Aoife McLysaght - 'The Descent of Man, 150 Years On'. (The HAI's Darwin Day Lecture 2021)

so uh ladies and gentlemen you're all very welcome to the 2021 uh darwin day lecture uh thank you all for so much so much for joining us um i'll be in different different circumstances to the norm of course uh we're celebrating the birthday of charles darwin which is actually tomorrow on february 12th and for the last few years this event has filled the robert emmett theater on trinity's campus about 160 people each time and judging by where the numbers are going i'd imagine by the time we actually get started we could be looking at something similar as well in 2021 which is great and wonderful to see so thanks all for giving up part of your evening to be here my name is eamon murphy i'm events coordinator with the humanist association of ireland um i'm going to be as brief as possible with some little bits of housekeeping before passing over to david mcconnell who'll give the opening address first thing is to say that this event is being recorded i believe it's customary to give you warning in that regard uh secondly i'd ask that you please keep your microphones muted for the duration of the evening unless you're called on to speak or ask a question uh towards the end in order to kind of somewhat mitigate the uh impersonal nature of having to hold these events remotely we much preferred it in these sessions um people should be able to ask their own questions the main thing about that though is that we need to trust you then in the webs function not the webinar function to keep people's uh microphones on mute please don't take offense if i i do mute you on my control panel here you can leave your cameras on if you wish but i recommend selecting speaker view rather than gallery view so that you can get a better glimpse of david and then if when they're speaking and you can control that with the little functionality in the top right hand corner of your screen as i've alluded to once ifa has finished speaking we're going to have a q a and to draw your attention to your desire to speak during the q a by virtually raising your hand what you do is you click on the participants icon at the bottom of your zoom screen and a tab will appear on the right showing all the attendees at the bottom of that there's a button that says raise hands so i'll remind you how to do that later but yeah again you do it by clicking on participants and then at the raise hand button at the bottom of the right hand screen now it's tradition to preface every humanist association meeting with a short explanation of what humanism actually is um so very quickly humanism is an ethical life stance it takes a rational outlook towards life attaching primary importance to human matters rather than those of a divine or supernatural nature and humanists aim to live meaningful and ethical lives without being guided by religion essentially we aim to be good without god and our key values are reason equality and compassion now um any questions that you have on the hei or about humanism either you can google the amsterdam humanist declaration or you can give me an email at events humanism dot ie and with all that out of the way without any further ado uh it has been tradition for the last number of years that our honorary president has given the opening address of this event so it's always something that i look forward to almost as much as the lecture itself and i'm pleased that he's agreed to maintain the tradition even in lockdown especially as he's a man who uh himself knows a thing or two about genetics so i'll pass you over now to the honorary president of the ati professor david mcconnell thank you even and good evening to everybody there seems to be a little bit of overtalk i don't know whether i'm the only one hearing it any case off we go so it's an enormous pleasure always to take part in the darwin day ceremony lecture and it's a very special uh pleasure for me uh today because of this evening that's because evan gleicert uh is going to give the talk not the first time that she's given it uh but um this happens to be special for two reasons um many but i mentioned two one it is the 150th anniversary of the publication of the descent of man uh by darwin 1871. it's also the 20th anniversary of the publication of the draft sequence of the human genome sequence and ifa at the time a student a graduate student was a co-author on that paper one of the milestones in the history of genetics so we're celebrating two anniversaries eva now if i'm not going to give an address really because i'll just say a few words i really want to listen to ifa and i think the rest of you should too uh just reminding you that in 1859 darwin published the origin of species and certainly one of the two or three most influential books i would say in the history of science and he introduced his theory of natural selection and he was deeply aware of the impact book was likely to have because he knew of course that his theory of evolution by natural selection applied to people as much as it did to any other organisms but in the entire book he only referred to that question once the famous sentence he said light will be thrown on the origin of man and his history by the way he was a broad-minded person he was using the conventions of his and man and uh you know typical of the time which i suppose many of us did until maybe 30 years ago now he followed this in 1871 and it's if you think about 1859 to 1871 it's only 12 years later he published one of his other most influential books um the descent of man and it had a subtitle not so much a subtitle because it came in two parts and selection in relation to sex so it was an extraordinary book but um he noted around about the time he said everyone is talking about it without being shocked and on to say proof of the increasing liberality of england so whereas the origin species had created a furore the descent of man was greeted with um i won't say equanimity but by that time the thinking reading public in britain he says england he wasn't a little englander by the way but he meant britain and ireland indeed uh the thinking and reading public uh at the time were no longer shocked by the idea of evolution a very large percentage of thoughtful people had already accepted the idea a that evolution had occurred and a large number of them had reckoned that he probably had the right answer that had occurred by natural selection and by the way sexual selection is uh a branch if you like of natural selection so there was no shock and as time has gone by of course uh his great ideas and there were so many of them in the origin of species and otherwise expanded in these many other books including in the descent of man so many of them have turned out to be correct and he had an enormous insight there was that let's be said there were huge problems you read the origin of species you'll find that he's really rather careful to mention the large number of difficulties uh with the theory of evolution by natural selection one of them which bothered him well for a long time but in the end he got over it he tried to imagine how an eye could evolve over great periods of time during the evolution of animals how could such an incredible organ as the eye appear by the time he gets to 1871 he's there about he's writing to say that he's got over that problem he just thinks that i started off as something very very very very very simple and got more and more and more complicated as the millions of years rolled by but the peacock's tale bothered him intensely because why would evolution lead to something so outrageously apparently useless even damaging and difficult as a peacock's tail that all gets sorted out by the way in his theory of sexual selection now it goes on i mean when darwin is such a rich rich rich thinker i'll give you one other thing that occurred to me in thinking about the descent of man which i have to confess i have not read but um in it he makes and maybe we'll talk about this but he is quite clear that all people on the planet are members of the same species and remember we're talking about the middle to late 19th century slavery was not very far in the past indeed it was to some extent still in the present and of course the echoes are so strong even today but he was an absolutely no doubt that all people on the planet were members of the same species and further well it's lovely to read a little bit about his about his life he started off life as a medical student in edmond he spent two years there and there he met a man called jed ed john edmundson who was a negro brought from guyana by a scottish uh business person i don't know adventurer given his freedom in uh scotland and he became a teacher of taxidermy in the in the medical school at uh at edinburgh and darwin learned from him and came to know him and delight in him and wrote about him about what a splendid person he was and how intelligent he was so quite early on he was only 17 or 18 years of age at this time by the way he was he had met a wonderful black person and was in no doubt at the time of course about that person's enormous value and uh dignity as a human being so when he traveled around the world on the voyage of the beagle and he met people of many different races and so on he was already well prior to think of people of being of all human being being of the same species now he also in the descent of man talks about social evolution he realized that as human civilization had developed that social evolution had begun to have a very big effect on the evolution of people and that of course was something that his cousin john galton [Music] thought and wrote and talked about and is much maligned in some ways but darwin nails his colors to the mast in no uncertain terms that even if social evolution has given us the power to as it were thwart natural selection a person like myself who is blind as a bat would not have lasted very long he nevertheless was quite clear that we had a great duty and indeed fundamental belief in the value of everybody to look after everybody in society so one thing which comes through whenever you read whenever i read darwin is the great humanity of the man now that said my main duty this evening is to say something about evil and i'm lucky enough to have known her longer than almost any of you and although i don't know the entire audience uh tonight but i was lucky enough to meet her when she was a second year junior officer student in trinity she took a problem course which i had set she got a hundred percent and uh that summer i asked her would she help me to set the exam for the next year and this is one of the great pleasures of being a teacher when you find students who are much smarter than you are she went on to a splendid career in genetics a wonderful degree a wonderful phd under ken wolfe she is the academic granddaughter of paul sharp who invented the theory not the theory but the field of molecular evolution in ireland and in her work she has shown just wonderful i would say imagination and genius just terrific qualities and we were very lucky she went off to the university of california at irvine spent a year there but then she came home and she has been with us since i think uh 200 2003 and has contributed absolutely enormously to not only genetics worldwide but i would say thrown herself heart and soul into the teaching and fostering of genetics in every possible way in trinity if i were to characterize her work or focus of her work in one or two words she's been very interested in showing how genes have been added to genomes so ken wolff had shown uh that yeast at a particular time that is the ordinary saccharomyces cerevisiae the ordinary brewers he said suddenly doubled its number of chromosomes efo went on to show that vertebrates had not just doubled but quadrupled their number of chromosomes so we are in a funny kind of way a tetraploid species that's not quite the right way of saying it and then i remember the time when she actually discovered that since humans had separated from the great apes she discovered new genes had been added and she showed how they had been added absolutely wonderful wonderful work so much fun to see it uh being discovered and seeing the cleverness with which she identified these new genes so she's been in trinity uh for the last uh 18 years as a member of staff highly valued she's written a very large number of scientific papers um many of them really characterized by uh i think i use the word genius again and cited a very very large number of times absolutely terrific she's a brilliant teacher and that leads me just to mention the joy of being a teacher the beauty of being a teacher is that every year you find new students and they sort of keep you up to the mark but i want to mention that if i had a teacher i hope he might be watching tonight i asked him to join in dr nick fruen at st andrews college a brilliant secondary school biology teacher who turned out three four or five wonderful students for the genetics department e for being one of them and she has shown an enormous commitment to teaching not just inside college but outside i mean i don't think know of any other academic colleague in the country who has appeared at electric picnic she's given tedx talks she's talked at the royal institution christmas lectures these are enormous indications measures of her brilliance as a teacher known i want to say from and you can see it from those comments on worldwide for her capacity to inspire people and to educate people professionally she was awarded the president of ireland young researchers award in 2005 she has won research grants from the european research council that is an extraordinary achievement in any scientific field starter grant in 2013 and then not many starters go on to consolidate and get a consolidator grant which she has at the moment starting in 2018. and then to have had the honor of being asked to give the jbs haldane lecture to the genetical society and then the accolade perhaps of which well we are very very proud she was became the president of the society for molecular biology and evolution that's the international society essentially based in the united states but in 2017 she became the president of that society now many of you will be aware i hope you have been uh that uh she has contributed enormously in founding the irish uh society for uh independent advice giving independent advice uh to the government on the covid uh crisis she's been a great great uh pillar of that of that uh organization i should also say that she is now my successor as the head of the genetics department so um it is with enormous pleasure uh and indeed anticipation ether that i look forward to your lecture tonight thank you very much for being willing to do it thank you thanks david i think i'm going to be a letdown after such a wonderful introduction i can't possibly live up to that um but thank you so much and um if dr froon is in the audience that'll be fabulous um i i uh definitely credit him with starting everything in terms of inspiring me and to think about science and to think like a scientist i think it was an always an extraordinary example of how um teaching isn't just delivering information but making you think and i really think that's what it is to be a scientist and it started in a classroom setting i have a copy of the scent of man here and which is pilfered from the genetics department um library it has like the department of genetics and a little code but i didn't nick it you did david because um this is one of the this was in one of the boxes you gave me when you were moving house and you needed to to downsize your bookshelves so um i'm innocent i'm only a beneficiary of the theft um but um anyway so uh yeah i was looking through this and taking some some bits out of it so um i'm gonna talk today so about this book because it is the anniversary and i am going to just give me a second i will share my screen okay so eamon um i'm not permitted to share my screen right now could i do that please okay yeah it's letting me do it now okay so everybody should be able to see that so um and i'm just going to there should be a way for me to make a little laser pointer um yes okay so if i want to point at things so um as david mentioned there's an anniversary this week 100 and now this month 150 years since the publication of the descent of man so this this is not a first edition so i don't think it's a valuable one that you pilfered david but it's still lovely to have and to halt and so what i thought i would do today is um i was going to try and talk about this book in a modern context and it's really uh quite a challenge because the book includes so much so i'm going to talk through some of the ideas there's a few places where it's really interesting to see how right darwin was and you know given the information he had at the time but there are other things where you can clearly see the information just wasn't there and most notably i think they just at that time didn't have the idea of the gene or dna or whatever was the heritable material and and there's bits in the book where he sounds a bit like lamarck which is funny because we usually set up darwin's ideas and lamarck's ideas as the opposite but he does mention how he has a section where he's talking about you know um certain people um you know using their muscles more and maybe their children will also develop to have more muscles and things like that and bigger muscles or particular physical features that are are useful in their their daily life so it does sound a bit like lamarckism but um he possibly meant it a bit more a bit slightly differently than that or at least uh it could work slightly differently than that so as david mentioned that the book has two titles the descent of man and selection in relation to sex so it's actually i think more than two titles it's basically two books because um the selection in relation to sex is a whole topic unto itself and in that section he's not really talking about humans anymore and talking about all kinds of other animals so um i dispense of this one quickly because i decided that i couldn't do everything and it would be very very interesting and exciting to have a talk about sexual selection all by itself and but instead i'll just really briefly say and it is discussed and it is um basically a special case of natural selection so natural selection as i think everybody here probably attends these lectures every um every year so maybe you're all far too knowledgeable for the kind of things i'm talking about today but um natural selection of course being just that idea of there are there are variations which are heritable variations and those variations that help you do better in your life so survive better get better you know get your food better and all of those things um will be the ones that get passed on because you're going to be a reproductive success story and then sexual selection is a special case of this because mostly in natural selection those things that help us um survive better and reap like have a better chance of passing on our genes it's because they make us healthier or because they make us better at something you know better at avoiding a predator or better at finding your food or all of these kind of um these kind of activities or these features we can think of and then when you get to something like the peacock's tail it's it's doesn't seem to fit those criteria because it's this enormous showy target sign that the animal has displayed so and not only a big target sign that makes it so ostentatiously visible but also probably makes it easier to catch because it's a it's a big thing you can catch on to and um take hold of and so it was this um puzzle in a sense in terms of evolution because how could something that's so obviously an impediment have evolved and and that's where darwin came up with the idea well there's a special case of natural selection which is all it's in the eye of the beholder so this beautiful tale evolved because the p hen likes it and for no other reason so the only advantage the unique advantage that the peacock's tail gives it is that the p hen likes it and so he has a better chance of finding a mate and of course this is um a very elaborate extraordinary structure and it didn't happen in one mutation to go from a like a more typical bird's tail to a peacock's tail but it's a case of what would be described as runaway natural selection so the female has a slight preference for a bigger tail and then you've got a slightly bigger tailed peacocks and then one of them has a mutation and his tail is a bit bigger and that that one does even better at attracting a mate and so on and so on until you've got the most extraordinary showy ostentatious catch me if you can sign on there on on the the peacock um these things you tend to see in um in males in nature so when you're talking about animals you tend to see the showy animal is the male and and that's because typically in nature it's the females who were doing all the choosing and so the females you'll know this if you look at any birds in your garden the females tend to be more plain and they have more plain plumage and and the males are the showy ones this also happens in fish for example in guppy fish the males are quite colored and showy looking um but the females are much more plain and um this is another example where it's an advantage for the male to be colorful because it helps him attract a mate but for the female there's no advantage so it's only only a disadvantage if she was colorful because then she's more visible to a predator so she gets all the the pain but none of the gain so this is the thing we see um throughout something we see in general throughout nature but i'm just going to talk about the first uh part of the book and which is all to do with human evolution and it has a few different sections on this so i have here just the the chapter headings and you can see the general topic so the first two chapters i'm putting them together and essentially what he's starting out here so as david mentioned the origin of species just had that um very brief mention of human evolution light will be shed so he waited a few years and he's shedding that light now and you can see where he's starting his arguments from because he is arguing in many ways from first principles you know that he's trying to say first of all you know that uh humans aren't separate from all of nature so humans are animals just like any other animal really and and he also then um talks about so he's talking about here various structures that are shared and in the section second chapter he's taking on um this kind of following on the same idea he's talking about inheritance and especially the laws of variation are the same in man as in the lower animal so basically you know genetics is the language of life he didn't know the words genetics and he didn't know how genetics works but this is why um this is why evolution is such a powerful concept and such an important concept because it uh unites all of the life on this planet and it does it through the fact that uh that genetics and genes are the same everywhere so his basic arguments he was looking for similarities in form across different animals he also talked about rudiments so um of ancestral forms so certain forms that were just still hanging around um in in a rudiment rudimentary form and which is evidence of some of the shared ancestry and then of course that the laws of variation are the same so this idea of similarities in form is um probably well known to everybody and it was his contemporary owen who um had a drawing a bit like this one looking at the forelimbs of various vertebrates so even though these vertebrates are very different like so humans have a hand at the end of the forelimb cats have this paw whale has a fin and a bat has a wing so these are all of these different vertebrates are extraordinarily different but when you look at them and you can see that the same bone structure is there essentially even though it's been stretched and distorted in the different animals so in this picture the colors are showing you the equivalent bones so you've got one big bone one big bone one big bone one big bone followed by two smaller bones so you got one two one two one two one two followed by a whole lot and so these are the yellow green and blue so you see the same structure in all of them so even though these have been um changed uh you you can see that similarity and so this was this was the kind of argument that was being used at the time and also and one of the oh sorry yeah so we can see this in our bones but then we can see the same pattern essentially in our genes so the same logic applies so here you see a slightly different version of the long big blue bone slightly different versions of this orange bone that you can recognize are the same even though they're changed and we can do the same with genes as well so here i have some gene sequences some dna sequences and i have actually i must have cut off the the label so this was human bat armadillo and horse if my memory serves correctly and so you see here the letters so this is just the way we write dna i think most people are familiar with this by now gcs a's and t's and so you've got across the top line is human um bat armadillo horse and then it's human bat armadillo horse it's just the the sequence is looping over the pages around around the page and um what you can see here is the dark coloring shows you when it's the same across all four of them the slightly paler is when it's the same in three and then the the pale blue is if it's just in two out of the four so you don't have to be very clever with mats to see that these are really very much the same across these four different animals so even though i've taken dna sequence from these four different animals you can see the huge similarity between them so this is like seeing that the the bones are the same across the different limbs and in fact i picked this gene because this particular gene is hoxay 13 i think or 14 and it is responsible for forelimb development so i picked the gene that is actually driving the development of the front limb the forelimb so we see it's the same gene i don't think anybody would dispute that this looks like the same thing in these totally these genomes from very different vertebrates but with a few little changes so we can see bits where uh there's differences so we can see just like we see in the bones we see variations of the same form and it's showing the ancestry you see this very very clearly in the genes so this the common ancestry is really really clear so this is these dna sequences like every dna sequence was inherited from the parents and the parents and the parents so there's an unbroken chain going back of inheritance right back to the common ancestors and the common ancestors of all of these different vertebrates even though they've got very different forelim structures and so and this dna sequence has remained almost undisturbed some very small changes over most of vertebrate evolution and part of the reason this works um is what darwin was referring to when he was talking about the laws of heredity being the same and so um of course we all know by now that we all have um dna uh every living thing except for viruses we all know about viruses now especially rna viruses so um some viruses of dna but some viruses only have an rna genome but this is a common uh common thread all through all of life and the way a gene works is the same everywhere as well so this what i'm showing you here is basically it's a eukaryotic cell so it's not a bacteria it's not a virus but the the principles are the same in bacteria so you've got the dna which is really really long contains all the genes and this can be transcribed and processed into an mrna which everybody now knows about as well because we've been talking about mrna vaccines over the last year and the mrna is a messenger so the m stands for messenger so the rna is just a version slightly different chemical version of the dna this gets sent out into the main body of the cell where it gets converted into a protein so we know about this now because this is the basis for the some of the vaccines that have been produced against the sarsko v2 coronavirus so the the the moderna and the pfizer vaccines are both using mrna technology which is taking advantage of the fact that this is the common language of biology so you can take a sequence from a virus which is what they did you can and just read it in your computer you can synthesize it and you can then insert and what the vaccine does is it delivers an mrna which codes for instead of any human protein codes for the spike protein on the outside of the coronavirus so when this gets taken up in the cell this bit of cellular machinery the ribosome comes along it reads it it follows the instructions because those instructions are universal it doesn't matter that it came from that it's supposed to be a virus sequence it's universal language of biology so it builds the correct protein building one amino acid at a time and the protein it builds is a spike protein of the coronavirus so that gets presented to the immune system and it learns to recognize it as farming and that's how you're that's how that vaccine works so this works because of this common language of biology so it doesn't so in this book darwin is is arguing that um the the laws of biology and the laws of variation apply also to humans they didn't know about viruses yet but it implies the the same laws apply there and we're also learning about virus evolution aren't we lately seeing how the virus is changing when it's given the opportunity when there are selective selection pressures that um that gets a competitive advantage and the competitive advantage of course one of them is um making more copies of itself by being more transmissible so we're seeing that there's a lessons in molecular biology and uh genetics and evolution happening worldwide in the last year or so so um so in the book then uh darwin then comes to the conclusion that humans are animals just like any other animals so man is liable to numerous slight and diversified variations which are induced by the same general causes are governed and transmitted in accordance with the same general laws as in the lower animals so um it seems that when he first wrote the origin of species he was um you know the idea appeared controversial he was perhaps hesitant to apply it to humans but here he makes this very clear statement and um david said it wasn't even too controversial by then so that is already uh good news so when we think about those so the next thing that darwin started to think about was development and the laws of development so here i'm showing you these pictures of the head of a fly a drosophila melanogaster fruit fly so this is a normal head as it normally should look and um you see there are these little antennae as well so these are the eyes the big fly eyes and these are the mouth parts and the antennae coming out and then we have this monstrous mutant it isn't a small mutant it's an extraordinarily enormous mutant because instead of having a small change it actually has legs growing where the antennae should be so it's a it's a monster and um the weird thing here is that this monster came about by a very small genetic change so in this experiment they were making they were inducing small genetic changes and the small genetic change created a monster so it was a huge big step um in terms of what good like the difference that this mutation caused and but this was really powerful because it was the first indication that there were universal master well there were master genes in terms of controlling uh body development that there is a gene that a small change in one gene can make a whole structure grow in the wrong place and these were uh labeled hox genes so you might have heard about them before but this was um one of the first discoveries so this particular gene was called antennapedia because it was making it was making the leg grow where the antennae should be and so when these discoveries so the same in the same idea as darwin thinking about um you know how he can apply uh how these laws apply er do they apply to humans and do they apply to other animals equally and there was this challenge in thinking about the whole process of development and how the genes can encode the instructions for a complex structure to grow so this um is from 1984 and and i'm including this statement um just because it's in hindsight embarrassingly wrong i wouldn't be here maybe i'm you know i'm picking on this person but um here we have he says that embryologists are confronted with an ensemble of unique phenomena we cannot expect to discover a general theory of development rather we are faced with a near infinitude of particulars which have to be sorted out case by case so this particular person was very pessimistic that there could be any commonality in development between uh different animals and if you think about something like the fly so not only does this fly look so radically different from us for example or fish or pick any other animal you like it also goes through like its development is very weird as well because it's first born as a larva and it spends some of its time in a larval state state and it goes through a metamorphosis before it becomes the adult form a bit like a caterpillar becomes a butterfly the idea that there might be anything in common between us and something so peculiar was quite strange but um the ink wasn't quite dry on this statement when it was discovered that the similarities in development um exists really very very deeply so this is um the way darwin was looking at it so this picture is from it's there's not very many pictures in the descent of man but this is from the descent of man and it's showing different embryos so on the top we have a human embryo and on the bottom we have a dog embryo and and what he's pointing out here is the similarities in form at these various stages of development and this is a well-known phenomenon and well recognized that as you look through development you see different stages which are very similar to each other and sometimes almost difficult to tell which is going to be which so we have these similarities that you can observe during embryology and then when we look at what's happening with the um the genes that lay out the body plan what you can see is at the top here we have uh an embryo or a larval form of uh i think probably the embryo here of um fly and at the bottom i think we can recognize the mouse and um they we have these genes which are these hox genes that i mentioned already like the one that makes when it's mutated makes the antenna go out of the wrong place so that's that one there antp is antennapedia so that's the one that got mutated to get the antenna the legs growing where the antenna should be and if you look this this is the the length of the the growing embryo and here we have in a row the genes are represented so the line is just uh the dna strand and the boxes are just representing the genes these have all been given colors and actually the color um of the gene is represented up here as well which is the region where that gene operates so in laying out the body plan in the fly you can see these genes are expressed in particular domains which makes the body plan come out the way it comes out so a leg grows here because the correct um to the the antennapedia the red is is growing here where the legs are supposed to grow so when you get antennapedia expressed you get the legs if you express antenapedia in the wrong place a leg is going to grow out of the wrong place so we see this similarity in the embryos and we also see the similarity in the genes so here we have what's happening in the fly but then you have the same genes that are also in a mouse and in us and in all vertebrates we have actually instead of just one string one line with the colored boxes on them we have four and that's because of one of the things that david mentioned in his introduction that there was a doubling and a doubling again in the origins of vertebrate so one became two and two became four and that's how we end up with four copies but we have so we have the same genes although in more copies and we see the same phenomenon that the the genes at one end get expressed in one end of the body and the genes at the other end get expressed in the other end of the body so this statement that there'd be no general laws of development and turned out to be extremely wrong because not only are there general laws but the genes are the same so you see that the genes that make a fly body develop correctly are the same as the genes that make a mouse body and indeed a human body give even given how dramatically different they are and it even goes further than that because in all kinds of different animals with all kinds of strange structures we see the same thing happening so again we see the the genes are in a row and the colors are showing you both the correspondences well they're lined up the lining up shows you the correspondences between the different animals and the colors show you where the the genes are turned on in the different uh growing animals and you see here okay we're in with the tetrapods so we look like something like that at an embryonic stage we can see in fish with the same we see the the color the rainbow colors all in order we talked about the fly already and then these polycheats these funny insects down here and these ones that aren't they're just outside the vertebrates and they're quite different and then you get these things like urchins which also have these genes and so these genes are really very very common throughout life and of different animals and we see that there's this commonality so even these extraordinarily different body plans very very different like this one has this uh radial symmetry and these extraordinarily different body plans all have the same fundamental genetics under them so these laws certainly apply and are certainly universal so another thing that um darwin was looking at then was what he was calling rudiments so he had this is um a picture he has and he's obsessed with this little um bit of cartilage or little uh detail that some people have in their ear and if you look at it in so he he has it here in the descent of man but if you look at it in later textbooks they call it darwin's something so this little structure is named after darwin now and what he believed this to be was if you imagine a pointed ear of a different primate that this was uh what's the rudiment of the point having kind of slightly folded in so not everybody has this little structure in their ear but some people do and um it so he considered this to be a rudiment of the the ancestral pointed ear that's just become folded in he wasn't totally um he wasn't going to bet his house on this he said you know there's a chance this could be just an anomaly of cartilage but i think he was pretty um confident on this and then of course if we look again at the developing human embryo you can see a very obvious tale as well which at this stage is um even more prominent than the limbs and so that's another example of some rudiment we have you know something that is not there in the final structure and not needed not used by us anymore but it's a legacy of the shared ancestry and of course this is our coccyx in in an adult form so we can see these things so darwin was looking at these structures because this is what was available to him but we also see this in the genes in terms of genetics so this picture here is uh is a representation of the first ever um clinical trial so um where there were case control a case control experiment on a medical intervention which was done for scurvy so and these are sailors on a ship and and sailors on ship could frequently suffer from scurvy and it wasn't known what was causing the scurvy and um lint was uh actually not sure that he was he was must have been a doctor and but he decided to try different treatments for the scurvy and he'd actually one of the things he tried was lemon juice and the account that i read of it was actually he didn't really think that lemon juice was a credible treatment he just put it in uh anyway kind of like as a it wasn't one of it wasn't his favorite hypothesis when he started but of course the the individuals who received lemon juice were the ones who did well because we know they didn't know then but we know that the lemon juice contained vitamin c and scurvy is caused by a vitamin c deficiency so we and we need vitamin c um a vitamin by definition is something that we must obtain in our diet but we only need in small quantities so we need vitamin c we only need a little bit of it and but we need it because we can't make it inside our own bodies so vitamin d is not a true vitamin by that definition because we can make it in our own bodies in sunlight but we used to be able to make ancestrally we could have made um we could have made vitamin c which is to say that not our human ancestors but but like uh vertebrate ancestors so there's this gene which has this catchy name el gulano gulano gammalactone oxidase which is the last step that is this gene carries out the very final step in the vitamin c biosynthetic pathway so when you have this gene you can make vitamin c from other ingredients and you can do it in your body because you can it can it's a biochemical process to make the vitamin c inside your body and this is this gene so it's broken up here into 12 parts that's just because the gene is broken up um in the genome and these uh green this green coloring is just showing you that it's this is kind of how it's been what you find is you don't find the gene you essentially find a rudiment of the gene you find um where you find that kind of broken structure in the same way that we have a hint of a tail but not a real tail we have a hint of this gene but we don't really have it so these um yellowy shaded boxes are actually deleted they're missing in the human genome so this gene is only partial and the partial gene doesn't work so it is it is not a complete gene so that is because we are missing this we can no longer make uh vitamin c inside our own bodies and independently and but similarly the guinea pig cannot make vitamin c so if anybody has a pet guinea pig i guess you need to give it some vitamin c in its diet and but so what happened why did we lose this gene especially considering um without vitamin c we suffer quite badly well um there is no um we don't know a hundred percent for sure why we lost this gene but the a very uh a plausible explanation is that actually we had at some point our ancestors so this is lost in other great apes as well so it wasn't just in humans so in in the primate ancestry we were possibly living with a rich dietary source of vitamin c whatever we were eating habitually had a what had a lot of vitamin c so it doesn't your survival doesn't depend on how you get your vitamin c so if you get your vitamin c because you're eating it or you get your vitamin c because you're making it inside your own body there's no difference all that matters is that you got vitamin c and you don't get sick so if you then are in a member of a population or species that's eating these fruits for example commonly um and you get a mutation one individual gets a mutation that deletes the first chunk of this gene so that it no longer works anymore that individual isn't going to suffer in a natural selection sense they're going to pass on their genes as well as anybody else because they're not missing vitamin c they don't make it in their own body but they're not missing it so there's no disadvantage to losing the gene in that context and because there was no disadvantage to losing it there was nothing that was preserving it so it wasn't being kept so it's this kind of idea use it or lose it so there's no preservation force so because natural selection a lot of what natural selection does is it preserves things keeps things as they are and that's why when we looked when i showed you that gene sequence of the hux gene that's um determining the the forelimb we saw that really strong similarity across the different animals that's because natural selection is preserving it when a mutation occurs those individuals um aren't surviving as well as the others so that mutation gets rejected by natural selection here the mutation didn't get rejected because the individuals did just fine so we see this so it's the same principle as darwin was talking about um but it's we can see it now in a genetic context we see these leftovers so he pretty compellingly showed convincingly showed that um there's a this really strong connection between humans and all of the other animals so he says we have given man a pedigree of prodigious lengths but not it may be said of noble quality so anybody who wanted to claim they were better than the animals or superior and all of that and doesn't really have a leg to stand on so it that's i think it's a it's a lovely uh quote so then in the next section of the book i'm not going to talk for too long about it because it's uh it's harder but it's he's talking about um the comparison of the mental powers so and um so we do know though that when we consider ourselves superior as we are want to do and we think it's all to do with our big brains and uh so evolution of the human brain is a very interesting um very interesting phenomenon and it's very interesting thing to understand and so when we think about it when we look at it just to briefly show you in here in this paper what they've done is they're looking at these four different primates so we've got bonobo and chimpanzee which are quite closely related to each other we've got human and we've got macaque and so we carry those colors over here so the the macaque monkey is uh green the human is red then we got the bonobo is the purple and the chimpanzee is the blue and so this is just an analysis of the genetic variation and the variation of genes expressed in the brain and one thing you can see is that you can see this difference you can see that um the bonobo and the chimpanzee are close to each other and so they have less difference and not much difference but then the macaque is clearly different and the human is clearly different and you can think about these in terms of where they're expressed in the brain but the um important thing is that we find the same genes again we find the same genes are present in the brains of these different primates so it's not we don't find the there's no magic key there's no single thing that we can find that says this is what makes the human brain different from other brains is what makes the human brain bigger it would make what makes it capable of the more uh abstract reasoning or all of these things that we might think are important and and so we don't find a single genetic cause and so what we find is small differences but they're we find the differences but they are individually small but maybe with a large cumulative effect and darwin talked about this um because he was talking about it then he said you know it's not that we're separate we're not a totally different kind of thing we're just a bit more in one direction so he's about then the difference in mind between man and the higher animals great as it is certainly is one of degree and not of kind and he talks about this idea a fair bit in the book where he talks about is this a difference of degree or is it a difference of kind is it that you're just you know is is is this something that's totally entirely novel or is it just edging one way or another he also goes on to um i think when the interesting things he talks about again i think he was he was probably very much interested in getting the readers to know their place and not feel too superior because he then talks about how ants have such an incredible intelligence so ants are capable of complex communication they carry out these tasks and all of this thing and they are tiny and therefore their brain is tiny and he says something along the lines of gram for gram or ounce for ounce whatever he would have used that the the ant brain has probably the most spectacular brain on the planet okay so then the last sections of the descent of man as opposed to the sexual selection is where darwin then talks about you know the origins of humans so he spends the first bit talking about you know putting um that you know we are part of nature and the same laws apply to us but then he starts thinking about um you know the origins um of humans so he thinks about where did we come from you know how did how did we arise and how are different humans related to each other and what is the significance or the value of our differences are these differences important so this is where um as david mentioned in his introduction he has this whole chapter which he describes as on the the racists races of man and it um i think it's quite uh you know if you're when you're used to thinking about things in modern language because he is talking about whether um he's asking the question can we be considered all one species or are we different species so and i think it's not you know it's it's uncomfortable to read that but the way he approaches it is quite interesting because he says if you were a naturalist and you came along and you were looking at these creatures for the first time with some of those creatures being you know him one of those creatures being himself and how would you analyze them and what are the tools you would use to analyze them and how would you decide how they're related or how they're different and so um he talks about how um if you wanted to categorize um you know there are some [Music] features that you can see are different if you wanted to but then there are so many things that are constant across all of them but then i think importantly even on the features that you might think are different and of course skin color being the most uh immediately obvious one you cannot put them and this is i think uh the most convincing point which shows where like as as david said like where his conclusions lay is you can't put them into categories because it's more like a continuum so if you think of skin color as a sample you can go from very very dark to very very pale skin but you don't have categories inside that you basically got all the shades in between as well and so he kind of says well you can talk about three races or five races or maybe you took about 20 or 300 and that tells you that it's not sensible at all if you can't you can't even describe what difference you're trying to to look at but in terms of um where we come from and we think about it and we can of course these days look at this from a genetic point of view and there's been extraordinary work done on this um in recent years because the availability of dna sequencing and how cheap dna sequencing is these days has made a huge difference so this is one way of looking at um which is down a microscope and these are so it's chromosome one they're a little bit bent and twisted chromosome two three four and the human chromosomes are numbered in order of size just except for the x and the y which are of course special because uh they're to do with sex determination but the other ones are numbered in terms of size and so you can see them down the chromosome here and we've got two cup two chromosome ones two chromosome twos etc but if you just count one of each we've got 3.2 billion letters of dna or so and of course we represent the letters as a c t g and if you pick any two individuals at random in the world um unrelated individuals so not ones with a close relationship but they're going to be different on average in one in a thousand letters so that's the same no matter which people you pick so if you pick somebody from africa and somebody from south america or if you pick somebody from east asia and somebody from europe you're gonna find this difference is around about the same so that's our first interesting observation that we are a very young species and the the diversity we have and the the relationships are all pretty equal you know we find this one in a thousand difference more or less for anybody and so we can think though we can still think about so most of the differences like that are um you know quite constant or consistent across the world but we still can there is a residual small amount of difference that we can do which can be used to trace um geography so we can use it to trace geography as well so and these this picture here is um the laetoli footprints in africa which are fossilized footprints showing upright or bipedal sorry uh walking so these footprints um have been studied then and they are the first known example of bipedal walking so they're considered a very important discovery in terms of understanding human evolution and we can think about genomic footprints not only physical footprints you know in terms of tracing how humans have moved around the world and so we can do this with a kind of very simple principle which i'll explain here so if we imagine we have this starting population here so and here each circle is an individual and the slightly different colors are just showing you the genetic variation so this is a population of different individuals and there is genetic variation and this is a reasonably big population in this pretend example so um it can carry a fair amount of diversity so if you have just two people in your population that you're studying that's obviously got a limited carrying capacity for genetic variation you can have you've got two copies of each chromosome um in in each person so maximum is that you got a version on your one copy and a different version on your second copy and the same in the other individual so you got an absolute cap on the amount of genetic diversity that can be carried at any one position in the genome so you've got more people it's just got more capacity to carry more variation so this big-ish genetic this big-ish population has been around for a while and this diversity has accumulated over time in this population this is our starting population and let's just imagine a scenario where some individuals from this population migrate and found a new population somewhere else but it's only a small number of individuals so three in this pretend example so by definition they can't carry all of the genetic diversity that existed in this big population so they're just carrying a subset of the variation so in this case a green orange and blue variant and then that can grow up over time and we see this new population has got bigger but so far and it hasn't um gained any new diversity so we see these two populations and this one it can be recognized as a subset of the diversity of this one and then the same process can happen again some individuals from here found a new population and and so on so we can see this effect so we can see what's uh this these founders the ones who found a new population in new place and each time you're sampling the diversity so we've got a lot of diversity here you take a sample that found this new population a sample that founds that one and we basically do this analysis um globally on humans and you can see this type of pattern and so what you find is that the area of the world with the greatest amount of diversity is africa so in africa we find the the largest amount of genetic diversity and then as you step out from africa you can see this sampling effect so as you step out from africa you see the a sample of this diversity is here and then go left go right there's a sample here and then samples sample and you see this sampling effect so this is really useful because it allows us then retrace the genomic footprints which are actually tracing literal footprints because people of course would have walked as they migrated around the world so genetically it's absolutely unambiguous that our species originated in africa and that we migrated from there gradually over time and then we can look then in a more modern context at you know looking at the diversity the genetic diversity globally and this is a really famous image in science circles which is uh probably a little niche but there you go but um this paper is uh it's from 2008 so it is a good few years old now but um it is very much a classic paper and this type of analysis has been repeated over and over on different human populations so what they did here was they got dna samples from individuals around europe and they did a statistical analysis on these dna sequences that they had taken so as i said before you know most of the genome is really so most of the interesting parts of the genome is really conserved we see a lot of like a lot mostly uh similarity across all of the globe and this average one in a thousand still applies and then there's a small amount then of the other variation that we can see this other kind of residual signal in and so what they did was they did this genetic analysis which essentially is a statistical analysis that just sorts out the differences so this is pc1 and pc2 it's a principal component analysis in case anybody's really into their statistics but um a principal component is just a statistical um measure which is kind of saying what's what is the um axis if you like that finds the most uh variation and then the second most and the third most and the fourth most and you can go on to lots and lots of principle components but here we're just spreading it out in 2d space statistically um decided so the information that went into this analysis was just the genetic information but then they colored their data points um in this graph afterwards according to the country where they had taken the dna sample so if you look at this you can see here's ireland with great britain beside it even scotland in the north of great britain just like in the map then we've got france here with uh spain and portugal down below it so here we've got the atlantic coast of europe italy projecting out into the mediterranean and then you can see uh germany and denmark sweden and norway finland poland czechoslovakia so the genetic variation is mirroring the map of europe extraordinarily well and when you think about that this analysis was done entirely um blind to the origins of the samples the samples were all treated the same and this coloring in only happened at the end to illustrate the point so the the genetic analysis showing the is really powerful and showing these little in these these differences and these geographic origins or geographic relationships actually so this is not comparing to the past it's only comparing to the present so it's saying that the italians uh you know are like each other basically and the irish are like each other it's not saying um where things came from and this i will emphasize mainly because sometimes this type of thing gets misused this is a really tiny amount of the variation that gives us this kind of signal you know it's a small bit of the genetic diversity that is not like most of the genetic diversity is global and you find it all over the place but this is really this is shows i think uh some of what's really interesting and powerful that you can do in terms of understanding uh human genetic diversity and origins but um when we look at the general we'd say the kind of diversity we see and the genome is mostly inconsequential and i mean totally inconsequential as in nothing happens so you have um that 3.2 billion letters of your dna only about two percent of that is really genes and the rest of it is just stuff and most of the time when that stuff changes nothing happens so we can use it um when we're doing these genetic analyses and that's probably the kind of thing we're seeing here there are variations in the stuff and just the packing and not the actual genes but they're useful they're informative if you're interested in history sometimes they have an effect but they're not that important an example of a variation that has an effect but we don't think is terribly important would be for example your blood group alleles so this picture is showing you the frequency of the a allele so you have the blood groups so you can and somebody will be so there's a b and o alleles that give you the a blood group the a b blood group the b blood group and the o blood group so this is just showing you a and the darker the color the dark blue is the highest frequency white is the lowest and then we've got this yellowy red and so you can see there's quite dramatic variation in the frequency of this a blood group allele across the world like it's really really low in south america for example it's really high in this bit here of north america really high here um in finland and then you see intermediate in other places so this is a genetic variation it's got a global distribution that looks uh interesting but it doesn't change your health status it doesn't um not that we know of give you any advantage or disadvantage so it has an effect but it's not important but sometimes we have variations that are really interesting so the classic one of these that you've probably heard about before is an evolution of resistance to malaria and so there's a very interesting pattern if you look at the map of africa and this dark green is showing you where there is malaria infection and this orange is showing you where you find a particular variation of one of your hemoglobin genes so your alpha and beta globin um together make up your hemoglobin and there's a mu there's a variation there's a mutation different version of the beta globin that is common in parts of the world where you find malaria and utterly rare everywhere else and this um is this mutation causes your red blood cells to form this weird shape which looks a bit like a sickle so it's called sickle cell um and so you can see here that's the normal shape of a red blood cell and this is the sickle so it turns out if you have sickle cell um if you have if you carry one normal copy of the beta globe and in one sickle cell copy you're going to have some of your cells will some of your red blood cells are going to be uh malformed like this into a sickle and um if you have two of your two of the sickle forms you're gonna have all of your blood malformed like that and i think you'd be very very ill but if you have one and one male formed like that you have some of your cells are some of the one one of your copies of the gene is the sickle then only some of your red blood cells will be shaped like this and so it turns out so those the reason you get um sick with sickle cell is those red blood cells when they're in that shape don't work so well and they you can get a lot of pain and you get uh so a lot of other effects and then um quite anemic as well but when you carry um only one copy of that gene you're anemic you have some consequences and if you're living in europe and you just have anemia and it's no advantage at all but if you're living in a malarial area it turns out having these sickle cells helps you clear the malarial parasite out of your body better and so you don't get malaria you're resistant at least resistant to malaria and so it's partly it seems to be because these sickle cells are targeted for recycling more efficiently and so the malaria parasite gets picked up and recycled out and so this is a case where this is an advantage this is a mutation that is regional geographically regional this allele is common um in this part of the world and rare everywhere because it gives an advantage in that part of the world and not in other places but there's another um interesting localized uh genetic adaptation which appears to be an adaptation to diving so um in southeast asia there's these uh this group of people who are known as the bajau i'm possibly mispronouncing that um who have uh who who dive essentially for their food collections they go fishing by diving and this is a long established tradition and so there has been over many many many many generations um selection in this population apparently for being better divers and being able to hold their breath for longer and what we see is in this um population there's a mutation in this gene and that mutation results in a larger spleen and a larger spleen and helps these individuals retain more oxygen from in their body for longer so that's a really interesting example of where we have some of these interesting and useful differences globally and then this picture summarizes a whole pile of these because there are loads of them so um this one this jean edar one is associated with thick hair you can see there's a little key here at the bottom so um people of east asian ancestry tend to have beautiful thick uh strong hair and it's due to um it's due to a variation in this particular gene we see um again these are uh variations uh in genes adaptations which give resistance to malaria so that's the mosquito there which carries the the malarial parasite so hbb is hemoglobin beta the the beta globin that we mentioned already and there's some other known there and there are examples that are to do with dietary adaptations so there's adaptation to a dairy diet which is basically lactase persistence so milk is baby food and in most animals um after weaning the um the uh the animals can't digest milk anymore because they don't normally eat it and but in um humans of various groups of humans so some humans of european descent so we have it up here in europe as well but also in the middle east and africa it's occurred independently that there has been this adaptation to milk to eating milk in adulthood so it basically that enzyme lactase keeps being produced even into adulthood which means you can digest the lactose sugars in milk if you don't have lactase you're going to be lactose intolerant and when you drink a glass of milk you're going to get a very upset tummy and but then we see other examples so adaptation to cold adaptation to altitude this e-pass one is very interesting because this particular adaptation was possibly acquired from denisovans so this at this adaptation exists in a region of the genome which has actually been in tibetans is found in tibetans and in the denisovan which is an archaic human a bit like neanderthal and so we see these different parts of the world got these different adaptations to diet and to disease resistance so um and adaptations the the um the hair in this particular case and the most plausible exam explanation for that is that it is an example of perhaps sexual selection that it was just a preference and the the beautiful glossy hair so that's it that's my uh summary uh my um big kind of whistle stop tour through uh darwin's first part of the dissenter man because i could i could do a whole lecture on each chapter i think because there's so much that we now know but um hope that was interesting hope it wasn't boring for those of you who've seen many darwin day lectures before but um it's a tough crowd in this place you're all far too well informed and um so and i i'm really happy to hang about and chat and take any questions or whatever you like it's awesome thanks so much that was fantastic i can assure you that uh there was nobody bored and the 140 people that were here to the end is a good sign of um well this way i think that uh david's compliments and your your skills as a teacher were are clearly well-founded so i think the uh the traditional way of expressing um appreciation in these circumstances when you're muted is to uh okay well thanks very much everyone everybody doing that um dude you were speaking there for an hour do you want to was i sorry i'm okay and there you go sorry about that does anybody stop certainly no need to apologize don't worry about that um i guess just to remind people i i can't actually see this in my screen because i'm the meeting organizer or whatever but i believe and i tested this at the weekend if you click on participants uh a tab should appear on the right hand side of your screen and there'll be a raise hand button at the bottom of that yeah there's another way of doing that as well eamonn across the bottom you have reactions and oh no actually sorry it's not it's only in the webinar version so you're right go ahead there i see it though i see it in the raised hand but i just see other questions oh somebody's asking me if pfizer or moderna are better than oxford russian or chinese they're all different and so i mean this is my own fault for mentioning the vaccines but so the pfizer and the moderna um are very good but um like one of the big advantages of the oxford is the ease of distribution so it's you know is uh you know one with a slightly lower efficacy but that is easier to get to more of the population might overall be the better vaccine in terms of because in terms of vaccination the protection is um there's an individual protection potentially but the better protection is the population protection so the better thing is that it gets to as many people as possible and somebody else is asking for the about the vitamin c sorry am i moderating why am i taking your job and what i was going to do was uh just kind of more conversational some people asking questions in the chat me hogan kerrigan uh you can you're gonna mute yourself there if you want to ask your question on vitamin c so people understand the context if you're not looking in the chat box hi hiya um i was asking about you were talking about vitamin c and the fact that because humans didn't need it because there was enough source around them uh it kind of got dropped somewhere along the way but what about the fact that you know we actually do need it and most of us are not getting enough for various reasons would it be a possibility to re-evolve that's all just what you know how evolution's still going on i'm assuming yeah so it it is a possibility but it's not an easy possibility because the way the gene has been broken essentially it's not easy to resurrect that specific gene and so it would be it'd be easier if it was just let's say if it was there but turned off it could be maybe easily turned back on again but um that's my dog shaking sorry if you can hear the jingling um but because there's actually been bits of the sequence totally destroyed and it wouldn't be easy for that to happen again obviously that gene evolved um once before at least so it could happen again but it's probably more likely it's probably it's it's a relatively unlikely scenario so um but we are still evolving yes yes okay that covers about this okay thank you uh tom do you wanna fire head uh yeah it's just a supplementary to that uh you mentioned that the humans aren't unique uh amongst the upper apes and primates um of having lost the ability to manufacture vitamin c in their bodies i was wondering whether uh baboons and other species uh have a scurvy-like disease for a want of vitamin c if they're deprived of it and the environment yeah yeah um i actually don't know that i mean certainly they would have the potential to have it i mean so i'm i can't remember now which of the primates i know it's definitely also gorillas and chimpanzees but i can't remember where in the primate lineage off the top of my head that uh that gene was lost so i can't remember if it's baboons but let's say chimpanzees and gorillas they would have the potential to have a scurvy equivalent and whether they that actually occurs naturally and probably depends on what they're habitually eating but having the absence not being able to biosynthesize um vitamin c they would have the same problem that we would have in terms of if you don't have vitamin c um you have all kinds of deficiencies i think the one that is the most um obvious is the effect it has on collagen which is why um one of the effects they see is uh that the collagen totally breaks down which is making up a lot of your skin integrity and um these very other various parts but they so it ought to happen but i haven't read about it it ought to be potentially possible but um i haven't read about it actually happening good evening everyone just i asked a question there about crispr cast the new gene editing techniques and in 2018 the european court of justice basically said that gene editing techniques should be regulated like gmos and of course uh steve mcconnell said many many years ago um you the eu will bury our heads in the sand perhaps regarding gm technology and we do the same again like with crispr cass how important is crispr cass in your research for medical medical uses and i know it's important for plants but this is something that is can be really important from an irish point of view and also from an eu point of view thank you ava a great lecture by the way thank you tom so um i'll say so in my specific research in my lab i'm not using it but i can talk generally and that i know that my colleagues are using crispr cast 9 technology for almost anything so not necessarily as a medical uh therapy not necessarily because but it could be that it's being used um as a research tool it's a really really really valuable research tool it could be it can also be eventually incorporated into medical therapies but it is a very important tool in developing many fundamental understandings because a classic way of understanding things in genetics was always to make a mutation in the lab in a gene say in a fly or in a bacteria or something like that or in cells that could be human cells growing in a plate and with casper the crispr cas9 um you can do it in a deliberate targeted way and not trying to just get you know so it it it's really really powerful and i know my colleagues are using it a lot so this this law that meant it was basically um more difficult for them to do this research i think it was a it was a short-sighted uh ruling if that helps david can probably give him much more better much more elaborated answer at some point whenever we open up the conversation um ian do you want a firehead okay thanks evan had a little bit of a heck up there if uh i just wondered uh about categories and about difference in kind and just how do we how do we distinguish species at a genetic level um it's actually not that easy and it is like a perennial problem so um you will find people arguing indefinitely on this and maybe doing a whole phd on like how do you actually define what a species is so there are the easy ones you know which are easy to define so you get past a certain amount of difference and that's easy so and there are um there's a concept which is called the biological species concept which essentially just says that if these um are capable of interbreeding successfully then they are the same species so successfully means that the offspring are also fertile so a horse and a donkey can breed and they produce a mule or a honey depending on which way which one's mom and which one's dad but um those are sterile so that tell you know so that is convincing evidence that those are different species but that's easy it's easier when they're so different the the challenges um when they're less different how much difference is enough difference and part of the problem there is that speciation is usually a gradual process rather than a single one-day event so um there are going to be different degree there's different stages along that process so you might be witnessing and what they might call incipient speciation so something that's on its way to becoming a new species but it could even still be reversible at this point like it can go so it they could be getting different from each other so two groups will be getting different from each other and that if this continues as they will be different species and but it could be it could be still that they could get back together and or or you can go to past a certain point where it's no longer reversible so it's a very very difficult problem and there isn't a single metric that tells you the answer because you could get um a genetic incompatibility between uh the groups based on a potentially small amount of um difference or but it could be a large accumulation of lots of difference and though that can happen in different ways in different times and places so there's there isn't one answer there's not one rule thank you kelly do you want to go ahead uh yeah thank you very much if it's a great pleasure actually a very nice lecture i'm always i'm always um like um concerned about this um example of nature and nurture and you have mentioned the example of the diving and the sickle cell anemia and as um [Music] acute medical physician myself i deal with some practical uses of genetics in my daily life situation and wonder about dating of a specific gene for example did you say dating yes yep like dating us by age so uh can i say uh this game started to exist in the human species at this point of history and it's been introduced because of such um a kind of factor whether it is nature or um effects from other species or some weather changes and uh can i also find out a mutation that happened at some point of history because of such uh intervention between uh the species the the human being and nature thank you very much so um kind of yes you can sometimes i mean so some so sometimes you can trace um the origins of particular mutation you might be able to get a fairly accurate date on when it arose and but not always and sometimes you can find a pretty plausible explanation for the circumstances that meant that that g that new that new mutation then rose in frequency so but we can't so it rising in frequency to become the dominant one like so or or at least at a high frequency like the example of the the sickle cell anemia and we understand why that is why that rose in frequency we see the advantage it gives and we don't always have that um information though so some it and it so sometimes you can sometimes you can't and sometimes it takes a lot of work to do it so and one of the ways you might know how old a particular mutation is is by looking at how common that mutation is around the world so if something is very geographically restricted and you would you could make a fairly justified assumption that it's relatively recent and it's just in you know maybe a big like an extended family group if it's if it's uh very broad around the globe it looks like an older mutation that has had time to move as those individuals moved and things like that though even saying that there is a phenomenon where you can get essentially the same mutation happening independently um in different parts of the world and that's because some parts of the genome are a bit more prone to mutations so the same what looks like the same event can happen in one individual and happen again in another individual a bit like um trisomy 21 you know getting an extra chromosome 21 happens independently each time so you have different versions of that as in smaller smaller duplications for example can happen independently so we don't always know why that a particular um mutation rises in frequency and it doesn't always have a good reason so one example i think that is um evolutionarily interesting and medically relevant is the one that's called um you might have heard of it ccr5 delta 32 so the cytochrome um five is it slightly no anyway it's uh um cytochrome receptor five and delta 32 is a deletion of 32 letters from the middle of it so this particular version of so the ccr5 the normal one and there's the delta 32 one the delta q1 is associated with resistance to hiv infection so that i was very disappointed when i heard about it in college uh when uh there are certain people they can't carry hiv but they cannot show any aids manifestation well basically the virus doesn't survive in their bodies because it can't it's what happens is um when hiv enters the the t cells it's binding onto this uh chemical receptor five it binds there and that's what it how it docks and enters the cell so people who have this mutant version of that protein hiv doesn't dock and bind so it doesn't get into the cell so it just dies out again quickly but this was very interesting when this was discovered it was discovered by accident and by doctors in france i believe who noticed that certain individuals despite living what you might describe as high risk lifestyles you know sharing needles and things like that were not getting infected even though their friends were getting infected and they looked for what was different in these people and they found that they had this particular mutation so this looks like wow is this a some evolutionary adaptation to a privilege hiv except it's not because we you look at this and you see this particular mutation is much older than hiv hiv is a relatively new virus that infect affects humans it came from um chimpanzees and the we know roughly when hiv entered human populations and we can see that this ccr5 delta 32 is much older than that so then people were going well is it something else was it another protection that this um gene gave this particular variant of the gene gave and so one idea was well maybe it gave protection to plague because or maybe gave protection to uh and all of these different ideas were explored but none of them um really looks convincing so it looks like it's just a fluke so even though this is a very medically um relevant mutation and it's probably just it's just one of those things a bit like um blood group variation it's just one of those variants that exists and it's there because of genetic drift so anyway so you have these stories like this it's very interesting actually i'm personally interested in them and uh looking forward to see which genome is more uh prone to decay by time and give out to medical some medical conditions which can be preventable um you know so thank you very much for that very interesting thank you thanks khalid um i think just just to put a limit on it we don't want to keep if uh very a lot of your time this year well i mean i'll i'll tell you when i'm wrecked because i or maybe you're trying to politely tell me to go but i mean i've got nowhere else to be it's locked down like the next point yeah maybe we'll say like yeah maybe like a few more minutes i will go to we've got uh we've got three more questions lined up the next one is from uh sima sharma and then we'll go with ono lynching and then ben quinn and we might then call her today hopefully around or who knows yeah hi uh thank you it was great uh session and and i'm really happy to i was being able to join from india actually and it's here here it's here 2 43 so it's it's quarter you know it's going to be 3 p.m here sorry a.m but today is darwin's you know uh you know that day so i just wanted to ask this particular question which is there in my mind since ages that why homo sapiens uh you know that you know there there is a single thing homo sapiens for male and female why there is no categorization uh is there not sufficient genetic difference or whatever the criteria is because from my understanding uh being a science person i think that there's a huge you know difference uh where uh women or female can get some genesis species you know so i i need your help to make myself understand sorry maybe i think i need you to um ask the question again because i'm not 100 sure so you're asking about categorization in humans yeah because yeah yeah homo sapiens you know homo sapiens means uh you know strong men you know sorry why is men thinking wise men so what about the women you know and and and that is one thing and the second thing is that the female there is a difference you know there is a genetic com difference in male and female so i think if you can you know give homo you know genetic species name different to the different categories and why male and female what is what is that why it is that i think i understand your question so in a species you would always give the males and the females the same name so you wouldn't separate them out into different species because they um you know they they go together in that sense you know we talk about a species as something that's um interbreeding um then they are all one species so i i suppose um in that sense the the homo um is it's like saying man in the same way that darwin said it in his book it's just meaning human but um so yeah you in in any species you group the the males and females which is not to say that there aren't uh differences of course i mean the most obvious genetic difference is the x chromosomes two x chromosomes in the female and an x and y in the male but that is a genetic variation the same way that any other genetic variation is it's just one of the possible variations it doesn't sep it it doesn't make them separate species okay but there is a bias in the name itself so i guess there is some it should have been something then because i feel that you know this thing need little more justification because it's not very justified which i don't want to get into that conversation but this really sounds uh very uh not very suitable uh you know so thank you very much for your response i was expecting this kind of response only but but yeah i'm happy that you know um iman uh murphy uh took my question and and i got my response and thank you for staying up so late to watch the video thank you so much yeah great thanks thanks i'm done thank you thank you oh and do you want to fire a head yes can you hear me yeah my question may be totally irrelevant thank you very much by the way for a very interesting talk uh you spoke about the the brains and similarities between the brains of all the species uh now there is i think a difference in the level of consciousness between the species uh they call it the hard problem do you have any opinion about the origin of the consciousness i think it's a hard problem and yeah no i am afraid it's um i think it's a fascinating question but i don't think i have anything very clever to say about that unfortunately and i think we do it is worth being aware or just being conscious of the fact that we are a very egotistical species so we know more about ourselves and what our brains are capable of and the way we can think and um you know we possibly underestimate somewhat what the other animals are capable of and i think you know it's uh you know jane goodall's work with chimpanzees where she changed how people um think about what chimpanzees are capable of and people were very confident that they weren't capable of of any kind of communication or tool building and things like that but yes i mean clearly our i mean our brains are um we're capable of imaginative thought and all of these things that i don't know that other animals are capable of but um i don't i i it's i find it an extraordinary problem i find lots of things extraordinary problems in terms of you know how can such a thing be encoded in the dna which it self-evidently is encoded in dna but i i can't get my mind around that how that can how that is so but um yeah sorry i don't have anything better i think you're not the only person who can't get his mind either her mind around it well at least i take comfort in that thank you very much thanks thanks for that i want uh ben hi but thanks very much that was really really interesting talk my question just related to a documentary so i played a number of years ago now and i think they talk about two very isolated populations i think one was in iceland the other in a valiant switzerland where they had suffered famine quite a number of generations ago but they continued to remain pretty isolated in terms of of uh breeding of that and people they weren't they didn't mix too much with with outside populations according to this documentary at least they were they were finding that damage done to the to genes that direction were the damage was caused by by famine that this persisted from one generation to the next now i don't know whether that was just a period being advanced and whether that theory has just been discounted or or whether there's any truth in that but i often ordered in terms of families here in ireland i think the west of ireland is the system you know is a much higher occurrence i think than in western ireland than in many other parts of europe even i think it's city workforce i might be wrong with that but uh i just wondered have you any comment on that at all so um with regard to the famine thing i'm not sure i heard the exact example you heard but i did hear a similar um story that was um supposed to be um in dutch people who lived uh through world war ii and experienced an extreme famine and there was um evidence that there were uh some genetic changes that apparently persisted for a couple of generations but um i haven't so i haven't tracked that literature and paid attention to that literature very very attentively but what i remember was that um the explanation was that if for example um uh let's say i i lived through uh world war ii as a female living in world war ii um and i experienced famine and as a female um my ovaries contain all the eggs that i will ever have from birth right i don't produce them later so the ovaries were there and potentially um are affected and then any children i have were then potentially affected and if they uh you know so there was that potential of uh effect like that rather than it being a more durable effect over more more generations than that so that's um that's the way i heard about it but as i say there could be more to it than that than because i haven't been tracking that literature very carefully with regard to cystic fibrosis yes so we have a very high frequency i think in ireland we have the highest frequency um of carriers of mutations in the gene which then can if somebody carries two of those they will have the condition and there's other conditions which are kind of peculiarly high in ireland another one is hemochromatosis which again is another genetic condition and which leads to abnormally high iron retention and which can accumulate and cause problems and in both of those cases um we don't have a clear explanation for why it would be that those are high in ireland and it could be just one of those things so with respect to europe ireland is kind of at an extreme and if you remember um the the idea i had of that serial founding uh effect you know so you have a group and some of them move and some of them move and so one possible explanation is just um of the people who migrated to occupy this island and you know if one of them carried a gene for this particular mutation that um causes cystic fibrosis and you know only a hundred people moved and one of them carries it then all of a sudden you know what what might have been a one in a ten thousand frequency in the starting population is now a one in a thousand or maybe it's a one in a hundred depending on how many people move so you get that kind of um chance event and that could be the same for hemochromatosis as well there's another possibility that's been mentioned for cystic fibrosis but i don't know if the evidence is very strong but the idea is similar to the one to do with the malaria and the the sickle cell in that having one faulty copy might have an advantage under certain circumstances and the potential circumstances were actually that it might give some resistance to tb and being a farming traditionally farming um culture people have encountered uh encountered tb through bovine tb so that's an idea um it has merit as an idea but i don't know if it's uh i don't know if it's been really demonstrated but that's one potential idea is that the cystic fibrosis the the mutation that causes cystic fibrosis when you have one of those and one ordinary copy that you would have uh this advantage in terms of potentially resistance to tb but like i say i can't i can't say for sure that that's that's true but i think it's an interesting idea so i hope that helps if we have a beer dancing their virtual arms by uh seeing if they can squeeze a question in there would you mind taking two more from sorry may i be the one to ask questions thank you very much for the lecture by the way it was terrific thank you sister i am a scientist but one question i would like to ask is what is the main cause of mutations and also are viruses particularly susceptible to these because they're single chain unlike dna where the chains are locked together and a little supplementary i mean what fraction of these mutations tends to improve the chances of survival okay in other words be useful to the viruses so um in terms of how mutations happen in general mutations happen when you copy the the dna or if it's the rna so it's during the replication process so for humans the only time that matters is the replication that produces either the sperm or the egg cell because so in when your body grows you can get mutations as well and if i was to sequence the dna from a skin cell on your left hand and on your right hand i would probably find some differences very small amount right but um i would find some because every time a cell replicates the dna has to be replicated for that too and every time you do that there's just a chance that a mistake occurs but in our cells we have a lot of um error checking mechanisms dna repair mechanisms in fact the nobel prize and went for dna repair understanding dna repair a few years ago because it went to a few different people and and so even when errors occur they can be reversed and there's certain mechanisms to do that so in a virus um even if it's some some viruses only have a single strand like you said the rna viruses some of them are dna but um they don't have the error checking so they tend to so the rna ones evolve um even faster because the most basic error checking is at least that the two sides match each other and go together because the two sides are complements so dna has that as its most basic kind of error check but with rna which is only the single strand there's not even anything to compare it against so they change faster and in terms of and how many of these are beneficial so in the context of a human genome you i would say on average zero percent which is so we got these 3.2 billion letters of dna and it's basically the the idea is it's much easier to break something than make it better if you throw a hammer at a car engine you might improve it you might but more than likely you're going to break it but with the viruses and the uh they take advantage of the laws of large numbers so and viruses replicate so some they make so so many copies of themselves and even if um the number of changes the the changes that might well so there's a there's another thing as well which is their genomes are much more complex compact so our genome contains a lot of um stuff that doesn't matter so you could even cut it out entirely and you wouldn't notice but the the virus genome is the bare minimum so all of it almost all of it is doing something so almost any change is going to have an effect but it may be for better or for worse so um so they and then they employ the the laws of large numbers in that sense because they make so many copies of themselves that they um it's you can think of it like exploring all of the possible space which is why when you have countries with huge numbers of viral infections it's not a surprise that that's where we find uh these interesting variants of concern but basically it's um it's all down to relatively simple probability but when you get lots and lots and lots of numbers of viruses then those very improbable things happen and even just to take the current case and one of the mutations that people are very interested in is this one that's been called e484k so this is just a numbering system so the number is the position in the protein so it's in spike protein so 484 is the position in the protein and an e has changed to a k and those letters just symbolize the amino acids in the proteins so it's a glutamic acid became a lysine this happened in south africa it happened in brazil and it happened in the uk now most recently so the the uk variant has now got a new mutation on top of it in some individuals which is this new so this mutation the same thing happened independently in three different parts of the world which is really improbable but there's so many so many so many cases so many viruses and every time they replicate they can mutate so even though this this apparently rare event happened in a very short period of time independently in different parts of the world so that's kind of what happens thank you very much you're welcome i can't hear you amen i can see your lips moving sorry um before we go to the last question of the evening from peter boylan um one of our members keen harley noticed that uh it's what appears to be a necklace representing healthy red blood cells yes okay that's an accident for jack okay i'll pretend it was watch planned um peter do you want to far ahead with the last question uh you need to unmute yourself thanks ava that was a really uh fascinating lecture and uh i just really have a comment that i think crispr is probably going to become an established practice in in medical practice in hopefully the not too distant future and it's kind of basic research like you guys are doing that is going to facilitate the development of that that advance and uh so thanks again it's just a comment uh it's late in the evening so i don't want to delay anybody too much thank you well thanks very much and yeah so it's my my wonderful colleagues who are doing that kind of work and um yeah so there are um some of my colleagues in genetics and trinity that are actually developing genetic therapies which are based on some crispr technology and it's it's extraordinary it's such exciting stuff and and it's so precise it's like the i because it is described as editing and it the metaphor is very apt i think you know it is like you have a typo and you can fix the typo um and it's such a precise technology um that can really get to just fixing the problem and not doing anything else so yeah it is extraordinary i think it will it will be very important in medicine i agree the whole idea of personalized medicine so i also admire that good thank you thanks very much thanks uh thanks peter and and thanks fifa as well i think um rather than me saying any more words about it i think just reading some of the comments from the chat box kind of sum up the thoughts of the attendees almost 90 of whom are still here two hours after we started rosie mcadams said really interesting lecture could have listened for hours fascinating talk uh there's plenty of complimentary comments i i'm not going to do them justice uh i suppose it just kind of remains me to say um thanks so much to you for giving up your your time we're really appreciative of the effort that goes into preparing something i think a lot of parties to be here i suppose it's that we're at that point in the in the pandemic of course but all the same to to put the effort into preparing and delivering this uh we're really appreciative uh and have somebody who's held in such a high esteem within the science scientific community ready and willing to come and speak to us as well is great as well and thank you as well to david for giving the opening address always a pleasure to listen to you um and thanks everybody for coming and for for participating and giving your questions as well otherwise it's just myself david ifa and alan tuffrey in a virtual room uh talking about genetics and it's not that any of us would uh couldn't think of um you know worse ways spending our time but it's great to be engaged with so many uh humanist association members as well um i think just to conclude if we all give if another huge round of applause virtual one thank you and um thanks hopefully hopefully we'll see you again at some point if uh thank you yeah yeah when we're back at the world again it won't be on zoom the next time yeah yeah thanks very much and uh thank you it's a it's a pleasure and thanks for the invitation and um thanks for the amazing audience who stuck through that i didn't realize this spoke for so long so it's i can't claim it's uncharacteristic though you're very easy to listen to don't worry thanks very much thank you okay all right everyone nice thank you

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Published: Thu Feb 11 2021