Instant Genius - What makes me 'me'? - Aoife McLysaght

Episode Date: December 26, 2018

Evolutionary geneticist Aoife McLysaght is joining Alice Roberts as a guest at this year’s Royal Institution Christmas Lectures. Together, they’re exploring where we come from, what makes us human, and what makes each of us unique. Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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So you can experience exceptional sound at home. Music just as the artist intended. Visit name audio.com to learn more. The genes that lay out the body plan so that define the patterning in the body in terms of which is the head end, which is the tail end and where do the limbs and things grow out of, the genes that lay out the body plan in human development or in any mammalian development are actually the same as the ones that do it in fly development, even though when we're looking at the outside of the fly,

we can't find any recognisable similarities. You're listening to the Science Focus podcast from the BBC Focus magazine team. We're the UK's best-selling science and technology monthly, available in print and in several digital formats throughout the world. Find out more at ScienceFocus.com or look out for us in your app store. Hello and welcome to the Science Focus podcast. us. I'm Alexander McNamara, the online editor at BBC Focus magazine. In this year's Royal Institution Christmas Lectures, Professor Alice Roberts and Eva MacLicert asked the most

fundamental question, Who Am I? In true Christmas lecture style, they explore the topic with live animals, over-the-top experiments and a ton of audience participation. They start big, exploring the similarities we share with other species, then dive down into what makes us human, despite sharing 99% of our DNA with chimps. Then they go even further to figure out what causes the diversity we see between people. Professor Ethan Mcglissert brings her expertise in evolutionary genetics to the topic, discussing how our genes connect us to every living thing on the planet, and asking how much we can predict about a person by examining their genome.

In this episode, she speaks to BBC Focus editorial assistant Helen Glennie about what we can learn about evolution by looking at our genes, how we should manage gene editing as it becomes ever more possible, and what this year's Royal Institution Christmas lectures are all about. The question we're asking is, who am I? And so we're trying to look at that in terms of where you come from, how did we get here in terms of our evolution as humans, and then what really makes you new and your genetic individuality.

So that's the theme that runs across the lectures. So we're stepping through this question, Who am I, at different levels of resolution. And lecture one is looking at you, us, each of us, with respect to the entirety of the animal kingdom and not just the animal kingdom, actually. We see the concept spread to all life on Earth. And so we're looking at these similarities.

And the way it works between me and Alice, I think, is really nice. So Alice is originally a medic and anatomist and then developed this huge interest in evolution. And so she, her usual way of looking at it, or her preferred way of looking at it, is by comparative anatomy. So she's looking at the bones. And then I'm a geneticist looking at molecular evolution. So I come in and I go, well, you know, this same thing you've just done, which is notice that the bone pattern is the same in the front limb of a horse, an armadillo, a bat and a human. That it's basically the same bones slightly different, you know, maybe a bit elongated one way.

the other, but they're recognizably the same thing. We can do this with the genes as well. And so you can look at genes and you can see that you basically have the same gene in these different species. And we actually take an example from these same species from a gene that is involved in the four limb development. And we look at the sequence and you can see it's recognizably the same sequence. When you print a DNA sequence out, it's just a string of letters, ACT and G in a particular sequence. And you can see that they're recognizably the same. And you can see that they're recognises be the same, even if it doesn't read like a word to you, you can see that it's mostly the same. And then there's a few changes, some changes, some differences only in human,

some differences only in horse. So we were showing how these concepts are really compatible. They give us different angles on this question, you know, how am I related to other things? And then we extended this beyond the kind of things that you can compare with bones. So we went out to fruit flies, which don't even have bones, and then you can still find these really deep fundamental similarities when you look at the genetics. And actually, in the case, the example we used, it's a really famous example, but it's a stunning one, which is that the genes that lay out the body plan, so that define the patterning in the body in terms of which is the head end, which is the tail end, and where do the limbs and things grow out of, the genes that lay out the body

plan in human development or in any mammalian development are actually the same as the ones that do it in fly development, even though when we're looking at the outside of the fly, we can't find any recognisable similarities. So we have this thing where we can see these really, really deep relationships through everything that lives. And then in lecture two, we're going to move on and say, okay, so we're asking this question, who am I? First answer in lecture one is basically, you're an animal, you're a part. part in nature. Lecture too is, well, you're not just any old animal, you're a human.

And we talk about human evolution and origins and relationships to other closely related species, living species like chimpanzees and gorillas. But then we also look at some of our extinct ancestors or sorry, yeah, extinct ancestors and extinct relatives like Neanderthal and Denise of one of these archaic human. humans. And we look at human origins that way. And then in lecture three, we go, yeah, but you're not just any old human. You're you and you're a total one-off. And even if you're an identical twin, you are totally unique. And that's because your genes don't determine everything. And even when I say your genes don't determine everything, some of those differences are actually

inborn. So they're not things that happen to you during your life necessarily. And like, handedness is just an example of something where a child doesn't choose to be right-handed or left-handed. They're born that way, but it's not strictly, totally genetic either. There's a tendency. The genetics create a tendency, but they don't determine the outcome. If it's not genetics and it's not choice or environmental, then what is it? Well, it's basically stochastic variations during development. It's an easy answer, eh? Yeah, sure. But so the process of development is growing from a single cell,

which is a fertilized egg, up to the finished product, you know, the adult form. So we as humans basically have two periods of development. One of them occurs in the womb and the second one is adolescence. Or actually, old of childhood is development in a certain way, but adolescence is a particular burst. but most of development takes place in the womb. And when that single cell is multiplying, growing, dividing and taking shape, there are a little fluctuation.

So not everything is totally governed by the genes. The genes might create a landscape that something's more likely to go this way than that way, but it doesn't totally force it. And so with handedness, it's one of those things that most people are right-handed. but some people are left-handed and it's just small little make somebody left-handed.

Fantastic. And you're coming in and joining Professor Alice Roberts as a lecturer for the set of Christmas lectures. What's your academic specialty? What background are you coming from? I'm a geneticist and I specialize in molecular evolutionary genetics. So I look at evolution

by studying DNA sequences. So this is a really, really powerful way of studying evolution because every living thing has DNA. And so once you start comparing DNA sequences, it means you can compare any living thing across all life. You can even start making inferences about the earliest life forms on the planet. And you have abundant data because it's really easy now to get DNA sequences. And so we have all of these sequences. We develop, we try to develop, clever ways. of analysing them and it gives us an insight into really, really amazing diversity, but also

it allows us understand how our genes have evolved and how we've evolved, which might sound like kind of some version of a history lesson, you know, that you're going, okay, it's interesting and it's curious to know about the past, but it's actually very informative for the presence as well because based on the patterns of how genes evolve, you can actually make predictions and can have understanding about which genes might also be implicated in disease. And this is because the patterns of evolution will be determined by that susceptibility to disease in a certain, if when you mutate a particular gene it causes disease, we're going to notice that in terms of evolutionary patterns as well,

because it means those mutations will be disadvantageous, and there's a distinct signal for that. So without having to do lots and lots of studies, and get lots of samples from lots and lots of people, we can actually make predictions just on patterns of evolution about which genes are involved in diseases, and therefore we might have a shortcut to better diagnostics. And in genetics, there always seems to be this question of what's genetic and what's environmental.

How do you go about determining which things are genetic and which things are environmental? The classic way of doing that is by looking at identical twins. as compared to non-identical twins. So, and this is because identical twins share all of their genes and then also the majority of their environment. So they are in the same womb at the same time. So they have that exactly in parallel. They grow up in the same family usually

and have the same experiences. Whereas non-identical twins share all of those things in terms of the same womb environment and the same family environment, but on average, only have 50% of their genes in common. And so if identical twins are more similar to each other than non-identical twins for a particular trait, then you say, well, the difference between those is genetics, because

everything else is the same. And that's part of how you know if something is genetic or not. So kind of a silly example that anybody could understand is which language you speak. So we know this isn't genetic, right? So if you speak German, if your parents speak German to you and you learn it as a baby and you speak English, if your parents speak English to you. But, you know, so if you look at non-identical and identical twins, they're going to be exactly the same in this. So that's just a kind of a stupid example to illustrate the point. But that, it would be a totally environmental thing.

And if you have something kind of on the other end, like something like, say, hair color, that is extremely genetic. There's probably some little bit of variation. course, with aging as well, there's variation, but it's going to be much more similar between identical twins on average than between non-identical twins. You're not at all surprised if you have non-identical twins where one has blonde hair and one has brown hair, for example, but you would be quite surprised if you found that in, you'd be very surprised, in fact, if you got that in identical twins. It just wouldn't happen really. So you mentioned hair colour is something that is determined genetically.

Can you give us some examples of things that are definitely determined genetically and some things that are definitely not genetic? Or I guess maybe a low level, genetic on a low level. It's really, I suppose, a continuum because my kind of quick answer is something that's definitely not genetic could be, for example, scarring. So I have a particular scar on my right hand from one time. I slipped with a knife when I was a child and cut my finger. And obviously that's not heritable.

But it's a little fuzzy as well because my tendency to scar and how your skin reacts, that would be genetic. So how good your skin is at repairing itself is partly genetic. So the fact that my skin does scar quite easily is going to be genetic. So everything is a little bit fuzzy. But then traits that are totally genetic, there are. I mean, some of the ones that we know best are unfortunately disease traits, and this is possibly because this is where a lot of effort was put in,

but there's a condition known as Huntington's disease, which is later life neurodegenerative disease, and that is determined by a single gene. So if there's mutation in one particular gene, which has been called Huntington, then you get that disease and if you don't carry the mutation, you don't. And that's a very clear example where it's a really yes-no thing. There are other traits, I don't know if you ever heard before, of something called sickle cell,

which is to do with your red blood cells, which normally look like kind of nice little saucers, but sometimes they can look more like a sickle, as in a hammer and sickle, that kind of crescent actually. And this is caused by mutations in one of the globin genes that make up hemoglobin, which carry the oxygen in your red blood cells. And that's, again, just a single mutation that means that you will have this different shaped blood cell. This matters because actually being a carrier for the sickle cell gives you resistance to malaria. So in parts of the world where malaria is common, we tend to find that that.

gene is also common. But then things that aren't genetic at all. So, yeah, scarring is one example. But then there's also a lot of the way you wear your hair and all of these kind of things. But once it's a biological trait, it's going to have some genetic basis. It's almost impossible that it doesn't have any. And now we're starting to get to this point where scientists are beginning to be able to modify genomes and even the human genome.

What question should we be asking ourselves around the ethics of that sort of experimentation? A huge number. That is a really, really powerful technology, and it is not something that should be undertaken lightly. But I think the fundamental question, I mean, so there are people who specialize in dissecting ethical questions and they would give a more sophisticated answer than I would. And in fact, we do bring in a bioethicist in lecture three. So that's to look forward to. But a fundamental question, I think, or one way of approaching it is who benefits and what's the benefit. So I personally would say that if you're talking about a particular condition that somebody suffers

with and suffering would be the, I suppose that's subjective, but if you suffer with a particular trait or circular condition, then you should. I think you're kind of a moral obligation to help that person if you can. So, you know, it seems immoral not to help somebody if you can. But if it's just some kind of cosmetic or preference thing or even a prejudicial thing, well, then I would argue strongly that you absolutely should not do it. And there's also, in terms of the technology for gene editing, There are two, broadly speaking, two ways of doing it.

One way is as a therapy for that individual. So, for example, any of us that's already born, your reproductive organs are totally separate from the rest of your body. And let's just imagine then you have somebody with a particular form of heritable blindness. If you could give them a gene therapy and that would only affect the tissues in their eyes. So it would prevent the. onset of disease, let's say, the onset of blindness. You could do that as a therapy for that individual, but it wouldn't be anything,

it wouldn't affect all their reproductive system, so it would not at all affect the next generation. So you're not interfering with future generations, whereas if you did it in such a way that the, you did it early during very, very early in embryogenesis, so maybe at a zygote stage, you know, really, really just a few cells, then everything in the body is going to be modified, including the genes that get passed on to the next generation. So when you do that, you're not only affecting one individual, you're having an impact on future generations.

And that is something that is much more tricky. It's something that you better understand before you do it. There might be cases where you can say, well, that's okay. So I already gave the example of Huntington's. You know, if I was a carrier, I would like, I'd prefer not to put. pass that on. And if that could be achieved in one way or another, I think I'd be happy with that. But that's a clear case where it is a debilitating disease and it's clearly something that you suffer with. It's not just, oh, I'd prefer to be this or I, you know, it's not like the designer

baby kind of question. So I think there are, there are really challenging questions there, and it's definitely something that should not be undertaken likely. And what about when it comes to stuff like intelligence or athletic ability, things like that that are not, it's not fixing something that's gone wrong. It's giving people traits that might be desirable but are not necessary for their survival. What do you think about the ethics around that? Two answers there. One answer is I don't particularly think that that should be done, partly because it's quite subjective what you decide is the attractive or valuable trait. But even aside from that, it actually is just kind of scientifically illiterate in a certain way

because like we've just been saying, so many things are not fully genetic. And so the kind of traits you're talking about, they're going to have a large component from things other than genes. So you're fooling yourself if you think you can. determine these things, you can force these traits to be one way or another just by messing with genes. So you do all this big messy technology, make this big intervention, and you still don't get the outcome you were trying to get. And that's because there are, in the case of intelligence and athletic ability, there are many, many, many things throughout the genome. It's not just one little

change in one part. There are many, many, many different parts of the genome that contribute to this. and they interact with each other and they interact with the environment and it's all a big complicated mess and it's just arrogance to think that you could even do such a thing as edit genes to improve intelligence. But I think the first thing is the more important one

because if it was possible, I still wouldn't support that because I think it's a form of prejudice really and I think it also falls back down on to what is it you think you're measuring and what is it you're valuing. And there are different types of intelligence. And people talk about, say, mathematical intelligence, but creative intelligence and different things like that. And is there going to be one particular thing that's valuable? And actually, the thing I value is diversity. And so it's important to keep lots of

diversity. And it's good for everybody. Yeah. So about the Christmas lectures in general, can you explain to us what they are? Well, there are these wonderful lectures that have been running for How many years now is it? Over 200 years, started by Michael Faraday in the Royal Institution in London with the idea of bringing science to the public, but not just the public, because specifically with the Royal Institution Christmas lectures are for children. So the target audience is 11 to 17-year-olds. And having already done one lecture, I can attest that they are very enthusiastic, 17-year-olds.

And the idea is that you bring in an expert and they give lectures to the children explaining something exciting and new and fascinating to them. And there is this really fun tradition of the Christmas lectures is that you need to have demos and examples and experiments and things like that. And so that's been part of the challenge

and the fun in doing the lectures. has been coming up with physical manifestations, sometimes kind of abstract ideas. And so, you know, trying to explain, well, how does development work? And how do genes kind of influence but not determine the outcome and trying to make some physical demonstration of that, that we can get kids to act out or we can have a model that does something. And that's been a challenge, but it's been loads of fun. And so the lecture is, it's a huge honor to be involved in them because they've got this wonderful wonderful long history and tradition

and it's actually been loads of fun as well and the audience is really amazing and so one of the things we do is we call on volunteers from the audience a lot and they are so enthusiastic that at one point in yesterday's lecture when Alice said, and I'm going to need a human, she was about to introduce somebody

who was coming in from the wings but as soon as she said, I need a human, 20 arms shot off because they're, pick me! So there's a really fun atmosphere. But it's really, really good. We do it in a fun way, but we're talking about real science and we're talking about lots of difficult, challenging topics,

including the ethical questions we've been discussing already. And I think it's a really good audience. I think children at that age, they are really willing to engage and to think about these things. So it's fun. We did it in a fun way, but not at all a condescending way. It's really, they're really challenging topics that we're bringing to them.

So why do you think this kind of science communication is important? In general, I think science communication is important for two reasons. One is that science is a part of human culture. And same way that music and art are parts of human culture. And it belongs to everybody and we should all be able to enjoy it. So personally, I'm not much of a musician. I learn to play piano, but that doesn't mean I can't enjoy music. It doesn't mean that music isn't important to me.

So you don't have to be a professional at something for to be part of your life. And I feel that way about science as well. You don't need to be a professional scientist for science to be something that can be part of your enjoyment of life. And one of the things that you get some pleasure from understanding and thinking about. And so that's the first point. And the second point is there is a huge amount of scientific literature. And, you know, I don't even know everything in my field, let alone in all the other fields that exist. And so I could say, or you could give a glib answer, you know, oh, you can Google things or you can, you know, all the papers are there and all the scientific publications are all available.

But there's so much you couldn't possibly find your way through it in a reasonable amount of time or perhaps in a lifetime. So you need a guide. and science communicators are those guides who show you your way through and help you understand things and point out the highlights. Fantastic. And do you have any favourite moments

from past Christmas lectures that you've seen? I do know, I do like it when they bring in animals. That's always lovely. And we have some lovely animals as people already have seen in the first lecture, had a horse, which is beautiful, beautiful horse, a hairy armadillo, a bat and, of course, humans. The part people didn't see is just before the lectures started, the horse peed in the lecture

theatre. So we had to quickly run for a bucket, a really big bucket. And I brought in fruit flies, which compete with Alice bringing in all those fabulous animals. But it is really nice to have animals up close and personal and it's it is always dramatic and it's always wonderful and so yeah i've seen some old clips of davidatnborough where he's cuddling a lemur and that's just beautiful and it's fun and yeah actually but i haven't seen all the david andrew ones because there's some missing tapes there's some of the old lectures are missing there's actually an appeal out if anybody can check their attics and see if they have an old VHS they might have recorded back in the day The BBC doesn't have the tapes anymore,

and they're hoping that somebody around the country might have kept one from all those years ago. There's one of the David Attenborough lectures and a few of the others. So I haven't seen them all, but yeah, him with the lemur is lovely. It's just, it looks like a really affectionate moment. That was Eva McLeicett talking about the evolutionary genetics expertise she's bringing to this year's Royal Institution Christmas lectures. You can watch the whole lecture from the 26th to the 28th of December on BBC 4

and read up on the history of this iconic event in the latest issue of BBC Focus magazine. In the mag, we also explore seven radical ideas that will expand your mind, and lot the mysteries of ASMR, and find out if party drug MDMA can help treat alcoholism. The magazine is available in newsagents and supermarkets now, where you can also find our latest special edition, The Science of True Crime. In it, we find out how psychological profiling changed to the FBI, whether maths can help us predict terrorist attacks and how brain injuries can help create criminals,

along with much more. Thank you for listening to the Science Focus podcast from the BBC Focus magazine team. We're the UK's best-selling science and technology monthly, available in print and in several digital formats throughout the world. Find out more at ScienceFocus.com will look out for us in your app store. This podcast is sponsored by name, audio and focal.

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