David Linden

Our Genes in the Pandemic

Air Date: December 7, 2020

Johns Hopkins University neuroscientist David Linden discusses his new book “Unique: The New Science of Human Individuality.”


HEFFNER: I’m Alexander Heffner, your host on The Open Mind. I’m delighted to welcome to our broadcast today. David Linden, he’s professor of neuroscience at the Johns Hopkins University School of Medicine. Thank you so much for your time today, Professor.


LINDEN: Thanks for having me on.


HEFFNER: Let me ask you about the new science of human individuality. Your book “Unique,” what have you found during this period of the pandemic to be most resonant in thinking about the unique personalities of homosapiens, of human beings, what has struck you during this, this unique and unprecedented once in a century type event?


LINDEN: Well, I would say we’re unique whether we’re whether we’re dealing with COVID or not. But I think the thing that is clearest to me is that when there’s much more that contributes to our individuality than most people imagine. A lot of times people get go to the phrase nature versus nurture, meaning what is not hereditary must come from nurture, meaning how your parents raised you, how your community raised you. The thing that I think is clearest from recent work in genetics and neuroscience is that that formulation is simply untrue. That nurture is only one small part of the experience that forms us as individuals, that it’s not just experienced in the family or even social experience or experience that could be written down as memories, but everything that impinges upon us from our time in the womb to our last day, including the foods we eat, and this is actually very relevant to COVID, I found a way to bring it back. We know that if your mother is fighting off an infectious disease while she’s carrying you, that this increases your chance of developing schizophrenia or autism by about four-fold. We know this from the 1918, 1919 pandemic flu, for example, where women were carrying their babies, the winter of 1918, 1919, and we followed up with them. What we don’t know is whether women who are carrying children now and are fighting off COVID, will see a similar effect in their offspring.


HEFFNER: Let me ask you about the genetic predisposition or what I would call genetic preparedness for events like pandemics, but the way that we ought to analyze the genome and be prepared for different eventualities, it doesn’t seem like there was enough thinking early on in the pandemic on how we could employ the study of the genome and our genetics to help us fight this thing.


LINDEN: Well, I mean, in truth, there was very little work on coronaviruses at all. So, people got interested in them briefly during SARS, which was also a coronavirus. And then later during MERS the Middle Eastern Respiratory Syndrome, which was a camel-transmitted coronavirus and then funding for it just crashed. And as you know funding to study chromosomes in the wild, including the reservoir of bats in China, where, where, where this virus likely came from crashed as well. You’re absolutely right though that genetic individuality makes a difference. Viruses enter cells, not by just smashing through the wall of the cell like a tank through the wall of a building, but rather they gain entry by binding to particular receptor proteins. And those are separate proteins are encoded by genes. So, the same way that there are long-term non progressors with HIV, because the receptor that HIV uses to get into the T cell in the blood doesn’t readily bind the HIV virus, there are very likely people who are fortunate, who bear mutations in the appropriate receptor for coronavirus that renders them partially or completely immune. And that would be extremely interesting to know about.


HEFFNER: Is that kind of work going on now in your department and others, that is how we can understand our genes better to prepare for the rest of this pandemic and potential next pandemics?


LINDEN: Well, understanding. I mean, so it used to be that just to sequence the human genome was a worldwide hundreds of million-dollar effort. And you probably remember during Bill Clinton’s time, it was a big deal. We finally got the human genome, but of course there is no the genome, there are all the subtle differences in all the human genomes of all the individuals. Right now, technology has advanced to the point where can sequence the human genome for about a thousand dollars, maybe even a little less. And so, as a consequence now we’re in an era where the promise of individualized medicine will soon be realized. You know, there are already things that we know about. We can test you genetically and say, well, if you have this gene, you’re very likely to get breast cancer so, you should probably take preventative measures, or you’re likely to react badly to this drug so we won’t give it to you. But this will expand enormously. And it will be very interesting to see how that interacts, particularly with infectious disease.


HEFFNER: In the scientific community right now, to what extent is there, if at all, skepticism around the individualized approach, because it was in some ways, something that folks were afraid of delving into too deeply as a result of eugenics movements and sort of the tendency to associate genes with skin color or race and to castigate cohorts of society. I’m wondering what the climate is right now in the scientific community.


LINDEN: Well, you know, I think it’s, it’s something that is very actively debated right now. And I think there are several levels of debate. One is, is it a good use of limited resources, right, is individualized medicine which right now is a rather expensive thing to do that is only really going to be, it’s really only going to be available to people who have really good health care. Is that really the best way we as a society can marshal our forces to increase the public health? So that’s one issue. Another one, as you say, has to do with, with eugenic and racial concerns. And certainly, there is a history of this, and there’s a lot of misunderstanding. For example, a lot of people and a lot of doctors think that sickle cell disease is a disease of people of African ancestry. And it’s true that people with African ancestry do have a higher rate of sickle cell, but sickle cell exists because if you have one copy of the sickle cell gene, it is protective against malaria. What that means is this was an evolutionary adaptation, but it wasn’t just an Africa. It was anywhere that malaria was endemic. So, if you look at people from Sicily or Sardinia or certain places in the Middle East or certain places in Asia, where malaria is endemic, they also have sickle cell trait. So, these things are true and can guide medical decisions, but they have to be unburdened of the stereotypes that have long come with them.


HEFFNER: You write a lot about how the human experience is a result of and interacts with our genetic makeup. But one question I had for is the physiological reaction to an aftermath of this pandemic. Science is far more sophisticated, I would say then it was after the 1918 flu as, especially in your area of expertise. When we think of the neuroscience, and you mentioned the example of infected pregnant women and their offspring, but what about what we’re, what we should be looking at for our radar on how neurologically we’re going to be impacted by this pandemic?


LINDEN: Well, see, that’s really very much an open question. Right now we know so little about the broad impacts of the, of the coronavirus. I mean, we know that you can find coronavirus in many different organ systems in the body. It’s not even though it is largely transmitted in a respiratory fashion. It gets many more places besides the respiratory system and coronavirus has been found in the brain and the nervous system and what it does there and what the problems are and how, if those problems may linger in people who are having so-called long COVID, you know, we really, we really don’t know, it’s extraordinarily early days.


HEFFNER: What about the questions that are most central to genetic factors contributing to our behavior, both during the pandemic and in the aftermath of the pandemic, do you think that there will be a comprehensive enough study of human beings, you know, not just folks who were, who were seeking any kind of treatment for mental health concerns or issues that arose from isolation. The question being to you, you know, what kind of comprehensive plan should there be to understand how this has further metamorphosized our genome, if you will?


LINDEN: Well, I mean, there is no evidence that COVID integrates into the genome. So, in other words, it’s not like COVID gets into your DNA and then you pass it onto your kids. It’s, it’s, it’s not a retrovirus.

HEFFNER: I suppose. I mean more in terms of our predisposition and, and, and how our genetics will interact with our behavior or vice versa in the future. It may not have the kind of consequential affect that my question is sort of premised on, but I wonder if, if there’s sort of a way to understand the neuroscience in the, the physiological results, which will be long-term, not so much the medical challenge of how COVID plagues your various systems, but more in terms of, you know, how it affects our human decision-making going forward.


LINDEN: Well. You know, that is a that’s a really good question. And that’s really, that’s really a question more for more for psychologists, I think, than me. In other words, it’s more of an issue of how people respond to fear and to, to risk and to low probability, but high impact events. And so, you know, there is a lot of study of decision-making in that time, but that’s not really my area of expertise at all. You know, that’s something where you want to sort of get a sort of neuro-economist.


HEFFNER: What would you say is, is in writing about our uniqueness as individuals and individuality, what, what would you say is sort of the most important scientific advance in understanding our individuality, that, you know, the lay population, the non-scientific community should be interested in?


LINDEN: Well, I think the most important thing for people to understand is that there’s randomness; that your individuality is determined by experience. And of course, that means your experience broadly considered, not just the experience of in your family, or your social experience, as well as what the genes you inherit, but there’s something else. And that is our, our DNA is not a set of detailed instructions to build the body and the brain. It doesn’t precisely say every cell should connect to every cell this way. It’s not a blueprint. It’s not a wiring diagram. Rather, it’s a set of vague instructions. And that’s why so-called identical twins, monozygotic twins have the very same DNA grow up in the womb right next to each other, even at birth they’re not truly identical either in appearance or in temperament. So, you think, well, how did this come about? And it comes about because the genome is only approximate. You know, there’s a set of cells in the brain, and it might get instructions to say, hey, about half the neurons grow up here. And then you cross the midline and then you’d grow some more. But in one identical twin, it might be 40 percent of those neurons will cross the midline and another identical twin it might be 60 percent over those neurons that cross the midline. So, I think the factor that people don’t think about when they’re thinking about individuality is the third factor, and that is developmental randomness.


HEFFNER: And what’s the best way for tracking or accounting for the randomness?


LINDEN: I don’t know that we can really track it in people because we’re talking about, about subtle alterations that, that we can’t see with scanning devices. I mean, in animals, we can study this a little more easily, a great animal for this is the nine banded Armadillo. They’re always born as monozygotic, quadruplets, genetically identical quadruplets. And so, you can take them, and you can, you know, you can look at him, you can say, oh my gosh, this one, even though these are genetically identical, and they wound up and they grew right together in their Armadillo womb, this one has a liver that’s 30 percent bigger than that one. And this one has a response to stress in terms of stress, hormone secretion that’s twice as big as that other one. And this is because of developmental randomness. And the interesting thing about developmental randomness is that it’s probably there for a reason. In other words, when you have a population of critters, you don’t want them to be too much alike because then, if there is some catastrophic thing that happens, everybody doesn’t get wiped out because everybody doesn’t have the same traits and the same proclivities. If you have a group of insects and they all like to live under a leaf, and then under the leaf gets flooded, they’re all gone. But if some weirdos like to live, not under the leaf, well, then they survive to seed the population of them to, into the future.


HEFFNER: In terms of the randomness of, you know, what makes us tick and what makes us tick uniquely, you study in particular, a question of our memory function, the capacity to store memories you study the molecular basis of how addiction actually occurs, something we’ve talked about pretty frequently on this program over these past years. When I ask you about tracking the randomness, I am thinking in those terms of, you know, things that are not necessarily things that show up in a scan, like the precise makeup of memory, or the way that molecules you know, functioning in your particular brain, as it relates to processes, whether it’s addictive processes or other processes, but how do those things figure into our uniqueness?


LINDEN: Well, so most behavioral traits have a heritable component. So, for example, if we were to take a trait that psychologists like to talk about, like risk-taking, novelty seeking behavior, that is something that is estimated to be about 40 percent heritable or to say about 40 percent of the variability in that trait can be attributed to the genes you inherit. So, then the question becomes, well, what’s the rest? And most people would say, oh, it’s stuff like, you know, how your parents raised you when your birth order in the family. And shockingly, it isn’t. Like, those things have almost nothing do with personality traits. You know, there is, for example, people say, oh, you know, people firstborns are leaders. And you know, the middle child is a negotiator. And, you know, the youngest kid has to be kind of clever and find their way in the crowd. And while it’s true that these things hold for interactions within the family, once you get out of the family, these stereotypes completely fall apart, and you can understand why it is that the oldest kid who’s the, the big cheese in the family, they go on the playground, they’re not the biggest anymore, or the strongest or the fastest or the smartest. And so, and so behavioral traits are fascinating. And some of what determines them is heritable a lot is not, sometimes there are things that determine them that are not heritable, but are nonetheless biological, like the hormones that you were subjected to in utero or early development. I don’t want to say that social experience isn’t important, but it’s more important for some things than others. It’s important for conveying a moral sense. It’s important for convenient work habits and specific ideas about religion or employment, but it’s not important in determining what psychologists measure in personality tests.


HEFFNER: So, I don’t quite know if you’re saying it’s nature versus nature instead of nature versus nurture, or if it’s the question that we haven’t properly defined the, you know, wherein people are being nurtured, because you’re saying that the family structure is over emphasized in the nurturing effect.


LINDEN: Well, it is when it comes to personality, right? And it is in something like, for example, sexual orientation, right? So sexual orientation in cis-gendered males is about 40 percent heritable and in cis gendered females is about 20 percent heritable. And that leaves a whole lot of other things to happen. But remarkably, when the American psychological association did a huge meta -analysis, they found the child rearing had nothing to do with it at all. In other words, child rearing can determine like whether or not you feel comfortable enough to come out in your family and your community, but in terms of what you feel inside yourself, what people report seems to make no difference at all.


HEFFNER: Buy it strikes me that memory is, and how we remember events is something that is maybe in the, you know, wrongly characterized as part of the nurture, but it’s actually the nature. And we don’t really know the extent to which our friends, our family, you know, we’re not studying how they’re remembering things, but it strikes me that that is a very important part of individuality.


LINDEN: Memory is crucial for individuality. Absolutely. That’s, that’s an important factor for, for how we are formed through our life experiences, but it’s not all of it. And I think the important thing to realize is that experiences in the world when they affect your mental processes, ultimately do so by effecting the biology of your brain. When psychotherapy works, when talk therapy works, it works because it’s changing your brains biology. When meditation works, when mindfulness work, these things don’t work on some mystical woo plane. They ultimately work ‘cause they change the brain. And so, you know, a lot of things that people think are in opposition really aren’t ultimately, there are biological reasons why these social manipulations are indeed efficacious. My father was a psychoanalyst. He did a lot of good for people. And ultimately he did it by changing people’s brains, literally.

HEFFNER: So, with respect to memory, how much of memory do we have control over for the average person who is not the victim of a brain injury? You know, what are the different categories of memory that and how much, how much agency, if you will do, we have over what we decide to remember?


LINDEN: Well, you know, memory is the sort of thing that is, we tend, when we sit, when we talk about memory, we tend to think about memory for facts and events, but that’s only a small part of memory. Memory also includes like things like getting better at a sport or your heart races when you, when you hear a sound that, was traumatic in your past, all of these are forms, memories. Some of them are, are just other social non-declarative forms of memory. I think the important thing about memory for facts and events, particularly about memory for events is that it’s only as good as it needs to be. And the example I like to use is if you’ve been to the beach, once you’re going to remember everything about it with great fidelity, but if you’ve been to the beach a hundred times, you’re probably not going to remember many of the details of visit number 47, unless something really unusual happened. And you might think, oh, that’s a problem. My memory is degraded. I’m confusing one thing with another; how can this be good? How could this be adaptive and helped me get my genes in the next generation? And the answer is a generic memory is actually more useful to you. Them a highly, a high-fidelity individual memory of all a hundred times. You went to the beach when, when memory fails, it fails in specific ways. And those ways are oftentimes more of a feature than above a memory isn’t useful to us when it’s a static card catalog memory is useful to us when we could integrate it with our subsequent experience and with every emotional state that follows.


HEFFNER: Is memory only as good as we want it to be David, or is it only as good as we need it to be?


LINDEN: Well, I would say it’s, it’s only as good as, as we need it to be, we now be the species, right? There are variations in terms of, of how people experience memory and, you know, memory isn’t unitary. I think we all know, like for example, people have perfect memory for faces or, or for song lyrics or, or for wine aromas.

HEFFNER: When I’m asking you that though, I’m also asking it in terms of those people who, who may not want to remember certain things; who choose not to remember, you know what I mean?

LINDEN: Well, you know, memory can be good or bad, right? I mean, so you know, post-traumatic stress disorder is memory gone awry, right? When you have a memory that’s written so strongly that you can’t help but bring it to mind that interferes with your subsequent life. That’s, that’s a memory and the memory might be accurate, but it’s not doing you any good at all. You know, generally speaking emotion is the currency for the strength of memory. Things that are emotionally salient, whether they’re good or bad are likely to be written into memory strongly. Things that aren’t are more likely to be discarded or distorted. But I think one of the important things is that you store a memory and then every time you recall it, you actually change it a little bit. Every time you recall a memory, it becomes subsequent to… It becomes susceptible to manipulation. And this is a good thing because this is what our allows our memories to be integrated with our, with our presence. And the thing is that memory is subjective from the first moment. So, for example, if you and I are standing next to each other on the street, and there’s a house fire, and we watch the firetrucks roll up, if I had a traumatic experience with fire in the past, and you didn’t, my experience of that event is already different from yours from the very first moment it happens, right? Its memory is always the experience of an event, not the event itself,


HEFFNER: David Linden, author of “Unique: The New Science of Human Individuality.” Thank you so much for your knowledge and your insight today, David.


LINDEN: Thank you for having me on it was fun.

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