No Easy Answers in Bioethics Podcast
Genes, Behavior, and the Brain: Cabrera and Reimers - Episode 17
November 5, 2019
We can look at an individual’s DNA and know what their hair color is, but what about their behavioral traits? This episode features Center for Ethics Assistant Professor Dr. Laura Cabrera, and Dr. Mark Reimers, Associate Professor in the Neuroscience Program in MSU’s College of Natural Science. Drawing from their expertise as neuroscience researchers, they discuss what we know about how our DNA affects our behavior—from IQ scores to mental illness. They also explore possible ethical issues that may arise in the near future related to the study of behavioral genetics and gene expression.
This episode was produced and edited by Liz McDaniel in the Center for Ethics. Music: "While We Walk (2004)" by Antony Raijekov via Free Music Archive, licensed under a Attribution-NonCommercial-ShareAlike License.
- Gray JR, Thompson PM. Neurobiology of intelligence: science and ethics. Nature Reviews Neuroscience. 2004;5:471-482. DOI: 10.1038/nrn1405.
Liz McDaniel: Hello and welcome to another episode of No Easy Answers in Bioethics, the podcast from the Center for Ethics and Humanities in the Life Sciences at the Michigan State University College of Human Medicine. Today’s guests are Center for Ethics Assistant Professor Dr. Laura Cabrera, and Dr. Mark Reimers, Associate Professor in the Neuroscience Program in MSU’s College of Natural Science. Drawing from their expertise as neuroscience researchers, they discuss what we know about how our DNA affects our behavior—from IQ scores to mental illness. They also explore possible ethical issues that may arise in the near future related to the study of behavioral genetics and gene expression.
Laura Cabrera: Hi! Hello, I'm Dr. Laura Cabrera, I'm an assistant professor at the Center for Ethics and Humanities in the Life Sciences, and my research focus is neuroethics. And today with me I have my colleague and friend Dr. Mark Reimers. He is an associate professor at the Institute for Quantitative Health, and he does very interesting research in terms of quantitative computational work that really intersects with neuroscience and, and genetics. And so for today we're gonna be talking a little bit about genes, behavior, and brain, and some of the work that Dr. Reimers does in the area. But also to look a little bit into the ethics or ethical issues associated with the field. One thing to say is that Dr. Reimers and I have a very shared interest in ethical implications of neuroscience research, and that has led us to have joined journal clubs, and reading groups, so it's been really fun interaction, and really interesting discussions around ethical issues beyond just genes, behavior, and brain. So when we think about human brain development, how, you know, the interaction with genes and environmental influences today, it is relevant to, you know, to see what or how genes and behavior are related. So it might be good to start if Dr. Reimers can tell us a bit, a little bit more, how do genes affect behavior and brain?
Mark Reimers: So I guess, hi Laura, the short answer is we really don't know, but we think that they do, and the evidence for that historically has been that identical twins behave more similarly than fraternal twins, and behave more similarly than brothers or sisters from the same family and certainly more similarly than people sort of taken at random who are friends. So, when we see that kind of characteristic that twins are more similar than non-twins, we think there may be a heritable component. However, we've had a great deal of difficulty actually trying to identify specific genes that influence any aspect of behavior over, you know, a large number of people. So even though many traits, particularly things of popular interest like intelligence quotients, are very highly heritable, or mental illness. In some cases psychosis is very highly heritable. We can't find any specific common genetic variants of large effect. We can't find, you can't look at somebody's DNA and tell them that you're going to be high IQ, you're going to be, you're going to have serious mental illness, whereas we can look at someone's DNA and tell you what your hair color is, roughly what height you're going to, you are, and, you know, even some extent what your face looks like.
LC: Wow I mean that's very, very interesting. Now before I ask you a little bit about what your particular research focuses on, you mentioned something about, you know, about variants.
LC: So, maybe can you explain that a little bit more?
MR: Sure. So, you know, we, we've known for a while that each cell in your body has about 3 billion bases of information. And typically about one in 500 of those differ between you and, let's say, somebody else picked at random from the human population. Maybe differs at, you know, one in a 1000 places from people from your ethnic group, but maybe more from people from different parts of the world. So we say a genetic variant is one of those one in a 1000 places. But of course one in a 1000 doesn't seem like a lot, but if you have 3 billion bases that's, you know, going to be 3 million places. And actually if we're looking at the whole human population we sort of estimate the number of places where there's common differences to be something like 10 million places.
LC: Wow. Yeah it's kind of interesting when you put in, in context, how it does, it does matter. So, well, I mean this is a perfect place for, for now for you to tell us a little bit more about your research on genes and the brain.
MR: Sure. So, I'm interested in two kinds of things, working on two kinds of projects. First is what we'll call behavioral genetics or psychiatric genetics, and that is just by looking at DNA how much can you predict about a person's behavior or, or likelihood of psychosis, or any other behavioral trait. Including things like IQ. And that's what most people mean by genetics. That is how much is sort of born into you that you can't really change, or that life experience doesn't change much. How much is sort of hardwired at birth and that you can't do much about. And the second line of research that I'm pursuing is gene expression. And that is more a measure of how the cells are responding to their situation. So when we talk about gene expression, you have those genes on your DNA, but how much of them are actually being transcribed or copied into active cell compartments is variable depending on a whole lot of things, like your mood, your recent infection history, how much exercise you're doing. All kinds of things. And that's, so we can use gene expression as sort of an index of how the cells are coping with their, their lives sitting in your brain.
LC: Right, well both are, sound fascinating. But I guess one question that relates, and we're going to touch a little bit more into this in a couple more minutes, but, so in the field of behavioral genetics, the first one that you mentioned, it's been very debated, whether we should ,through genetic manipulation, you know, be able to create or manipulate the genome, to create, for example, super high IQ babies or similar. So you already mentioned that IQ is genetic, but how much, how much is IQ depending on genetics?
MR: So that's a very much debated question. So when I give you those estimates of heritability like 80 percent heritability, which is a commonly cited figure for IQ. That's based on, you know, twin studies showing that sort of identical twins have very similar IQs. That if you know your identical twin's IQ, you have a pretty good idea, an 80 percent accuracy, in predicting your IQ.
MR: But, that doesn't seem to translate very readily into specific genetic variants. So I can't read your DNA and very, get a very good idea of your IQ. Now it may be that I don't know enough, maybe we, maybe the field doesn't know enough about which genetic variants contribute. And maybe in some future time, you'll be able to look at someone's DNA and predict their IQ. I don't believe that's likely. And one reason for that is that almost all the twin studies are done with middle-class people who respond to questionnaires.
MR: That's actually a minority of the human population. It's very hard to track down and do studies on people who don't answer questionnaires or don't even answer the doorbell or may have moved since you've last talked to them. But if, you know, when people do those kinds of studies, go to the effort, they typically find that the heritability estimates for IQ and many other things are much, much lower. Typically for IQ they're finding more like 20 or 30 percent rather than 80 percent. Which suggests that it's not all sort of hardwired at birth, it has, you know, IQ has a lot to do with your experiences, but most middle-class people in stable families have relatively similar experiences.
LC: And what about other things like, like personality?
MR: So, again, you know we have a saying, you know, "the apple doesn't fall far from the tree" to describe, or, you know, "like father like son" or "like mother like daughter," to describe how similar behavioral traits seem to run in families. But, again it's very hard to identify specific genes that mediate those kinds of behavioral characteristics. So while we know that neuroticism runs in families, people who are worried and get worked up about things tend to have children who are like that. Only the very largest studies have been able to identify any specific genetic variations that tilt your, your likelihood of becoming neurotic ever so slightly. The effect sizes are infinitesimal, meaning, you know, less than one percent of one percent.
MR: So, again, you can't look at somebody's DNA and say, okay this person's a neurotic person, or highly neurotic, or medium neurotic, or not neurotic, or well adjusted. And I, I don't think that it's very likely that we will be able to do that.
LC: So we talk about neuroticism, but is there any particular behavior or personality trait that we know more about that is more likely to be affected by genes compared to neuroticism?
MR: Well we, we certainly know that IQ is affected by genes. We've identified almost 100 specific genetic variants that each infinitesimal, very very slightly, they might move your needle, you know, on average a fraction of an IQ point. So we can look at people's DNA and say, well, you know, other things being equal this person is slightly more likely to have a higher IQ than that person.
LC: So recently in the news there was something about, you know, that they identify some genes that could predict the sexual orientation of people.
MR: Oh yeah.
LC: What was your reaction to that?
MR: Well I was not at all surprised. Again they took a very very large data set, so they were able to find very very small effects, and be confident that they were real. But they found four genetic variants that, again, had, in total, less than a one percent of one percent effect on, you know, the probability of being gay or not gay.
MR: And they didn't, you know, they, again, they can't look at somebody's DNA and say, you know, at birth, this person's going to be gay or this person's not. One thing about, just back to the, to the IQ issue, although we can't identify common variants that are very predictive of IQ, we can certainly identify lots of variants that are predictive of low IQ. So intellectual disability is something that is largely correlated with harmful mutations in genes that are quite rare. But that are detectable. So, when I say that, well, we're not, you know, we're not going to take more or less healthy people and say your IQ is going to be 120 and yours is going to be a 110, we can certainly look at some people's DNA and say, well, this person is very likely to have a very low IQ.
LC: It's interesting because we get wrapped up in knowing more about how the gene will help us know things about people, whereas the environment already can tell us a lot. I don't know if more, but certainly...
LC: ...We can do also...
MR: I mean if we're, if we're concerned about raising IQ, a better investment is better schools.
LC: Exactly. Well now, let me ask you a couple of things about the other area that you focus on, gene expression. So you talk a little bit about, you know, how the genetics and the origin of disease, and so how this relates to, to work on gene expression. Now are there any mental disorders, since this is an area that you focus on most, for which we have well mapped the gene expression in the brain?
MR: Well, we've certainly done lots of studies. There are now hundreds of people with severe mental illnesses who have donated their brains to research, and whose brains have profiled in a variety of ways. And we don't have a sort of prototypical or stereotypical picture of what the brain of a schizophrenic looks like, or what the brain of a depressed person looks like, with a couple of important exceptions. And that is that we know that if a person's had a diagnosis of schizophrenia for quite a long time, often their brain is smaller, and they seem to have lost some grey matter. And we believe that's largely a loss of synapses. We don't really know why, and we can't look at the specifics of gene expression and say, well we've got a single cause for this shrinkage of the brain, and the delusions, and also negative affect that goes along with schizophrenia. We have some ideas though. We can say that probably there are some individuals who are becoming schizophrenic for different causes or different reasons than others. And we think that some of the reasons have to do with, with severe inflammation. They have a stronger inflammatory response in their brain. And where that comes from of course we don't know unless we collect life history data, which we typically don't have.
LC: Mm-hmm. Now how can research in this area to be useful in the treatment of mental disorders?
MR: So I think that the real hope, and I think it's likely to be realized, is if we can understand the different mechanisms or the different sort of stories behind mental illness, like schizophrenia or bipolar disorder, or even depression, or perhaps a condition like autism, that we can have some hope of intervening more effectively if we can identify what kind of, what version of the disorder you have. One of the big breakthroughs in let's say the treatment of breast cancer was when it was realized about 20 years ago or shown that actually there are at least three major kinds of breast cancer. And let's say some of them are largely driven by estrogen. So, those particular kinds of cancers can be effectively treated by shutting down estrogen, and that's a treatment that's used. But estrogen doesn't do anything, shutting down estrogen doesn't do anything for the other major types of breast cancer.
LC: So basically knowing the gene expression will help us know what to shut down or activate or...
MR: It'll give us some idea, at least for some people, of the mechanisms behind their particular mental illness. And that I think will enable some effective treatment.
LC: So it would be kind of the equivalent of personalized medicine in mental health.
MR: Yes, I think that that's really what we need, and what I hope that a combination of genomic and behavioral studies will show is that, you know, each person's depression is not necessarily the same as everybody else's depression. Or one person's psychosis is not necessarily the same and treatable the same way as another person's psychosis.
LC: Well that's a whole world there to continue studying and exploring. So I guess now just before we end this conversation today, since, you know, we are both interested in ethics, I wanted to ask what do you see as the most pressing ethical issues connected to the areas that we discussed today?
MR: So I think that one ethical issue that will come up fairly soon is not so much are we going to create a designer babies with IQ 200. I would be very surprised to see that practical. But rather, as we get a catalog of those rare variants, those mutations that do raise the risk of either intellectual disability or mental illness quite substantially, what should we do with that knowledge? Should we discourage people who are carriers of those mutations from having children. That I can imagine would be quite a fraught discussion.
MR: And so that, that's what I see some as the most pressing ethical issue that's likely to come up soon. I don't envision a sort of 'Gattaca'-like world where most of the interesting aspects of a person can be predicted from their DNA. I don't see that it's likely that we'll see predictions of temperament or IQ for most people in the normal range from DNA. But I think rare variants that have been fairly well linked to intellectual disability or behavioral problems, like aggression, might well prompt a conversation about, well, should we discourage people who are carrying these variants from having children.
LC: Or you could also have the conversation, should we be selecting babies that are less likely to have those. For those couples that decide to go that way.
LC: Instead of, you know, going the natural way, if we may call it that, that way. So now are there any, you mention a lot of gathering of, you know, thousands of tissue and samples that you need to carry out this studies. So I guess there are also a couple of ethical issues in, you know, how people give consent to having their tissue, maybe some privacy of how you might, or scientists might be able to de-identify their samples? Have you encountered any of those discussions so far?
MR: At the moment it's mostly, you know, the NIH has historically, I think, come down on the side of overcaution. And so, for example, in many, you know, what we would like to have is some indication of the life history of the people whose brains are donated to understand, for example, why we're seeing expression of genes associated, let's say, with inflammation or with pain or with, you know, some other kinds of specific characteristics we can identify.
MR: Because certainly not everybody has the same, everybody with a particular diagnosis, has the same gene expression profile. So we'd like to know what's different. And it's not that they have genetic variants that seem to be, to seem to explain that very much. It explains a little bit the specific gene variants that they have are very slightly related to the gene expression. But the majority of the variation does not seem to come from the DNA, but seems to come, well, seems to me that it's likely to come from their life experiences. So it would really help to know what life experiences they had. So it's a, you know, from a researcher's point of view it's a serious impediment that we don't have that information, but it would expose a lot of privacy concerns, and we would need to do something to address those if we're going to have that information.
LC: Well thank you so much for your time Dr. Reimers, it was my pleasure to having you here and hopefully people enjoy learning more about this topic.
MR: Okay. Thank you Laura.
LM: Thank you for joining us today on No Easy Answers in Bioethics. Please visit us online at bioethics.msu.edu for full episode transcripts and other resources related to this episode. A special thank you to H-Net: Humanities and Social Sciences Online for hosting this series. This episode of No Easy Answers in Bioethics was produced and edited by Liz McDaniel in the Center for Ethics. Music is by Antony Raijekov via Free Music Archive.