Karl Deisseroth: Depression, Schizophrenia, and Psychiatry | Lex Fridman Podcast #274

Where are the darkest places you've ever gone in your life? The following is a conversation with Karl Deisseroth, professor of bioengineering, psychiatry and Behavioral sciences at Stanford University. He's one of the greatest living psychiatrists and neuroscientists in the world. He's also just a fascinating human being. We discuss both the darkest and the most beautiful places that the human mind can take us. He explores this in his book called A Story of Human Emotions. I highly recommend it. It's written masterfully. This is the Lex Friedman podcast to support it. Please check out our sponsors in the description. And now, dear friends, here's Karl Deisseroth. You open your book called Projections, a story of Human Emotions, with a few beautiful words that summarize all of humanity. The book draws insights about the human mind from modern psychiatry and neuroscience. So if it's okay, let me read a few sentences from the opening. You gotta give props to beautiful writing when I see it in the Art of Weaving. Warp threads are structural and strong and anchored at the origin, creating a frame for crossing fibers as the fabric is woven, projecting across the advancing edge into free space. Warp threads bridge the formed past to the ragged present to the yet featureless future. Yet featureless future. Well done. Well done, sir. The tapestry of the human story has its own warp threads rooted deep in the gorges of East Africa, connecting the shifting textures of human life over millions of years. Spanning pictographs, backdrop by creviced ice, by ungulated forestry, by stone and steel, and by glowing rare earths. The inner workings of the mind give form to these threads, creating a framework within us upon which the story of each individual can come into being. Personal grain and color arise from the cross threads of our moments and experiences. The fine weft of life embedding and obscuring the underlying scaffold with. With intricate and sometimes lovely detail. Here are stories of this fabric fraying in those who are ill, in the minds of people for whom the warp is exposed and raw and revealing. What have you learned about human beings, human nature and the human mind from those who suffer from psychiatric maladies. For those for whom this fabric is warped.

One thing we learn as biologists is that when something breaks, you see what the original unbroken part was for. And we see this in genetics, we see this in biochemistry. It's known that when you have a mutated gene, sometimes the gene is turned up in strength or turned down in strength, and that lets you see what it was originally for. You can infer true function from dysfunction. And this is A theme that I thought needed to be shared and. And needed to be made communicable to the lay public, to everybody. People who. Which is, I think, almost all of us, who think and care about the inner workings of our mind, but who also care for those who have been suffering, who have mental health disorders, who face challenges. But then more broadly, it's a very much larger story than the present. There's a. A story to be told where the protagonist really is the human mind. And that was one thing I wanted to share as well. In Projections is that broader story, but still anchored in the moment of patience, of people, of experiences of the moment.

Is there a clear line between dysfunction and function, disorder and order?

This is always debated in psychiatry. Probably more so than any other, you know, medical specialty. I'm a psychiatrist. I treat patients still. I see acutely ill people who come to the emergency room where there's no doubt that this is not something that's working well, where the manifestation of disease is so powerful, where the person is suffering so greatly, where they cannot continue as they are. But of course, it's a spectrum. And there are people who are closer to the. To the realm of being able to work okay in their jobs, but suffer from some small dysfunction. And everywhere in between in psychiatry, we're careful to say we don't call it a disease or a disorder unless there's a disruption in social or occupational functioning. But, of course, psychiatry has a long way to go in terms of developing quantitative tests. We don't have blood draws. We don't have imaging studies that we can use to diagnose. And so that line, ultimately, that you're asking about, between order and disorder, function and dysfunction, it's operational of the moment. How are things working?

Can we just, like, linger on the terms for a second? So this disease, dysfunction, how careful should we be using those words? Can we just. Even in this conversation, from a sort of technical perspective, but also a human perspective, how quick should we be in saying that? Schizophrenia, depression, autism, as we kind of go down across the spectrum of different maladies, just to use the word dysfunction and disease, I would say to give.

Ourselves license to capture the whole spectrum. Let's say disorder, because that. That captures truly, I think, the essence of it, which is we need to talk about it when it's not working, when there's disorder, and that's the fairest and most inclusive term to use.

So is it fair to assume that basically every member of the human species suffers from a large number of disorders, then? Well, and we just have to pick which ones are debilitating. And for each person, if you look.

At the numbers, if you look at how our mental health disorders are currently defined, you can look at population prevalence values for all these disorders and you can come up with estimates that somebody will have a lifetime prevalence of having a psychiatric disorder that approaches 25% or so. And so that's. And in some studies it could be more, some studies it could be less. Now what do we do with that number? What does that mean? And in some ways that's the essence of what I was hoping to approach with the book is to reflect on this spectrum that exists for all the disorders. There is taking nothing away from the severity and the suffering that comes at the extreme end of these illnesses. But nearly every one of them exists on a spectrum of severity from nearly functional to completely dysfunctional, life threatening and even fatal. And so that number 25%, more or less, it doesn't capture that spectrum of.

Severity on that number. Where do those numbers come from? Is it self report? Is it people who show up and say I need help, Is it somebody else that points out that person needs help? Or is it like estimates that even go beyond that for people who don't ask for help that are suffering quietly?

When you look at self report numbers, then those numbers get even higher, beyond 25% or more. The most rigorous studies are done with structured psychiatric interviews where people who are trained in eliciting symptoms carefully do complete psychiatric inventories of individuals. And these are time consuming, laborious studies that not often repeated. When they're done, they're done well, but, but very often you'll see a report of something in the news of a very high number for some disorder or symptom. And very often if it's shockingly high, that's coming from a self report of a person. And so that's another issue that we have. Again, take nothing away from the severity and reality and biological nature of these disorders, which are very genetic. We understand that these are very biological. And yet we lack right now the lab tests and the blood draws to make the diagnoses.

We'll talk about it just how biological they are. Because that too is a mystery, you know, in terms of from a perspective of how to probe into the disease, how to understand it, how to help it. So some of it could be in your biological, some of it could be just the dance of human emotion and interaction. And the it's like is love when it works and is love when it breaks down biological or is it something else? So we're going to talk about it, but let me just like to linger. In terms of disorder, what about genius? You know, that sort of cliche saying, like the madness and genius that they kind of dance together. What about if the thing we see as disorder is actually genius, unheard or misunderstood?

Well, here again, the numbers help us. And here's where being rigorous and quantitative actually really helps. If you look at disorders like autism and bipolar disorder and eating disorders, anorexia nervosa, for example, these, you know, particularly bipolar and anorexia, these can be fatal. They can cause immense suffering. But they are heavily genetic, all three of these. And what's very interesting is each one of these three is actually correlated positively, positively with measures of intelligence, of educational attainment, and even of income. And so you look at this severe disorders, in many cases causing quite immense morbidity and mortality, and yet they are positively correlated at the population level with positive things.

Can you say the three again? Autism.

Autism, anorexia, and bipolar disorder.

Bipolar, right. What's that book? Forgot the book name. But is intelligence a burden?

Well, people can get into trouble when they think they're smarter than they are. I will say that.

I don't know. Sometimes, in the deepest meaning of that statement, I think ignorance is bliss. I'm a big fan of Prince Myshkin from the Idiot and Alyosha from Brother Karamazov. Optimism can be seen as naivete and dumbness, but I think it's a kind of deep intelligence, maybe inability to reason sort of about the mechanics of the world, but instead kind of feel the world. It seems like that's one of the paths to happiness.

There is how much you think versus how much you feel. This comes up all the time in medicine. We encounter this all the time. When you, day after day, you encounter this abyss of suffering from patients, how much do you let yourself feel? Or how much do you make it abstract and objective and try to make it clinical? And that range, how you're able to move yourself on that spectrum, is very important for survival as a physician. And the way you protect yourself and your feelings turns out to be very important.

So you quote Finnegan's Wake. Mad props for that James Joyce book. I took a class on James Joyce in college. I think I read parts of Finnegan Wake. I might have been on drugs or some kind, or I. I somehow got an A in that class, which probably refers to some kind of curve where nobody understood anything. The only thing I understood and really enjoyed is his short stories the Dead and then Ulysses. I Kind of, I think, read a few Cliff Notes that kind of got to the point and then Finnegan's wake was just a hopeless. For people who haven't looked at it. Maybe you can elucidate to me better, but I felt like I was reading things, words and the words made sense, like standing next to each other. But when you kind of read for a while, you realize you didn't actually understand anything that was said.

Right. But did you have a feeling, though? That's one thing I found interesting about Finnegan's week. I never fully understood it, but the words caused feelings in me, which I found fascinating. And sometimes I couldn't predict it from the semantic know, black and white context of what I was seeing in front of me on the page, but the rhythm or the melody would. Would make me feel certain ways. And that's. That was what I always was intrigued by with Joyce, of course, that was his.

He.

He existed on a spectrum too. And he wrote, as you say, you know, more accessible works. You know, I learned a lot about Irish history from, you know, Portrait of the Artist as a young man. And there was just. He could be as objective as he wanted to be, but then when he let himself loose, he was in this realm where the words had their own purpose, separate from semantic meaning from their dry dictionary definition.

There's a funny story that was told, doesn't matter if it's true or not, but they said that James Joyce, when he was young, when he was in his teen years, would go around Ireland drinking and so on, and telling everybody that he's going to be one of, if not the greatest writers of the 20th century. And he turned out to be that. So I always think about that little story that somebody told me because I have a lot of people come up to me, including myself. I'm a bit of a dreamer. You get into certain moods where you say, I'm going to be the greatest anything ever you get. People tell you this, especially young people, and it kind of. It makes me feel all kinds of ways. But that story reminds me that, like, you just might be one of the greatest writers of the 21st century, for example, if somebody were to tell me that. And like, don't immediately disregard that, because one of the people that say that, that's almost like a pre. Condition. That's like a requirement just to believe in yourself. Maybe it's not a full requirement, but it's an interesting story.

Well, I think when someone tells you that, then it creates. One sees an opportunity and then it would be A tragedy if the opportunity weren't captured. Right? And so then that creates some impetus, some motivation to do something good.

I think the mind, it's like, I guess that's what books like, or books or whatever. I don't even know if it's a book. The secret plugs into. They kind of make a whole industry out of it. But there is something about the mind believing something, making it a reality. It is just time and time again with Steve Jobs, like your belief in yourself, your belief in an idea, sort of embracing the me versus the world, embracing the madness of this idea and making it a life pursuit, somehow morphs reality around you for some tiny fraction of the population. For everybody else, you descend into.

You.

Know, all the beautiful ways that failure materializes in our lifetime.

Well, you know, you mentioned love earlier. I mean, that's a great example of how belief in something makes it real, right? It's not reasonable on the face of it, but because you believe it's reasonable, then it actually does become reasonable, and then it is real. And so that's a good example. That doesn't happen. I'm also in a bioengineering department. We don't imagine that a bridge is soundly built and that it is soundly built. That's something that it doesn't come up in too many realms of human existence, but love is one of them. And the ability to have a fixed idea and to say it's true and then it is true.

A bridge is a kind of manifestation of love. So maybe it does work a little bit, but it can break down like Chernobyl did. You can't just say it's safe. You have to also prove it's safe. But on Finnegan's wake, I think maybe, correct me if I'm wrong, you're using kind of Finnegan's wake to give one perspective on what madness is, of what's going on in the mind. How much of that is that? We're simply unable to communicate with the person on the other side of their mind. Like, there's almost like a little person inside the brain and they have some circuitry that's used to communicate emotion, communicate ideas to the outside world. And there's something about that circuitry that makes it difficult to communicate with the little person on the other side.

So if you look at what shows up in schizophrenia, with many cases, what we call thought disorders, what we call the individual speech symptoms of schizophrenia, Finnegan's wake is loaded with them, and it's just full of them. We talk about Clang associations in schizophrenia, where the word that is said echoes in some way the previous word. And we call that a clang association because there's no other reason than the similarity of the sound, like a clang of a. Of a garage door being hit. And it has a. And sometimes it's not even a word. And we call that a neologism, a new word being created. And of course, Finnegan's Wake is full of that. And then we also, in schizophrenia, where there's what we call loose associations or tangential thought processes, of course, full of that, where things just go off in directions that are not linear or logical. And you can't read Finnegan's wake, I think, without. Certainly as a psychiatrist, you can't read it without thinking about schizophrenia. And then when we look at the families of people with schizophrenia, and Joyce was no exception, there very often are people within the family who are on the spectrum. Some have it, some are able to see it from a distance, from a safe distance. There's an association between schizophrenia and. And what we call schizotypal personality disorder, where people are not quite in this severe state of schizophrenia, but have some magical thinking, have some unusual thought patterns. Very often those are family members of people with schizophrenia. So this points to this, again, to this idea that there is a range, even along this very severe, very genetic, biological illness, that human beings dwell on different spots along that spectrum.

I should mention that we have my friend Sergey pulling up stuff. Young Sergey or old Sergey, I don't know what to call you, but there's drafts of Finnegan's wake. Yeah, I actually saw pictures of this from. I think it was on Instagram or something. These are early drafts of Finnegan's Way. And it's so beautiful to see for people who are just listening, there's just random paragraphs and writing all over the page with stuff crossed out. And it's great to see that Joyce himself was thinking in this kind of way. As you're putting it together. How much do you think he was thinking about the schizophrenic mind?

I think a lot. I think it's known that his daughter suffered from schizophrenia. And what's depicted here on the page is something that I'm sure he either felt himself and some level was able to access this non linearity of processing, or had seen enough in family that he knew what it was and was able to reflect it down in black and white on the paper. So what he was able to do was quite authentic in that sense. Of course, I don't want to pigeonhole him. He was doing much more than that. It was much more than talking about altered human thought processes and thought disorders. But that was an aspect that he was so good at representing that it had to be intentional to some extent.

A tiny tangent. What does your own writing look like for this book? Because it's extremely well written. How many edits did you just drink? Some whiskey. And like, I'm imagining Hemingway style. What's a very different. The. The writing is very different. I mean, it's really, really well written, which was like, I was reading. Makes you realize, because I was expecting sort of a science kind of. Which it, you know, Lucy dating something about the human mind kind of thing. But you could also probably write really strong, like, novels. So maybe that's in the future. But anyway, what is your. How many edits? How many. What's your style? Does it look like that? Is it more structured, organized?

Unfortunately, I used a laptop, so I didn't have this sort of beautiful record.

Of typewriter, cigarette and whiskey.

I did explore. I was, you know, which was there a particular altered state that would help me to be most creative. And. And I found actually I actually did the best while sober, but slightly disinhibited in the late hours of the night or early morning. Yeah, particularly late hours of the night there. I have a friend who would tell me that she thought that very early in the morning her inner critic was still asleep and she could write more effectively before her inner critic woke up. And I actually found that outstanding advice for me that I often found that there was. I was looser and could write more in the morning. But the other interesting thing is each chapter, each story, it's about a different human being with a different class of psychiatric disorder. That's what each story, each chapter is anchored in. But I'm trying to use words and style of writing and diction that captures the feeling of the disorder. And so it's different in each story. In the story about mania, which is a very expansive, exuberant, at least briefly uplifting state where the words come out in a torrent and they're complex and pressured and elaborate, I try to capture that feeling with the words used in that chapter. And then in the schizophrenia or psychosis chapter, where things slowly fragment over time and become looser and separated, I tried to capture that in the writing, too. So for each. It wasn't as if there was a single mode I could be in for the whole book. For each chapter, I had to put myself into a different mode to capture that inner feeling of the disorder.

When you put yourself in that mode, does that change you?

Yeah, I couldn't turn it on and off right away. I had to. First I would start by thinking about the person or the people, one or two people, based on real patients and the stories that are put forth. The symptom descriptions are real, they're from the patients. Of course, all details change to protect privacy, but the actual symptoms descriptions are real. And I would sit with them and really try to inhabit the space of the mind of that person that I knew. And that's not instantaneous. It would take take some time. I needed quiet, I needed to be still. That's another reason late at night is good.

Sergey posted that drowsiness gives creativity boost according to Andrew Huberman. Thank you, Andrew.

He's not wrong. Is that wrong?

Why projections is it. I mean there's a. Instead of putting words into your mouth because I can imagine a lot, I mean I, to me, I will start putting words in your mouth, despite what I just said. So I mean to me, projections working on neural networks, for example, from an artificial neural networks, from a machine learning perspective, it's often that's exactly what you're doing. You have an incredibly complex thing and you're trying to find simple representations in order for you to make sense of it. So I was kind of thinking about in that way, which is like this incredibly complex neuronal network that is kind of projecting itself onto the world through this low bandwidth expression of emotion and speech and all that kind of stuff. And the way it. We only have that window into your soul, the eyes and the speech and so on. So that in that way we're. When there's any kind of disorder, we get to only see that disorder through that narrow window as opposed to the full complexity of its origins.

The word projections definitely serves that purpose here. But it's got a few other really appropriate other connotations as well. So the first thing is a projection in terms of neuroscience is this long range connection that goes from one part of the brain to another. And so it's what binds to parts of our brain together. There are projections, long range connections of axons. These are the outgoing threads that connect one part of the brain to another part. There's a, there's a projection that links, for example, auditory cortex, where we hear things to reward centers where we can feel where feelings of pleasure and reward are initiated. And it's been shown that if you have reduced connectivity along that dimension, you are less able to enjoy MUSIC and so these connections, these projections matter. They define how effectively two parts of the brain can engage with each other and join together to form a joint representation of something. So that's one meaning. It's pure neuroscience. The word projection is used all the time. And it happens to be something that optogenetics, a technique that we maybe we'll talk about a little later, works particularly well with. We can use light to turn on or off the activity along these projections from one spot of the brain to another.

And this is particularly referring to the long range connections.

It's particularly straightforward along these long range projections that connect different parts of the brain, but it works over shorter range too. But then there's this other meaning of projections which you were bringing up, which is very relevant, which is at some point you can reduce something from one level of dimensionality to another. You can project down into a lower dimensional space, for example. And then finally there's a psychiatric term, projections, which comes up all the time, which is we very often will look at our internal states and to understand somebody else, we'll project them onto somebody else. We'll try to understand someone else's behavior and make sense of it by projecting our own inner feelings, our own sort of narrative onto them and use that as a way to help us understand them better. And we'll do the reverse too. We'll take things we see in the outside world and we'll bring them into ourselves and see how we they map, how well they align. That's called introjection. So projections turns out to be a really rich word. And then finally, of course, there's the very common sense of it as a projector that illuminates by conveying information across space with light. So for English language, perfect word to use for this book. But what's funny is not every. There are a lot of international translations now and all those rich connotations aren't captured in other languages. And so for some translations, connections is used instead of projections. In fact, even in England, the British version is connections instead of projections. Because apparently projections doesn't have the full connotation. I was told you have to sacrifice.

Some of the rich ambiguity of meaning with connections. That's interesting. I mean, words are so interesting, they have so many meanings. I love language and how much is lost in translation. I'm very fortunate enough to be able to speak. I'm not good at languages. I was just, I guess, forced to by life circumstance to learn two languages, Russian and English. And it's just so interesting to watch how much of culture, how much of people, how much of history is lost in translation? The poetry, the. The music, the history, the pain, the way the scientists actually express themselves. Which is funny. I mean, just. It's so sad to see how much brilliant work that was written in Russian. There's a whole culture of science in the Soviet Union that is not lost. It makes me wonder in the modern day how much incredible science is going on in China that is lost in translation. And I'll never. I mean, that makes me very sad because I'll never learn Chinese in the same way that I've learned English and Russian. Maybe whenever I say stuff like that, people are like, well, there's still time. Yeah, that's actually fair. I think the 21st century, both China and US, will have very important roles in the scientific development, and we should actually bridge the gap through language. And that doesn't just mean convincing Chinese to speak English, that means also learning Chinese.

Well, we need these bridge people who can do both. Nabokov, for example, writing in English beautifully. One of my favorite poets, Borges, who mentioned earlier, he wrote both in English and in Spanish, I think beautifully in both. We need those people who can serve as bridges across cultures who really can do both.

You mentioned Borges. So you open your book with a few lines from a poem by Jorge Luis Borges, a love poem. I'm going to read parts of it because it's a damn good poem. It's called Two English Poems. I mean, there's. I'd like to understand why you used it and the specific parts you used, which is interesting. But then when I read the full thing. So I think you used it.

As.

A sort of beautiful description of what it means to delve deep into understanding, offering yourself to the task of understanding another human being. But if you look at the full context of the poem, it's also a damn good description of being hit by love and overtaken by it and sort of. And trying to figure out how to make sense of the world now that you've been stricken by it. It says a bunch of things about chatting and significantly with friends and all those kinds of things. And then the poem reads, the big wave brought you. This is the moment, I guess, of the universe where the two people you fall in love. Maybe. I'm totally misreading this poem, by the way. Doesn't matter. You can't misread the poem. So it goes on. Words, any words. Your laughter and you. So lazily and incessantly beautiful. We talked and you have forgotten the Words. The shattering dawn finds me in a deserted street of my city. Your profile turned away. The sounds that go to make your name the lilt of your laughter. These are the illustrious toys you have left me. So these little memories of these peculiar little details he remembers. Those are the illustrious toys. I apologize to mix my own words with the poem, but you should definitely read it. I turn them over in the dawn. I lose them, I find them. I tell them to the few stray dogs and to the few stray stars of the dawn, your dark, rich life. I must get at you somehow. I put away those illustrious toys you have left me. I want your hidden look, your real smile, that lonely, mocking smile your cool mirror knows. I want your hidden look, your real smile. So this is the first part of the poem, and then it goes on, which is some of the parts that you reference. Second part is what can I hold you with? I offer you lean streets, desperate sunsets, the moon of the jagged suburbs. I offer you the bitterness of a man who has looked long and long in a lonely moon. I offer you my ancestors, my dead men, the ghosts that living men have honored in bronze. My father's father killed in the frontier of Buenos Aires, two bullets through his lungs, and so on, so on. I offer you whatever insights my books may hold, whatever manliness, I humor my life. I offer you the loyalty of a man who has never been loyal. I offer you that kernel of myself that I have saved somehow. The central heart that deals not in words, traffics not with dreams, and is untouched by time, my joy and adversities. And I think this is where the part they include in the book. I offer you the memory of a yellow rose seen at sunset years before you were born. I. Damn, that's a good line. Okay. I offer you explanations of yourself, theories about yourself, authentic and surprising news of yourself. I can give you my loneliness, my darkness, the hunger of my heart. I'm trying to bribe you with uncertainty, with danger, with defeat. That is a man who's in love and longing if taken. But I just want to go back to. Maybe you could say why you want to include that poem, but also your dark, rich life. I must get at you somehow. I put away those illustrious toys you have left me at one year. I want your hidden look, your real smile, that lonely, mocking smile, your cool mirror nose. What? Sometimes I meet a stranger and I just. It's like a double take. It's like, who are you? Have we met before somewhere? Who's that person behind there? And I want to get at that. Whatever that is. And of course, maybe that's what love is, because maybe that's the whole pursuit, like a lifelong pursuit of getting at that person. Maybe that's what that is. And like that insatiable sort of curiosity to keep getting, like, well, who's that person in your own private life?

Yeah. So that. Absolutely. I think that it was a beautiful description of what you just said. When there's that first moment and then you want to dive deeper, you want to know what the hidden mysteries are. In a way, it's a love poem. As a scientist, though, it also. It's a bit of how a scientist can love science. And that wanting to dive deeper is. It's almost like, again, where the. It could be a love affair with investigating the human mind, for example, and. And that was one reason it spoke to me also, again, thinking about the broader sweep of where the human mind came from, the steps it took to get where it is today, what was given up along the way, what compromises were made. And here's where the darkness of the poem starts to come in a little bit, too. It doesn't shy away from the negativity, from the confusion, from the danger. And then at the very end, the Borges is offering up scenes from his life, parts of himself. And this is how we connect with people. We offer up parts of ourselves, just here it is. And then we see how well does that map onto what you have. And it's that offering up that I liked, and not the good stuff. Not only the good stuff. The Yellow Rose is nice, but he's offering up the bad stuff, too. And that, to me, was important for the book because I'm offering up hard stuff, too, in fact, a lot of it, and also hard stuff from within me, from my own personal side, too. And there's a lot of vulnerability that comes with that, but that comes with love, that comes with writing. You have to be open, you have to be vulnerable. And so I thought that reflected what I was trying to do, and I thought it was as an epigraph, it kind of made it clear how vulnerable I was in taking this step, but also what could come out of it.

And also in a meta way, because I was not familiar with this poem, it made me curious of the poem itself to pull at that thread, of finding out more. You picked a very particular part that kind of made you want to pull at that thread and see where did these few lines come from? Because I read it as a curiosity of a scientist, those lines alone, and also as a desperate human being. Searching, like offering himself for understanding or connection with another human being. And then, because I wasn't sure if it's a love poem or not, or if it's desperation or if it's curiosity, whatever it is. And then you see the love poem. I mean, I don't know that that's going to stick with me for a while. The. Your dark, rich life. And then a few lines in here are just. I mean, those are. I'm going to just use them as pickup lines at a bar. I offer you the memory of a yellow rose seen at sunset years before you were born. Now, that's a pickup line if I've ever heard one. Anyway, sorry, but this is universal.

You see it in so many forms of art. We're in Texas now. You see this in country and western songs. It's often a list of things. Here's how I describe myself. There's this and there's that, and there's the other thing. And here you are. These things matter to me, and I hope they matter to you, too. It's a pretty universal form. But he did it in this very artful and very vulnerable way. It was. It was both. Both beautiful. And you could. You could feel the hurt coming from him, too. And that was important.

The dark stuff, too. I offer you my ancestors, my dead men, the ghosts that living men have, honored in bronze and talking about two bullets through his lungs, bearded and dead, wrapped by his soldiers in the hide of a cow. My mother's grandfather, just 24, heading a charge of 300 men in Peru now, ghosts on vanished horses. So all of it, the whole history of it, since it is a love poem. What do you think about love, Carl? What's the role of love in the human condition? We'll talk about the dark stuff, but maybe love is the dark stuff, too.

I mean, it's the most powerful connection we can form. And that's its. That's what makes it so important to us. It's the strongest and most stable connection that we can form with another person. And that matters immensely. It matters for the human family to have evolved to be something that could survive against the odds that we've faced over the years. That unreasonable bond that becomes reasonable by virtue of its own existence. And of course, that joy, the wild, raw joy of love is not a bad thing either. So you put these together. The strongest bridge we can form, and the reward and the joy that it brings. That's what love is to me. And from my perspective, this is something that, you know, it can be hard to capture fairly, because you want to talk about the positive and the negative sides at once. They need to be wrapped up together for a full, honest description of what it is. And that's hard to do in a compact form. And so you have to take time to talk about love. You have to take time to do it justice. It takes a book or at least.

A poem or several thousands of them. I don't know. Sergey is there. Could you pull up. There's a video I saw. Yeah, like, right here. So can you pause for a second? So this is more to the penguins. So you always see, like, penguins huddling together against. I mean, sorry if I see just metaphors and everything, but them huddling together against the harshness of the conditions around them. That's very kind of. That's like a metaphor for life, like finding this connection. That's kind of what love is. It's like it allows you to forget, whatever the absurdity, whatever the suffering of life is together. You get to, like, huddle for warmth. And that's why I love the sort of. Just the honesty and the intensity of the way penguins, just in the middle of, like, the cold, do this. And then this video I saw a lonely. This is misinformation. So the name of the video is Lonely Deranged Penguin. I don't know if he's derang. So if you play it. So he left his pack, and there's a nice voiceover, and you don't need to play it. But he, for some reason, left the pack and journeyed out into the mountains. And so the narrator says that he's deranged, he's lost his mind. Now I'd like to project the idea that he's. Actually. There's so many stories you could think of. He's returning to his homeland. He's an outsider, thinking, journeying out into the unknown, thinking he may be able to discover something greater than the tribe. He might be looking for a lost love. Why is he deranged immediately? Why has he lost his mind anyway? But this. People should look up this video because to me, I might be the only one who romanticizes this. But it's such a nice kind of. It's both a picture of perhaps a mental disorder, which is what the video kind of describes. And it may be some deeper explanation that has to do with the motivation of a mind. Yeah, I don't know if you have a deeper analysis on this penguin.

Well, like you as a psychiatrist, I would want to sit down with the penguin and go through. I want to See the notes from his prior therapist. But this actually is relevant. Not knowing what was that Penguin's motivation. We have very clear situations where there are both within an individual. We go through periods of time when we stay in one place and we reap the benefits from what we've built. And then we go through periods of foraging, of wandering, even if there may be resources where we are. We have periods of time in our lives where we wander, where we are, where we go in an exploratory mode. And different people express that trait in different ways. This is not a human specific trait. If you go down to the tiny little nematode worm c. Elegans with 302 nervous system cells, they go through these phases of foraging and rest. And different individuals have different propensity to forage or to rest and stay in one place. At the level of the species, that's really good that there's that diversity in their willingness to forage. Some stay where they are. The species is somewhat on a firm footing then. But some carry a burden, a risk for themselves. But it's good for the species that they are explorers and they will venture out. The migration patterns that different species blunder into and that turn out to be really good, they weren't logically derived. They. They most certainly started from something like this, an exploration.

Humans do this too, you think?

And we do it too. In fact, it's something we do extremely well.

Let's talk about psychiatry a little bit. So my book, you're a rock star. First of all, for people who don't know, aside from sort of the neurological view of the brain and neuroscience view of the brain, you're also one of the great psychiatrists of our time. I've always, not always, but when I was younger I dreamed about being a psychiatrist. So it's like. It's like getting to meet your heroes and also, you know, getting to meet the people who. The best at the top of the world at the thing you've failed to pursue. So there's. I'm getting a free therapy session on top of that. Okay, so what big picture, what is the practice, the goal, the hope of modern psychiatry, if you could try to describe the discipline as you see it maybe historically, throughout the 20th century in contrasting to what it is today. Or maybe if you want to describe to what you hope psychiatry becomes or longs to become in the 21st century.

Yeah, it's been an interesting journey. It Psychiatry started out pretty firmly grounded in neurology and pathology. Some of the initial founders effectively of the field were very well grounded in microscopy, looking at cells, working with patients, particularly on the neurological side. And this certainly included, you know, Freud and some of his contemporaries. But they rapidly discovered that what they could work with at the level of cells and microscopy was so far from the realm of what they could get from a human being. And what they were getting from the human being was so much more interesting and had was so mysterious and so unknown that many of them just said, we're going to inhabit this domain and we're going to work with the people with their words and understand what we can based on verbal communication. Because that was the only tool that people really had. And that was a very important step for the field. I would say one of the interesting things that came from the early decades of psychiatry really was this distinction between the conscious and the unconscious mind. And paying particular attention to the unconscious mind is something that was worthy of consideration, that might be important in explaining people's actions, and that perhaps even insight into that was valuable in its own right. And out of that, psychoanalysis became a practice that was not always focused on cures or treatment, but was more focused on insight. What does it mean? How can we help people understand why they're feeling something or thinking something or dreaming something? And that insight, separate even from treatment, was an interesting thing. As long as one was honest about that and said, we're going for understanding, we're going for insight, maybe it's useful.

To just pause on that. If we look at the father of psychoanalysis, Sigmund Freud, what do you make of the ideas that he had? So you mentioned taking the unconscious, the subconscious seriously. That's like step one, like that there could be worlds we do not have direct access for and we probe them through conversation. Or is that too simplistic to call psychoanalysis conversation?

That's not too simplistic, but that's right. And I think that was valuable. Where Freud ended up breaking from some of his contemporaries, he was very focused on this unconscious as being so tightly linked to libido. And really he, from his perspective, you couldn't really separate the operation of the unconscious mind from these aspects of the libidinous aspects. And that was one reason. Libidness aspects, sexual, sexually related drives. Carl Jung, who was his contemporary, that's one factor that led to them separating was Carl Jung felt there was a lot more to the unconscious than this libidinous aspect of it. And he saw it as a much more complete alternate representation of the, the conscious self, one that maybe reflected a whole range of different motivations and, and desires. And to properly treat it, one had to consider all of them rather than the ones that Freud was focused on. Thank you.

Thank you for the high level of, of images that Sergey is pulling up for people who are just listening. He pulled up a. It's a quote from Sigmund Freud. It's a meme. Your mom quote. Freud. So the, the shadow, the Carl Young shadow encompasses everything, not just the desire to have sex with your mother or sex, period.

That's right. That's right.

If you look at those two folks en masse, I mean, there's a kind of, it's almost like a technique for philosophical exploration of human mind, human motivations. So it's not even like necessarily. It also doubles as a methodology for helping people, but it's almost like a, it's a kind of philosophical method.

Right. This is the fascinating thing about, about psychoanalysis and, and it, even though it's, it's, I would say, mostly not considered a treatment today, it persists for a couple reasons. One is it, it's. It's thought that, that it gives people. But second, there's been a huge influence on literature, on philosophy, on art. And the opening up of discussion about what was below our conscious mind was so fertile in the implications that it sort of reverberated and still does throughout all these different realms of human endeavor, from different artistic experiences that people have can be colored by this concept of the unconscious. Now the other thing that was interesting is this distinction. What are the parts of the unconscious? And so there were these ID and ego and superego subdivisions that Freud, for example, would talk about them. And the ID was the primal drives that an infant would have or that a very young child, just warmth and feeding. And then later the sexual or libidinous aspects.

And for Freud, the later happened very quickly. That's the controversial thing about him. I guess he thought even children had sexual desires that they're dealing with, contending with. So it's the full thing. Hungry, wanting to eat, wanting to poop, wanting to have sex.

Yeah, and he was extremely focused on that aspect. But then there was, then there was this, the super ego, which brought on these later sort of moralistic sort of codes of conduct. And that of course was very often intentioned, but all this could play out subconsciously. And then the ego, this third aspect was mediating and for its conception, mediated this tension between the different parts. Now, I think that's interesting. I will say that in some ways it's maybe unnecessary from the perspective of Modern neuroscience to divide things up that way from the, you know, the, the moralistic drives and the, the primal gratification drives. In some ways, they're all drives, and maybe they're even all primal drives. You know, the, the moralistic drives. They're. They're taught, and they're taught in ways that ultimately relate back to survival and you could even say selfish aspects of, of health and life for the self and family. And so this is. I don't. I think it's maybe an artificial distinction. The concept of the unconscious is very valuable and very interesting, but these categorizations of ID and. And superego may not map onto neurobiology in any particular way, is there's a town hall of competing drives and desires, and they interrelate to each other. They involve different aspects of the brain and the history of the person and actions and choices come out of the result of that overall shouting in the town hall.

So in some sense, Carl Jung was a step into the direction of liberating yourself from such harsh categorizations. Do you think? I mean, you have Daniel Kahneman with System one and System two. There's just these very compelling categorizations of the human mind that seem to be sticky in our. In the super ego. No, in the, you know, how we talk about these ideas and so on.

Yeah.

Do you think those are. How forward do they get in the way? Is it some kind of balance in terms of deeper understanding of how the mind actually works?

You know, it's. From the, from modern neuroscience. Whenever we seem to get closer to addressing a question like this at the level of cells, it seems to get farther away. And I'll give you an example of what I mean by that. So one thing I'm doing in my laboratory and many people are doing is we are listening in on the activity of cells, neurons in the brain of mice or rats or fish or monkeys.

Individual cells.

Individual cells, exactly. Of which there are in our brain many billions. And when we do, and we try to predict what action will be taken by an animal to address this question, where does the choice arise? Where does the impetus to make a particular selection of one action versus another action? Where does that start in the brain? If you're recording, listening in on the activity of cells all across the brain, where's the earliest spot you can pick up a choice being made? Well, that's so awesome. Yeah. At one level, you might think, how excited would Jung have been to see this or Freud or the early psychoanalysts to see where this starts? But it's not so simple because an emerging theme in very recent neuroscience, literally over the last few years is that things sort of all start together all across the brain. And so you can be recording from the cortex, this rim of cells at the surface of the brain, or you can be recording deeper in a structure called the striatum, which is a little older, it's more tightly linked to action. And then structures called the thalamus, other parts of the brain. And if you record from these, these all sort of represent the action and the choice, more or less all at about the same time, very close. And so you can't point to a particular spot and say, here's where the choice or the action originates.

It's a group finding the free will neuron.

It's relevant to that question. Nobody is close to being able to point to such a thing.

Well, close is a relative term and nobody. What did I tweet today? All generalizations are wrong. So including this one. Let's actually talk about that. So the study of individual cells, if you can linger on your sense that as you get closer to that understanding, it feels like you're getting farther away. Why is that? Because that often is the feeling until you're actually there. So, so like, you know, that's when I'm running and I know there's only a mile left. It just feels like that mile is just getting longer and longer. But eventually you finish. So maybe we're getting close to cracking open these like beginnings of a sense, like we'll talk about consciousness or these very difficult big questions about the human mind. Where do they start?

You're right to say we shouldn't generalize or make absolutist statements. But I would say right now the reason things are looking even harder to crack than we had initially thought. We now have the data streams that we've wanted for so long in terms of activity patterns all across the brain at the level of cells. We can literally see what cells are doing. Immense data sets. You know, we get these are, you know, time series of one individual cell with, you know, sub second resolution. And you can collect this from enormous numbers of cells across the brain. So very rich data sets that we've wanted for a long time. And yet having these has not led to an understanding of truly where actions initiate in terms of regions or locations.

Ask a few questions on that is the answer high level question by your intuition, is the answer within the data or do we need different kind of data? So we should also say that when you collect data about the brain, there's like the richness of information you're collecting, but there is also a human doing stuff like, and information, so static information about the human and dynamic information about the human. And you can get them to do different stuff and you can select different humans. And that's part of the collection of data aspect. So like when you're collecting data about the brain, there's some truths that you can, you know, in machine learning, like annotations, like supervised learning, there's some true things you can hold on to before you look at the full rich mess complexity of the human mind. So given the data you've looked at, do you think the answer for the, for the origin of free will in the human mind is, can be found?

Well, one, one amazing thing is that nobody's, nobody's found it, but we have these rich data sets and then there's a conundrum which is, is it in the data? And we just don't know how to look at it. Maybe we don't know the right scale, the right projection to make of the data, the right way to interpret it. And here's where causal testing becomes very valuable because then instead of just passively observing, well, here are, here are the activity patterns and then here's the choice made by the animal. As we've gotten more powerful at reaching in and causing things to happen in the brain, turning up or down the activity of certain types of cells or defined populations of cells and seeing how that affects actions, these causal perturbations have turned out to be very valuable. We're just now getting to the point where we can apply these in very wide swaths of the brain at cellular resolution. And so we're going to be able hopefully to make some headway on this question with causality. And that's the one thing that optogenetics provides us, this way of using light that we developed to control cells. This is an untapped, relatively untapped at this broad brain wide scale and hopefully we can get there in the near future. But I would say that the answer may be maybe in the data, but we don't know how to find it.

Well, there's this interactive element where you can cause stuff that's really powerful because you get to, I mean as opposed to collecting data passively, you're collecting data actively. So can you maybe describe one of the many things you're known for? One of the big things is called optogenetics. What is it?

Optogenetics is a way of causing things to happen. It's a way of determining what actually matters in terms of the activity of the brain for the amazing things it does. Sensation, cognition, action. And what it does is it provides activity. It's a way of playing in, if you will, activity patterns into precisely defined cells. And the way we do it is pretty cool. I think right away there's a problem if you think about how do we do this, how could we play in well defined activity patterns? Patterns provide a stream of activity into this cell and that cell and that cell, but not these other cells.

But just for, for context, we're talking about the brains of mice, monkeys, humans. And then the goal is to try to control accurately the behavior of a single neuron and then to be able to monitor single collection of single neurons to then say, well, to draw some deeper insight about the origins, first of all, the function of different parts of the brain, different neurons, different kinds of neurons, but also the origins of the big things, the flap of the butterfly wing that leads to an actual behavioral thing.

So if you could. Exactly. So if you could turn on or off the brain or parts of the brain or cell types or individual cells at the natural rate and rhythm and timing of normal brain activity, that would be immensely valuable because you could determine what actually mattered, what could cause complex things to happen, and what could prevent complex things from happening in a specific way. But right away you've got a problem if you want to do this. And scientists, neuroscientists have wanted to do this for a long time. Francis Crick, of Double helix of DNA fame, he wrote a famous paper in 1999. He got interested in neuroscience later in life. And he said, what we need in neuroscience is a way that we could turn on or off the activity of individual types of neurons in a behaving animal. And he even said the ideal signal would be light because it's, it would be fast. It could penetrate through the brain to some extent. And he had no idea how to do it. He said this would probably be very far fetched, but it would be a good thing.

And so that's what you're actually saying, like, if you want to do this kind of thing, and then it's. You imagine like, how do I get inside the brain? It's pretty difficult to do.

It's pretty difficult. And then even once you get in, it's hard because all brain cells are electrical, all neurons are electrically activated. And so if you wanted to use electricity as what you were putting in, you won't have any specificity at all. If you have an Electrode, a wire, and you put it in the brain and you send current through it. All the cells near the electrode will be stimulated.

It's like trying to control fish by spraying them with water.

Yeah, right, because there's already a lot of electricity going around anyway, and you're adding more. But there's no specificity even among the different kinds of cells either, because all around the wire that you've put in, there are going to be so many different cells doing totally different things, many of them in opposition to each other. We know that's one way the brain is set up. There are parts of the brain where neurons side by side are doing completely different things and maybe even antagonistic to each other. So what do you do? How do you play in activity with any kind of specificity? Well, what you do is use. What we found is, what you can do is make some cells responsive to light. Now, normally, no cells deep in the, in the brain really respond to light. They're not built for that. There's no reason for them to respond to light in there, which is a great situation to start with, because any light sensitivity you can provide to some cells will be a huge signal above the noise. And so that's what we do with optogenetics. We take genes, bits of DNA from microbes, single celled organisms. And these single celled organisms, like algae, they make little proteins that sit in the surface of their cells that receive light, capture a photon of light and open up a little hole in the membrane of the cell and let charged particles, ions like sodium and potassium, flow across the membrane of the cell. And that these algae and bacteria, they do this for their own reasons because that helps them move, it helps them make and use energy.