back to indexKarl Deisseroth: Depression, Schizophrenia, and Psychiatry | Lex Fridman Podcast #274
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Where are the darkest places you've ever gone in your life?
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The following is a conversation with Karl Deisseroth,
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professor of bioengineering, psychiatry,
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and behavioral sciences at Stanford University.
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He's one of the greatest living psychiatrists
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and neuroscientists in the world.
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He's also just a fascinating human being.
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We discuss both the darkest and the most beautiful places
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that the human mind can take us.
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He explores this in his book called
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Projections, A Story of Human Emotions.
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I highly recommend it.
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It's written masterfully.
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This is the Lex Friedman podcast.
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To support it, please check out our sponsors
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in the description.
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And now, dear friends, here's Karl Deisseroth.
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You open your book called Projections,
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A Story of Human Emotions with a few beautiful words
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to summarize all of humanity.
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The book draws insights about the human mind
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from modern psychiatry and neuroscience.
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So if it's okay, let me read a few sentences
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You gotta give props to beautiful writing when I see it.
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Quote, in the art of weaving, warp threads are structural
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and strong and anchored at the origin,
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creating a frame for crossing fibers
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as the fabric is woven.
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Projecting across the advancing edge into free space,
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warp threads bridge the formed past
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to the ragged present to the yet featureless future.
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Yet featureless future, well done, well done, sir.
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The tapestry of the human story has its own warp threads,
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rooted deep in the gorges of East Africa,
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connecting the shifting textures of human life
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over millions of years, spanning pictographs
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backdroped by crevice ice, by angulated forestry,
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by stone and steel, and by glowing rare earths.
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The inner workings of the mind give form to these threads,
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creating a framework within us,
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upon which the story of each individual can come into being.
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Personal grain and color arise from the crossed threads
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of our moments and experiences, the fine weft of life,
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embedding and obscuring the underlying scaffold
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with intricate and sometimes lovely detail.
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Here are stories of this fabric fraying in those who are ill.
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In the minds of people for whom the warp
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is exposed and raw and revealing.
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What have you learned about human beings,
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human nature and the human mind,
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from those who suffer from psychiatric maladies,
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for those for whom this fabric is warped?
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And one thing we learn as biologists
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is that when something breaks,
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you see what the original unbroken part was for.
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And we see this in genetics, we see this in biochemistry.
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It's known that when you have a mutated gene,
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sometimes the gene is turned up in strength
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or turned down in strength,
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and that lets you see what it was originally for.
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You can infer true function from dysfunction.
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And this is a theme that I thought needed to be shared
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and needed to be made communicable
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to the lay public, to everybody.
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People who, which is, I think, almost all of us,
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who think and care about the inner workings of our mind,
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but who also care for those who have been suffering,
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who have mental health disorders, who face challenges.
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But then more broadly,
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it's a very much larger story than the present.
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There's a story to be told
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where the protagonist really is the human mind.
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And that was one thing I wanted to share as well
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in projections, is that broader story,
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but still anchored in the moment of patients,
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of people, of experiences of the moment.
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Is there a clear line between dysfunction and function,
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disorder and order?
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This is always debated in psychiatry,
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probably more so than any other medical specialty.
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I'm a psychiatrist, I treat patients still.
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I see acutely ill people who come to the emergency room
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where there's no doubt that this is not something
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that's working well, where the manifestation of disease
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is so powerful, where the person is suffering so greatly,
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where they cannot continue as they are.
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But of course, it's a spectrum,
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and there are people who are closer
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to the realm of being able to work okay in their jobs,
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but suffer from some small dysfunction.
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And everywhere in between.
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In psychiatry, we're careful to say
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we don't call it a disease or a disorder
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unless there's a disruption
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in social or occupational functioning.
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But of course, psychiatry has a long way to go
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in terms of developing quantitative tests.
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We don't have blood draws, we don't have imaging studies
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that we can use to diagnose.
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And so that line, ultimately, that you're asking about
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between order and disorder, function and dysfunction,
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it's operational at the moment.
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How are things working?
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Can we just linger on the terms for a second?
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So this disease, dysfunction,
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how careful should we be using those words?
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Can we just, even in this conversation,
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from a sort of technical perspective,
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but also a human perspective,
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how quick should we be
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in saying that schizophrenia, depression, autism,
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as we kind of go down across the spectrum
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of different maladies,
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to use the word dysfunction and disease?
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I would say to give ourselves license
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to capture the whole spectrum, let's say disorder,
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because that captures truly, I think, the essence of it,
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which is we need to talk about it when it's not working,
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when there's disorder.
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And that's the fairest and most inclusive term to use.
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So is it fair to assume that basically every member
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of the human species suffers from a large number
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of disorders then?
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Well, we just have to pick which ones are debilitating
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You know, if you look at the numbers,
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there are, if you look at how our mental health disorders
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are currently defined,
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you can look at population prevalence values
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for all these disorders,
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and you can come up with estimates
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that somebody will have a lifetime prevalence
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of having a psychiatric disorder
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that approaches 25% or so.
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And so that's, and in some studies it could be more,
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some studies it could be less.
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Now, what do we do with that number?
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What does that mean?
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And in some ways, that's the essence
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of what I was hoping to approach with the book,
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is to reflect on this spectrum that exists
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for all the disorders.
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There is, and taking nothing away from the severity
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and the suffering that comes at the extreme end
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of these illnesses, but nearly every one of them exists
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on a spectrum of severity, from nearly functional
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to completely dysfunctional, life threatening,
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And so that number, 25%, more or less,
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it doesn't capture that spectrum of severity.
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To look at that number, where do those numbers come from?
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Is it self report?
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Is it people who show up and say, I need help?
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Is it somebody else that points out that person needs help?
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Or is it like estimates that even go beyond that
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for people who don't ask for help
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or are suffering quietly alone?
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When you look at self report numbers,
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then those numbers get even higher, beyond 25% or more.
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Those, the most rigorous studies are done
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with structured psychiatric interviews
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where people who are trained in eliciting symptoms carefully
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do complete psychiatric inventories of individuals.
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And these are time consuming laborious studies
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that are not often repeated.
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When they're done, they're done well.
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But very often you'll see a report or something
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in the news of a very high number
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for some disorder or symptom.
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And very often, if it's shockingly high,
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that's coming from a self report of a person.
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And so that's another issue that we have, again,
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take nothing away from the severity and reality
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and biological nature of these disorders,
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which are very genetic, very, you know,
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we understand that these are very biological.
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And yet, we lack right now the lab tests
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and the blood draws to make the diagnoses.
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We'll talk about it, just how biological they are,
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because that too is a mystery.
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You know, in terms of from our perspective
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of how to probe into the disease,
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how to understand it, how to help it.
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So some of it could be neurobiological,
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some of it could be just the dance
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of human emotion and interaction.
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And it's like, is love when it works
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and is love when it breaks down biological
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or is it something else?
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So we're gonna talk about it.
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But let me just like to linger in terms of disorder.
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What about genius?
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You know, that sort of cliche saying,
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like the madness and genius
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that they kind of dance together.
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What about if the thing we see as disorder
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is actually genius, unheard or misunderstood?
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Well, here again, the numbers help us.
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And here's where being rigorous
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and quantitative actually really helps.
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If you look at disorders like autism
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and bipolar disorder and eating disorders,
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anorexia nervosa, for example,
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these, you know, particularly bipolar and anorexia,
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these can be fatal, they can cause immense suffering,
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but they are heavily genetic, all three of these.
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And what's very interesting is each one of these three
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is actually correlated positively,
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positively with measures of intelligence,
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of educational attainment, and even of income.
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And so you look at this severe disorders
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in many cases causing quite an immense morbidity
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and mortality, and yet they are positively correlated
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at the population level with positive things.
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Can you say the three again, autism?
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Autism, anorexia, and bipolar disorder.
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What's that book, forgot the book name,
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but is intelligence a burden?
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Well, you know, people can get into trouble
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when they think they're smarter than they are,
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Sometimes, like, in the deepest meaning of that statement,
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I think ignorance is bliss.
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I'm a big fan of Prince Mishkin from The Idiot
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and Aliosha from Brother Karamazov.
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Optimism can be seen as naivety and dumbness,
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but I think it's a kind of deep intelligence.
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Maybe inability to reason sort of about the mechanics
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of the world, but instead kind of feel the world.
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It seems like that's one of the paths to happiness.
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How much you think versus how much you feel,
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this comes up all the time.
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In medicine, we encounter this all the time.
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Day after day, you encounter the abyss of suffering
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How much do you let yourself feel?
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Or how much do you make it abstract and objective
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and try to make it clinical?
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And that range, how you're able to move yourself
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on that spectrum, is very important for survival
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as a physician, and the way you protect yourself
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and your feelings turns out to be very important.
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You quote Finnegan's Wake, mad props for that,
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I took a class in James Joyce in college.
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I think I read parts of Finnegan's Wake.
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I might have been on drugs of some kind,
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or I somehow got an A in that class,
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which probably refers to some kind of curve
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where nobody understood anything.
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The only thing I understood and really enjoyed
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is his short stories, The Dead, and then Ulysses.
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I kind of, I think, read a few Cliff Notes
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that kind of got to the point,
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and then Finnegan's Wake was just a hopeless.
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For people who haven't looked at it,
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maybe you can elucidate to me better,
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but I felt like I was reading things, words,
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and the words made sense, like standing next to each other,
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but when you kind of read for a while,
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you realize you didn't actually understand
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anything that was said.
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Right, but did you have a feeling, though?
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That's one thing I found interesting about Finnegan's Wake.
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I never fully understood it,
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but the words caused feelings in me,
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which I found fascinating,
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and sometimes I couldn't predict it
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from the semantic black and white context
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of what I was seeing in front of me on the page,
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but the rhythm or the melody
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would make me feel certain ways,
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and that was what I always was intrigued by with Joyce.
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Of course, that was his, he existed on a spectrum, too,
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and he wrote, as you say, more accessible works.
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I learned a lot about Irish history
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from Portrait of the Artist as a Young Man,
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and there was just, he could be as objective
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as he wanted to be, but then when he let himself loose,
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he was in this realm where the words
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had their own purpose separate from semantic meaning
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from their dry dictionary definition.
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You know, there's a funny story that was told,
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doesn't matter if it's true or not,
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but they said that James Joyce, when he was young,
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when he was in his teen years,
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would go around sort of Ireland drinking and so on
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and telling everybody that he's going to be one of,
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if not the greatest writers of the 20th century,
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and he turned out to be that.
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So I always think about that little story
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that somebody told me,
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because I have a lot of people come up to me,
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including myself, I'm a bit of a dreamer.
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You get into certain moods where you say
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I'm going to be the greatest anything ever.
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You get people tell you this, especially young people,
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and it kind of, it makes me feel all kinds of ways,
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but that story reminds me that you just might be
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one of the greatest writers of the 21st century,
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for example, if somebody were to tell me that,
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and don't immediately disregard that,
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because one of the people that say that,
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that's almost like a precondition,
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that's a good requirement just to believe in yourself.
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Maybe it's not a full requirement,
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but it's an interesting story.
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I think when someone tells you that,
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then it creates, one sees an opportunity,
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and then it would be a tragedy
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if the opportunity weren't captured, right?
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And so then that creates some impetus,
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some motivation to do something good.
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I think the mind, it's like, I guess that's what
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books or whatever, I don't even know if it's a book,
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The Secret plugs into, they kind of make
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a whole industry out of it.
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But there is something about the mind
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believing something, making it a reality.
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It is just time and time again with Steve Jobs,
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your belief in yourself, your belief in an idea,
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sort of embracing the me versus the world,
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embracing the madness of this idea
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and making it a life pursuit,
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somehow morphs reality around you
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for some tiny fraction of the population.
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For everybody else, you descend into
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all the beautiful ways that failure
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materializes in our lifetime.
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Well, you know, you mentioned love earlier.
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I mean, that's a great example of how
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belief in something makes it real, right?
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It's not reasonable on the face of it,
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but because you believe it's reasonable,
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then it actually does become reasonable,
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and then it is real.
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And so that's a good example.
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That doesn't happen.
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I'm also in a bioengineering department.
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We don't imagine that a bridge is soundly built
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and then it is soundly built.
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That's something that, it doesn't come up
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in too many realms of human existence,
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but love is one of them.
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And the ability to have a fixed idea
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and to say it's true, and then it is true.
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A bridge is a kind of manifestation of love.
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So maybe it does work a little bit,
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but it can break down like Chernobyl did.
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You can't just say it's safe.
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You have to also prove it's safe.
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But on Finnegan's Wake, I think,
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maybe correct me if I'm wrong,
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you're using kind of Finnegan's Wake
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to give one perspective on what madness is,
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of what's going on in the mind.
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How much of that is that we're simply unable
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to communicate with the person
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on the other side of their mind?
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Like there's almost like a little person inside the brain
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and they have some circuitry that's used
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to communicate emotion, communicate ideas
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to the outside world.
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And there's something about that circuitry
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that makes it difficult to communicate
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with the little person on the other side.
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So if you look at what shows up in schizophrenia,
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with many cases, what we call thought disorders,
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what we call the individual speech symptoms
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of schizophrenia, Finnegan's Wake is loaded with them.
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And it's just full of them.
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We talk about clang associations in schizophrenia
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where the word that is said echoes in some way
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the previous word.
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And we call that a clang association
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because there's no other reason
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than the similarity of the sound,
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like a clang of a garage door being hit.
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And it has a, and sometimes it's not even a word,
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and we call that a neologism, a new word being created.
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And of course, Finnegan's Wake is full of that.
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And then we also, in schizophrenia,
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where there's what we call loose associations
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or tangential thought processes,
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of course, full of that where things just go off
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in directions that are not linear or logical.
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And you can't read Finnegan's Wake, I think,
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without, certainly as a psychiatrist,
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you can't read it without thinking about schizophrenia.
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And then when we look at the families of people
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with schizophrenia, and Joyce was no exception,
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there very often are people within the family
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who are on the spectrum.
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Some are able to see it from a distance,
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from a safe distance.
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There's an association between schizophrenia
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and what we call schizotypal personality disorder
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where people are not quite in this severe state
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of schizophrenia but have some magical thinking,
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have some unusual thought patterns.
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Very often, those are family members
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of people with schizophrenia.
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So this points to this, again, to this idea
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that there is a range, even along this very severe,
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very genetic biological illness that human beings dwell
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on different spots along that spectrum.
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I should mention that we have my friend, Sergey,
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pulling up stuff, young Sergey or old Sergey,
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I don't know what to call you,
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but there's drafts of Finnegan's Wake.
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Yeah, I actually saw pictures of this from,
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I think it was on Instagram or something.
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These are early drafts of Finnegan's Wake.
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And it's so beautiful to see.
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For people who are just listening,
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there's just random paragraphs and writing
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all over the page with stuff crossed out.
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And it's great to see that Joyce himself
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was thinking in this kind of way
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as you're putting it together.
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How much do you think he was thinking
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about the schizophrenic mind?
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I think it's known that his daughter suffered
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from schizophrenia.
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And this is, what's depicted here on the page
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is something that I'm sure he either felt himself
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in some level was able to access
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this nonlinearity of processing
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or had seen enough in family that he knew what it was
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and was able to reflect it down
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in black and white on the paper.
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So what he was able to do was quite authentic
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Of course, I don't want to pigeonhole him.
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He was doing much more than that.
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It was much more than talking about altered human
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thought processes and thought disorders.
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But that was an aspect that he was so good at representing
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that it had to be intentional to some extent.
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And a tiny tangent.
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What does your own writing look like for this book?
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Because it's extremely well written.
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Did you just drink some whiskey
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and like I'm imagining Hemingway style?
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What's a very different, the writing is very different.
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I mean, it's really, really well written,
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which was like, I was reading it.
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It makes you realize,
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because I was expecting sort of a science kind of,
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which it is like elucidating something
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about the human mind kind of thing.
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But you could also probably write really strong novels.
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So maybe that's in the future.
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But anyway, what is your, how many edits?
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What's your style?
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Does it look like that?
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Is it more structured, organized?
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Unfortunately, I used a laptop,
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so I didn't have this sort of a beautiful record.
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No typewriters, cigarette, and whiskey.
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I did explore which was their particular altered state
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that would help me to be most creative.
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And I found actually, I actually did the best
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while sober, but slightly disinhibited
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in the late hours of the night or early morning.
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Yeah, particularly late hours of the night there.
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I have a friend who would tell me
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that she thought that very early in the morning,
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her inner critic was still asleep
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and she could write more effectively
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before her inner critic woke up.
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And I actually found that outstanding advice for me
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that I often found that I was looser
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and could write more in the morning.
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But the other interesting thing is each chapter,
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each story, it's about a different human being
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with a different class of psychiatric disorder.
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That's what each story, each chapter is anchored in.
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But I'm trying to use words and style of writing
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and diction that captures the feeling of the disorder.
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And so it's different in each story.
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In the story about mania, which is a very expansive,
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exuberant, at least briefly uplifting state
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where the words come out in a torrent
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and they're complex and pressured and elaborate.
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I try to capture that feeling
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with the words used in that chapter.
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And then in the schizophrenia or psychosis chapter,
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where things slowly fragment over time
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and become looser and separated,
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I try to capture that in the writing too.
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So for each, it wasn't as if there was a single mode
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I could be in for the whole book.
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For each chapter, I had to put myself into a different mode
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to capture that inner feeling of the disorder.
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When you put yourself in that mode, does that change you?
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Yeah, I couldn't turn it on and off right away.
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I had to, first I would start by thinking about the person
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or the people, one or two people based on real patients
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and the stories that are put forth.
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The symptom descriptions are real,
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they're from the patients.
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Of course, all details change to protect privacy,
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but the actual symptom descriptions are real.
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And I would sit with them and really try to inhabit
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the space of the mind of that person that I knew.
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And that's not instantaneous.
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It would take some time.
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I needed quiet, I needed to be still.
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That's another reason late at night is good.
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Sergey posted that drowsiness gives creativity boosts,
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according to Andrew Huberman.
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Thank you, Andrew.
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He's not wrong, he's not wrong.
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Is it, I mean, instead of putting words into your mouth,
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because I can imagine a lot.
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I mean, to me, I will start putting words in your mouth,
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despite what I just said.
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So, I mean, to me, projections,
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working on neural networks, for example,
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from an artificial neural networks,
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from a machine learning perspective,
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it's often, that's exactly what you're doing.
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You have an incredibly complex thing
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and you're trying to find simple representations
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in order for you to make sense of it.
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So I was kind of thinking about in that way,
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which is like this incredibly complex neural network
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that is kind of projecting itself onto the world
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through this low bandwidth expression of emotion and speech
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and all that kind of stuff.
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And the way it's, we only have that window into your soul,
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the eyes and the speech and so on.
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So in that way, when there's any kind of disorder,
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we get to only see that disorder through that narrow window
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as opposed to the full complexity of its origins.
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The word projections definitely serves that purpose here,
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but it's got a few other really appropriate
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other connotations as well.
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So the first thing is a projection
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in terms of neuroscience is this long range connection
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that goes from one part of the brain to another.
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And so it's what binds two parts of our brain together.
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There are projections, long range connections
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of axons, these are the outgoing threads
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that connect one part of the brain to another part.
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There's a projection that links, for example,
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auditory cortex where we hear things to reward centers
link |
where we can feel, where feelings of pleasure
link |
and reward are initiated.
link |
And it's been shown that if you have reduced connectivity
link |
along that dimension, you are less able to enjoy music.
link |
And so these connections, these projections matter.
link |
They define how effectively two parts of the brain
link |
can engage with each other and join together
link |
to form a joint representation of something.
link |
So that's one meaning, it's pure neuroscience.
link |
The word projection is used all the time.
link |
And it happens to be something that optogenetics,
link |
a technique that maybe we'll talk about a little later
link |
that works particularly well with,
link |
we can use light to turn on or off the activity
link |
along these projections from one spot of the brain
link |
And this is particularly referring
link |
to the long range connections.
link |
It's particularly straightforward
link |
along these long range projections
link |
that connect different parts of the brain,
link |
but it works over shorter range too.
link |
But then there's this other meaning of projections
link |
which you were bringing up, which is very relevant,
link |
which is at some point you can reduce something
link |
from one level of dimensionality to another,
link |
and you can project down into a lower dimensional space,
link |
And then finally, there's a psychiatric term projections
link |
which comes up all the time, which is we very often
link |
will look at our internal states
link |
and to understand somebody else,
link |
we'll project them onto somebody else.
link |
We'll try to understand someone else's behavior
link |
and make sense of it by projecting our own inner feelings,
link |
our own sort of narrative onto them
link |
and use that as a way to help us understand them better.
link |
And we'll do the reverse too.
link |
We'll take things we see in the outside world
link |
and we'll bring them into ourselves
link |
and see how well they map, how well they align.
link |
That's called introjection.
link |
So projections turns out to be a really rich word.
link |
And then finally, of course, there's the very common
link |
sense of it as a projector that illuminates
link |
by conveying information across space with light.
link |
So for English, for English language,
link |
perfect word to use for this book.
link |
But what's funny is not every,
link |
there are a lot of international translations now
link |
and all those rich connotations
link |
aren't captured in other languages.
link |
And so for some translations, connections is used
link |
instead of projections.
link |
In fact, even in England,
link |
the British version is connections instead of projections
link |
because apparently projections
link |
doesn't have the full connotation, I was told.
link |
So you have to sacrifice some of the rich ambiguity
link |
of meaning with connections, that's interesting.
link |
I mean, connect, man, words are so interesting.
link |
They have so many meaning.
link |
I love language and how much is lost in translation.
link |
I'm very fortunate enough to be able to speak.
link |
I'm not good at languages.
link |
I was just, I guess, forced to by life's circumstance
link |
to learn two languages, Russian and English.
link |
And it's just so interesting to watch
link |
how much of culture, how much of people,
link |
how much of history is lost in translation.
link |
The poetry, the music, the history, the pain,
link |
the way the scientists actually express themselves,
link |
I mean, it's so sad to see how much brilliant work
link |
that was written in Russian.
link |
There's a whole culture of science in the Soviet Union
link |
It makes me wonder, in the modern day,
link |
how much incredible science is going on in China
link |
that is lost in translation.
link |
And I'll never, I mean, that makes me very sad
link |
because I'll never learn Chinese in the same way
link |
that I've learned English and Russian.
link |
Maybe, whenever I say stuff like that,
link |
people are like, well, there's still time.
link |
But, you know, yeah, that's actually fair,
link |
that I think the 21st century, both China and U.S.
link |
will have very important roles in the scientific development
link |
and we should actually bridge the gap through language.
link |
And that doesn't just mean convincing Chinese
link |
That means also learning Chinese.
link |
Well, we need these bridge people who can do both.
link |
You know, Nabokov, for example, writing in English
link |
beautifully, one of my favorite poets, Borges,
link |
who I mentioned earlier, he wrote both in English
link |
and in Spanish, I think beautifully in both.
link |
We need those people who can serve as bridges
link |
across cultures who really can do both.
link |
You mentioned Borges, so you open your book
link |
with a few lines from a poem by Jorge Luis Borges,
link |
I'm gonna read parts of it because it's a damn good poem.
link |
It's called Two English Poems.
link |
I mean, there's, I'd like to understand why you used it
link |
and the specific parts you used, which is interesting.
link |
But then when I read the full thing,
link |
so I think you used it as a sort of beautiful description
link |
of what it means to delve deep into understanding,
link |
offering yourself to the task of understanding
link |
another human being.
link |
But if you look at the full context of the poem,
link |
it's also a damn good description of being hit by love
link |
and overtaken by it and sort of,
link |
and trying to figure out how to make sense of the world
link |
now that you've been stricken by it.
link |
It says a bunch of things about chatting
link |
and significantly with friends and all those kinds of things
link |
and then the poem reads, the big wave brought you.
link |
I get, this is the moment, I guess, of the universe
link |
where the two people you fall in love.
link |
Maybe I'm totally misreading this poem, by the way.
link |
Doesn't matter, you can't misread a poem.
link |
So it goes on, words, any words, your laughter,
link |
and you're so lazily and incessantly beautiful.
link |
We talked and you have forgotten the words.
link |
The shattering dawn finds me in a deserted street
link |
of my city, your profile turned away.
link |
The sounds that go to make your name.
link |
The lilt of your laughter.
link |
These are the illustrious toys you have left me.
link |
So these little memories of these peculiar little details,
link |
he remembers, those are the illustrious toys.
link |
I apologize to mix my own words with the poem,
link |
but you should definitely read it.
link |
I turn them over in the dawn, I lose them.
link |
I tell them to the few stray dogs
link |
and to the few stray stars of the dawn.
link |
Your dark, rich life.
link |
I must get at you somehow.
link |
I put away those illustrious toys you have left me.
link |
I want your hidden look, your real smile.
link |
That lonely, mocking smile your cool mirror knows.
link |
I want your hidden look, your real smile.
link |
So this is the first part of the poem,
link |
and then it goes on, which is some of the parts
link |
that you reference.
link |
Second part is, what can I hold you with?
link |
I offer you lean streets, desperate sunsets,
link |
the moon of the jagged suburbs.
link |
I offer you the bitterness of a man
link |
who has looked long and long at a lonely moon.
link |
I offer you my ancestors, my dead men,
link |
the ghosts that living men have honored in bronze.
link |
My father's father killed in the frontier of Buenos Aires,
link |
two bullets through his lungs, and so on, so on.
link |
I offer you whatever insights my books may hold,
link |
whatever manliness or humor in my life.
link |
I offer you the loyalty of a man who has never been loyal.
link |
I offer you that carnival of myself
link |
that I have saved somehow, the central heart
link |
that deals not in words, traffics, not with dreams,
link |
and is untouched by time, my joy, and adversities.
link |
And I think this is the part that you include in the book.
link |
I offer you the memory of a yellow rose seen at sunset,
link |
years before you were born, I, damn, that's a good line.
link |
Okay, I offer you explanations of yourself,
link |
theories about yourself,
link |
authentic and surprising news of yourself.
link |
I can give you my loneliness, my darkness,
link |
the hunger of my heart.
link |
I'm trying to bribe you with uncertainty,
link |
with danger, with defeat.
link |
That is a man who's in love and longing.
link |
If I've taken, but I just wanna go back to,
link |
maybe you could say why you wanted to include that poem,
link |
but also your dark, rich life, I must get at you somehow.
link |
I put away those illustrious toys you have left me at.
link |
I want your hidden look, your real smile,
link |
that lonely, mocking smile, your cool mirror nose.
link |
Sometimes I meet a stranger, and I just,
link |
it's like a double take.
link |
It's like, who are you?
link |
Have we met before somewhere?
link |
Who's that person behind there?
link |
And I wanna get at that, whatever that is.
link |
And of course, maybe that's what love is,
link |
because maybe that's the whole pursuit,
link |
like a lifelong pursuit of getting at that person.
link |
Maybe that's what that is,
link |
and like that insatiable sort of curiosity to keep getting.
link |
Like, well, who is that person in your own private life?
link |
Yeah, so that, absolutely, I think that,
link |
it was a beautiful description of what you just said,
link |
when there's that first moment,
link |
and then you wanna dive deeper.
link |
You want to know what the hidden mysteries are.
link |
In a way, it's a love poem.
link |
As a scientist, though, it also,
link |
it's a bit of how a scientist can love science,
link |
and that wanting to dive deeper is,
link |
it's almost like, again, where the,
link |
it could be a love affair
link |
with investigating the human mind, for example.
link |
And that was one reason it spoke to me also.
link |
Again, thinking about the broader sweep
link |
of where the human mind came from,
link |
and the steps it took to get where it is today,
link |
what was given up along the way,
link |
what compromises were made.
link |
And here's where the darkness of the poem
link |
starts to come in a little bit, too.
link |
It doesn't shy away from the negativity,
link |
from the confusion, from the danger.
link |
And then at the very end,
link |
the boardface is offering up scenes from his life,
link |
parts of himself, and this is how we connect with people.
link |
We offer up parts of ourselves, just here it is,
link |
and then we see how well does that map onto what you have.
link |
And it's that offering up that I liked,
link |
and not the good stuff, or not only the good stuff.
link |
The yellow rose is nice,
link |
but he's offering up the bad stuff, too.
link |
And that, to me, was important for the book,
link |
because I'm offering up hard stuff, too.
link |
In fact, a lot of it.
link |
And also, hard stuff from within me,
link |
from my own personal side, too.
link |
And that was, there's a lot of vulnerability
link |
that comes with that, but that comes with love,
link |
that comes with writing.
link |
You have to be open, you have to be vulnerable.
link |
And so, I thought that reflected what I was trying to do,
link |
and I thought it was, as an epigraph,
link |
it kind of made it clear how vulnerable I was
link |
in taking this step, but also what could come out of it.
link |
And also, in a meta way,
link |
because I was not familiar with this poem,
link |
it made me curious of the poem itself
link |
to pull at that thread of finding out more.
link |
You picked a very particular part
link |
that kind of made you want to pull at that thread,
link |
and see where did these few lines come from?
link |
Because I read it as a curiosity of a scientist,
link |
those lines alone.
link |
And also, as a desperate human being,
link |
searching, like offering himself for an understanding,
link |
or connection with another human being.
link |
And then, because I wasn't sure if it's a love poem or not,
link |
or if it's desperation, or if it's curiosity,
link |
whatever it is, and then you see the love poem.
link |
I mean, I don't know, that's gonna stick with me
link |
for a while, your dark, rich life.
link |
And then a few lines in here are just,
link |
I mean, those are, I'm gonna just use them
link |
as pickup lines at a bar.
link |
I offer you the memory of a yellow rose
link |
seen at sunset years before you were born.
link |
No, that's a pickup line I've never heard,
link |
if I've ever heard one, anyway, sorry.
link |
But this is universal.
link |
You see it in so many forms of art.
link |
Like, we're in Texas now,
link |
you see this in country and western songs.
link |
It's often a list of things.
link |
Like, here's how I describe myself.
link |
There's this, and there's that,
link |
and there's the other thing, and here you are.
link |
These things matter to me,
link |
and I hope they matter to you, too.
link |
It's a pretty universal form,
link |
but he did it in this very artful
link |
and very vulnerable way.
link |
It was both beautiful, and you could feel the hurt
link |
coming from him, too, and that was important.
link |
The dark stuff, too.
link |
I offer you my ancestors, my dead men,
link |
the ghosts that living men have honored in bronze,
link |
and talking about two bullets through his lungs,
link |
bearded and dead, wrapped by his soldiers
link |
in the hide of a cow,
link |
a mother's grandfather just 24,
link |
heading a charge of 300 men in Peru,
link |
now ghosts on vanished horses.
link |
So all of it, the whole history of it.
link |
Since it is a love poem, what do you think about love?
link |
Carl, what's the role of love in the human condition?
link |
We'll talk about the dark stuff.
link |
But maybe love is the dark stuff, too.
link |
I mean, it's the most powerful connection we can form,
link |
and that's what makes it so important to us.
link |
It's the strongest and most stable connection
link |
that we can form with another person,
link |
and that matters immensely.
link |
It matters for the human family to have evolved
link |
to be something that could survive against the odds
link |
that we've faced over the years.
link |
That unreasonable bond that becomes reasonable
link |
by virtue of its own existence.
link |
And of course, that joy, the wild, raw joy of love,
link |
is not a bad thing, either.
link |
So you put these together,
link |
the strongest bridge we can form,
link |
and the reward and the joy that it brings.
link |
That's what love is to me,
link |
and from my perspective, this is something that,
link |
it can be hard to capture fairly,
link |
because you wanna talk about the positive
link |
and the negative sides at once.
link |
They need to be wrapped up together
link |
for a full, honest description of what it is,
link |
and that's hard to do in a compact form.
link |
And so you have to take time to talk about love.
link |
You have to take time to do it justice.
link |
It takes a book, or at least a poem.
link |
Or several thousands of them.
link |
I don't know, could you pull up,
link |
there's a video I saw, yeah, like right here.
link |
So can you pause for a second?
link |
So there's March of the Penguins.
link |
So you always see penguins huddling together against,
link |
I mean, sorry if I say just metaphors and everything,
link |
but them huddling together against the harshness
link |
of the conditions around them.
link |
That's very kind of, that's like a metaphor for life,
link |
like finding this connection.
link |
That's kind of what love is.
link |
It's like it allows you to forget whatever the absurdity,
link |
whatever the suffering of life is,
link |
together you get to like huddle for warmth.
link |
And that's why I love sort of just the honesty
link |
and the intensity of the way penguins,
link |
just in the middle of like the cold do this.
link |
And then this video I saw, a lonely,
link |
this is misinformation.
link |
So the name of the video is Lonely Deranged Penguin.
link |
I don't know if he's deranged.
link |
So if you play it.
link |
So he left his pack and there's a nice like voiceover
link |
and you don't need to play it,
link |
but he for some reason left the pack
link |
and journeyed out into the mountains.
link |
And so the narrator says that he's deranged,
link |
he's lost his mind.
link |
Now I'd like to project the idea that he's actually,
link |
there's so many stories you could think of.
link |
He's returning to his homeland.
link |
He's an outsider thinking,
link |
journeying out into the unknown,
link |
thinking he may be able to discover
link |
something greater than the tribe.
link |
He might be looking for a lost love.
link |
Why is he deranged immediately?
link |
Why has he lost his mind?
link |
Anyway, but this, people should look up this video
link |
because to me, I might be the only one
link |
who romanticizes this, but it's such a nice kind of,
link |
it's both a picture of perhaps a mental disorder,
link |
which is what the video kind of describes.
link |
And it may be some deeper explanation
link |
that's not, that has to do with the motivation of a mind.
link |
But yeah, I don't know if you have a deeper analysis
link |
Well, I, like you as a psychiatrist,
link |
I would want to sit down with a penguin and go through,
link |
I want to see the notes from his prior therapist.
link |
But this actually is relevant,
link |
not knowing what was that penguin's motivation.
link |
We have very clear situations
link |
where there are both within an individual,
link |
we go through periods of time when we stay in one place
link |
and we reap the benefits from what we've built.
link |
And then we go through periods of foraging, of wandering.
link |
Even if there may be resources where we are,
link |
we have periods of time in our lives
link |
where we wander, where we go in an exploratory mode.
link |
And different people express that trait in different ways.
link |
This is not a human specific trait.
link |
If you go down to the tiny little nematode worm,
link |
C. elegans with 302 nervous system cells,
link |
they go through these phases of foraging and rest
link |
and different individuals have different propensity
link |
to forage or to rest and stay in one place.
link |
At the level of the species, that's really good
link |
that there's that diversity in their willingness to forage.
link |
Some stay where they are,
link |
the species is somewhat on a firm footing then,
link |
but some carry a burden, a risk for themselves,
link |
but it's good for the species that they're explorers
link |
and they will venture out.
link |
The migration patterns that different species blunder into
link |
and that turned out to be really good,
link |
they weren't logically derived.
link |
They most certainly started
link |
from something like this, an exploration.
link |
And humans do this too, you think?
link |
In fact, it's something we do extremely well.
link |
Let's talk about psychiatry a little bit.
link |
So in my book, you're a rockstar.
link |
First of all, for people who don't know,
link |
aside from sort of the neurological view of the brain
link |
and neuroscience view of the brain,
link |
you're also one of the great psychiatrists of our time.
link |
I've always, not always, but when I was younger,
link |
I dreamed about being a psychiatrist.
link |
So it's like getting to meet your heroes
link |
and also getting to meet the people who,
link |
the best at the top of the world
link |
at the thing you've failed to pursue.
link |
So I'm getting a free therapy session on top of that.
link |
Okay, so what big picture, what is the practice,
link |
the goal, the hope of modern psychiatry?
link |
If you could try to describe the discipline
link |
as you see it, maybe historically
link |
throughout the 20th century,
link |
in contrasting to what it is today.
link |
Or maybe if you want to describe
link |
to what you hope psychiatry becomes
link |
or longs to become in the 21st century.
link |
It's been an interesting journey.
link |
Psychiatry started out pretty firmly grounded
link |
in neurology and pathology.
link |
Some of the initial founders effectively of the field
link |
were very well grounded in microscopy, looking at cells,
link |
working with patients, particularly on the neurological side,
link |
and this certainly included Freud
link |
and some of his contemporaries.
link |
But they rapidly discovered that what they could work with
link |
at the level of cells and microscopy
link |
was so far from the realm of what they could get
link |
from a human being and what they were getting
link |
from the human being was so much more interesting
link |
and was so mysterious and so unknown
link |
that many of them just said,
link |
we're gonna inhabit this domain
link |
and we're gonna work with the people with their words
link |
and understand what we can based on verbal communication,
link |
because that was the only tool that people really had.
link |
And that was a very important step for the field.
link |
I would say one of the interesting things
link |
that came from the early decades of psychiatry
link |
really was this distinction
link |
between the conscious and the unconscious mind
link |
and paying particular attention to the unconscious mind
link |
as something that was worthy of consideration
link |
that might be important in explaining people's actions
link |
and that perhaps even insight into that was valuable
link |
And out of that, psychoanalysis became a practice
link |
that was not always focused on cures or treatments,
link |
but was more focused on insight.
link |
What does it mean?
link |
How can we help people understand
link |
why they're feeling something or thinking something
link |
or dreaming something?
link |
And that insight separate even from treatment
link |
was an interesting thing.
link |
As long as one was honest about that
link |
and said we're going for understanding,
link |
we're going for insight.
link |
Maybe it's useful to just pause on that.
link |
If we look at the father of psychoanalysis, Zygmunt Freud,
link |
what do you make of the ideas that he had?
link |
So you mentioned taking the unconscious,
link |
the subconscious seriously.
link |
That's like step one,
link |
like that there could be worlds
link |
we do not have direct access for
link |
and we probe at them through conversation
link |
or is that too simplistic
link |
to call psychoanalysis conversation?
link |
That's not too simplistic, but that's right.
link |
And I think that was valuable.
link |
Where Freud ended up breaking
link |
from some of his contemporaries,
link |
he was very focused on this unconscious
link |
as being so tightly linked to libido.
link |
And really from his perspective,
link |
you couldn't really separate the operation
link |
of the unconscious mind from these aspects
link |
of the libidinous aspects.
link |
And that was one reason.
link |
What's a libidinous aspect?
link |
You know, sexually related drives.
link |
Carl Jung, who was his contemporary,
link |
that's one factor that led to them separating
link |
was Carl Jung felt there was a lot more
link |
to the unconscious than this libidinous aspect of it.
link |
And he saw it as a much more complete
link |
alternate representation of the conscious self,
link |
one that maybe reflected a whole range
link |
of different motivations and desires.
link |
And to properly treat it one had to consider all of them
link |
rather than the ones that Freud was focused on.
link |
Carl Jung, shut your mouth.
link |
Thank you for the high level of images
link |
that Sergei's pulling up.
link |
For people who are just listening,
link |
he pulled up a quote from Sigmund Freud's meme,
link |
your mom quote Freud.
link |
So the shadow, the Carl Jung shadow encompasses everything,
link |
not just the desire to have sex with your mother
link |
That's right, that's right.
link |
If you look at those two folks en masse,
link |
I mean, there's a kind of,
link |
it's almost like a technique for philosophical exploration
link |
of human mind, human motivations.
link |
So it's not even like necessarily,
link |
it's also doubles as a methodology for helping people,
link |
but it's almost like a,
link |
it's a kind of philosophical method.
link |
Right, this is the fascinating thing about psychoanalysis.
link |
And even though it's, I would say,
link |
mostly not considered a treatment today,
link |
it persists for a couple of reasons.
link |
One is it's thought that it gives people some insight.
link |
But second, there's been a huge influence on literature,
link |
on philosophy, on art.
link |
And the opening up of discussion
link |
about what was below our conscious mind
link |
was so fertile in the implications
link |
that it sort of reverberated and still does
link |
throughout all these different realms of human endeavor
link |
from different artistic experiences that people have
link |
that can be colored by this concept of the unconscious.
link |
Now, the other thing that was interesting
link |
is this distinction,
link |
you know, what are the parts of the unconscious?
link |
And so there were these id and ego
link |
and superego subdivisions that,
link |
you know, that Freud, for example, would talk about them.
link |
And the id was the primary, the primal drives
link |
that an infant would have or that a very young child
link |
just warmth and feeding and then later
link |
the sexual or libidinous aspects.
link |
And for Freud, the later happened very quickly.
link |
That's the controversial thing about him, I think.
link |
I guess he thought like even children had sexual desires,
link |
that they're like dealing with, contending with.
link |
So it's the full thing.
link |
Hungry, wanting to eat, wanting to poop,
link |
wanting to have sex.
link |
Yeah, and he was extremely focused on that aspect.
link |
But then there was the superego,
link |
which brought on these later sort of moralistic
link |
sort of codes of conduct.
link |
And that, of course, was very often in tension,
link |
but all this could play out subconsciously.
link |
And then the ego, this third aspect was mediating,
link |
and Freud's conception mediated this tension
link |
between the different parts.
link |
Now, I think that's interesting.
link |
I will say that in some ways, it's maybe unnecessary
link |
from the perspective of modern neuroscience
link |
to divide things up that way from the moralistic drives
link |
and the primal gratification drives.
link |
In some ways, they're all drives,
link |
and maybe they're even all primal drives.
link |
The moralistic drives, they're taught,
link |
and they're taught in ways that ultimately relate
link |
back to survival, and you could even say,
link |
selfish aspects of health and life
link |
for the self and family.
link |
And so this is, I think it's maybe an artificial distinction.
link |
The concept of the unconscious is very valuable
link |
and very interesting, but these categorizations
link |
of id and superego may not map onto neurobiology
link |
in any particular way.
link |
If there's a town hall of competing drives and desires,
link |
and they interrelate to each other,
link |
they involve different aspects of the brain
link |
and the history of the person,
link |
and actions and choices come out of the result
link |
of that overall shouting in the town hall.
link |
So in some sense, Carl Jung was a step into the direction
link |
of liberating yourself from such harsh categorizations.
link |
Do you think, I mean, you have Daniel Kahneman
link |
with System One and System Two.
link |
There's just these very compelling categorizations
link |
of the human mind that seem to be sticky
link |
in the superego, no, in how we talk about these ideas
link |
Do you think those are helpful or do they get in the way?
link |
Is it some kind of balance in terms of deeper understanding
link |
of how the mind actually works?
link |
You know, it's from modern neuroscience,
link |
whenever we seem to get closer to addressing a question
link |
like this at the level of cells,
link |
it seems to get farther away.
link |
And I'll give you an example of what I mean by that.
link |
So one thing I'm doing in my laboratory
link |
and many people are doing is we are listening in
link |
on the activity of cells, neurons in the brain
link |
of mice or rats or fish or monkeys.
link |
Individual cells, exactly.
link |
Of which there are, in our brain, many billions.
link |
And when we do and we try to predict
link |
what action will be taken by an animal
link |
to address this question, where does the choice arise?
link |
Where does the impetus to make a particular selection
link |
of one action versus another action,
link |
where does that start in the brain?
link |
If you're recording, listening in on the activity of cells
link |
all across the brain, where's the earliest spot
link |
you can pick up a choice being made?
link |
That's so awesome.
link |
Yeah, at one level, you might think,
link |
how excited would Jung have been to see this
link |
or Freud or the early psychoanalyst
link |
to see where this starts.
link |
But it's not so simple because an emerging theme
link |
in very recent neuroscience,
link |
literally over the last few years,
link |
is that things sort of all start together
link |
all across the brain.
link |
And so you can be recording from the cortex,
link |
this rim of cells at the surface of the brain,
link |
or you can be recording deeper
link |
in a structure called the striatum,
link |
which is a little older.
link |
It's more tightly linked to action.
link |
And then structures called the thalamus,
link |
other parts of the brain.
link |
And if you record from these,
link |
these all sort of represent the action and the choice
link |
more or less all at about the same time, very close.
link |
And so you can't point to a particular spot and say,
link |
here's where the choice or the action originates.
link |
Finding the free will neuron.
link |
It's relevant to that question.
link |
Nobody is close to being able to point to such a thing.
link |
Well, close is a relative term.
link |
And nobody, what I tweet today,
link |
all generalizations are wrong.
link |
So including this one.
link |
Let's actually talk about that.
link |
So the study of individual cells.
link |
If you could linger on your sense
link |
that as you get closer to that understanding,
link |
it feels like you're getting farther away.
link |
Because that often is the feeling
link |
until you're actually there.
link |
So like, you know, see that's when I'm running
link |
and I know there's only a mile left,
link |
it just feels like that mile
link |
is just getting longer and longer,
link |
but eventually you finish.
link |
So maybe we're getting close
link |
to cracking open these beginnings of a sense,
link |
like we'll talk about consciousness
link |
or these very difficult, big questions
link |
about the human mind.
link |
Where do they start?
link |
You're right to say we shouldn't generalize
link |
or make absolutist statements,
link |
but I would say right now,
link |
the reason things are looking even harder to crack
link |
than we had initially thought,
link |
we now have the data streams
link |
that we've wanted for so long
link |
in terms of activity patterns all across the brain
link |
at the level of cells.
link |
We can literally see what the cells are doing.
link |
Immense data sets.
link |
You know, we get, these are time series
link |
of one individual cell with sub second resolution
link |
and you can collect this from enormous numbers of cells
link |
So very rich data sets that we've wanted for a long time
link |
and yet having these has not led
link |
to an understanding of truly where actions
link |
initiate in terms of regions or locations.
link |
And let's get a few questions on that.
link |
Is the answer, high level question by your intuition,
link |
is the answer within the data?
link |
Or do we need different kind of data?
link |
So we should also say that when you collect data
link |
about the brain, there's like the richness
link |
of information you're collecting,
link |
but there's also human doing stuff.
link |
And information, so static information about the human
link |
and dynamic information about the human
link |
and you can get them to do different stuff
link |
and you can select different humans
link |
and that's part of the collection of data aspect.
link |
So like when you're collecting data about the brain,
link |
there's some truths that you can,
link |
you know, in machine learning is like annotations,
link |
like supervised learning.
link |
There's some true things you can hold on to
link |
before you look at the full rich mess complexity
link |
of the human mind.
link |
So given the data you've looked at,
link |
do you think the answer for the origin of free will
link |
in the human mind can be found?
link |
Well, one amazing thing is that nobody's found it,
link |
but we have these rich data sets
link |
and then there's a conundrum which is,
link |
is it in the data and we just don't know
link |
how to look at it.
link |
Maybe we don't know the right scale,
link |
the right projection to make of the data,
link |
the right way to interpret it.
link |
And here's where causal testing becomes very valuable
link |
because then instead of just passively observing,
link |
well, here are the activity patterns
link |
and then here's the choice made by the animal.
link |
As we've gotten more powerful at reaching in
link |
and causing things to happen in the brain,
link |
turning up or down the activity
link |
of certain types of cells or defined populations of cells
link |
and seeing how that affects actions,
link |
these causal perturbations have turned out
link |
to be very valuable.
link |
We're just now getting to the point
link |
where we can apply these in very wide swaths of the brain
link |
at cellular resolution and so we're gonna be able,
link |
hopefully to make some headway on this question
link |
with causality and that's the one thing
link |
that optogenetics provides us this way of using light
link |
that we develop to control cells.
link |
This is an untapped, relatively untapped
link |
at this broad brain wide scale
link |
and hopefully we can get there in the near future.
link |
But I would say that the answer may be in the data
link |
but we don't know how to find it.
link |
Well, there's this interactive element
link |
like where you can cause stuff that's really powerful
link |
because you get to, I mean,
link |
as opposed to collecting data passively,
link |
you get your collecting data actively.
link |
So can you maybe describe one of the many things
link |
you're known for, one of the big things
link |
is called optogenetics, what is it?
link |
Optogenetics is a way of causing things to happen.
link |
It's a way of determining what actually matters
link |
in terms of the activity of the brain
link |
for the amazing things it does,
link |
sensation, cognition, action.
link |
And what it does is it provides activity.
link |
It's a way of playing in, if you will,
link |
activity patterns into precisely defined cells.
link |
And the way we do it is pretty cool, I think.
link |
It's, you know, right away there's a problem
link |
if you think about how do we do this?
link |
How could we play in well defined activity patterns
link |
and provide a stream of activity into this cell
link |
and that cell and that cell but not these other cells?
link |
So just for context, we're talking about the brains
link |
of mice, monkeys, humans,
link |
and then the goal is to try to control accurately
link |
the behavior of a single neuron
link |
and then to be able to monitor single collection
link |
of single neurons to then say, well,
link |
to draw some deeper insight about the origins,
link |
first of all, the function of different parts of the brain,
link |
different neurons, different kinds of neurons,
link |
but also the origins of the big things,
link |
the flap of the butterfly wing that leads
link |
to an actual behavioral thing.
link |
Yeah, so if you could, exactly, so if you could turn on
link |
or off the brain or parts of the brain or cell types
link |
or individual cells at the natural rate and rhythm
link |
and timing of normal brain activity,
link |
that would be immensely valuable
link |
because you could determine what actually mattered,
link |
what could cause complex things to happen
link |
and what could prevent complex things from happening
link |
in a specific way.
link |
But right away, you've got a problem if you wanna do this
link |
and scientists, neuroscientists have wanted to do this
link |
Francis Crick of Double Helix of DNA fame,
link |
he wrote a famous paper in 1999.
link |
He got interested in neuroscience later in life
link |
and he said, what we need in neuroscience is a way
link |
that we could turn on or off the activity
link |
of individual types of neurons in a behaving animal.
link |
And he even said the ideal signal would be light
link |
because it would be fast, it could penetrate
link |
through the brain to some extent.
link |
And he had no idea how to do it.
link |
He said this would probably be very farfetched,
link |
but it would be a good thing.
link |
And so that's what you're actually saying,
link |
like if you wanna do this kind of thing
link |
and you imagine like, how do I get inside the brain?
link |
It's pretty difficult.
link |
It's pretty difficult and then even once you get in,
link |
it's hard because all brain cells are electrical,
link |
all neurons are electrically activated.
link |
And so if you wanted to use electricity
link |
as what you were putting in,
link |
you won't have any specificity at all.
link |
If you have an electrode, a wire,
link |
and you put it in the brain and you send current through it,
link |
all the cells near the electrode will be stimulated.
link |
That's like trying to control fish
link |
by spraying them with water.
link |
Yeah, right, because there's already a lot of electricity
link |
going around anyway and you're adding more,
link |
but there's no specificity
link |
even among the different kinds of cells either
link |
because all around the wire that you've put in,
link |
there are gonna be so many different cells
link |
doing totally different things,
link |
many of them in opposition to each other.
link |
We know that's one way the brain is set up.
link |
There are parts of the brain
link |
where neurons side by side
link |
are doing completely different things
link |
and maybe even antagonistic to each other.
link |
So what do you do?
link |
How do you play in activity with any kind of specificity?
link |
Well, what you do is use,
link |
what we found is what you can do is
link |
make some cells responsive to light.
link |
Now, normally no cells deep in the brain
link |
really respond to light.
link |
They're not built for that.
link |
There's no reason for them to respond to light in there,
link |
which is a great situation to start with
link |
because any light sensitivity you can provide to some cells
link |
will be a huge signal above the noise.
link |
And so that's what we do with optogenetics.
link |
We take genes, bits of DNA from microbes,
link |
single celled organisms,
link |
and these single celled organisms like algae,
link |
they make little proteins
link |
that sit in the surface of their cells
link |
that receive light, capture a photon of light
link |
and open up a little hole in the membrane of the cell
link |
and let charged particles, ions like sodium and potassium
link |
flow across the membrane of the cell.
link |
And that, these algae and bacteria,
link |
they do this for their own reasons
link |
because that helps them move,
link |
it helps them make and use energy.
link |
But that's a beautiful thing for neuroscience
link |
because movement of ions,
link |
charged particles across the membrane of the cell
link |
is exactly the kind of electricity that neurons work with.
link |
So if we can take this bit of DNA
link |
that encodes this beautiful protein
link |
that turns light into electricity from algae,
link |
and if we can put it into some neurons,
link |
but not other neurons, which we can do using genetic tricks,
link |
then you've got a situation,
link |
then you can shine on the light
link |
and only the cells that have the gene
link |
and that are expressing the gene
link |
will be the initial direct cells
link |
that are activated by the light.
link |
And so that's the essence of optogenetics
link |
is the ability to do that.
link |
We get that initial specificity
link |
that you could never get with an electrode.
link |
So let me say that this is,
link |
we recently got the Alaska Prize for this.
link |
It's a brilliant idea.
link |
So I talked to Andrew Huberman,
link |
who's a friend of yours, friend of mine,
link |
so not to jinx things,
link |
but he believes that you deserve the Nobel Prize for this.
link |
So, I do too, but what, my votes.
link |
Anyway, the thing is, it doesn't matter.
link |
Prizes will be all forgotten, all of us will be forgotten.
link |
When the cool idea is a cool idea,
link |
that's a really powerful idea.
link |
It's actually, the origins of it
link |
you might be interested in are even, are very deep.
link |
There was a botanist in St. Petersburg
link |
named Andre Fomensen.
link |
In 1866, he published a paper
link |
on the single celled green algae.
link |
And he was the botanist who first noticed
link |
that they moved in response to light.
link |
These are tiny single celled algae that have flagella,
link |
so they swim through the water.
link |
And he noticed this, he was a botanist,
link |
and he published this.
link |
It was a paper, you know, he wrote in German,
link |
but he published it in a French journal,
link |
and he was doing it from St. Petersburg,
link |
so it was a very international effort.
link |
But you have to go back to 1866,
link |
and that, I like to highlight how far back
link |
that discovery goes is back to Andre Fomensen.
link |
And this is a, it highlights the value
link |
of just pure basic science discovery.
link |
That always originates somewhere
link |
in the Eastern European block.
link |
But I don't think he expected the splicing
link |
of genetic material from the algae into the human brain.
link |
And one of the cool things we've been able to do now
link |
with modern methods is to really study these proteins.
link |
And so we've discovered some of these proteins,
link |
other groups have as well.
link |
We've dived deep into their structure,
link |
just like the double helix structure of DNA
link |
was uncovered with X ray crystallography.
link |
We used the same method in X ray crystallography
link |
to see how these beautiful little proteins work.
link |
We reengineered them for all kinds of function.
link |
We can make them, instead of responding to blue light,
link |
we can make them respond to red light.
link |
We can speed them up, slow them down.
link |
We can make them, with genetic engineering,
link |
we can make them have different ions flow through them.
link |
And so it's this convergence, as you said,
link |
like the botanist in 1866 couldn't have predicted
link |
what we could do with this.
link |
And the fact that we've been able to discover
link |
how these beautiful proteins work
link |
and then apply them to neuroscience
link |
is really a thrilling story.
link |
Is it possible to achieve scale, do you think, with this?
link |
Meaning, like what is the progress of the next 50 years,
link |
100 years looks like in terms of the precision
link |
and the scale of control of using light?
link |
It's going so fast it's hard to predict.
link |
I'll give you a sense of it though.
link |
First paper we published in 2005,
link |
that was just encultured neurons.
link |
By 2007, so that was in a dish.
link |
By 2007, we had it working in behaving mice.
link |
By 2009, we had it pretty general.
link |
So we had methods to really make it a versatile method.
link |
It could be applied to essentially any cell.
link |
By 2012, we could get to single cell resolution.
link |
We used light guidance strategies
link |
to target individual cells in the brain of a living mouse.
link |
By 2019, we were able to control up to 20 to 50
link |
individually specified single cells
link |
in the brain of a mouse in ways that specifically changed
link |
its behavior, that could bias its decisions one
link |
In fact, we could take a mouse and without any visual stimulus
link |
at all, we could make it act as if it
link |
had seen a particular visual stimulus
link |
by playing in, using the single cell resolution optogenetics,
link |
a specific pattern of activity into 20 or 25
link |
individually specified cells.
link |
That's 2019 to your question of scale.
link |
Now in 2022, we're controlling hundreds
link |
of individually specified single cells
link |
over all of visual cortex of a mouse, all the part
link |
of the brain that is the initial direct target
link |
of the incoming information from the retina.
link |
Are you constrained to specific types of cells currently?
link |
Like you mentioned, long range is easier.
link |
Is there constraints on which cells?
link |
Now there really isn't.
link |
Now that we have this individual cell guidance,
link |
we can target any individual kind of cell very reliably.
link |
And so now to your question of scale, how far can we go?
link |
Well, things are moving quickly.
link |
We can access individual cells across the entire brain now.
link |
If you look 10, 20 years in the future,
link |
I think we'll surprise ourselves.
link |
But the fact that we're already able to cause
link |
specific perceptions to happen and specific actions
link |
means we're essentially where we want to be.
link |
And now it's a matter of just more experiments,
link |
But the basic principles are clear now.
link |
The basic capability is there.
link |
Is there a pathway to doing the same for humans?
link |
Optogenetics is primarily, it's a discovery tool
link |
that really is well suited for use in mice and rats
link |
and monkeys because it involves putting in a gene
link |
and also delivering light.
link |
And those are two things that you can do in human beings,
link |
but you'd want to do in a very careful way.
link |
Now that said, there is actually just less than a year ago,
link |
my friend Botan Droska in Switzerland,
link |
he did the first human optogenetics therapy.
link |
And he published this in the journal Nature Medicine.
link |
So about 10, 12 years ago, he and I
link |
published a paper together where we gave him
link |
one of our optogenetic tools, one
link |
of these light activated regulators of ion flow.
link |
These are called microbial opsins, by the way, opsins.
link |
And he put one of those into an extracted retina
link |
from a human being who had died.
link |
So it was a cadaveric retina.
link |
And he was able to show that optical control in this paper
link |
was able to turn on or off individual cells
link |
in the human retina.
link |
So that was a while back.
link |
He spent about 10 years of going through all the regulatory
link |
hoops and hurdles and going through primate studies.
link |
And finally, he was able to take a human being
link |
with a retinal degeneration syndrome, so someone
link |
who was blind in both eyes.
link |
And he gave one of these opsins into one eye of this human
link |
being who was blind and with the goal
link |
of conferring light sensitivity onto this retina that
link |
was not able to see light.
link |
And he was able to make this person see through that eye.
link |
So he took a blind person.
link |
And the blind person could see now,
link |
could reach for objects selectively on a table.
link |
And he published this in Nature Medicine.
link |
And it was, you know, that's an amazing thing.
link |
Do you know the title of the paper?
link |
What's his name again?
link |
And you look up the Nature paper.
link |
So that's sort of proof of principle.
link |
Now, the retina is very accessible.
link |
It's near the surface.
link |
You can use natural light, or you
link |
can use brighter natural light.
link |
I'm myself, I see optogenetics as a discovery tool.
link |
It's a way to figure out the principles by which the brain
link |
works and how it operates.
link |
Partial recovery of visual function
link |
in a blind patient after optogenetic therapy.
link |
So he went through the full process of doing primates
link |
and then going, wow, that's dedication
link |
and that's really exciting to see.
link |
As beautiful as that is, and I'm glad he did all that work,
link |
there are so many other ways that optogenetics
link |
could help with therapies.
link |
Once you know the principles, then any kind of therapy
link |
can become more powerful.
link |
Once you know the causal cells in a symptom,
link |
like in lack of motivation or inability
link |
to enjoy things or altered sleep or altered energy,
link |
once you know the cells that are causal,
link |
then you can make medications that address those cells.
link |
You could address brain stimulation treatments that
link |
might address those cells.
link |
Also, diagnosis, very effective systematic way of diagnosing,
link |
or at least providing you rich data
link |
to some of these deep questions about schizophrenia,
link |
about bipolar, all of those kinds of things.
link |
The tools are low resolution currently
link |
for determining the degree to which you have a thing
link |
and whether you have a thing at all.
link |
And so the hope is that's a great example
link |
of how you can cure or you can provide
link |
some relief for a symptom of a person who has
link |
a serious degenerative disease.
link |
But the principles are what we're after,
link |
and that's why I spend, even though I'm a psychiatrist,
link |
even though I still see patients, I'm not myself
link |
trying to drive any clinical trials in the lab.
link |
I'm trying to discover, and then any kind of therapy
link |
could result from that.
link |
What do you think about my friend,
link |
Elon Musk, and his efforts with Neuralink?
link |
So this is another, there's a lot of things to say here,
link |
because there's a lot of ideas under the umbrella
link |
of Neuralink, but one of them is to use electrical signals
link |
to stimulate, and then you also record,
link |
you collect electrical signals from the brain
link |
at a higher and higher resolution,
link |
and you go implant surgically the methods
link |
by which you do the stimulation and the data collection.
link |
So it's possible for the ideas of optogenetics
link |
to play well with this, and we can even zoom out
link |
outside of just Neuralink, and just the whole idea
link |
of brain computer interfaces.
link |
What are your thoughts?
link |
Well, I think the engineering that they've done
link |
is actually pretty cool.
link |
Yeah, from the design perspective,
link |
and it was a design approach that wasn't being taken
link |
in academia, and it's great that they did it,
link |
and I think it's pretty cool.
link |
Also, there are many ways that you can record
link |
from many thousands of neurons, and that's not the only way.
link |
It's a very interesting way.
link |
We and others are using brain penetrating electrodes
link |
that actually get quite deep.
link |
This whole structure of the brain is very interesting.
link |
There's the surface cortex, where it's the most recently
link |
emergent part of the brain in evolution.
link |
Reptiles have something a little bit like it,
link |
but it's not really the full thing.
link |
This is a very recent thing.
link |
That's what we can access with some of these,
link |
like the Neuralink approach,
link |
and with some of these short electrodes.
link |
This part of the brain, the cortex,
link |
is only a few millimeters thick.
link |
There's so much that's deep, though, that's so important.
link |
There's the striatum, there's the thalamus.
link |
There are the parts of the brain that drive motivation,
link |
that drive hunger and thirst and social interaction
link |
and parenting and flight and fear and anxiety.
link |
All these things are, there's so much that's deep
link |
that these surface approaches are not getting to.
link |
And so we and others are using these very long electrodes
link |
that help us get deep, and we can still record
link |
for many cells, many thousands of cells.
link |
We can have multiple of these at once in the same animal.
link |
And so there's a diversity of methods to get to this goal.
link |
I think it's great that people coming from
link |
outside academia will bring ideas
link |
that weren't being worked on, at least approaches.
link |
They may turn out to be synergistic.
link |
These things do work very well with optogenetics
link |
because all these electrical recording methods,
link |
that's one channel of information flow.
link |
Light delivery is a separate, more or less independent.
link |
There can be some artifacts that happen,
link |
but if you're careful,
link |
it's another independent pathway of information flow.
link |
And we've done really fun experiments in mice
link |
where we play in patterns of activity with light,
link |
and we record activity from across the brain of a mouse
link |
electrically, and so using optical and electrical together
link |
is extremely powerful.
link |
So like optoelectric brain computer interfaces.
link |
Which, by the way, there's efforts on the computing side
link |
to build optoelectric servers,
link |
so like where you have both electricity.
link |
So because optics is really interesting,
link |
light is a very interesting method of communication
link |
that's, like you said, orthogonal in many ways.
link |
It doesn't have some of the constraints of bandwidth
link |
that electricity does going through wires,
link |
but you're able to,
link |
but less ability to control precisely at scale.
link |
So like there's challenges and there's benefits,
link |
and having those two interplays
link |
really, really, really fascinating,
link |
especially when obviously on the other side
link |
of your signal is a biological mesh, mush, mushy mesh.
link |
Well, the mushy mesh is kind of interesting
link |
because there are problems with light.
link |
Light scatters in the brain,
link |
so the photons don't just go linearly through.
link |
Whenever they hit an interface between fat and water,
link |
lipid and water, they bounce off in different directions.
link |
And so you can come in with all the resolution you want.
link |
You could play in an incredibly detailed,
link |
high resolution pattern of light,
link |
but the photons start scattering quite quickly,
link |
and by the time you've gone a couple of millimeters deep,
link |
you've lost almost all that fine spatial information.
link |
So, but we've developed workarounds.
link |
The longer wavelength light you use,
link |
if you get into the infrared, there's less scattering.
link |
You can use two photon methods or three photon methods
link |
where the photons have to arrive all together
link |
You can put in fiber optics.
link |
We developed these fiber optic methods in 2007
link |
where you can access these deep structures
link |
with fiber optic methods,
link |
and you can put many of these fiber optics
link |
at the same time in an animal.
link |
We've used holographic methods, 3D holograms,
link |
to play in hundreds of individual cell size spots of light,
link |
and we can change those quickly.
link |
So there are a lot of tricks,
link |
a lot of interesting optics engineering
link |
that has come together with neuroscience
link |
in a pretty exciting way.
link |
Well, that is engineering, too.
link |
It was just super, super, super exciting.
link |
I should mention, because I remember I mentioned Elon.
link |
I recently got, for the first time ever, got COVID.
link |
Well, how did I go so long without,
link |
finally, so I'm all vaccinated and everything like that.
link |
And so I got, because I think he mentioned it publicly
link |
so I can mention it,
link |
but I won't mention anybody else involved.
link |
But hanging out, we all got, Elon got COVID.
link |
And the interesting thing about,
link |
maybe you can comment about this.
link |
So I was only sick for like a half a day.
link |
I got a fever of like 104.
link |
I just went up and then crashed.
link |
And then I was, now maybe I'm just seeing
link |
the silver lining of everything,
link |
but afterwards, I have like a greater clarity
link |
You just think it's greater clarity.
link |
Maybe, maybe I just, it was so,
link |
maybe so intensely the mind fog kind of thing
link |
for such a short amount of time.
link |
But the people who were involved were also reporting this.
link |
It's kind of interesting.
link |
It's like, because I do know like the immune system
link |
is involved with the brain in very interesting ways.
link |
So like the human mind also incorporates all these other,
link |
it's not just the, it's not just the nervous system.
link |
And I just wonder, because everyone always says,
link |
no, not like, everyone always says like COVID
link |
does all these bad things or whatever the disease is
link |
or whatever the virus.
link |
But I wonder like, I hate to be a Steven Pinker on this,
link |
but like, I wonder what the benefits of certain disease are
link |
if you're able to recover.
link |
Like what, is there some like, again,
link |
don't want to romanticize it,
link |
but if your system goes to some kind of hardship
link |
and you come out on the other end,
link |
I wonder sometimes if there's a greater,
link |
maybe killed off a bunch of neurons
link |
that didn't need anyway,
link |
and they were actually getting in the way.
link |
There were the hater neurons.
link |
Well, that was your inner critic that I was talking about.
link |
You killed off your critic.
link |
Well, you know, there are mechanisms for what you,
link |
the potential mechanisms for what you're talking about.
link |
There are, there's actually been a fair bit of research
link |
on post COVID neurological function.
link |
Actually, my wife, Michelle Monjay, who's at Stanford,
link |
she's done a lot of this work.
link |
Akiko Iwasaki at Yale has done a lot of this.
link |
But what they found is that there's a loss of myelin.
link |
This is the coating of those long range projections
link |
that go from one part of the brain to another.
link |
Myelin is this sort of insulator
link |
that coats these long range projections
link |
and makes the impulses go faster and more reliably.
link |
And there's altered function of the myelin producing cells
link |
and altered myelin in the case of COVID.
link |
They've looked in both mouse and human brains.
link |
And, but of course it could be very idiosyncratic.
link |
Many people have cognitive problems post COVID.
link |
You're definitely aware of that.
link |
So many people report this persistent brain fog
link |
and the ability to function.
link |
But it depends on where the inflammation was.
link |
Maybe the people who have dysfunction post COVID,
link |
they had a global effect.
link |
Maybe you lost some of these projections
link |
that were restraining you in some way.
link |
And these plausibly exist.
link |
And it's known that there are cell populations
link |
in the prefrontal cortex that actively restrain
link |
deeper structures from expressing what they do.
link |
And it's theoretically possible that you had a lucky.
link |
Somebody has to get lucky, right?
link |
Somebody has to get lucky, yeah.
link |
All right, if we can actually go back to this idea
link |
of trying through optogenetics
link |
to find origins of when the wave first starts.
link |
Origins of a decision.
link |
Origin of maybe consciousness
link |
or the subjective experience.
link |
So origin of things in the mind.
link |
So one thing, Carl Jung, is there a God neuron?
link |
Is there a belief neuron?
link |
Is there, so through this methodology of optogenetics,
link |
can you start getting to where a belief begins
link |
or an idea begins?
link |
And especially looking at the strongest of our beliefs.
link |
Maybe beliefs of love and hate,
link |
but religious belief into something really grand,
link |
on the grandest of scale.
link |
Yeah, neuroscience and neurology point us a little bit.
link |
We don't have an answer to that, but for example.
link |
A lot of these questions I'm gonna ask you,
link |
there's no good answer, but you're providing the tools
link |
that give us hope to find the answer one day.
link |
Yeah, and we have early clues.
link |
So for example, when patients with epilepsy
link |
have experiences of religiosity as part of their seizure
link |
or the aura before their seizure,
link |
very often those are in the temporal lobe,
link |
in these parts of the brain that are at the side.
link |
And so that's an initial clue.
link |
There are also parts of the brain that are involved
link |
in the definition of the self
link |
and defining the borders or boundaries of the self.
link |
And we know this, this is some experiments that we did
link |
in my lab, there's a part of the brain
link |
where if there's a rhythm of a particular type,
link |
you can cause a separation of the sense of self
link |
from the sense of the body.
link |
What's normally bound up and unitary,
link |
we normally think of ourself and our body
link |
as pretty tightly bound up together,
link |
those can be separated, it turns out.
link |
We can't take that for granted.
link |
And there are certain conditions,
link |
certain patterns of activity in one part of the brain
link |
called the retro splenial cortex,
link |
where you can actually separate those two out.
link |
And so if you think about these very big questions,
link |
you know, what is, where are the origins of religiosity?
link |
Where, how do we define the boundaries of who we are
link |
relative to others and to the world?
link |
How do we link ourself to our body
link |
and how can that become separated?
link |
These are actually, believe it or not,
link |
now accessible and rigorously and quantitatively so.
link |
We did an experiment with optogenetics
link |
where we provided this abnormal rhythm
link |
to this particular part of the mouse brain
link |
and we saw this separation of detection of a stimulus
link |
and caring about it.
link |
So that's like stimulating something about the mouse brain
link |
that affects these neurons that give the conception of self.
link |
So you're able to dissociate the experience
link |
from the impact of the experience onto you.
link |
That's right, exactly right.
link |
So like these are the goals of meditation.
link |
These are the goals whenever I get drunk,
link |
pretty much effective.
link |
I mean, that's not a scientific statement,
link |
just an experiential anecdotal one.
link |
Also psychedelics seek to this,
link |
to attain this kind of state.
link |
That's so interesting.
link |
Well, you mentioned psychedelics, you know,
link |
DMT and 5MeO DMT, these create this religious experience,
link |
this connection, people describe them
link |
as a strong connection to God.
link |
That in theory, these are accessible with modern methods.
link |
Now that we have these rich recording methods,
link |
we can explore what are the precise millisecond resolution,
link |
cellular resolution, brain wide manifestations
link |
of these altered states.
link |
So like you could look at an altered state like on DMT,
link |
record it across many people,
link |
and then from there see where do these experiences
link |
originate in the brain in terms of single neurons,
link |
and then how do they propagate
link |
and interact with everything else?
link |
And if there's some kind of common signal,
link |
like how do you narrow down the set of neurons
link |
that are responsible for particular experience
link |
or for a particular behavioral effect?
link |
Yeah, here's where optogenetics is so useful
link |
because anytime you give an agent like ketamine or PCP,
link |
which we used for our dissociation experiments
link |
that I was mentioning,
link |
or you have a psychedelic LSD or DMT
link |
for this altered perceptual state,
link |
if you give either of those,
link |
these change everything across the brain, okay?
link |
So just the fact that you maybe give them to a mouse,
link |
let's say, or eventually to a human,
link |
you won't know yet which cells to home in on
link |
as the causal players in all this
link |
just by recording the activity.
link |
But then what we found is that optogenetics
link |
providing a causal pattern of activity
link |
guided by what you see can let you test hypotheses.
link |
And we saw this rhythm with ketamine and PCP
link |
for dissociation, and then we said, okay,
link |
let's test what's causal.
link |
We came in and provided that rhythm.
link |
We tried a few different things,
link |
but only one of the causal tests we tried
link |
actually caused the behavioral dissociation.
link |
And so that's how we home in on what actually matters.
link |
And is it repeatable once you see the causality?
link |
So like that's one definition of causality
link |
is like you try and it repeats across different mice
link |
and all that kind of stuff.
link |
And so you could do that for DMT.
link |
You could do that for the really fascinating
link |
mind expanding, thank you, thank you.
link |
So the meme for people just listening,
link |
this is again another disagreement
link |
between Freud and Carl Jung.
link |
Religion and spirituality.
link |
This is the, I guess the ring scene from Lord of the Rings.
link |
Religion and spirituality, Freud says,
link |
cast it into the fire, destroy it.
link |
Carl Jung says, no.
link |
So for people who don't know,
link |
Sergei is the Slavic Lord of the Meme.
link |
Thank you, I appreciate that.
link |
So what we're talking about,
link |
so there is, I mean, I think a connection
link |
between DMT and religious experiences
link |
are some of these psychedelics.
link |
Do you think it's possible to
link |
sort of stimulate religious experiences?
link |
And so religious experiences are one of the most
link |
deep kind of experiences.
link |
And so here you could first understand
link |
where they originate, how they propagate
link |
through the brain, and then to stimulate them.
link |
And so this is, and these can happen
link |
in people who had no predisposition.
link |
People who are as agnostic or atheistic as you'd like,
link |
they can have these, they can feel connected
link |
to God in these states.
link |
Now, to be clear, I'm not advocating these.
link |
We don't know what's safe in human beings,
link |
but we definitely have not yet.
link |
But we definitely can do these experiments in mice,
link |
and that was already very productive
link |
in understanding dissociation.
link |
So we can already imagine making headway on these methods.
link |
And then I had a, and this does map
link |
onto the non psychedelic human experience.
link |
I had a patient who was actually described
link |
in the book Projections.
link |
This was the patient that's in the mania chapter,
link |
the bipolar chapter.
link |
Here was a guy who had never had a psychiatric illness
link |
or symptom in his life.
link |
He was a retirement age gentleman,
link |
and nobody in his family either.
link |
So no family history, no personal history
link |
of any psychiatric illness, and he'd never been religious,
link |
particularly before either.
link |
Certainly no passionate type of religion.
link |
But he, not through any psychedelic or drug,
link |
he had a stressful experience,
link |
actually a post 9 11 change in how he was thinking.
link |
And he was pushed into a mania, a manic state,
link |
revealing that he had bipolar,
link |
never before known in this case, in this person.
link |
And his mania, his elevated state in bipolar
link |
included this profound religiosity,
link |
which he had never had before.
link |
And he was preaching in a elevated,
link |
vigorous way to his family.
link |
And so this state can be created in people
link |
even late in life who had no predisposition for it
link |
and even without a neurochemical.
link |
So the causality of that is very interesting to explore.
link |
How did the manic state unleash this religiosity?
link |
But you see that in other realms of psychiatry too.
link |
OCD can manifest as religiosity also.
link |
You can take people who never really had
link |
a religion, never played a powerful role in their life,
link |
but then when their obsessive compulsive symptoms
link |
become severe, they can manifest in this.
link |
I think I'm in that group, so I'm a bit OCD.
link |
We have, I think this is subreddits,
link |
when there's oddly satisfying things.
link |
So there's certain things that are really satisfying
link |
to my OCD, in my mild OCD.
link |
I think it's pretty much a religious experience.
link |
So I understand that if it's not direct,
link |
it's at least rhymes.
link |
So maybe can you speak to the,
link |
Sergei's probably desperately scrambling
link |
to pull up oddly satisfying, thank you.
link |
People can check it out themselves.
link |
It is, as the subreddit promises, oddly satisfying.
link |
Can we talk about bipolar and maybe depression?
link |
Well, let's talk about, I mean, I don't know if there's
link |
a nice way to discuss the differences
link |
in the full landscape of suffering that's here,
link |
but maybe what is depression?
link |
And what are the types of depression?
link |
What kind of depression have you seen and experienced
link |
and researched and how can people overcome it?
link |
How can humans overcome it and deal with it,
link |
live with it and overcome it?
link |
So this is my clinical specialty.
link |
I see patients in my outpatient clinical work
link |
with treatment resistant depression.
link |
So very hard to treat severe illness
link |
where medications haven't been working.
link |
I also see patients with autism spectrum disorders.
link |
These are my two clinical focal areas,
link |
but then I do emergency room work as well.
link |
But the depression, why do I focus on that?
link |
It's so, one feels tantalizingly close to helping
link |
these people who are suffering so deeply.
link |
And that's why I focused on it is these are people who,
link |
there may not even be anything situational
link |
that's difficult or challenging in their life.
link |
You can have people who seem to have everything
link |
that you would want.
link |
Every objective measure of their life is fine,
link |
yet they can be just hit with this unstoppable hopelessness
link |
and inability to see into the future,
link |
a discounting of the value of their own action.
link |
Anything they can imagine themselves doing seems worthless
link |
or they are unable to enjoy things.
link |
We call this anhedonia.
link |
There's no reward, no pleasure, not in food,
link |
social interaction, movies, books,
link |
anything that they would enjoy, positivity gone.
link |
They can have a profound negative internal state,
link |
psychic pain, and these things can seem,
link |
and in the severe cases, are inescapable.
link |
So what is going on?
link |
Why is this state part of human existence?
link |
It's got a strong biological, genetic link, we know that.
link |
It's been linked to certain genes,
link |
certain regions of the chromosomes, and twin studies.
link |
There's a clear genetic link.
link |
It doesn't explain everything, but it's a big part of it.
link |
Genetics are a strong contributor.
link |
And although you can have depression
link |
without anything terrible going on in your life,
link |
the symptoms can be made worse by stressors, by trauma.
link |
But at a very deep level,
link |
there's nothing we can measure in a person objectively,
link |
so we don't have, there's not a known chemical,
link |
not a known structure that's different,
link |
not a known brain activity pattern
link |
that we can pick up with EEG.
link |
A lot of people are exploring this,
link |
but right now we have no objective measures.
link |
All we do is talk to people and we elicit these symptoms.
link |
We explore them, distinguish them from other possible causes,
link |
and then what do we do?
link |
Well, we have a lot of things that we can do.
link |
Well, we have a range of treatments.
link |
We have medications that can help people,
link |
do help people, but not everybody.
link |
And if they don't work,
link |
then we can go to brain stimulation methods.
link |
We can do things even like electroconvulsive therapy,
link |
which is very effective,
link |
but it's sort of the final thing we go to in the end.
link |
And so we have treatments.
link |
They work for some people.
link |
They don't do everything we'd like.
link |
But here's the problem is at a very deep level,
link |
we don't understand really what's going on in the brain.
link |
We don't have a physical interpretation of the problem.
link |
We have all these symptoms,
link |
but we can't yet point to a set of cells
link |
or a set of circuits or an activity pattern
link |
that is causing major depression,
link |
this disease state per se in human beings.
link |
Why do you think you can't yet
link |
from an optogenetics perspective?
link |
Is it because there's so many possible causes?
link |
Is it so many things involved?
link |
So I think the answer is there are many things involved
link |
and all these different symptoms that I've mentioned,
link |
those we can study and those we can fix,
link |
the individual symptoms.
link |
And we can do this in animals to be clear.
link |
So in a mouse, for example,
link |
we can instantaneously and precisely
link |
turn up or down the motivation of an animal
link |
to overcome a challenge.
link |
We can turn up or down its ability
link |
to be motivated by, or we think experience reward
link |
from situations or actions.
link |
We can increase its apparent energy level,
link |
its drive to meet challenges.
link |
We can turn up or down social interaction.
link |
All these individual features of depression,
link |
individual symptoms, we now can point to exact projections
link |
and cells that are causal in mediating these.
link |
But we don't know is why all these different symptoms
link |
show up together in major depression
link |
and the human disease syndrome.
link |
And that's the mystery.
link |
It's sort of, in other fields of medicine,
link |
someone with congestive heart failure
link |
who comes into the clinic,
link |
they have very different symptoms.
link |
They have shortness of breath and they have swollen feet.
link |
Couldn't be two more different across the body
link |
Neither one obviously related to the heart,
link |
but they're both happening
link |
because the heart is not working as a pump, okay?
link |
And now, thankfully in cardiology,
link |
we understand these disparate symptoms
link |
that seem totally unrelated can be completely understood
link |
because there's an altered pump action of the heart.
link |
That's what we are hoping for in psychiatry
link |
and in the study of depression or any disease.
link |
These different symptoms,
link |
the inability to enjoy things, the hopelessness.
link |
What's the unifying principle?
link |
I mean, is there some truth to that Tolstoy quote
link |
that all happy families are alike
link |
and each unhappy family is unhappy in its own way?
link |
So basically, I mean, this is the human condition.
link |
And basically, the physicists long to find
link |
a theory of everything, isn't understanding depression
link |
essentially require you to really have
link |
the big theory of everything for the human mind?
link |
I think we, it would certainly be nice to have that,
link |
a theory of everything.
link |
Don't get me wrong.
link |
I don't think we need it.
link |
The understatement of the century, it would be nice.
link |
Well, it's also a good question if it's possible.
link |
Well, that I have some thoughts on too.
link |
But to this specific question,
link |
I don't think we need a theory of everything.
link |
I think there will be unifying principles we can get to.
link |
But even shy of that, we can treat symptoms
link |
and that's a big step.
link |
And as you say, different unhappy families are different,
link |
different unhappy people are different.
link |
If we have somebody who comes to the clinic
link |
and I see someone with a profound anhedonia
link |
as one of their main symptoms,
link |
inability to enjoy things,
link |
and if I know based on optogenetics work and animal work
link |
that a particular medication can treat anhedonia,
link |
even if it doesn't fix major depression in everybody,
link |
if I treat that one symptom in that one person,
link |
that's a good thing.
link |
And so we don't need the theory of everything
link |
and we don't even need the unifying principle
link |
to help people with insights that come from optogenetics.
link |
How much does talking help for diagnosis
link |
and for treatment, would you say, for depression?
link |
It's a big part of what we do.
link |
Every good psychiatrist should be pretty adept
link |
in these verbal communications and talk therapy
link |
as part of what they do.
link |
I give medications, I deliver brain stimulation treatments,
link |
but a big, big part of everything I do with every patient
link |
is talk therapy because it works so well together
link |
with these other modalities.
link |
Even alone, it can help people with moderate
link |
or mild depression by itself.
link |
People with severe depression,
link |
people with other psychiatric illnesses that are severe,
link |
you don't wanna do talk therapy alone,
link |
that's not gonna do it.
link |
But it still is crucial to do together with the others.
link |
And it's critical because it's part of how
link |
you reshape cognitions, complex activity patterns,
link |
and you won't get to that with a medication
link |
or a brain stimulation treatment.
link |
Do you have advice for people who suffer
link |
from mild forms of depression or feel as they might,
link |
both for those people, and do you have advice
link |
for people who love the people who suffer
link |
from depression and want to help?
link |
Yeah, one of the incredibly frustrating things
link |
about depression is the very nature of it makes it hard
link |
for the people who suffer to get treatment
link |
because they're hopeless,
link |
so they don't think treatment will help.
link |
They have low energy, so they're not motivated
link |
to participate in treatment in many cases.
link |
Sometimes they're actively suicidal.
link |
That certainly doesn't help.
link |
They have all these things that seem to prevent treatment
link |
from being effective.
link |
So the loved ones, that's where the loved ones
link |
are so important, is helping them overcome these barriers
link |
to treatment, the motivation, the safety, and the insight.
link |
That's critical, and particularly for the severe cases.
link |
For the mild cases, where people still have some insight
link |
and motivation and energy to get something done,
link |
there are many things you can do.
link |
Exercise is extremely important in mood maintenance.
link |
Regulation of sleep and getting sufficient
link |
and regular enough sleep is very important.
link |
And talk therapy can be helpful in those mild
link |
or moderate cases, just looking at cognitions,
link |
looking at patterns of thought that people
link |
may have fallen into, where they catastrophize,
link |
where they spiral from small things into big things.
link |
A little bit of talk therapy, 10, 12 sessions,
link |
can help people identify those patterns they may have
link |
in themselves that are taking occasional negative thoughts,
link |
which everybody has, and magnifying those
link |
into more persistent negative states.
link |
If you work at this, and it's kind of like homework,
link |
this is what we call cognitive behavioral therapy.
link |
It's very structured, very organized.
link |
It requires insight and motivation,
link |
and you have to be motivated.
link |
But if you are, then you can identify these triggers
link |
that send you down particular pathways.
link |
And work to intercept them.
link |
And that is amazingly very effective
link |
in mild to moderate cases.
link |
So you basically have to train yourself
link |
to see the world as a collection of triggers.
link |
And you have to first understand, like collect the data,
link |
like basically see every experience
link |
as a thing that creates a follow on emotion, a feeling.
link |
And like, I've learned this, you know, like on social media,
link |
where like early on, you know, like all of us,
link |
you know, I'll say something,
link |
I kind of respond to negativity with negativity.
link |
And then you observe the results of that.
link |
And then over time, you think, wait a minute.
link |
This thing that I've been doing where
link |
when somebody says, you suck, and you say, no, you suck.
link |
That never produces the result you thought it might.
link |
And so might not want to just, don't say you suck back.
link |
And I do this through a lot of things in life.
link |
I'm very fortunate to not suffer from depression,
link |
but first of all, I have had and have people in my life
link |
who do, and also, you know, all of us have depression
link |
who don't suffer from depression, have depression out.
link |
Like, it's always knocking on the door.
link |
And so you have mild, I mean,
link |
if you're very careless with the triggers all around you,
link |
then you're just, I think all of us have the capacity
link |
to really suffer from that kind of chemical
link |
or psychological or philosophical existential crisis.
link |
But then it raises a question, why are we built this way?
link |
It seems like it doesn't make sense, right?
link |
And here's where some of us thinking about
link |
where we came from as the human family
link |
is kind of interesting.
link |
It doesn't make sense that somewhere on that spectrum
link |
that it's good to detect that there's an array
link |
of adverse forces out there in the world right now
link |
at this moment and to withdraw, to hunker down,
link |
to not fight, not strive, not try to meet the challenge
link |
and outweigh these negative forces
link |
that are present out there.
link |
And that makes a lot of sense, and all animals
link |
that have been studied in one form or another show this.
link |
Even the worm that I mentioned earlier,
link |
C. elegans with 302 neurons, it can effectively give up
link |
in challenging situations.
link |
We've done this with zebrafish,
link |
tiny little transparent fish.
link |
You can give them a challenging situation
link |
and they will give up, but then if you stimulate
link |
a couple very specific brain regions in particular ways,
link |
you can motivate them to overcome the challenge.
link |
And if you inhibit those regions,
link |
they give up much more easily than they would otherwise.
link |
You can do this in mice, you can do this in rats.
link |
So this is an ancestral conserve pattern
link |
to detect that things are pretty bad out there
link |
and to conserve energy, to hunker down,
link |
to wait out the storm.
link |
So as you, unfortunately, many of our maladies
link |
have useful roots that contribute to our survival.
link |
So both depression and motivation have uses.
link |
And sometimes it's nice to just shut the hell up
link |
and huddle with the penguins versus,
link |
for some unknown reason, venture out on your own
link |
into the mountains like a David Goggins type character.
link |
So what's the difference to you between,
link |
you see patients, between sort of rigorous psychoanalysis?
link |
I don't know if you consider talk therapy
link |
and psychoanalysis, are they neighbors,
link |
are they overlapping?
link |
They're neighbors.
link |
Psychoanalysis is, they're relatively,
link |
it's not nearly done as much as the talk therapy,
link |
like the cognitive behavioral therapy I mentioned.
link |
The psychoanalysis is a little more niche now
link |
and partly because it's not, the data isn't,
link |
in terms of actual treatment of actual therapeutic effects,
link |
data not as supportive as for cognitive behavioral therapy.
link |
But it's still interesting as for insight,
link |
people, a lot of people still do it
link |
to gain insight into themselves.
link |
And in general, it's a good sort of conversation starter.
link |
Those methods, they're good for getting things out.
link |
We don't focus on dreams typically these days
link |
in psychiatry, but they're great conversation starters.
link |
They're great ways to get things out if people have,
link |
and so we like to use those methods
link |
just to get the ball rolling sometimes,
link |
get people to open up a little bit.
link |
But the actual treatment tends not to involve
link |
these psychoanalytic approaches where you are really
link |
probing the unconscious mind and its manifestation
link |
through dreams, for example, as the goal.
link |
That's not the goal.
link |
Modern talk therapy, we're really focusing on treatment,
link |
how to get people to feel better.
link |
See, I use that as a conversation opener,
link |
the Freudian thing where I try to delve at a bar
link |
of the deep sexual desires in a person's subconscious
link |
and I find that opens up possibilities very quickly.
link |
Now, what's, I mean, this is a silly sounding question,
link |
but what's the difference between
link |
cognitive behavioral therapy and conversation?
link |
So, because I personally, as a fan of conversations,
link |
as a fan of just, I like listening to podcasts
link |
versus like audio book, I like both,
link |
but they're very different and I like conversation.
link |
I like, it makes me personally very anxious,
link |
so I like to be the listener, like a third wheel,
link |
like overhearing a conversation kind of thing,
link |
but it's a really powerful method for humans
link |
to explore each other's mind, just raw conversation.
link |
So, do you think it can be more productive
link |
to be very systematic about it or is conversation itself
link |
the art form of helping each other,
link |
understanding each other and helping each other?
link |
There are forms of talk therapy
link |
that are essentially conversational
link |
or they much more approach pure conversation.
link |
There's a befriending therapy,
link |
there's interpersonal therapy.
link |
These are approaches that are purely talk therapy,
link |
but they're not as structured
link |
as cognitive behavioral therapy.
link |
Cognitive behavioral therapy is,
link |
there are manuals, there are guidelines.
link |
You can almost go through it in a very cookbooky way.
link |
There's homework that you get done.
link |
So, it's in its fullest form,
link |
it's very different from these
link |
more conversational strategies.
link |
But what's interesting is sometimes people compare them
link |
and so you'll see almost like randomized controlled studies
link |
comparing cognitive behavioral therapy
link |
with interpersonal therapy, for example.
link |
And they both can work and actually in some studies,
link |
they look comparable.
link |
So, to your point, conversation and insights
link |
that come from conversation, if done well,
link |
if done artfully, can be as powerful.
link |
This reminds me of Robin Williams.
link |
I have to ask you several questions here on that.
link |
But one of my favorite movies is Good Will Hunting.
link |
I don't know if you've seen it with Robin Williams.
link |
So, as a psychiatrist yourself,
link |
can you do a deep analysis of this other famous psychiatrist
link |
which is the movie character played by Robin Williams
link |
at Good Will Hunting?
link |
Is it just a caricature between a psychiatrist
link |
and patient relationship?
link |
Or is there something to you that was moving
link |
about his ability to connect
link |
to this obviously struggling young kid?
link |
I think you hit on the key thing there
link |
which is the depth of the connection.
link |
If there's too powerful a connection,
link |
that can impair therapy
link |
because it could impair open communication.
link |
If someone, if a patient has a, sees the role,
link |
sees the relationship in a particular way,
link |
like in a friendly way maybe,
link |
or like a parental child type way,
link |
that can cause problems because then what they choose
link |
to share, what they choose to bring up is selected
link |
to be appropriate for that view of the relationship.
link |
And so, I and many other talk therapists actually prefer
link |
not to let things get, not let the connection get that deep.
link |
You wanna have trust.
link |
You wanna have a therapeutic alliance, we sometimes call it.
link |
But it's got to be enough of a blank slate
link |
that the patient is not consciously
link |
or unconsciously constrained in what they choose to share.
link |
And so, great movie, great actors, all good,
link |
no complaints except realistically,
link |
the relationship should be a little more arm's length
link |
Let's pretend this is real life.
link |
Sometimes can't you leave a little bit of yourself
link |
in the interaction with the patient?
link |
I mean, it's another human being.
link |
Yes, so there's a balance.
link |
And actually you do need some of it
link |
because let's say this person is having challenges,
link |
interpersonal challenges in their life.
link |
The best way to notice what those are
link |
and to identify them and to work with them
link |
is if you can elicit some of those problems
link |
in the office, in the therapeutic interaction.
link |
And this is really powerful.
link |
As long as you're alert to it, aware of it,
link |
and you don't let it go out of hand,
link |
this transference, we call it,
link |
is when you transfer in between
link |
the current therapeutic relationship
link |
and external relationships
link |
that the patient may have had with others.
link |
And so if the therapist starts to feel
link |
an inner feeling like anger, let's say.
link |
So let's say you have a patient
link |
who is stirring frustration in you
link |
or even in extreme cases, anger,
link |
the best thing for the therapist to do in that case
link |
is to recognize it and to realize
link |
that's probably being stirred by other people
link |
in the patient's life.
link |
And that could be the source of a lot of problems.
link |
And so instead of trying to wall it off,
link |
and say, oh, I shouldn't be feeling that,
link |
I better be a better therapist instead,
link |
and recognize it and use it,
link |
and help the patient that way.
link |
And so you've gotta be a human being.
link |
You've gotta be a person who feels.
link |
You've gotta be open.
link |
But be in control of it and be aware of it.
link |
If I may, I just wanna read,
link |
because it's one of my favorite scenes.
link |
Probably one of the greatest scenes,
link |
one of the greatest scenes in movie history
link |
because Robin Williams does a single take.
link |
I didn't know that.
link |
So this is a very interesting interaction between them.
link |
So Will, and I'm sure this is a common interaction,
link |
maybe with a therapist and a patient,
link |
maybe with a father and son,
link |
where Will, the young character,
link |
the young, brilliant mathematician,
link |
and Sean is the therapist, the older therapist,
link |
where Will looks at a painting that Sean painted
link |
and then does a deep, critical analysis of the painting
link |
that basically describes pretending
link |
as if he can understand another human being completely
link |
by just looking at their painting.
link |
And then Sean gives this whole speech
link |
that contrasts sort of raw intelligence
link |
and the wisdom of experience.
link |
And Sean says, single take.
link |
He says, you've never been out of Boston, right?
link |
And Will says, nope.
link |
All this in a sexy Boston accent, by the way.
link |
And then Sean gives the speech.
link |
If I asked you about art,
link |
you'd probably give me the skinny
link |
and about every art book ever written.
link |
Michelangelo, you know a lot about him.
link |
Life's work, political aspirations,
link |
him and the Pope, sexual orientation,
link |
the whole works, right?
link |
But I bet you can't tell me what it smells like
link |
in the Sistine Chapel.
link |
You never actually stood there
link |
and looked up at that beautiful ceiling, seeing that.
link |
If I asked you about women,
link |
you'll probably give me a syllabus
link |
of your personal favorites.
link |
You may have even been laid a few times.
link |
The language here is just beautiful.
link |
But you can't tell me what it feels like
link |
to wake up next to a woman and feel truly happy.
link |
You're a tough kid.
link |
If I asked you about war,
link |
you'd probably throw Shakespeare at me, right?
link |
Probably not, but let's say.
link |
Once more into the breach here, friends.
link |
But you've never been near one.
link |
You've never held your best friend's head on your lap
link |
and watched him gasp his last breath,
link |
looking to you for help.
link |
If I asked you about love,
link |
you'd probably quote me a sonnet.
link |
But you've never looked at a woman
link |
and be truly vulnerable,
link |
known someone who can level you with their eyes,
link |
feeling like God put an angel on earth just for you,
link |
who could rescue you from the depths of hell
link |
and you wouldn't know what it's like to be her angel.
link |
To have that love for her,
link |
be there forever, through anything, through cancer.
link |
And you wouldn't know about sleeping,
link |
sitting up in a hospital room for two months,
link |
holding her hand because the doctors could see in your eyes
link |
the terms visiting hours don't apply to you.
link |
You don't know about real loss
link |
because that only occurs when you love something
link |
more than you love yourself.
link |
I doubt you've ever dared to love anybody that much.
link |
I don't see an intelligent, confident man.
link |
I see a cocky, scared, shitless kid.
link |
But you're a genius, Will.
link |
No one denies that.
link |
No one can possibly understand the depths of you.
link |
But you presume to know everything about me
link |
because you saw a painting of mine
link |
you ripped my fucking life apart.
link |
You're an orphan, right?
link |
Do you think I know the first thing
link |
about how hard your life has been,
link |
how you feel, who you are because I read Oliver Twist?
link |
Does that encapsulate you?
link |
Personally, I don't give a shit about all that
link |
because you know what?
link |
I can't learn anything from you
link |
that I can't read in some fucking book
link |
unless you want to talk about you, who you are.
link |
And I'm fascinated, I'm in.
link |
But you don't want to do that, do you, sport?
link |
You're terrified of what you might say.
link |
Well done, sir, I know it's a movie.
link |
It's interesting, right?
link |
So some of that conversation
link |
is at some intellectual level, too.
link |
It's not just emotional, it's something,
link |
it's like, the reason I kind of connect with that is
link |
that's a lot of work for a therapist.
link |
Like, to really understand another,
link |
because he's, I mean, from, okay, I know this is fictional,
link |
but just, there's calculation happening.
link |
He deeply cares to say the words
link |
that the other person needs to hear,
link |
but also a little bit loses himself in the pride,
link |
but then catches himself again,
link |
switches from anger to connection.
link |
A lot is brought up there.
link |
You're right, there has to be some emotion
link |
in the therapist to care enough to keep going,
link |
to keep probing, to open up as he's doing so, right?
link |
He revealed a lot about himself, his own vulnerabilities,
link |
but that gave him authenticity.
link |
He had to open himself up
link |
so that the kid would see the authenticity
link |
and open himself up in return.
link |
So how do you do that as a psychiatrist, as a therapist?
link |
You have to be careful.
link |
You don't wanna do too much,
link |
but opening up a little bit does help.
link |
It does create a chance.
link |
You're offering up something
link |
and that helps the patient come back in return,
link |
and it gives you that believability and authenticity.
link |
Do you pay the price for that, for opening it up?
link |
You have a family.
link |
You have an incredibly difficult research.
link |
You're doing a lot of things in your world.
link |
I mean, it's the price you pay for like.
link |
Well, this was one of the terrifying things
link |
about writing the book was I do open up
link |
in a little bit about my own personal life,
link |
my own personal challenges,
link |
and that was a considered decision
link |
because I could have done the patient work
link |
and the science work
link |
and the history of the human family work
link |
and tied it all together,
link |
but it wasn't, and in an early draft, it was like that,
link |
but it wasn't real yet.
link |
It wasn't something that everybody could connect with,
link |
and I said, then I realized, look, if I'm gonna do this,
link |
I've gotta open up myself,
link |
and then people can connect with me
link |
and see what I'm really saying, and so I did,
link |
and that was not something that I'd gone in planning to do.
link |
In retrospect, I learned a lot about myself.
link |
It was actually really, I think, a good thing that I did,
link |
Where are the darkest places you've ever gone in your life?
link |
You know, I had, things haven't always been easy,
link |
personally or professionally.
link |
I had moments, you know, I was effectively a single dad
link |
for a while, a number of years,
link |
and these came at probably the hardest,
link |
also, professional lifetimes for me, too,
link |
the absolute hardest days of late medical school,
link |
internship, taking call, getting up at 3 a.m.,
link |
surgery, medicine, rounds, unforgiving environments,
link |
and then all the while, personal life,
link |
stripped down to the bare, and these were low moments,
link |
and then I was hit particularly hard by
link |
just experiences on the clinical ward,
link |
connecting too deeply with patients,
link |
like a child with a brain tumor,
link |
and feeling it too strongly, and those things,
link |
when you get down to those lowest of the low moments,
link |
when everything is stripped away,
link |
and there's only this raw core,
link |
well, that's pretty hard.
link |
That was probably the lowest moment,
link |
and you learn a lot about yourself in those moments,
link |
you know, what's left, and then what are the roots out
link |
from there, and that can be powerful to see in yourself.
link |
Have you thought about killing yourself?
link |
Have you seen that thought in the distance?
link |
I am fortunate that that has not come to my mind,
link |
and I have not seen it, even in the distance,
link |
and in some ways, I've wondered if that's made me,
link |
am I a less effective psychiatrist because of that?
link |
I've been, I've felt everything stripped away.
link |
I've been at the lowest of the low, and yet, that.
link |
There's still hope.
link |
There's a light of hope still at the end of the tunnel.
link |
So you never lost, even for brief moments, that.
link |
You don't know why.
link |
There was no reason.
link |
You don't know why.
link |
No reason to feel hope at that moment, honestly.
link |
Uh, so it was just the light without reason.
link |
Yeah, that's right.
link |
What wisdom do you draw from that time?
link |
About, so first of all, you said something funny,
link |
which is, I wonder if it, that it's somehow
link |
not having thoughts of suicide limits your capacity
link |
to truly understand somebody who is having those thoughts.
link |
So how many demons must a psychiatrist have
link |
in order to be a good psychiatrist?
link |
You know, this is a really interesting question.
link |
I think everybody knows, and I can say this,
link |
that psychiatrists can be a little unusual.
link |
We think about ourselves, right?
link |
We think about our brains.
link |
That may be one reason why we become psychiatrists
link |
is we think, oh, that's interesting going on in there.
link |
What's that about?
link |
So a little introspective, a little introverted maybe,
link |
and that's what can make us good when we're good.
link |
And, but also that may select for people
link |
who have some unusual aspects,
link |
but you don't have to have all of them.
link |
There's a lot that can go wrong in the psychiatric realm.
link |
I think having some of those, some of it,
link |
but not all of it is enough.
link |
You get to see how low things can get.
link |
You can get, you get empathy from that,
link |
even if the symptoms are not the same.
link |
Just empathy for struggle, for suffering.
link |
That's right, that's right.
link |
Do you yourself have to practice observing triggers
link |
just as a human operating in this world?
link |
I've definitely, those skills that have come from therapy,
link |
I've found them useful, yeah.
link |
If I noticed that, we've all been through experiences
link |
where we wonder, oh, I got really mad in that interaction.
link |
Why did I get that mad?
link |
Yeah, sure, maybe I could have been irritated,
link |
but man, why did I?
link |
And then thinking about it and realizing,
link |
okay, back up here, think about the broader context.
link |
Think about how that relates to prior events in my life.
link |
Okay, yeah, so this is a thing for me
link |
when something of this class happens, then it triggers me.
link |
So going forward, I'm gonna be aware of that.
link |
And I've definitely used that
link |
because you don't wanna be out of control of those emotions.
link |
You wanna identify them.
link |
You wanna know where they come from
link |
and you wanna head them off
link |
as a civilized human being living on this earth,
link |
trying to get along with other people.
link |
You wanna understand those moments.
link |
Let me return to Robin Williams for a second
link |
and looking at Robin Williams, the actor,
link |
because you mentioned for depression,
link |
you can have everything going well.
link |
And I think there's just famous cases of just public figures
link |
because a lot of people know them,
link |
where they suffer quietly
link |
and it seems like from the outside perspective
link |
that they have everything going for them,
link |
that they're at the top of their career.
link |
Two people that come to mind
link |
are Robin Williams and Anthony Bourdain.
link |
What insight do you have in why either of those have taken,
link |
why Robin Williams, a comedian,
link |
one of sort of the most jolly humans?
link |
Obviously, there was always the darkness
link |
that he was channeling in order to present the happiness,
link |
but it feels like that realness is only possible
link |
when you're deeply self honest and analytical
link |
and then if you're deeply self honest,
link |
you're going to realize that there's a lot
link |
of beautiful things about life that you can discover
link |
and if you do that,
link |
how can you possibly then take your own life?
link |
I mean, you go through all of these thoughts
link |
and I think a lot of people really loved Robin Williams,
link |
which is why it was really difficult to see
link |
how can even him, how can even Robin Williams
link |
take his own life?
link |
So I don't know if there's something to be said
link |
about the nature of depression
link |
from just looking at his case.
link |
I think the action of suicide is not well understood.
link |
It doesn't always, although often,
link |
is correlated with depression.
link |
There are cases of suicide where there is not
link |
clear depression, that's in the minority.
link |
By the way, if I just,
link |
because you said it so interesting,
link |
action of suicide, because there's also thoughts of suicide
link |
and probably those, they're probably somewhat understood,
link |
but it's an interesting, because you can think of suicide,
link |
if you have suicidal ideation,
link |
you can think of that for so many reasons.
link |
And I mean, thoughts sometimes, like painful thoughts,
link |
angry thoughts, or thoughts in general,
link |
can be very different, like fantasies, for example.
link |
You can fantasize, like sexual fantasies.
link |
You can fantasize, I was just for humor's sake
link |
wanted to mention stuff, but then people think I'm serious,
link |
so I'm not gonna mention anything.
link |
But sexual fantasies, and then there's,
link |
I know there's people that have sexual fantasies
link |
and they don't wanna actually do that in real life.
link |
That sexual fantasy serves some kind of purpose
link |
in imagination only, and in that same way,
link |
suicide might serve a purpose in imagination only,
link |
is very unlikely to lead to action.
link |
And yet there's other thoughts that maybe are more amorphous
link |
that do lead to action, and that leap,
link |
yeah, that, oh boy, that's a fascinating,
link |
and that's such a philosophically powerful thought
link |
to not exist, like that question, that's the,
link |
is it Sarcher or Camus, Camus?
link |
Well, the myth is Sisyphus, Camus, who says,
link |
like basic question of why live?
link |
So that's a great question, actually,
link |
and there are other related questions.
link |
Some people may have the thought of suicide
link |
because there seems no point, there's no joy in life.
link |
That's one reason that some people can put forward.
link |
Sometimes there's an, it's not just the absence of joy,
link |
there's an active pain, an active psychic pain
link |
in some people, and that, the inescapability of that
link |
is enough to drive the thoughts of suicide.
link |
And then there are interpersonal and cultural reasons
link |
as well that can show up.
link |
But the act, this act of ending of the self is,
link |
in all these cases, there's no real way to study this
link |
in animals, no other animal as far as we know
link |
that we can study has this concept of this is myself,
link |
the situation is not tolerable, therefore,
link |
I will end the self.
link |
To our knowledge, this is not something
link |
that can be studied in other animals.
link |
So it remains this very poorly understood action.
link |
And in predicting it, so what do we do as psychiatrists?
link |
We have this challenge.
link |
People come to the emergency room, they say they're suicidal
link |
or their friends say they're suicidal
link |
or they've taken some action that didn't lead to death.
link |
Well, there's a whole range of options.
link |
Was it a suicidal gesture in the sense
link |
of not intending death or was the intent death?
link |
And if it was the intent was death,
link |
what were the reasons?
link |
Are the reasons transient?
link |
Are they gone now?
link |
What's the probability that it'll be repeated?
link |
So we do all these things just to decide
link |
what sort of treatment should be carried out,
link |
but nowhere is there a deep understanding of the biology,
link |
of the cells and circuits and activity patterns
link |
that underlie the action to end the self.
link |
It's a very, it's this frustrating thing.
link |
It's so timely, it's so common, it shows up in veterans,
link |
it shows up in kids, it shows up in people
link |
at every stage of life, and yet we're very bad
link |
at understanding it and we're relatively poor
link |
at predicting it and our tools are not very powerful.
link |
We can put people in a locked unit,
link |
we can give them care, therapy for a while.
link |
At some point, we release them
link |
and there's only so much we can do.
link |
It's one of the most frustrating things,
link |
the suffering that is linked to suicidality.
link |
But it is a decision and it is an action
link |
and if you look at optogenetics,
link |
you should be able to one day sort of understand
link |
the dynamics of such weighty decisions.
link |
The individual causes then, if someone is anhedonic,
link |
if there is no joy in life, that very likely
link |
is addressable by optogenetics.
link |
We know how to turn that dial very robustly in animals.
link |
The motivation to overcome challenges,
link |
that we have some hope of understanding.
link |
Psychic pain, internal negative states,
link |
we have actually a handle on that as well.
link |
There's a structure in the brain called the habenula
link |
and some linked structures around it
link |
that seems to generate this negative internal state.
link |
It's active when a state of acute disappointment,
link |
acute outcomes that go wrong, not as expected.
link |
Moments of unexpected pain.
link |
The habenula is there, it seems,
link |
it's active to report on internal negativity
link |
And so you could imagine strategies
link |
to target this brain structure
link |
that might have the effect of reducing psychic pain,
link |
reducing the negativity of internal states.
link |
That is a very concrete hope.
link |
It's precise, it's anatomical.
link |
Optogenetics has given us all the firm foundation we need
link |
to go after that question.
link |
So I think there is hope.
link |
If you look at the individual causes,
link |
the individual symptoms relating to suicide,
link |
and then it's like a puzzle,
link |
you put together the puzzle pieces.
link |
By the way, I do think my habenula is
link |
very functioning, very actively.
link |
And I wonder if it's like,
link |
because you can also learn to channel these things, right?
link |
Some of the things we suffer from,
link |
I mean, there's degrees of suffering,
link |
can be a source of progress and personal growth
link |
and development and all those kinds of things.
link |
I mean, I, what is it?
link |
Nietzsche suffered from stomach issues.
link |
I wonder if he's written some of those things
link |
if his stomach was all great.
link |
I mean, there's, I kind of think that
link |
a difficult life in some form,
link |
you can get, you get to choose in some regard
link |
and some of you don't.
link |
The difficulties you have and the ones you do have,
link |
it's nice to use if possible.
link |
Sometimes it's nice to treat,
link |
sometimes it's nice to use.
link |
Well, the way you phrase it, I think you're using it.
link |
I could be wrong, but if you,
link |
you phrased in this semi humorous way about your habenula,
link |
it seems to me that you're using that to good effect.
link |
Now, but one never really knows
link |
what someone else's internal state is.
link |
As I look at you, I don't know the depths of what's going on
link |
and it's possible that it's a much harder situation
link |
So that's, I actually worry about this a lot.
link |
So I'm extremely self critical,
link |
like in the privacy of my own mind,
link |
which is an interesting thing
link |
when you get to meet the internet
link |
and the internet will tell you you suck.
link |
But for now, now this is what I worry about
link |
and I'm very paying attention.
link |
For now it's really, I just have this like very negative
link |
voice, but that voice seems to be very useful
link |
for productivity and so I channel it.
link |
I just put it on the table and let that voice like
link |
talk to me, but I'm very, I'm like monitoring that voice
link |
because looking at Robin Williams, you know,
link |
you get older, your brain changes or like you're,
link |
and then that voice can now all of a sudden grow, right?
link |
And then where you can't control as much,
link |
you have to be very careful with these kinds of things.
link |
You're very right about that.
link |
So my negativity, I have this,
link |
I never think I've done enough is sort of where my
link |
negativity comes from inside.
link |
I never think that I've met the potential of the moment.
link |
I haven't done, I haven't, you know,
link |
made the most of the opportunities that are available.
link |
Still early, I haven't, you know,
link |
progressed as far as I should.
link |
And exactly as you're saying, that works for a while.
link |
But then what happens as you get later in life
link |
and there's less runway to, you know, fix that.
link |
And then maybe then that negative voice is a problem.
link |
But also at that point, the negative voice
link |
starts having more and more of a point.
link |
When you're being very successful,
link |
it's easy to be like, no, okay, well,
link |
like because later in life, you're really literally
link |
just sitting there on a rocking chair doing nothing.
link |
And then it's, or maybe any kind of tragedy happens.
link |
Loss of a loved one, loss of a job,
link |
loss or you get screwed over in some kind of way.
link |
And then all of a sudden the negative voice
link |
is just you and the negative voice
link |
for days and days and days.
link |
And so I don't know, to go back to your example
link |
of Robin Williams, I don't know what was going on inside him.
link |
I don't know the nature of his internal state.
link |
Was it active psychic pain that?
link |
May I mention, may I interrupt to just say
link |
that Sergei posted an examination of Robin Williams.
link |
His brain tissue suggested that he suffered from quote,
link |
diffuse LEWY, Lewy body dementia, LBD.
link |
Depression is a symptom of LBD and it's not about psychology.
link |
It's rooted in urology.
link |
This is words from Sergei.
link |
His brain was falling apart.
link |
Yeah, Lewy body dementia.
link |
This is a very interesting neurological disorder
link |
where among other things, there's neuron death indeed.
link |
So you've got frank neuron loss.
link |
It's not just a matter of some longstanding psychic pain,
link |
but you've got a progressive loss.
link |
And so clearly you've got a situation
link |
where he could have finally reached a point
link |
where the balance that he'd worked out
link |
between negativity and positivity was disrupted due to loss.
link |
The wrong cells died, the wrong projections were cut.
link |
By the Lewy body dementia.
link |
Certainly dopamine neurons die in Lewy body dementia.
link |
Those are neurons that give rise to much of the feelings
link |
of reward and pleasure that we experience among other roles.
link |
So clearly in his case, there could have been
link |
a very concrete cellular neurological issue
link |
that was progressive and pushed him to that point.
link |
But were you about to make a point about broader
link |
that if there is not a neurological degeneration?
link |
Yeah, so in his case, not knowing that,
link |
it could have been simply that,
link |
let's say he had an internal psychic pain state
link |
and he was in sort of a compensated mode
link |
for much of his life, able to generate enough joy
link |
from his comedy and his social interactions.
link |
But eventually later in life, those things drop away,
link |
the balance shifts.
link |
You get tired of fighting the pain for that long.
link |
So you've got this time dependent non stationarity
link |
that happens and then the same symptom
link |
becomes no longer tolerable in the end.
link |
What do we know about autism?
link |
Human beings exist on a spectrum of how social we can be.
link |
And this is pretty interesting actually, scientifically,
link |
but also very important clinically.
link |
There are hyper social states where people
link |
are almost too social.
link |
There are chromosomal deletion states
link |
where people have instant affinity and bonding
link |
and rich deep seeming connections with people, very verbal.
link |
On the other end, people with autism spectrum disorder
link |
are not able to keep up with social interactions
link |
and it's a spectrum.
link |
Some have mild to moderate difficulties.
link |
They may have inability to understand
link |
what the next thing to do in a social situation is,
link |
but may have perfectly good language abilities.
link |
And as you progress further along the spectrum,
link |
that gets more and more severe
link |
so they can't make eye contact because it's too overwhelming
link |
to think about what has to be done next
link |
if a person looks in a particular way.
link |
And then as you go farther,
link |
then language and social communication themselves break down
link |
so there's no reciprocity, there's no shared enjoyment.
link |
And that this gets very hard then
link |
as you get to this far end of the spectrum
link |
where there's really an absence of social cognition at all
link |
and social bonding.
link |
So why does this exist?
link |
It's very genetic.
link |
As I mentioned, it's one of the top three or four
link |
most biological in the sense of most genetically determined
link |
of the psychiatric illnesses.
link |
It does have these interesting positive correlations,
link |
slight positive correlations
link |
with intelligence and education.
link |
And the reason for that
link |
is kind of interesting to think about.
link |
Is there something good about it?
link |
Just like, or at least with at least part of the spectrum,
link |
is there something good about it?
link |
Just as we were talking about for depression,
link |
as you could say for mania,
link |
as you could say for schizophrenia.
link |
And here it's kind of interesting
link |
to think about the underlying science
link |
of what it means to be good at a social interaction.
link |
Someone who's very good at a social interaction
link |
is incredibly good at dealing
link |
with unpredictable information,
link |
is able to handle this torrent of information
link |
coming through rapidly changing
link |
model of the other person and of the interaction
link |
and their model of you, your model of them.
link |
With each word that changes,
link |
with each new bit of information
link |
that comes in through the conversation,
link |
each bit of body language, all this is rapidly changing.
link |
And some people are able to keep up
link |
with that firehose of information perfectly well.
link |
But that's a special brain state to be in.
link |
That's working with unpredictability.
link |
That's the only way that can be done
link |
is most likely by constantly running models
link |
of what the other person might be about to say.
link |
So you can't stop and think, oh, what did that word mean?
link |
What did that shift in eye contact mean?
link |
What do they mean together?
link |
There has to be some advanced work going on
link |
where you're predicting what's going on
link |
if you're to keep up with a rich
link |
and fast social interaction.
link |
Now, on the flip side, there are brain states
link |
that maybe don't have to work so fast
link |
but that are extremely important still.
link |
Dealing with something that's not moving
link |
or that's predictable, still complex,
link |
like mathematical proof or a very complex arrangement
link |
of geometrical shapes, a large number
link |
of individual nonmoving things.
link |
There's possibly a way of being that's particularly good
link |
at dealing with these static, unmoving,
link |
or predictable situations and less so
link |
with these rapidly changing social situations.
link |
And so the way I conceptualize autism
link |
is these are people whose brains are not so good
link |
with the high bit rate, unpredictable information,
link |
but may be quite good at given enough time,
link |
given the grace to work with the system,
link |
to look at it from different angles,
link |
to take different perspectives with a confidence
link |
that it's not changing in between perspectives.
link |
That's a brain state that's valuable.
link |
It's something that has probably contributed
link |
to a lot of the success of the human family,
link |
being able to design something,
link |
being able to consider all the different contributions
link |
to a static, predictable system.
link |
So autism, in a sense, is a spectrum
link |
that has identifiable characteristics
link |
about the way people deal with dynamic information,
link |
often expressed itself as like social dynamic information.
link |
But you critically, your use of the word often there
link |
is really, I think, smart,
link |
because it's not just social interaction
link |
that is a challenge in autism.
link |
And so many people conceptualize it purely
link |
as a social dysfunction disorder.
link |
But it's really any unpredictable information
link |
that's a problem, that's a challenge
link |
for people on the spectrum.
link |
They react very negatively to unexpected sounds,
link |
even if not social sounds, unexpected lights,
link |
unexpected touches, and so it's really
link |
unpredictable information that is, in my view,
link |
the core problem with the processing in autism,
link |
Social just shows up because it's so unpredictable.
link |
Yeah, it's so interesting.
link |
I mean, I try to not to think about that stuff.
link |
I'm afraid of thinking about disorders
link |
and things like that because just like I don't like
link |
sort of economics or game theory,
link |
I want to be careful with it because it,
link |
whenever you have a category or a model,
link |
it's too easy to just, for everything,
link |
I mean, it's the OCD thing.
link |
I like models too much.
link |
I like categories too much.
link |
The moment you acknowledge yourself,
link |
well, I have an eating disorder, for example,
link |
or something like that, as opposed to just being a,
link |
well, I'll just leave it at that
link |
from my own critical understanding of myself.
link |
Let's just say I don't know how to moderate eating fruit.
link |
People make fun of me.
link |
They think all fruit is healthy.
link |
I don't know how to moderate anything,
link |
but even fruit, apples and cherries, is a nightmare.
link |
Anyway, that's such a psychiatrist thing to say.
link |
But there's characteristics and it's interesting
link |
to think about, like for example,
link |
I have trouble making eye contact,
link |
but I actually, as you said it now,
link |
it's not that I'm shy at all in that sense.
link |
It's literally, I'm getting way too much information
link |
and it's distracting me.
link |
Like I need to just close my eyes so I can,
link |
like all the things that people seem to be able to do
link |
in parallel, it's just, you just asked me a question.
link |
For me to think about the answer to that question,
link |
I can't have all this cool, rich visual information
link |
That's literally, because I often close my eyes to think.
link |
It's not because I'm afraid of something, whatever.
link |
It's just like too much information happening here.
link |
Well, that's a beautiful description.
link |
It's amazing that that is how you experience
link |
the eye contact aspect.
link |
I think that's, I mean, you've articulated
link |
what captures it for so many people,
link |
which is that it's overwhelming.
link |
There's just too much information just coming in
link |
through the eyes and to keep up with it,
link |
to know you're gonna be expected to keep up with it,
link |
first of all, so there's that aspect.
link |
You know, you've learned socially
link |
that there's gonna be an expectation
link |
if you're making eye contact.
link |
People are gonna think you're keeping up with it,
link |
and you don't want to because you wanna focus
link |
on other things and make progress in other dimensions.
link |
Yeah, and so then there's a strong desire
link |
to look away or to close the eyes
link |
because it's overwhelming, it's a distraction,
link |
and it's gonna cause errors of understanding.
link |
And of course, our eyes, that's part,
link |
the way we use our eyes is part of the human communication,
link |
so you have to kind of be aware of that,
link |
of that element of it.
link |
So yeah, I mean, but it's fascinating.
link |
You should be aware of your own self
link |
in those little characteristics,
link |
whether it's classified on some aspect
link |
of the autism spectrum or just in general,
link |
whether it's eating, whether it's depression,
link |
whether it's even like schizophrenia
link |
that I hope we get a chance to talk to a little bit.
link |
Yeah, but those things are all made up
link |
of different symptoms and characteristics,
link |
and use them as a superpower, I suppose,
link |
is the best we can hope for in mild cases, I guess.
link |
I do think both brain states can't coexist
link |
The way of dealing with something unpredictable
link |
and dealing with something predictable,
link |
those are different ways of being,
link |
here's a huge opportunity for very creative
link |
model building in theoretical neuroscience
link |
and linking that to these data streams
link |
we're getting across the brain that we talked about earlier,
link |
these immense data sets of activity across the brain.
link |
Here's where I think there could be
link |
a real convergence of theoreticians and experimentalists
link |
to say, okay, given what we know about wiring of the brain,
link |
here is what the brain state is likely to be
link |
that deals well with unpredictable information,
link |
and here's the brain state
link |
that deals with predictable information.
link |
Here's why they're incompatible, at least at the same time.
link |
Here's why you've gotta be able to detect
link |
which state you should be in.
link |
Here's how you could switch between them.
link |
Here's the kind of cells that you would predict,
link |
almost like predicting the Higgs boson.
link |
Here's the kind of circuitry that I would predict
link |
should govern the switching,
link |
or might make one state too sticky, too hard to get out of.
link |
That is a huge opportunity for an interaction
link |
from the theoretical and experimental side together.
link |
Make one state too sticky.
link |
The sort of measure the stickiness of the state
link |
and how to lessen the stickiness.
link |
Get some oil in the machine.
link |
Yes, yeah, what would predict the kind of oil
link |
that would work well.
link |
What, in your practice, is treatment or advice
link |
for the people on the autism spectrum?
link |
So right now, there's no real medical treatment.
link |
There are behavioral treatments
link |
that are most effective early in life.
link |
They make sure people don't fall too far behind.
link |
If you're not interacting socially,
link |
you create this vicious cycle
link |
where you fall farther and farther behind
link |
because you're not interacting.
link |
And these therapies which are applied early in life,
link |
therapists work with the kids,
link |
train them to deal with these things
link |
that otherwise would be aversive to them,
link |
teach them how to predict things and interact,
link |
and that has a big effect.
link |
But it's behavioral therapy.
link |
There's no medicine that works.
link |
There are ways of reducing individual symptoms though
link |
that sometimes come along with autism
link |
and those do respond to medications.
link |
So you can, one thing, very often,
link |
my patients with autism are very anxious
link |
because they live in a world
link |
that they have a really hard time
link |
predicting what's gonna happen.
link |
And so they find, and some of these are high functioning,
link |
Silicon Valley types who they may make great livings
link |
but they're very unhappy because they're on the spectrum.
link |
They don't understand how social interactions really work.
link |
They're very anxiety provoking
link |
because they don't know what to say.
link |
They don't have any clue how anybody else knows what to say.
link |
They're constantly worried they're gonna say something
link |
that's completely inappropriate
link |
and so they're very anxious.
link |
And I can treat their anxiety.
link |
It doesn't touch the autism per se
link |
but I can help them with their anxiety.
link |
What I just talked about, eye contact.
link |
I am richly, even with eyes closed
link |
and all those kinds of things,
link |
I'm richly experiencing the world.
link |
And it's not like you're afraid of the world
link |
or you're not able, I don't know what to do.
link |
No, I know everything.
link |
In fact, I know way too much.
link |
There's so many cool options.
link |
Like at any one moment, there's all the stuff happening
link |
and it's all beautiful.
link |
And at any one moment, you can do anything you want.
link |
You can take off your clothes.
link |
You can punch that guy over there.
link |
You can go in for a hug.
link |
You can say something profound and deep
link |
or you can say something generic
link |
or you can do so many things you can say.
link |
And then it'll go, it'll unravel in all these kinds of ways
link |
and this moment could be completely life changing
link |
or it can be mundane and meaningless.
link |
And all of those options are before you at any one moment.
link |
And so it's like, it's amazing and overwhelming
link |
if you allow yourself to think about it,
link |
which whatever, exactly.
link |
Like, well, I'm fortunate with chess,
link |
you have a few set options.
link |
Two dimensional, at least dimensional is constraints.
link |
There is unlimited possibilities
link |
and unlimited beautiful things happening all around you.
link |
So I don't think there's a kind of sense
link |
that somehow you're limited in the places of,
link |
in the way you can see the world
link |
and how you can interact with that world.
link |
I am overwhelmed by the lack of limit.
link |
That all of us should be, have you looked around?
link |
You can do whatever the hell you want.
link |
Nobody will remember you anyway.
link |
All of us will be dead one day.
link |
You could do anything.
link |
You can, I don't know, you can get naked
link |
and run around the city,
link |
as long as you're not hurting anybody,
link |
and it doesn't matter.
link |
So it's Austin, anyway.
link |
Austin, yeah, exactly.
link |
Seems like a to do item for anybody living in Austin,
link |
But the spectrum is an interesting concept
link |
because that is, when I say,
link |
when I refer to the spectrum,
link |
I'm actually referring to, it's a precise clinical term,
link |
but you're right, it's been coopted more broadly
link |
and it is widely used and it can be
link |
an unfair categorization of someone
link |
who's socially and occupationally very healthy.
link |
And that is critical
link |
because we don't define a disorder
link |
unless there's social or occupational dysfunction.
link |
It doesn't matter what the symptoms are.
link |
I've had patients who are pleasantly hallucinating,
link |
so frankly, psychotic, but doesn't affect their lives,
link |
so I don't give that person a diagnosis
link |
because there's not social or occupational dysfunction.
link |
Same with anything on this,
link |
any of the diverse symptoms of autism spectrum disorder.
link |
If someone has them,
link |
but they're successful socially and occupationally,
link |
we don't say that there's a disorder.
link |
But then you're right, that the concept of the spectrum
link |
does become a useful pigeonholing device,
link |
which is maybe not the best thing.
link |
Yeah, and the eye contact is an interesting one,
link |
is an interesting one.
link |
I'm torn about the usefulness of eye contact
link |
because people kind of make fun of it,
link |
but let me just say one thing about eye contact
link |
and about life in general.
link |
It's okay to be weird,
link |
but like some people, when you have your eyes closed
link |
and there's that weird, what is happening to this creature?
link |
Like you see a weird creature on the side of the road.
link |
And you wanna, I mean, the weird stuff,
link |
I'm gonna go back to Robin Williams with the,
link |
that's the good stuff, right?
link |
He has that whole speech about him and his wife
link |
and what he loves all the little peculiarities,
link |
all the weird stuff.
link |
And that, like let those flourish.
link |
Let those, like celebrate those in yourself
link |
and not in some kind of woke way,
link |
but in some like very human way.
link |
This is what makes us, this is the weirdness.
link |
Yeah, I'm 100% on board with that.
link |
And I don't think, you know, people who are happy
link |
and who have people in their lives who are happy with them,
link |
these are, I think, let the weirdness flourish.
link |
Let the, all the different ways members
link |
of the human family can be different.
link |
Let's see them all.
link |
That's one of our, that's one of the joys of being alive
link |
is seeing all the ways we can be human.
link |
And I think about it all the time.
link |
Why do we have all these ways of being human?
link |
And even within one individual,
link |
you go through phases of life
link |
where you express different sides of your way of being,
link |
which is also a pretty fun opportunity, right?
link |
You can go through phases where you're in one mode
link |
and phases when you're in another mode.
link |
And let that, you know, just let that flourish too.
link |
Let the ways that you can be you vary as well.
link |
I think that's important for people to explore.
link |
And I should, like, as if you can address the internet,
link |
but I would like to sort of ask the internet
link |
to celebrate the weirdness of people.
link |
Like, that's, it's the Robin Williams,
link |
people call these imperfections,
link |
but they're not, that's the good stuff.
link |
For any one individual person,
link |
find the weird stuff and celebrate it,
link |
as opposed to what the internet often does,
link |
which is find the weird stuff and criticize it.
link |
Because when you criticize the weird stuff,
link |
you're creating conformity, which is another human thing.
link |
But that conformity creates a boring world.
link |
You want the weird, you want the crazy.
link |
That's what fun is made of.
link |
That's the foundation of humor
link |
and all of the ways in which we deal
link |
with the suffering in the world,
link |
with the injustices in the world,
link |
is like this like huge variety of weird.
link |
Yeah, I don't know.
link |
And that's what, at the depth of psychiatry,
link |
is like you wanna acknowledge the weird,
link |
celebrate the weird, like step around it
link |
to find the particular aspects of weird
link |
that are debilitating, like you said.
link |
They're somehow negatively affecting your ability
link |
to function in the world,
link |
as opposed to trying to shut it all down.
link |
Well, on that topic, I mean,
link |
I'd love to talk to you about schizophrenia.
link |
What is schizophrenia?
link |
From your research and from your general understanding,
link |
and what is the full landscape of suffering
link |
and wisdom that schizophrenia explores?
link |
Schizophrenia is a state where
link |
there is a break from reality.
link |
And so this can show up, as we call them,
link |
the positive symptoms of schizophrenia.
link |
These include hallucinations,
link |
hearing something or seeing something that's not there,
link |
usually auditory hallucinations.
link |
Paranoia, people can have complex fears.
link |
Delusions, which we call fixed false beliefs,
link |
people get an extremely unshakable
link |
but completely implausible idea about something.
link |
Sometimes it relates to themself, sometimes to the world.
link |
These we call the positive symptoms,
link |
break from reality as we know it.
link |
Then there are the negative symptoms that come with it,
link |
and these are progressive.
link |
These are flattening of emotion, as we call it,
link |
so starting to express less and less positive emotion,
link |
ending more in a neutral or flat state.
link |
Thought disorder, inability to work with complex patterns
link |
of planning or thinking, so you can't make plans,
link |
you'd have poor working memory,
link |
you can't keep track of where you were in a conversation,
link |
in a sequence of actions.
link |
So poor and impaired working with the thoughts of oneself
link |
and then these positive symptoms of break from reality.
link |
Okay, now why do these come together?
link |
What's the neurobiology of it?
link |
Again, we don't know.
link |
Schizophrenia, extremely genetically determined.
link |
If you look at the numbers,
link |
could be upwards of 80% genetically determined.
link |
1% of the human population around the world,
link |
it's universal, okay?
link |
It's not confined to any one culture,
link |
not even really biased in one culture or another,
link |
about 1% around the world.
link |
And has this progressive quality to it, untreated,
link |
so it's very interesting.
link |
There's a break that happens, we call it first break,
link |
when someone experiences their first disruption of reality,
link |
they can have a completely typical life up until that point.
link |
So you might have a, and I've seen just heartbreaking cases
link |
of like this in the Stanford emergency room
link |
where a kid has come there,
link |
who's been extremely high functioning in that sense
link |
of academic achievement and athletic and interpersonal,
link |
and then comes to college.
link |
Usually in men, it's around 18, 19 when the first break
link |
happens, some terrifying paranoia hits
link |
or some auditory hallucinations start.
link |
They're getting screamed at by a voice in their head.
link |
With women, comes on also often a little later,
link |
sometimes in the 20s, and it can be progressive.
link |
If it's not treated, it just progresses and progresses.
link |
The voices become overwhelming, the delusions
link |
and paranoia extend and expand.
link |
The thought, the negative symptoms particularly
link |
become more and more severe.
link |
So one can't even maintain thoughts
link |
in any sort of ordered fashion.
link |
And then eventually, it can be fatal,
link |
it can lead to suicide, it can lead to erratic behavior
link |
that leads to accidents.
link |
Now, it can be treated.
link |
There are medications that help, fortunately.
link |
They have side effects, so they're not perfect.
link |
You can have movement problems and actually a whole host
link |
of different side effects that come from the medications.
link |
But we can help people now with schizophrenia
link |
very, very significantly.
link |
But the amazing thing, and this is emblematic
link |
of where psychiatry stands, we don't have
link |
the deep understanding, just like with depression,
link |
we don't have that heart as a pump level of understanding
link |
that we'd like to have with schizophrenia,
link |
despite it being so biological, so genetic in its nature.
link |
So is there a way to return to the other side
link |
of the first break?
link |
So when you have a break with reality,
link |
is there a way to kind of stitch it together?
link |
So some people, that works, but we don't really know how.
link |
So medications, antipsychotic medications, we call them,
link |
they block a particular neurotransmitter receptor
link |
called the serotonin 2A receptor,
link |
and they modulate dopamine as well
link |
and other neurotransmitters.
link |
These can take someone who's actively hallucinating,
link |
actively paranoid, put them back in a completely normal
link |
state, and some people stay that way indefinitely.
link |
So you can bring people back from that,
link |
back to the other side, have it stitched together.
link |
More typically, you'll end up in some intermediate state
link |
where symptoms are reduced powerfully,
link |
but there might be still something there
link |
and you've got a drop down in functioning
link |
that may be persistent for a while.
link |
But concepts, what physically is going on?
link |
One idea is that it's communication within the brain.
link |
One part of the brain is not able to tell
link |
other parts of the brain what it's doing.
link |
And so the auditory hallucinations
link |
are very interesting in this regard.
link |
They often have this conversational,
link |
inner monologue like quality.
link |
As we're walking along the street,
link |
we may have an inner monologue,
link |
thoughts about what's going on.
link |
If we see somebody we don't like,
link |
we may have a thought,
link |
wish somebody would punch that guy, something like that,
link |
or maybe I should punch that guy.
link |
But these are so far below where we would ever act
link |
or even think of acting,
link |
but they're just things that come up.
link |
And in people with schizophrenia,
link |
those inner thoughts, that inner monologue,
link |
is not recognized as the inner monologue of the self.
link |
And so it's perceived as something coming from the outside
link |
or from inside, but from another entity.
link |
Another, oh, another, I thought you meant
link |
like another room inside the same building.
link |
Another room inside there, yeah.
link |
And so that's, so it could be conceptualized
link |
as a communication within the brain problem,
link |
notifying another part of the brain what's going on.
link |
And there's some evidence consistent with that.
link |
I don't know if you can help with this,
link |
but I sometimes, so I've been talking
link |
to quite a few homeless folks recently,
link |
just, so what I do is I hang out at night
link |
and talk to interesting people.
link |
And some of them, and I've known people in the past
link |
who suffer from schizophrenia,
link |
and some of them, like self, will describe
link |
as that as something they suffer from.
link |
And they seem to understand something deeply
link |
I don't know if it's correlated
link |
or maybe it's another aspect of like depression,
link |
all those things that I've encountered in my own life
link |
is maybe just the struggle and the suffering
link |
has taken you through a life
link |
where you think deeply about life.
link |
Like there's like self reflection
link |
that society forces on you
link |
because it's a disorder of some kind.
link |
It's interesting, I guess my only sort
link |
of anecdotal observation is people who suffer
link |
from schizophrenia seem to be very interesting
link |
and very thoughtful in a nonlinear way about the world.
link |
I've noticed that it's not always positive.
link |
There are unusual ways they view the world.
link |
It was, but it's always interesting.
link |
That could be conspiratorial thinking too.
link |
Like, but like the theories they have
link |
about the way the world functions,
link |
often very well read, which is also interesting
link |
because they're almost like looking
link |
for helpful answers from somewhere.
link |
And so they're, they might be citing
link |
some very interesting literature
link |
and then using that to, there's a stickiness
link |
in their mind to different models of the world
link |
and trying to make sense of that world.
link |
And those models could include conspiracy theories.
link |
Yeah, they're very attuned to complexity
link |
and they come up with unlikely explanations,
link |
which is one of the things that makes them,
link |
it makes it hard for them to function in the world
link |
is how unlikely their explanations are.
link |
But you're right, there's a depth of consideration
link |
of the complexity of the world and a concern about it
link |
and a work, an impulse to work to understand it
link |
that is actually quite refreshing.
link |
But the first case in the medical literature,
link |
there was a classical schizophrenia.
link |
There was a patient named James Tilly Matthews
link |
who had this, he sketched out for his doctor
link |
the experiences he was sensing
link |
and he drew himself as a cowering figure
link |
on the ground controlled by a loom,
link |
a weaving device that was sending threads,
link |
long threads, projections across space
link |
from the loom to him, to his arms and to his body
link |
and controlling him from afar.
link |
And he called this the air loom, a loom in the air.
link |
And it was such an evocative thing
link |
because this was the start of the Industrial Revolution
link |
or mid and it was where really industrial strength,
link |
looms and weaving devices were really kind of the emblematic
link |
of the most complex, powerful technological achievements
link |
of the time and so that was the explanation available
link |
to him to explain how his body was seemingly moved
link |
without his volition and these days, of course,
link |
people with schizophrenia will have more technology
link |
appropriate interpretations, they'll have delusions
link |
of satellite or alien control or beamed information,
link |
very, very common to have this delusion
link |
of a government agency sending electromagnetic
link |
or radio frequency information to control their limbs.
link |
But it's the same thing, whether it's a thread
link |
from an Industrial Revolution loom
link |
or RF radiation, it's the same thing just adapted
link |
to the moment explaining, trying to explain
link |
the world they live in and their relationship to the world.
link |
But unconstrained by sort of the thing
link |
that's socially acceptable,
link |
which is both refreshing and dangerous.
link |
I wrote down a question.
link |
Are tears a window to some depths
link |
that we ourselves don't know?
link |
I almost wanna make fun of myself for that question,
link |
but you do talk seriously about crying in the book.
link |
In fact, the whole first chapter really tussles
link |
with crying as why do we do it, what does it mean,
link |
why is it involuntary?
link |
It seems like a weakness, right?
link |
Because it's so involuntary and it's reflecting
link |
something true and inside.
link |
At the level of the individual,
link |
that seems like a problem, right?
link |
Wouldn't it be better if we could control it,
link |
if we could not show that emotion when it's not useful,
link |
show it when it's useful?
link |
But it's not, it's largely involuntary.
link |
And so there's a value to it, I think,
link |
as an honest reporter of a need,
link |
of hope and frailty at the same time.
link |
I am a human being, there's a frailty to myself
link |
or my situation where I need social help,
link |
I need help from my community.
link |
I have hope that that is possible,
link |
but I'm not enough for myself, I need the community.
link |
That I think is what the social signal of crying is.
link |
Now people have studied crying, it's an extreme,
link |
you can quantify the extent to which the presence of tears
link |
on a face triggers reactions in onlookers.
link |
And you can show the same face in the presence
link |
or absence of tears and show that to people
link |
under quantifiable and rigorous psychological conditions.
link |
And tears are much more powerful at stirring
link |
the desire to help in viewers
link |
than any other facial feature.
link |
Which is pretty interesting that it's the honest one
link |
that's also the most powerful, right?
link |
It kind of indicates there's a certain logic
link |
to our design as social beings
link |
that we have an honest report.
link |
That's hard to control.
link |
But is it well understood how that connects
link |
to the internal state of emotion?
link |
Yeah, there are long range projections that come,
link |
so where is crying generated?
link |
This is the confusing thing about it.
link |
So that we have a little tear duct, the lacrimal gland
link |
that leads to the release of fluid,
link |
it ejects fluid and it comes out.
link |
And those of course, that whole system was designed
link |
to keep the eye clean, to wash out particulate irritants.
link |
So it's a long standing, as long as we've had eyes
link |
and have been out of the water in our evolution,
link |
we've needed this sort of thing.
link |
So long standing biological structure,
link |
recently co opted it seems by our evolution
link |
as social primates.
link |
Now, how could that happen?
link |
Well, the lacrimal gland is controlled by structures
link |
in the pons, which is a structure deep in our,
link |
just above our neck, between our neck and our head.
link |
And reflecting its ancient origin, right?
link |
As you go farther down toward the spinal cord,
link |
these are the more basic early evolved structures.
link |
And in the pons, that's where breathing is controlled,
link |
tear duct contraction.
link |
And what we found and with optogenetics,
link |
we helped sort this out,
link |
there are long range projections
link |
from fear and anxiety regions in the forebrain
link |
that project all the way to the pons
link |
in and around those areas.
link |
The reason those are there,
link |
we think is to regulate the respiratory rate changes,
link |
the breathing changes of fear and anxiety.
link |
So we know when we're in a state of fear and anxiety,
link |
we need, we cope better if we have elevated heart rate,
link |
elevated respiratory rate, more blood pumping around,
link |
more oxygenated blood,
link |
we're ready to meet the threat if it happens.
link |
All those cells are down there in the pons too,
link |
right next to the lacrimal duct, the tear gland neurons.
link |
And so almost certainly this fear anxiety induced crying
link |
arose from a very slightly misdirected long range projection
link |
that was there to regulate breathing.
link |
And a little twist, just a little misdirection,
link |
a little missing of one sign post to stop here,
link |
going on a little farther,
link |
getting to the lacrimal gland neurons gave us crying.
link |
And that's, and we just have it,
link |
that peculiar sort of structure, neuronal structure
link |
that resulted in that, that's what we're stuck with.
link |
And that ends up being, in terms of social interaction,
link |
one of the more important, authentic,
link |
involuntary displays of interstate.
link |
And social communication.
link |
Oh, yeah, is there other stuff like that?
link |
I mean, do you, yeah, I mean, the human face is fascinating
link |
as a display of emotion, as a display of truth and lying
link |
and all those kinds of things.
link |
I personally, I mean, we're all, I suppose,
link |
have different sensors that are sensitive
link |
to certain aspects of the human face.
link |
But to me, it seems like the eyes
link |
are really important communication or something.
link |
You know, I've talked to a few sort of girls
link |
about like Botox and stuff like that.
link |
And it always bothers me when,
link |
I guess guys can do this too,
link |
but like when women speak negatively
link |
of, I guess you can call them wrinkles,
link |
at the tips of an eye.
link |
But like to me, when you smile, when you wink,
link |
not wink, but like narrow the eyes,
link |
something is communicated and those,
link |
that stuff is really useful, the human face.
link |
And when it's gone, something is missing.
link |
And a lot of little stuff, it feels like it really,
link |
it's almost involuntary, I guess,
link |
but it's harder to describe as the presence
link |
or absence of tears.
link |
It's like something about this person,
link |
you can tell they're not bullshitting you.
link |
And so that was what made, presumably,
link |
that tear recruitment so powerful,
link |
is it just landed in this very high value real estate
link |
for social communication.
link |
If it had gone to, you know,
link |
there's a lot of neurons in the pons
link |
that control movement of large muscles elsewhere,
link |
that would have been much less effective
link |
as a social signal than something around the eye.
link |
So it was, however that little misdirection happened,
link |
it landed in a great area for social communication.
link |
And because it was coming from the fear and anxiety circuits
link |
that regulate that necessary involuntary change
link |
in heart rate and respiratory rate,
link |
it also was involuntary and that became valuable
link |
as a truth signal, as social beings.
link |
So very interesting when you think about
link |
the origins of the human family,
link |
the origins of social structures
link |
and our ability and need to call for help
link |
when there's hope, but need at the same time.
link |
What is consciousness, Carl?
link |
So you're actually using techniques.
link |
I mean, even putting psychiatry aside,
link |
just looking at optogenetics,
link |
you're trying to understand some of these deep aspects
link |
of the human mind.
link |
And maybe this is a good time to return to a question
link |
you mentioned you might have an opinion on
link |
if there's such a thing as a theory of everything
link |
for the human mind.
link |
Because surely answering of what is consciousness
link |
is as, well, that's not sure.
link |
But it seems like it's a fundamental part
link |
of the human experience in the human mind
link |
and solving that question will result in solving
link |
the bigger thing about the human mind.
link |
The flip side could be consciousness
link |
is just the few neurons that are generating
link |
some useful thing that make us,
link |
it's like the sense of self
link |
that you talked about in the mice.
link |
Maybe it's a subset of those cells
link |
that are just creating a richer sense of self
link |
So this is a great question.
link |
All neuroscientists think about this
link |
and a lot of non neuroscientists too.
link |
It's the reason a lot of people came to the study
link |
of the brain is to think about consciousness
link |
and not just being awake or alert
link |
but really what's sometimes called
link |
the hard problem of consciousness
link |
which is what is that nature of that inner
link |
subjective sense we have?
link |
Not just information processing
link |
but feeling something about the information.
link |
What is that inner state of subjectivity physically?
link |
And that's called the hard problem of consciousness
link |
and it's not a extremely well defined question.
link |
Everybody has sort of a sense of what it means
link |
but it's such a hard problem
link |
because you run into paradoxes quite quickly
link |
the more you think about it
link |
and that is exciting also
link |
because it makes us think
link |
actually there's some fundamental,
link |
there's a big thing that we're missing.
link |
The brain is not just a collection of little tricks.
link |
There is a big, big concept.
link |
So that's your sense of the big
link |
because a flip side could be with optogenetics.
link |
You can, there's an engineering question.
link |
Can you turn consciousness on and off like a light switch?
link |
Okay, so here's where exactly consciousness
link |
frames the problem extremely well
link |
and it frames it the following way.
link |
So I told you earlier that we can stimulate
link |
20 or 25 cells in the visual cortex of a mouse
link |
and we can make it behave and we can make its brain act
link |
as if it's seeing something that isn't there.
link |
We have that level of control now.
link |
We can pick out 25 neurons, play in activity
link |
and both behavior and in the brain,
link |
it's as if it's seeing something specific.
link |
Okay, now let's do a thought experiment,
link |
you know, a Gedanken experiment and let's play this out.
link |
Let's say we could do the same thing
link |
for every single neuron in the brain of a human being.
link |
Let's say we had total control
link |
and I could do something like,
link |
I could show you a rich deep color red
link |
and you could look at it and you would be aware
link |
that it's red, but also you might have some feelings
link |
about it, something would be stirred in you,
link |
some subjective sense as you looked at that rich color red
link |
and then I would take away the visual stimulus
link |
and I would, in this thought experiment,
link |
I would, using some hyperoptogenetics,
link |
I would play in exactly the same pattern of activity
link |
in every cell in your brain for as long as was needed,
link |
whatever, 15 seconds, something like that,
link |
that exactly matched what was going on
link |
when you were feeling that inner subjective sense.
link |
Okay, so in that thought experiment,
link |
a question for you is would you be feeling
link |
that same inner subjective sense?
link |
Stimulus is gone, every neuron's doing the same thing
link |
because I'm controlling it.
link |
There's a philosophical question there.
link |
If you ask me specifically, I would say yes.
link |
Okay, good, most people would say that
link |
because it's hard to say no, right?
link |
It's very hard to say no.
link |
If every cell in your brain is doing what it was doing,
link |
what else could be different?
link |
How could? Well, most normal people would say yes.
link |
Of course, philosophers would then start saying no.
link |
They're the ones that say,
link |
I'm in sort of parallel and sorry
link |
if it's a bit of an interruption,
link |
but if there's a robot that's conscious in front of you,
link |
if it appears conscious, then it's conscious.
link |
Like to me, of course, philosophers again speak up
link |
and say, well, no, how do you know it's conscious?
link |
Well, how do you know anything is conscious?
link |
And sort of as normal humans,
link |
we tend to lean on the experience
link |
versus some kind of philosophical concept.
link |
So the great thing about what you just said,
link |
the Turing test is it's very practical.
link |
If it acts conscious, it is conscious.
link |
But I think that's limiting.
link |
I like the thought experiment.
link |
I think it's actually more informative.
link |
And so I'm halfway to the conclusion there,
link |
but let's take it as your answer was yes,
link |
that you would be feeling the same thing.
link |
Okay, now here's where it gets fun.
link |
Now that every cell in your brain knows what it has to do
link |
in the sense that we know it and we're providing it,
link |
your brain cells don't need to be in your head
link |
anymore at all, right?
link |
The only reason they're next to each other,
link |
the only reason they're wired together
link |
is to affect each other, to stimulate or inhibit each other.
link |
But we don't need that anymore
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because optogenetically,
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we're providing that activity pattern
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for as long as needed.
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We're providing the effect of the communication.
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They don't need to be connected anymore.
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They don't even need to be in your head.
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I could spread your neurons all over the continent,
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all over the galaxy,
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and I could still provide the same stimulus pattern
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over 10 or 15 seconds to all those neurons.
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And somewhere Lex Friedman would have to be,
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even though no longer existing as a physical object anymore,
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would be feeling that subjective feeling.
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And it's inescapable
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because it's exactly the same as the previous situation.
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All the neurons have to be spatially,
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like the locality constraint,
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they have to be spatially close to each other.
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And you talk about light opto,
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which is funny because light is the fastest traveling thing
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Maybe let's not put them all over the universe
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because we might get relativistic problems then.
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Let's just keep them out.
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Let's keep all your neurons.
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Let's spread them over North America, okay?
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And let's play them out, same pattern of activity.
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And right, it seems absurd, right?
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There's no way that could be true.
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There's no way that Lex would be feeling
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that internal sense
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if his neurons were spread all over North America.
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And yet it's exactly the same as the previous situation
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where you said, sure.
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So we've got a paradox.
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And this is what makes people think.
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Is it a paradox though, sorry?
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Well, maybe paradox is the wrong word.
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We got a problem because it reveals
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that there's something big about those,
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that internal subjective state that we're not explaining.
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And we don't really have a hope of explaining
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in the near future.
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But don't you think we would still have that?
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It's just the word internal loses meaning,
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but don't you think we still have
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that internal subjective state?
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Or if not, then where the heck is the magic coming from?
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Okay, well, I just think,
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I think one of the problems
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that I think we need to let go of
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is we tend to, outside of the experience of consciousness,
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the hard problem of consciousness,
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we tend to think that we individual humans
link |
are really special.
link |
Not the subjective experience,
link |
but the entirety of it, like the body
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that contains the thing.
link |
So the local, the constraint of all the stuff
link |
has to be together, and it's all mine.
link |
That's a very, I don't know if that has anything to do
link |
with the mechanisms that are creating this.
link |
So in fact, one really nice way to break through that
link |
is to either observe or create consciousness
link |
that spans multiple organisms.
link |
Sort of like, let's say it's not an organism dependent
link |
phenomena, that the phenomena can,
link |
that's just a peculiar way it has evolved on Earth,
link |
but it's a phenomena that doesn't have anything to do
link |
with a specific biological system.
link |
Right, so and we have different parts of our brain exist
link |
and sometimes create complex awarenesses of things
link |
that involve different neurons that are distributed widely
link |
and that need to communicate with each other
link |
to form this joint representation,
link |
this state of consciousness.
link |
But indeed, why do they have to be in the same head?
link |
We don't know why that would be the case that they do.
link |
And so that's a huge unanswered question in the field
link |
is what is it that binds the activity of neurons together
link |
so they can form a joint representation?
link |
And actually this comes back to the dissociation experiment
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we talked about before, where your sense of self
link |
becomes separated from your body.
link |
Those things that were fused in a joint representation,
link |
the same concept, unitary, are now separate.
link |
And in late 2020, we published a paper in Nature
link |
showing how this could be.
link |
We used optogenetics to drive this rhythm
link |
that ketamine and PCP cause in retrosplenial cortex
link |
and we got different parts of the brain to be out of sync
link |
and when they were active, never able to be active
link |
at the same time, never able to form
link |
a joint representation at the same time.
link |
And so we've got a toehold into these questions.
link |
We don't have the answers, but.
link |
And that mimics the dynamics of ketamine effects.
link |
And you're able to find that kind of oscillation.
link |
I see if you get even greater and greater control
link |
with more control over individual neurons
link |
and understanding, like if you think of certain neurons
link |
that having some role to play in the sense of self,
link |
you can play like an orchestra.
link |
That, to create certain degrees of consciousness,
link |
degrees of subjectivity, and thereby understand
link |
what is consciousness.
link |
But by having a very complicated light switch essentially.
link |
And here's the challenge is the nice thing
link |
about the thought experiment is it kind of highlights
link |
that we're gonna hit a point where
link |
we're addressing some very, very fundamental questions.
link |
What allows the activity of two sets of neurons
link |
to become mutually relevant to each other?
link |
This is in some ways maybe one of the deepest
link |
remaining questions in neuroscience is what allows
link |
activity patterns to become relevant to each other?
link |
Do they have to be in sync temporarily?
link |
Do they need to be, is there some other quality
link |
that we don't know about that also needs to be present
link |
to allow cells to fuse together into a joint representation?
link |
Just so I understand, because it feels close
link |
to some very, very deep idea.
link |
So there's a bunch of semi distributed signals
link |
going on in the brain.
link |
And you're saying there could be something
link |
like a theory of everything if one to exist
link |
is to understand why, how and why signals
link |
close to each other start becoming relevant to each other
link |
as part of some very much bigger signal
link |
that they're producing.
link |
How they coordinate, essentially.
link |
Because it's very distributed.
link |
I mean that's a kind of, within a distributed system,
link |
how is order achieved?
link |
And this is a very specific kind of distributed system
link |
that is one of the most intelligent that we're aware of
link |
in the known universe.
link |
In that would maybe be something also,
link |
an understanding of the full conscious experience too.
link |
That this kind of coordination.
link |
How does the coordination between different neurons
link |
that are responsible for sense of self,
link |
how do they begin to form a big picture
link |
that we see as a human experience?
link |
That's really, really interesting.
link |
So uniting the small and the,
link |
I mean that's actually literally theory of everything.
link |
Uniting the small, the sort of the theory of the neuron.
link |
The functioning of the neuron with the big.
link |
Just the functioning of the entire mind.
link |
And I think keeping a toehold in both
link |
at the cellular level of resolution
link |
and the brain wide resolution will be critical.
link |
If you lose touch with either,
link |
I think you'll miss the big insight.
link |
So that's what we're trying to do.
link |
Keeping grounded in the cellular resolution.
link |
Trying to keep the broadest brain wide perspective
link |
and meet in the middle.
link |
Do you think you'll see it in your lifetime?
link |
A major breakthrough in that dimension.
link |
It's very hard to predict what will happen
link |
with big things like this.
link |
If we don't get there,
link |
there'll be plenty of other exciting stuff.
link |
But the other aspect of this whole thing
link |
is that your life is pretty short.
link |
Yeah, that's true.
link |
So first of all, you can die any day.
link |
I tend to try to think about that,
link |
that it ends, it can end any moment
link |
because it really, really can.
link |
And if not, it'll be soon anyway.
link |
Do you think about that?
link |
Do you think about your mortality?
link |
It comes back to what we talked about earlier.
link |
I never think I've done enough
link |
and it's relevant to that for sure.
link |
There's a deadline.
link |
Do you think there's ever going to be a feeling
link |
where you sit back and you're really proud of yourself?
link |
Like, I've done enough.
link |
I've done everything there is.
link |
Because the thing is,
link |
a warrior has some number of battles in them.
link |
And at a certain point, if you're deeply honest,
link |
it's like, well, that was a pretty good run.
link |
As far as runs goes, that was pretty good.
link |
And you can hang up your helmet
link |
and then go sort of drink some ale,
link |
listen to some music with the old lady,
link |
and say, I did pretty good.
link |
You think you'll get there?
link |
You know, with something,
link |
nature always has surprises for us.
link |
The curious mind is always after more.
link |
But biology gives us other rewards.
link |
Children and family, community.
link |
And one can feel good about those things.
link |
Biology is full of rewards.
link |
But do you think about those rewards?
link |
What do you think is the why of those rewards?
link |
What's the meaning of life and this existence?
link |
What's the why of biology?
link |
What does it want from us?
link |
Why are all these cells very busy
link |
putting together an organism
link |
that seems to want to just be in a hurry to do stuff
link |
and survive, but it's not happy being survived.
link |
Like you said, it's curious.
link |
It keeps wanting to get into more trouble.
link |
Yeah, you know, we're clearly designed for that, right?
link |
We're clearly designed to ask why and to answer.
link |
And that, I think, is,
link |
I don't know the meaning of all life.
link |
I think a meaning of our lives is that.
link |
And this is the Aristotelian happiness.
link |
An organism is happy, an animal's happy
link |
if it's performing to its design, right?
link |
If it's doing what it was made for.
link |
Yeah, well, you have to understand, what's the design?
link |
And, you know, who is the designer
link |
and what were they up to and how hard is it?
link |
Do you have to build the whole universe?
link |
And does the design even know what the hell they're doing?
link |
Because, you know, maybe the designer built humans
link |
to find out about themselves.
link |
That's what I would do.
link |
Like, if I had the power to build clones,
link |
I would build a lot of clones
link |
and I would get them into different trouble
link |
to understand, like, what am I designed,
link |
what's this body designed to do?
link |
How far can I go that way?
link |
And then, and I dissociate myself completely
link |
from having any way to know, like, that I know that person.
link |
I mean, I suppose you could do that
link |
in a single person's body, but dissociation, you could.
link |
Yeah, but I do wonder what,
link |
if you look at Earth as a collection of humans,
link |
as a collection of biological organisms,
link |
it seems that we're busy doing something
link |
and it just seems too beautiful and too special
link |
to be a random, a random experiment.
link |
It seems like it's an experiment that's cleverly designed
link |
by some forces of nature
link |
that are beyond our current understanding.
link |
And maybe that's part of our design,
link |
is to keep asking why.
link |
I'm not sure that's part of the design, the answer.
link |
I think we're given just the sufficiently limited
link |
cognitive capability that we know how to long
link |
to find the answer and we lack the ability
link |
to find the answer.
link |
That's basically a summary of your career.
link |
No, I'm just kidding.
link |
And then we give each other Nobel Prizes
link |
for having even an inkling of a good step
link |
towards the right direction.
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Carl, you're an incredible human being.
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I'm a huge fan of who you are as a person,
link |
who you are as a scientist, who you are as a writer.
link |
I just thank you so much.
link |
I'm so honored that you would sit down
link |
and talk to me today.
link |
It's been incredibly fun.
link |
Let's do it again sometime.
link |
Let's do it again.
link |
It's been really great.
link |
Your insights and wit and modesty
link |
are really quite rewarding.
link |
Thank you so much, man.
link |
Thanks for listening to this conversation
link |
with Carl Diceroth.
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To support this podcast,
link |
please check out our sponsors in the description.
link |
And now, let me leave you with some words from Carl Jung.
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Knowing your own darkness is the best method
link |
for dealing with the darkness of other people.
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Thank you for listening and hope to see you next time.