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27 Sep, 2019 06:16

We are all mutants – evolutionary biologist

Evolution has subjected our genome to countless changes, resulting in what we are today – very much alike and yet incredibly unique. Can technology make our DNA even more perfect? And where can this playing with nature possibly lead us? We talked to Armand Marie Leroi, professor of evolutionary biology at Imperial College London.

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Sophie Shevardnadze: Armand Leroi, it's a great pleasure to have you on our show. So we're going to start off with the book that you wrote earlier and I know that you moved on but we'll talk about the topics that are inspiring you just in a little bit. But let's start with “Mutants: On Genetic Variety and the Human Body”. In that book, you put forward the idea of genetic exploration, genetic experiments being a good thing, yes?

Armand Leroi: Yes.

SS: Ok, we shouldn’t be afraid of them. So, in your own words tell me what does it mean? Is it OK to actually maybe change the human race manually?

AL: Oh, well. Let's backtrack a little bit. So, “Mutants”, the book, it wasn't really about changing us. It was mostly about how we get changed naturally, about all the variety that humans show, when we look at each other. Some of it good, some of it bad. When I say bad I mean medically bad. And so what the book is all about was... What is all that variety tell us about how we as humans are constructed? How the human body starts out as a single cell and then multiplies into a walking-talking-copulating-thinking creature, doing all the stuff that humans do - that genetic programme. And it turns out that all that variety is mutations, some of which are terrible in the way they afflict us. Once we identified the genes we can reverse engineer the human body as it were, we can discover the programme that makes us. That's what’s the story that the book told. But what you asked is something a little bit different, it’s about, “Well, now that we know so much about how to make a human body, about the genes that make us, can we and should we manipulate them to make something new?” Well, that's a very difficult question to answer. There are different kinds of manipulation that you can do. One, which I think is coming and which is basically OK, is to use the information in our genomes in order to discover what we should do in life. You got a kid, sequenced its genome, you discover the diseases that it’s most likely to be at risk of and possibly you can prevent those diseases, right? 

SS: That's the good side of it. 

AL: That's the good side of it, and I think most people are going to do that. And I think it's now understood that within our lifetimes everybody is going to get their genome sequenced. I mean within your and my lifetime, and already here in Britain there are huge programmes underway to sequence every kid who comes along, and we can then use that information to say what kind of diseases they get. Especially the possibility of really deleterious late-life diseases such as Alzheimer's and so on, or breast cancer most obviously, which in principle we could intervene in if we knew that they were coming down the road.

SS: Before we get to the disease part, and correct me if I’m wrong ‘cause I may not be understanding everything in the way that you wanted to put forward in the book. But from what I understand the availability of genetic information, people will start to choose partners based on genetic compatibility. Right? OK, so do you really think that humans will actually forego this whole thing of attraction, and chemistry, and all that jazz just for the sake of being compatible genetically?

AL: No. What is sex all about ultimately?

SS: Chemistry?

AL: No, come on, it's about having babies. 

SS: No, there's so many people who don't want to have babies!

AL: I know.

SS: And they have sex all the time. 

AL: I know. But speaking as a biologist, actually, sex was designed for making babies. 

SS: Who said that?

AL: Biologists do. And believe me, we know more about sex than anyone.

SS: Okay, I'll take your word for it.

AL: So, let’s assume what I’m talking about.

SS: Let’s assume biologists’ point of view that sex is designed to just make babies, Then what?

AL: Well, all the rest is just incidental. It’s just getting us to that point, right? So the question is…

SS: There's no sex without attraction. There's no way of getting to sleep with a woman if there isn’t the irrational attraction part, right?

AL: Oh, I think it's completely rational though. 

SS: Yes?

AL: Yes, totally. I mean, I think that there's a little algorithm in our heads which does a little calculation when we look at each other, and we think: “Yes, I do you”.

SS: So that's what I'm saying: how can you forego that?

AL: Another calculation is getting all sorts of things are going into it, but we don't necessarily know what they are. We're evaluating someone's beauty, right? We're looking at their face, right? And we are evaluating their intelligence. Do they have a good sense of humour, GSOH, right? What we're asking really is - are they witty and funny, are they smart, right? We're looking at their earning power - stuff like that, right? All that stuff goes into a calculation. Really I think that what we're doing is we are evaluating in many ways their genetic health, we are asking are they going to make us a good baby. 

SS: Really? 

AL: Sure. What I'm suggesting only is that our DNA sequences as it were - our genomes - could provide another source of information about that person, and a very important source of information. Because even if I look at you, for example, and say, “So beautiful, so clever. Wouldn't you be perfect?” What I don't know is how your genome would combine with mine. It's conceivable that you are the carrier of a recessive genetic disorder or some disease, cystic fibrosis, most obviously, we’re both northern Europeans. Said there's a high frequency of the disease...

SS: Oh, I'm actually from the south - I'm Georgian.

AL: I see. But let's suppose... It just makes you even better for me. So let us suppose so there's a…  You could be the carrier of some disease. I could be the carrier of a genetic disease. Neither of us would know because it's not expressed in either of us because it's a recessive mutation and yet if we are both carriers then our child would have a 25 per cent chance of having that disease, and that disease could be a very terrible one such as cystic fibrosis. And the only way in which we could know that is not by looking at our family histories. The only way we could do that is if we sequenced our genomes and put them together and made little virtual babies in a computer and see how they pop out. And I'm suggesting that that is what we are going to want to do. And I suggest that any couple who is rational in this day and age or very soon from now, before they decide to have babies they will want to look at their genomes and see the possibility of each genetic disease. And from now, it is only a small step to say, even before we fall in love, we should take a look at our genomes. 

SS: OK, but I'm still trying to figure it out.

AL: Is this crazy? This is just rational. This is just like asking…

SS: All this human race DNA-matching to me is sort of akin eugenics of the 30s. Just hear me out, because let's take Bill, like you say, in this DNA, would discover that he carries some chances of fathering a child with Down syndrome or could be schizophrenic. Bill most probably will end up alone and childless because no one would ever want to associate with him. I mean it's kind of like what Nazis were doing. Only it would be forced onto people. Do you know what I mean?

AL: The one thing that we know is that the Eugenics Society is here already, and it has been with us for a very-very long time. The number of children with Down's syndrome that are being born is declining all the time. It is now vanishingly small. And you can do the calculation and ask what fraction of the children who are conceived with Down's syndrome are actually born. And the answer is: in countries like France for example, about 90 per cent of them just disappear. Why did they disappear? The answer is that they’re terminated. They’re diagnosed and terminated. That is pure eugenics. It is basically said, here is a child with a genetic disorder and we are going to remove it. Why? Because the parents don't want to. And this is the same thing, except it is even less acute, because I am not asking to terminate the life of a child - I'm just saying we're making our choices in the embryos. But morally my position is far, far easier for anyone to accept surely than to terminate the life of the child of which, by the way, I make no judgment.

SS: Absolutely. But let me just ponder on this. Because we, humans, are really pretty silly beings. It's so easy to sort of fool ourselves, our brain. We believe in everything we want. So we always believe that there is like this special made-up ideal that we will strive for. So with this whole eugenics, we'll probably end up breeding specialised humans like dogs. You know people are better soldiers, better artists, someone with an acute night vision, and when that sort of resolve into this whole caste-based society like in the middle ages, because they have peasants who are from peasants and soldiers that were from the soldier class, and it will be just like that only not social but like a biological norm?

AL: It's worthwhile pointing out that for the most part at the moment we still have a very poor understanding of the genetic variation that allows people to excel in one kind of profession and another. We know some genes for instance that are important for certain kinds of athletes. We know almost nothing about the genetics of intelligence at the moment still. And so we can point a few things. But the notion that you can breed people for particular aspects, although in principle is possible, in practice is very far away. What we do is we, what I'm suggesting will happen soon, is selection for certain attributes and the number of choices that you get are relatively few. What I simply mean is that: you've only got a handful of eggs and embryos in a petri dish and you can only make a limited number of choices between them. And the choices that you're going to make on them are basically to eliminate the bad things. You're not going to be breeding soldiers or separate super-intelligent kids out of that, right?

SS: You can do that now with genome editing.

SS: Just enlighten me on the process of mutation in general. What is it? Is it random or does it slowly actually lead humanity to somewhere? Or is it just us adapting to the changing environment around us?

AL: So, mutations occur in all our genomes. They are variations, they are just changes in the letters, the genetic letters in nucleotides that make up our genes. And they happen all the time. And we are riddled with mutations. When I say that, you have to distinguish between mutations and variants. They are really the same thing. There’re just differences in DNA, but variants are the things that are relatively common in the population, especially considered globally. The things that make us look different from each other, especially geographically. Right? You know, you have auburn hair, I used to have brown hair, right? These are the things that make us different. These are just natural genetic variants. They are either useful or at least they're not harmful. Does that make sense? So, mutations are much the same except they're rather rare. And the reason they are rare is because mostly they are harmful, and they cause this…

SS: Does mutation have a harmful connotation?

AL: That's correct.

SS: So, an embryo actually becoming a full-fledged human is not, in essence, a mutation?

AL: Well, no. An embryo becoming a full-fledged human is just development. But the question is what sort of human did you get out on the other end. Do you get a perfectly healthy human or do you get one that is unhealthy in some way. And the answer is if it's unhealthy in some way then it's a mutant. But here's the thing, it's important to understand that we are all mutants. We are all a little bit messed up by our DNA in some way or another. Look at me. I'm bald. That surely isn't such a great thing.

SS: No I'm sure you look better now than when you had hair.

AL: Well, it's nice of you to say so but I went bald when I was 25 and it wasn't so great then, right? Anyway so my point… Sorry, I shouldn’t have brought my own physical features into this. But we are all messed up in some way, but the thing is that some of us are more mutants than the others, right? 

SS: Is it all about how much more messed up we\re? For instance, I have a huge nose and my sister from the same parents has a tiny nose. Neither of those noses are harmful to us but is that a kind of mutation too? Do you know what I mean?

AL:  That, I would say, it’s more variant, insofar it doesn’t seem to me that your nose is enormous so that it has hindered your career as a broadcaster. So I'm guessing. It's not such a bad thing, right? So when I talk about bad mutations I really mean the things that we inherit that causes all the sorts of inherited diseases. And there are catalogues of these inherited diseases, and there are tens of thousands of them. These are the diseases that parents grapple with all the time, right? As their kids are messed up in one sort of way, and many of them are psychological. You know, schizophrenia is inherited, autism is inherited, all these diseases, right? Depression is inherited to a considerable degree. And then there are all the things that make our bodies go wrong in various ways. And actually there's an epidemic of these diseases, so we don't actually perceive it. And the reason is because there're so many diseases and because there are so many of these diseases they're not viewed as one thing, and yet this is the mutational burden that weighs upon our species. If the possibility comes of lifting this burden from our species, I suggest to you that we will take it. 

SS: Well, I suppose that the fundamental problem in what you're saying is not what you're saying, it’s that where do humans draw a line of just using that and stopping there, because as far as we know, and we know the history of humans, we probably won't stop there. For instance, all those edit-it-yourself or do-it-yourself genome editing kits that people do at home. They actually do that at home. What do you think of that?

AL: On bacteria. To my knowledge nobody's doing it at home, nobody's engineering human babies at home. That would be truly...

SS: Are we really that far away from doing that? 

AL: At home?

SS: Yes.

AL: Yes. Mammalian reproductive technology is really-really tricky. You basically need a really good lab to do it. So I would have said to you a short while ago that we are very far, we are still quite far away from gene editing humans not for technical reasons but for ethical reasons, but of course that has been blown away recently by the announcement that there are some kids in China who have been edited for the CCR5 delta 32 mutation, a mutation that can confer resistance against HIV. There, as you know, has been no published proof of this yet but the claim has been made that it’s been done and people are taking it seriously that it’s been done. 

SS: And that you can do that editing on yourself and if that's possible then how do we save ourselves from ourselves? It's kind of like getting that horrible tattoo at 19 somewhere at Glastonbury and then being stuck with it for the rest of your life?

AL: Nobody's doing that sort of stuff. I mean, that's not like some kind of grown-up person, we can’t edit our genes. We're talking about editing embryos in the test-tube, right? Let's just be clear about this. I mean by the time you're grown up, it's kind of too late. There are certain gene-editing things you can do to cure diseases, serious kinds of cancers and so forth, but that's a sort of a separate issue. But currently you are what you are, right? So the only question is can you add a gene at a baby. And the answer is technically in principle there is no reason, you cannot. There's an ethical reason you arguably should not. That's the consensus.

SS: Do you think genetics is actually something that's going to make pharmaceuticals obsolete in the future?

AL: No, I think it's not in the near future. What I think and most people would view it this way, is that it's going to make pharmaceuticals more precise, that is to say the kinds of drugs that you're going to get if you've got a disease is going to depend upon the results of getting your genome sequenced. And we already have lots of this. If you have breast cancer, you will get now your genome and your tumour’s genome sequenced, and they will give you the drugs accordingly. Because for some kinds of breast cancers certain drugs are better, and for the others others do. That's personalised medicine. 

SS: Okay. Let's talk about something you really want to talk about. So, you apply your evolutionary biology as a method to research not only human bodies on cells but also products of human action like music.

AL: I do.

SS: And you're using all these algorithms and Internet mapping. So I really wonder because music is also such an abstract, product of the mind. How can science really actually study that, so subjective?

AL: Well. 

SS: It's not written for innovation. You know what I mean? It's just written. So how do you sort of follow that and validate that? Scientifically.

AL: So, I'm an evolutionary biologist, and as an evolutionary biologist I study the diversity of life - all the stuff in the world that evolution has made. And the way I study that is by looking at the genes as we've been talking about - the genomes - and that is to say by analysing information. But there's a whole other domain of things, which evolution has produced. Not organic evolution, cultural evolution. And that is the stuff that fills our world that we have made. Because art itself has a history and sometimes a surprisingly deep history. And because humans have a history and a very deep history, a genomic evolutionary history it seems possible that sometimes those things can in fact coincide. So we know, for instance, that human language is very ancient. And we know that if we look at the distribution of genes, genetic variation in people around the world, to a considerable degree it maps on to the distribution of languages, right? Indo-Europeans who speak all the Indo-European languages, including English, they are genetically relatively similar to each other because of that shared ancestry. So the reason that they share a language and their genes it's the same thing. That's because they've migrated out and spread across Europe in much the same way. And you can do that with all the other people in the world. The match isn't of course perfect, because, of course, you can learn a language even if you belong to some or altogether different genetic group, right? So, here's the surprising thing. It turns out and this is one of the things which we've been studying is that music can have a surprisingly deep history too. You can show that there are certain styles of music which are very, very ancient and which map ontogenetic variation. Let me give you an example. You can listen to the seven kinds of singers in Siberia, the throat singers. And you can listen to the Ainu of Japan, sort of these obscure group of people living in the north of Japan. And you could listen to the Inuit of the Arctic, and you can listen to the rec-recordings of the now extinct Patagonia Amerindians. And you can just hear this, that they all sing and sort of pretty much the same way. Basically, they're all just sort of groaning. [SINGS] Sort of like that. And it goes on for hours, and it varies a little bit. But it's style of singing that stretches right across the Americas into Siberia around the north of Japan. That is all remarkably consistent, remarkably similar. And you can show that numerically because you can analyse those songs. 

SS: What does it tell you about the history of that music, that particular style?

AL: Well, it raises the question, how is it that the same kind of music is spread right across the Americas and through Siberia, yes? And one obvious explanation is that it came across into the Americas from Siberia. Precisely when the original people came across which is ten-fifteen thousand years ago. Even longer, right? If that's true then these song styles are thousands and thousands of years old. That's what we're listening to. And who would have supposed if that were true. We think of music as changing all the time. And that's because we're listening to the modern world, right? We listen to modern music, to pop music which seems to change all the time. Though we've recently shown that it's remarkably conservative. But it's the songs that change but actually the music remains the same. And it turns out that you can show this all over the world. For instance, you can show that there's a style of singing. A call and response, sort of a harmony that you can hear in the blues. And that's an African style which you can find throughout Sub-Saharan Africa. You can hear it among the Zulu, you can hear it among the Swazi. You can hear right throughout Cameroon and through the Kongo. And that maps entirely onto the Bantu people, and the Bantu emerged out of the area of the Cameroon's West Africa around two and a half thousand years ago, and they speak very closely related set of languages. So the language, the genes, and it turns out the way in which they sing, are all deeply related and then carried across into America where it became the basis of the blues and therefore much of American music.

SS: This is really fascinating. Thank you very much for this one, for your wonderful insight and your bright ideas, and we wish you all the best of luck with all your future endeavours.

AL: It's been my pleasure.