269.505,"endTime":2272.899,"body":"So unless you're an identical twin, your particular type of MHC will not be the"},{"startTime":2272.899,"endTime":2273.805,"body":"same as anybody else."},{"startTime":2273.905,"endTime":2276.165,"body":"And that is because it's advantageous."},{"startTime":2276.165,"endTime":2280.672,"body":"If you're thinking about using this to detect and display foreign pathogens, you want a"},{"startTime":2280.672,"endTime":2285.179,"body":"range of different options available to you because sometimes one version is better at displaying"},{"startTime":2285.179,"endTime":2288.485,"body":"i adeno bacteria and another version is better at displaying viruses."},{"startTime":2288.625,"endTime":2292.325,"body":"And so you want that, that diverse options like having a toolkit of different tools."},{"startTime":2293.505,"endTime":2297.125,"body":"So diversity amongst MHC proteins is a, is a benefit."},{"startTime":2298.065,"endTime":2301.921,"body":"Um, and so if you are choosing a mate, what you really want is the"},{"startTime":2301.921,"endTime":2305.777,"body":"ability to say, I want to find someone with a different set of MHC, says"},{"startTime":2305.777,"endTime":2308.605,"body":"that my kids will have the maximum diversity available to them."},{"startTime":2309.225,"endTime":2311.325,"body":"The problem is you can't see mhc."},{"startTime":2311.625,"endTime":2313.885,"body":"Um, and uh, so how do you, how do you know that?"},{"startTime":2313.885,"endTime":2316.842,"body":"And it turns out that we do know that in a way that we have"},{"startTime":2316.842,"endTime":2319.405,"body":"no understanding of at all, and we know it apparently, uh, by smell."},{"startTime":2320.025,"endTime":2324.236,"body":"Um, so there's a rather fabulous experiment in which you take, uh, uh, yucky sweaty"},{"startTime":2324.236,"endTime":2327.325,"body":"t-shirts worn by men, um, and you give them to women."},{"startTime":2327.785,"endTime":2331.073,"body":"Um, and you say, which of these sweaty t-shirts is the, is either the most"},{"startTime":2331.073,"endTime":2333.485,"body":"attractive or the least repellent, depending on how sweaty they are."},{"startTime":2333.825,"endTime":2336.285,"body":"Um, and therefore use that as a measure of attractiveness."},{"startTime":2336.285,"endTime":2340.193,"body":"And what it turns out is if you take a random sample of women, they"},{"startTime":2340.193,"endTime":2344.101,"body":"never choose the same t-shirt, but what they choose is the T-shirt from the person"},{"startTime":2344.101,"endTime":2345.925,"body":"who is most genetically dissimilar to them."},{"startTime":2346.395,"endTime":2351.103,"body":"They are sniffing out literally the person who has a different set of MHC to"},{"startTime":2351.103,"endTime":2352.045,"body":"maximize that diversity."},{"startTime":2352.705,"endTime":2353.765,"body":"We dunno how they do that."},{"startTime":2354.035,"endTime":2356.525,"body":"It's no idea how how that happens, but it does seem to happen."},{"startTime":2356.825,"endTime":2360.914,"body":"Um, and so I think this is a fantastic example where actually evolution is happening"},{"startTime":2360.914,"endTime":2362.005,"body":"without us knowing it."},{"startTime":2362.585,"endTime":2366.103,"body":"We also don't know, not only how, how it happens, but what it's long term"},{"startTime":2366.103,"endTime":2369.621,"body":"effect is because this is a, a process, if you think about it, where it"},{"startTime":2369.621,"endTime":2370.325,"body":"is not directional."},{"startTime":2370.535,"endTime":2372.285,"body":"We're not all choosing the same person."},{"startTime":2372.385,"endTime":2376.09,"body":"So we're not all choosing a strong person or someone who's good at gathering food,"},{"startTime":2376.09,"endTime":2377.325,"body":"we're choosing someone who's different."},{"startTime":2377.325,"endTime":2378.685,"body":"We're maximizing diversity."},{"startTime":2379.105,"endTime":2382.617,"body":"And so in some senses, it's jumbling up the evolution all the time, and we"},{"startTime":2382.617,"endTime":2384.725,"body":"don't know how, um, impactful that is long term."},{"startTime":2384.725,"endTime":2387.631,"body":"But I think a fascinating example and maybe want to think about if you haven't"},{"startTime":2387.631,"endTime":2390.537,"body":"yet chosen your partner, give 'em a good sniff beforehand and, and see what they"},{"startTime":2390.537,"endTime":2390.925,"body":"smell like."},{"startTime":2393.265,"endTime":2396.743,"body":"So let me finish off in the last few minutes by thinking about this is"},{"startTime":2396.743,"endTime":2400.222,"body":"everything I've talked about has been either inadvertent, we haven't deliberate on it, or it's"},{"startTime":2400.222,"endTime":2403.005,"body":"been sort of deliberate, but we haven't known what we've been doing."},{"startTime":2403.005,"endTime":2406.445,"body":"We've been choosing, you know, wheat, that's great, or cows that produce more milk."},{"startTime":2406.545,"endTime":2408.485,"body":"But we haven't known how that has happened."},{"startTime":2409.545,"endTime":2414.222,"body":"But in the last hundred years, pretty much we've suddenly gained the ability to really"},{"startTime":2414.222,"endTime":2417.965,"body":"understand what happens in evolution and to start to shape it deliberately."},{"startTime":2419.615,"endTime":2423.75,"body":"We've gained the ability to control our own evolution and the evolution of other, uh,"},{"startTime":2423.75,"endTime":2425.405,"body":"species in a very directed way."},{"startTime":2425.405,"endTime":2426.565,"body":"And we do this all the time now."},{"startTime":2426.585,"endTime":2430.771,"body":"So for example, if you're a farmer, it's absolutely routine to do genetic testing on"},{"startTime":2430.771,"endTime":2433.005,"body":"your cows or your chickens or whatever else."},{"startTime":2433.425,"endTime":2437.108,"body":"Um, and then to mate them according to their genotype and to get the maximum"},{"startTime":2437.108,"endTime":2437.845,"body":"possibility you want."},{"startTime":2438.665,"endTime":2442.681,"body":"But where it's about to change life, I think, forever, is in ourselves, in humans"},{"startTime":2442.681,"endTime":2446.697,"body":"because we now have the ability to control our own evolution in an incredibly directed"},{"startTime":2446.697,"endTime":2446.965,"body":"way."},{"startTime":2448.145,"endTime":2450.816,"body":"And actually we've been doing this already a little bit, uh, for the last sort"},{"startTime":2450.816,"endTime":2451.885,"body":"of a hundred years or so."},{"startTime":2452.265,"endTime":2454.62,"body":"Um, so for example, this is baby, obviously if you don't know it's a baby,"},{"startTime":2454.62,"endTime":2455.405,"body":"you're in the wrong lecture."},{"startTime":2455.625,"endTime":2457.965,"body":"Um, this so, so, and this is a healthy baby."},{"startTime":2458.745,"endTime":2462.616,"body":"But there are, as we know, some tragic and, and, and very disturbing, um, diseases"},{"startTime":2462.616,"endTime":2464.165,"body":"that are inherited of, of babies."},{"startTime":2464.585,"endTime":2467.085,"body":"Um, and I think all parents kind of want to try and avoid those."},{"startTime":2467.675,"endTime":2471.747,"body":"Very early on, uh, when genetics was kind of in its infancy at the beginning"},{"startTime":2471.747,"endTime":2475.82,"body":"of the 19 hundreds, people realized that these disorders were often inherited and therefore that"},{"startTime":2475.82,"endTime":2479.893,"body":"you had to kind of control over them if you could work out, um, their"},{"startTime":2479.893,"endTime":2480.165,"body":"impact."},{"startTime":2480.165,"endTime":2485.993,"body":"And this was adopted, uh, by many populations quite extensively, particularly populations in which particular"},{"startTime":2485.993,"endTime":2488.325,"body":"diseases were, um, were more prominent."},{"startTime":2488.825,"endTime":2491.605,"body":"And the best example of this is disease called Sachs disease."},{"startTime":2492.115,"endTime":2497.005,"body":"It's a neurodegenerative condition that children are born with, um, and, uh, it's lethal."},{"startTime":2497.275,"endTime":2501.085,"body":"They have a pretty appalling neurodegeneration and, and die in infancy."},{"startTime":2502.115,"endTime":2506.172,"body":"This disease is relatively rare overall in the world, but there are particular populations in"},{"startTime":2506.172,"endTime":2507.525,"body":"which it's much more common."},{"startTime":2507.825,"endTime":2512.263,"body":"And that is due to this process that we talked about in an early electrical,"},{"startTime":2512.263,"endTime":2516.702,"body":"the founder effect, where a small population has grown from a handful of individuals, it"},{"startTime":2516.702,"endTime":2521.141,"body":"often over represents particular genetic mutations that are rare overall, but if they happen to"},{"startTime":2521.141,"endTime":2525.285,"body":"be common in that starter population, they stay common, uh, when the population expands."},{"startTime":2525.545,"endTime":2530.525,"body":"So this is often seen, for example, in groups where they may have migrated so"},{"startTime":2530.525,"endTime":2535.505,"body":"particularly to the new world, um, and where they tend to reproduce within that continue"},{"startTime":2535.505,"endTime":2537.165,"body":"to reproduce within that group."},{"startTime":2537.385,"endTime":2542.34,"body":"So for example, religious communities that were persecuted in Europe that then fled to America,"},{"startTime":2542.34,"endTime":2546.965,"body":"but retained within their community structure often have a higher frequency of particular disorders."},{"startTime":2546.965,"endTime":2551.165,"body":"And so SAC is particularly common in some of those communities, especially the Orthodox Jewish"},{"startTime":2551.165,"endTime":2555.365,"body":"community, where the rate of taste acts is about a hundred fold higher than in,"},{"startTime":2555.365,"endTime":2557.325,"body":"in the random population of the world."},{"startTime":2557.865,"endTime":2561.488,"body":"Uh, and this community realized that very early on, and actually there's been a program"},{"startTime":2561.488,"endTime":2565.112,"body":"running now for, um, many decades in which you can have yourself tested to see"},{"startTime":2565.112,"endTime":2567.045,"body":"whether you carry the gene for this disease."},{"startTime":2567.385,"endTime":2569.645,"body":"And if you do, um, you can then phone a helpline."},{"startTime":2569.645,"endTime":2572.726,"body":"You can work out if you're about to marry somebody, whether or not they carry"},{"startTime":2572.726,"endTime":2574.165,"body":"that, uh, ine in, in as well."},{"startTime":2574.625,"endTime":2577.339,"body":"And if you do, you might choose either to not to marry them in the"},{"startTime":2577.339,"endTime":2580.054,"body":"first place, um, or to marry, but not have kids, um, or of course, uh,"},{"startTime":2580.054,"endTime":2582.045,"body":"more recently to have genetic testing of your, of your children."},{"startTime":2582.385,"endTime":2589.12,"body":"And this process has very, very rapidly reduce the frequency of this mutation in that"},{"startTime":2589.12,"endTime":2591.365,"body":"population because of directed evolution."},{"startTime":2591.425,"endTime":2596.039,"body":"If you like, directed reproduction, that's a relatively blunt tool to test yourself and decide"},{"startTime":2596.039,"endTime":2597.885,"body":"shall we have babies or not."},{"startTime":2598.105,"endTime":2601.861,"body":"But of course, what has happened in the last less than 50 years is our"},{"startTime":2601.861,"endTime":2604.365,"body":"ability to do this in a very, very precise way."},{"startTime":2604.745,"endTime":2609.5,"body":"And in particular with the advent of in in vitro fertilization, IVF, so IVF now"},{"startTime":2609.5,"endTime":2614.256,"body":"almost 50 years old, of course, is the ability to create embryos and then implant"},{"startTime":2614.256,"endTime":2615.525,"body":"them, uh, in vitro."},{"startTime":2616.275,"endTime":2620.55,"body":"Initially it was done purely as a process of producing babies for people who couldn't"},{"startTime":2620.55,"endTime":2621.405,"body":"have them naturally."},{"startTime":2621.755,"endTime":2625.619,"body":"More recently, of course, what we've started to do is use this to couple this"},{"startTime":2625.619,"endTime":2627.165,"body":"with genetics to test for diseases."},{"startTime":2627.165,"endTime":2630.792,"body":"So if you go for IVF now, you will be offered a very extensive range"},{"startTime":2630.792,"endTime":2632.485,"body":"of genetic tests if you want them."},{"startTime":2632.675,"endTime":2636.525,"body":"Several hundred diseases can be identified in embryos."},{"startTime":2636.525,"endTime":2639.965,"body":"And so classically what happens is you might have multiple embryos created."},{"startTime":2640.435,"endTime":2644.198,"body":"They might test multiple embryos and say, uh, here is one that doesn't carry any"},{"startTime":2644.198,"endTime":2646.205,"body":"of the 300 main mutations we're looking for."},{"startTime":2646.495,"endTime":2648.765,"body":"Let's implant this one and not the other ones."},{"startTime":2649.905,"endTime":2654.57,"body":"And so what we're doing with IVF in some senses is selecting away some of"},{"startTime":2654.57,"endTime":2658.925,"body":"these bigly big disadvantageous uh, diseases, but we're also changing the frequency of genes."},{"startTime":2658.925,"endTime":2663.013,"body":"So the diseases you can test for in IVF include lethal, uh, many, many lethal"},{"startTime":2663.013,"endTime":2666.285,"body":"diseases, but they also include things that are actually relatively late onset."},{"startTime":2666.285,"endTime":2670.958,"body":"So things like early onset Parkinson's disease, uh, for example, is one of the tests"},{"startTime":2670.958,"endTime":2672.205,"body":"that you can have."},{"startTime":2673.105,"endTime":2676.577,"body":"Now, early onset Parkinson's disease is a grim disease, and as a parent, you probably"},{"startTime":2676.577,"endTime":2680.05,"body":"wouldn't want your child to have it, but that child would grow up to be"},{"startTime":2680.05,"endTime":2682.365,"body":"an adult and potentially have reproduced despite carrying that mutation."},{"startTime":2682.785,"endTime":2687.544,"body":"So you've intervened and changed the frequency of a gene in a way that has"},{"startTime":2687.544,"endTime":2689.765,"body":"never previously happened by by diagnosing it."},{"startTime":2691.395,"endTime":2695.75,"body":"That tool is still, I guess it's still relatively blunt, much more sharp than the"},{"startTime":2695.75,"endTime":2699.525,"body":"the previous one of testing yourself and choosing to reproduce, but relatively blunt."},{"startTime":2699.525,"endTime":2703.314,"body":"But what has happened just in the last decade or so, is our ability to"},{"startTime":2703.314,"endTime":2704.325,"body":"do really remarkable things."},{"startTime":2704.705,"endTime":2708.205,"body":"Um, and this perhaps is one of the most, uh, remarkable ones to be reported"},{"startTime":2708.205,"endTime":2709.605,"body":"just in the last few years."},{"startTime":2709.605,"endTime":2713.462,"body":"Here's John Zang, who's a clinician in the United States, and he is holding, um,"},{"startTime":2713.462,"endTime":2716.805,"body":"what is now sort of slightly ancy known as the three parent baby."},{"startTime":2718.145,"endTime":2721.378,"body":"Um, and the reason this, they, it doesn't really have three parents, but let me"},{"startTime":2721.378,"endTime":2724.611,"body":"explain why it's called that this is a baby born to a couple who have"},{"startTime":2724.611,"endTime":2727.845,"body":"an inherited, they know they have a risk of an inherited disease called Lee syndrome."},{"startTime":2728.425,"endTime":2732.231,"body":"And Lee Syndrome is, uh, one of a group of diseases that are called mitochondrial"},{"startTime":2732.231,"endTime":2732.485,"body":"diseases."},{"startTime":2732.485,"endTime":2733.605,"body":"And let me explain what that means."},{"startTime":2733.705,"endTime":2738.04,"body":"So if you, uh, reproduce normally, uh, what you have, I hope this is not"},{"startTime":2738.04,"endTime":2739.485,"body":"a spoiler alert for anybody."},{"startTime":2739.485,"endTime":2741.045,"body":"What you have is a sperm and an egg, right?"},{"startTime":2741.365,"endTime":2742.565,"body":"Sperm fuses with egg."},{"startTime":2742.745,"endTime":2746.007,"body":"Um, and what you end up with, uh, is an embryo in which you have"},{"startTime":2746.007,"endTime":2747.965,"body":"a mixed set of genes from both your parents."},{"startTime":2748.025,"endTime":2752.165,"body":"But there's a slight caveat here, the the red dot and the big blue.here on"},{"startTime":2752.165,"endTime":2754.925,"body":"the nuclei where your genetic material is, um, uh, contained."},{"startTime":2755.585,"endTime":2759.689,"body":"Um, and all of us are roughly speaking a 50 50 mix of those nuclear"},{"startTime":2759.689,"endTime":2761.605,"body":"genes from our mum and our dad."},{"startTime":2761.825,"endTime":2766.159,"body":"But there's a tiny little bit of genetic material that you don't inherit from both"},{"startTime":2766.159,"endTime":2770.205,"body":"your parents, and it's carried in the little blue, um, ovals here called mitochondria."},{"startTime":2771.295,"endTime":2775.282,"body":"These are parts of your cell that produce energy you need, you have in all"},{"startTime":2775.282,"endTime":2779.269,"body":"your cells pretty much, um, and they are working your way to produce energy, but"},{"startTime":2779.269,"endTime":2782.725,"body":"they have a tiny, tiny bit of DNA from themselves, just 37 genes."},{"startTime":2782.945,"endTime":2787.223,"body":"So the nucleus has about 20,000 genes, but the mitochondria has 37 genes, but they"},{"startTime":2787.223,"endTime":2788.365,"body":"are very important ones."},{"startTime":2788.625,"endTime":2792.858,"body":"And actually, interestingly, that's because mitochondria's origin million, billions of years ago is as a"},{"startTime":2792.858,"endTime":2796.245,"body":"free living bacteria that has now been kind of co-opted into us."},{"startTime":2796.545,"endTime":2798.165,"body":"But you see your mitochondria have their own genome."},{"startTime":2798.435,"endTime":2803.016,"body":"When you fuse a sperm and an ache, you fuse those 20,000 genes for your"},{"startTime":2803.016,"endTime":2805.765,"body":"nucleus, but you only inherit mitochondria from your mum."},{"startTime":2806.235,"endTime":2806.525,"body":"Okay?"},{"startTime":2806.905,"endTime":2810.427,"body":"So all of us, you know, who are dads, um, we are actually slightly less"},{"startTime":2810.427,"endTime":2813.245,"body":"inherited in our kids, uh, than your, your partner, your female partner."},{"startTime":2814.545,"endTime":2819.528,"body":"If you have a mutation on your mitochondria that causes disease, um, this can be"},{"startTime":2819.528,"endTime":2820.525,"body":"very disa disadvantageous."},{"startTime":2820.825,"endTime":2824.849,"body":"Um, and because the, the MIT might not function, and there are actually a large"},{"startTime":2824.849,"endTime":2828.605,"body":"number of syndromes that are driven by mutations in one of those 37 genes."},{"startTime":2829.505,"endTime":2833.125,"body":"Um, and so for most of human history, this has been unavoidable."},{"startTime":2833.125,"endTime":2836.249,"body":"There's been a problem, and there are lots of these conditions out there, but what"},{"startTime":2836.249,"endTime":2839.165,"body":"has happened just in the last few years is the ability to overcome this."},{"startTime":2839.745,"endTime":2843.506,"body":"Um, and so what John Zang did, uh, with this couple who knew that they"},{"startTime":2843.506,"endTime":2847.268,"body":"carried a mutation in the mitochondria in the, in the, uh, wife's mitochondria, they'd had"},{"startTime":2847.268,"endTime":2849.525,"body":"two babies previously with Lee Syndrome who had died."},{"startTime":2849.745,"endTime":2851.645,"body":"Um, and they were desperate to have another one that would be healthy."},{"startTime":2852.225,"endTime":2855.136,"body":"Um, so what they did was they created what is now known as the three"},{"startTime":2855.136,"endTime":2855.525,"body":"parent baby."},{"startTime":2855.625,"endTime":2860.485,"body":"So sperm from the dad as per normal mum's egg and a donor egg, okay?"},{"startTime":2861.675,"endTime":2865.673,"body":"What you do is you take a donor egg in here in blue from a"},{"startTime":2865.673,"endTime":2869.405,"body":"healthy individual who doesn't carry the mutation, you remove from that egg, the nucleus."},{"startTime":2869.745,"endTime":2873.801,"body":"So all the genetic material except for the mitochondria, you transfer in the nucleus from"},{"startTime":2873.801,"endTime":2875.965,"body":"the mum who wants to have the baby."},{"startTime":2876.305,"endTime":2878.485,"body":"And then you fuse this egg with this sperm."},{"startTime":2878.485,"endTime":2882.921,"body":"And what you end up with is a baby in which the same 20,000 genes"},{"startTime":2882.921,"endTime":2887.358,"body":"are a mixture of mum and dad, but critically, the mitochondria come from the donor,"},{"startTime":2887.358,"endTime":2889.725,"body":"pseudo mother, if you like the other one."},{"startTime":2890.545,"endTime":2892.685,"body":"And this is exactly what has happened in this baby here."},{"startTime":2892.685,"endTime":2898.151,"body":"So this baby, for the first time ever in human history, has genetic material from"},{"startTime":2898.151,"endTime":2899.245,"body":"three immediate parents."},{"startTime":2899.675,"endTime":2903.725,"body":"It's only a tiny amount, 37 genes from the other mum."},{"startTime":2904.025,"endTime":2906.805,"body":"But nonetheless, it's something that would never have happened naturally."},{"startTime":2906.805,"endTime":2911.428,"body":"And so we have created, if you like, a totally novel genetic combination, uh, in"},{"startTime":2911.428,"endTime":2912.045,"body":"this baby."},{"startTime":2912.585,"endTime":2914.205,"body":"Uh, and I think, you know, for very good reasons."},{"startTime":2914.305,"endTime":2916.485,"body":"But of course this opens a whole new door of Eli."},{"startTime":2918.035,"endTime":2921.977,"body":"More critically, we have now got tools to start to do this also on those"},{"startTime":2921.977,"endTime":2924.605,"body":"genes that are within the nucleus, those other 20,000 genes."},{"startTime":2924.605,"endTime":2929.428,"body":"And in particular, um, this process of CRISPR editing, which won the Nobel Prize a"},{"startTime":2929.428,"endTime":2932.965,"body":"couple of years ago, allows us to very precisely edit genes."},{"startTime":2933.495,"endTime":2937.77,"body":"There is a global moratorium preventing this being done in humans because a change that"},{"startTime":2937.77,"endTime":2942.045,"body":"you make in a gene of a baby in this way will be inherited forever."},{"startTime":2942.545,"endTime":2945.558,"body":"And so there is an agreement globally not to do this in, in children, but"},{"startTime":2945.558,"endTime":2946.965,"body":"like most agreements, people break the rules."},{"startTime":2947.185,"endTime":2948.285,"body":"And indeed it has happened."},{"startTime":2948.585,"endTime":2952.128,"body":"Uh, so there were twins born in China a few years ago who had been"},{"startTime":2952.128,"endTime":2952.365,"body":"edited."},{"startTime":2952.365,"endTime":2956.14,"body":"They had been edited for all the right reasons to render them resistant to HIV"},{"startTime":2956.14,"endTime":2958.405,"body":"'cause they've been born to an HIV positive mother."},{"startTime":2958.905,"endTime":2962.165,"body":"Um, but, uh, they are, they are different."},{"startTime":2962.195,"endTime":2966.516,"body":"They are different, fundamentally different from any baby born before because they have been precisely"},{"startTime":2966.516,"endTime":2966.805,"body":"edited."},{"startTime":2967.395,"endTime":2972.485,"body":"That mutation could have arisen randomly anyway, but it has been directed, uh, and produced."},{"startTime":2972.485,"endTime":2974.005,"body":"And the person who did this ended up in prison."},{"startTime":2974.065,"endTime":2978.82,"body":"But nonetheless, the twins are alive and out there and are a new type, if"},{"startTime":2978.82,"endTime":2980.405,"body":"you like, of human evolution."},{"startTime":2980.605,"endTime":2985.725,"body":"I think this, this kind of totally transforms our understanding of evolutionary direction because now"},{"startTime":2985.725,"endTime":2990.845,"body":"we have a process which has reshaped, if you like, a gene pool, uh, forever."},{"startTime":2991.665,"endTime":2994.045,"body":"Um, we'll have to see what happens, who knows what will happen going forward."},{"startTime":2994.065,"endTime":2997.815,"body":"But I think these tools open a new box and potentially a whole new era"},{"startTime":2997.815,"endTime":2998.565,"body":"in human evolution."},{"startTime":2998.785,"endTime":3002.623,"body":"And I guess one which would be very interesting to watch, and my personal feeling"},{"startTime":3002.623,"endTime":3006.461,"body":"is I suspect ultimately it will start to shape human populations in ways that we"},{"startTime":3006.461,"endTime":3007.485,"body":"have never predicted before."},{"startTime":3007.485,"endTime":3012.551,"body":"And who knows, this interesting mixing pot of human species might start to have all"},{"startTime":3012.551,"endTime":3016.605,"body":"sorts of genetic mutations that have been created rather than spontaneously selected."},{"startTime":3016.945,"endTime":3019.18,"body":"Uh, which is something we'll talk about in the final lecture of the series in"},{"startTime":3019.18,"endTime":3019.925,"body":"a couple of months time."},{"startTime":3020.065,"endTime":3021.005,"body":"Uh, but that's it for tonight."},{"startTime":3021.005,"endTime":3021.605,"body":"Thank you very much."},{"startTime":3025.455,"endTime":3025.925,"body":"Thank you."},{"startTime":3026.025,"endTime":3031.085,"body":"Um, the sweaty t-shirt test \u003claugh\u003e, does it only work with women doing the sniffing?"},{"startTime":3031.345,"endTime":3034.885,"body":"So is it a bit like peacocks, it's the women, the females doing the selection,"},{"startTime":3034.885,"endTime":3037.245,"body":"or does it work the other way around as well?"},{"startTime":3037.675,"endTime":3039.685,"body":"Yeah, um, it is just like peacocks."},{"startTime":3039.685,"endTime":3042.085,"body":"So for the guys in the room, disappointing, but we are rubbish at it."},{"startTime":3042.305,"endTime":3046.645,"body":"Uh, so, so yes, so women can detect, uh, diversity in, in male t-shirts."},{"startTime":3046.645,"endTime":3049.405,"body":"There's no evidence that men can even more interesting."},{"startTime":3049.405,"endTime":3053.287,"body":"There's actually a bit of data suggesting that how good women are depends on the"},{"startTime":3053.287,"endTime":3053.805,"body":"menstrual cycle."},{"startTime":3053.905,"endTime":3057.665,"body":"So you're better at some periods of the month than others in a way which"},{"startTime":3057.665,"endTime":3060.925,"body":"seems to reflect fertility, um, which, which actually brings a whole new perspective."},{"startTime":3060.985,"endTime":3062.965,"body":"You go clubbing on a Friday night, so what's going on?"},{"startTime":3063.185,"endTime":3063.405,"body":"But"},{"startTime":3063.725,"endTime":3069.045,"body":"\u003claugh\u003e it was about, um, the way that genes naturally select."},{"startTime":3069.485,"endTime":3074.094,"body":"I read something recently about a garfish and about how similar the genes are to"},{"startTime":3074.094,"endTime":3076.245,"body":"how they were millions of years ago."},{"startTime":3076.425,"endTime":3080.481,"body":"Is that, is that, is that something that's, is that new or is this something"},{"startTime":3080.481,"endTime":3082.645,"body":"that's been found in other populations as well?"},{"startTime":3082.915,"endTime":3086.756,"body":"Yeah, so the, so the rate, there are basically two big drivers of the rate"},{"startTime":3086.756,"endTime":3087.525,"body":"of genetic change."},{"startTime":3087.825,"endTime":3091.6,"body":"Um, so the first one is I guess how much you might need to, so"},{"startTime":3091.6,"endTime":3095.375,"body":"what we see quite often are species that apparently have existed more or less unchanged"},{"startTime":3095.375,"endTime":3096.885,"body":"for a long period of time."},{"startTime":3096.885,"endTime":3100.539,"body":"So the sealer camp people are familiar with is this kind of ancient fish, for"},{"startTime":3100.539,"endTime":3104.194,"body":"example, in the Indian ocean that appears not to have changed for, uh, hundreds of"},{"startTime":3104.194,"endTime":3104.925,"body":"millions of years."},{"startTime":3104.925,"endTime":3108.615,"body":"We of course don't have genetic data going back that far, um, but it looks"},{"startTime":3108.615,"endTime":3109.845,"body":"really like fossil seed cans."},{"startTime":3110.105,"endTime":3116.09,"body":"Um, and that is most likely because essentially if you are optimally, um, evolved your"},{"startTime":3116.09,"endTime":3118.085,"body":"environment, there'll be subtle changes."},{"startTime":3118.625,"endTime":3121.365,"body":"But if the environment doesn't change, you don't need to evolve to these."},{"startTime":3121.365,"endTime":3125.141,"body":"There'll be random mutation, but actually you are kind of not under the same pressure"},{"startTime":3125.141,"endTime":3125.645,"body":"to go."},{"startTime":3125.645,"endTime":3130.302,"body":"And actually that graph I showed of human genes, most human genes are not evolving"},{"startTime":3130.302,"endTime":3134.959,"body":"very fast because the, the kind of gene you need to, I dunno, metabolize carbohydrate"},{"startTime":3134.959,"endTime":3138.685,"body":"or, you know, produce sperm or eggs, they haven't changed that much."},{"startTime":3138.685,"endTime":3141.445,"body":"What you see is only the ones that have a direct impact have evolved fast."},{"startTime":3141.445,"endTime":3145.149,"body":"So that, so one reason is if the environment's not changing, um, the other reason"},{"startTime":3145.149,"endTime":3147.125,"body":"there might be constraints on those particular genes."},{"startTime":3147.125,"endTime":3150.632,"body":"So one of the things we often see is that a gene that relies on"},{"startTime":3150.632,"endTime":3153.205,"body":"another gene and another, another gene, is much harder to evolve."},{"startTime":3153.205,"endTime":3156.647,"body":"Because if you, so if you imagine for example, a protein and it's receptor, if"},{"startTime":3156.647,"endTime":3160.089,"body":"this one changes and it doesn't stick anymore, then this one has to change at"},{"startTime":3160.089,"endTime":3161.925,"body":"the same time, otherwise it's not gonna work."},{"startTime":3161.925,"endTime":3164.325,"body":"And it's much harder to evolve those multiple things."},{"startTime":3164.385,"endTime":3168.365,"body":"So anything where you are dependent on a much more complicated network evolves more slowly."},{"startTime":3168.825,"endTime":3173.206,"body":"And that is one of the potential saving graces for antimicrobial resistance is if you"},{"startTime":3173.206,"endTime":3177.587,"body":"can combine lots of treatments in ways that it's very hard to evolve individual resistance"},{"startTime":3177.587,"endTime":3181.968,"body":"to, you'll reduce the rate of evolution in the bacteria because they can't do 19"},{"startTime":3181.968,"endTime":3182.845,"body":"things at once."},{"startTime":3183.105,"endTime":3185.965,"body":"Uh, not an easy fix, but yeah, that's, that's, that's one of the reasons."},{"startTime":3187.105,"endTime":3189.245,"body":"Um, I'm gonna take a, a, a couple online."},{"startTime":3189.505,"endTime":3194.255,"body":"The, the now you, you, you, like a disturbing number of bre college professors have,"},{"startTime":3194.255,"endTime":3199.005,"body":"have, have, have forecast ways in which the human, uh, species might come to extent."},{"startTime":3199.455,"endTime":3204.676,"body":"We've, we've, we've had asteroids when, and we've, uh, the sun exploding and, uh, the,"},{"startTime":3204.676,"endTime":3206.765,"body":"uh, climate change dragons more recently."},{"startTime":3207.105,"endTime":3213.089,"body":"Um, uh, and talking about dragons, \u003claugh\u003e and uh, and adding, uh, an uh, and"},{"startTime":3213.089,"endTime":3214.685,"body":"antibiotic resistant, uh, bacteria."},{"startTime":3215.305,"endTime":3220.967,"body":"Um, can you sort of give us a bit more insight into, um, the, uh,"},{"startTime":3220.967,"endTime":3226.63,"body":"how, how often we're able to create new antibiotics versus the speed at which the,"},{"startTime":3226.63,"endTime":3230.405,"body":"uh, the, the, the bacteria are trying to beat us?"},{"startTime":3230.635,"endTime":3230.925,"body":"Yeah."},{"startTime":3230.945,"endTime":3232.525,"body":"Uh, it's another bad news story, I'm afraid."},{"startTime":3232.525,"endTime":3235.666,"body":"So one does not equal the other and it's not in our favor at the"},{"startTime":3235.666,"endTime":3236.085,"body":"moment, \u003claugh\u003e."},{"startTime":3236.145,"endTime":3240.06,"body":"Um, so, so how often, how rapidly we can develop antibiotics, it's actually a bit"},{"startTime":3240.06,"endTime":3241.365,"body":"different how often we have."},{"startTime":3241.425,"endTime":3245.198,"body":"So we have not developed new antibiotics at all much in the last sort of"},{"startTime":3245.198,"endTime":3246.205,"body":"40 or 50 years."},{"startTime":3246.705,"endTime":3249.085,"body":"Um, and that is largely for two reasons."},{"startTime":3249.185,"endTime":3250.565,"body":"One of all, people thought it was fixed."},{"startTime":3250.585,"endTime":3254.125,"body":"We thought 1960s, great, give people antibiotics, job done, no need for research."},{"startTime":3254.485,"endTime":3256.725,"body":"Secondly, they're not very economically rewarding."},{"startTime":3256.725,"endTime":3260.059,"body":"If you're an investor, a drug that you only use for a very brief period"},{"startTime":3260.059,"endTime":3263.394,"body":"of time in a few people who get sick and actually needs to be quite"},{"startTime":3263.394,"endTime":3266.285,"body":"cheap as otherwise they're not gonna take it, is not a great investment."},{"startTime":3266.545,"endTime":3270.236,"body":"Versus something like a monoclonal antibody for cancer where you might be taking it for"},{"startTime":3270.236,"endTime":3272.205,"body":"years and it costs huge amount of money."},{"startTime":3272.305,"endTime":3274.685,"body":"So there has not been much investment in the market."},{"startTime":3275.385,"endTime":3279.341,"body":"How, if we can get over that economic hurdle, how easy is it about new"},{"startTime":3279.341,"endTime":3279.605,"body":"antibiotics?"},{"startTime":3279.605,"endTime":3282.325,"body":"There's a lot of activity now in looking in the natural environment."},{"startTime":3282.465,"endTime":3286.565,"body":"So many antibiotics come from other species that create them as a kind of way"},{"startTime":3286.565,"endTime":3288.205,"body":"of microbial warfare that's quite promising."},{"startTime":3288.555,"endTime":3292.085,"body":"Most recently, one of the most exciting things is directed antibiotic production."},{"startTime":3292.085,"endTime":3296.093,"body":"So you can look at a protein, for example, a bacteria really needs and design"},{"startTime":3296.093,"endTime":3298.765,"body":"a molecule that might fit and make it stop working."},{"startTime":3299.425,"endTime":3303.405,"body":"Um, that is sort of in its infancy, but kind of starting to come."},{"startTime":3303.625,"endTime":3305.725,"body":"So I'm, I guess I'm cautiously optimistic."},{"startTime":3305.725,"endTime":3307.965,"body":"I think we have the ability to solve this problem."},{"startTime":3308.425,"endTime":3310.405,"body":"Uh, like, but it's a bit like climate change."},{"startTime":3310.405,"endTime":3311.805,"body":"We have the ability to reverse climate change."},{"startTime":3311.805,"endTime":3312.565,"body":"Will we do it in time?"},{"startTime":3312.965,"endTime":3313.645,"body":"Hmm, good question."},{"startTime":3314.125,"endTime":3319.125,"body":"\u003claugh\u003e."},{"startTime":3315.165,"endTime":3315.325,"body":"Excellent."},{"startTime":3315.505,"endTime":3317.565,"body":"Um, uh, gentleman back,"},{"startTime":3321.105,"endTime":3326.063,"body":"Uh, coming back to the SM test, is there any evidence of a difference between"},{"startTime":3326.063,"endTime":3331.021,"body":"populations where women can choose husbands and where the husband had chosen for them so"},{"startTime":3331.021,"endTime":3333.005,"body":"that the SM test wouldn't apply?"},{"startTime":3334.635,"endTime":3338.965,"body":"Yeah, so, so that's, so the, the choice of partner is a very interesting thing."},{"startTime":3338.965,"endTime":3343.133,"body":"So, so there will be differences because obviously what you might choose for your children,"},{"startTime":3343.133,"endTime":3347.302,"body":"for example, or in the case of think about royal family, where sort of your,"},{"startTime":3347.302,"endTime":3351.471,"body":"your citizens kind of nudge you in a direction of a political reasons, um, are"},{"startTime":3351.471,"endTime":3355.085,"body":"not necessarily evolutionary functions, but they are nonetheless, they have an evolutionary impact."},{"startTime":3355.425,"endTime":3359.795,"body":"So for instance, if you think about, um, uh, the British royal family, uh, you"},{"startTime":3359.795,"endTime":3364.166,"body":"know, going back a couple hundred years where there's this very strong incentive for European"},{"startTime":3364.166,"endTime":3368.537,"body":"stability, um, and you know, it's no sort of big surprise that, uh, genetic disorders"},{"startTime":3368.537,"endTime":3372.325,"body":"like hemophilia were more common in the British royal family into fairly recently."},{"startTime":3372.625,"endTime":3377.525,"body":"Uh, because essentially you are, you are breeding within a, a less diverse gene pool"},{"startTime":3377.525,"endTime":3379.485,"body":"than the rest of us commoners."},{"startTime":3379.825,"endTime":3382.765,"body":"Um, so, so those kind of processes do still influence evolution."},{"startTime":3383.225,"endTime":3386.98,"body":"Um, I think one of the, one of the most interesting things is that very"},{"startTime":3386.98,"endTime":3390.485,"body":"often the reason you're choosing partners is based on sort of cultural behavioral things."},{"startTime":3390.825,"endTime":3394.654,"body":"Um, and, and many of those are, there probably is a genetic component, but it's"},{"startTime":3394.654,"endTime":3395.165,"body":"much weaker."},{"startTime":3395.265,"endTime":3398.49,"body":"You know, you are, there's no evidence, for example, there's genetic inheritance of the kind"},{"startTime":3398.49,"endTime":3399.565,"body":"of religion you might have."},{"startTime":3399.565,"endTime":3403.941,"body":"There is actually some evidence that how, uh, religious or not you are is partially"},{"startTime":3403.941,"endTime":3404.525,"body":"genetically determined."},{"startTime":3404.705,"endTime":3407.911,"body":"Um, but your choice of whether you're Christian or Muslim or anything else is not"},{"startTime":3407.911,"endTime":3408.125,"body":"driven."},{"startTime":3408.125,"endTime":3411.48,"body":"But that has been historically a very big driver of who you were, um, you"},{"startTime":3411.48,"endTime":3414.165,"body":"know, married off to either from yourself or from from your parents."},{"startTime":3414.425,"endTime":3418.105,"body":"So those kind of genetic effects are probably much weaker in human society, but, you"},{"startTime":3418.105,"endTime":3420.805,"body":"know, look hard enough, you might find some of those influences."},{"startTime":3422.225,"endTime":3424.365,"body":"Um, I, I'll take another one on online there."},{"startTime":3424.405,"endTime":3429.642,"body":"A couple of people asked, um, quite similar questions about the, uh, the extent to"},{"startTime":3429.642,"endTime":3434.88,"body":"which, um, you, you, you, when you look at your dog example, we've transformed dogs"},{"startTime":3434.88,"endTime":3437.325,"body":"in size and shape, um, quite dramatically."},{"startTime":3437.945,"endTime":3441.976,"body":"Um, but we haven't done the same with other domesticated animals in quite the same"},{"startTime":3441.976,"endTime":3442.245,"body":"scale."},{"startTime":3442.545,"endTime":3448.938,"body":"Is is there a reason that we haven't done that level of change in other"},{"startTime":3448.938,"endTime":3449.365,"body":"animals?"},{"startTime":3449.995,"endTime":3453.965,"body":"Yeah, so, so largely I think that's about what your sort of objective is."},{"startTime":3453.965,"endTime":3454.725,"body":"So we have done that."},{"startTime":3454.725,"endTime":3459.245,"body":"I mean, cattle, pigs, chickens, you know, chicken derives from a jungle fowl."},{"startTime":3459.245,"endTime":3460.725,"body":"There's not a lot of similarity between this anymore."},{"startTime":3460.745,"endTime":3463.365,"body":"So, so we have massively done it in some species."},{"startTime":3463.785,"endTime":3464.205,"body":"Others."},{"startTime":3464.385,"endTime":3468.401,"body":"So cats are a good example where actually cats are much less sort of, you"},{"startTime":3468.401,"endTime":3469.205,"body":"know, uh, precise."},{"startTime":3469.205,"endTime":3471.645,"body":"They're obviously breeds of cats, but they're not quite as, as diverse."},{"startTime":3471.755,"endTime":3474.481,"body":"Some people would say that's 'cause cats have domesticated us rather than the other way"},{"startTime":3474.481,"endTime":3474.845,"body":"around \u003claugh\u003e."},{"startTime":3474.865,"endTime":3476.205,"body":"Um, uh, but, but that's true."},{"startTime":3476.305,"endTime":3481.433,"body":"Uh, there are no real genetic barriers to that with the slight exception that inbreeding"},{"startTime":3481.433,"endTime":3483.485,"body":"is generally quite a bad thing."},{"startTime":3483.545,"endTime":3486.986,"body":"So you, you start to accrue these, uh, mutations, um, and depending on the amount"},{"startTime":3486.986,"endTime":3490.428,"body":"of these mutations that are present in the original stock, that may be a bigger"},{"startTime":3490.428,"endTime":3491.805,"body":"problem for some breeds than others."},{"startTime":3492.145,"endTime":3494.045,"body":"Um, so, so, but there's no real barriers."},{"startTime":3494.125,"endTime":3497.407,"body":"It's largely just about which species we have sort of chosen, if you like to"},{"startTime":3497.407,"endTime":3497.845,"body":"select for"},{"startTime":3498.635,"endTime":3498.925,"body":"True."},{"startTime":3499.425,"endTime":3501.725,"body":"Um, any more questions in the room?"},{"startTime":3502.825,"endTime":3507.645,"body":"Uh, okay, so I'll, I'll I'll take, uh, 1, 1, 1 last one, uh, online."},{"startTime":3508.185,"endTime":3513.144,"body":"Um, and that's, uh, would we, where we've developed resistance to antibiotics, uh, what about,"},{"startTime":3513.144,"endTime":3518.103,"body":"uh, other forms of drugs such as, uh, where for painkillers will they follow the"},{"startTime":3518.103,"endTime":3518.765,"body":"same path?"},{"startTime":3519.505,"endTime":3522.983,"body":"So for drugs that work on humans, they won't, unless obviously unless they kill the"},{"startTime":3522.983,"endTime":3526.462,"body":"human, in which case it's quite a strong selective pressure, but there's also quite a"},{"startTime":3526.462,"endTime":3529.245,"body":"strong pressure on drug companies not to design drugs that kill people."},{"startTime":3529.785,"endTime":3534.357,"body":"Um, so, so that we, where, but a, a drug that works on another organism,"},{"startTime":3534.357,"endTime":3537.405,"body":"um, would, would potentially select it in the same way."},{"startTime":3537.705,"endTime":3540.818,"body":"Um, and so for example, one of the very interesting areas is not really a"},{"startTime":3540.818,"endTime":3543.725,"body":"drug is, is the gut microbiomes a lot of interest in the gut microbiome."},{"startTime":3543.825,"endTime":3547.89,"body":"People starting to change their diet or their behavior and stuff in a way that"},{"startTime":3547.89,"endTime":3549.245,"body":"will influence their gut microbiome."},{"startTime":3550.005,"endTime":3553.605,"body":"Evolutionary speaking, the gut microbiome or the organisms in it will then also evolve in"},{"startTime":3553.605,"endTime":3554.325,"body":"response to that."},{"startTime":3554.325,"endTime":3557.719,"body":"So if we all start eating more, I dunno, yogurt, um, what you will find"},{"startTime":3557.719,"endTime":3561.113,"body":"is that the organisms in your gut adapt to that and start to evolve in"},{"startTime":3561.113,"endTime":3562.245,"body":"a way that uses it."},{"startTime":3562.245,"endTime":3565.267,"body":"And, uh, you know, let's find out a couple of thousand years from now, maybe"},{"startTime":3565.267,"endTime":3567.685,"body":"we'll all have, you know, McDonald's optimized, uh, microbiomes, who knows \u003claugh\u003e,"},{"startTime":3568.545,"endTime":3569.525,"body":"Uh, ladies and gentlemen."},{"startTime":3569.525,"endTime":3573.372,"body":"Uh, so an air of sadness, I have to actually draw proceedings for a close"},{"startTime":3573.372,"endTime":3573.885,"body":"this evening."},{"startTime":3574.145,"endTime":3578.535,"body":"Um, we have had only so many Gresham college lectures, which have managed to combine"},{"startTime":3578.535,"endTime":3582.925,"body":"into one talk for the inevitable extinction of the human species and sweaty t-shirt \u003claugh\u003e."},{"startTime":3583.385,"endTime":3588.832,"body":"Um, uh, please join me in thanking this evening speaker, our Gresham College professor of"},{"startTime":3588.832,"endTime":3590.285,"body":"physics, professor Robin, me."}]}