{"version":"1.0.0","segments":[{"startTime":5.035,"endTime":6.045,"body":"Good evening everybody."},{"startTime":6.055,"endTime":7.245,"body":"Thank you so much for coming."},{"startTime":7.295,"endTime":10.365,"body":"Thank you to those joining us online, uh, from your sofa."},{"startTime":10.535,"endTime":11.845,"body":"Great to have you as ever."},{"startTime":12.265,"endTime":15.085,"body":"Uh, this is my second lecture in this series about evolution."},{"startTime":15.305,"endTime":19.55,"body":"And for those of you who have seen the first one, you'll know, we talked"},{"startTime":19.55,"endTime":19.833,"body":"a bit about, uh, evolutionary ideas, where they came from, why they're important, and maybe"},{"startTime":19.833,"endTime":20.116,"body":"why they're more important today than they were even when they were first thought of"},{"startTime":20.116,"endTime":28.325,"body":"today."},{"startTime":28.365,"endTime":32.725,"body":"I want to take a slightly different tack and talk about randomness in evolution."},{"startTime":33.025,"endTime":37.6,"body":"Um, and the reason I want to talk about that is because I think people"},{"startTime":37.6,"endTime":41.565,"body":"quite often sort of labor under this illusion about what evolution is like."},{"startTime":41.905,"endTime":43.565,"body":"Um, and quite often that's wrong."},{"startTime":44.505,"endTime":49.318,"body":"So very often we think of evolution, and sometimes we picture it like this, um,"},{"startTime":49.318,"endTime":51.565,"body":"exactly like this, like a linear process."},{"startTime":51.705,"endTime":56.141,"body":"We started out billions of years ago as a kind of simple blob down here,"},{"startTime":56.141,"endTime":57.325,"body":"um, very little structure."},{"startTime":57.745,"endTime":60.685,"body":"And over time, life has got more and more complex."},{"startTime":61.025,"endTime":64.682,"body":"Um, and if you go back particularly to the Victorian era, you can see these"},{"startTime":64.682,"endTime":67.365,"body":"rather wonderful posters in which, you know, everything else is irrelevant."},{"startTime":67.365,"endTime":71.665,"body":"And the pinnacle of evolution is humanity, preferably a guy with a big beard, actually"},{"startTime":71.665,"endTime":72.525,"body":"in Victorian era."},{"startTime":72.865,"endTime":77.421,"body":"Um, and, and obviously that was the, uh, the, the kind of culmination of evolutionary"},{"startTime":77.421,"endTime":77.725,"body":"processes."},{"startTime":78.385,"endTime":81.045,"body":"Um, and nothing actually could be further from the truth."},{"startTime":81.185,"endTime":82.845,"body":"Uh, evolution is certainly not linear."},{"startTime":83.225,"endTime":84.685,"body":"It doesn't have a master plan."},{"startTime":84.685,"endTime":87.965,"body":"We're not all traipsing our way towards some kind of ultimate goal."},{"startTime":88.265,"endTime":90.445,"body":"Um, it is at its heart random."},{"startTime":90.785,"endTime":94.525,"body":"Um, and in particular it is diverse and it is branched."},{"startTime":95.145,"endTime":97.525,"body":"So if you think about that, it makes a lot of sense, right?"},{"startTime":97.525,"endTime":101.62,"body":"If we map out every species, uh, on the planet, they're all related to each"},{"startTime":101.62,"endTime":103.805,"body":"other in some kind of large tree-like way."},{"startTime":103.805,"endTime":108.386,"body":"And this is a very old diagram, um, from actually not long after Darwin published"},{"startTime":108.386,"endTime":108.692,"body":"his book, but showing already at that stage, people thinking about evolution, uh, as a"},{"startTime":108.692,"endTime":113.885,"body":"tree of branches."},{"startTime":114.585,"endTime":119.319,"body":"Uh, and the really important thing to think about, of course, is that branches split,"},{"startTime":119.319,"endTime":119.635,"body":"they grow, uh, but they also end all the time species are going extinct, things"},{"startTime":119.635,"endTime":124.685,"body":"are stopping."},{"startTime":125.105,"endTime":129.163,"body":"Uh, there are entire branches of this evolutionary tree that no longer exist."},{"startTime":129.465,"endTime":131.525,"body":"Um, and that is part of the natural process."},{"startTime":132.865,"endTime":137.615,"body":"Uh, and broadly speaking, extinction is just as important as creation of new species in"},{"startTime":137.615,"endTime":138.565,"body":"terms of evolution."},{"startTime":138.825,"endTime":143.085,"body":"Uh, and species go extinct, really, uh, for one of kind of three reasons."},{"startTime":144.425,"endTime":148.782,"body":"The first and the one we think about most often is they can be poorly"},{"startTime":148.782,"endTime":150.525,"body":"adapted to the environment they're in."},{"startTime":150.525,"endTime":152.325,"body":"Typically, they were quite well adapted."},{"startTime":152.395,"endTime":156.205,"body":"Something has changed in the environment, and now they are less well adapted."},{"startTime":156.425,"endTime":158.845,"body":"Um, and the unfortunate dodo is a good example of that."},{"startTime":159.105,"endTime":164.131,"body":"Um, being a big fat flightless pigeon on an island, uh, was actually really good"},{"startTime":164.131,"endTime":164.466,"body":"idea for a long period of time, millions of years probably, um, until Dutch sailors"},{"startTime":164.466,"endTime":164.801,"body":"arrived, uh, and realized that being a large flightless pigeon on an island was an"},{"startTime":164.801,"endTime":175.525,"body":"excellent source of protein."},{"startTime":175.945,"endTime":179.125,"body":"Um, and within 50 or 60 years, of course, the dodo was extinct."},{"startTime":179.505,"endTime":181.245,"body":"It was well adapted to its environment."},{"startTime":181.465,"endTime":185.485,"body":"The environment changed by the introduction of another species, IE humans."},{"startTime":185.985,"endTime":187.645,"body":"Um, and it was then maladapted."},{"startTime":187.645,"endTime":191.005,"body":"It couldn't fly away, couldn't run away, uh, and became extinct."},{"startTime":191.065,"endTime":193.165,"body":"And species go extinct like that all the time."},{"startTime":193.165,"endTime":196.285,"body":"When the environment changes, it gets hotter or colder."},{"startTime":196.395,"endTime":200.365,"body":"Food sources change, predators appear, predators disappear."},{"startTime":200.665,"endTime":202.125,"body":"All sorts of things, uh, change."},{"startTime":202.985,"endTime":205.885,"body":"But that's not the only reason why species go extinct."},{"startTime":206.675,"endTime":210.525,"body":"They can also go extinct if they're out competed by a similar lineage."},{"startTime":210.525,"endTime":215.559,"body":"They haven't changed in their, uh, adaptations and the environment hasn't really changed, but a"},{"startTime":215.559,"endTime":218.245,"body":"competitor has come in and has displaced them."},{"startTime":218.245,"endTime":221.408,"body":"And this, of course, is something that is sort of happening as we speak in"},{"startTime":221.408,"endTime":222.885,"body":"the United Kingdom to the red squirrel."},{"startTime":223.265,"endTime":225.885,"body":"So the red squirrel is our endemic native squirrel."},{"startTime":226.585,"endTime":231.342,"body":"Um, uh, and, uh, as you know, uh, the gray squirrel introduced from the Americas"},{"startTime":231.342,"endTime":233.245,"body":"is bigger, faster, um, more aggressive."},{"startTime":233.425,"endTime":238.508,"body":"But in particular, the gray squirrel carries a disease squirrel ps uh, to which it"},{"startTime":238.508,"endTime":239.525,"body":"is fairly resistant."},{"startTime":239.525,"endTime":241.125,"body":"And red squirrels definitely are not."},{"startTime":241.505,"endTime":245.865,"body":"Um, and so the red squirrel has been pushed really into a very marginal species"},{"startTime":245.865,"endTime":249.645,"body":"in the United Kingdom by competition from a closely related, uh, other species."},{"startTime":249.705,"endTime":254.299,"body":"And this idea of species, species competition happens quite a lot and is quite a"},{"startTime":254.299,"endTime":255.525,"body":"common cause of extinction."},{"startTime":257.545,"endTime":261.82,"body":"But the, the cause of extinction that I want to dwell on for a moment"},{"startTime":261.82,"endTime":265.525,"body":"tonight, um, is this one the entirely arbitrary and random cause of extinction."},{"startTime":265.665,"endTime":268.933,"body":"And the most famous example of that, of course, is the one, um, that you"},{"startTime":268.933,"endTime":269.805,"body":"have the illustrated here."},{"startTime":270.105,"endTime":274.655,"body":"Uh, this is the collision with a meteorite that is now, uh, well understood to"},{"startTime":274.655,"endTime":279.205,"body":"have brought to a close the era of the dinosaurs about 66 million years ago."},{"startTime":279.785,"endTime":284.818,"body":"Um, and so this big lump of rock, we estimate about, uh, 10 kilometers, six"},{"startTime":284.818,"endTime":285.153,"body":"miles wide collided with the earth, caused an unbelievable ecosystem upheaval, uh, and led to"},{"startTime":285.153,"endTime":294.885,"body":"the extinction of we estimate three out of every four species present at the time."},{"startTime":295.835,"endTime":300.405,"body":"This is not an event to which you can be adaptively optimized by evolution, right?"},{"startTime":300.405,"endTime":303.605,"body":"There are not species out there that are kind of bulletproof to asteroid impacts."},{"startTime":303.905,"endTime":307.317,"body":"Um, this is random and it is so random because if that asteroid had been,"},{"startTime":307.317,"endTime":307.545,"body":"you know, a few miles to the left or a few miles to the right,"},{"startTime":307.545,"endTime":313.005,"body":"much earlier in its journey, it would not have collided."},{"startTime":313.305,"endTime":316.71,"body":"And who knows what would've happened, but whatever it was, we wouldn't have had this"},{"startTime":316.71,"endTime":317.165,"body":"mass extinction."},{"startTime":317.425,"endTime":319.845,"body":"Um, and, and, uh, eradication of the dinosaurs."},{"startTime":321.225,"endTime":323.245,"body":"So chance plays quite an important role."},{"startTime":323.585,"endTime":327.501,"body":"Um, and the important thing about chance is that it has lots and lots of"},{"startTime":327.501,"endTime":328.285,"body":"knock on implications."},{"startTime":328.745,"endTime":334.002,"body":"So clearly, when a species go extinct, there are big losers, not least the species"},{"startTime":334.002,"endTime":335.405,"body":"that has gone extinct."},{"startTime":335.405,"endTime":338.885,"body":"It was probably quite depressing, um, to be a dinosaur and go extinct, I imagine."},{"startTime":338.965,"endTime":342.165,"body":"I dunno, maybe it's great to be extinct, but, but the dinosaurs themselves lost out"},{"startTime":342.165,"endTime":342.805,"body":"by going extinct."},{"startTime":342.805,"endTime":347.885,"body":"But of course, so did lots of other species about which we know absolutely nothing."},{"startTime":348.175,"endTime":354.873,"body":"There were, however, undoubtedly things like tape worms specific to different dinosaurs, um, parasitic invertebrates,"},{"startTime":354.873,"endTime":361.125,"body":"fleas, mites, lice, um, that we know today are typically very, uh, ho specific."},{"startTime":361.385,"endTime":365.885,"body":"And so it's probable, in fact, I would say almost undoubtedly, uh, true that the"},{"startTime":365.885,"endTime":368.285,"body":"dinosaurs had their own species living on them."},{"startTime":368.555,"endTime":372.787,"body":"They might have had, for example, invertebrates that fed on their d all of which"},{"startTime":372.787,"endTime":375.045,"body":"went extinct when the in dinosaurs went extinct."},{"startTime":375.045,"endTime":379.485,"body":"So there is a knock on consequence of extinction to many, many other species."},{"startTime":379.985,"endTime":383.39,"body":"We tend to get kinda less wedded as, as humans, you know, we get very"},{"startTime":383.39,"endTime":384.525,"body":"worried about rhinos going extinct."},{"startTime":384.525,"endTime":386.285,"body":"We don't worry so much about the rhino tapeworm."},{"startTime":386.335,"endTime":387.005,"body":"Maybe we should."},{"startTime":387.225,"endTime":390.956,"body":"Um, but nonetheless, those species do, uh, get a knock on impact at the same"},{"startTime":390.956,"endTime":391.205,"body":"time."},{"startTime":392.825,"endTime":396.925,"body":"But as well as losers during extinction, you have of course winners."},{"startTime":397.305,"endTime":401.388,"body":"Um, and say for example, this image here, uh, these two little chaps are what's"},{"startTime":401.388,"endTime":402.205,"body":"called Sids Sids."},{"startTime":402.585,"endTime":407.478,"body":"Um, these were organism small animals, um, that were present at the time of the"},{"startTime":407.478,"endTime":407.805,"body":"dinosaurs."},{"startTime":408.105,"endTime":413.645,"body":"Um, and they were largely fairly small in, in physique, um, and we believe nocturnal."},{"startTime":414.305,"endTime":418.019,"body":"And the reason they were fairly small and nocturnal, uh, was because if they had"},{"startTime":418.019,"endTime":418.267,"body":"evolved to be fairly big and roam around by day, uh, they would've been eaten"},{"startTime":418.267,"endTime":422.725,"body":"by things like this."},{"startTime":423.265,"endTime":426.645,"body":"Um, so they were sort of forced into this ecological niche."},{"startTime":427.025,"endTime":431.729,"body":"You can think of things like mice and rats today, um, by hiding from the"},{"startTime":431.729,"endTime":433.925,"body":"dominant predator type dinosaurs at the time."},{"startTime":435.305,"endTime":439.611,"body":"So when the asteroid came along and wiped out these chaps, there was a big"},{"startTime":439.611,"endTime":439.898,"body":"fat ecological niche into which this lineage could expand, and that is exactly what it"},{"startTime":439.898,"endTime":444.205,"body":"did."},{"startTime":444.205,"endTime":448.765,"body":"And Therapsids went on to form the basis of all, uh, modern mammalian species."},{"startTime":449.505,"endTime":454.535,"body":"Um, and it's pretty reasonable to argue that had that mass extinction not happened and"},{"startTime":454.535,"endTime":459.565,"body":"the dinosaurs not been wiped out, therapsids would never have evolved into this mammalian lineage."},{"startTime":459.745,"endTime":462.948,"body":"And actually the world as we know it would look radically different, uh, except that"},{"startTime":462.948,"endTime":463.161,"body":"we wouldn't know it 'cause we wouldn't be here either since we descend from this"},{"startTime":463.161,"endTime":466.365,"body":"lineage."},{"startTime":467.225,"endTime":472.485,"body":"So that chance event has shaped evolution for the following 66 million years."},{"startTime":474.455,"endTime":480.365,"body":"These kind of chance effects, these massive asteroid strikes are fortunately, uh, very, very rare."},{"startTime":480.785,"endTime":483.278,"body":"Um, they do happen, but they are, they are pretty rare on the scale of"},{"startTime":483.278,"endTime":483.445,"body":"things."},{"startTime":483.465,"endTime":488.285,"body":"But that doesn't mean that random chance is not an important feature in evolution."},{"startTime":488.285,"endTime":492.665,"body":"In fact, it's a very important feature in a much less dramatic, but much more"},{"startTime":492.665,"endTime":494.125,"body":"common, uh, sort of way."},{"startTime":494.865,"endTime":498.485,"body":"You don't need mass extinctions to show the importance of chance."},{"startTime":499.545,"endTime":502.749,"body":"Um, and, uh, to illustrate that, let me go back to, uh, an illustration I"},{"startTime":502.749,"endTime":504.885,"body":"did in my previous lecture, those who've seen it before."},{"startTime":505.025,"endTime":506.325,"body":"Uh, you can doze off for a minute."},{"startTime":506.325,"endTime":507.885,"body":"Those who haven't, um, stick with me."},{"startTime":508.305,"endTime":511.685,"body":"So, uh, let's imagine there's a species, uh, that has arisen."},{"startTime":511.685,"endTime":512.765,"body":"This is a blue blob here."},{"startTime":513.025,"endTime":516.645,"body":"Uh, and the basic principle of evolution is that species reproduce."},{"startTime":516.715,"endTime":518.044,"body":"They over reproduce."},{"startTime":518.044,"endTime":522.164,"body":"They typically produce more offspring than can be supported by the environment they're in."},{"startTime":522.985,"endTime":528.662,"body":"Um, and genetic processes such as mutation, recombination, um, pairing, if you're in a, if"},{"startTime":528.662,"endTime":533.205,"body":"you're a sexually reproducing organism, uh, lead to diversity in your offspring."},{"startTime":533.205,"endTime":535.925,"body":"So your offspring don't all look exactly like you do."},{"startTime":536.905,"endTime":540.861,"body":"Um, and they're, they have different phenotypes, they have different abilities to survive in the"},{"startTime":540.861,"endTime":541.125,"body":"environment."},{"startTime":541.185,"endTime":545.125,"body":"The ones that are not well suited to their environment then, uh, die very rapidly."},{"startTime":545.305,"endTime":547.725,"body":"Say for example here, the little red star, that was a bad organism."},{"startTime":547.755,"endTime":548.205,"body":"It's gone."},{"startTime":549.065,"endTime":552.005,"body":"Um, but some new diversity is retained."},{"startTime":552.025,"endTime":555.683,"body":"And over time, if that new diversity is optimal for the environment, uh, they will"},{"startTime":555.683,"endTime":555.927,"body":"go on to reproduce and you'll end up with new species, for example, over time"},{"startTime":555.927,"endTime":560.805,"body":"and so on and so forth."},{"startTime":560.805,"endTime":562.885,"body":"That species might then diversify some more."},{"startTime":563.065,"endTime":566.085,"body":"Um, and, uh, this is what leads to that, that tree of life."},{"startTime":567.785,"endTime":570.485,"body":"So, um, that is the basic process of evolution."},{"startTime":570.485,"endTime":571.725,"body":"But let's, let's run that clock again."},{"startTime":571.885,"endTime":573.085,"body":"So imagine the same process here."},{"startTime":573.085,"endTime":574.525,"body":"We have the original founder organism."},{"startTime":574.585,"endTime":575.525,"body":"It has its offspring."},{"startTime":575.525,"endTime":577.725,"body":"Some offspring are not well suited, they die."},{"startTime":578.385,"endTime":582.355,"body":"Um, but at this point here, you have two offspring, which are essentially equally well"},{"startTime":582.355,"endTime":586.325,"body":"suited to the environment and in the previous image go off to form two lineages."},{"startTime":587.065,"endTime":590.279,"body":"But imagine this is happening back in the era of the dinosaurs in the, in"},{"startTime":590.279,"endTime":591.565,"body":"a kind of warm puddle somewhere."},{"startTime":591.785,"endTime":596.095,"body":"And at that very moment, a passing, I'd know iguanodon or something, puts its foot"},{"startTime":596.095,"endTime":600.405,"body":"wrong and steps on one of these lineages, it's gone extinct before it even existed."},{"startTime":600.745,"endTime":604.33,"body":"And now you have reshaped the entire rest of the tree because now you haven't"},{"startTime":604.33,"endTime":605.525,"body":"got a lineage down here."},{"startTime":605.825,"endTime":611.285,"body":"So that chance effect, that squishing of that early microbe has changed the subsequent evolution."},{"startTime":612.025,"endTime":613.245,"body":"That's one sort of chance of effect."},{"startTime":613.245,"endTime":614.085,"body":"But what about a second one?"},{"startTime":614.085,"endTime":616.565,"body":"So imagine this other lineage is still going like it did before."},{"startTime":617.035,"endTime":618.485,"body":"It's evolving in a normal way."},{"startTime":618.485,"endTime":620.765,"body":"So it's producing offspring that are slightly different."},{"startTime":620.765,"endTime":623.925,"body":"So here we have, for example, two dark blue ones and a pale blue ones."},{"startTime":624.705,"endTime":630.125,"body":"In the previous example there is continued growing and diversifying the same place."},{"startTime":630.265,"endTime":633.746,"body":"But imagine now in that muddy puddle back in sort of the dinosaur era, um,"},{"startTime":633.746,"endTime":633.978,"body":"there is some kind of current, I know that it rains and, and the water"},{"startTime":633.978,"endTime":640.245,"body":"washes one direction or the wind blows and the droplet goes somewhere else."},{"startTime":640.705,"endTime":646.039,"body":"Um, and what happens, uh, by chance, completely by chance, is these two slightly different"},{"startTime":646.039,"endTime":648.885,"body":"organisms are in different places, different physical places."},{"startTime":649.785,"endTime":652.405,"body":"And now imagine that some kind of barrier comes between them."},{"startTime":652.425,"endTime":655.791,"body":"So maybe they've, you know, it rained a lot and they washed out and then"},{"startTime":655.791,"endTime":658.485,"body":"it stopped raining and now it's dry and they can't get back."},{"startTime":659.825,"endTime":663.165,"body":"You now have two slightly different organisms in two slightly different places."},{"startTime":663.195,"endTime":665.165,"body":"They can't reintroduce to each other."},{"startTime":665.665,"endTime":667.485,"body":"Um, but they carry on, they reproduce."},{"startTime":667.485,"endTime":672.085,"body":"And what you end up with essentially are two populations that are different and isolated"},{"startTime":672.085,"endTime":673.005,"body":"from each other."},{"startTime":673.865,"endTime":677.147,"body":"And if millions of years later, a biologist like me comes along and has a"},{"startTime":677.147,"endTime":677.365,"body":"look at it, they might think to themselves, oh, well clearly this one here is"},{"startTime":677.365,"endTime":677.584,"body":"well adapted to this environment and there's something different up there that makes that blue"},{"startTime":677.584,"endTime":684.805,"body":"one better adapted to it."},{"startTime":684.805,"endTime":685.405,"body":"But that's not true."},{"startTime":685.585,"endTime":687.765,"body":"That's, this is a random process, right?"},{"startTime":688.425,"endTime":693.604,"body":"And this process of randomness, um, is, has been a really big shaping factor, um,"},{"startTime":693.604,"endTime":693.949,"body":"in the evolution of many, many species and is a process that we know today"},{"startTime":693.949,"endTime":700.165,"body":"as the founder effect."},{"startTime":700.945,"endTime":704.181,"body":"Um, and to illustrate the founder facts, I'm going to, I'm going to borrow a"},{"startTime":704.181,"endTime":705.045,"body":"volunteer if I may."},{"startTime":705.265,"endTime":707.165,"body":"Um, does anyone care to come up front?"},{"startTime":707.785,"endTime":708.325,"body":"Be brave."},{"startTime":709.545,"endTime":710.525,"body":"Oh, someone dropped something."},{"startTime":710.525,"endTime":711.685,"body":"That's an excellent volunteer."},{"startTime":711.685,"endTime":712.045,"body":"Come on."},{"startTime":712.045,"endTime":712.405,"body":"Who was that?"},{"startTime":712.405,"endTime":714.485,"body":"Who dropped something and wants to, wants to admit it?"},{"startTime":714.485,"endTime":718.285,"body":"I promise I'd retain you unharmed in a few moments, but maybe I can, maybe"},{"startTime":718.285,"endTime":719.045,"body":"I can borrow."},{"startTime":719.045,"endTime":720.925,"body":"Can I borrow this gentleman on the end there with the beard?"},{"startTime":720.925,"endTime":722.005,"body":"Are you brave enough to come up?"},{"startTime":722.395,"endTime":723.325,"body":"Yeah, come on."},{"startTime":723.395,"endTime":723.685,"body":"Come."},{"startTime":724.225,"endTime":725.685,"body":"You say what happens if no one volunteers?"},{"startTime":725.685,"endTime":726.685,"body":"We have to volunteer somebody."},{"startTime":727.235,"endTime":729.813,"body":"This is the moment to run away if your family don't know you are here"},{"startTime":729.813,"endTime":730.845,"body":"and they think something really important."},{"startTime":731.165,"endTime":731.325,"body":"Excellent."},{"startTime":731.415,"endTime":733.085,"body":"Thank you so much for having, what's your name, sorry?"},{"startTime":733.295,"endTime":733.645,"body":"Feris."},{"startTime":733.855,"endTime":734.205,"body":"Feris."},{"startTime":734.275,"endTime":735.765,"body":"Okay, so welcome on board."},{"startTime":735.765,"endTime":736.245,"body":"Thank you very much."},{"startTime":736.315,"endTime":737.725,"body":"It's got a really difficult task for you."},{"startTime":737.745,"endTime":742.205,"body":"So here, um, I have a population of organisms, other organisms are available."},{"startTime":742.225,"endTime":743.725,"body":"If you're watching this, I'll cover the brand name."},{"startTime":743.865,"endTime":746.325,"body":"So there's a population of diverse organisms like the ones here."},{"startTime":746.665,"endTime":748.605,"body":"Now, what I'd like to do is grab a big handful of those."},{"startTime":750.035,"endTime":751.765,"body":"Well, oh, this is a man who's done this before."},{"startTime":751.765,"endTime":752.525,"body":"Look at that, right?"},{"startTime":752.825,"endTime":754.525,"body":"And we're going to distribute those on this."},{"startTime":754.525,"endTime":754.965,"body":"Thank you."},{"startTime":755.145,"endTime":759.461,"body":"So what we've done here, we have samples of population, um, of organisms, and it"},{"startTime":759.461,"endTime":760.325,"body":"is very diverse."},{"startTime":760.545,"endTime":765.205,"body":"So if you take this population somewhere new like that might puddle, it will grow."},{"startTime":765.205,"endTime":767.974,"body":"And you'll still have organisms that look a bit like this and organisms that look"},{"startTime":767.974,"endTime":770.005,"body":"like a bit like this and so on and so forth."},{"startTime":770.365,"endTime":770.805,"body":"Excellent example."},{"startTime":771.065,"endTime":773.645,"body":"But now do that again."},{"startTime":773.645,"endTime":776.405,"body":"Take a smaller handful, smaller than that."},{"startTime":776.885,"endTime":777.965,"body":"\u003claugh\u003e, I see you've done this before."},{"startTime":777.965,"endTime":778.485,"body":"That's much better."},{"startTime":778.485,"endTime":778.845,"body":"Well done."},{"startTime":778.845,"endTime":779.365,"body":"Thank you very much."},{"startTime":780.065,"endTime":782.005,"body":"God, don't invite him to your party below me."},{"startTime":782.145,"endTime":786.33,"body":"Um, so now we have a very small population and now we have only two"},{"startTime":786.33,"endTime":787.725,"body":"organisms, two types of organisms."},{"startTime":788.025,"endTime":789.645,"body":"So we've got in our island."},{"startTime":789.945,"endTime":792.365,"body":"Now, uh, these two organisms, they're reproducing."},{"startTime":792.365,"endTime":794.885,"body":"But this one, for example, is essentially extinct."},{"startTime":795.005,"endTime":795.765,"body":"'cause it wasn't picked."},{"startTime":796.235,"endTime":797.765,"body":"This is a founder effect."},{"startTime":798.025,"endTime":801.725,"body":"You've picked a small number, other genes have been left somewhere else."},{"startTime":802.185,"endTime":806.997,"body":"And now whatever happens to this population, unless new organisms come in, can only ever"},{"startTime":806.997,"endTime":810.205,"body":"involve the genes that are present in these two organisms."},{"startTime":810.465,"endTime":811.925,"body":"And that is a founder effect."},{"startTime":811.925,"endTime":812.965,"body":"And you get the chocolates as a present."},{"startTime":812.965,"endTime":813.645,"body":"Thank you very much."},{"startTime":814.225,"endTime":815.805,"body":"Bra round of applause for our volunteer."},{"startTime":819.465,"endTime":821.405,"body":"You didn't get the whole handful up, you just be greedy."},{"startTime":821.435,"endTime":821.725,"body":"Okay?"},{"startTime":821.725,"endTime":822.685,"body":"So that's a founder effect."},{"startTime":822.685,"endTime":827.308,"body":"Founder effects happen when a small chunk of a population by chance, are separated from"},{"startTime":827.308,"endTime":827.925,"body":"the other."},{"startTime":828.265,"endTime":832.322,"body":"And all the genes that are not present in those individuals are therefore not present"},{"startTime":832.322,"endTime":833.405,"body":"in the subsequent lineage."},{"startTime":833.705,"endTime":835.485,"body":"Um, and they happen quite a lot in evolution."},{"startTime":835.485,"endTime":841.599,"body":"They particularly happen in geographical sites where you have restrictions to the movement of organisms"},{"startTime":841.599,"endTime":844.045,"body":"in and out such as islands."},{"startTime":844.145,"endTime":847.045,"body":"So islands very often exhibit founder effects."},{"startTime":847.545,"endTime":849.861,"body":"Um, and there are lots and lots of examples of this, but this is one"},{"startTime":849.861,"endTime":850.325,"body":"of my favorites."},{"startTime":850.325,"endTime":853.658,"body":"So this island here, dunno if anyone's been, this is Dennie, this is one of"},{"startTime":853.658,"endTime":854.325,"body":"the channel islands."},{"startTime":854.325,"endTime":859.275,"body":"So just off the coast of France, it's very, very small island and Dennie, um,"},{"startTime":859.275,"endTime":860.925,"body":"does not have native hedgehogs."},{"startTime":861.035,"endTime":861.325,"body":"Okay?"},{"startTime":861.325,"endTime":865.15,"body":"So the rest of the United Kingdom, um, has hedgehogs that they like this, but"},{"startTime":865.15,"endTime":867.445,"body":"all the new does not, didn't have native hedgehogs."},{"startTime":867.445,"endTime":872.287,"body":"However, in, uh, the 1950s and sixties, um, some slightly, uh, uh, you know, probably"},{"startTime":872.287,"endTime":876.485,"body":"unwise individuals, they decide what they do is they keep some pet hedgehogs."},{"startTime":876.485,"endTime":877.045,"body":"So they're quite cute."},{"startTime":877.585,"endTime":881.55,"body":"Um, and then in a story that is very familiar for human intervention all around"},{"startTime":881.55,"endTime":881.815,"body":"the globe, of course the pet hedgehogs escaped, um, and thought, wow, it's a whole"},{"startTime":881.815,"endTime":886.045,"body":"island here."},{"startTime":886.045,"endTime":886.645,"body":"This is brilliant."},{"startTime":886.865,"endTime":888.645,"body":"Um, and set up a, a population."},{"startTime":888.645,"endTime":890.045,"body":"So now Als has hedgehogs."},{"startTime":890.555,"endTime":894.696,"body":"However, if you go to Alny and look at their hedgehogs, um, roughly 50% of"},{"startTime":894.696,"endTime":898.285,"body":"the hedgehogs that you might pick from Alden knee, uh, look like this."},{"startTime":898.305,"endTime":898.965,"body":"How cute is that?"},{"startTime":898.965,"endTime":902.365,"body":"That is a blonde hedgehog, um, blonde hedgehog."},{"startTime":902.365,"endTime":905.045,"body":"So this is a mutation, uh, not an albino mutation."},{"startTime":905.045,"endTime":906.725,"body":"It's called a istic, uh, mutation."},{"startTime":906.745,"endTime":909.005,"body":"It cause them to be paler colored."},{"startTime":909.875,"endTime":915.134,"body":"It's a mutation that occurs in, uh, the native hedgehog population at an incredibly low"},{"startTime":915.134,"endTime":915.485,"body":"frequency."},{"startTime":915.485,"endTime":916.285,"body":"It's very, very rare."},{"startTime":916.835,"endTime":922.469,"body":"However, by complete chance, we believe the Albany population started from about four or five"},{"startTime":922.469,"endTime":922.845,"body":"individuals."},{"startTime":923.025,"endTime":927.685,"body":"And by complete chance, one of those individuals presumably carried this mutation."},{"startTime":927.875,"endTime":930.045,"body":"It's a recessive mutation, so you don't see it."},{"startTime":930.205,"endTime":933.565,"body":"A hedgehog like this could actually still have one copy of that gene."},{"startTime":934.025,"endTime":935.565,"body":"Um, but it was present in that hedgehog."},{"startTime":935.705,"endTime":940.453,"body":"And because the entire population descends only from those four or five individuals, now this"},{"startTime":940.453,"endTime":944.885,"body":"is a very common mutation on Albany, even though it's still rare everywhere else."},{"startTime":945.185,"endTime":950.232,"body":"So this is a founder effect, and it's happened because the original population was small"},{"startTime":950.232,"endTime":952.925,"body":"and there has not been incoming gene flow."},{"startTime":952.955,"endTime":956.161,"body":"It's not that hedgehogs, you know, swim across the alderney from the mainland, uh, to,"},{"startTime":956.161,"endTime":958.085,"body":"to, you know, go and find a new partner."},{"startTime":958.425,"endTime":961.085,"body":"Um, they are stuck, they're trapped in this sort of genetic island."},{"startTime":962.025,"endTime":965.365,"body":"And those kind of, uh, founder effects happen a lot."},{"startTime":965.625,"endTime":968.085,"body":"Uh, not only in islands, things like mountain tops."},{"startTime":968.085,"endTime":971.818,"body":"Also, if you're a, an isolated mountain peak and there are no other mountains around,"},{"startTime":971.818,"endTime":972.565,"body":"that's another example."},{"startTime":972.865,"endTime":976.495,"body":"Um, and in the sea you have it as well where you have areas, for"},{"startTime":976.495,"endTime":980.125,"body":"example, of particularly shallow water or particularly deep water surrounded by other types of water."},{"startTime":982.505,"endTime":985.765,"body":"So founder effects is quite important and they are chance, it's completely random, right?"},{"startTime":985.785,"endTime":989.441,"body":"The fact that there was a blond gene present in that hedgehog, um, was not"},{"startTime":989.441,"endTime":989.685,"body":"predictive."},{"startTime":989.685,"endTime":990.445,"body":"It was not adaptive."},{"startTime":990.555,"endTime":993.445,"body":"It's not a benefit in Albany, it's just chance."},{"startTime":994.825,"endTime":999.0,"body":"Um, they're kinda interesting to ecologists, but much more interesting to, uh, to me as"},{"startTime":999.0,"endTime":999.278,"body":"someone who's particularly interested in human uh, and human disease in particular, the fact that"},{"startTime":999.278,"endTime":1004.845,"body":"these effects also happen in humans."},{"startTime":1005.795,"endTime":1007.965,"body":"They can happen in humans for the same reason."},{"startTime":1008.145,"endTime":1012.885,"body":"So populations that were geographically very isolated can also show founder effects."},{"startTime":1012.905,"endTime":1017.687,"body":"But of course, today the vast majority of the world, the human world is not"},{"startTime":1017.687,"endTime":1018.325,"body":"geographically isolated."},{"startTime":1018.325,"endTime":1020.325,"body":"You can get on an airplane and go almost anywhere."},{"startTime":1021.305,"endTime":1026.03,"body":"Um, and yet we still see founder effects and we see them not for geographical"},{"startTime":1026.03,"endTime":1027.605,"body":"isolation, but for cultural isolation."},{"startTime":1028.065,"endTime":1032.927,"body":"So in particular, the place we see them most often are in human societies, uh,"},{"startTime":1032.927,"endTime":1033.251,"body":"which practice what we call endo omy, IE, the idea that you would only marry"},{"startTime":1033.251,"endTime":1042.005,"body":"or mate with somebody from the same cultural, societal, religious group as yourself."},{"startTime":1042.385,"endTime":1047.697,"body":"Uh, so for example, uh, these are often orthodox religious groups like the Amish Orthodox"},{"startTime":1047.697,"endTime":1050.885,"body":"Judaism, um, but also they can be cultural constraints."},{"startTime":1050.885,"endTime":1055.622,"body":"So if you're from a culture with a very strict social hierarchy and you're only"},{"startTime":1055.622,"endTime":1060.045,"body":"expected to marry within your social strata, um, that's another form of genetic isolation."},{"startTime":1060.545,"endTime":1062.405,"body":"Um, and sometimes there are all sorts of other reasons."},{"startTime":1062.405,"endTime":1065.957,"body":"There can be even just, uh, sort of cultural reasons in the sense that you"},{"startTime":1065.957,"endTime":1068.325,"body":"have a particular belief system, not necessarily religious belief system."},{"startTime":1068.485,"endTime":1073.051,"body":"I know you are a, um, a extremely passionate vegan and you will only associate"},{"startTime":1073.051,"endTime":1073.965,"body":"with other vegans."},{"startTime":1073.965,"endTime":1077.085,"body":"That's a, that's a type of genetic isolationism as well."},{"startTime":1078.705,"endTime":1083.608,"body":"So these are small populations, and particularly in the case of many religious groups, um,"},{"startTime":1083.608,"endTime":1083.935,"body":"who essentially fled persecution typically in Europe, um, to, uh, the Americas is the most"},{"startTime":1083.935,"endTime":1089.165,"body":"common destination."},{"startTime":1089.835,"endTime":1092.845,"body":"Many of those originating populations were very small, right?"},{"startTime":1092.845,"endTime":1094.765,"body":"So the Amish, for example, is a great example."},{"startTime":1095.275,"endTime":1099.843,"body":"Very small groups of people from Europe fled to America, um, and essentially have remained"},{"startTime":1099.843,"endTime":1100.147,"body":"isolated because they rarely, uh, marry and have children outside of that group for a"},{"startTime":1100.147,"endTime":1105.325,"body":"long period afterwards."},{"startTime":1105.385,"endTime":1108.565,"body":"And so that is the condition in which you find founder effects."},{"startTime":1108.865,"endTime":1112.853,"body":"Um, and we do find them quite commonly because the way they present most often"},{"startTime":1112.853,"endTime":1116.045,"body":"or the most visible if you like, are when they cause problems."},{"startTime":1116.515,"endTime":1120.405,"body":"Most of the human founder effects we know about are genetic diseases."},{"startTime":1120.705,"endTime":1125.165,"body":"Um, so for instance, there is a particularly awful disease called Tacs."},{"startTime":1125.595,"endTime":1128.365,"body":"Tacs disease is a neurodegenerative disease."},{"startTime":1128.475,"endTime":1133.322,"body":"It's caused by the lack of an enzyme hexa a if you don't have enough"},{"startTime":1133.322,"endTime":1133.645,"body":"of that enzyme, when you are born, uh, your nerves fail to develop properly and"},{"startTime":1133.645,"endTime":1141.725,"body":"you end up with a, a, a really awful neurodegenerative condition."},{"startTime":1142.025,"endTime":1145.775,"body":"Uh, and typically babies born with sacs, uh, degenerate over two or three years and"},{"startTime":1145.775,"endTime":1147.525,"body":"typically die before they go to school."},{"startTime":1148.995,"endTime":1152.205,"body":"This disease is extremely rare in the globe as a whole."},{"startTime":1152.205,"endTime":1155.725,"body":"It's about one in 300,000, uh, live births across the globe."},{"startTime":1156.065,"endTime":1161.068,"body":"But in particular populations, including the Armes Orthodox today that Ashkenazi Jewish populations, um, this"},{"startTime":1161.068,"endTime":1165.405,"body":"is about a hundred times more common than it is in other populations."},{"startTime":1165.665,"endTime":1170.242,"body":"And it's because when those populations were founded, the, the frequency of that gene was"},{"startTime":1170.242,"endTime":1170.547,"body":"higher by chance than it is in the rest of the population and has been"},{"startTime":1170.547,"endTime":1175.125,"body":"retained."},{"startTime":1176.465,"endTime":1180.381,"body":"And it's really important, um, to think about these things, I think because of the"},{"startTime":1180.381,"endTime":1181.165,"body":"implications they have."},{"startTime":1181.165,"endTime":1185.707,"body":"And actually, one of the interesting examples of this founder effect, so this mutation that"},{"startTime":1185.707,"endTime":1189.645,"body":"causes sax is also found in another founder effect, um, in Jacob's sheep."},{"startTime":1189.905,"endTime":1195.501,"body":"So, uh, these many livestock breeds, especially pedigree livestock breeds also suffer from founder effects"},{"startTime":1195.501,"endTime":1195.875,"body":"because they typically originate from a very small number of, um, original Ghana grandparents, if"},{"startTime":1195.875,"endTime":1201.845,"body":"you like."},{"startTime":1202.025,"endTime":1206.278,"body":"And those of us who have, for example, dogs, quite often there are particular dog"},{"startTime":1206.278,"endTime":1209.965,"body":"breeds that are associated with genetic problems because of the same founder effects."},{"startTime":1210.195,"endTime":1214.474,"body":"It's got an interesting example where the same mutations crops up in two completely unrelated,"},{"startTime":1214.474,"endTime":1215.045,"body":"uh, organisms."},{"startTime":1216.305,"endTime":1218.285,"body":"So why is it important to know about founder effects?"},{"startTime":1218.285,"endTime":1222.328,"body":"Well, the first and almost obvious reason for thinking about founder effects is because it"},{"startTime":1222.328,"endTime":1224.485,"body":"can help with medical treatment and medical diagnosis."},{"startTime":1224.505,"endTime":1228.587,"body":"And in fact, um, in terms of Tay Sachs disease, uh, uh, the Jewish population"},{"startTime":1228.587,"endTime":1232.125,"body":"in, in the US in particular has taken this very strongly on board."},{"startTime":1232.125,"endTime":1236.41,"body":"And now a very, very large number of people, uh, undergo genetic testing before marrying"},{"startTime":1236.41,"endTime":1238.125,"body":"and before having children in order."},{"startTime":1238.185,"endTime":1241.835,"body":"And that has really helped a lot in reducing, um, the number of babies born"},{"startTime":1241.835,"endTime":1242.565,"body":"with this disease."},{"startTime":1242.745,"endTime":1246.66,"body":"So it can help in terms of preventing, um, we can't treat taste acts in"},{"startTime":1246.66,"endTime":1247.965,"body":"that condition in other conditions."},{"startTime":1247.965,"endTime":1249.925,"body":"It can of course help, uh, with treatment too."},{"startTime":1250.785,"endTime":1256.33,"body":"But it's also really important when we think about things like, uh, human intervention in"},{"startTime":1256.33,"endTime":1256.7,"body":"ecosystems and in particular when we think about conserving endangered species, because by definition endangered"},{"startTime":1256.7,"endTime":1263.725,"body":"species have very few individuals."},{"startTime":1264.225,"endTime":1268.296,"body":"Um, and so if we are doing things like a captive breeding program, it's really"},{"startTime":1268.296,"endTime":1269.925,"body":"important to think about founder effects."},{"startTime":1269.945,"endTime":1275.003,"body":"And that's one of the reasons why, for instance, um, international zoo organizations often trade"},{"startTime":1275.003,"endTime":1275.34,"body":"individual animals to make sure that they're not getting these founder effects where they're all"},{"startTime":1275.34,"endTime":1282.085,"body":"locked into the same genetic background."},{"startTime":1282.085,"endTime":1285.998,"body":"So I think there's a lot of useful learning from understanding this and knowing about"},{"startTime":1285.998,"endTime":1288.085,"body":"the scale of the impact of those mutations."},{"startTime":1289.515,"endTime":1293.913,"body":"Also, of course, applies when we think about much more direct human interventions, in particular"},{"startTime":1293.913,"endTime":1294.206,"body":"livestock or crop breeding where, you know, you can inadvertently, you select for a particular"},{"startTime":1294.206,"endTime":1298.605,"body":"trait."},{"startTime":1298.725,"endTime":1302.7,"body":"I know red tomatoes or you know, beautiful petunias, but you are bringing with it"},{"startTime":1302.7,"endTime":1305.085,"body":"a number of other genetic changes in the background."},{"startTime":1305.085,"endTime":1309.127,"body":"And if you're not careful, you can get these subtle genetic, uh, uh, founder effects"},{"startTime":1309.127,"endTime":1310.205,"body":"in those situations too."},{"startTime":1312.315,"endTime":1313.605,"body":"Okay, so that's enough about founder effects."},{"startTime":1313.605,"endTime":1316.794,"body":"Let's think a bit more about kind of what's going on in the chance level"},{"startTime":1316.794,"endTime":1317.645,"body":"in terms of evolution."},{"startTime":1317.865,"endTime":1322.121,"body":"So I said a few slides ago, the basic principle of evolution is stuff is"},{"startTime":1322.121,"endTime":1322.405,"body":"changing."},{"startTime":1322.505,"endTime":1326.245,"body":"You can't prevent that even if you are a clonal organism like a bacteria."},{"startTime":1326.955,"endTime":1331.005,"body":"Even so your offspring are not genetically identical because of the rate of mutation."},{"startTime":1331.225,"endTime":1336.04,"body":"So there is this permanent changing of genes in a population, something that we refer"},{"startTime":1336.04,"endTime":1337.325,"body":"to as genetic drift."},{"startTime":1337.355,"endTime":1341.382,"body":"This idea that even if you do nothing at all, the types of genes in"},{"startTime":1341.382,"endTime":1342.725,"body":"the population change over time."},{"startTime":1343.985,"endTime":1347.053,"body":"Um, and uh, this has been something that has concerned or has people have thought"},{"startTime":1347.053,"endTime":1348.485,"body":"about for well over a hundred years."},{"startTime":1348.585,"endTime":1353.516,"body":"Now, how does that kind of random process equate to, uh, adaptation to a particular"},{"startTime":1353.516,"endTime":1353.845,"body":"environment?"},{"startTime":1354.105,"endTime":1356.805,"body":"So let's think about, um, this process of genetic drift."},{"startTime":1356.805,"endTime":1361.738,"body":"And the person who thought most about this was the pioneering geneticist back in about"},{"startTime":1361.738,"endTime":1362.725,"body":"1930 Sewell Wright."},{"startTime":1362.985,"endTime":1367.605,"body":"And he introduced this idea of a fitness landscape that looks something like this."},{"startTime":1368.145,"endTime":1373.534,"body":"In other words, if you think about, uh, any organism, an organism is, uh, existing"},{"startTime":1373.534,"endTime":1378.205,"body":"in a, in a environment, that environment varies over time and over space."},{"startTime":1378.745,"endTime":1382.292,"body":"Um, and typically most organisms are quite well adapted to the environment they're in at"},{"startTime":1382.292,"endTime":1382.765,"body":"the minute."},{"startTime":1383.225,"endTime":1386.445,"body":"Uh, but, uh, there are potentially better combinations."},{"startTime":1386.465,"endTime":1390.554,"body":"So here is a fitness landscape, and if you imagine what we're looking at here,"},{"startTime":1390.554,"endTime":1390.826,"body":"there are places, uh, where you are very well adapted, like down here in the"},{"startTime":1390.826,"endTime":1391.099,"body":"valleys and places where actually your particular complement of genes is not good for that"},{"startTime":1391.099,"endTime":1399.005,"body":"environment."},{"startTime":1399.105,"endTime":1400.125,"body":"Up here on the peaks."},{"startTime":1400.505,"endTime":1404.429,"body":"So here we have a little organism and it's sitting in a valley, it's well"},{"startTime":1404.429,"endTime":1407.045,"body":"adapted, it could be even better adapted over here, right?"},{"startTime":1407.045,"endTime":1407.845,"body":"This is even better."},{"startTime":1408.585,"endTime":1414.635,"body":"But to get there, it has got to change its genes over this maladaptive, over"},{"startTime":1414.635,"endTime":1415.845,"body":"this disadvantageous peak."},{"startTime":1416.705,"endTime":1421.379,"body":"So actually, when you think about random chance, so this organism's gonna reproduce, it's gonna"},{"startTime":1421.379,"endTime":1421.69,"body":"change its gene slightly on average, what's gonna happen is it's gonna become less fit,"},{"startTime":1421.69,"endTime":1426.365,"body":"okay?"},{"startTime":1426.365,"endTime":1427.605,"body":"It's going halfway up the mountain."},{"startTime":1427.955,"endTime":1431.885,"body":"Because essentially, if you think about, I dunno, think about a piano for example."},{"startTime":1432.095,"endTime":1434.805,"body":"There are about a hundred thousand ways you can break a piano."},{"startTime":1435.175,"endTime":1437.845,"body":"There are very few ways you can make a piano even better."},{"startTime":1438.145,"endTime":1439.485,"body":"And that is the same for genes."},{"startTime":1439.485,"endTime":1442.085,"body":"There are lots and lots of mutations that will wreck a gene."},{"startTime":1442.455,"endTime":1446.045,"body":"There are very few mutations that will improve the function of that gene."},{"startTime":1446.585,"endTime":1449.325,"body":"So most of the time when an organism mutates, it gets worse."},{"startTime":1449.785,"endTime":1454.261,"body":"Um, and therefore what happens over time is that natural selection eliminates those changes and"},{"startTime":1454.261,"endTime":1457.245,"body":"pushes it back to where it was in the beginning."},{"startTime":1457.395,"endTime":1459.405,"body":"This is called stabilizing selection."},{"startTime":1460.745,"endTime":1464.221,"body":"So how then might you as an organism evolve from this position to an even"},{"startTime":1464.221,"endTime":1464.685,"body":"better position?"},{"startTime":1464.685,"endTime":1465.885,"body":"There are sort of two routes really."},{"startTime":1466.185,"endTime":1470.215,"body":"Um, you can do something really dramatic and we'll talk about that in a minute"},{"startTime":1470.215,"endTime":1470.484,"body":"or, um, what you can do is you can gain a mutation, for example, that"},{"startTime":1470.484,"endTime":1470.753,"body":"is actually on its own not particularly good, but if it's not selected against very"},{"startTime":1470.753,"endTime":1471.021,"body":"fast, you might be able to retain that mutation in the background for a period"},{"startTime":1471.021,"endTime":1482.845,"body":"of time."},{"startTime":1483.305,"endTime":1488.069,"body":"And then perhaps another mutation will come on board, which is beneficial and pushes you"},{"startTime":1488.069,"endTime":1491.245,"body":"therefore right over the edge into this new better location."},{"startTime":1491.305,"endTime":1494.465,"body":"So there is a, there is a chance process of just hanging on long enough"},{"startTime":1494.465,"endTime":1494.676,"body":"and it's a bit like, I dunno, if you had sort of revising for an"},{"startTime":1494.676,"endTime":1494.886,"body":"exam, there's that moment if you remember that when you're revising, you think, God, I"},{"startTime":1494.886,"endTime":1503.525,"body":"feel like I know less now than I did when I started revising."},{"startTime":1503.665,"endTime":1507.205,"body":"But if you keep going, keep going, eventually you realize that you've kind of pushed"},{"startTime":1507.205,"endTime":1509.565,"body":"forwards and you now know more than you did before."},{"startTime":1510.665,"endTime":1512.925,"body":"And this process we see in the fossil record."},{"startTime":1513.025,"endTime":1516.536,"body":"So for example, someone at the last lecture asked me a bit about the evolution"},{"startTime":1516.536,"endTime":1517.005,"body":"of flight."},{"startTime":1517.225,"endTime":1518.565,"body":"And this is quite a good example."},{"startTime":1518.705,"endTime":1520.605,"body":"So this is a fossil early bird."},{"startTime":1520.825,"endTime":1524.125,"body":"Uh, and you can see up here just about I think these little stubby wings."},{"startTime":1524.945,"endTime":1528.125,"body":"Um, this bird probably couldn't fly very well."},{"startTime":1528.545,"endTime":1533.723,"body":"Um, uh, it may not even have been as good as the flightless equivalent that"},{"startTime":1533.723,"endTime":1534.068,"body":"went before, but if those little stubby wings were not hugely disadvantageous and were retained"},{"startTime":1534.068,"endTime":1543.045,"body":"long enough, then additional mutations might have pushed those wings even further."},{"startTime":1543.465,"endTime":1545.525,"body":"And now you have a fully flighted bird."},{"startTime":1545.525,"endTime":1550.662,"body":"So you can go through this less fit intermediate to become a more optimal, uh,"},{"startTime":1550.662,"endTime":1551.005,"body":"organism."},{"startTime":1551.995,"endTime":1554.605,"body":"There's a second important point about this random process."},{"startTime":1554.865,"endTime":1559.32,"body":"So this is a reconstruct reconstruction, uh, of op tricks, one of the very early"},{"startTime":1559.32,"endTime":1560.805,"body":"birds that we know about."},{"startTime":1560.805,"endTime":1562.685,"body":"And you can see here it's got it little stubby wings."},{"startTime":1562.825,"endTime":1566.021,"body":"It remains a bit unclear where the arch tricks could really, really fly or whether"},{"startTime":1566.021,"endTime":1568.365,"body":"it could just glide or kind of flap around a bit."},{"startTime":1568.625,"endTime":1572.402,"body":"Um, but either way it was probably not, I mean, it's not flying like an"},{"startTime":1572.402,"endTime":1574.165,"body":"albatross, it was not a spectacular flyer."},{"startTime":1574.825,"endTime":1578.845,"body":"Um, uh, and yet it was sort of on its way to become a fully"},{"startTime":1578.845,"endTime":1581.525,"body":"flighted, uh, bird, uh, like for example the Arctic 10."},{"startTime":1581.525,"endTime":1586.403,"body":"But there's a really important point here, which is that it is almost impossible for"},{"startTime":1586.403,"endTime":1589.005,"body":"evolution to go backwards, directly backwards at least."},{"startTime":1589.005,"endTime":1593.164,"body":"So if you remember on that previous fitness landscape you had, you know, it was,"},{"startTime":1593.164,"endTime":1593.441,"body":"it was relatively fit here somewhere, it went up the mountain came a long way"},{"startTime":1593.441,"endTime":1601.205,"body":"down the other side, going back up a very high mountain is incredibly difficult."},{"startTime":1601.225,"endTime":1604.045,"body":"And so it is with real evolution in real life."},{"startTime":1604.385,"endTime":1608.967,"body":"If you think of arches, if conditions changed and having these little stubby wings was"},{"startTime":1608.967,"endTime":1609.273,"body":"not a good thing, natural selection could fairly easily have selected for mutants that got"},{"startTime":1609.273,"endTime":1616.605,"body":"smaller and smaller wings and went back the other way."},{"startTime":1617.745,"endTime":1622.365,"body":"If you're an Arctic 10, you are optimally evolved for life in the air."},{"startTime":1622.365,"endTime":1624.405,"body":"You're an incredible precision flying machine."},{"startTime":1625.025,"endTime":1629.69,"body":"Any mutation that messes with your wings is gonna be so strongly selected against it"},{"startTime":1629.69,"endTime":1634.045,"body":"will be extremely difficult for you to evolve back to an unf flighted version."},{"startTime":1634.105,"endTime":1635.245,"body":"And we see that again and again."},{"startTime":1635.245,"endTime":1640.451,"body":"So what tends to happen instead is organisms become specialized more and more specialized and"},{"startTime":1640.451,"endTime":1640.798,"body":"then ultimately go extinct rather than des specializing back into some more generic organism over"},{"startTime":1640.798,"endTime":1646.005,"body":"time."},{"startTime":1647.545,"endTime":1652.592,"body":"So that process of sort of, of gentle genetic drift and selection across the landscape"},{"startTime":1652.592,"endTime":1652.929,"body":"is something that happens a lot in many species, but it's not the only way"},{"startTime":1652.929,"endTime":1661.005,"body":"that you can have new, um, innovation if you like."},{"startTime":1661.005,"endTime":1667.141,"body":"In evolution, you can also have these processes called genetic shifts, really big leaps in"},{"startTime":1667.141,"endTime":1670.005,"body":"evolution and they're much harder to understand."},{"startTime":1670.005,"endTime":1673.476,"body":"So here we are in our fitness landscape, again, here's our little organism and there"},{"startTime":1673.476,"endTime":1676.485,"body":"is a place on this landscape where the organism can be even fitter."},{"startTime":1676.755,"endTime":1677.925,"body":"It's right over here, right?"},{"startTime":1678.585,"endTime":1680.605,"body":"But it's got a long journey to get there."},{"startTime":1680.665,"endTime":1686.081,"body":"It would have to have all these disadvantageous mutations and climb this mountain in order"},{"startTime":1686.081,"endTime":1687.165,"body":"to get there."},{"startTime":1687.385,"endTime":1691.244,"body":"It would have to essentially not be selected against, even though it's a bit rubbish"},{"startTime":1691.244,"endTime":1693.045,"body":"for a very long period of time."},{"startTime":1693.045,"endTime":1697.717,"body":"And that is highly unlikely, much more likely, but still very, very unlikely is or"},{"startTime":1697.717,"endTime":1698.029,"body":"much more successful, if you like, would be to do all of this journey in"},{"startTime":1698.029,"endTime":1703.325,"body":"one go, right?"},{"startTime":1703.505,"endTime":1709.205,"body":"To jump right over here, some huge genetic change, nevermind all these incremental mutations, do"},{"startTime":1709.205,"endTime":1713.005,"body":"something really radical and leap over that, that boundary problem."},{"startTime":1714.635,"endTime":1716.725,"body":"What you need is a big genetic innovation."},{"startTime":1716.725,"endTime":1718.205,"body":"But this is very difficult to think about."},{"startTime":1718.265,"endTime":1721.925,"body":"And and there's an example I think we can take from, um, human behaviors here."},{"startTime":1721.945,"endTime":1726.045,"body":"So this is the inside of an internal combustion engine, okay?"},{"startTime":1726.305,"endTime":1729.667,"body":"So for most of us, those of us who drive for most of our driving"},{"startTime":1729.667,"endTime":1731.685,"body":"lives, we've driven something that runs on this, right?"},{"startTime":1731.685,"endTime":1735.0,"body":"You put petrol or diesel in one end and essentially you burn it and it"},{"startTime":1735.0,"endTime":1735.885,"body":"drives your car along."},{"startTime":1736.835,"endTime":1738.165,"body":"This is the internal combustion engine."},{"startTime":1738.165,"endTime":1742.337,"body":"However, for some of us, more recently we've started driving something that looks a bit"},{"startTime":1742.337,"endTime":1744.285,"body":"like this, uh, an electric car, okay?"},{"startTime":1744.985,"endTime":1749.47,"body":"You cannot get from this thing at the back to this thing here by a"},{"startTime":1749.47,"endTime":1750.965,"body":"series of incremental evolutionary steps."},{"startTime":1751.365,"endTime":1754.445,"body":"I can't go into an internal combustion engine and say, oh, you know what?"},{"startTime":1754.445,"endTime":1756.725,"body":"I'll take out the oil, you know, no oil, get rid of that."},{"startTime":1757.105,"endTime":1758.685,"body":"Um, and we'll replace in the air."},{"startTime":1758.955,"endTime":1761.645,"body":"I'll take out, I'd know the car Beretta and put something else in."},{"startTime":1761.945,"endTime":1765.765,"body":"Um, you can't move partially from a petrol engine to an electric engine."},{"startTime":1765.865,"endTime":1767.965,"body":"You either do it in one go or you don't."},{"startTime":1768.985,"endTime":1771.045,"body":"And so it is also with evolution."},{"startTime":1771.045,"endTime":1777.897,"body":"There are some big evolutionary innovations that essentially could only happen in one big go,"},{"startTime":1777.897,"endTime":1779.725,"body":"these radical innovative ideas."},{"startTime":1779.825,"endTime":1783.405,"body":"Now these things are incredibly unlikely to occur, right?"},{"startTime":1783.985,"endTime":1787.97,"body":"But we've had life on this planet for the best part of 4 billion years"},{"startTime":1787.97,"endTime":1789.565,"body":"and it's a really big planet."},{"startTime":1789.905,"endTime":1793.833,"body":"Um, so if you roll enough dice enough times, you know, sometimes you can get"},{"startTime":1793.833,"endTime":1795.405,"body":"25 sixes in a row, right?"},{"startTime":1795.705,"endTime":1799.165,"body":"Um, and these are the kind of radical innovations that we're talking about."},{"startTime":1799.275,"endTime":1803.725,"body":"Very, very rare, but nonetheless, very important for the process of evolution."},{"startTime":1803.725,"endTime":1806.725,"body":"And the example of this that I most like is one that I can show"},{"startTime":1806.725,"endTime":1807.125,"body":"you here."},{"startTime":1807.145,"endTime":1810.727,"body":"So what you see on the screen in front of you, um, is an immune"},{"startTime":1810.727,"endTime":1811.205,"body":"response, okay?"},{"startTime":1811.475,"endTime":1813.725,"body":"This is some work that we did in my, in my other job at Birmingham."},{"startTime":1813.725,"endTime":1816.525,"body":"So this is looking at the response of your T cells."},{"startTime":1816.745,"endTime":1821.461,"body":"You remember those T cells, they're part of your, um, uh, immune response that fights"},{"startTime":1821.461,"endTime":1822.405,"body":"viruses in particular."},{"startTime":1823.385,"endTime":1825.65,"body":"And what you see, in fact, lemme go back and uh, play that one again"},{"startTime":1825.65,"endTime":1826.405,"body":"if it, there we go."},{"startTime":1826.435,"endTime":1828.805,"body":"What you see here is these T cells are the green cells."},{"startTime":1829.715,"endTime":1833.565,"body":"They start off green and if they, if they replicate, they lose their color."},{"startTime":1833.565,"endTime":1837.813,"body":"So what you see over the course, this video is those T cells less and"},{"startTime":1837.813,"endTime":1838.096,"body":"less green because they're busy replicating and they're replicating because they are responding to, uh,"},{"startTime":1838.096,"endTime":1844.045,"body":"an immune response, an immune, um, antigen."},{"startTime":1844.705,"endTime":1847.723,"body":"And that is being presented here by this rather blobby cell you see in the"},{"startTime":1847.723,"endTime":1847.925,"body":"middle."},{"startTime":1847.925,"endTime":1848.925,"body":"This is a dendritic cell."},{"startTime":1849.145,"endTime":1853.495,"body":"Now, hopefully pretty much all of us in this room have fairly recently had AC"},{"startTime":1853.495,"endTime":1854.365,"body":"ovid 19 vaccination."},{"startTime":1854.865,"endTime":1859.256,"body":"Um, and when you've had that or indeed any other vaccination, what you've had is"},{"startTime":1859.256,"endTime":1859.549,"body":"a bit of foreign protein produced in, in various different ways depending on which vaccine"},{"startTime":1859.549,"endTime":1865.405,"body":"you had injected into your body."},{"startTime":1865.435,"endTime":1870.751,"body":"That foreign protein has been picked up by these cells and has been waved around"},{"startTime":1870.751,"endTime":1875.005,"body":"to stimulate T cells and mount an immune response to protect you."},{"startTime":1876.265,"endTime":1880.661,"body":"The way it does that is that your body has something in the order of,"},{"startTime":1880.661,"endTime":1883.885,"body":"you know, 400 billion, uh, T cells floating around inside it."},{"startTime":1884.865,"endTime":1889.205,"body":"Almost every one of those has a different receptor on its surface."},{"startTime":1889.305,"endTime":1893.687,"body":"And this is my rather rubbish cartoon of that, a different receptor on its surface"},{"startTime":1893.687,"endTime":1897.485,"body":"that is looking for foreign proteins, each one specific for a different protein."},{"startTime":1898.225,"endTime":1902.533,"body":"So what happens when you have c ovid 19 vaccination or indeed a covid Ovid"},{"startTime":1902.533,"endTime":1902.82,"body":"19 infection, is that those foreign proteins are being displayed by these cells and T"},{"startTime":1902.82,"endTime":1903.107,"body":"cells are zipping past going, don't recognize it, don't recognize it, don't recognize it, don't"},{"startTime":1903.107,"endTime":1911.725,"body":"recognize it."},{"startTime":1911.945,"endTime":1914.365,"body":"And eventually one goes, oh yeah, that's the one that fits with me."},{"startTime":1914.565,"endTime":1915.405,"body":"Brilliant ta-da."},{"startTime":1915.985,"endTime":1919.805,"body":"And as soon as it does this t-cell then starts reproducing."},{"startTime":1920.065,"endTime":1923.405,"body":"It will mount an immune response against the infection if it's the full virus."},{"startTime":1923.825,"endTime":1927.69,"body":"Um, and regardless of whether it's a virus or a vaccine, it will also produce"},{"startTime":1927.69,"endTime":1930.525,"body":"memory cells, which is what protects you the next time around."},{"startTime":1930.525,"endTime":1932.085,"body":"And that's the principle of vaccination."},{"startTime":1933.065,"endTime":1934.445,"body":"But there's a problem here, right?"},{"startTime":1934.865,"endTime":1940.055,"body":"The human genome has about 20,000 genes in it, and yet you have got billions"},{"startTime":1940.055,"endTime":1945.245,"body":"of T cells with billions of different combinations of t-cell receptor on, on the surface."},{"startTime":1945.785,"endTime":1948.765,"body":"How can 20,000 genes give you a receptor?"},{"startTime":1949.235,"endTime":1953.552,"body":"That varies in such an enormous way and it has to vary in such an"},{"startTime":1953.552,"endTime":1953.84,"body":"enormous way because it is no good being able to recognize any 20,000 proteins, uh,"},{"startTime":1953.84,"endTime":1961.325,"body":"because there are far more proteins on far more pathogens than that."},{"startTime":1961.325,"endTime":1964.245,"body":"You need a much bigger repertoire of things to recognize."},{"startTime":1964.745,"endTime":1967.959,"body":"So we have a problem, you've only got 20,000 genes, but you need to come"},{"startTime":1967.959,"endTime":1969.245,"body":"up with millions of different combinations."},{"startTime":1970.065,"endTime":1973.245,"body":"And that is a problem that has been solved invertebrates."},{"startTime":1973.245,"endTime":1978.805,"body":"So organisms like ourselves, um, by this remarkable process of modular genes."},{"startTime":1979.905,"endTime":1984.535,"body":"So if you look at the gene that encodes that T-cell receptor, it's not a"},{"startTime":1984.535,"endTime":1989.165,"body":"single straightforward gene, it's a gene that is arranged in modules like Lego blocks basically."},{"startTime":1989.345,"endTime":1992.005,"body":"So it has a bunch of blocks over here, another bunch here, another bunch there."},{"startTime":1992.545,"endTime":1996.628,"body":"To make the functional protein, you only need one of these, one of these and"},{"startTime":1996.628,"endTime":1997.445,"body":"one of these."},{"startTime":1998.065,"endTime":2002.722,"body":"And so what happens during the development of each T-cell is that a certain point,"},{"startTime":2002.722,"endTime":2003.965,"body":"an enzyme comes along."},{"startTime":2003.965,"endTime":2008.85,"body":"This one up here, it's called rag and rag cuts up the DNA only at"},{"startTime":2008.85,"endTime":2009.176,"body":"this particular location and sticks it together again in a random way to rearrange those"},{"startTime":2009.176,"endTime":2015.365,"body":"Lego blocks into a receptor."},{"startTime":2016.145,"endTime":2019.245,"body":"And so you can imagine now if you have, I dunno, a bag of red"},{"startTime":2019.245,"endTime":2019.451,"body":"lego and a bag of blue and a bag of yellow, there are lots and"},{"startTime":2019.451,"endTime":2024.205,"body":"lots of different combinations you can make of that."},{"startTime":2024.545,"endTime":2028.502,"body":"And so with a very small number of modules, you can come up with a"},{"startTime":2028.502,"endTime":2030.085,"body":"very large number of T-cell receptors."},{"startTime":2030.745,"endTime":2033.845,"body":"Now the really surprising thing about this, so this is a weird process, right?"},{"startTime":2033.845,"endTime":2037.002,"body":"This is an enzyme that is cutting your own DNA and sticking it together sounds"},{"startTime":2037.002,"endTime":2037.845,"body":"like a bad idea."},{"startTime":2038.345,"endTime":2040.125,"body":"Um, and it doesn't exist anywhere else."},{"startTime":2040.145,"endTime":2044.765,"body":"If you look in evolutionary trees, invertebrates don't have this, plants don't have this."},{"startTime":2044.835,"endTime":2046.845,"body":"Only vertebrates have this, okay?"},{"startTime":2046.845,"endTime":2050.975,"body":"So it arose around the time that fish arose and it arose all of a"},{"startTime":2050.975,"endTime":2054.005,"body":"sudden there's nothing like it in animals that were there before."},{"startTime":2054.304,"endTime":2055.885,"body":"And then tatara is suddenly there."},{"startTime":2056.105,"endTime":2057.364,"body":"And that is really weird."},{"startTime":2057.585,"endTime":2060.764,"body":"How does an entire system evolve in the middle of nowhere?"},{"startTime":2061.344,"endTime":2064.813,"body":"And it feels almost like it's kind of being jettisoned in from outer space or"},{"startTime":2064.813,"endTime":2065.045,"body":"something."},{"startTime":2065.074,"endTime":2066.165,"body":"It's massive innovation."},{"startTime":2066.395,"endTime":2071.78,"body":"It's like that car suddenly going from a combustion engine to a, a battery-based electric"},{"startTime":2071.78,"endTime":2072.139,"body":"engine overnight without figuring out where it's coming from, but it's not coming from outer"},{"startTime":2072.139,"endTime":2077.525,"body":"space."},{"startTime":2077.665,"endTime":2080.565,"body":"In fact, what we now know where it's come from is really quite unique."},{"startTime":2080.565,"endTime":2083.764,"body":"And we know that by looking at the underlying protein that does it."},{"startTime":2084.025,"endTime":2088.215,"body":"So that protein that cuts and sticks your DNA together rag it's called, um, you"},{"startTime":2088.215,"endTime":2088.495,"body":"can make a three dimensional structure of, um, and you don't need to worry about"},{"startTime":2088.495,"endTime":2092.965,"body":"the details."},{"startTime":2093.025,"endTime":2096.085,"body":"The protein is the blue and the yellow EBIT here, okay?"},{"startTime":2096.085,"endTime":2097.365,"body":"So it's like a, it's like a barrel."},{"startTime":2098.185,"endTime":2101.895,"body":"And what you can see here if you're in aficionado is the DNA, which is"},{"startTime":2101.895,"endTime":2105.605,"body":"that double helix here, two strands of DNA going through the middle of the protein."},{"startTime":2106.425,"endTime":2110.643,"body":"So what's happening in your T-cell is this protein is cutting and sticking this DNA"},{"startTime":2110.643,"endTime":2110.925,"body":"together."},{"startTime":2111.905,"endTime":2115.205,"body":"But now if you look in all the other proteins we know about, there's another"},{"startTime":2115.205,"endTime":2115.645,"body":"protein here."},{"startTime":2115.645,"endTime":2118.495,"body":"And I don't think you have to be a biochemist to say, Hey, these two"},{"startTime":2118.495,"endTime":2119.445,"body":"proteins actually look pretty similar."},{"startTime":2119.545,"endTime":2123.245,"body":"So this protein here, the yellow bit looks really like the yellow bit here."},{"startTime":2123.785,"endTime":2126.005,"body":"The biggest difference is what it's doing with the DNA."},{"startTime":2126.005,"endTime":2127.565,"body":"It's folding the DNA in a different way."},{"startTime":2127.825,"endTime":2129.925,"body":"But nonetheless, these two proteins are very similar."},{"startTime":2130.585,"endTime":2133.445,"body":"And this protein has nothing to do with the immune system."},{"startTime":2133.515,"endTime":2137.965,"body":"This is present in, in a, uh, a piece of DNA called a transposon."},{"startTime":2138.585,"endTime":2143.445,"body":"And transposons are selfish pieces of DNA that are found in pretty much all organisms."},{"startTime":2143.445,"endTime":2144.685,"body":"They're a little bit like viruses."},{"startTime":2144.955,"endTime":2149.045,"body":"They sit in your genome, they copy themselves, and they move themselves around."},{"startTime":2149.235,"endTime":2150.485,"body":"They have typically no benefit."},{"startTime":2150.825,"endTime":2152.085,"body":"Uh, in fact they're often detrimental."},{"startTime":2152.085,"endTime":2156.365,"body":"They're kind of parasitic, but they have existed for, well, hundreds of millions of years."},{"startTime":2156.365,"endTime":2159.215,"body":"We we can't go back far enough to find out when they, when they were"},{"startTime":2159.215,"endTime":2159.405,"body":"created."},{"startTime":2160.025,"endTime":2163.205,"body":"Um, and so why, why do these two things look the same?"},{"startTime":2163.205,"endTime":2163.925,"body":"Well, they look the same."},{"startTime":2164.125,"endTime":2168.146,"body":"'cause if you're a transposon, if you're a piece of DNA that needs to replicate"},{"startTime":2168.146,"endTime":2168.414,"body":"and move yourself around, you need an enzyme that cuts yourself and sticks yourself somewhere"},{"startTime":2168.414,"endTime":2174.045,"body":"else, which is what this does here."},{"startTime":2175.225,"endTime":2179.181,"body":"And so what looks like it has happened, in fact we're now pretty convinced it's"},{"startTime":2179.181,"endTime":2179.445,"body":"happened, is during evolution at the time, just prior to the, the origin of vertebrates"},{"startTime":2179.445,"endTime":2179.709,"body":"is presumably a transposon jumped into the DNA of an early, uh, animal that was"},{"startTime":2179.709,"endTime":2189.205,"body":"going to lead to the, to the vertebrates."},{"startTime":2189.745,"endTime":2194.045,"body":"And when it jumped out again, it left behind this gene for this enzyme."},{"startTime":2194.625,"endTime":2199.046,"body":"And over the millions of years since that enzyme has turned out to be rather"},{"startTime":2199.046,"endTime":2199.341,"body":"useful because it can be co-opted into cutting and pasting together these modular gene elements"},{"startTime":2199.341,"endTime":2207.005,"body":"that go to make your t-cell receptors and indeed also your antibodies."},{"startTime":2207.425,"endTime":2212.261,"body":"And so we have borrowed this idea, just like electric cars have borrowed the idea"},{"startTime":2212.261,"endTime":2212.584,"body":"of batteries from mobile phones and everything else, and lifted it lock, stock and barrel"},{"startTime":2212.584,"endTime":2220.645,"body":"into our own physiology in order to drive our immune systems."},{"startTime":2220.665,"endTime":2224.205,"body":"And this is radical innovation evolution style in one game."},{"startTime":2226.545,"endTime":2228.925,"body":"So innovation does happen, randomness happens."},{"startTime":2229.345,"endTime":2233.122,"body":"Um, but I kind of want to end on a, on the, the idea about"},{"startTime":2233.122,"endTime":2234.885,"body":"just how important random luck has been."},{"startTime":2234.885,"endTime":2237.245,"body":"And and before I do that, lemme just take a straw poll here."},{"startTime":2237.545,"endTime":2242.885,"body":"So generally people think of themselves as either being typically lucky or typically unlucky, right?"},{"startTime":2242.885,"endTime":2245.872,"body":"So are are you the kind of person who always hits the red light, especially"},{"startTime":2245.872,"endTime":2246.071,"body":"if you're late or are you the kind of person who you know, gets in"},{"startTime":2246.071,"endTime":2246.27,"body":"just as the train is pulling out and manages to jump into the door and"},{"startTime":2246.27,"endTime":2252.245,"body":"the light?"},{"startTime":2252.245,"endTime":2255.045,"body":"So those of you who think you are lucky, please raise your hand."},{"startTime":2256.435,"endTime":2257.165,"body":"Very interesting."},{"startTime":2257.165,"endTime":2259.205,"body":"And those who think you're unlucky, raise your hand."},{"startTime":2259.985,"endTime":2261.605,"body":"Ooh, it's, well clearly you are here."},{"startTime":2261.665,"endTime":2262.525,"body":"The lucky ones are winning."},{"startTime":2262.525,"endTime":2263.085,"body":"What can I say?"},{"startTime":2263.085,"endTime":2263.925,"body":"You we'll come to the lecture."},{"startTime":2264.425,"endTime":2267.714,"body":"Um, so, so, so what I want to convince you, all of those of you"},{"startTime":2267.714,"endTime":2270.565,"body":"who raised your hand second, who think you're unlucky, you are so wrong."},{"startTime":2270.705,"endTime":2272.045,"body":"You are incredibly lucky."},{"startTime":2272.185,"endTime":2273.285,"body":"All of us are incredibly lucky."},{"startTime":2273.345,"endTime":2276.645,"body":"Let me demonstrate one reason why we're so lucky."},{"startTime":2277.545,"endTime":2281.866,"body":"If you think about human evolution, this is diagram, uh, by Chris Stringer over the"},{"startTime":2281.866,"endTime":2282.154,"body":"Natural History Museum, uh, now slightly outta date, but that shows, uh, the last couple"},{"startTime":2282.154,"endTime":2288.205,"body":"of million years of human evolution, right?"},{"startTime":2288.505,"endTime":2293.335,"body":"So as you maybe know, uh, for most of the time in which human-like organisms"},{"startTime":2293.335,"endTime":2298.165,"body":"have existed, there have been multiple species present on the planet at the same time."},{"startTime":2298.225,"endTime":2302.246,"body":"In fact, this is the moment we are living in is one of the very"},{"startTime":2302.246,"endTime":2302.515,"body":"rare moments when as far as we know, we are the only human-like species on"},{"startTime":2302.515,"endTime":2306.805,"body":"the planet."},{"startTime":2307.065,"endTime":2311.605,"body":"But for most of human history, actually we've shared the planet with other human-like organisms."},{"startTime":2311.705,"endTime":2315.503,"body":"So here, um, going back to one and a half, 2 million years, homoerectus is"},{"startTime":2315.503,"endTime":2316.01,"body":"over here."},{"startTime":2316.155,"endTime":2320.06,"body":"This is for people who are kind of keen on this is what's called the"},{"startTime":2320.06,"endTime":2322.925,"body":"Hobbit, the ensis small, um, uh, small human from, uh, Indonesia."},{"startTime":2323.705,"endTime":2326.045,"body":"But these organisms lived, they they separated."},{"startTime":2326.045,"endTime":2328.605,"body":"We had different species like antecessor, so on and so forth."},{"startTime":2328.605,"endTime":2333.645,"body":"And the only one lineage went on to produce modern homosapiens, uh, which is this"},{"startTime":2333.645,"endTime":2335.325,"body":"heidelberg against this lineage here."},{"startTime":2335.545,"endTime":2340.312,"body":"Uh, that led to Neanderthals, Deni Havens and ourselves and what we now know from"},{"startTime":2340.312,"endTime":2344.445,"body":"work published just a few weeks ago actually, uh, which is quite remarkable."},{"startTime":2344.755,"endTime":2349.45,"body":"What you can do is you can look at all the diversity of modern human"},{"startTime":2349.45,"endTime":2349.763,"body":"genomes and you can work out from that how big the population of humans was"},{"startTime":2349.763,"endTime":2355.085,"body":"at its narrowest."},{"startTime":2355.155,"endTime":2359.533,"body":"Because if you think about that, so if you think more ge genetic diversity must"},{"startTime":2359.533,"endTime":2361.285,"body":"have come from a bigger population."},{"startTime":2361.285,"endTime":2364.525,"body":"So the more narrow you are like that founder effect, the less diverse you have."},{"startTime":2364.525,"endTime":2368.725,"body":"And you can do some very fancy mathematical modeling and you can work out based"},{"startTime":2368.725,"endTime":2369.005,"body":"on, uh, modern human genomes, how many or how few humans there have been at"},{"startTime":2369.005,"endTime":2373.485,"body":"different points."},{"startTime":2373.585,"endTime":2379.563,"body":"And the most remarkable thing about this new work is that it indicates fairly confidently"},{"startTime":2379.563,"endTime":2379.962,"body":"that back about 900,000 years ago, the human population or the population of breeding individuals"},{"startTime":2379.962,"endTime":2390.325,"body":"that led to modern humans was no more than about 1,300 individuals."},{"startTime":2390.825,"endTime":2395.925,"body":"And most remarkably, it was at that level for probably a hundred thousand years."},{"startTime":2397.185,"endTime":2402.122,"body":"So just to put that in perspective, 1,300 individuals is about the same number as"},{"startTime":2402.122,"endTime":2405.085,"body":"we currently have of giant pandas in the wild."},{"startTime":2405.785,"endTime":2410.601,"body":"Uh, and it's 10 times more, uh, than the number of snow leopards we have"},{"startTime":2410.601,"endTime":2411.565,"body":"in the wild."},{"startTime":2412.105,"endTime":2415.245,"body":"Um, it's also slightly smaller than the average secondary school."},{"startTime":2415.665,"endTime":2419.538,"body":"Um, and is roughly the number of people that you are estimated to have met"},{"startTime":2419.538,"endTime":2421.605,"body":"by the time you're about 13 or 14."},{"startTime":2422.265,"endTime":2426.561,"body":"And the hu entire human population was at that level for about a hundred thousand"},{"startTime":2426.561,"endTime":2430.285,"body":"years, a whisker away from extinction for a really long period of time."},{"startTime":2430.825,"endTime":2433.992,"body":"And so I think on that particular note, all of you, especially those of you"},{"startTime":2433.992,"endTime":2434.203,"body":"who think you're unlucky, should actually sit back and think, wow, it's pretty amazing lucky"},{"startTime":2434.203,"endTime":2438.005,"body":"that I'm just here."},{"startTime":2438.545,"endTime":2441.504,"body":"And maybe on your way home after this particular lecture, you could slip into the"},{"startTime":2441.504,"endTime":2442.885,"body":"casino or buy yourself a lottery ticket."},{"startTime":2442.885,"endTime":2444.445,"body":"Just to round off, thank you very much,"},{"startTime":2455.655,"endTime":2456.005,"body":"Robin."},{"startTime":2456.095,"endTime":2456.525,"body":"Thank you."},{"startTime":2456.525,"endTime":2460.96,"body":"That was an absolutely fascinating lecture and I'm sure we're all feeling pretty lucky right"},{"startTime":2460.96,"endTime":2464.805,"body":"now, but let's see if you get quite so lucky on the questions."},{"startTime":2465.525,"endTime":2467.325,"body":"I feel like there should be a drum roll for that \u003claugh\u003e."},{"startTime":2468.665,"endTime":2469.365,"body":"Yep, indeed."},{"startTime":2469.675,"endTime":2475.622,"body":"Okay, so, um, actually I'm gonna combine a couple of questions which are asking sort"},{"startTime":2475.622,"endTime":2477.605,"body":"of, sort of similar things."},{"startTime":2477.705,"endTime":2484.192,"body":"So we have a question from, uh, Bernard, can two species merge eg by interbreeding"},{"startTime":2484.192,"endTime":2488.085,"body":"rather than one replacing the other by out competing?"},{"startTime":2488.085,"endTime":2491.285,"body":"It, isn't this what happened with Neanderthals and us?"},{"startTime":2491.345,"endTime":2494.953,"body":"So that sort of goes back to what you, you were just talking about a"},{"startTime":2494.953,"endTime":2495.194,"body":"moment ago, but I'm gonna combine that with Lawrence's question, which sort of talks roughly"},{"startTime":2495.194,"endTime":2499.525,"body":"similar sort of area."},{"startTime":2500.185,"endTime":2505.233,"body":"If a small population is separated and develops unique traits like the hedgehogs on ,"},{"startTime":2505.233,"endTime":2505.57,"body":"what are the possible effects if they are ever reintroduced and then they sort of"},{"startTime":2505.57,"endTime":2511.965,"body":"breed with the original population."},{"startTime":2511.965,"endTime":2514.005,"body":"So a lot of interbreeding there for you, Robin."},{"startTime":2514.115,"endTime":2517.006,"body":"Yeah, that's one of the things that, one of the delights to work on evolutionary"},{"startTime":2517.006,"endTime":2517.199,"body":"biology is you get to talk about all sorts of inappropriate things like, you know,"},{"startTime":2517.199,"endTime":2522.405,"body":"uh, interbreeding, um, even just to to, you know, to young school children."},{"startTime":2522.705,"endTime":2525.645,"body":"Um, okay, so the first question, can two species recombine?"},{"startTime":2525.645,"endTime":2526.125,"body":"Yes they can."},{"startTime":2526.665,"endTime":2531.852,"body":"Um, so the place that most often happens actually is when you've had, uh, that"},{"startTime":2531.852,"endTime":2534.965,"body":"process that we talked about earlier called allat speciation."},{"startTime":2534.965,"endTime":2539.192,"body":"When something has split geographically to two areas and has then gone off its own"},{"startTime":2539.192,"endTime":2541.165,"body":"particular direction, it can be quite distinct."},{"startTime":2541.385,"endTime":2545.642,"body":"Uh, but then if they're reintroduced, if they're still sexually compatible and able to mate"},{"startTime":2545.642,"endTime":2548.765,"body":"with each other, they they can and do, uh, into breed."},{"startTime":2549.065,"endTime":2550.565,"body":"And there are some quite good examples of that."},{"startTime":2550.565,"endTime":2554.517,"body":"In fact, there are examples if you think about things like, uh, Scottish wildcat in"},{"startTime":2554.517,"endTime":2555.045,"body":"this country."},{"startTime":2555.065,"endTime":2559.421,"body":"So there's quite a big concern that Scottish wildcats, which is an endangered species, um,"},{"startTime":2559.421,"endTime":2562.325,"body":"are capable of interbreeding with domestic cats and indeed do."},{"startTime":2562.705,"endTime":2566.887,"body":"Um, and so, uh, as those, as those two species come together, you see them"},{"startTime":2566.887,"endTime":2567.445,"body":"as assimilating."},{"startTime":2567.445,"endTime":2571.208,"body":"There is quite a concern that the wildcat will no longer exist because essentially everything"},{"startTime":2571.208,"endTime":2572.965,"body":"will be a hybrid, uh, before long."},{"startTime":2572.965,"endTime":2574.005,"body":"So that that certainly happens."},{"startTime":2574.825,"endTime":2578.652,"body":"The second question from Lawrence about, um, what might happen if you have a a,"},{"startTime":2578.652,"endTime":2578.907,"body":"a founder effect population that's reintroduced, there're essentially sort of, uh, two or three kind"},{"startTime":2578.907,"endTime":2583.245,"body":"of options there."},{"startTime":2583.745,"endTime":2588.67,"body":"So the first one is that they might just blend in quite smoothly, um, because"},{"startTime":2588.67,"endTime":2588.999,"body":"if they're still sexually compatible and they're not selected against, you might end up reintroducing"},{"startTime":2588.999,"endTime":2593.925,"body":"'em."},{"startTime":2593.925,"endTime":2599.045,"body":"So for example, blonde hedgehogs do occur albeit very, very infrequently on mainland uk."},{"startTime":2599.305,"endTime":2602.735,"body":"So if you introduce the population of blonde hedgehogs, it's possible that you just end"},{"startTime":2602.735,"endTime":2604.565,"body":"up with, you know, a very diverse population."},{"startTime":2604.805,"endTime":2608.971,"body":"I suspect I don't have evidence this, I suspect being a blonde hedgehog is not"},{"startTime":2608.971,"endTime":2609.805,"body":"a great move."},{"startTime":2609.835,"endTime":2613.796,"body":"Generally like white things in the night that get eaten kind of risky, but you"},{"startTime":2613.796,"endTime":2614.325,"body":"never know."},{"startTime":2614.465,"endTime":2615.605,"body":"Um, so they might, they might survive."},{"startTime":2615.605,"endTime":2618.925,"body":"Second one is that they might be, um, selected against for some particular reason."},{"startTime":2618.985,"endTime":2624.262,"body":"And actually lots of animals, particularly humans unfortunately, um, are very good, good in innovative"},{"startTime":2624.262,"endTime":2628.485,"body":"at selecting against things that look quite like them but not quite."},{"startTime":2628.865,"endTime":2633.507,"body":"Um, and so you might end up that the population is either eliminated or retained,"},{"startTime":2633.507,"endTime":2635.365,"body":"but genetically distinct, uh, within it."},{"startTime":2635.585,"endTime":2639.015,"body":"Um, and the third option of course is that maybe whilst they've been isolated, they've"},{"startTime":2639.015,"endTime":2642.445,"body":"accrued some kind of additional changes that are actually turned out to be really beneficial."},{"startTime":2642.865,"endTime":2647.515,"body":"Um, less likely that, but it's possible that a founder effect, um, population might then"},{"startTime":2647.515,"endTime":2648.445,"body":"move to dominance."},{"startTime":2648.445,"endTime":2652.376,"body":"And that's what sometimes happens on, uh, some islands for example, where a founder population"},{"startTime":2652.376,"endTime":2656.045,"body":"moves from one island to another and actually is really good and takes over."},{"startTime":2656.265,"endTime":2658.165,"body":"Uh, so all options are on the table there."},{"startTime":2658.995,"endTime":2659.685,"body":"Okay, great."},{"startTime":2660.625,"endTime":2664.365,"body":"Um, haha, do we have any questions from the floor?"},{"startTime":2665.955,"endTime":2666.245,"body":"Okay."},{"startTime":2666.705,"endTime":2666.925,"body":"Um,"},{"startTime":2668.705,"endTime":2671.565,"body":"So a microphone coming whistling down the corridor corridor here, one"},{"startTime":2671.565,"endTime":2672.765,"body":"Of the front he'll start here."},{"startTime":2672.895,"endTime":2673.325,"body":"Don't worry."},{"startTime":2673.385,"endTime":2674.005,"body":"Say you'll get,"},{"startTime":2674.665,"endTime":2675.525,"body":"You'll get a chance."},{"startTime":2675.785,"endTime":2680.965,"body":"Um, one, one thing which I heard was that you can't go backwards."},{"startTime":2681.985,"endTime":2687.685,"body":"Uh, how does that explain the laws of ity by Mendel where he has predicted"},{"startTime":2687.685,"endTime":2688.065,"body":"that, you know, from the ninth generation things can happen right up to the ninth"},{"startTime":2688.065,"endTime":2693.765,"body":"generation?"},{"startTime":2694.425,"endTime":2700.98,"body":"And also, uh, if you can explain amongst the, uh, the, the, our ancestors humans,"},{"startTime":2700.98,"endTime":2701.417,"body":"all other species, uh, like uh, the minan man have all disappeared and only homo"},{"startTime":2701.417,"endTime":2701.854,"body":"sapiens are there and we don't seem to be combining to produce anything of a"},{"startTime":2701.854,"endTime":2714.965,"body":"new type,"},{"startTime":2715.535,"endTime":2715.885,"body":"Right?"},{"startTime":2715.935,"endTime":2716.285,"body":"Right."},{"startTime":2716.315,"endTime":2720.171,"body":"Okay, so, so the, so the first question, so it's not that you can't ever"},{"startTime":2720.171,"endTime":2722.485,"body":"go backwards, but it's generally very strongly selected against."},{"startTime":2722.485,"endTime":2726.418,"body":"And if you think about it, that's because you tend to get, organisms tend to"},{"startTime":2726.418,"endTime":2727.205,"body":"get more specialized."},{"startTime":2727.505,"endTime":2732.398,"body":"So for instance, giraffes have evolved longer and longer, longer necks to deal with higher"},{"startTime":2732.398,"endTime":2732.725,"body":"canopies."},{"startTime":2733.055,"endTime":2736.965,"body":"There are other things that have shorter necks and browse the canopy below."},{"startTime":2736.965,"endTime":2740.94,"body":"So if the giraffe was to now move backwards to that shorter neck variant, it's"},{"startTime":2740.94,"endTime":2743.325,"body":"competing with other things that have occupied that niche."},{"startTime":2743.425,"endTime":2746.765,"body":"So it's quite hard to go backwards, um, easier to go forward."},{"startTime":2746.785,"endTime":2751.06,"body":"It does occasionally happen, um, but it's difficult to do in terms of, but what"},{"startTime":2751.06,"endTime":2751.345,"body":"you are referring to with Mendel, and I think that's that's a really good point"},{"startTime":2751.345,"endTime":2751.63,"body":"is that if you have very genetically distinct organisms that can steal into breed, what"},{"startTime":2751.63,"endTime":2763.885,"body":"you often get is this, uh, the, the hybrids from those look sort of ancestral."},{"startTime":2763.965,"endTime":2765.005,"body":"And this is a, this is a process."},{"startTime":2765.145,"endTime":2769.33,"body":"So Francis Galton back, um, shortly after Darwin published his book actually talked about this"},{"startTime":2769.33,"endTime":2771.005,"body":"as, uh, regression to the mean."},{"startTime":2771.005,"endTime":2773.765,"body":"This idea that you go back to some kind of, uh, standard thing."},{"startTime":2773.765,"endTime":2776.787,"body":"And it's a little bit like if you breed different breeds of dog together, you"},{"startTime":2776.787,"endTime":2779.205,"body":"tend to get something that looks sort of like a wolf really."},{"startTime":2779.385,"endTime":2783.516,"body":"Um, because the combination of different genes they have tend to blend together to come"},{"startTime":2783.516,"endTime":2785.445,"body":"back to that sort of, um, thing."},{"startTime":2785.445,"endTime":2788.797,"body":"So it's not really going backwards, but it is sort of a blend to an"},{"startTime":2788.797,"endTime":2789.245,"body":"ancestral characteristic."},{"startTime":2789.785,"endTime":2791.565,"body":"The question of humans is a great one."},{"startTime":2791.825,"endTime":2792.725,"body":"Why is that only us?"},{"startTime":2792.985,"endTime":2795.685,"body":"Um, and uh, I mean I can't answer that 'cause we don't really know."},{"startTime":2795.945,"endTime":2799.805,"body":"Uh, but uh, what I would say is that they're not really completely dead."},{"startTime":2799.865,"endTime":2804.957,"body":"So if you are, um, so for most of us in this room in fact"},{"startTime":2804.957,"endTime":2805.297,"body":"are harboring some Neal DNA, so we know, know that homo sapiens and Neals into"},{"startTime":2805.297,"endTime":2814.125,"body":"bred and most, um, Europeans for example carry about 2% Neal, DNA."},{"startTime":2814.345,"endTime":2819.795,"body":"Um, and if you are from, uh, Polynesia that part of the world, you also"},{"startTime":2819.795,"endTime":2825.245,"body":"have typically about 3%, uh, um, genetic information from the Denis, another now extinct lineage."},{"startTime":2825.265,"endTime":2827.565,"body":"So we did breed and we did incorporate things."},{"startTime":2827.805,"endTime":2832.581,"body":"Actually there's some really great examples in the immune system of genes that are today"},{"startTime":2832.581,"endTime":2836.085,"body":"beneficial that we have inherited essentially from the Anals and Denis."},{"startTime":2836.085,"endTime":2840.315,"body":"So this idea of re taking the best and moving on, uh, why they went"},{"startTime":2840.315,"endTime":2841.725,"body":"extinct is an interesting question."},{"startTime":2841.845,"endTime":2844.495,"body":"I mean, lots of people speculate maybe we made them extinct 'cause we, you know,"},{"startTime":2844.495,"endTime":2846.085,"body":"bashed them over the head and stole their food."},{"startTime":2846.385,"endTime":2850.0,"body":"Um, uh, or maybe the climate changed and somehow, somehow we were adapted to it"},{"startTime":2850.0,"endTime":2851.205,"body":"and, and they were not."},{"startTime":2851.265,"endTime":2853.405,"body":"But you can't run the clock backwards to find out, sadly."},{"startTime":2854.815,"endTime":2855.365,"body":"There we go."},{"startTime":2855.365,"endTime":2859.459,"body":"We're all going to be sort of looking around the room wondering who's got the"},{"startTime":2859.459,"endTime":2860.005,"body":"most Neanderthal."},{"startTime":2860.995,"endTime":2863.885,"body":"It's gonna pop back to the uh, pad for the next question."},{"startTime":2864.185,"endTime":2867.125,"body":"And, uh, uh, this is, this is a really good question."},{"startTime":2867.285,"endTime":2873.81,"body":"I think, what are the ethical implications of intervening or not in relation to evolutionary"},{"startTime":2873.81,"endTime":2874.245,"body":"processes?"},{"startTime":2874.245,"endTime":2878.867,"body":"Especially as, as someone like me coming from a historical background, very aware that there's"},{"startTime":2878.867,"endTime":2879.175,"body":"a sort of lot of historical and quite politicized framing and loading around what we"},{"startTime":2879.175,"endTime":2879.483,"body":"decide is desirable trait that we want to preserve and what we decide is a"},{"startTime":2879.483,"endTime":2890.885,"body":"undesirable trait that we need to, to deal with."},{"startTime":2890.945,"endTime":2891.565,"body":"So love"},{"startTime":2891.565,"endTime":2891.685,"body":"It."},{"startTime":2891.835,"endTime":2895.687,"body":"Yeah, that's a nice tool and I mean the history of evolution unfortunately has got"},{"startTime":2895.687,"endTime":2895.944,"body":"lots of very, very dark periods when, uh, when exactly that has been sort of,"},{"startTime":2895.944,"endTime":2902.365,"body":"um, misused in my view for all sorts of nefarious aims."},{"startTime":2902.705,"endTime":2903.765,"body":"So what are the ethics?"},{"startTime":2904.045,"endTime":2906.784,"body":"I think the biggest challenge we have, so there's two parts that I think is"},{"startTime":2906.784,"endTime":2908.245,"body":"the human part and the other animal part."},{"startTime":2908.945,"endTime":2913.928,"body":"So, um, the, the other animal part, I think generally we can use this as"},{"startTime":2913.928,"endTime":2914.925,"body":"a beneficial information."},{"startTime":2914.945,"endTime":2917.657,"body":"So for example, when you're doing captive breeding programs, you should be thinking about this"},{"startTime":2917.657,"endTime":2919.285,"body":"to make sure you don't get these found effects."},{"startTime":2920.205,"endTime":2923.738,"body":"A a good question and a tricky one that I obviously can't answer is to"},{"startTime":2923.738,"endTime":2926.565,"body":"what extent should you try and bring back something that's not there?"},{"startTime":2926.565,"endTime":2930.583,"body":"So there's a big active discussion about should we try and get dodos or mammoths"},{"startTime":2930.583,"endTime":2930.851,"body":"or these things back up because they, they've gone, especially species that we have made"},{"startTime":2930.851,"endTime":2935.405,"body":"extinct like dodos."},{"startTime":2935.705,"endTime":2938.785,"body":"Um, and that is very tricky I think, because on the one hand you say,"},{"startTime":2938.785,"endTime":2941.045,"body":"well, we, we made them extinct, we should probably fix that."},{"startTime":2941.385,"endTime":2944.405,"body":"On the other hand, you know, we are part of evolution too."},{"startTime":2944.495,"endTime":2946.445,"body":"Human predation is an evolutionary force."},{"startTime":2946.905,"endTime":2950.217,"body":"Um, and to what extent do you say, okay, so maybe we should reverse all"},{"startTime":2950.217,"endTime":2950.438,"body":"the ones that we made extinct, but what about the ones that have been driven"},{"startTime":2950.438,"endTime":2950.658,"body":"extinct by our pet cats or our dogs or by rats or, you know, uh,"},{"startTime":2950.658,"endTime":2957.725,"body":"so very, very thorny."},{"startTime":2957.725,"endTime":2963.062,"body":"So I think no, no great answer there for humans, as it stands at the"},{"startTime":2963.062,"endTime":2968.045,"body":"moment, um, essentially every country in the world prohibits what's called somatic gene therapy."},{"startTime":2968.265,"endTime":2972.448,"body":"So you can't change genes in an individual in a way that would be inherited"},{"startTime":2972.448,"endTime":2973.285,"body":"by your offspring."},{"startTime":2973.285,"endTime":2976.488,"body":"So if you've got a genetic disorder, um, you can absolutely, you can screen embryos,"},{"startTime":2976.488,"endTime":2976.702,"body":"you can do all this kind of stuff, but you can't change your genes even"},{"startTime":2976.702,"endTime":2976.915,"body":"though we now have the power to do that in a way that permanently alters"},{"startTime":2976.915,"endTime":2984.605,"body":"that in your, in your DNA to inherit."},{"startTime":2985.025,"endTime":2986.125,"body":"And that is very difficult."},{"startTime":2986.125,"endTime":2988.943,"body":"And the reason we say that is because clearly if you start doing that, you"},{"startTime":2988.943,"endTime":2989.131,"body":"are into whole process of eugenics and you know, the, who gets to decide what"},{"startTime":2989.131,"endTime":2994.205,"body":"is and is not a legitimate change and so on and so forth."},{"startTime":2994.945,"endTime":2999.451,"body":"On the other hand, I do take, you know, I see that the, the challenge"},{"startTime":2999.451,"endTime":2999.751,"body":"that people, particularly people who know they're carrying mutations that might be particularly dangerous to"},{"startTime":2999.751,"endTime":3000.052,"body":"their children and would wish to permanently change that as opposed to, you know, onic"},{"startTime":3000.052,"endTime":3008.765,"body":"screening."},{"startTime":3008.995,"endTime":3010.245,"body":"Very tricky ethical issue."},{"startTime":3010.245,"endTime":3011.925,"body":"And I think one that's not gonna go away anytime soon."},{"startTime":3011.925,"endTime":3015.105,"body":"In fact, it's gonna get bigger and bigger as we get more and more powerful"},{"startTime":3015.105,"endTime":3016.165,"body":"genetic tools to change it."},{"startTime":3016.775,"endTime":3020.15,"body":"We're just carrying on on this line for a couple of moments, couple more questions"},{"startTime":3020.15,"endTime":3021.725,"body":"in and around this sort of area."},{"startTime":3022.505,"endTime":3027.403,"body":"So, I mean, for example, you mentioned the sax disease, obviously very terrible, um, and"},{"startTime":3027.403,"endTime":3027.729,"body":"anyone with it dies early, but are there ever advantages to having certain, or being,"},{"startTime":3027.729,"endTime":3028.056,"body":"you know, having these sort of isolated groups that carry certain genes, you know, can,"},{"startTime":3028.056,"endTime":3039.485,"body":"can there ever be good news stories?"},{"startTime":3039.745,"endTime":3044.123,"body":"And then related to that, and again, coming back to this sort of slightly more"},{"startTime":3044.123,"endTime":3044.415,"body":"historical consciousness of, of, you know, the process of, you know, the space in which"},{"startTime":3044.415,"endTime":3049.085,"body":"science operates."},{"startTime":3049.865,"endTime":3056.153,"body":"How do researchers differentiate between what they're confident to call random chance, naturally, quite strongly"},{"startTime":3056.153,"endTime":3060.765,"body":"deterministic factors like the cultural, um, influences that you were describing."},{"startTime":3061.575,"endTime":3061.925,"body":"Great."},{"startTime":3061.925,"endTime":3063.005,"body":"So I'm gonna start with the second one."},{"startTime":3063.025,"endTime":3066.245,"body":"So how do you know it's random versus, um, sort of somehow selective?"},{"startTime":3066.345,"endTime":3067.205,"body":"So there are ways to do that."},{"startTime":3067.305,"endTime":3072.042,"body":"And one, one way you can do it mathematically is, uh, DNA is made of"},{"startTime":3072.042,"endTime":3074.885,"body":"these different letters, um, and it encodes proteins, right?"},{"startTime":3074.885,"endTime":3077.125,"body":"So essentially there are 20 amino acids."},{"startTime":3077.385,"endTime":3081.642,"body":"So a change in your DNA that changes in amino acid will have a functional"},{"startTime":3081.642,"endTime":3084.765,"body":"consequence, like your eyes go from blue to brown or whatever."},{"startTime":3085.145,"endTime":3087.365,"body":"Um, a change in your DNA that doesn't change."},{"startTime":3087.385,"endTime":3089.445,"body":"The protein generally is invisible."},{"startTime":3089.865,"endTime":3093.612,"body":"And so what you can do in an organism is you can measure the number"},{"startTime":3093.612,"endTime":3093.861,"body":"of invisible genetic changes and the visible ones and then you can, and basically if"},{"startTime":3093.861,"endTime":3094.111,"body":"the, if the visible ones are more present than you'd expect by chance you say,"},{"startTime":3094.111,"endTime":3102.605,"body":"okay, this gene is under selection."},{"startTime":3102.905,"endTime":3106.346,"body":"Um, so a very good example of that, uh, for example is the gene for"},{"startTime":3106.346,"endTime":3106.805,"body":"lactose tolerance."},{"startTime":3106.945,"endTime":3111.433,"body":"And we see in the human population, uh, that that gene, particularly in Europe, um,"},{"startTime":3111.433,"endTime":3114.725,"body":"is, has changed massively more than you would expect by chance."},{"startTime":3114.785,"endTime":3118.373,"body":"And that is because historically there was a big advantage in being able to metabolize"},{"startTime":3118.373,"endTime":3121.005,"body":"lactose when you didn't have any other food around, for example."},{"startTime":3121.025,"endTime":3125.0,"body":"So you can see that process of randomness, um, uh, which is, yeah, so that's,"},{"startTime":3125.0,"endTime":3126.325,"body":"that, that is definitely present."},{"startTime":3126.905,"endTime":3130.805,"body":"Um, in terms, and the other question was on oh, beneficial mutations."},{"startTime":3130.805,"endTime":3131.165,"body":"That's right."},{"startTime":3131.265,"endTime":3135.279,"body":"So, so I think this is a, there's a really good point here about, um,"},{"startTime":3135.279,"endTime":3135.547,"body":"uh, probably the strongest argument about intervening against intervening is that you can't predict what's"},{"startTime":3135.547,"endTime":3140.365,"body":"gonna be useful, right?"},{"startTime":3140.365,"endTime":3143.568,"body":"So we're sitting here in the middle of London, those of us in the room"},{"startTime":3143.568,"endTime":3143.781,"body":"today, for example, being able to, I know, see stuff and respond very rapidly is"},{"startTime":3143.781,"endTime":3143.995,"body":"quite an advantageous trait if you're in London because if you cross the road and"},{"startTime":3143.995,"endTime":3152.965,"body":"you don't look first, that that is a very strong selective pressure against you."},{"startTime":3153.425,"endTime":3157.15,"body":"Um, four or 500 years ago, uh, a much better selective trait would've been, you"},{"startTime":3157.15,"endTime":3157.398,"body":"know, being able to wield a sword and, I don't know, whittle sticks to make"},{"startTime":3157.398,"endTime":3162.365,"body":"fire all sorts of different things."},{"startTime":3162.785,"endTime":3166.165,"body":"Um, and so what has been beneficial has changed over time."},{"startTime":3166.625,"endTime":3170.237,"body":"Um, and you know, you couldn't have predicted 400 years ago that a mutation that"},{"startTime":3170.237,"endTime":3172.405,"body":"helps you spot cars coming would be beneficial, right?"},{"startTime":3172.865,"endTime":3175.125,"body":"Um, so I think you can't kind of look forwards in that way."},{"startTime":3175.465,"endTime":3180.348,"body":"Uh, but there are definitely examples of mutations that have become beneficial, um, particularly around"},{"startTime":3180.348,"endTime":3181.325,"body":"things like sight."},{"startTime":3181.345,"endTime":3185.748,"body":"So some, so in fact, that's quite an interesting example that, um, it, the different"},{"startTime":3185.748,"endTime":3189.565,"body":"individuals in this room will have different ability to, to perceive different colors."},{"startTime":3189.985,"endTime":3192.565,"body":"Um, and generally that's probably not advantageous."},{"startTime":3192.865,"endTime":3196.601,"body":"Uh, but if you are out in the wild, if you like, the ability to"},{"startTime":3196.601,"endTime":3196.85,"body":"see different pigments might be advantageous in terms of looking at fruit, um, that is"},{"startTime":3196.85,"endTime":3201.085,"body":"ripe, for example."},{"startTime":3201.265,"endTime":3202.925,"body":"So there are mutations that might be useful."},{"startTime":3203.145,"endTime":3206.371,"body":"And I think the best argument against us trying to think ahead for that is"},{"startTime":3206.371,"endTime":3206.586,"body":"that, you know, if you make a genetic change that seems like a really good"},{"startTime":3206.586,"endTime":3206.801,"body":"idea today, it might turn out to be a really bad idea in a couple"},{"startTime":3206.801,"endTime":3213.685,"body":"of hundred years time."},{"startTime":3213.785,"endTime":3217.996,"body":"So, um, there is definitely something, at least for me about retaining the randomness, um,"},{"startTime":3217.996,"endTime":3221.085,"body":"as a, a sort of insurance policy for the future evolution."},{"startTime":3221.455,"endTime":3221.805,"body":"Great."},{"startTime":3222.465,"endTime":3224.285,"body":"We have a question from the floor."},{"startTime":3231.935,"endTime":3237.893,"body":"We're quite often asked to worry about extinctions and endangered species, but as a specialist,"},{"startTime":3237.893,"endTime":3239.085,"body":"are you worried"},{"startTime":3239.805,"endTime":3241.805,"body":"\u003claugh\u003e, am I worried about extinctions?"},{"startTime":3241.905,"endTime":3243.045,"body":"Oh, I am actually quite worried."},{"startTime":3243.045,"endTime":3247.82,"body":"And the reason for that, so extinction is a natural part of evolution, but the"},{"startTime":3247.82,"endTime":3250.685,"body":"pace of extinction is what is radical different now."},{"startTime":3250.705,"endTime":3254.759,"body":"So if you look at, uh, you know, the sort of history of life on"},{"startTime":3254.759,"endTime":3255.03,"body":"this planet, there have been probably five or six mass extinctions, um, very, very fast"},{"startTime":3255.03,"endTime":3259.085,"body":"ones."},{"startTime":3259.085,"endTime":3261.685,"body":"They're caused by things like meteorites hitting the piece in the planet."},{"startTime":3262.065,"endTime":3266.725,"body":"We are essentially creating our own mass extinction at the moment, um, as a pet."},{"startTime":3266.725,"endTime":3269.045,"body":"And we think it's slow, but it's not really slow in evolutionary terms."},{"startTime":3269.425,"endTime":3273.13,"body":"Um, and uh, so, so I am worried in the sense that I'm worried kind"},{"startTime":3273.13,"endTime":3274.365,"body":"of firstly as a human."},{"startTime":3274.485,"endTime":3277.421,"body":"I think it's, it's kind of a bit miserable to think that we're sort of"},{"startTime":3277.421,"endTime":3278.205,"body":"denuding the world's ecosystem."},{"startTime":3278.785,"endTime":3283.189,"body":"But secondly, with a very pragmatic hat on, every time a species go extinct, you"},{"startTime":3283.189,"endTime":3286.125,"body":"lose all of its genetic innovation to the future, right?"},{"startTime":3286.425,"endTime":3290.738,"body":"Um, and the place that we, that I think that's most important, if you think"},{"startTime":3290.738,"endTime":3294.765,"body":"very selfishly about medicines, most of our antibiotics come from organisms out the environment."},{"startTime":3294.765,"endTime":3296.405,"body":"Typically bacteria or fungi."},{"startTime":3296.815,"endTime":3300.993,"body":"Every time a an uncharacterized bacteria or fungal species goes extinct, you don't know whether"},{"startTime":3300.993,"endTime":3301.272,"body":"that one was actually producing the compound that was gonna cure your cancer or your"},{"startTime":3301.272,"endTime":3306.565,"body":"heart disease or something else."},{"startTime":3306.905,"endTime":3308.805,"body":"And now you never will 'cause it's gone extinct."},{"startTime":3308.945,"endTime":3311.485,"body":"So I do think it's really important to try and reign in that."},{"startTime":3311.745,"endTime":3314.463,"body":"Um, that's not to say you can ever stop extinction, it's part of the normal"},{"startTime":3314.463,"endTime":3314.645,"body":"process."},{"startTime":3315.145,"endTime":3318.997,"body":"Um, but the pace at which humans are doing it sort of willy nilly I"},{"startTime":3318.997,"endTime":3321.565,"body":"think is is a big concern, unfortunately a bit depressing."},{"startTime":3323.235,"endTime":3323.525,"body":"Okay,"},{"startTime":3324.705,"endTime":3326.285,"body":"So just time for a couple more."},{"startTime":3326.765,"endTime":3330.845,"body":"I think, um, humans would not exist if they did not reproduce, right?"},{"startTime":3331.025,"endTime":3331.365,"body":"Got that."},{"startTime":3332.025,"endTime":3338.325,"body":"Do you believe that today's society fails to acknowledge the instinct we have to procreate?"},{"startTime":3339.065,"endTime":3340.845,"body":"Oh, that's a nice thorny one, isn't it?"},{"startTime":3341.465,"endTime":3342.365,"body":"Are we sure gonna take that one?"},{"startTime":3342.365,"endTime":3342.925,"body":"Shall I just leave now?"},{"startTime":3342.925,"endTime":3343.125,"body":"Now?"},{"startTime":3343.125,"endTime":3343.285,"body":"Okay."},{"startTime":3343.285,"endTime":3343.445,"body":"Right."},{"startTime":3343.505,"endTime":3346.765,"body":"Um, uh, so, uh, so humans would all exist if we didn't reproduce."},{"startTime":3346.765,"endTime":3347.525,"body":"That's definitely true."},{"startTime":3347.865,"endTime":3350.525,"body":"Um, do I, do I think that we are reigning in?"},{"startTime":3350.525,"endTime":3353.765,"body":"No, I don't think I, well, so let's play that."},{"startTime":3354.065,"endTime":3358.125,"body":"If, if we didn't reign in our desire to reproduce, um, then what we would"},{"startTime":3358.125,"endTime":3361.645,"body":"be doing is subjecting ourselves to the full weight of natural selection, right?"},{"startTime":3361.645,"endTime":3365.057,"body":"So we might all have 25 babies and the vast majority of those babies would"},{"startTime":3365.057,"endTime":3365.285,"body":"die."},{"startTime":3365.665,"endTime":3368.605,"body":"Um, and so you'd be acting like a normal wild species."},{"startTime":3368.805,"endTime":3371.805,"body":"I think most of us as conscious human beings would say that's a bad idea."},{"startTime":3372.225,"endTime":3375.325,"body":"Um, you shouldn't be bringing organisms into the world just to die."},{"startTime":3375.865,"endTime":3378.205,"body":"Um, so, so I, so I'm not concerned."},{"startTime":3378.245,"endTime":3379.045,"body":"I think it is a good thing."},{"startTime":3379.065,"endTime":3382.557,"body":"And actually I think, you know, reigning in human reproduction, um, uh, more is probably"},{"startTime":3382.557,"endTime":3384.885,"body":"not a bad thing for the planet as a whole."},{"startTime":3385.225,"endTime":3390.529,"body":"Um, I think there's a sort of secondary questionnaire, I guess, about to what extent,"},{"startTime":3390.529,"endTime":3393.005,"body":"um, that process might shape future evolution."},{"startTime":3393.005,"endTime":3394.085,"body":"And that is very interesting."},{"startTime":3394.165,"endTime":3399.035,"body":"I mean, typically in most western societies, uh, many western countries are not at self"},{"startTime":3399.035,"endTime":3399.685,"body":"replacement, right?"},{"startTime":3399.685,"endTime":3403.485,"body":"Many of us on average don't have two children, um, who then go on to"},{"startTime":3403.485,"endTime":3404.245,"body":"have other children."},{"startTime":3404.265,"endTime":3406.845,"body":"And so, uh, the population is shrinking, other parts of the world are growing."},{"startTime":3406.845,"endTime":3410.857,"body":"And so you get an evolutionary change with that because genes are different in different"},{"startTime":3410.857,"endTime":3411.125,"body":"places."},{"startTime":3411.665,"endTime":3412.605,"body":"Um, is that a problem?"},{"startTime":3412.805,"endTime":3413.805,"body":"I don't particularly think so."},{"startTime":3414.105,"endTime":3418.188,"body":"Um, the interesting question becomes when you start to think about things like the impact"},{"startTime":3418.188,"endTime":3419.005,"body":"it might have."},{"startTime":3419.345,"endTime":3423.483,"body":"So clearly we are living at a time when many of us have met partners"},{"startTime":3423.483,"endTime":3423.759,"body":"from very far-flung parts of the world, um, who you wouldn't have met even a"},{"startTime":3423.759,"endTime":3428.725,"body":"few hundred years ago."},{"startTime":3428.745,"endTime":3432.365,"body":"You're bringing together interesting genetic combinations, and I personally think that's fabulous."},{"startTime":3432.665,"endTime":3436.033,"body":"Um, but it is really interesting to think thousands of years from now whether, you"},{"startTime":3436.033,"endTime":3436.258,"body":"know, a future geneticist will look and go, wow, look at this massive bloom of"},{"startTime":3436.258,"endTime":3440.525,"body":"diversity in the human population."},{"startTime":3440.565,"endTime":3443.51,"body":"I wonder what happened back then and not realize it was 'cause we had, you"},{"startTime":3443.51,"endTime":3444.885,"body":"know, transatlantic airplanes all of a sudden."},{"startTime":3446.785,"endTime":3451.369,"body":"And finally, um, we've done a lots of talking when sometimes it's sometimes sort of"},{"startTime":3451.369,"endTime":3451.675,"body":"seen for this, uh, hapless population that things kind of just happen to us and"},{"startTime":3451.675,"endTime":3451.981,"body":"the best we can do is kind of try and respond intelligently to the random"},{"startTime":3451.981,"endTime":3460.845,"body":"chance."},{"startTime":3460.985,"endTime":3465.963,"body":"But Ellen wants to know, are there models of evolution that acknowledge or incorporate a"},{"startTime":3465.963,"endTime":3466.295,"body":"bit more of a sense of how, um, a population kind of impacts back on"},{"startTime":3466.295,"endTime":3474.925,"body":"the niche they're in and that actually changes alters that that environment."},{"startTime":3475.625,"endTime":3475.845,"body":"Yes."},{"startTime":3476.065,"endTime":3478.685,"body":"Um, there are, and well, humans I guess are the prime example of that."},{"startTime":3478.705,"endTime":3482.14,"body":"And this is something that's elaborated on quite a lot by, uh, people like Richard"},{"startTime":3482.14,"endTime":3483.285,"body":"Dawkins in his extended phenotype."},{"startTime":3483.545,"endTime":3488.115,"body":"So this idea, so the phenotype is your sort of the physical manifestation of your"},{"startTime":3488.115,"endTime":3488.725,"body":"genetic changes."},{"startTime":3489.105,"endTime":3493.194,"body":"And the point he makes in that book is that, you know, an immediate physical"},{"startTime":3493.194,"endTime":3493.467,"body":"manifestation is brown eyes, blue eyes that are, but if you think about something like"},{"startTime":3493.467,"endTime":3493.74,"body":"the beaver building a dam that is also manifest of they're genetically programmed to build"},{"startTime":3493.74,"endTime":3494.012,"body":"a dam, and so they are shaping their environment, um, by genes and therefore they"},{"startTime":3494.012,"endTime":3507.645,"body":"are selected by evolution to do particular things."},{"startTime":3507.945,"endTime":3511.886,"body":"Um, and I guess you could argue that humans are very much doing that at"},{"startTime":3511.886,"endTime":3512.149,"body":"the moment because what are beneficial genes today are very often completely unrelated to our"},{"startTime":3512.149,"endTime":3512.412,"body":"ability to just survive and procreate right now, if you think about the things like"},{"startTime":3512.412,"endTime":3512.674,"body":"your ability to get a steady job and to, you know, meet a nice partner"},{"startTime":3512.674,"endTime":3512.937,"body":"and all that kind of stuff, which are related to traits that are not about"},{"startTime":3512.937,"endTime":3513.2,"body":"being able to, you know, get, most of us can't forage while mushroom is successfully,"},{"startTime":3513.2,"endTime":3534.485,"body":"for example, and we don't die because we can't do that."},{"startTime":3534.865,"endTime":3539.307,"body":"Um, but a complete inability to function in society that as computers and reading and"},{"startTime":3539.307,"endTime":3542.565,"body":"literacy and all those kind of things is quite a disadvantage."},{"startTime":3542.945,"endTime":3548.003,"body":"Um, so there you've got essentially an extended phenotype that we have created ourselves, and"},{"startTime":3548.003,"endTime":3552.725,"body":"now we are selecting each other based on this ecosystem that we have produced."},{"startTime":3552.745,"endTime":3556.295,"body":"And I think that's a very interesting kind of extended phenotype that we're living in,"},{"startTime":3556.295,"endTime":3557.005,"body":"right the minute"},{"startTime":3557.665,"endTime":3559.325,"body":"And on that extended phenotype."},{"startTime":3559.325,"endTime":3562.845,"body":"Ladies and gentlemen, please join me in thanking Professor Robin."}]}