Karl Deisseroth, M.D., PhD: Where Behavior Lives in the Brain

Karl Deisseroth is a psychiatrist, neuroscientist and bioengineering professor at Stanford. Karl is also the author of Projections: The New Science of Human Emotion, which is a beautiful revisitation and exploration of his time as a psychiatry resident, where he encountered all sorts of people who didn’t quite understand what was happening to their brains—and by extension their minds.

In the book—and in our conversation today—Karl explores mania, autism spectrum disorder, eating disorders, borderline personality disorder, psychopathy, and dementia, all in gorgeous prose. Karl runs a lab at Stanford that focuses on optogenetics, mind-blowing science that can pinpoint where adaptive and maladaptive behaviors begin in the brain. He’s won the Kyoto Prize and Heineken Prize for his research, which is not surprising—it just might change the entire world of psychiatry.

Today’s conversation is far-ranging and it’s also surprising, including a conversation about how some of these disorders—like eating disorders, which can be deadly, can also be strangely adaptive. Please stick with us. Okay, let’s get to our conversation.

MORE FROM KARL DEISSEROTH, M.D., PhD:

Projections: The New Science of Human Emotion

Follow Karl Deisseroth on Twitter

TRANSCRIPT:

ELISE LOEHNEN: Well, I loved your book. It's funny because when I ordered it, I was like, oh, is this about like Carl Jung's shadow world and projections? And it's not, but it's not disconnected, obviously. But why projections? Why is that the title?

KARL DEISSEROTH: Yeah. Projections is a bit of a play on words that works really well in English. It was a problem with a lot of the translations in different languages to find exactly the right connotation. And even in British English, actually, they decided it didn't have the richness of the connotations in American English, so they went with a different title, Connections, but it's the same book. So it works in American English, though, and what it is, It brings together several different meanings of the word. In neuroscience, when we think about what a projection is, it's a long range connection from one part of the brain to another. And brain cells send out these tiny little thread like connections called axons, and they project across the brain. And in a fundamental way, they govern how one part of the brain can communicate with another or how one part of the self can communicate with another part of the self, and in doing so even define the self, because if you're not pulled together into the brain state of the moment, it's not really the self. Topic of speculation for a long time but anatomy was there. We knew these projections were present. And then, that's one meaning. Another meaning comes from psychiatry. I'm a psychiatrist, this is my office here where I treat patients and we use The word projection, when we talk about how one person understands themselves better by projecting a map onto somebody else, or they understand somebody else better by aligning a map of the other person onto their own inner structure. And this is really valuable. People are complicated. We can't always, in real time, read and understand and predict everything about somebody. So it helps to have a model. And we do this all the time. We project all the time. And it helps. It can go wrong and it can be taken to extremes and can misdirect things. If you understand that it's happening, it can be actually very, very powerful and useful, even in, in treatment. So that's a whole second meaning of projections. And then finally, it has this connotation of, you think of a projector sending light and creating an image. And here it alludes to this technology we developed right here at Stanford called optogenetics, which is a way of using light to turn on or turn off groups of cells, individual cells in the brain, make them fire away or be quiet and see what happens to feelings, emotions, complex thoughts, memories, motivations, desires. These are things that all we found boil down to the activity of individual groups of cells, and so it conveys that use of light to send meaningful information.

ELISE: Yeah, at the beginning of your book, you write about how you came to be a psychiatrist. And you write about this, like you love words. And that's very clear as a writer myself, but reading you, it seems like that's, in many ways, where your heart is as much as maybe your mind is into decoding Psychiatric illness, but you write sort of about this like I don't know if it's a paradox but like we have the brain and then we have the mind and interrogating the mind requires language and interrogating the brain is a scientific endeavor or medical endeavor and Psychiatry is such a strange type of medicine, right? Because you have to bring the two together. Can you talk a bit about that? Because the way that you describe it is so beautiful.

KARL: Well, like you, I grew up loving reading and words and how they could make someone feel. I was entranced by how the right combination of words, even two words, even one word in the right context could evoke a meaningful feeling and deep within me. I was always introspective. I always was curious about that, how that worked. And of course, context mattered, but also meaning mattered, but the two of them together the meaning of the word and the context of the word created feeling, created emotion. And I wanted to be a writer. That was the first path. I went down, I went to college, I started in creative writing, and I got entranced in a different way later by medicine and biology, so I got pulled in that direction. But all along I was writing experiences, thoughts, phrases things that resonated with me, things that people said, patients that I saw, turns of phrase that to me carried the meaning of the moment in powerful ways.

And I didn't know that psychiatry would be the branch of medicine I would end up in, but in medical school, there are exposures that medical students have to different fields and they're required actually. And you can't graduate from medical school without having exposure to a specific subset of fields. Surgery is one, pediatrics is one, obstetrics, gynecology is one, and psychiatry is one. And I would probably never have picked that if it hadn't been required. But I did my psychiatry rotation and I was absolutely enthralled by the nature of the practice of this field of medicine. The use of words is everything in psychiatry. It's diagnosis. In many cases, it's treatment. It's our equivalent of lab tests, and it's our equivalent of the most precise intervention or treatment that can be delivered. Not to say we don't do a lot of other amazing things in psychiatry. It's a rapidly advancing field. I prescribe medications here too. I do brain stimulation treatments. There's a brain stimulation device that acts through a nerve that goes through the neck and goes to the brain. We do very advanced work here, but at the core of it, it's all words. It's all the artful use of words to draw things out from people, what they're feeling. I appreciated that, and then at the same time, I saw the need in psychiatry, the immensity of the mystery, the, and also the suffering, and how little we knew and how much we had to know to make progress. There was no turning back at that point. For me, it was, it brought these two parts of myself together very well.

ELISE: Yeah. And, you mentioned sort of the words we use to try to express this inner state or emotions, our feelings, but also the stories we tell about our lives. And to be able to sort of hear that or match that or say, like, there's a concordance between this story and this pattern or this diagnostic code has to be profound to sort of hold that key in some ways and to say like, I understand, I understand your story. As much as everyone's story is their own story, but I loved that about your book. And I mean, we could spend an hour talking about any one of the sort of chapters as you're going through your residency and encountering theoretically different diagnostic codes, but it's more about like the profundity of these stories and the emergence of this experience and how real it is and how deeply felt and your own feeling which I think is so important because you juxtapose that with optogenetics, which tweaks my brain, I'll be honest. But this idea, this core question too, which is when we think about ourselves as these biological processes or mechanisms. What? Why must a state? This is your question. Why must a state feel bad or good? And when feeling bad is gratuitous or feels like it should be gratuitous. So can you talk a little bit about that? Like where it goes wrong and why we have feelings?

KARL: Yes, it's a core mystery of human existence and I don't claim at all to be the first to articulate it. Actually, if you've read Catch 22, for example Joseph Heller articulated it very well. It's of course a raucous, hilarious book, but there's a chapter in the middle the Eternal City where he really gets into a very dark, somber moment reflecting on the horrors of war and the trauma. And the main character, Yossarian, articulates this question very well. He says, why do we have to feel pain? We have to know something's happening, but why can't it be a heavenly chime of bells alerting us to a problem? It's a very artful description of a core biological question is why, if we're evolved, if we're designed To avoid things that are harmful to us, why should we have to feel bad about it? Why should there not just be an alert and then an action that's triggered? And wouldn't that be the more merciful design? And wouldn't that work just as well, evolutionarily? Why do we have these negative internal states? And long, long held mystery, but recently with the, some of the technologies that we've developed here in our neuroscience based approaches, we've made headway on that question. And what we found is that the value, the subjective valence or sign, positive or negative, of an internal state is a feature that can be added or subtracted very, almost disturbingly easily. There are groups of neurons that represent positive state or negative state. If I use optogenetics to turn them on or turn them off, I can instantly make a complex behaving mammal, like a mouse for example, I can make that mouse ascribe very positive associations with something completely neutral, like a room or part of a maze, or I can make it feel very negative about it. And how do I know how it feels? It reports to me how it feels by its behavior. It can avoid this formerly neutral room, like the plague, or it can come toward it and seek to spend all its time in this formerly neutral room. Based on how I've turned up or down these interstate neurons using these optical methods we developed, optogenetics.

And at the same time I was developing these methods, I was right here in this room you know, I see patients with depression and also autism. These are my core clinical specialties. And I remember very well, I had a patient here, an elderly gentleman who was describing his depression, and he said, when I'm in the depths of depression, I can see just an object and I can feel bad about that object. I can see a piece of paper on the floor. I can feel profoundly, profoundly bad about that. It feels horrible, that neutral thing. This was going on at the same time as we were doing the laboratory research. And for me, it brought things together so powerfully that I, that was one of the main motivations I had in writing a book is to share this with people that science has brought us to a point where we now understand this mystery at some level, at some level we understand where these internal states come from. Now, finally, the deeper question still is why, why do we have to experience these? And there, and I talk about this in the book a little bit, that internal state, good or bad, it's a bit of a currency exchange, right? We have so many different categories of things that we have to worry about all the time. It's not all just a zero to a hundred ranking of how good something is. We've got life plan decisions, we've got interpersonal relationships, we've got hunger, we've got thirst. We have all these things that are categorically different, all important, but we have to at any one moment, we have to take an action and sometimes a very consequential action.

And so all these different categories have to come together and we have to act. And how do you do that? You've got to route them all through a currency exchanger and put them all into a constant currency at some level, at some point, because you have to act, you have to make a choice. We all know this. We've all struggled with these. Fundamental life choice decisions, you know, relationships, career, and they're so hard because they're different categories, right? They don't translate, but at some level, if you reflect enough, you let the currency converters in your brain operate and you let yourself feel, you have to let yourself feel that internal state, and that's, I think, when people really come to the right decisions, they've taken the time to let that process play out. You talk about a gut feeling, that's when, Things have consolidated, and it might be close, but the conversion leads you to one final choice over another. And so that is where the science and where the practice of medicine have brought us. And I think it was, it's important for people to know about, and I was excited to share it in the book.

ELISE: You write about how optogenetics is so complex at this point, it can't be co opted, right? Like it's not like a transportable or usable... nobody is going to be sort of turning these things on in people's brains anytime soon. But when you go into the future, is that sort of the great thing psychiatric unlock? Is that there would be a mechanism for balancing or bringing someone back into homeostasis. I mean, clearly some people, I know you mentioned that autism is one of your specialties, that people's brains are built differently or have different filters. Do you imagine at some point there'll be some like, factory resetting where we all are optogenetically optimized? I mean, it's like chilling and then I also recognize it might resolve a lot of suffering.

KARL: It's a great question. So first you're right, as it currently exists, the technology doesn't act at a distance. Although it's somewhat disturbing when you think about it to have prospect of precise turning up or down of needs and wants and emotions motivations. And by the way, with our laboratory animals, we've shown this over the past 10 or 15 years, we can turn up or down the motivation of an animal for anything, including mating choices, parenting, even whether or not to nurture the young all kinds of memory hunger, thirst, fundamental primal drives. All these are instantaneously and precisely tunable. We've tracked down the cells and the connections and the projections that, that govern these these fundamental motivations. So, all this done in animals right now, all this, it's for science, it's for basic discovery, but you're right that if you look at the bigger picture and you say, well, a lot of suffering comes from these potentially tunable neural activity processes that are going on. And in the book, I talk about those as you mentioned, from autism to eating disorders, to borderline personality, dementia, things that touch all of us. In principle, there's a route into all of them with this new understanding. At the same time, though, you have to, of course, keep in mind the ethical questions. We wouldn't want to have an arbitrary situation where people were tuning their motivations and desires arbitrarily. I think we'd lose a great deal of what makes us special, what makes us human if we did that.

And the way I think about this is that what optogenetics does is it's an engine of discovery. It helps us identify what matters, what's causing things to happen in the brain. And we know now the cells and the connections make these powerful motivations and drives manifest. That opens the door to any kind of new treatment, right? If you know the cells, then you can look at the DNA and the RNA in those cells. You can see what proteins those cells are making, and that gives you clues for medication targets. You can say, okay, this cell has these proteins on its surface, that would give us an idea for a pill, for a medication that might act specifically on that cell that now we know for the first time is causal. It's not just correlated with, it's actually causing these symptoms or the resolution of these symptoms. And if we can now design a medication that targets that cell, we might have a treatment. And what's reassuring about that is then that brings things under a more traditional framework with a new precision, but a way that perhaps seems less unsettling, let's say.

ELISE: Yeah, so I want to park eating disorders because that chapter was so fascinating and there's something very, in some ways specifically different about that. And it feels like some of what you write about, like bipolar or autism, obviously very different things, but that those are attenuated, I think we can all sense, I recognize what I'm describing is not bipolar, but where, you know, the way that my own energy ebbs and flows, right? Where I can summon a huge amount of energy to be incredibly productive for a week and then go into this sort of latent state to recover. You write about it as like a maladaptive evolutionary experience where someone is obviously in a very extreme state. So there's that, there's autism, which I definitely want to hear you talk about. And then there are the, like, borderline, you don't write about NPD, but do you feel like those are biological or more environmental? Can we talk about those as separate groups? I don't even know how you would categorize them, but how do you think about it?

KARL: Yeah, the personality disorders, we do group those separately and they are grouped separately from the more treatable classical psychiatric diseases for a couple of reasons. The things like borderline personality narcissistic personality, histrionic personality, these are lifelong patterns, first of all, they're present from a very early age. Relatively constant, relatively untreatable by medication. So they have this almost structural quality to them. They certainly do have genetic underpinnings. So they are biological, at least in part which fits with this lifelong character. But they also can be influenced by events. So for example, borderline personality. There is an association between some of the symptoms of borderline personality and early life trauma. And so we know it's a mix genetics and experience that can underlie even some of these personality disorders, but they're very hard to treat with medication because they seem very, very much locked in and don't respond very well. Our hope is that with deeper understanding, treatments will come and that's one perspective I tried to bring out is still it's it sells in the brain, right? That's where feelings Thoughts and actions all come from, and that's where the symptoms of borderline personality come. It's feelings, it's thoughts, and it's actions, and it's all coming from cells. And we're making headway now on what those cells are. So my hope is that even though it's, at some level, baked in and hard to treat with existing medications, deeper understanding will bring us there.

ELISE: Interesting. And then for the ones where you feel like that are more treatable that are maybe like a bipolar, maladaptive, responding to some sort of existential threat with mania and hyperactivity. I'm throwing words around probably inappropriately. But is that sort of going to be the first place where something like optogenetics could dramatically affect someone's life?

KARL: Yeah, I think that's right. And we're already starting to see that. So if you look at disorders and not to say that the classical psychiatric diseases don't also have genetic components, they do, but they tend to come on later. Often they're triggered by a stressor or a particular developmental stage. Bipolar can be triggered certainly by stressors. And I write in the book about a patient I treated here, who had a completely normal life, was in retirement age, and then 9 11 happened and he flipped into a classic mania, classic bipolar mania. No hint of that had ever appeared in his life before. So it was certainly not a personality disorder, certainly you know, classical, bipolar type 1, as we call it, mania. A few weeks of incredibly elevated and oddly semi appropriate energy. Goal directed activity, this was a retirement age gentleman, but he wanted to go join the special forces and go and fight overseas. And so he started training himself, reading about theories of war. He would run through the canyons at night preparing, writing letters to the government. And it was obviously not something that was reasonable for him, but it was aligned in some way to the perceived threat of the moment. And so for me, that was a very illuminating example. It made me think, well, there's a certain logic to why we're capable of entering into these states. And for bipolar, that's true, for depression, that's true. All these things can be triggered by events and there's an underlying predisposition. Not everybody went manic after 9 11. So there's also an interaction with something inside, but indeed these are more, I think more treatable by medication because they don't have that lifelong character they come on later and so are perhaps more susceptible to treatment.

ELISE: and then let's talk a little bit about autism, because the way that you described it and wrote about it is how I've come to understand it, or it made a lot of sense to me, this mismatch between filtering the world and overwhelming stimulus versus your ability to sort of moderate it and respond back. I'm curious about your understanding of autism, why you think that it seems like we're better at diagnosing it or recognizing a range of neurodiverse or neurodivergent reactions, but talk to us about autism.

KARL: The autism, it's my other clinical specialty besides depression. And I treat patients here, even adult patients on the autism spectrum. It's very hard to treat with medication, it starts early in life. One of the core diagnostic features is it has to be picked up early in life. And it's tantalizing because at least for the mild cases, there are some clear positive aspects to it. There are these clear adaptive qualities. Of course, on the extreme end, it's very maladaptive and causes a lot of difficulties. But this is one of the three psychiatric diseases where if you look overall at everybody on the spectrum, it's actually a net positive. If you look at educational attainment, if you look at income. There are three classes of psychiatric disorders that are actually net positive if you look at these measures, and that includes autism, it includes bipolar, and it includes eating disorders and this has always tantalized me, and this has underlined a lot of the thinking about the book too, is this tells us something important, right? This tells us that, that the features of these disorders, Are in the right context in the right setting, probably of some value and autism has this, there's a very emotional quality to it as a parent. I spent 6 months in the autism clinic here at Stanford with the new diagnosis cases, people coming in for an evaluation, and my own first son was at the same age as these kids.

And so for me, it was a very emotional thing as I was going through this, going through the diagnostic process, seeing the concern, the worry of the parents and seeing these traits of the children and thinking about how is this going to cause problems for the child or for the family, but also at some level, there's a probably for some of them a hidden strength and thinking about that really helped me understand and empathize and ultimately, I think, help treat the patients better. Of course, autism, we still don't have treatments that directly affect the core symptoms. But we can help some of their associated symptoms. People with autism are very anxious because social situations are very hard for them to keep up with, to keep track of, and they get very agitated about this. So I can treat their anxiety. I can help them with that at least. And at the same time, the science is going to bring us to specific treatments for the core symptoms.

ELISE: Mm. Yeah, it's my son. I guess he would qualify as neurodivergent. He has an auditory processing disorder and he is fascinating. I mean, to your point, it's incredibly adaptive. His brain is amazing. It's also difficult and he doesn't process information in the same way and he could tell you about, you know, particle physics, but he can't like add, he can't spell or follow basic directions, but like, he'll probably solve world peace, like he's fascinating, but it is exactly this where you're like, how do I bridge him essentially to the place where he's going to be... I'm sure he'll be fine. But like getting him some of those core competencies has proven difficult.

KARL: And by the way, this extends to essentially every psychiatric disorder at some level, even the ones that don't fall into this trio of those that are net adaptive at the population level. Others that are not like bipolar for example, even at the individual level, there, there could be some hidden strength there. And so it really made me think broadly about psychiatry. Autism is a great example though, because it's a spectrum. Of course, people at different points on the spectrum will have more or fewer challenges, but you want to take a light touch and thinking about treatment, right? We do have to think what we mean by treatment, and we don't want to untowardly suppress things that make humanity magical, right? I have no doubt, you know, here in Silicon Valley, the world that we live in and the things that are, that we love about the world, the easy access to information, for example, a lot of that was built by, I think by people on the autism spectrum. I see this in in the community here quite remarkably. How could you even think about treating this? It would be like treating humanity. This is who we are, right? We're capable of having people with this power in our human family and we need to live with it. We need to work with it and celebrate it. And at the same time, though, I see the severe cases and I know how agonizing and incredibly heart wrenchingly difficult it is. So, each day I walk that line and I tried to share some of that perspective in the book as well.

ELISE: Yeah, no, two of my best friends have children with autism and it's like as all things like both beautiful and really hard and there's a lot of hope, you know, of like someday I'm going to unlock this child. So I commend you for, subspecialty because it is, I'm sure incredibly difficult. It's interesting that you had listed eating disorders on that list. I think I understand why, but we know how deadly they are, and all of these things can be incredibly dangerous, right? And eating disorders are so deadly. I thought the way that you wrote about was so beautiful, in the sense of working with, you know, it's obviously it affects boys and men as well, but you write about a girl and trying to understand this mechanism by which someone acts against their sort of core essential survival need and the dialectic between the enslavement and co conspiracy of these parts of ourselves, which is so interesting. Can you talk a bit about that?

KARL: Yeah, all the chapters do start with these patient stories and the one in the eating disorders chapter was a inpatient case that I had as a resident here some years back. And first of all, it was a case that taught me the value of Just creating space to let people talk and I talk a little bit about that in the story, probably wouldn't have gotten to the diagnosis of this patient who had a very severe case of bulimia nervosa without the right amount of space allowed. In fact, the first clue didn't come until I was slowly walking out the door and the patient started to reveal then some of what was going on with her. So that was interesting from the point of view of helping the patient and also my own medical development. But the case was also very hard for me because there was a moment when we thought we might have lost the patient she, was an inpatient on the Stanford psychiatry service and she'd started to reveal that she might have an eating disorder and she escaped the unit and was gone. We didn't know where she was. And some of that fear of losing a patient, which is, you know, for every physician and every healthcare professional, every first responder, this is something that strikes to the heart of you and when you lose one, you never quite come back fully. You're different forever. We had the feeling that we had lost her. And for me, although in the end I won't reveal all details of the ending, but the lesson that came out of that was that. This was a person who was incredibly smart, talented, controlled, and driven, and doing extraordinarily well in school. And here's where it comes to your question of what's the, why is this a net positive at the population level? The people who end up going down this path, the eating disorder path, you can't go down that path without incredible control. You can't go down that path without being driven to be able to recognize a need, to realize that you can reshape yourself to address that goal, and then do it, and make it happen, and make it stick. And then the problem is for both anorexia and bulimia, the cases where you restrict food access and become too thin, like anorexia, or where you binge and purge, eat large amounts, and then purge it out by various methods, both of these are life threatening, and can absolutely, sadly, tragically do kill people, but they only can exist because of this immense control that this new way of dealing with food, the most primal thing, as long as life has existed from single cell organisms, it's all about the intaking of resources from the environment to survive. There's nothing more fundamental than that.

And to achieve cognitive control over that is mind boggling. So I tried to reflect some of the realization that the fact that this can happen in people tells us a great deal about who we are, how far our brains have come, that we can achieve this astonishing level of control over how our brains work. And then what does that mean that we've come that far, that our brains can do this? And so for me, it was just as illuminating because it raises very philosophical questions almost, you start to talk about these different parts of the brain being in conflict with each other. And then you've got to ask, Well, which is the self? Which is the one that's making things happen? And when you talk about hunger, is the source of hunger the self? Is the self asking for food? Or is the self the one that feels the hunger? Or, as I ended up concluding in the end, the self is what actually can say no. I'm not going to take a traditional response to that drive. I see it's there I know it's there, but I'm going to choose to say that's not me, and I'm not going to take the traditional path toward it. And I ended up concluding that that was part of the self. And then that ended up mapping onto, just as with some of the other stories that mapped onto, some of our optogenetic neuroscience work and we can now point to some brain regions that we think are starting to answer this very, very old question of what is the self and where is the self. So for me, it was an incredibly illuminating journey but we were able to help her in the end.

ELISE: Yeah, I mean, in some ways, I'm like, I don't want you to know what the self is, right? But the way that you outlined it, and you talked about it too in the context of, I think it was about addiction, this like, you say, " The power of either anorexia or bulimia nervosa, as with the compulsion of drug addiction, still can derive from an initial, even momentary consent of the governed. Later, this authority becomes malevolent. Freedom is lost as time passes and patient and disease move closer and closer until, like any stellar dyad, twin suns spinning around each other. They become locked in a gravitational well, a hole deep and dark, destroying mass with every cycle collapsing into a singularity."

I mean, beautiful. But that's that's so interesting, and such a subtle shift of the submission, the governed, the initial co conspiratorial action of like, oh, I can do this, and then sort of where it goes completely off the rails. So in your mind, when you think about the adaptive trait, is that it sort of begins and ends with the ability to occasionally supersede your desire, which might be to like sleep all day.

KARL: That's right. So it's the, I think the underlying trait that is adaptive or positive, it is that discipline. It's the control and discipline, which of course, it's wonderful that different levels of that kind of discipline exists in the human family, of course, too. It's great that there are some people that are more controlled. It's great that there are some people that are a little less controlled, you know, that's beautiful, but it's the people who are able to manifest this extraordinary level of discipline. Of course, that is going to manifest in other domains of life too, right? And many of those will be positive for that person. But then, when you see it happen in a patient, this spinning out of control, it's initially under control. It's initially just a manifestation of this very strong self and this self discipline. And then with enough time, it becomes really a self reinforcing system, and then it's out of control of the self completely. And that process, how that happens, it gets reinforced, the reward of seeing what can happen, of seeing the control working, of seeing the discipline having the initial goal achieved, which might be a socially driven weight loss, for example, the incredible reward of that ends up feeding back and strengthening the circuits that made it happen in the first place. And they become so strong that they become immune to outside intervention. They're riding at the top. It's the circuits that are ultimately, to the extent that it's possible, are able to manifest brain states, to control things across the brain. And when they become self reinforcing, they achieve a direction of their own, and it's very hard to break down that state and to restore it back to how things were initially. Takes time, takes many months or years, and still, no medication truly works for eating disorders. There are therapies, inpatient programs, partial hospitalization programs, mixes of medications and therapies, but nothing that truly gets to the heart of it all.

ELISE: And you're often contending with a part of the self that doesn't want to relinquish the disease, right?

KARL: right. And that makes the treatments very hard. And I talk about that a little bit in the book as well. When you're working with a patient with an eating disorder, it's a little bit like working with a patient with a drug addiction, you both know, the physician knows and the patient knows that there's a third entity in the room with you. Patients with substance abuse disorder are very open about this. They articulate it very well, whether it's alcohol or opiates, they know there's another entity there. And what makes the eating disorder, that other entity so difficult is it's very intimate. It's much more entwined with everything else about the person. It's almost like a being that is internal and known, whereas patients with substance use disorder, there is this other entity, but it's more viewed as external. And so it's even harder for eating disorders.

ELISE: For addiction, which you didn't sort of directly write about, and it seems like there's ways, there's medicines, there's suboxone, there are these blockers, right? For these receptors of opiates and there are similar drugs for alcohol. Do you feel like there'll be some point where you will be able to turn that down as well?

KARL: I am optimistic about substance use disorder. It is something that becomes structural at some level, this rewarding cycle, like with eating disorders, that gets entrenched, but I do think that there's enough hints of progress that I think we'll end up with precise treatments for substance use disorder in the end. And we're already starting to see some very small steps being taken.

ELISE: As you, I don't know, you probably don't spend a lot of time on the internet. But as we sort of therapize each other and throw around all of this diagnostic pathologizing like, you know, everyone's a narcissist. I don't know if you know this, but it does feel like there's this rise. And I think that the internet and certainly social media makes this more apparent. I don't know if it's more prevalent. That's one of my questions. But these like dark triad personality traits, it feels like our culture is at the mercy of sort of dark triad. Do you feel like there's a higher occurrence of this type of behavior? And if so, do you know why?

KARL: Yeah. It's a great question. I think what we're seeing in our more interconnected world is that the reach of people with negative personality disorders is greater. Their reach would have been more local in the past. It's much easier for them to have a broader impact. And this is so that it's not so much about incidents or prevalence, it's more about reach. So that creates a lot of questions, right? How do we deal with this? How do we structure our society to protect ourselves? Given the fact that's not going to go away, right? The increased interconnectedness the extent to which people can reach out and affect each other is going to stay greater and, you know, politicians are one example of cases where you can have personality disorders, but also other folks as well. So it's not limited to any one field or profession or a group of people, the personality disorders are present everywhere. They're present at, you know, low rates, but if it's someone in a position of power, the impact is substantial. And so I'm a big fan of checks and balances. I'm a big fan of open communication. I'm a big fan of not letting one person dominate a discourse. And in my view, the path forward for us is to make sure that there are checks and balances, that there are honest, open, free conversations. And myself seeing what happens in a therapist's office like this one is that's where you get to the truth. And that's where you get to healing, is when people can speak freely and other people can speak freely. And you can come together in an honest conversation. So that's my hope that we can structure society, not just in a aspirational way, but in a really structural way where checks and balances and open free communication are what drives us.

ELISE: Yeah, and for people who don't know what dark triad, what I was referring to, it's that triangle of narcissism, Machiavellianism, and sociopathy. And I don't know if Machiavellian, it's probably not a real diagnostic code. But I do think, I mean, it's funny, it's like, I feel like sometimes culturally we throw around these ideas and they lose their value. But I do think that having a culture that is more literate. Around like there are a lot of sociopaths and sociopaths function very well. I mean it seems also like one of those traits that can be highly adaptive and a lot of our leaders our CEOs are High on sociopathy, right? I do think it can only be good that people understand these underlying instincts in part so that you can be conscious of what's at play? I don't know. Does it make you happy that there's more awareness or do you think our understanding is off?

KARL: I think it would be good if awareness were further increased you know, the recognition of antisocial personality disorder, and to be clear for the lay audience, this is the sociopathy, this is the criminal type thing we talk about when we say antisocial personality disorder. This is something that most psychiatrists and therapists have gotten pretty good at detecting over the years. And it would be wonderful if more people could detect this. Ultimately, as a physician, my hope is to also help them as well. Of course I want to help them. Many of them can't constitute Internal states of empathy that other people can they can't do projection onto themselves around other people as well. There's something structurally different. It's not their fault. Of course, it's not a good thing. And we have to help certainly protect society from negative consequences. And also ultimately the hope is to see if there's something restorative could be done for them, but detecting it is part of it. And understanding is part of it. I think that'll bring us a long way. What helps us is that a lot of times, the truly antisocial, they don't even really know what they're missing they don't understand the more typical way of feeling emotions and representing emotions. And so they're easy, once you know that, they're easy to pick up because they're like a child hiding a toy behind their back and hoping the parent doesn't see it. And the parent can see the hands are behind the back and you can get to that level where it's that easy to see. And it would be, of course in all seriousness, wonderful if, if we could help people pick that up.

ELISE: Yeah. Well, thank you for your book. Thank you for your work. And I can't wait to see what's next.

Well, Projections is a beautiful subtle book and fascinating, particularly in the way of imaging a world where we can adjust these levels. I don’t know how to feel about it, it’s so complex and conflicted. But to relieve peoples suffering would obviously be the goal, and hope for any treatment, while also allowing the wide diversity that we see, because we are not machines. He writes about this: “The fact that individual can be so instantaneously and powerfully altered in their expression of violence points to deep questions of moral philosophy. In teaching optogenetics to undergraduates, I have found it striking to see the responses they exhibit upon seeing videos—peer-reviewed and published in major journals—of instantaneous optogenetic control of violent aggression in mice. Afterward, the students often need a period of discussion, almost a dose of therapy, simply to process and incorporate into their worldviews what has been observed. What does it mean about us, that violent aggression can be so specifically and powerfully induced by turning on a few cells deep in the brain? As a professor I can transmit the perspective that this is not entirely a new effect—aggression has previously been modulated to varying degrees, over decades, with genetic, pharmacological, surgical, and electrical means.” Well, let’s see what happens. I’ll see you next time.