Kevin Mitchell: how much of our personality is innate?
Kevin Mitchell, image courtesy of Kevin Mitchell
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But where does our personality come from? Obviously our brains have a lot to do with it, but is it genetic differences in our brains that lead to differences in how we think? Is it all in our upbringing and childhood experiences? Or is it something else?
To tackle this question, Sally Le Page sat down with Kevin Mitchell, an Associate Professor of Genetics and Neuroscience at Trinity College Dublin. In 2018, he wrote a book on the subject called Innate: How the wiring of our brains shapes who we are. So to begin our discussion, Sally wanted to know what was happening in 2018 that made him want to write this book…
Kevin: My own background is in developmental neurobiology, trying to figure out how the brain gets put together during development. What are the instructions in the genome that direct those processes?
Kevin: At the same time, I was interested in behavioural genetics and especially psychiatric genetics, which is looking at how variation in genetics leads to variation in cognition or personality traits or predisposition or risk of psychiatric illness. And what seemed to be coming clear was that those two fields of developmental neurobiology and psychological genetics might actually be really overlapping.
Kevin: That in fact, the variation, the genetic variation that manifests in differences in our personality and cognition and so on may actually be affecting the way the brain develops. And in fact, that behavioural genetics may be developmental neurogenetics. They may be the same thing.
Kevin: And so really what I wanted to do was write that book, which was trying to unite those very different fields, you know, they come from very different disciplines and traditions, so that that overlap would be apparent. And also, I guess, to make the point that if we want to understand how genotypes, how variation in DNA sequence is related to variation in really high level cognitive functions and psychiatric symptoms and psychological traits, we need to take a developmental lens.
Kevin: The only way you get from genotypes to phenotypes is through those processes of development. So if you think about that relationship in too linear or direct a way, you're really making a mistake and people I think have tried to look for very direct relationships between mutations in or variations in gene X or gene Y and said, "This is a gene for language," or "This is a gene for sociability" or for conscientiousness or something like that.
Kevin: And I think that's a mistake. I don't think those kinds of high level cognitive functions have direct molecular underpinnings. I think they have neural underpinnings, but the way that those neural circuits and systems get set up depends on the genes that specify those instructions for development.
Sally: How is a brain made? Brains are really complicated. So like we think of how a heart is made. There are genes that tell you that this is where you build your muscle fibres. This is where you put your nerve fibres. We're all good. It gets a bit bigger as we grow older. Brains seem to be still developing well after birth, even. So how, at the most basic level, how do you make a brain? What's involved?
Kevin: What's involved? Okay. So the first steps in making a brain are similar to making any other kind of part of the embryo, right? So you have to make your muscles in the right place and your skin in the right place and guts and liver and heart and so on. And you have to make your nervous system in the right place as well.
Kevin: So there's patterning signals as the fertilised egg develops, right? As it divides and you get more and more cells, they start to become different from each other. So they're turning on different profiles of genes. Some genes are active and some are not. And that's what makes a liver cell different from a skin cell.
Kevin: And within the whole embryo, all of those cell differentiation processes have to be spatially coordinated and temporally coordinated. So you start by making the neural tube, basically setting the nervous system apart from the rest of the embryo. And then that gets subsequently divided so that you have, you know, the forebrain becomes different from the midbrain and the hindbrain and the spinal cord, and they develop as they should.
Kevin: And that process of subdivision and specialisation just keeps happening in the brain. And what's different with the nervous system, first of all, is that the number of cell types is vast. I mean, even in the retina, which is really part of the central nervous system, there are hundreds of different cell types, even just in that little part of the nervous system.
Kevin: And they're designed in circuits to do different kinds of computations in different parts of the brain. And of course, then all those parts have to talk to each other as well. So that's the problem that the genome in a sense has to solve.
Sally: And we're gonna be talking about the differences between different individuals' brains. So where do those differences happen? Is it in which genes are switched on and off? Is it in the timing of it? The connections?
Kevin: Yeah. It's in all of those things. Basically any of those processes that I described of the differentiation of the cells, establishment of their morphology, establishment of their electrical and biochemical properties, the laying down of the connections and so on, all of those things are specified by some protein. So they're cellular processes carried out by many, many different proteins. Thousands and thousands of them. And the result normally of all of them working together is that you get a brain within the sort of viable range for a human being.
Kevin: But all of those genes that encode those proteins are subject to some kind of genetic variation that just arises all the time. Every time DNA is copied, when sperm or eggs are made, some errors creep in. Not many. I mean, it's amazingly faithful, but some errors creep in. And so genetic variation accumulates in the population over time. You get some new ones, but you also have some older ones that were inherited from generations ago.
Kevin: And that inevitably means that all of those processes are subject to some individual variation. So we have, if you like, a kind of a recipe or a program in 'the human genome' for making 'the human brain', but we all have our own individual variation on that for making a brain like ours.
Sally: It's like in the second challenge in The Great British Bake Off; they give everyone the same recipe and then they present eight different choux buns or what have you at the end. But they never look the same.
Kevin: They never do. So do and the first point is that those sort of instructions have to be interpreted by the cell and by the embryo as it's going along. The genome doesn't do anything by itself. The DNA is really chemically inert.
Kevin: But the second point there is - and the baking analogy is a good one - because even if you gave the same person the same recipe and asked them to do it over and over again, you can never bake the same cake twice. And really what that highlights is that when you start thinking of this relationship of genotypes to phenotypes as being mediated by development, you realise that development itself is another source of variation.
Kevin: It's not just differences in genes that set up the thing and then maybe experience an environment and so on. It's also just development itself that is really an overlooked third source of variation.
Sally: We had a whole episode earlier this series where Kat Arney was talking about nature, nurture and what she calls 'the wobble'. Just the random factor. You know, sometimes your molecule just hits this bit instead of hitting that bit and who knows what happens.
Kevin: Absolutely.
Sally: So we've kind of set the framework for how a brain is made, but a lot of your book talks about - and the bit that gave me multiple mini existential crises while reading it, I had to just take some time out was - it's all about personality, right? And this higher level, so we've got intellect, cognition. So firstly, when you are talking about 'personality', what does that include? When we're talking about "Where do personality traits come from? Are they fixed? Are they flexible?" which traits are we considering in that?
Kevin: Yeah. So that's a really tricky question. And to be honest, it goes to the field of personality psychology, where there's lots of different ways to define what we would view as personality traits of different people.
Kevin: So it rests on the idea that people do have some personality traits. There's some aspects about them, some ways of behaving that you would say, "Well, that's typical. Sally behaves like that. I totally expected her to do that. I predicted that she would. That's absolutely in character for her."
Kevin: And so the trick in personality psychology is to try and look at that vast array of different ways people behave in different situations and extract from all of that variation a few dimensions along which you can categorise a lot of the behavioural differences. And there's lots of different ways to do that. But the most popular version fixes on five major traits, which are called extraversion conscientiousness, openness to experience, agreeableness and neuroticism.
Kevin: And together those constructs capture a fair amount of the variability in personality traits in an abstracted fashion. That is, we're trying to get at something that removes the context, right? It's averaged across context of individuals and across context of situation.
Kevin: So those are the tools we have to work with and psychologists have come up with ways to put a number on them, which is a little arbitrary, but you can ask, you know, you can give people questionnaires, you can tott up scores to say, "Well, look, this person's more extraverted than that person."
Kevin: So those measures are useful, but we should keep in mind that they're artificial, statistical constructs. And one question is, "What do they mean?" If, say, we identify this statistical construct like extraversion from looking at all these questionnaires and clusters of different ways of behaving, what does that mean? Does that mean there's some circuit in the brain that's 'doing' extraversion? Some particular part where we could look in the brain and say, "Oh, look, this is the bit. It's bigger in this person than that person. That means they're more extraverted."
Kevin: And, you know, people have looked for decades using neuroimaging and other tools to try and find those brain correlates of these personality constructs and really come up empty. There's no good replicated biomarkers or physical correlates in the brain for those kinds of traits.
Kevin: And my own view is that they actually represent not one thing. There's not one latent variable in your brain that's contributing to all these different manifestations of extraversion or neuroticism. There's lots and lots of things that are varying, that are tuned differently between different people, that may collectively contribute to you having a high level of extraversion or a low level of neuroticism or whatever it is.
Sally: So if I gave you a brain, you couldn't tell me, "Ah! This is the brain of even an extreme extravert!" Or an extreme introvert?
Kevin: No. And you can't even do it across groups. Even if you gave me thousands of people, you just can't come up with crude measures, simple, single things in the brain where you could say, "This is the bit that explains how conscientious somebody is."
Kevin: And, I mean, it makes sense, because it's a very crude, reductive way of thinking. It's like phenology, really, going back to bumps on the skull and so on. And just empirically it has turned out not to be true.
Sally: So if there isn't a 'bit of the brain' for each of these five traits, does that mean that it's all to do with the environment. So we all start off with the same brain and then it's just what happens to it.
Kevin: No, not at all. So we definitely don't start as a blank slate. There's definitely variation in the neural systems that contribute to a high level descriptor like extraversion or neuroticism. It's not that there is no neural basis to those things. It's that there isn't one. There's not just one thing that you could point to. There's lots and lots of things.
Kevin: And what I tried to do in the book was link the human personality psychology to the neuroscience of decision making that we know about in animals. So when you're working with animals, obviously you can do experiments that you can't do in humans. And one of the tools that we have these days is called 'optogenetics', where you can use a protein that's sensitive to light; it's an ion channel, so when light is shon on it, it will open up a channel in the membrane that lets electrical ions into the cell. And if that's a neuron, well, that's the same mechanism that neurons use to initiate an action potential. So what that means is that using those tools, if we express those proteins in very specific sets of neurons, and then we can use optical fibres to activate them in mice, then we turn off or on neurons in an animal while it's behaving.
Sally: This was fascinating to me. I worked on fruit flies, their behaviour, but in the lab next door, they were doing more of the neuroscience. And they would shine a light on these flies - because they're transparent enough it goes into their brains - and it would make them fly or make them stop flying.
Sally: Literally at the flick of a switch, you control individual nerve cells.
Kevin: Yeah. It's incredible. And you can kind of remote control some simple actions and that's true in a mouse or a rat as well. You can make them walk, you can make them freeze, you can make them sleep or fight or hunt or try to mate, or, all kinds of things. You can make them turn right or turn left and so on.
Kevin: But what's really interesting is that you can actually not just change what they're doing, you can change what they're thinking. You can isolate circuits that when an animal is making a decision, say, it makes them more or less confident, or it makes them more or less risk averse or sensitive to threats. Or it will make them more patient when waiting for a reward.
Kevin: So what you can find in the brain is that there are circuits that control those aspects of decision making. So when you're making a decision, you have to weigh up a whole bunch of different options. You have to evaluate whether they're good or bad. Is this one going to lead to a reward or a punishment? That obviously links to prior memories and experience. But also, if I say, "Yeah, this is gonna be rewarding," well, my reward tuning circuits might be a little higher tuned than yours say. So I might find it more subjectively rewarding than you would and my behaviour might therefore be different from what yours would be.
Sally: So even if we both have the same experience, I don't know, betting on horses and we both receive a hundred pounds from it, our brain differences that are fixed at birth might change how... I might be like, "Oh, a hundred pounds. That was alright," and you might be like, "Wow, that's the best thing in the world!"
Kevin: Yeah, exactly. Except for the 'fixed at birth' bit. I think they're prewired at birth. And it's inevitable. If our genome - the human genome - specifies generally how a human brain is put together, it's inevitable that there will be genetic variation that affects those tunings. And it's also inevitable that there will be developmental variation because there isn't enough information in the genome to specify the wiring of the nervous system down to every cell and every connection, it just specifies some rules.
Kevin: So we are inevitably born with some differences in those kinds of tunings that, I think, ultimately, collectively, in sort of complicated ways, manifest as these high level statistical traits that psychologists have identified now. That doesn't necessarily mean that our patterns of behaviour are fixed. Those are just underlying predispositions and then they inform our behaviour somewhat. So if someone is slightly risk averse, that's going to affect their behaviour over their lifetime in a statistical sense.
Kevin: I mean, not in every situation. Sometimes they'll take a risk. It's just most of the time or on average, they'll take risks less than somebody else. But that doesn't mean we're just robots with certain tunings. And I think one of the key that I don't want to suggest is that just because we have these innate predispositions, that those determine our behaviour over our lifetimes. They don't. They influence it, but our behaviour emerges through a trajectory of the experiences that we have, which are not just things that happen to us. We're actively involved in selecting our experiences and crafting our own environments and choosing the kinds of things that we do through time.
Kevin: So as our character emerges from these early aspects of temperament or personality, along with all of our experiences and the accrued accumulated choices that we're making and decisions, even about what type of person we want to be or how we think we should behave, that to me gives a much more nuanced and accurate view of how early genetic differences contribute to the emergence of our character, as opposed to simply dictating in some deterministic way exactly how we're gonna behave on a moment to moment basis.
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Now, back to our interview with geneticist and neuroscientist, Kevin Mitchell. We've been hearing about how early brain development can predispose a person to one personality type over another and the interplay between genetics and the environment. I was curious about what evidence we have for the role of genetics on personality.
Sally: A lot of the evidence that you present in the book comes from twin studies. Thank God I'm not a twin because I swear every scientist would be interested in me if I was. And it is very often 'identical' twins, so same genetics. I say 'identical' in inverted commas because obviously we know that they're not identical, but identical twins who were raised apart. Firstly, how many are there? What are the sample sizes of these kind of experiments?
Kevin: Yeah. Well, first of all, that's one of the sources. So what you're talking about is the field of behavioural genetics, which is coming at the same problem that I've been talking about from a different angle. So if it's true that genetic variation affects all these processes, as I've been saying, and contributes to making us all different from each other, the flip side of that is that people who are more related to each other should be more similar to each other.
Kevin: And that's what things like twin studies and family studies try to look at. And they're using tools that actually were developed in animal breeding and plant breeding. When people wanted to know they're looking at some trait like milk yield in cattle or something like that. And they want to know "If I breed for this, how successful is this going to be in changing the yield of these cattle?" And so you can work out basically how much genetic variation in your population influences variation in the trait versus how much the environment or something else does. Could be developmental variation.
Kevin: And so in humans, it's the same idea. If you're trying to infer that something has some genetic basis to the variation in it, then you can simply look at people who are related to each other and say, "Are they more similar to each other?" And so, if you look at height, for example, everyone knows that people who are related to each other tend to be more similar in height, right? But that's also true for wealth. And wealth is not genetically determined, it's environmentally or culturally determined. So just looking at family members doesn't really distinguish genetic effects from some family environment effect.
Kevin: And the way to do that is to use these twin studies. There's a few different ways to do it. You can look at identical twins who are reared in different families, as you suggested, and there's a surprising number of those...
Sally: Is this like hospital mix up type scenarios?
Kevin: No, no. It's from very large adoption programmes where some people have been studying these for 30 or 40 years.
Kevin: The surprising thing that came from a lot of these studies was that for a lot of these personality constructs that I was talking about earlier, they're quite highly genetic. That is a lot of the variation that you see across the population is due to genetic differences. And there's surprisingly little effect of the family environment. It seems the way you're raised doesn't really affect those particular traits.
Sally: Yeah. This baffled me. Because one of the things you said in the book is adoptive siblings - so these are people who are not genetically related, but grew up in the same family - do not resemble each other for psychological traits any more than two strangers in the street. But they grew up together! They have this shared cultural experience!
Kevin: Yeah. I know. It's really surprising.
Sally: Yeah. Is that just because nothing we do after birth matters?
Kevin: It certainly isn't. No, but that has been an interpretation of it and I think that's too simplistic, but it's understandable given the way that that science has been presented.
Kevin: To me, it comes down to what are the things that you're measuring? And if you're just measuring these things like extraversion and neuroticism and conscientiousness, well, yeah, maybe they really are biologically innate predispositions. That doesn't mean that the character of those individuals is not affected by their upbringing. There's all kinds of other things that psychologists don't tend to measure because they don't tend to be as stable or they're not as easy to measure. There are character traits like bravery or kindness or humility or honesty or those sorts of things. They're much harder to measure. They haven't been done on the same kind of scale. They have some genetic component to them, but they also have much more of a family upbringing to them.
Sally: One of the things I find interesting about identical twins is that, as I alluded to before, they're not identical. And you have this thought experiment in your book where you take the same exact genome, so even the same epigenetic markers and you say, "Egg, produce me this genome into a full human a hundred times." How similar are those 100 clones going to be?
Sally: And that's essentially what identical twins are, they are, "Here's the exact same genome, work it out." So obviously some genomes...you get two identical twins who are indistinguishable from each other, and then you can get two identical twins who look as if they're just normal siblings. And you suggest there might be a genetic component to that. How does that work? That's some meta level genetics.
Kevin: Yeah. This is some meta level stuff and it gets really tricky. Some genomes will produce clones with more variation than others. That is, the amount of development of variation is itself a genetic trait, which I find really fascinating. And there's good evidence from organisms like flies or mice that you can manipulate the variability of a phenotype genetically without manipulating the mean value of that phenotype. So you're really not changing the trait. You're just changing the variance around the trait.
Kevin: And where it becomes important is that that robustness is not just manifested in variability of the outcome. It also manifests as the ability to buffer the effects of serious mutations like the ones that contribute to psychiatric illness, for example. And a lot of work in psychiatric genetics has on the one hand, tried to find those rare mutations that increase risk of things like schizophrenia or autism or intellectual disability quite significantly by themselves. But, you could find two different people who have the same mutation and one of whom has autism and the other doesn't. And so there's an idea that the genetic background also affects how well the embryo, as it's developing, can buffer the effects of those mutations.
Sally: Surely everyone would want a genome that can buffer against bad mutations? Why would we have genomes that can't?
Kevin: Yeah. Well, that's a great question. If natural selection were completely efficient at removing all of the new mutations that arise, then we would all have the same genome, right? There would be no genetic variation. Because it's not completely efficient, genetic variation accumulates, but it can accumulate to greater or lesser degree in different people.
Kevin: And actually paradoxically, one of the reasons why it can accumulate is because the genome has to deal with this noise - it's making some proteins, but those proteins go off and diffuse, they connect with each other, they diffuse away, it's all very noisy molecular processes - the genome has had to evolve systems that can robustly accommodate that variation. As a result of that. it also allows genetic variation to accumulate because you can get some genetic variants and the genome's like, "Actually it's fine. I can totally deal with that."
Sally: One of the studies you cited was that [identical] twins that are raised in different families, their IQs. So their intelligence gets more similar over time. At the start, being in different families seems to have a big impact on their intelligence, but that they converge to their underlying genetics. Does that mean that we can't really do anything to get out of our genetics? Like, our intelligence is just fixed and we can make small changes to it, but it's always going to naturally want to come back to this true genetic value?
Kevin: Yeah. It's tricky. So that's a difficult result to interpret. It's a fairly robust one. It's been observed multiple times in different studies. So the heritability of something like IQ when you measure it in children is high, but there's also an effect of the shared family environment. And that effect of the shared family environment goes away.
Kevin: So it's not necessarily that the genetics is getting stronger. It's that the environmental effect that you see maybe is sort of temporary.
Sally: But you'd think that the early childhood, that's when the brain is most plastic. If any bit of the environment's going to affect intelligence permanently, it's going to be that early childhood bit.
Kevin: Yeah. So for me, I think one of the ways to think about this - it's not very satisfying, frankly - is again, the key is thinking of a trajectory through time, right? It's a little easier maybe with personality stuff than with IQ to think that people tend to follow their initial sort of personality traits in choosing to do the kinds of things that they naturally like to do. And then they get better at them so they do them more. Say for extraversion; really extraverted people, they go out, they socialise. There's some skills to that and they get better at it.
Sally: They practice more.
Kevin: They practice and they like it and they keep doing it. Whereas people who are slightly less extraverted to begin with may do that less, but over time, those differences amplify between those two people because of this self-reinforcing trajectory of driving our own behaviour through time and then reinforcing it. And I think maybe something like that is happening with IQ or cognitive kinds of things as well. That maybe some people are naturally inclined to the kinds of activities that foster cognitive skills that would be measured on an IQ test and maybe other people are more inclined to spend their time in different ways.
Kevin: And therefore you can get, again, this kind of amplification of initial differences over this trajectory through time, but that's the only way to understand the relationship. You have to view it across that trajectory of the lifetime. Just like understanding the relationship between genotypes and phenotypes at birth, you have to view through the trajectory of development.
Sally: Now, something like extraversion, it's fairly neutral. I mean, as a Western society, we tend to prefer extraverts to introverts anyway. But talking about something neuroticism, so that's being anxious, depressed, guilty, low self-esteem. If that's something innate to my brain, a combination of the genes I inherited and how those genes developed my brain, does that mean I'm doomed to be neurotic for the rest of time, regardless of what I do about it, if it's very stable and very innate?
Kevin: So neuroticism, it is a loaded term, right?
Sally: Yeah. No one wants to be neurotic.
Kevin: Yeah. It makes it sound like being highly neurotic is terrible and being low in neuroticism is great.
Kevin: And, you know, to a certain extent being really high in neuroticism is a risk factor, for example, for some psychiatric illness and for just not being very happy in life. So there is something bad to really high values. But there's also something bad to really low values in the sense that that might make people really reckless and more impulsive. They're not thinking about the possible negative consequences of their actions. I mean during a pandemic, for example, being neurotic may be great. You're more of a worrier. Well, great. You take more precautions under risky situations.
Kevin: So evolution has not tried to maximize or minimize these traits. In fact, the average, you would think, is actually the sort of evolutionarily optimal value. It's very much situation dependent and frequency dependent and so on. So it becomes a much more complex picture.
Sally: So I can't do much environmentally to change my level of neuroticism, but that that might not necessarily be a bad thing.
Kevin: Yeah. I took pains at one point to say that the book was not a self-help book, but having said that, I think just the realisation that we may have some traits that we can't change those things about ourselves can be empowering because you can stop wasting your time wishing you were different from the way you are and put your efforts into accommodating to yourself as it were.
Kevin: And I think that the same is true for other people. You know, realising that people really are wired differently in many ways that they see the world differently and feel the world differently. And they value different kinds of things from you is just helpful in dealing with people and accepting that variability and even embracing it.
