Karl Deisseroth: Depression, Schizophrenia, and Psychiatry
生物与进化心理与人性音乐与艺术技术与编程哲学与宗教
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braindonhumaninterestingcellsablesociallightstateneuronstalkpersondepressionstuffgoingactivityhelptogethertherapydeep
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🎙️ 完整对话（4196 条）
Lex Fridman (00:01.040)
Where are the darkest places you've ever gone in your life?
你一生中最黑暗的地方在哪里？
Lex Fridman (00:07.400)
The following is a conversation with Karl Deisseroth,
以下是与 Karl Deisseroth 的对话，
Lex Fridman (00:10.560)
professor of bioengineering, psychiatry,
生物工程、精神病学教授，
Lex Fridman (00:12.600)
and behavioral sciences at Stanford University.
和斯坦福大学的行为科学。
Lex Fridman (00:15.600)
He's one of the greatest living psychiatrists
他是当今最伟大的精神科医生之一
Lex Fridman (00:18.200)
and neuroscientists in the world.
和世界上的神经科学家。
Lex Fridman (00:20.480)
He's also just a fascinating human being.
他也是一个迷人的人。
Karl Deisseroth (00:23.600)
We discuss both the darkest and the most beautiful places
我们讨论最黑暗和最美丽的地方
Lex Fridman (00:26.400)
that the human mind can take us.
人类的思想可以带领我们。
Karl Deisseroth (00:28.560)
He explores this in his book called
他在他的书《
Lex Fridman (00:31.000)
Projections, A Story of Human Emotions.
预测，人类情感的故事。
Karl Deisseroth (00:33.840)
I highly recommend it.
我强烈推荐它。
Lex Fridman (00:35.760)
It's written masterfully.
写得真高明。
Karl Deisseroth (00:38.300)
This is the Lex Friedman podcast.
这是莱克斯·弗里德曼的播客。
Lex Fridman (00:40.240)
To support it, please check out our sponsors
为了支持它，请查看我们的赞助商
Karl Deisseroth (00:42.160)
in the description.
在描述中。
Lex Fridman (00:43.360)
And now, dear friends, here's Karl Deisseroth.
现在，亲爱的朋友们，这是卡尔·戴瑟罗斯 (Karl Deisseroth)。
Karl Deisseroth (00:48.060)
You open your book called Projections,
你打开一本名为“预测”的书，
Lex Fridman (00:50.600)
A Story of Human Emotions with a few beautiful words
用几句美丽的文字讲述一个人类情感的故事
Karl Deisseroth (00:53.440)
to summarize all of humanity.
来概括全人类。
Lex Fridman (00:56.080)
The book draws insights about the human mind
Karl Deisseroth (00:58.140)
from modern psychiatry and neuroscience.
Lex Fridman (01:01.200)
So if it's okay, let me read a few sentences
Karl Deisseroth (01:03.480)
from the opening.
Lex Fridman (01:05.000)
You gotta give props to beautiful writing when I see it.
Karl Deisseroth (01:08.800)
Quote, in the art of weaving, warp threads are structural
Lex Fridman (01:13.920)
and strong and anchored at the origin,
Karl Deisseroth (01:16.960)
creating a frame for crossing fibers
Lex Fridman (01:19.200)
as the fabric is woven.
Karl Deisseroth (01:22.040)
Projecting across the advancing edge into free space,
Lex Fridman (01:25.200)
warp threads bridge the formed past
Karl Deisseroth (01:27.840)
to the ragged present to the yet featureless future.
Lex Fridman (01:32.000)
Yet featureless future, well done, well done, sir.
Karl Deisseroth (01:35.720)
The tapestry of the human story has its own warp threads,
Lex Fridman (01:38.860)
rooted deep in the gorges of East Africa,
Karl Deisseroth (01:41.560)
connecting the shifting textures of human life
Lex Fridman (01:44.280)
over millions of years, spanning pictographs
Karl Deisseroth (01:47.760)
backdroped by crevice ice, by angulated forestry,
Lex Fridman (01:52.680)
by stone and steel, and by glowing rare earths.
Karl Deisseroth (01:56.040)
The inner workings of the mind give form to these threads,
Lex Fridman (01:59.420)
creating a framework within us,
Karl Deisseroth (02:01.960)
upon which the story of each individual can come into being.
Lex Fridman (02:05.760)
Personal grain and color arise from the crossed threads
Karl Deisseroth (02:08.920)
of our moments and experiences, the fine weft of life,
Lex Fridman (02:13.440)
embedding and obscuring the underlying scaffold
Karl Deisseroth (02:16.600)
with intricate and sometimes lovely detail.
Lex Fridman (02:19.520)
Here are stories of this fabric fraying in those who are ill.
Karl Deisseroth (02:24.520)
In the minds of people for whom the warp
Lex Fridman (02:26.840)
is exposed and raw and revealing.
Lex Fridman (02:31.180)
What have you learned about human beings,
Lex Fridman (02:33.020)
human nature and the human mind,
Karl Deisseroth (02:34.560)
from those who suffer from psychiatric maladies,
Lex Fridman (02:38.240)
for those for whom this fabric is warped?
Lex Fridman (02:41.240)
And one thing we learn as biologists
Lex Fridman (02:43.420)
is that when something breaks,
Karl Deisseroth (02:45.560)
you see what the original unbroken part was for.
Lex Fridman (02:50.800)
And we see this in genetics, we see this in biochemistry.
Karl Deisseroth (02:54.040)
It's known that when you have a mutated gene,
Lex Fridman (02:57.440)
sometimes the gene is turned up in strength
Karl Deisseroth (02:59.900)
or turned down in strength,
Lex Fridman (03:01.320)
and that lets you see what it was originally for.
Karl Deisseroth (03:03.280)
You can infer true function from dysfunction.
Lex Fridman (03:06.940)
And this is a theme that I thought needed to be shared
Lex Fridman (03:11.160)
and needed to be made communicable
Lex Fridman (03:13.320)
to the lay public, to everybody.
Karl Deisseroth (03:15.080)
People who, which is, I think, almost all of us,
Lex Fridman (03:19.440)
who think and care about the inner workings of our mind,
Lex Fridman (03:21.800)
but who also care for those who have been suffering,
Lex Fridman (03:26.360)
who have mental health disorders, who face challenges.
Lex Fridman (03:31.920)
But then more broadly,
Lex Fridman (03:33.760)
it's a very much larger story than the present.
Karl Deisseroth (03:36.720)
There's a story to be told
Lex Fridman (03:39.960)
where the protagonist really is the human mind.
Lex Fridman (03:42.200)
And that was one thing I wanted to share as well
Lex Fridman (03:44.400)
in projections, is that broader story,
Lex Fridman (03:47.380)
but still anchored in the moment of patients,
Lex Fridman (03:50.480)
of people, of experiences of the moment.
Karl Deisseroth (03:53.960)
Is there a clear line between dysfunction and function,
Lex Fridman (03:57.320)
disorder and order?
Karl Deisseroth (03:59.840)
This is always debated in psychiatry,
Lex Fridman (04:02.440)
probably more so than any other medical specialty.
Karl Deisseroth (04:06.440)
I'm a psychiatrist, I treat patients still.
Lex Fridman (04:09.680)
I see acutely ill people who come to the emergency room
Karl Deisseroth (04:14.320)
where there's no doubt that this is not something
Lex Fridman (04:16.520)
that's working well, where the manifestation of disease
Karl Deisseroth (04:19.980)
is so powerful, where the person is suffering so greatly,
Lex Fridman (04:22.980)
where they cannot continue as they are.
Lex Fridman (04:26.680)
But of course, it's a spectrum,
Lex Fridman (04:28.000)
and there are people who are closer
Karl Deisseroth (04:30.000)
to the realm of being able to work okay in their jobs,
Lex Fridman (04:34.560)
but suffer from some small dysfunction.
Lex Fridman (04:36.280)
And everywhere in between.
Lex Fridman (04:37.860)
In psychiatry, we're careful to say
Karl Deisseroth (04:39.400)
we don't call it a disease or a disorder
Lex Fridman (04:41.160)
unless there's a disruption
Karl Deisseroth (04:43.200)
in social or occupational functioning.
Lex Fridman (04:46.360)
But of course, psychiatry has a long way to go
Karl Deisseroth (04:49.320)
in terms of developing quantitative tests.
Lex Fridman (04:51.800)
We don't have blood draws, we don't have imaging studies
Karl Deisseroth (04:55.840)
that we can use to diagnose.
Lex Fridman (04:57.800)
And so that line, ultimately, that you're asking about
Karl Deisseroth (05:00.920)
between order and disorder, function and dysfunction,
Lex Fridman (05:04.440)
it's operational at the moment.
Lex Fridman (05:05.800)
How are things working?
Lex Fridman (05:08.440)
Can we just linger on the terms for a second?
Lex Fridman (05:10.800)
So this disease, dysfunction,
Lex Fridman (05:15.440)
how careful should we be using those words?
Karl Deisseroth (05:17.960)
Can we just, even in this conversation,
Lex Fridman (05:21.560)
from a sort of technical perspective,
Lex Fridman (05:24.400)
but also a human perspective,
Lex Fridman (05:26.560)
how quick should we be
Karl Deisseroth (05:31.360)
in saying that schizophrenia, depression, autism,
Lex Fridman (05:38.920)
as we kind of go down across the spectrum
Karl Deisseroth (05:42.860)
of different maladies,
Lex Fridman (05:44.680)
to use the word dysfunction and disease?
Karl Deisseroth (05:48.720)
I would say to give ourselves license
Lex Fridman (05:50.760)
to capture the whole spectrum, let's say disorder,
Karl Deisseroth (05:53.000)
because that captures truly, I think, the essence of it,
Lex Fridman (05:57.160)
which is we need to talk about it when it's not working,
Karl Deisseroth (05:59.680)
when there's disorder.
Lex Fridman (06:00.680)
And that's the fairest and most inclusive term to use.
Lex Fridman (06:08.040)
So is it fair to assume that basically every member
Lex Fridman (06:12.600)
of the human species suffers from a large number
Lex Fridman (06:15.840)
of disorders then?
Lex Fridman (06:17.380)
Well, we just have to pick which ones are debilitating
Lex Fridman (06:22.040)
for each person?
Lex Fridman (06:23.080)
You know, if you look at the numbers,
Karl Deisseroth (06:25.200)
there are, if you look at how our mental health disorders
Lex Fridman (06:29.880)
are currently defined,
Karl Deisseroth (06:30.840)
you can look at population prevalence values
Lex Fridman (06:34.560)
for all these disorders,
Lex Fridman (06:35.560)
and you can come up with estimates
Lex Fridman (06:37.880)
that somebody will have a lifetime prevalence
Karl Deisseroth (06:42.200)
of having a psychiatric disorder
Lex Fridman (06:44.680)
that approaches 25% or so.
Lex Fridman (06:46.960)
And so that's, and in some studies it could be more,
Lex Fridman (06:50.200)
some studies it could be less.
Lex Fridman (06:51.480)
Now, what do we do with that number?
Lex Fridman (06:53.300)
What does that mean?
Lex Fridman (06:54.140)
And in some ways, that's the essence
Lex Fridman (06:55.560)
of what I was hoping to approach with the book,
Karl Deisseroth (06:58.920)
is to reflect on this spectrum that exists
Lex Fridman (07:01.080)
for all the disorders.
Karl Deisseroth (07:02.040)
There is, and taking nothing away from the severity
Lex Fridman (07:05.480)
and the suffering that comes at the extreme end
Karl Deisseroth (07:07.880)
of these illnesses, but nearly every one of them exists
Lex Fridman (07:10.480)
on a spectrum of severity, from nearly functional
Karl Deisseroth (07:14.920)
to completely dysfunctional, life threatening,
Lex Fridman (07:17.320)
and even fatal.
Lex Fridman (07:19.240)
And so that number, 25%, more or less,
Lex Fridman (07:22.520)
it doesn't capture that spectrum of severity.
Lex Fridman (07:27.640)
To look at that number, where do those numbers come from?
Lex Fridman (07:30.480)
Is it self report?
Lex Fridman (07:31.320)
Is it people who show up and say, I need help?
Lex Fridman (07:35.080)
Is it somebody else that points out that person needs help?
Karl Deisseroth (07:38.720)
Or is it like estimates that even go beyond that
Lex Fridman (07:41.160)
for people who don't ask for help
Lex Fridman (07:42.880)
or are suffering quietly alone?
Lex Fridman (07:45.640)
When you look at self report numbers,
Karl Deisseroth (07:47.600)
then those numbers get even higher, beyond 25% or more.
Lex Fridman (07:52.440)
Those, the most rigorous studies are done
Karl Deisseroth (07:55.780)
with structured psychiatric interviews
Lex Fridman (07:57.600)
where people who are trained in eliciting symptoms carefully
Karl Deisseroth (08:02.360)
do complete psychiatric inventories of individuals.
Lex Fridman (08:05.520)
And these are time consuming laborious studies
Karl Deisseroth (08:09.520)
that are not often repeated.
Lex Fridman (08:10.860)
When they're done, they're done well.
Lex Fridman (08:13.160)
But very often you'll see a report or something
Lex Fridman (08:16.320)
in the news of a very high number
Karl Deisseroth (08:19.020)
for some disorder or symptom.
Lex Fridman (08:22.080)
And very often, if it's shockingly high,
Karl Deisseroth (08:24.500)
that's coming from a self report of a person.
Lex Fridman (08:27.880)
And so that's another issue that we have, again,
Karl Deisseroth (08:31.120)
take nothing away from the severity and reality
Lex Fridman (08:33.600)
and biological nature of these disorders,
Karl Deisseroth (08:35.840)
which are very genetic, very, you know,
Lex Fridman (08:37.520)
we understand that these are very biological.
Lex Fridman (08:40.920)
And yet, we lack right now the lab tests
Lex Fridman (08:43.520)
and the blood draws to make the diagnoses.
Karl Deisseroth (08:45.440)
We'll talk about it, just how biological they are,
Lex Fridman (08:48.240)
because that too is a mystery.
Karl Deisseroth (08:51.920)
You know, in terms of from our perspective
Lex Fridman (08:53.760)
of how to probe into the disease,
Lex Fridman (08:55.360)
how to understand it, how to help it.
Lex Fridman (08:57.640)
So some of it could be neurobiological,
Karl Deisseroth (09:00.000)
some of it could be just the dance
Lex Fridman (09:03.920)
of human emotion and interaction.
Lex Fridman (09:05.680)
And it's like, is love when it works
Lex Fridman (09:11.160)
and is love when it breaks down biological
Lex Fridman (09:14.400)
or is it something else?
Lex Fridman (09:15.520)
So we're gonna talk about it.
Lex Fridman (09:17.320)
But let me just like to linger in terms of disorder.
Lex Fridman (09:21.560)
What about genius?
Karl Deisseroth (09:23.520)
You know, that sort of cliche saying,
Lex Fridman (09:25.760)
like the madness and genius
Karl Deisseroth (09:28.100)
that they kind of dance together.
Lex Fridman (09:30.720)
What about if the thing we see as disorder
Lex Fridman (09:33.360)
is actually genius, unheard or misunderstood?
Lex Fridman (09:38.560)
Well, here again, the numbers help us.
Lex Fridman (09:40.280)
And here's where being rigorous
Lex Fridman (09:41.720)
and quantitative actually really helps.
Karl Deisseroth (09:43.280)
If you look at disorders like autism
Lex Fridman (09:46.160)
and bipolar disorder and eating disorders,
Karl Deisseroth (09:50.240)
anorexia nervosa, for example,
Lex Fridman (09:53.160)
these, you know, particularly bipolar and anorexia,
Karl Deisseroth (09:56.920)
these can be fatal, they can cause immense suffering,
Lex Fridman (10:00.760)
but they are heavily genetic, all three of these.
Lex Fridman (10:04.480)
And what's very interesting is each one of these three
Lex Fridman (10:07.760)
is actually correlated positively,
Karl Deisseroth (10:10.440)
positively with measures of intelligence,
Lex Fridman (10:13.680)
of educational attainment, and even of income.
Lex Fridman (10:18.240)
And so you look at this severe disorders
Lex Fridman (10:20.840)
in many cases causing quite an immense morbidity
Lex Fridman (10:25.480)
and mortality, and yet they are positively correlated
Lex Fridman (10:28.920)
at the population level with positive things.
Lex Fridman (10:31.200)
Can you say the three again, autism?
Lex Fridman (10:33.640)
Autism, anorexia, and bipolar disorder.
Karl Deisseroth (10:37.320)
Bipolar, right.
Lex Fridman (10:38.400)
What's that book, forgot the book name,
Lex Fridman (10:40.340)
but is intelligence a burden?
Lex Fridman (10:45.240)
Well, you know, people can get into trouble
Karl Deisseroth (10:48.080)
when they think they're smarter than they are,
Lex Fridman (10:49.560)
I will say that.
Karl Deisseroth (10:51.440)
I don't know.
Lex Fridman (10:52.440)
Sometimes, like, in the deepest meaning of that statement,
Karl Deisseroth (10:56.840)
I think ignorance is bliss.
Lex Fridman (10:58.220)
I'm a big fan of Prince Mishkin from The Idiot
Lex Fridman (11:00.940)
and Aliosha from Brother Karamazov.
Lex Fridman (11:04.420)
Optimism can be seen as naivety and dumbness,
Lex Fridman (11:08.120)
but I think it's a kind of deep intelligence.
Lex Fridman (11:13.200)
Maybe inability to reason sort of about the mechanics
Karl Deisseroth (11:17.920)
of the world, but instead kind of feel the world.
Lex Fridman (11:20.680)
It seems like that's one of the paths to happiness.
Karl Deisseroth (11:24.280)
There is.
Lex Fridman (11:25.120)
How much you think versus how much you feel,
Karl Deisseroth (11:26.880)
this comes up all the time.
Lex Fridman (11:28.160)
In medicine, we encounter this all the time.
Karl Deisseroth (11:31.640)
Day after day, you encounter the abyss of suffering
Lex Fridman (11:36.120)
from patients.
Lex Fridman (11:36.960)
How much do you let yourself feel?
Lex Fridman (11:39.500)
Or how much do you make it abstract and objective
Lex Fridman (11:44.560)
and try to make it clinical?
Lex Fridman (11:46.580)
And that range, how you're able to move yourself
Karl Deisseroth (11:49.080)
on that spectrum, is very important for survival
Lex Fridman (11:52.960)
as a physician, and the way you protect yourself
Lex Fridman (11:57.800)
and your feelings turns out to be very important.
Lex Fridman (12:00.200)
You quote Finnegan's Wake, mad props for that,
Karl Deisseroth (12:04.120)
James Joyce book.
Lex Fridman (12:05.200)
I took a class in James Joyce in college.
Karl Deisseroth (12:07.740)
I think I read parts of Finnegan's Wake.
Lex Fridman (12:10.600)
I might have been on drugs of some kind,
Karl Deisseroth (12:12.440)
or I somehow got an A in that class,
Lex Fridman (12:15.720)
which probably refers to some kind of curve
Karl Deisseroth (12:18.000)
where nobody understood anything.
Lex Fridman (12:19.800)
The only thing I understood and really enjoyed
Karl Deisseroth (12:21.420)
is his short stories, The Dead, and then Ulysses.
Lex Fridman (12:24.720)
I kind of, I think, read a few Cliff Notes
Karl Deisseroth (12:27.360)
that kind of got to the point,
Lex Fridman (12:28.880)
and then Finnegan's Wake was just a hopeless.
Karl Deisseroth (12:34.260)
For people who haven't looked at it,
Lex Fridman (12:35.680)
maybe you can elucidate to me better,
Lex Fridman (12:38.180)
but I felt like I was reading things, words,
Lex Fridman (12:43.400)
and the words made sense, like standing next to each other,
Lex Fridman (12:47.760)
but when you kind of read for a while,
Lex Fridman (12:51.520)
you realize you didn't actually understand
Karl Deisseroth (12:53.000)
anything that was said.
Lex Fridman (12:54.080)
Right, but did you have a feeling, though?
Karl Deisseroth (12:55.880)
That's one thing I found interesting about Finnegan's Wake.
Lex Fridman (12:59.280)
I never fully understood it,
Lex Fridman (13:00.600)
but the words caused feelings in me,
Lex Fridman (13:02.240)
which I found fascinating,
Lex Fridman (13:03.880)
and sometimes I couldn't predict it
Lex Fridman (13:06.840)
from the semantic black and white context
Karl Deisseroth (13:09.680)
of what I was seeing in front of me on the page,
Lex Fridman (13:11.960)
but the rhythm or the melody
Karl Deisseroth (13:13.240)
would make me feel certain ways,
Lex Fridman (13:14.520)
and that was what I always was intrigued by with Joyce.
Karl Deisseroth (13:17.600)
Of course, that was his, he existed on a spectrum, too,
Lex Fridman (13:20.880)
and he wrote, as you say, more accessible works.
Karl Deisseroth (13:24.920)
I learned a lot about Irish history
Lex Fridman (13:26.440)
from Portrait of the Artist as a Young Man,
Lex Fridman (13:28.740)
and there was just, he could be as objective
Lex Fridman (13:31.120)
as he wanted to be, but then when he let himself loose,
Karl Deisseroth (13:35.240)
he was in this realm where the words
Lex Fridman (13:37.780)
had their own purpose separate from semantic meaning
Karl Deisseroth (13:42.680)
from their dry dictionary definition.
Lex Fridman (13:46.120)
You know, there's a funny story that was told,
Karl Deisseroth (13:48.360)
doesn't matter if it's true or not,
Lex Fridman (13:49.700)
but they said that James Joyce, when he was young,
Karl Deisseroth (13:53.000)
when he was in his teen years,
Lex Fridman (13:54.360)
would go around sort of Ireland drinking and so on
Lex Fridman (13:57.800)
and telling everybody that he's going to be one of,
Lex Fridman (14:00.040)
if not the greatest writers of the 20th century,
Lex Fridman (14:03.040)
and he turned out to be that.
Lex Fridman (14:06.980)
So I always think about that little story
Karl Deisseroth (14:09.740)
that somebody told me,
Lex Fridman (14:11.700)
because I have a lot of people come up to me,
Karl Deisseroth (14:14.160)
including myself, I'm a bit of a dreamer.
Lex Fridman (14:17.880)
You get into certain moods where you say
Karl Deisseroth (14:19.480)
I'm going to be the greatest anything ever.
Lex Fridman (14:22.780)
You get people tell you this, especially young people,
Lex Fridman (14:27.200)
and it kind of, it makes me feel all kinds of ways,
Lex Fridman (14:32.200)
but that story reminds me that you just might be
Karl Deisseroth (14:36.240)
one of the greatest writers of the 21st century,
Lex Fridman (14:39.400)
for example, if somebody were to tell me that,
Lex Fridman (14:41.440)
and don't immediately disregard that,
Lex Fridman (14:44.960)
because one of the people that say that,
Karl Deisseroth (14:47.320)
that's almost like a precondition,
Lex Fridman (14:49.320)
that's a good requirement just to believe in yourself.
Karl Deisseroth (14:51.600)
Maybe it's not a full requirement,
Lex Fridman (14:53.080)
but it's an interesting story.
Karl Deisseroth (14:57.120)
I think when someone tells you that,
Lex Fridman (14:58.300)
then it creates, one sees an opportunity,
Lex Fridman (15:02.880)
and then it would be a tragedy
Lex Fridman (15:03.960)
if the opportunity weren't captured, right?
Lex Fridman (15:05.560)
And so then that creates some impetus,
Lex Fridman (15:09.080)
some motivation to do something good.
Karl Deisseroth (15:12.000)
I think the mind, it's like, I guess that's what
Lex Fridman (15:16.320)
books or whatever, I don't even know if it's a book,
Karl Deisseroth (15:18.820)
The Secret plugs into, they kind of make
Lex Fridman (15:21.320)
a whole industry out of it.
Lex Fridman (15:23.440)
But there is something about the mind
Lex Fridman (15:26.200)
believing something, making it a reality.
Karl Deisseroth (15:28.400)
It is just time and time again with Steve Jobs,
Lex Fridman (15:32.040)
your belief in yourself, your belief in an idea,
Karl Deisseroth (15:35.840)
sort of embracing the me versus the world,
Lex Fridman (15:39.080)
embracing the madness of this idea
Lex Fridman (15:42.000)
and making it a life pursuit,
Lex Fridman (15:44.420)
somehow morphs reality around you
Karl Deisseroth (15:46.440)
for some tiny fraction of the population.
Lex Fridman (15:48.620)
For everybody else, you descend into
Karl Deisseroth (15:54.080)
all the beautiful ways that failure
Lex Fridman (15:56.680)
materializes in our lifetime.
Karl Deisseroth (15:59.400)
Well, you know, you mentioned love earlier.
Lex Fridman (16:00.920)
I mean, that's a great example of how
Lex Fridman (16:02.800)
belief in something makes it real, right?
Lex Fridman (16:05.360)
It's not reasonable on the face of it,
Lex Fridman (16:08.200)
but because you believe it's reasonable,
Lex Fridman (16:09.560)
then it actually does become reasonable,
Lex Fridman (16:10.920)
and then it is real.
Lex Fridman (16:11.760)
And so that's a good example.
Karl Deisseroth (16:13.120)
That doesn't happen.
Lex Fridman (16:13.960)
I'm also in a bioengineering department.
Karl Deisseroth (16:15.960)
We don't imagine that a bridge is soundly built
Lex Fridman (16:18.480)
and then it is soundly built.
Karl Deisseroth (16:19.520)
That's something that, it doesn't come up
Lex Fridman (16:21.760)
in too many realms of human existence,
Lex Fridman (16:23.280)
but love is one of them.
Lex Fridman (16:24.520)
And the ability to have a fixed idea
Lex Fridman (16:29.560)
and to say it's true, and then it is true.
Lex Fridman (16:32.400)
A bridge is a kind of manifestation of love.
Lex Fridman (16:34.600)
So maybe it does work a little bit,
Lex Fridman (16:36.000)
but it can break down like Chernobyl did.
Karl Deisseroth (16:38.400)
You can't just say it's safe.
Lex Fridman (16:40.200)
You have to also prove it's safe.
Lex Fridman (16:43.240)
But on Finnegan's Wake, I think,
Lex Fridman (16:45.880)
maybe correct me if I'm wrong,
Karl Deisseroth (16:47.120)
you're using kind of Finnegan's Wake
Lex Fridman (16:48.760)
to give one perspective on what madness is,
Karl Deisseroth (16:52.320)
of what's going on in the mind.
Lex Fridman (16:53.760)
How much of that is that we're simply unable
Karl Deisseroth (16:59.600)
to communicate with the person
Lex Fridman (17:01.000)
on the other side of their mind?
Karl Deisseroth (17:03.800)
Like there's almost like a little person inside the brain
Lex Fridman (17:07.560)
and they have some circuitry that's used
Karl Deisseroth (17:10.360)
to communicate emotion, communicate ideas
Lex Fridman (17:12.840)
to the outside world.
Lex Fridman (17:14.040)
And there's something about that circuitry
Lex Fridman (17:15.640)
that makes it difficult to communicate
Karl Deisseroth (17:17.200)
with the little person on the other side.
Lex Fridman (17:18.880)
So if you look at what shows up in schizophrenia,
Karl Deisseroth (17:21.200)
with many cases, what we call thought disorders,
Lex Fridman (17:25.160)
what we call the individual speech symptoms
Karl Deisseroth (17:30.040)
of schizophrenia, Finnegan's Wake is loaded with them.
Lex Fridman (17:33.720)
And it's just full of them.
Karl Deisseroth (17:35.160)
We talk about clang associations in schizophrenia
Lex Fridman (17:39.880)
where the word that is said echoes in some way
Karl Deisseroth (17:44.000)
the previous word.
Lex Fridman (17:44.840)
And we call that a clang association
Karl Deisseroth (17:46.920)
because there's no other reason
Lex Fridman (17:47.880)
than the similarity of the sound,
Karl Deisseroth (17:49.320)
like a clang of a garage door being hit.
Lex Fridman (17:53.200)
And it has a, and sometimes it's not even a word,
Lex Fridman (17:56.600)
and we call that a neologism, a new word being created.
Lex Fridman (17:59.960)
And of course, Finnegan's Wake is full of that.
Lex Fridman (18:02.200)
And then we also, in schizophrenia,
Lex Fridman (18:05.200)
where there's what we call loose associations
Karl Deisseroth (18:06.960)
or tangential thought processes,
Lex Fridman (18:10.000)
of course, full of that where things just go off
Karl Deisseroth (18:11.840)
in directions that are not linear or logical.
Lex Fridman (18:15.280)
And you can't read Finnegan's Wake, I think,
Karl Deisseroth (18:18.640)
without, certainly as a psychiatrist,
Lex Fridman (18:21.480)
you can't read it without thinking about schizophrenia.
Lex Fridman (18:24.120)
And then when we look at the families of people
Lex Fridman (18:27.440)
with schizophrenia, and Joyce was no exception,
Karl Deisseroth (18:30.560)
there very often are people within the family
Lex Fridman (18:32.560)
who are on the spectrum.
Karl Deisseroth (18:33.840)
Some have it.
Lex Fridman (18:34.960)
Some are able to see it from a distance,
Karl Deisseroth (18:39.120)
from a safe distance.
Lex Fridman (18:40.840)
There's an association between schizophrenia
Lex Fridman (18:43.040)
and what we call schizotypal personality disorder
Lex Fridman (18:46.600)
where people are not quite in this severe state
Karl Deisseroth (18:49.880)
of schizophrenia but have some magical thinking,
Lex Fridman (18:51.880)
have some unusual thought patterns.
Karl Deisseroth (18:54.560)
Very often, those are family members
Lex Fridman (18:56.040)
of people with schizophrenia.
Lex Fridman (18:57.640)
So this points to this, again, to this idea
Lex Fridman (19:00.160)
that there is a range, even along this very severe,
Karl Deisseroth (19:05.800)
very genetic biological illness that human beings dwell
Lex Fridman (19:09.440)
on different spots along that spectrum.
Karl Deisseroth (19:11.480)
I should mention that we have my friend, Sergey,
Lex Fridman (19:14.360)
pulling up stuff, young Sergey or old Sergey,
Karl Deisseroth (19:16.840)
I don't know what to call you,
Lex Fridman (19:17.760)
but there's drafts of Finnegan's Wake.
Karl Deisseroth (19:21.720)
Yeah, I actually saw pictures of this from,
Lex Fridman (19:25.480)
I think it was on Instagram or something.
Karl Deisseroth (19:27.080)
These are early drafts of Finnegan's Wake.
Lex Fridman (19:29.240)
And it's so beautiful to see.
Karl Deisseroth (19:30.400)
For people who are just listening,
Lex Fridman (19:31.960)
there's just random paragraphs and writing
Karl Deisseroth (19:34.760)
all over the page with stuff crossed out.
Lex Fridman (19:37.080)
And it's great to see that Joyce himself
Karl Deisseroth (19:40.280)
was thinking in this kind of way
Lex Fridman (19:41.920)
as you're putting it together.
Lex Fridman (19:44.760)
How much do you think he was thinking
Lex Fridman (19:45.960)
about the schizophrenic mind?
Karl Deisseroth (19:48.320)
I think a lot.
Lex Fridman (19:49.160)
I think it's known that his daughter suffered
Karl Deisseroth (19:51.520)
from schizophrenia.
Lex Fridman (19:52.880)
And this is, what's depicted here on the page
Karl Deisseroth (19:56.840)
is something that I'm sure he either felt himself
Lex Fridman (1:00:01.480)
hopefully to make some headway on this question
Karl Deisseroth (1:00:03.280)
with causality and that's the one thing
Lex Fridman (1:00:07.320)
that optogenetics provides us this way of using light
Karl Deisseroth (1:00:10.120)
that we develop to control cells.
Lex Fridman (1:00:12.160)
This is an untapped, relatively untapped
Karl Deisseroth (1:00:15.440)
at this broad brain wide scale
Lex Fridman (1:00:17.160)
and hopefully we can get there in the near future.
Lex Fridman (1:00:18.880)
But I would say that the answer may be in the data
Lex Fridman (1:00:22.640)
but we don't know how to find it.
Karl Deisseroth (1:00:24.360)
Well, there's this interactive element
Lex Fridman (1:00:26.000)
like where you can cause stuff that's really powerful
Karl Deisseroth (1:00:28.720)
because you get to, I mean,
Lex Fridman (1:00:31.720)
as opposed to collecting data passively,
Karl Deisseroth (1:00:33.480)
you get your collecting data actively.
Lex Fridman (1:00:35.240)
So can you maybe describe one of the many things
Karl Deisseroth (1:00:38.400)
you're known for, one of the big things
Lex Fridman (1:00:40.960)
is called optogenetics, what is it?
Karl Deisseroth (1:00:43.560)
Optogenetics is a way of causing things to happen.
Lex Fridman (1:00:46.160)
It's a way of determining what actually matters
Karl Deisseroth (1:00:50.240)
in terms of the activity of the brain
Lex Fridman (1:00:52.200)
for the amazing things it does,
Karl Deisseroth (1:00:55.040)
sensation, cognition, action.
Lex Fridman (1:00:58.440)
And what it does is it provides activity.
Karl Deisseroth (1:01:01.720)
It's a way of playing in, if you will,
Lex Fridman (1:01:04.320)
activity patterns into precisely defined cells.
Lex Fridman (1:01:07.560)
And the way we do it is pretty cool, I think.
Lex Fridman (1:01:09.600)
It's, you know, right away there's a problem
Lex Fridman (1:01:12.260)
if you think about how do we do this?
Lex Fridman (1:01:13.360)
How could we play in well defined activity patterns
Lex Fridman (1:01:16.360)
and provide a stream of activity into this cell
Lex Fridman (1:01:20.080)
and that cell and that cell but not these other cells?
Lex Fridman (1:01:22.680)
So just for context, we're talking about the brains
Lex Fridman (1:01:25.920)
of mice, monkeys, humans,
Lex Fridman (1:01:32.040)
and then the goal is to try to control accurately
Lex Fridman (1:01:35.880)
the behavior of a single neuron
Lex Fridman (1:01:38.280)
and then to be able to monitor single collection
Lex Fridman (1:01:42.760)
of single neurons to then say, well,
Karl Deisseroth (1:01:45.840)
to draw some deeper insight about the origins,
Lex Fridman (1:01:50.600)
first of all, the function of different parts of the brain,
Karl Deisseroth (1:01:53.280)
different neurons, different kinds of neurons,
Lex Fridman (1:01:54.960)
but also the origins of the big things,
Karl Deisseroth (1:01:57.400)
the flap of the butterfly wing that leads
Lex Fridman (1:02:00.080)
to an actual behavioral thing.
Karl Deisseroth (1:02:03.480)
Yeah, so if you could, exactly, so if you could turn on
Lex Fridman (1:02:06.000)
or off the brain or parts of the brain or cell types
Karl Deisseroth (1:02:10.560)
or individual cells at the natural rate and rhythm
Lex Fridman (1:02:15.560)
and timing of normal brain activity,
Karl Deisseroth (1:02:18.880)
that would be immensely valuable
Lex Fridman (1:02:19.840)
because you could determine what actually mattered,
Lex Fridman (1:02:21.800)
what could cause complex things to happen
Lex Fridman (1:02:23.880)
and what could prevent complex things from happening
Karl Deisseroth (1:02:26.000)
in a specific way.
Lex Fridman (1:02:27.720)
But right away, you've got a problem if you wanna do this
Lex Fridman (1:02:29.880)
and scientists, neuroscientists have wanted to do this
Lex Fridman (1:02:33.280)
for a long time.
Karl Deisseroth (1:02:34.240)
Francis Crick of Double Helix of DNA fame,
Lex Fridman (1:02:37.240)
he wrote a famous paper in 1999.
Karl Deisseroth (1:02:40.560)
He got interested in neuroscience later in life
Lex Fridman (1:02:43.080)
and he said, what we need in neuroscience is a way
Karl Deisseroth (1:02:47.680)
that we could turn on or off the activity
Lex Fridman (1:02:50.560)
of individual types of neurons in a behaving animal.
Lex Fridman (1:02:56.640)
And he even said the ideal signal would be light
Lex Fridman (1:03:00.200)
because it would be fast, it could penetrate
Karl Deisseroth (1:03:04.560)
through the brain to some extent.
Lex Fridman (1:03:07.800)
And he had no idea how to do it.
Karl Deisseroth (1:03:10.800)
He said this would probably be very farfetched,
Lex Fridman (1:03:13.640)
but it would be a good thing.
Lex Fridman (1:03:15.480)
And so that's what you're actually saying,
Lex Fridman (1:03:17.120)
like if you wanna do this kind of thing
Lex Fridman (1:03:19.280)
and you imagine like, how do I get inside the brain?
Lex Fridman (1:03:22.800)
It's pretty difficult.
Karl Deisseroth (1:03:24.560)
It's pretty difficult and then even once you get in,
Lex Fridman (1:03:26.640)
it's hard because all brain cells are electrical,
Karl Deisseroth (1:03:29.160)
all neurons are electrically activated.
Lex Fridman (1:03:31.440)
And so if you wanted to use electricity
Karl Deisseroth (1:03:34.740)
as what you were putting in,
Lex Fridman (1:03:37.300)
you won't have any specificity at all.
Karl Deisseroth (1:03:39.480)
If you have an electrode, a wire,
Lex Fridman (1:03:41.360)
and you put it in the brain and you send current through it,
Karl Deisseroth (1:03:44.360)
all the cells near the electrode will be stimulated.
Lex Fridman (1:03:48.280)
That's like trying to control fish
Karl Deisseroth (1:03:50.160)
by spraying them with water.
Lex Fridman (1:03:53.160)
Yeah, right, because there's already a lot of electricity
Karl Deisseroth (1:03:56.280)
going around anyway and you're adding more,
Lex Fridman (1:03:58.240)
but there's no specificity
Karl Deisseroth (1:04:00.800)
even among the different kinds of cells either
Lex Fridman (1:04:02.560)
because all around the wire that you've put in,
Karl Deisseroth (1:04:05.040)
there are gonna be so many different cells
Lex Fridman (1:04:06.820)
doing totally different things,
Karl Deisseroth (1:04:08.520)
many of them in opposition to each other.
Lex Fridman (1:04:10.520)
We know that's one way the brain is set up.
Karl Deisseroth (1:04:12.260)
There are parts of the brain
Lex Fridman (1:04:14.240)
where neurons side by side
Karl Deisseroth (1:04:16.000)
are doing completely different things
Lex Fridman (1:04:17.360)
and maybe even antagonistic to each other.
Lex Fridman (1:04:20.240)
So what do you do?
Lex Fridman (1:04:21.080)
How do you play in activity with any kind of specificity?
Karl Deisseroth (1:04:23.700)
Well, what you do is use,
Lex Fridman (1:04:26.440)
what we found is what you can do is
Karl Deisseroth (1:04:28.840)
make some cells responsive to light.
Lex Fridman (1:04:33.200)
Now, normally no cells deep in the brain
Karl Deisseroth (1:04:36.700)
really respond to light.
Lex Fridman (1:04:37.640)
They're not built for that.
Karl Deisseroth (1:04:39.120)
There's no reason for them to respond to light in there,
Lex Fridman (1:04:42.360)
which is a great situation to start with
Karl Deisseroth (1:04:45.240)
because any light sensitivity you can provide to some cells
Lex Fridman (1:04:48.960)
will be a huge signal above the noise.
Lex Fridman (1:04:51.560)
And so that's what we do with optogenetics.
Lex Fridman (1:04:53.520)
We take genes, bits of DNA from microbes,
Karl Deisseroth (1:04:59.320)
single celled organisms,
Lex Fridman (1:05:02.040)
and these single celled organisms like algae,
Karl Deisseroth (1:05:05.080)
they make little proteins
Lex Fridman (1:05:09.360)
that sit in the surface of their cells
Karl Deisseroth (1:05:11.960)
that receive light, capture a photon of light
Lex Fridman (1:05:15.240)
and open up a little hole in the membrane of the cell
Lex Fridman (1:05:18.400)
and let charged particles, ions like sodium and potassium
Lex Fridman (1:05:21.840)
flow across the membrane of the cell.
Lex Fridman (1:05:24.440)
And that, these algae and bacteria,
Lex Fridman (1:05:27.440)
they do this for their own reasons
Karl Deisseroth (1:05:28.760)
because that helps them move,
Lex Fridman (1:05:30.280)
it helps them make and use energy.
Lex Fridman (1:05:34.320)
But that's a beautiful thing for neuroscience
Lex Fridman (1:05:36.560)
because movement of ions,
Karl Deisseroth (1:05:38.400)
charged particles across the membrane of the cell
Lex Fridman (1:05:40.680)
is exactly the kind of electricity that neurons work with.
Lex Fridman (1:05:43.960)
So if we can take this bit of DNA
Lex Fridman (1:05:47.240)
that encodes this beautiful protein
Karl Deisseroth (1:05:48.780)
that turns light into electricity from algae,
Lex Fridman (1:05:51.440)
and if we can put it into some neurons,
Lex Fridman (1:05:54.600)
but not other neurons, which we can do using genetic tricks,
Lex Fridman (1:05:58.200)
then you've got a situation,
Karl Deisseroth (1:05:59.440)
then you can shine on the light
Lex Fridman (1:06:01.240)
and only the cells that have the gene
Lex Fridman (1:06:03.920)
and that are expressing the gene
Lex Fridman (1:06:05.760)
will be the initial direct cells
Karl Deisseroth (1:06:08.160)
that are activated by the light.
Lex Fridman (1:06:09.200)
And so that's the essence of optogenetics
Karl Deisseroth (1:06:10.880)
is the ability to do that.
Lex Fridman (1:06:12.600)
We get that initial specificity
Karl Deisseroth (1:06:14.100)
that you could never get with an electrode.
Lex Fridman (1:06:15.840)
So let me say that this is,
Karl Deisseroth (1:06:18.240)
we recently got the Alaska Prize for this.
Lex Fridman (1:06:22.560)
It's a brilliant idea.
Lex Fridman (1:06:25.720)
So I talked to Andrew Huberman,
Lex Fridman (1:06:28.880)
who's a friend of yours, friend of mine,
Lex Fridman (1:06:32.040)
so not to jinx things,
Lex Fridman (1:06:33.520)
but he believes that you deserve the Nobel Prize for this.
Karl Deisseroth (1:06:36.720)
So, I do too, but what, my votes.
Lex Fridman (1:06:42.520)
Anyway, the thing is, it doesn't matter.
Karl Deisseroth (1:06:44.680)
Prizes will be all forgotten, all of us will be forgotten.
Lex Fridman (1:06:47.440)
When the cool idea is a cool idea,
Karl Deisseroth (1:06:49.880)
that's a really powerful idea.
Lex Fridman (1:06:51.600)
It's actually, the origins of it
Karl Deisseroth (1:06:53.760)
you might be interested in are even, are very deep.
Lex Fridman (1:06:57.580)
There was a botanist in St. Petersburg
Karl Deisseroth (1:06:59.820)
named Andre Fomensen.
Lex Fridman (1:07:01.520)
In 1866, he published a paper
Karl Deisseroth (1:07:05.600)
on the single celled green algae.
Lex Fridman (1:07:07.840)
And he was the botanist who first noticed
Karl Deisseroth (1:07:09.960)
that they moved in response to light.
Lex Fridman (1:07:12.060)
These are tiny single celled algae that have flagella,
Lex Fridman (1:07:14.500)
so they swim through the water.
Lex Fridman (1:07:16.440)
And he noticed this, he was a botanist,
Lex Fridman (1:07:20.080)
and he published this.
Lex Fridman (1:07:21.520)
It was a paper, you know, he wrote in German,
Lex Fridman (1:07:26.100)
but he published it in a French journal,
Lex Fridman (1:07:27.720)
and he was doing it from St. Petersburg,
Lex Fridman (1:07:29.640)
so it was a very international effort.
Lex Fridman (1:07:32.400)
But you have to go back to 1866,
Lex Fridman (1:07:34.120)
and that, I like to highlight how far back
Lex Fridman (1:07:37.080)
that discovery goes is back to Andre Fomensen.
Lex Fridman (1:07:40.840)
And this is a, it highlights the value
Lex Fridman (1:07:44.040)
of just pure basic science discovery.
Karl Deisseroth (1:07:45.720)
That always originates somewhere
Lex Fridman (1:07:48.380)
in the Eastern European block.
Lex Fridman (1:07:50.520)
But I don't think he expected the splicing
Lex Fridman (1:07:53.600)
of genetic material from the algae into the human brain.
Lex Fridman (1:07:57.920)
And one of the cool things we've been able to do now
Lex Fridman (1:07:59.440)
with modern methods is to really study these proteins.
Lex Fridman (1:08:02.040)
And so we've discovered some of these proteins,
Lex Fridman (1:08:04.280)
other groups have as well.
Karl Deisseroth (1:08:05.480)
We've dived deep into their structure,
Lex Fridman (1:08:07.640)
just like the double helix structure of DNA
Karl Deisseroth (1:08:09.920)
was uncovered with X ray crystallography.
Lex Fridman (1:08:12.560)
We used the same method in X ray crystallography
Karl Deisseroth (1:08:14.840)
to see how these beautiful little proteins work.
Lex Fridman (1:08:18.080)
We reengineered them for all kinds of function.
Karl Deisseroth (1:08:20.080)
We can make them, instead of responding to blue light,
Lex Fridman (1:08:22.360)
we can make them respond to red light.
Karl Deisseroth (1:08:24.520)
We can speed them up, slow them down.
Lex Fridman (1:08:26.400)
We can make them, with genetic engineering,
Karl Deisseroth (1:08:28.920)
we can make them have different ions flow through them.
Lex Fridman (1:08:32.320)
And so it's this convergence, as you said,
Karl Deisseroth (1:08:34.720)
like the botanist in 1866 couldn't have predicted
Lex Fridman (1:08:36.920)
what we could do with this.
Lex Fridman (1:08:38.440)
And the fact that we've been able to discover
Lex Fridman (1:08:40.680)
how these beautiful proteins work
Lex Fridman (1:08:42.240)
and then apply them to neuroscience
Lex Fridman (1:08:45.040)
is really a thrilling story.
Lex Fridman (1:08:46.280)
Is it possible to achieve scale, do you think, with this?
Lex Fridman (1:08:49.440)
Meaning, like what is the progress of the next 50 years,
Karl Deisseroth (1:08:53.760)
100 years looks like in terms of the precision
Lex Fridman (1:08:56.840)
and the scale of control of using light?
Karl Deisseroth (1:08:59.120)
It's going so fast it's hard to predict.
Lex Fridman (1:09:02.320)
I'll give you a sense of it though.
Karl Deisseroth (1:09:06.240)
First paper we published in 2005,
Lex Fridman (1:09:11.120)
that was just encultured neurons.
Karl Deisseroth (1:09:12.400)
By 2007, so that was in a dish.
Lex Fridman (1:09:14.520)
By 2007, we had it working in behaving mice.
Karl Deisseroth (1:09:17.520)
By 2009, we had it pretty general.
Lex Fridman (1:09:20.800)
So we had methods to really make it a versatile method.
Karl Deisseroth (1:09:23.320)
It could be applied to essentially any cell.
Lex Fridman (1:09:26.280)
By 2012, we could get to single cell resolution.
Karl Deisseroth (1:09:29.240)
We used light guidance strategies
Lex Fridman (1:09:31.080)
to target individual cells in the brain of a living mouse.
Karl Deisseroth (1:09:36.520)
By 2019, we were able to control up to 20 to 50
Lex Fridman (1:09:42.840)
individually specified single cells
Karl Deisseroth (1:09:44.840)
in the brain of a mouse in ways that specifically changed
Lex Fridman (1:09:48.600)
its behavior, that could bias its decisions one
Karl Deisseroth (1:09:50.920)
way or the other.
Lex Fridman (1:09:51.680)
In fact, we could take a mouse and without any visual stimulus
Karl Deisseroth (1:09:58.600)
at all, we could make it act as if it
Lex Fridman (1:10:01.160)
had seen a particular visual stimulus
Karl Deisseroth (1:10:03.440)
by playing in, using the single cell resolution optogenetics,
Lex Fridman (1:10:07.640)
a specific pattern of activity into 20 or 25
Karl Deisseroth (1:10:11.040)
individually specified cells.
Lex Fridman (1:10:12.960)
That's 2019 to your question of scale.
Karl Deisseroth (1:10:15.400)
Now in 2022, we're controlling hundreds
Lex Fridman (1:10:18.200)
of individually specified single cells
Karl Deisseroth (1:10:20.840)
over all of visual cortex of a mouse, all the part
Lex Fridman (1:10:24.560)
of the brain that is the initial direct target
Karl Deisseroth (1:10:28.800)
of the incoming information from the retina.
Lex Fridman (1:10:31.160)
Are you constrained to specific types of cells currently?
Karl Deisseroth (1:10:34.320)
Like you mentioned, long range is easier.
Lex Fridman (1:10:36.800)
Is there constraints on which cells?
Karl Deisseroth (1:10:39.680)
Now there really isn't.
Lex Fridman (1:10:41.040)
Now that we have this individual cell guidance,
Karl Deisseroth (1:10:43.600)
we can target any individual kind of cell very reliably.
Lex Fridman (1:10:48.840)
And so now to your question of scale, how far can we go?
Karl Deisseroth (1:10:55.520)
Well, things are moving quickly.
Lex Fridman (1:10:58.680)
It's hard to say.
Karl Deisseroth (1:11:00.000)
We can access individual cells across the entire brain now.
Lex Fridman (1:11:04.560)
If you look 10, 20 years in the future,
Karl Deisseroth (1:11:09.080)
I think we'll surprise ourselves.
Lex Fridman (1:11:11.880)
But the fact that we're already able to cause
Karl Deisseroth (1:11:14.520)
specific perceptions to happen and specific actions
Lex Fridman (1:11:17.600)
means we're essentially where we want to be.
Lex Fridman (1:11:19.480)
And now it's a matter of just more experiments,
Lex Fridman (1:11:25.960)
more discoveries.
Lex Fridman (1:11:26.800)
But the basic principles are clear now.
Lex Fridman (1:11:29.960)
The basic capability is there.
Lex Fridman (1:11:32.200)
Is there a pathway to doing the same for humans?
Lex Fridman (1:11:36.320)
Optogenetics is primarily, it's a discovery tool
Karl Deisseroth (1:11:38.400)
that really is well suited for use in mice and rats
Lex Fridman (1:11:41.760)
and monkeys because it involves putting in a gene
Lex Fridman (1:11:48.120)
and also delivering light.
Lex Fridman (1:11:49.720)
And those are two things that you can do in human beings,
Lex Fridman (1:11:52.600)
but you'd want to do in a very careful way.
Lex Fridman (1:11:55.760)
Now that said, there is actually just less than a year ago,
Karl Deisseroth (1:11:59.280)
my friend Botan Droska in Switzerland,
Lex Fridman (1:12:02.480)
he did the first human optogenetics therapy.
Lex Fridman (1:12:07.760)
And he published this in the journal Nature Medicine.
Lex Fridman (1:12:10.000)
So about 10, 12 years ago, he and I
Karl Deisseroth (1:12:14.760)
published a paper together where we gave him
Lex Fridman (1:12:17.240)
one of our optogenetic tools, one
Karl Deisseroth (1:12:21.000)
of these light activated regulators of ion flow.
Lex Fridman (1:12:26.000)
These are called microbial opsins, by the way, opsins.
Lex Fridman (1:12:29.840)
And he put one of those into an extracted retina
Lex Fridman (1:12:33.120)
from a human being who had died.
Lex Fridman (1:12:35.760)
So it was a cadaveric retina.
Lex Fridman (1:12:37.800)
And he was able to show that optical control in this paper
Karl Deisseroth (1:12:43.000)
was able to turn on or off individual cells
Lex Fridman (1:12:45.360)
in the human retina.
Lex Fridman (1:12:46.440)
So that was a while back.
Lex Fridman (1:12:48.480)
He spent about 10 years of going through all the regulatory
Karl Deisseroth (1:12:53.200)
hoops and hurdles and going through primate studies.
Lex Fridman (1:12:56.480)
And finally, he was able to take a human being
Karl Deisseroth (1:13:00.560)
with a retinal degeneration syndrome, so someone
Lex Fridman (1:13:03.280)
who was blind in both eyes.
Lex Fridman (1:13:06.480)
And he gave one of these opsins into one eye of this human
Lex Fridman (1:13:12.320)
being who was blind and with the goal
Karl Deisseroth (1:13:16.720)
of conferring light sensitivity onto this retina that
Lex Fridman (1:13:20.760)
was not able to see light.
Lex Fridman (1:13:23.440)
And he was able to make this person see through that eye.
Lex Fridman (1:13:26.440)
So he took a blind person.
Lex Fridman (1:13:27.640)
And the blind person could see now,
Lex Fridman (1:13:29.080)
could reach for objects selectively on a table.
Lex Fridman (1:13:33.760)
And he published this in Nature Medicine.
Lex Fridman (1:13:36.400)
And it was, you know, that's an amazing thing.
Lex Fridman (1:13:39.600)
Do you know the title of the paper?
Lex Fridman (1:13:40.480)
What's his name again?
Karl Deisseroth (1:13:41.480)
Rosca, R O S K A.
Lex Fridman (1:13:43.840)
And you look up the Nature paper.
Karl Deisseroth (1:13:45.680)
Nature Medicine.
Lex Fridman (1:13:46.760)
Nature Medicine.
Lex Fridman (1:13:47.680)
So that's sort of proof of principle.
Lex Fridman (1:13:49.360)
Now, the retina is very accessible.
Karl Deisseroth (1:13:51.200)
It's near the surface.
Lex Fridman (1:13:52.640)
You can use natural light, or you
Karl Deisseroth (1:13:54.280)
can use brighter natural light.
Lex Fridman (1:13:57.800)
I'm myself, I see optogenetics as a discovery tool.
Karl Deisseroth (1:14:01.960)
It's a way to figure out the principles by which the brain
Lex Fridman (1:14:04.520)
works and how it operates.
Karl Deisseroth (1:14:05.720)
Partial recovery of visual function
Lex Fridman (1:14:07.560)
in a blind patient after optogenetic therapy.
Lex Fridman (1:14:10.120)
So he went through the full process of doing primates
Lex Fridman (1:14:14.360)
and then going, wow, that's dedication
Lex Fridman (1:14:17.200)
and that's really exciting to see.
Lex Fridman (1:14:20.320)
As beautiful as that is, and I'm glad he did all that work,
Karl Deisseroth (1:14:23.920)
there are so many other ways that optogenetics
Lex Fridman (1:14:27.240)
could help with therapies.
Karl Deisseroth (1:14:28.520)
Once you know the principles, then any kind of therapy
Lex Fridman (1:14:31.760)
can become more powerful.
Karl Deisseroth (1:14:32.840)
Once you know the causal cells in a symptom,
Lex Fridman (1:14:36.720)
like in lack of motivation or inability
Karl Deisseroth (1:14:40.120)
to enjoy things or altered sleep or altered energy,
Lex Fridman (1:14:43.960)
once you know the cells that are causal,
Karl Deisseroth (1:14:46.080)
then you can make medications that address those cells.
Lex Fridman (1:14:49.640)
You could address brain stimulation treatments that
Karl Deisseroth (1:14:52.360)
might address those cells.
Lex Fridman (1:14:53.440)
Also, diagnosis, very effective systematic way of diagnosing,
Karl Deisseroth (1:14:58.720)
or at least providing you rich data
Lex Fridman (1:15:01.360)
to some of these deep questions about schizophrenia,
Karl Deisseroth (1:15:04.680)
about bipolar, all of those kinds of things.
Lex Fridman (1:15:08.800)
The tools are low resolution currently
Karl Deisseroth (1:15:11.720)
for determining the degree to which you have a thing
Lex Fridman (1:15:15.320)
and whether you have a thing at all.
Karl Deisseroth (1:15:17.920)
Yeah, exactly.
Lex Fridman (1:15:18.840)
And so the hope is that's a great example
Karl Deisseroth (1:15:23.040)
of how you can cure or you can provide
Lex Fridman (1:15:27.640)
some relief for a symptom of a person who has
Karl Deisseroth (1:15:30.120)
a serious degenerative disease.
Lex Fridman (1:15:33.120)
But the principles are what we're after,
Lex Fridman (1:15:36.200)
and that's why I spend, even though I'm a psychiatrist,
Lex Fridman (1:15:39.520)
even though I still see patients, I'm not myself
Karl Deisseroth (1:15:42.480)
trying to drive any clinical trials in the lab.
Lex Fridman (1:15:45.480)
I'm trying to discover, and then any kind of therapy
Karl Deisseroth (1:15:49.400)
could result from that.
Lex Fridman (1:15:50.880)
What do you think about my friend,
Lex Fridman (1:15:54.960)
Elon Musk, and his efforts with Neuralink?
Lex Fridman (1:15:58.360)
So this is another, there's a lot of things to say here,
Karl Deisseroth (1:16:02.840)
because there's a lot of ideas under the umbrella
Lex Fridman (1:16:05.360)
of Neuralink, but one of them is to use electrical signals
Karl Deisseroth (1:16:09.760)
to stimulate, and then you also record,
Lex Fridman (1:16:13.280)
you collect electrical signals from the brain
Karl Deisseroth (1:16:15.840)
at a higher and higher resolution,
Lex Fridman (1:16:17.920)
and you go implant surgically the methods
Karl Deisseroth (1:16:22.960)
by which you do the stimulation and the data collection.
Lex Fridman (1:16:26.440)
So it's possible for the ideas of optogenetics
Karl Deisseroth (1:16:30.520)
to play well with this, and we can even zoom out
Lex Fridman (1:16:34.080)
outside of just Neuralink, and just the whole idea
Karl Deisseroth (1:16:36.960)
of brain computer interfaces.
Lex Fridman (1:16:39.520)
What are your thoughts?
Karl Deisseroth (1:16:41.760)
Well, I think the engineering that they've done
Lex Fridman (1:16:43.600)
is actually pretty cool.
Lex Fridman (1:16:44.480)
So I like the.
Lex Fridman (1:16:46.120)
Robots.
Karl Deisseroth (1:16:47.000)
Yeah, from the design perspective,
Lex Fridman (1:16:49.480)
and it was a design approach that wasn't being taken
Karl Deisseroth (1:16:53.240)
in academia, and it's great that they did it,
Lex Fridman (1:16:55.760)
and I think it's pretty cool.
Lex Fridman (1:16:57.400)
So I'll say that.
Lex Fridman (1:16:59.000)
Also, there are many ways that you can record
Karl Deisseroth (1:17:01.560)
from many thousands of neurons, and that's not the only way.
Lex Fridman (1:17:06.320)
It's a very interesting way.
Karl Deisseroth (1:17:08.000)
We and others are using brain penetrating electrodes
Lex Fridman (1:17:12.400)
that actually get quite deep.
Karl Deisseroth (1:17:14.200)
This whole structure of the brain is very interesting.
Lex Fridman (1:17:16.440)
There's the surface cortex, where it's the most recently
Karl Deisseroth (1:17:20.440)
emergent part of the brain in evolution.
Lex Fridman (1:17:23.680)
Mammals have it.
Karl Deisseroth (1:17:24.800)
Reptiles have something a little bit like it,
Lex Fridman (1:17:27.000)
but it's not really the full thing.
Karl Deisseroth (1:17:29.880)
This is a very recent thing.
Lex Fridman (1:17:31.040)
That's what we can access with some of these,
Karl Deisseroth (1:17:33.600)
like the Neuralink approach,
Lex Fridman (1:17:35.080)
and with some of these short electrodes.
Karl Deisseroth (1:17:38.280)
This part of the brain, the cortex,
Lex Fridman (1:17:39.480)
is only a few millimeters thick.
Karl Deisseroth (1:17:40.680)
There's so much that's deep, though, that's so important.
Lex Fridman (1:17:42.880)
There's the striatum, there's the thalamus.
Karl Deisseroth (1:17:44.680)
There are the parts of the brain that drive motivation,
Lex Fridman (1:17:49.120)
that drive hunger and thirst and social interaction
Lex Fridman (1:17:52.960)
and parenting and flight and fear and anxiety.
Lex Fridman (1:17:58.120)
All these things are, there's so much that's deep
Karl Deisseroth (1:18:00.440)
that these surface approaches are not getting to.
Lex Fridman (1:18:02.800)
And so we and others are using these very long electrodes
Karl Deisseroth (1:18:06.600)
that help us get deep, and we can still record
Lex Fridman (1:18:08.800)
for many cells, many thousands of cells.
Karl Deisseroth (1:18:11.600)
We can have multiple of these at once in the same animal.
Lex Fridman (1:18:15.360)
And so there's a diversity of methods to get to this goal.
Karl Deisseroth (1:18:18.440)
I think it's great that people coming from
Lex Fridman (1:18:24.200)
outside academia will bring ideas
Karl Deisseroth (1:18:26.760)
that weren't being worked on, at least approaches.
Lex Fridman (1:18:29.040)
They may turn out to be synergistic.
Karl Deisseroth (1:18:31.160)
These things do work very well with optogenetics
Lex Fridman (1:18:33.600)
because all these electrical recording methods,
Karl Deisseroth (1:18:37.400)
that's one channel of information flow.
Lex Fridman (1:18:39.640)
Light delivery is a separate, more or less independent.
Karl Deisseroth (1:18:43.200)
There can be some artifacts that happen,
Lex Fridman (1:18:45.360)
but if you're careful,
Karl Deisseroth (1:18:46.200)
it's another independent pathway of information flow.
Lex Fridman (1:18:49.840)
And we've done really fun experiments in mice
Karl Deisseroth (1:18:53.160)
where we play in patterns of activity with light,
Lex Fridman (1:18:56.240)
and we record activity from across the brain of a mouse
Karl Deisseroth (1:18:59.480)
electrically, and so using optical and electrical together
Lex Fridman (1:19:02.320)
is extremely powerful.
Lex Fridman (1:19:04.000)
So like optoelectric brain computer interfaces.
Lex Fridman (1:19:09.760)
Which, by the way, there's efforts on the computing side
Karl Deisseroth (1:19:13.080)
to build optoelectric servers,
Lex Fridman (1:19:16.200)
so like where you have both electricity.
Lex Fridman (1:19:17.920)
So because optics is really interesting,
Lex Fridman (1:19:20.160)
light is a very interesting method of communication
Karl Deisseroth (1:19:22.880)
that's, like you said, orthogonal in many ways.
Lex Fridman (1:19:26.220)
It doesn't have some of the constraints of bandwidth
Karl Deisseroth (1:19:28.920)
that electricity does going through wires,
Lex Fridman (1:19:32.400)
but you're able to,
Lex Fridman (1:19:34.320)
but less ability to control precisely at scale.
Lex Fridman (1:19:38.640)
So like there's challenges and there's benefits,
Lex Fridman (1:19:40.680)
and having those two interplays
Lex Fridman (1:19:42.200)
really, really, really fascinating,
Karl Deisseroth (1:19:44.040)
especially when obviously on the other side
Lex Fridman (1:19:46.640)
of your signal is a biological mesh, mush, mushy mesh.
Karl Deisseroth (1:19:51.640)
Well, the mushy mesh is kind of interesting
Lex Fridman (1:19:54.660)
because there are problems with light.
Karl Deisseroth (1:19:56.460)
Light scatters in the brain,
Lex Fridman (1:19:57.980)
so the photons don't just go linearly through.
Karl Deisseroth (1:20:01.420)
Whenever they hit an interface between fat and water,
Lex Fridman (1:20:04.220)
lipid and water, they bounce off in different directions.
Lex Fridman (1:20:08.060)
And so you can come in with all the resolution you want.
Lex Fridman (1:20:10.820)
You could play in an incredibly detailed,
Karl Deisseroth (1:20:13.540)
high resolution pattern of light,
Lex Fridman (1:20:15.460)
but the photons start scattering quite quickly,
Lex Fridman (1:20:18.300)
and by the time you've gone a couple of millimeters deep,
Lex Fridman (1:20:20.980)
you've lost almost all that fine spatial information.
Karl Deisseroth (1:20:24.580)
So, but we've developed workarounds.
Lex Fridman (1:20:26.980)
The longer wavelength light you use,
Karl Deisseroth (1:20:29.140)
if you get into the infrared, there's less scattering.
Lex Fridman (1:20:31.140)
You can use two photon methods or three photon methods
Karl Deisseroth (1:20:33.900)
where the photons have to arrive all together
Lex Fridman (1:20:36.100)
at the same time.
Karl Deisseroth (1:20:37.620)
You can put in fiber optics.
Lex Fridman (1:20:39.220)
We developed these fiber optic methods in 2007
Karl Deisseroth (1:20:42.420)
where you can access these deep structures
Lex Fridman (1:20:44.220)
with fiber optic methods,
Lex Fridman (1:20:45.460)
and you can put many of these fiber optics
Lex Fridman (1:20:46.980)
at the same time in an animal.
Karl Deisseroth (1:20:48.860)
We've used holographic methods, 3D holograms,
Lex Fridman (1:20:53.300)
to play in hundreds of individual cell size spots of light,
Lex Fridman (1:20:56.900)
and we can change those quickly.
Lex Fridman (1:20:59.220)
So there are a lot of tricks,
Karl Deisseroth (1:21:00.340)
a lot of interesting optics engineering
Lex Fridman (1:21:01.860)
that has come together with neuroscience
Karl Deisseroth (1:21:03.860)
in a pretty exciting way.
Lex Fridman (1:21:04.820)
Well, that is engineering, too.
Karl Deisseroth (1:21:06.060)
It was just super, super, super exciting.
Lex Fridman (1:21:07.660)
I should mention, because I remember I mentioned Elon.
Karl Deisseroth (1:21:10.820)
I recently got, for the first time ever, got COVID.
Lex Fridman (1:21:15.740)
Well, how did I go so long without,
Karl Deisseroth (1:21:21.300)
finally, so I'm all vaccinated and everything like that.
Lex Fridman (1:21:24.340)
And so I got, because I think he mentioned it publicly
Lex Fridman (1:21:27.900)
so I can mention it,
Lex Fridman (1:21:28.980)
but I won't mention anybody else involved.
Lex Fridman (1:21:30.620)
But hanging out, we all got, Elon got COVID.
Lex Fridman (1:21:33.780)
And the interesting thing about,
Karl Deisseroth (1:21:35.180)
maybe you can comment about this.
Lex Fridman (1:21:36.540)
So I was only sick for like a half a day.
Karl Deisseroth (1:21:38.860)
I got a fever of like 104.
Lex Fridman (1:21:40.540)
I just went up and then crashed.
Lex Fridman (1:21:44.020)
And then I was, now maybe I'm just seeing
Lex Fridman (1:21:47.580)
the silver lining of everything,
Lex Fridman (1:21:48.700)
but afterwards, I have like a greater clarity
Lex Fridman (1:21:54.740)
about the world.
Karl Deisseroth (1:21:57.580)
You just think it's greater clarity.
Lex Fridman (1:21:58.740)
Maybe, maybe I just, it was so,
Karl Deisseroth (1:22:01.980)
maybe so intensely the mind fog kind of thing
Lex Fridman (1:22:06.140)
for such a short amount of time.
Lex Fridman (1:22:07.860)
But the people who were involved were also reporting this.
Lex Fridman (1:22:12.060)
It's kind of interesting.
Karl Deisseroth (1:22:13.180)
It's like, because I do know like the immune system
Lex Fridman (1:22:18.700)
is involved with the brain in very interesting ways.
Lex Fridman (1:22:21.860)
So like the human mind also incorporates all these other,
Lex Fridman (1:22:24.780)
it's not just the, it's not just the nervous system.
Lex Fridman (1:22:28.140)
And I just wonder, because everyone always says,
Lex Fridman (1:22:30.220)
no, not like, everyone always says like COVID
Karl Deisseroth (1:22:32.540)
does all these bad things or whatever the disease is
Lex Fridman (1:22:34.740)
or whatever the virus.
Lex Fridman (1:22:36.060)
But I wonder like, I hate to be a Steven Pinker on this,
Lex Fridman (1:22:39.740)
but like, I wonder what the benefits of certain disease are
Karl Deisseroth (1:22:42.180)
if you're able to recover.
Lex Fridman (1:22:43.860)
Like what, is there some like, again,
Karl Deisseroth (1:22:46.460)
don't want to romanticize it,
Lex Fridman (1:22:47.540)
but if your system goes to some kind of hardship
Lex Fridman (1:22:50.180)
and you come out on the other end,
Lex Fridman (1:22:51.900)
I wonder sometimes if there's a greater,
Karl Deisseroth (1:22:54.860)
maybe killed off a bunch of neurons
Lex Fridman (1:22:56.460)
that didn't need anyway,
Lex Fridman (1:22:57.420)
and they were actually getting in the way.
Lex Fridman (1:22:58.860)
There were the hater neurons.
Karl Deisseroth (1:23:00.580)
I don't know.
Lex Fridman (1:23:01.420)
Well, that was your inner critic that I was talking about.
Karl Deisseroth (1:23:02.540)
Exactly.
Lex Fridman (1:23:03.380)
You killed off your critic.
Karl Deisseroth (1:23:05.060)
Well, you know, there are mechanisms for what you,
Lex Fridman (1:23:07.340)
the potential mechanisms for what you're talking about.
Karl Deisseroth (1:23:10.460)
There are, there's actually been a fair bit of research
Lex Fridman (1:23:13.260)
on post COVID neurological function.
Karl Deisseroth (1:23:18.740)
Actually, my wife, Michelle Monjay, who's at Stanford,
Lex Fridman (1:23:20.940)
she's done a lot of this work.
Karl Deisseroth (1:23:22.340)
Akiko Iwasaki at Yale has done a lot of this.
Lex Fridman (1:23:25.500)
But what they found is that there's a loss of myelin.
Karl Deisseroth (1:23:30.300)
This is the coating of those long range projections
Lex Fridman (1:23:33.380)
that go from one part of the brain to another.
Karl Deisseroth (1:23:35.420)
Myelin is this sort of insulator
Lex Fridman (1:23:37.580)
that coats these long range projections
Lex Fridman (1:23:39.220)
and makes the impulses go faster and more reliably.
Lex Fridman (1:23:43.620)
And there's altered function of the myelin producing cells
Lex Fridman (1:23:49.860)
and altered myelin in the case of COVID.
Lex Fridman (1:23:52.660)
They've looked in both mouse and human brains.
Karl Deisseroth (1:23:56.620)
And, but of course it could be very idiosyncratic.
Lex Fridman (1:23:59.980)
Many people have cognitive problems post COVID.
Karl Deisseroth (1:24:03.380)
You're definitely aware of that.
Lex Fridman (1:24:04.500)
So many people report this persistent brain fog
Lex Fridman (1:24:07.260)
and the ability to function.
Lex Fridman (1:24:08.940)
But it depends on where the inflammation was.
Karl Deisseroth (1:24:11.460)
Maybe the people who have dysfunction post COVID,
Lex Fridman (1:24:14.980)
they had a global effect.
Karl Deisseroth (1:24:17.060)
Maybe you lost some of these projections
Lex Fridman (1:24:20.300)
that were restraining you in some way.
Lex Fridman (1:24:23.700)
And these plausibly exist.
Lex Fridman (1:24:25.300)
And it's known that there are cell populations
Karl Deisseroth (1:24:30.020)
in the prefrontal cortex that actively restrain
Lex Fridman (1:24:33.180)
deeper structures from expressing what they do.
Lex Fridman (1:24:36.380)
And it's theoretically possible that you had a lucky.
Lex Fridman (1:24:40.900)
Somebody has to get lucky, right?
Karl Deisseroth (1:24:42.380)
Somebody has to get lucky, yeah.
Lex Fridman (1:24:44.020)
Why not me?
Karl Deisseroth (1:24:45.140)
All right, if we can actually go back to this idea
Lex Fridman (1:24:48.900)
of trying through optogenetics
Karl Deisseroth (1:24:53.700)
to find origins of when the wave first starts.
Lex Fridman (1:24:59.580)
Origins of a decision.
Karl Deisseroth (1:25:01.780)
Origin of idea.
Lex Fridman (1:25:07.020)
Origin of maybe consciousness
Karl Deisseroth (1:25:10.180)
or the subjective experience.
Lex Fridman (1:25:12.700)
So origin of things in the mind.
Lex Fridman (1:25:15.140)
So one thing, Carl Jung, is there a God neuron?
Lex Fridman (1:25:21.980)
Is there a belief neuron?
Karl Deisseroth (1:25:24.020)
Is there, so through this methodology of optogenetics,
Lex Fridman (1:25:27.540)
can you start getting to where a belief begins
Lex Fridman (1:25:34.940)
or an idea begins?
Lex Fridman (1:25:37.340)
And especially looking at the strongest of our beliefs.
Karl Deisseroth (1:25:41.020)
Maybe beliefs of love and hate,
Lex Fridman (1:25:43.220)
but religious belief into something really grand,
Karl Deisseroth (1:25:51.100)
on the grandest of scale.
Lex Fridman (1:25:52.860)
Yeah, neuroscience and neurology point us a little bit.
Karl Deisseroth (1:26:00.580)
We don't have an answer to that, but for example.
Lex Fridman (1:26:02.900)
A lot of these questions I'm gonna ask you,
Karl Deisseroth (1:26:04.340)
there's no good answer, but you're providing the tools
Lex Fridman (1:26:07.380)
that give us hope to find the answer one day.
Karl Deisseroth (1:26:09.660)
Yeah, and we have early clues.
Lex Fridman (1:26:11.020)
So for example, when patients with epilepsy
Karl Deisseroth (1:26:14.700)
have experiences of religiosity as part of their seizure
Lex Fridman (1:26:19.700)
or the aura before their seizure,
Karl Deisseroth (1:26:22.620)
very often those are in the temporal lobe,
Lex Fridman (1:26:26.700)
in these parts of the brain that are at the side.
Lex Fridman (1:26:30.420)
And so that's an initial clue.
Lex Fridman (1:26:33.580)
There are also parts of the brain that are involved
Karl Deisseroth (1:26:37.780)
in the definition of the self
Lex Fridman (1:26:41.500)
and defining the borders or boundaries of the self.
Lex Fridman (1:26:45.900)
And we know this, this is some experiments that we did
Lex Fridman (1:26:48.980)
in my lab, there's a part of the brain
Karl Deisseroth (1:26:50.780)
where if there's a rhythm of a particular type,
Lex Fridman (1:26:55.420)
you can cause a separation of the sense of self
Karl Deisseroth (1:26:59.980)
from the sense of the body.
Lex Fridman (1:27:02.100)
What's normally bound up and unitary,
Karl Deisseroth (1:27:04.460)
we normally think of ourself and our body
Lex Fridman (1:27:06.060)
as pretty tightly bound up together,
Karl Deisseroth (1:27:08.180)
those can be separated, it turns out.
Lex Fridman (1:27:09.780)
We can't take that for granted.
Lex Fridman (1:27:11.020)
And there are certain conditions,
Lex Fridman (1:27:12.060)
certain patterns of activity in one part of the brain
Karl Deisseroth (1:27:14.900)
called the retro splenial cortex,
Lex Fridman (1:27:17.220)
where you can actually separate those two out.
Lex Fridman (1:27:20.900)
And so if you think about these very big questions,
Lex Fridman (1:27:25.180)
you know, what is, where are the origins of religiosity?
Karl Deisseroth (1:27:29.420)
Where, how do we define the boundaries of who we are
Lex Fridman (1:27:33.140)
relative to others and to the world?
Lex Fridman (1:27:36.660)
How do we link ourself to our body
Lex Fridman (1:27:40.460)
and how can that become separated?
Karl Deisseroth (1:27:42.100)
These are actually, believe it or not,
Lex Fridman (1:27:44.060)
now accessible and rigorously and quantitatively so.
Karl Deisseroth (1:27:48.900)
We did an experiment with optogenetics
Lex Fridman (1:27:50.820)
where we provided this abnormal rhythm
Karl Deisseroth (1:27:54.540)
to this particular part of the mouse brain
Lex Fridman (1:27:57.100)
and we saw this separation of detection of a stimulus
Lex Fridman (1:28:02.500)
and caring about it.
Lex Fridman (1:28:04.620)
So that's like stimulating something about the mouse brain
Karl Deisseroth (1:28:07.580)
that affects these neurons that give the conception of self.
Lex Fridman (1:28:11.940)
So you're able to dissociate the experience
Karl Deisseroth (1:28:15.380)
from the impact of the experience onto you.
Lex Fridman (1:28:17.940)
That's right, exactly right.
Lex Fridman (1:28:19.540)
So like these are the goals of meditation.
Lex Fridman (1:28:23.580)
These are the goals whenever I get drunk,
Karl Deisseroth (1:28:25.820)
pretty much effective.
Lex Fridman (1:28:27.300)
I mean, that's not a scientific statement,
Karl Deisseroth (1:28:28.980)
just an experiential anecdotal one.
Lex Fridman (1:28:32.060)
Also psychedelics seek to this,
Karl Deisseroth (1:28:35.900)
to attain this kind of state.
Lex Fridman (1:28:37.940)
That's so interesting.
Karl Deisseroth (1:28:39.100)
Well, you mentioned psychedelics, you know,
Lex Fridman (1:28:40.500)
DMT and 5MeO DMT, these create this religious experience,
Karl Deisseroth (1:28:45.580)
this connection, people describe them
Lex Fridman (1:28:47.580)
as a strong connection to God.
Karl Deisseroth (1:28:49.500)
That in theory, these are accessible with modern methods.
Lex Fridman (1:28:53.420)
Now that we have these rich recording methods,
Karl Deisseroth (1:28:56.180)
we can explore what are the precise millisecond resolution,
Lex Fridman (1:29:01.420)
cellular resolution, brain wide manifestations
Karl Deisseroth (1:29:05.300)
of these altered states.
Lex Fridman (1:29:06.660)
So like you could look at an altered state like on DMT,
Karl Deisseroth (1:29:11.020)
record it across many people,
Lex Fridman (1:29:14.540)
and then from there see where do these experiences
Karl Deisseroth (1:29:18.020)
originate in the brain in terms of single neurons,
Lex Fridman (1:29:21.540)
and then how do they propagate
Lex Fridman (1:29:25.260)
and interact with everything else?
Lex Fridman (1:29:26.540)
And if there's some kind of common signal,
Karl Deisseroth (1:29:30.980)
like how do you narrow down the set of neurons
Lex Fridman (1:29:34.340)
that are responsible for particular experience
Lex Fridman (1:29:36.740)
or for a particular behavioral effect?
Lex Fridman (1:29:38.740)
Yeah, here's where optogenetics is so useful
Karl Deisseroth (1:29:40.460)
because anytime you give an agent like ketamine or PCP,
Lex Fridman (1:29:46.860)
which we used for our dissociation experiments
Karl Deisseroth (1:29:49.500)
that I was mentioning,
Lex Fridman (1:29:50.660)
or you have a psychedelic LSD or DMT
Karl Deisseroth (1:29:55.020)
for this altered perceptual state,
Lex Fridman (1:29:57.900)
if you give either of those,
Lex Fridman (1:30:00.620)
these change everything across the brain, okay?
Lex Fridman (1:30:03.020)
So just the fact that you maybe give them to a mouse,
Karl Deisseroth (1:30:06.060)
let's say, or eventually to a human,
Lex Fridman (1:30:09.740)
you won't know yet which cells to home in on
Karl Deisseroth (1:30:13.660)
as the causal players in all this
Lex Fridman (1:30:17.180)
just by recording the activity.
Lex Fridman (1:30:19.380)
But then what we found is that optogenetics
Lex Fridman (1:30:21.900)
providing a causal pattern of activity
Karl Deisseroth (1:30:23.780)
guided by what you see can let you test hypotheses.
Lex Fridman (1:30:28.020)
And we saw this rhythm with ketamine and PCP
Karl Deisseroth (1:30:31.180)
for dissociation, and then we said, okay,
Lex Fridman (1:30:33.980)
let's test what's causal.
Karl Deisseroth (1:30:35.860)
We came in and provided that rhythm.
Lex Fridman (1:30:38.100)
We tried a few different things,
Lex Fridman (1:30:39.500)
but only one of the causal tests we tried
Lex Fridman (1:30:41.900)
actually caused the behavioral dissociation.
Lex Fridman (1:30:45.100)
And so that's how we home in on what actually matters.
Lex Fridman (1:30:47.260)
And is it repeatable once you see the causality?
Lex Fridman (1:30:49.220)
So like that's one definition of causality
Lex Fridman (1:30:51.260)
is like you try and it repeats across different mice
Lex Fridman (1:30:55.100)
and all that kind of stuff.
Lex Fridman (1:30:55.980)
Exactly.
Lex Fridman (1:30:58.100)
And so you could do that for DMT.
Lex Fridman (1:30:59.940)
You could do that for the really fascinating
Karl Deisseroth (1:31:02.140)
mind expanding, thank you, thank you.
Lex Fridman (1:31:06.780)
So the meme for people just listening,
Karl Deisseroth (1:31:08.380)
this is again another disagreement
Lex Fridman (1:31:10.140)
between Freud and Carl Jung.
Karl Deisseroth (1:31:13.460)
Religion and spirituality.
Lex Fridman (1:31:15.100)
This is the, I guess the ring scene from Lord of the Rings.
Karl Deisseroth (1:31:18.900)
Religion and spirituality, Freud says,
Lex Fridman (1:31:20.820)
cast it into the fire, destroy it.
Karl Deisseroth (1:31:23.460)
Carl Jung says, no.
Lex Fridman (1:31:25.260)
So for people who don't know,
Karl Deisseroth (1:31:26.580)
Sergei is the Slavic Lord of the Meme.
Lex Fridman (1:31:31.580)
Thank you, I appreciate that.
Lex Fridman (1:31:33.780)
So what we're talking about,
Lex Fridman (1:31:34.700)
so there is, I mean, I think a connection
Karl Deisseroth (1:31:36.700)
between DMT and religious experiences
Lex Fridman (1:31:38.540)
are some of these psychedelics.
Lex Fridman (1:31:40.340)
Do you think it's possible to
Lex Fridman (1:31:44.020)
sort of stimulate religious experiences?
Lex Fridman (1:31:47.300)
And so religious experiences are one of the most
Lex Fridman (1:31:50.060)
deep kind of experiences.
Lex Fridman (1:31:52.580)
And so here you could first understand
Lex Fridman (1:31:57.100)
where they originate, how they propagate
Karl Deisseroth (1:32:00.060)
through the brain, and then to stimulate them.
Lex Fridman (1:32:05.020)
And so this is, and these can happen
Karl Deisseroth (1:32:06.740)
in people who had no predisposition.
Lex Fridman (1:32:10.940)
People who are as agnostic or atheistic as you'd like,
Karl Deisseroth (1:32:15.940)
they can have these, they can feel connected
Lex Fridman (1:32:17.700)
to God in these states.
Karl Deisseroth (1:32:20.140)
Now, to be clear, I'm not advocating these.
Lex Fridman (1:32:21.980)
We don't know what's safe in human beings,
Lex Fridman (1:32:24.740)
but we definitely have not yet.
Lex Fridman (1:32:26.940)
But we definitely can do these experiments in mice,
Lex Fridman (1:32:29.540)
and that was already very productive
Lex Fridman (1:32:32.300)
in understanding dissociation.
Lex Fridman (1:32:33.700)
So we can already imagine making headway on these methods.
Lex Fridman (1:32:37.340)
And then I had a, and this does map
Karl Deisseroth (1:32:39.580)
onto the non psychedelic human experience.
Lex Fridman (1:32:42.980)
I had a patient who was actually described
Karl Deisseroth (1:32:45.740)
in the book Projections.
Lex Fridman (1:32:47.300)
This was the patient that's in the mania chapter,
Karl Deisseroth (1:32:49.740)
the bipolar chapter.
Lex Fridman (1:32:51.620)
Here was a guy who had never had a psychiatric illness
Karl Deisseroth (1:32:56.340)
or symptom in his life.
Lex Fridman (1:32:57.380)
He was a retirement age gentleman,
Lex Fridman (1:33:00.540)
and nobody in his family either.
Lex Fridman (1:33:02.900)
So no family history, no personal history
Karl Deisseroth (1:33:05.020)
of any psychiatric illness, and he'd never been religious,
Lex Fridman (1:33:07.260)
particularly before either.
Karl Deisseroth (1:33:08.820)
Certainly no passionate type of religion.
Lex Fridman (1:33:13.340)
But he, not through any psychedelic or drug,
Karl Deisseroth (1:33:15.900)
he had a stressful experience,
Lex Fridman (1:33:18.060)
actually a post 9 11 change in how he was thinking.
Lex Fridman (1:33:21.660)
And he was pushed into a mania, a manic state,
Lex Fridman (1:33:24.900)
revealing that he had bipolar,
Karl Deisseroth (1:33:26.780)
never before known in this case, in this person.
Lex Fridman (1:33:30.700)
And his mania, his elevated state in bipolar
Karl Deisseroth (1:33:33.940)
included this profound religiosity,
Lex Fridman (1:33:37.100)
which he had never had before.
Lex Fridman (1:33:38.260)
And he was preaching in a elevated,
Lex Fridman (1:33:44.180)
vigorous way to his family.
Lex Fridman (1:33:46.140)
And so this state can be created in people
Lex Fridman (1:33:50.020)
even late in life who had no predisposition for it
Lex Fridman (1:33:52.540)
and even without a neurochemical.
Lex Fridman (1:33:54.980)
So the causality of that is very interesting to explore.
Lex Fridman (1:34:00.740)
How did the manic state unleash this religiosity?
Lex Fridman (1:34:05.900)
But you see that in other realms of psychiatry too.
Karl Deisseroth (1:34:08.580)
OCD can manifest as religiosity also.
Lex Fridman (1:34:11.660)
You can take people who never really had
Karl Deisseroth (1:34:13.780)
a religion, never played a powerful role in their life,
Lex Fridman (1:34:18.500)
but then when their obsessive compulsive symptoms
Karl Deisseroth (1:34:21.120)
become severe, they can manifest in this.
Lex Fridman (1:34:23.180)
I think I'm in that group, so I'm a bit OCD.
Karl Deisseroth (1:34:26.340)
We have, I think this is subreddits,
Lex Fridman (1:34:29.740)
when there's oddly satisfying things.
Lex Fridman (1:34:32.860)
So there's certain things that are really satisfying
Lex Fridman (1:34:35.980)
to my OCD, in my mild OCD.
Karl Deisseroth (1:34:39.620)
I think it's pretty much a religious experience.
Lex Fridman (1:34:41.980)
So I understand that if it's not direct,
Karl Deisseroth (1:34:45.900)
it's at least rhymes.
Lex Fridman (1:34:48.360)
So maybe can you speak to the,
Karl Deisseroth (1:34:51.900)
Sergei's probably desperately scrambling
Lex Fridman (1:34:54.740)
to pull up oddly satisfying, thank you.
Karl Deisseroth (1:34:57.020)
People can check it out themselves.
Lex Fridman (1:34:58.300)
It is, as the subreddit promises, oddly satisfying.
Lex Fridman (1:35:03.020)
Can we talk about bipolar and maybe depression?
Lex Fridman (1:35:08.020)
Well, let's talk about, I mean, I don't know if there's
Karl Deisseroth (1:35:11.340)
a nice way to discuss the differences
Lex Fridman (1:35:13.900)
in the full landscape of suffering that's here,
Lex Fridman (1:35:17.660)
but maybe what is depression?
Lex Fridman (1:35:20.080)
And what are the types of depression?
Lex Fridman (1:35:23.240)
What kind of depression have you seen and experienced
Lex Fridman (1:35:28.380)
and researched and how can people overcome it?
Lex Fridman (1:35:31.300)
How can humans overcome it and deal with it,
Lex Fridman (1:35:33.560)
live with it and overcome it?
Lex Fridman (1:35:36.300)
So this is my clinical specialty.
Lex Fridman (1:35:38.940)
I see patients in my outpatient clinical work
Karl Deisseroth (1:35:42.020)
with treatment resistant depression.
Lex Fridman (1:35:44.420)
So very hard to treat severe illness
Karl Deisseroth (1:35:48.500)
where medications haven't been working.
Lex Fridman (1:35:51.580)
I also see patients with autism spectrum disorders.
Karl Deisseroth (1:35:54.620)
These are my two clinical focal areas,
Lex Fridman (1:35:58.540)
but then I do emergency room work as well.
Lex Fridman (1:36:02.580)
But the depression, why do I focus on that?
Lex Fridman (1:36:06.140)
It's so, one feels tantalizingly close to helping
Karl Deisseroth (1:36:13.220)
these people who are suffering so deeply.
Lex Fridman (1:36:16.860)
And that's why I focused on it is these are people who,
Karl Deisseroth (1:36:20.660)
there may not even be anything situational
Lex Fridman (1:36:23.000)
that's difficult or challenging in their life.
Karl Deisseroth (1:36:25.460)
You can have people who seem to have everything
Lex Fridman (1:36:28.120)
that you would want.
Karl Deisseroth (1:36:28.960)
Every objective measure of their life is fine,
Lex Fridman (1:36:30.800)
yet they can be just hit with this unstoppable hopelessness
Lex Fridman (1:36:41.180)
and inability to see into the future,
Lex Fridman (1:36:44.380)
a discounting of the value of their own action.
Karl Deisseroth (1:36:47.500)
Anything they can imagine themselves doing seems worthless
Lex Fridman (1:36:50.980)
or they are unable to enjoy things.
Karl Deisseroth (1:36:54.860)
We call this anhedonia.
Lex Fridman (1:36:56.420)
There's no reward, no pleasure, not in food,
Karl Deisseroth (1:36:59.580)
social interaction, movies, books,
Lex Fridman (1:37:02.180)
anything that they would enjoy, positivity gone.
Karl Deisseroth (1:37:05.820)
They can have a profound negative internal state,
Lex Fridman (1:37:09.220)
psychic pain, and these things can seem,
Lex Fridman (1:37:13.100)
and in the severe cases, are inescapable.
Lex Fridman (1:37:17.960)
So what is going on?
Lex Fridman (1:37:19.580)
Why is this state part of human existence?
Lex Fridman (1:37:23.380)
It's got a strong biological, genetic link, we know that.
Karl Deisseroth (1:37:27.620)
It's been linked to certain genes,
Lex Fridman (1:37:29.780)
certain regions of the chromosomes, and twin studies.
Karl Deisseroth (1:37:33.020)
There's a clear genetic link.
Lex Fridman (1:37:35.700)
It doesn't explain everything, but it's a big part of it.
Karl Deisseroth (1:37:37.740)
Genetics are a strong contributor.
Lex Fridman (1:37:41.100)
And although you can have depression
Karl Deisseroth (1:37:44.500)
without anything terrible going on in your life,
Lex Fridman (1:37:46.740)
the symptoms can be made worse by stressors, by trauma.
Lex Fridman (1:37:54.540)
But at a very deep level,
Lex Fridman (1:37:55.860)
there's nothing we can measure in a person objectively,
Lex Fridman (1:37:58.220)
so we don't have, there's not a known chemical,
Lex Fridman (1:38:01.700)
not a known structure that's different,
Karl Deisseroth (1:38:04.300)
not a known brain activity pattern
Lex Fridman (1:38:06.180)
that we can pick up with EEG.
Karl Deisseroth (1:38:08.220)
A lot of people are exploring this,
Lex Fridman (1:38:09.740)
but right now we have no objective measures.
Karl Deisseroth (1:38:11.540)
All we do is talk to people and we elicit these symptoms.
Lex Fridman (1:38:15.500)
We explore them, distinguish them from other possible causes,
Lex Fridman (1:38:20.940)
and then what do we do?
Lex Fridman (1:38:22.540)
Well, we have a lot of things that we can do.
Karl Deisseroth (1:38:24.900)
Well, we have a range of treatments.
Lex Fridman (1:38:27.340)
We have medications that can help people,
Karl Deisseroth (1:38:30.420)
do help people, but not everybody.
Lex Fridman (1:38:33.220)
And if they don't work,
Karl Deisseroth (1:38:34.260)
then we can go to brain stimulation methods.
Lex Fridman (1:38:36.700)
We can do things even like electroconvulsive therapy,
Karl Deisseroth (1:38:39.580)
which is very effective,
Lex Fridman (1:38:42.340)
but it's sort of the final thing we go to in the end.
Lex Fridman (1:38:47.060)
And so we have treatments.
Lex Fridman (1:38:49.260)
They work for some people.
Karl Deisseroth (1:38:52.100)
They don't do everything we'd like.
Lex Fridman (1:38:53.500)
But here's the problem is at a very deep level,
Karl Deisseroth (1:38:56.620)
we don't understand really what's going on in the brain.
Lex Fridman (1:38:59.500)
We don't have a physical interpretation of the problem.
Karl Deisseroth (1:39:03.140)
We have all these symptoms,
Lex Fridman (1:39:04.740)
but we can't yet point to a set of cells
Karl Deisseroth (1:39:07.740)
or a set of circuits or an activity pattern
Lex Fridman (1:39:10.480)
that is causing major depression,
Karl Deisseroth (1:39:12.180)
this disease state per se in human beings.
Lex Fridman (1:39:15.560)
Why do you think you can't yet
Lex Fridman (1:39:17.780)
from an optogenetics perspective?
Lex Fridman (1:39:19.300)
Is it because there's so many possible causes?
Lex Fridman (1:39:22.180)
Is it so many things involved?
Lex Fridman (1:39:24.940)
So I think the answer is there are many things involved
Lex Fridman (1:39:27.540)
and all these different symptoms that I've mentioned,
Lex Fridman (1:39:30.660)
those we can study and those we can fix,
Karl Deisseroth (1:39:32.900)
the individual symptoms.
Lex Fridman (1:39:34.580)
And we can do this in animals to be clear.
Lex Fridman (1:39:37.200)
So in a mouse, for example,
Lex Fridman (1:39:39.060)
we can instantaneously and precisely
Karl Deisseroth (1:39:42.840)
turn up or down the motivation of an animal
Lex Fridman (1:39:46.500)
to overcome a challenge.
Karl Deisseroth (1:39:48.100)
We can turn up or down its ability
Lex Fridman (1:39:50.300)
to be motivated by, or we think experience reward
Karl Deisseroth (1:39:54.500)
from situations or actions.
Lex Fridman (1:39:59.260)
We can increase its apparent energy level,
Karl Deisseroth (1:40:03.740)
its drive to meet challenges.
Lex Fridman (1:40:07.260)
We can turn up or down social interaction.
Karl Deisseroth (1:40:10.180)
All these individual features of depression,
Lex Fridman (1:40:12.340)
individual symptoms, we now can point to exact projections
Lex Fridman (1:40:17.220)
and cells that are causal in mediating these.
Lex Fridman (1:40:20.740)
But we don't know is why all these different symptoms
Karl Deisseroth (1:40:24.760)
show up together in major depression
Lex Fridman (1:40:27.500)
and the human disease syndrome.
Lex Fridman (1:40:29.060)
And that's the mystery.
Lex Fridman (1:40:30.640)
It's sort of, in other fields of medicine,
Karl Deisseroth (1:40:33.980)
someone with congestive heart failure
Lex Fridman (1:40:35.460)
who comes into the clinic,
Karl Deisseroth (1:40:36.740)
they have very different symptoms.
Lex Fridman (1:40:38.060)
They have shortness of breath and they have swollen feet.
Karl Deisseroth (1:40:42.100)
Couldn't be two more different across the body
Lex Fridman (1:40:46.260)
sets of symptoms.
Karl Deisseroth (1:40:47.780)
Neither one obviously related to the heart,
Lex Fridman (1:40:49.780)
but they're both happening
Lex Fridman (1:40:50.820)
because the heart is not working as a pump, okay?
Lex Fridman (1:40:53.060)
And now, thankfully in cardiology,
Karl Deisseroth (1:40:57.140)
we understand these disparate symptoms
Lex Fridman (1:40:59.900)
that seem totally unrelated can be completely understood
Karl Deisseroth (1:41:03.620)
because there's an altered pump action of the heart.
Lex Fridman (1:41:05.780)
That's what we are hoping for in psychiatry
Lex Fridman (1:41:10.340)
and in the study of depression or any disease.
Lex Fridman (1:41:13.620)
These different symptoms,
Karl Deisseroth (1:41:14.580)
the inability to enjoy things, the hopelessness.
Lex Fridman (1:41:20.660)
What's the unifying principle?
Karl Deisseroth (1:41:22.620)
Yeah, unifying.
Lex Fridman (1:41:23.460)
I mean, is there some truth to that Tolstoy quote
Karl Deisseroth (1:41:26.780)
that all happy families are alike
Lex Fridman (1:41:28.820)
and each unhappy family is unhappy in its own way?
Lex Fridman (1:41:31.740)
So basically, I mean, this is the human condition.
Lex Fridman (1:41:37.460)
And basically, the physicists long to find
Karl Deisseroth (1:41:42.260)
a theory of everything, isn't understanding depression
Lex Fridman (1:41:47.180)
essentially require you to really have
Lex Fridman (1:41:51.460)
the big theory of everything for the human mind?
Lex Fridman (1:41:55.380)
I think we, it would certainly be nice to have that,
Karl Deisseroth (1:41:58.360)
a theory of everything.
Lex Fridman (1:41:59.700)
Don't get me wrong.
Karl Deisseroth (1:42:00.720)
I don't think we need it.
Lex Fridman (1:42:01.560)
The understatement of the century, it would be nice.
Karl Deisseroth (1:42:05.260)
Well, it's also a good question if it's possible.
Lex Fridman (1:42:07.780)
Yeah, yeah.
Karl Deisseroth (1:42:08.780)
Well, that I have some thoughts on too.
Lex Fridman (1:42:11.940)
But to this specific question,
Karl Deisseroth (1:42:14.900)
I don't think we need a theory of everything.
Lex Fridman (1:42:16.340)
I think there will be unifying principles we can get to.
Lex Fridman (1:42:20.380)
But even shy of that, we can treat symptoms
Lex Fridman (1:42:23.540)
and that's a big step.
Lex Fridman (1:42:24.640)
And as you say, different unhappy families are different,
Lex Fridman (1:42:27.920)
different unhappy people are different.
Karl Deisseroth (1:42:30.060)
If we have somebody who comes to the clinic
Lex Fridman (1:42:31.740)
and I see someone with a profound anhedonia
Karl Deisseroth (1:42:34.700)
as one of their main symptoms,
Lex Fridman (1:42:36.360)
inability to enjoy things,
Lex Fridman (1:42:38.100)
and if I know based on optogenetics work and animal work
Lex Fridman (1:42:41.380)
that a particular medication can treat anhedonia,
Karl Deisseroth (1:42:44.700)
even if it doesn't fix major depression in everybody,
Lex Fridman (1:42:47.340)
if I treat that one symptom in that one person,
Karl Deisseroth (1:42:50.420)
that's a good thing.
Lex Fridman (1:42:51.620)
And so we don't need the theory of everything
Lex Fridman (1:42:55.300)
and we don't even need the unifying principle
Lex Fridman (1:42:58.420)
to help people with insights that come from optogenetics.
Lex Fridman (1:43:01.620)
How much does talking help for diagnosis
Lex Fridman (1:43:05.580)
and for treatment, would you say, for depression?
Karl Deisseroth (1:43:09.760)
It's a big part of what we do.
Lex Fridman (1:43:11.560)
Every good psychiatrist should be pretty adept
Karl Deisseroth (1:43:15.260)
in these verbal communications and talk therapy
Lex Fridman (1:43:18.200)
as part of what they do.
Karl Deisseroth (1:43:20.020)
I give medications, I deliver brain stimulation treatments,
Lex Fridman (1:43:22.900)
but a big, big part of everything I do with every patient
Karl Deisseroth (1:43:26.340)
is talk therapy because it works so well together
Lex Fridman (1:43:31.000)
with these other modalities.
Karl Deisseroth (1:43:33.300)
Even alone, it can help people with moderate
Lex Fridman (1:43:36.180)
or mild depression by itself.
Karl Deisseroth (1:43:39.980)
People with severe depression,
Lex Fridman (1:43:41.580)
people with other psychiatric illnesses that are severe,
Karl Deisseroth (1:43:46.260)
you don't wanna do talk therapy alone,
Lex Fridman (1:43:47.780)
that's not gonna do it.
Lex Fridman (1:43:48.860)
But it still is crucial to do together with the others.
Lex Fridman (1:43:52.220)
And it's critical because it's part of how
Karl Deisseroth (1:43:56.700)
you reshape cognitions, complex activity patterns,
Lex Fridman (1:44:01.300)
and you won't get to that with a medication
Karl Deisseroth (1:44:03.580)
or a brain stimulation treatment.
Lex Fridman (1:44:05.380)
Do you have advice for people who suffer
Karl Deisseroth (1:44:07.780)
from mild forms of depression or feel as they might,
Lex Fridman (1:44:12.660)
both for those people, and do you have advice
Karl Deisseroth (1:44:14.980)
for people who love the people who suffer
Lex Fridman (1:44:19.480)
from depression and want to help?
Karl Deisseroth (1:44:22.060)
Yeah, one of the incredibly frustrating things
Lex Fridman (1:44:26.340)
about depression is the very nature of it makes it hard
Karl Deisseroth (1:44:30.620)
for the people who suffer to get treatment
Lex Fridman (1:44:34.220)
because they're hopeless,
Lex Fridman (1:44:35.740)
so they don't think treatment will help.
Lex Fridman (1:44:37.460)
They have low energy, so they're not motivated
Karl Deisseroth (1:44:40.540)
to participate in treatment in many cases.
Lex Fridman (1:44:43.980)
Sometimes they're actively suicidal.
Karl Deisseroth (1:44:46.500)
That certainly doesn't help.
Lex Fridman (1:44:48.300)
They have all these things that seem to prevent treatment
Karl Deisseroth (1:44:53.780)
from being effective.
Lex Fridman (1:44:54.620)
So the loved ones, that's where the loved ones
Karl Deisseroth (1:44:56.340)
are so important, is helping them overcome these barriers
Lex Fridman (1:44:59.780)
to treatment, the motivation, the safety, and the insight.
Karl Deisseroth (1:45:05.100)
That's critical, and particularly for the severe cases.
Lex Fridman (1:45:09.460)
For the mild cases, where people still have some insight
Lex Fridman (1:45:13.780)
and motivation and energy to get something done,
Lex Fridman (1:45:17.420)
there are many things you can do.
Karl Deisseroth (1:45:20.740)
Exercise is extremely important in mood maintenance.
Lex Fridman (1:45:25.500)
Regulation of sleep and getting sufficient
Lex Fridman (1:45:28.260)
and regular enough sleep is very important.
Lex Fridman (1:45:31.140)
And talk therapy can be helpful in those mild
Karl Deisseroth (1:45:33.540)
or moderate cases, just looking at cognitions,
Lex Fridman (1:45:36.380)
looking at patterns of thought that people
Karl Deisseroth (1:45:40.700)
may have fallen into, where they catastrophize,
Lex Fridman (1:45:43.500)
where they spiral from small things into big things.
Karl Deisseroth (1:45:49.220)
A little bit of talk therapy, 10, 12 sessions,
Lex Fridman (1:45:52.640)
can help people identify those patterns they may have
Karl Deisseroth (1:45:55.680)
in themselves that are taking occasional negative thoughts,
Lex Fridman (1:46:00.980)
which everybody has, and magnifying those
Karl Deisseroth (1:46:03.820)
into more persistent negative states.
Lex Fridman (1:46:08.220)
If you work at this, and it's kind of like homework,
Karl Deisseroth (1:46:10.780)
this is what we call cognitive behavioral therapy.
Lex Fridman (1:46:14.060)
It's very structured, very organized.
Karl Deisseroth (1:46:15.620)
You work hard.
Lex Fridman (1:46:16.460)
It requires insight and motivation,
Lex Fridman (1:46:18.100)
and you have to be motivated.
Lex Fridman (1:46:20.340)
But if you are, then you can identify these triggers
Karl Deisseroth (1:46:23.380)
that send you down particular pathways.
Lex Fridman (1:46:25.300)
And work to intercept them.
Lex Fridman (1:46:27.100)
And that is amazingly very effective
Lex Fridman (1:46:30.500)
in mild to moderate cases.
Lex Fridman (1:46:32.340)
So you basically have to train yourself
Lex Fridman (1:46:35.460)
to see the world as a collection of triggers.
Lex Fridman (1:46:40.300)
And you have to first understand, like collect the data,
Lex Fridman (1:46:44.900)
like basically see every experience
Karl Deisseroth (1:46:48.780)
as a thing that creates a follow on emotion, a feeling.
Lex Fridman (1:46:53.780)
And like, I've learned this, you know, like on social media,
Karl Deisseroth (1:47:00.500)
where like early on, you know, like all of us,
Lex Fridman (1:47:05.600)
you know, I'll say something,
Karl Deisseroth (1:47:08.260)
I kind of respond to negativity with negativity.
Lex Fridman (1:47:12.820)
And then you observe the results of that.
Lex Fridman (1:47:16.380)
And then over time, you think, wait a minute.
Lex Fridman (1:47:21.300)
This thing that I've been doing where
Karl Deisseroth (1:47:24.020)
when somebody says, you suck, and you say, no, you suck.
Lex Fridman (1:47:29.020)
That never produces the result you thought it might.
Lex Fridman (1:47:32.980)
And so might not want to just, don't say you suck back.
Lex Fridman (1:47:38.420)
And I do this through a lot of things in life.
Karl Deisseroth (1:47:41.640)
I'm very fortunate to not suffer from depression,
Lex Fridman (1:47:46.460)
but first of all, I have had and have people in my life
Karl Deisseroth (1:47:51.980)
who do, and also, you know, all of us have depression
Lex Fridman (1:47:57.060)
who don't suffer from depression, have depression out.
Karl Deisseroth (1:48:00.740)
Like, it's always knocking on the door.
Lex Fridman (1:48:03.140)
Right, yeah.
Lex Fridman (1:48:04.380)
And so you have mild, I mean,
Lex Fridman (1:48:09.620)
if you're very careless with the triggers all around you,
Karl Deisseroth (1:48:14.280)
then you're just, I think all of us have the capacity
Lex Fridman (1:48:17.960)
to really suffer from that kind of chemical
Karl Deisseroth (1:48:22.300)
or psychological or philosophical existential crisis.
Lex Fridman (1:48:27.580)
But then it raises a question, why are we built this way?
Lex Fridman (1:48:30.220)
It seems like it doesn't make sense, right?
Lex Fridman (1:48:32.700)
And here's where some of us thinking about
Karl Deisseroth (1:48:34.720)
where we came from as the human family
Lex Fridman (1:48:38.940)
is kind of interesting.
Karl Deisseroth (1:48:40.500)
It doesn't make sense that somewhere on that spectrum
Lex Fridman (1:48:45.620)
that it's good to detect that there's an array
Karl Deisseroth (1:48:48.200)
of adverse forces out there in the world right now
Lex Fridman (1:48:51.900)
at this moment and to withdraw, to hunker down,
Karl Deisseroth (1:48:58.280)
to not fight, not strive, not try to meet the challenge
Lex Fridman (1:49:02.500)
and outweigh these negative forces
Karl Deisseroth (1:49:06.560)
that are present out there.
Lex Fridman (1:49:08.220)
And that makes a lot of sense, and all animals
Karl Deisseroth (1:49:13.220)
that have been studied in one form or another show this.
Lex Fridman (1:49:15.940)
Even the worm that I mentioned earlier,
Karl Deisseroth (1:49:18.260)
C. elegans with 302 neurons, it can effectively give up
Lex Fridman (1:49:22.360)
in challenging situations.
Karl Deisseroth (1:49:24.020)
We've done this with zebrafish,
Lex Fridman (1:49:25.900)
tiny little transparent fish.
Karl Deisseroth (1:49:28.420)
You can give them a challenging situation
Lex Fridman (1:49:30.340)
and they will give up, but then if you stimulate
Karl Deisseroth (1:49:33.980)
a couple very specific brain regions in particular ways,
Lex Fridman (1:49:37.180)
you can motivate them to overcome the challenge.
Lex Fridman (1:49:40.460)
And if you inhibit those regions,
Lex Fridman (1:49:41.780)
they give up much more easily than they would otherwise.
Karl Deisseroth (1:49:44.660)
You can do this in mice, you can do this in rats.
Lex Fridman (1:49:47.220)
So this is an ancestral conserve pattern
Karl Deisseroth (1:49:49.880)
to detect that things are pretty bad out there
Lex Fridman (1:49:54.940)
and to conserve energy, to hunker down,
Karl Deisseroth (1:49:58.660)
to wait out the storm.
Lex Fridman (1:50:00.260)
So as you, unfortunately, many of our maladies
Karl Deisseroth (1:50:04.300)
have useful roots that contribute to our survival.
Lex Fridman (1:50:10.240)
So both depression and motivation have uses.
Lex Fridman (1:50:14.900)
And sometimes it's nice to just shut the hell up
Lex Fridman (1:50:18.540)
and huddle with the penguins versus,
Karl Deisseroth (1:50:22.180)
for some unknown reason, venture out on your own
Lex Fridman (1:50:24.940)
into the mountains like a David Goggins type character.
Lex Fridman (1:50:28.060)
So what's the difference to you between,
Lex Fridman (1:50:31.660)
you see patients, between sort of rigorous psychoanalysis?
Karl Deisseroth (1:50:38.780)
I don't know if you consider talk therapy
Lex Fridman (1:50:41.100)
and psychoanalysis, are they neighbors,
Lex Fridman (1:50:42.740)
are they overlapping?
Lex Fridman (1:50:43.740)
They're neighbors.
Karl Deisseroth (1:50:45.220)
Psychoanalysis is, they're relatively,
Lex Fridman (1:50:49.140)
it's not nearly done as much as the talk therapy,
Karl Deisseroth (1:50:51.940)
like the cognitive behavioral therapy I mentioned.
Lex Fridman (1:50:56.540)
The psychoanalysis is a little more niche now
Lex Fridman (1:51:00.540)
and partly because it's not, the data isn't,
Lex Fridman (1:51:05.540)
in terms of actual treatment of actual therapeutic effects,
Karl Deisseroth (1:51:09.060)
data not as supportive as for cognitive behavioral therapy.
Lex Fridman (1:51:13.020)
But it's still interesting as for insight,
Karl Deisseroth (1:51:15.940)
people, a lot of people still do it
Lex Fridman (1:51:17.500)
to gain insight into themselves.
Lex Fridman (1:51:19.700)
And in general, it's a good sort of conversation starter.
Lex Fridman (1:51:23.140)
Those methods, they're good for getting things out.
Karl Deisseroth (1:51:27.460)
We don't focus on dreams typically these days
Lex Fridman (1:51:30.300)
in psychiatry, but they're great conversation starters.
Karl Deisseroth (1:51:32.540)
They're great ways to get things out if people have,
Lex Fridman (1:51:37.140)
and so we like to use those methods
Karl Deisseroth (1:51:39.020)
just to get the ball rolling sometimes,
Lex Fridman (1:51:41.060)
get people to open up a little bit.
Lex Fridman (1:51:42.900)
But the actual treatment tends not to involve
Lex Fridman (1:51:45.940)
these psychoanalytic approaches where you are really
Karl Deisseroth (1:51:49.860)
probing the unconscious mind and its manifestation
Lex Fridman (1:51:53.620)
through dreams, for example, as the goal.
Karl Deisseroth (1:51:58.020)
That's not the goal.
Lex Fridman (1:51:59.180)
Modern talk therapy, we're really focusing on treatment,
Lex Fridman (1:52:01.540)
how to get people to feel better.
Lex Fridman (1:52:03.020)
See, I use that as a conversation opener,
Karl Deisseroth (1:52:05.060)
the Freudian thing where I try to delve at a bar
Lex Fridman (1:52:09.780)
of the deep sexual desires in a person's subconscious
Lex Fridman (1:52:13.180)
and I find that opens up possibilities very quickly.
Lex Fridman (1:52:16.020)
Now, what's, I mean, this is a silly sounding question,
Lex Fridman (1:52:20.340)
but what's the difference between
Lex Fridman (1:52:22.180)
cognitive behavioral therapy and conversation?
Karl Deisseroth (1:52:25.580)
So, because I personally, as a fan of conversations,
Lex Fridman (1:52:30.340)
as a fan of just, I like listening to podcasts
Karl Deisseroth (1:52:34.060)
versus like audio book, I like both,
Lex Fridman (1:52:36.020)
but they're very different and I like conversation.
Karl Deisseroth (1:52:38.580)
I like, it makes me personally very anxious,
Lex Fridman (1:52:41.180)
so I like to be the listener, like a third wheel,
Karl Deisseroth (1:52:45.020)
like overhearing a conversation kind of thing,
Lex Fridman (1:52:47.660)
but it's a really powerful method for humans
Karl Deisseroth (1:52:51.140)
to explore each other's mind, just raw conversation.
Lex Fridman (1:52:54.340)
So, do you think it can be more productive
Karl Deisseroth (1:52:58.260)
to be very systematic about it or is conversation itself
Lex Fridman (1:53:01.740)
the art form of helping each other,
Lex Fridman (1:53:04.700)
understanding each other and helping each other?
Lex Fridman (1:53:06.740)
There are forms of talk therapy
Karl Deisseroth (1:53:08.580)
that are essentially conversational
Lex Fridman (1:53:10.940)
or they much more approach pure conversation.
Karl Deisseroth (1:53:13.460)
There's a befriending therapy,
Lex Fridman (1:53:17.100)
there's interpersonal therapy.
Karl Deisseroth (1:53:18.460)
These are approaches that are purely talk therapy,
Lex Fridman (1:53:23.060)
but they're not as structured
Karl Deisseroth (1:53:25.580)
as cognitive behavioral therapy.
Lex Fridman (1:53:26.780)
Cognitive behavioral therapy is,
Karl Deisseroth (1:53:28.980)
there are manuals, there are guidelines.
Lex Fridman (1:53:31.060)
You can almost go through it in a very cookbooky way.
Karl Deisseroth (1:53:33.700)
There's homework that you get done.
Lex Fridman (1:53:35.700)
So, it's in its fullest form,
Karl Deisseroth (1:53:38.700)
it's very different from these
Lex Fridman (1:53:39.700)
more conversational strategies.
Lex Fridman (1:53:42.140)
But what's interesting is sometimes people compare them
Lex Fridman (1:53:44.300)
and so you'll see almost like randomized controlled studies
Karl Deisseroth (1:53:49.540)
comparing cognitive behavioral therapy
Lex Fridman (1:53:51.340)
with interpersonal therapy, for example.
Lex Fridman (1:53:53.580)
And they both can work and actually in some studies,
Lex Fridman (1:53:56.180)
they look comparable.
Karl Deisseroth (1:53:59.180)
So, to your point, conversation and insights
Lex Fridman (1:54:03.340)
that come from conversation, if done well,
Karl Deisseroth (1:54:05.500)
if done artfully, can be as powerful.
Lex Fridman (1:54:09.060)
This reminds me of Robin Williams.
Karl Deisseroth (1:54:10.980)
I have to ask you several questions here on that.
Lex Fridman (1:54:13.980)
But one of my favorite movies is Good Will Hunting.
Karl Deisseroth (1:54:16.980)
I don't know if you've seen it with Robin Williams.
Lex Fridman (1:54:19.420)
So, as a psychiatrist yourself,
Lex Fridman (1:54:21.940)
can you do a deep analysis of this other famous psychiatrist
Lex Fridman (1:54:25.620)
which is the movie character played by Robin Williams
Lex Fridman (1:54:29.020)
at Good Will Hunting?
Lex Fridman (1:54:30.700)
Is it just a caricature between a psychiatrist
Lex Fridman (1:54:33.260)
and patient relationship?
Lex Fridman (1:54:35.340)
Or is there something to you that was moving
Karl Deisseroth (1:54:39.340)
about his ability to connect
Lex Fridman (1:54:41.220)
to this obviously struggling young kid?
Karl Deisseroth (1:54:45.140)
I think you hit on the key thing there
Lex Fridman (1:54:46.580)
which is the depth of the connection.
Karl Deisseroth (1:54:48.820)
If there's too powerful a connection,
Lex Fridman (1:54:55.580)
that can impair therapy
Karl Deisseroth (1:54:58.340)
because it could impair open communication.
Lex Fridman (1:55:01.140)
If someone, if a patient has a, sees the role,
Karl Deisseroth (1:55:05.540)
sees the relationship in a particular way,
Lex Fridman (1:55:08.140)
like in a friendly way maybe,
Karl Deisseroth (1:55:09.700)
or like a parental child type way,
Lex Fridman (1:55:15.580)
that can cause problems because then what they choose
Karl Deisseroth (1:55:17.860)
to share, what they choose to bring up is selected
Lex Fridman (1:55:21.700)
to be appropriate for that view of the relationship.
Lex Fridman (1:55:26.460)
And so, I and many other talk therapists actually prefer
Lex Fridman (1:55:32.060)
not to let things get, not let the connection get that deep.
Karl Deisseroth (1:55:37.500)
You wanna have trust.
Lex Fridman (1:55:39.180)
You wanna have a therapeutic alliance, we sometimes call it.
Lex Fridman (1:55:44.260)
But it's got to be enough of a blank slate
Lex Fridman (1:55:47.180)
that the patient is not consciously
Karl Deisseroth (1:55:50.820)
or unconsciously constrained in what they choose to share.
Lex Fridman (1:55:55.780)
And so, great movie, great actors, all good,
Karl Deisseroth (1:56:01.420)
no complaints except realistically,
Lex Fridman (1:56:06.300)
the relationship should be a little more arm's length
Karl Deisseroth (1:56:09.020)
than that.
Lex Fridman (1:56:11.220)
Let's pretend this is real life.
Karl Deisseroth (1:56:13.140)
Sometimes can't you leave a little bit of yourself
Lex Fridman (1:56:16.900)
in the interaction with the patient?
Karl Deisseroth (1:56:18.540)
I mean, it's another human being.
Lex Fridman (1:56:20.540)
Yes, so there's a balance.
Lex Fridman (1:56:22.420)
And actually you do need some of it
Lex Fridman (1:56:24.420)
because let's say this person is having challenges,
Karl Deisseroth (1:56:28.820)
interpersonal challenges in their life.
Lex Fridman (1:56:32.340)
The best way to notice what those are
Lex Fridman (1:56:36.500)
and to identify them and to work with them
Lex Fridman (1:56:39.740)
is if you can elicit some of those problems
Karl Deisseroth (1:56:43.220)
in the office, in the therapeutic interaction.
Lex Fridman (1:56:47.620)
And this is really powerful.
Karl Deisseroth (1:56:49.980)
As long as you're alert to it, aware of it,
Lex Fridman (1:56:54.420)
and you don't let it go out of hand,
Karl Deisseroth (1:56:56.980)
this transference, we call it,
Lex Fridman (1:56:58.980)
is when you transfer in between
Karl Deisseroth (1:57:04.700)
the current therapeutic relationship
Lex Fridman (1:57:06.380)
and external relationships
Karl Deisseroth (1:57:08.580)
that the patient may have had with others.
Lex Fridman (1:57:10.700)
And so if the therapist starts to feel
Karl Deisseroth (1:57:14.060)
an inner feeling like anger, let's say.
Lex Fridman (1:57:17.940)
So let's say you have a patient
Karl Deisseroth (1:57:18.940)
who is stirring frustration in you
Lex Fridman (1:57:22.260)
or even in extreme cases, anger,
Karl Deisseroth (1:57:24.420)
the best thing for the therapist to do in that case
Lex Fridman (1:57:26.900)
is to recognize it and to realize
Karl Deisseroth (1:57:31.100)
that's probably being stirred by other people
Lex Fridman (1:57:33.300)
in the patient's life.
Lex Fridman (1:57:34.860)
And that could be the source of a lot of problems.
Lex Fridman (1:57:37.020)
And so instead of trying to wall it off,
Lex Fridman (1:57:39.940)
and say, oh, I shouldn't be feeling that,
Lex Fridman (1:57:42.020)
I better be a better therapist instead,
Lex Fridman (1:57:44.300)
and recognize it and use it,
Lex Fridman (1:57:47.100)
and help the patient that way.
Lex Fridman (1:57:48.260)
And so you've gotta be a human being.
Lex Fridman (1:57:49.620)
You've gotta be a person who feels.
Karl Deisseroth (1:57:52.060)
You've gotta be open.
Lex Fridman (1:57:53.660)
But be in control of it and be aware of it.
Karl Deisseroth (1:57:56.540)
If I may, I just wanna read,
Lex Fridman (1:57:58.380)
because it's one of my favorite scenes.
Karl Deisseroth (1:58:00.020)
Probably one of the greatest scenes,
Lex Fridman (1:58:02.620)
one of the greatest scenes in movie history
Karl Deisseroth (1:58:04.540)
because Robin Williams does a single take.
Lex Fridman (1:58:08.540)
Is that right?
Karl Deisseroth (1:58:09.380)
I didn't know that.
Lex Fridman (1:58:10.220)
So this is a very interesting interaction between them.
Lex Fridman (1:58:12.060)
So Will, and I'm sure this is a common interaction,
Lex Fridman (1:58:17.380)
maybe with a therapist and a patient,
Karl Deisseroth (1:58:19.060)
maybe with a father and son,
Lex Fridman (1:58:21.300)
where Will, the young character,
Karl Deisseroth (1:58:23.500)
the young, brilliant mathematician,
Lex Fridman (1:58:25.060)
and Sean is the therapist, the older therapist,
Karl Deisseroth (1:58:28.380)
where Will looks at a painting that Sean painted
Lex Fridman (1:58:31.820)
and then does a deep, critical analysis of the painting
Karl Deisseroth (1:58:35.940)
that basically describes pretending
Lex Fridman (1:58:40.580)
as if he can understand another human being completely
Karl Deisseroth (1:58:43.420)
by just looking at their painting.
Lex Fridman (1:58:45.420)
And then Sean gives this whole speech
Karl Deisseroth (1:58:49.300)
that contrasts sort of raw intelligence
Lex Fridman (1:58:52.340)
and the wisdom of experience.
Lex Fridman (1:58:54.300)
And Sean says, single take.
Lex Fridman (1:58:56.860)
He says, you've never been out of Boston, right?
Lex Fridman (1:58:59.620)
And Will says, nope.
Lex Fridman (1:59:01.260)
All this in a sexy Boston accent, by the way.
Lex Fridman (1:59:03.660)
And then Sean gives the speech.
Lex Fridman (1:59:07.420)
If I asked you about art,
Karl Deisseroth (1:59:08.820)
you'd probably give me the skinny
Lex Fridman (1:59:10.340)
and about every art book ever written.
Karl Deisseroth (1:59:12.940)
Michelangelo, you know a lot about him.
Lex Fridman (1:59:15.700)
Life's work, political aspirations,
Karl Deisseroth (1:59:17.540)
him and the Pope, sexual orientation,
Lex Fridman (1:59:19.700)
the whole works, right?
Lex Fridman (1:59:21.380)
But I bet you can't tell me what it smells like
Lex Fridman (1:59:23.980)
in the Sistine Chapel.
Karl Deisseroth (1:59:26.060)
You never actually stood there
Lex Fridman (1:59:27.660)
and looked up at that beautiful ceiling, seeing that.
Karl Deisseroth (1:59:31.460)
If I asked you about women,
Lex Fridman (1:59:32.780)
you'll probably give me a syllabus
Karl Deisseroth (1:59:34.860)
of your personal favorites.
Lex Fridman (1:59:36.700)
You may have even been laid a few times.
Karl Deisseroth (1:59:40.220)
The language here is just beautiful.
Lex Fridman (1:59:42.700)
But you can't tell me what it feels like
Karl Deisseroth (1:59:45.420)
to wake up next to a woman and feel truly happy.
Lex Fridman (1:59:49.100)
You're a tough kid.
Karl Deisseroth (1:59:50.580)
If I asked you about war,
Lex Fridman (1:59:51.740)
you'd probably throw Shakespeare at me, right?
Karl Deisseroth (1:59:54.460)
Probably not, but let's say.
Lex Fridman (1:59:57.380)
Once more into the breach here, friends.
Lex Fridman (1:59:59.860)
But you've never been near one.
Lex Fridman (20:00.600)
in some level was able to access
Karl Deisseroth (20:03.440)
this nonlinearity of processing
Lex Fridman (20:06.280)
or had seen enough in family that he knew what it was
Lex Fridman (20:10.600)
and was able to reflect it down
Lex Fridman (20:13.360)
in black and white on the paper.
Lex Fridman (20:14.560)
So what he was able to do was quite authentic
Lex Fridman (20:17.640)
in that sense.
Karl Deisseroth (20:19.240)
Of course, I don't want to pigeonhole him.
Lex Fridman (20:21.880)
He was doing much more than that.
Karl Deisseroth (20:23.760)
It was much more than talking about altered human
Lex Fridman (20:29.400)
thought processes and thought disorders.
Lex Fridman (20:31.320)
But that was an aspect that he was so good at representing
Lex Fridman (20:34.800)
that it had to be intentional to some extent.
Lex Fridman (20:37.560)
And a tiny tangent.
Lex Fridman (20:38.760)
What does your own writing look like for this book?
Karl Deisseroth (20:42.000)
Because it's extremely well written.
Lex Fridman (20:44.240)
How many edits?
Karl Deisseroth (20:46.040)
Did you just drink some whiskey
Lex Fridman (20:48.120)
and like I'm imagining Hemingway style?
Karl Deisseroth (20:51.440)
What's a very different, the writing is very different.
Lex Fridman (20:53.480)
I mean, it's really, really well written,
Karl Deisseroth (20:55.680)
which was like, I was reading it.
Lex Fridman (21:00.200)
It makes you realize,
Karl Deisseroth (21:01.240)
because I was expecting sort of a science kind of,
Lex Fridman (21:03.640)
which it is like elucidating something
Karl Deisseroth (21:08.640)
about the human mind kind of thing.
Lex Fridman (21:09.920)
But you could also probably write really strong novels.
Lex Fridman (21:15.840)
So maybe that's in the future.
Lex Fridman (21:17.000)
But anyway, what is your, how many edits?
Lex Fridman (21:19.560)
What's your style?
Lex Fridman (21:20.400)
Does it look like that?
Lex Fridman (21:21.320)
Is it more structured, organized?
Lex Fridman (21:22.880)
Unfortunately, I used a laptop,
Lex Fridman (21:24.440)
so I didn't have this sort of a beautiful record.
Lex Fridman (21:26.480)
No typewriters, cigarette, and whiskey.
Karl Deisseroth (21:29.520)
I did explore which was their particular altered state
Lex Fridman (21:33.120)
that would help me to be most creative.
Lex Fridman (21:34.880)
And I found actually, I actually did the best
Lex Fridman (21:38.240)
while sober, but slightly disinhibited
Karl Deisseroth (21:42.640)
in the late hours of the night or early morning.
Lex Fridman (21:46.320)
Yeah, particularly late hours of the night there.
Karl Deisseroth (21:50.040)
I have a friend who would tell me
Lex Fridman (21:52.400)
that she thought that very early in the morning,
Karl Deisseroth (21:54.680)
her inner critic was still asleep
Lex Fridman (21:57.160)
and she could write more effectively
Karl Deisseroth (21:59.280)
before her inner critic woke up.
Lex Fridman (22:01.320)
And I actually found that outstanding advice for me
Karl Deisseroth (22:03.840)
that I often found that I was looser
Lex Fridman (22:07.000)
and could write more in the morning.
Lex Fridman (22:09.360)
But the other interesting thing is each chapter,
Lex Fridman (22:12.120)
each story, it's about a different human being
Karl Deisseroth (22:15.520)
with a different class of psychiatric disorder.
Lex Fridman (22:18.440)
That's what each story, each chapter is anchored in.
Lex Fridman (22:22.880)
But I'm trying to use words and style of writing
Lex Fridman (22:27.960)
and diction that captures the feeling of the disorder.
Lex Fridman (22:32.960)
And so it's different in each story.
Lex Fridman (22:34.840)
In the story about mania, which is a very expansive,
Karl Deisseroth (22:39.480)
exuberant, at least briefly uplifting state
Lex Fridman (22:43.240)
where the words come out in a torrent
Lex Fridman (22:45.160)
and they're complex and pressured and elaborate.
Lex Fridman (22:48.600)
I try to capture that feeling
Karl Deisseroth (22:50.280)
with the words used in that chapter.
Lex Fridman (22:52.480)
And then in the schizophrenia or psychosis chapter,
Karl Deisseroth (22:56.560)
where things slowly fragment over time
Lex Fridman (22:58.440)
and become looser and separated,
Karl Deisseroth (23:01.840)
I try to capture that in the writing too.
Lex Fridman (23:03.840)
So for each, it wasn't as if there was a single mode
Karl Deisseroth (23:06.720)
I could be in for the whole book.
Lex Fridman (23:08.320)
For each chapter, I had to put myself into a different mode
Karl Deisseroth (23:11.240)
to capture that inner feeling of the disorder.
Lex Fridman (23:14.400)
When you put yourself in that mode, does that change you?
Karl Deisseroth (23:17.520)
Yeah, I couldn't turn it on and off right away.
Lex Fridman (23:19.900)
I had to, first I would start by thinking about the person
Karl Deisseroth (23:23.880)
or the people, one or two people based on real patients
Lex Fridman (23:26.240)
and the stories that are put forth.
Karl Deisseroth (23:29.960)
The symptom descriptions are real,
Lex Fridman (23:31.360)
they're from the patients.
Karl Deisseroth (23:32.240)
Of course, all details change to protect privacy,
Lex Fridman (23:35.400)
but the actual symptom descriptions are real.
Lex Fridman (23:38.040)
And I would sit with them and really try to inhabit
Lex Fridman (23:41.240)
the space of the mind of that person that I knew.
Lex Fridman (23:45.640)
And that's not instantaneous.
Lex Fridman (23:47.520)
It would take some time.
Karl Deisseroth (23:48.840)
I needed quiet, I needed to be still.
Lex Fridman (23:51.200)
That's another reason late at night is good.
Karl Deisseroth (23:53.700)
Sergey posted that drowsiness gives creativity boosts,
Lex Fridman (23:56.800)
according to Andrew Huberman.
Karl Deisseroth (23:58.840)
Thank you, Andrew.
Lex Fridman (23:59.840)
He's not wrong, he's not wrong.
Lex Fridman (24:03.160)
Why projections?
Lex Fridman (24:04.840)
Is it, I mean, instead of putting words into your mouth,
Karl Deisseroth (24:09.840)
because I can imagine a lot.
Lex Fridman (24:11.320)
I mean, to me, I will start putting words in your mouth,
Karl Deisseroth (24:15.680)
despite what I just said.
Lex Fridman (24:18.120)
So, I mean, to me, projections,
Karl Deisseroth (24:20.480)
working on neural networks, for example,
Lex Fridman (24:22.000)
from an artificial neural networks,
Karl Deisseroth (24:23.360)
from a machine learning perspective,
Lex Fridman (24:25.240)
it's often, that's exactly what you're doing.
Karl Deisseroth (24:27.520)
You have an incredibly complex thing
Lex Fridman (24:29.280)
and you're trying to find simple representations
Karl Deisseroth (24:32.960)
in order for you to make sense of it.
Lex Fridman (24:34.640)
So I was kind of thinking about in that way,
Karl Deisseroth (24:36.760)
which is like this incredibly complex neural network
Lex Fridman (24:43.080)
that is kind of projecting itself onto the world
Karl Deisseroth (24:46.920)
through this low bandwidth expression of emotion and speech
Lex Fridman (24:51.040)
and all that kind of stuff.
Lex Fridman (24:52.280)
And the way it's, we only have that window into your soul,
Lex Fridman (24:57.000)
the eyes and the speech and so on.
Lex Fridman (24:58.440)
So in that way, when there's any kind of disorder,
Lex Fridman (25:03.440)
we get to only see that disorder through that narrow window
Karl Deisseroth (25:08.160)
as opposed to the full complexity of its origins.
Lex Fridman (25:11.120)
The word projections definitely serves that purpose here,
Lex Fridman (25:13.880)
but it's got a few other really appropriate
Lex Fridman (25:17.640)
other connotations as well.
Lex Fridman (25:19.360)
So the first thing is a projection
Lex Fridman (25:20.920)
in terms of neuroscience is this long range connection
Karl Deisseroth (25:24.800)
that goes from one part of the brain to another.
Lex Fridman (25:26.880)
And so it's what binds two parts of our brain together.
Karl Deisseroth (25:30.560)
There are projections, long range connections
Lex Fridman (25:33.080)
of axons, these are the outgoing threads
Karl Deisseroth (25:36.040)
that connect one part of the brain to another part.
Lex Fridman (25:39.760)
There's a projection that links, for example,
Karl Deisseroth (25:41.920)
auditory cortex where we hear things to reward centers
Lex Fridman (25:45.720)
where we can feel, where feelings of pleasure
Lex Fridman (25:48.360)
and reward are initiated.
Lex Fridman (25:50.080)
And it's been shown that if you have reduced connectivity
Karl Deisseroth (25:53.440)
along that dimension, you are less able to enjoy music.
Lex Fridman (25:56.520)
And so these connections, these projections matter.
Karl Deisseroth (25:58.720)
They define how effectively two parts of the brain
Lex Fridman (26:01.880)
can engage with each other and join together
Karl Deisseroth (26:04.520)
to form a joint representation of something.
Lex Fridman (26:07.760)
So that's one meaning, it's pure neuroscience.
Karl Deisseroth (26:09.360)
The word projection is used all the time.
Lex Fridman (26:11.440)
And it happens to be something that optogenetics,
Karl Deisseroth (26:13.800)
a technique that maybe we'll talk about a little later
Lex Fridman (26:16.040)
that works particularly well with,
Karl Deisseroth (26:17.200)
we can use light to turn on or off the activity
Lex Fridman (26:19.960)
along these projections from one spot of the brain
Karl Deisseroth (26:22.200)
to another.
Lex Fridman (26:23.040)
And this is particularly referring
Karl Deisseroth (26:24.080)
to the long range connections.
Lex Fridman (26:25.840)
It's particularly straightforward
Karl Deisseroth (26:27.360)
along these long range projections
Lex Fridman (26:28.700)
that connect different parts of the brain,
Lex Fridman (26:29.840)
but it works over shorter range too.
Lex Fridman (26:32.040)
But then there's this other meaning of projections
Karl Deisseroth (26:34.120)
which you were bringing up, which is very relevant,
Lex Fridman (26:35.760)
which is at some point you can reduce something
Karl Deisseroth (26:39.040)
from one level of dimensionality to another,
Lex Fridman (26:41.120)
and you can project down into a lower dimensional space,
Karl Deisseroth (26:43.280)
for example.
Lex Fridman (26:44.840)
And then finally, there's a psychiatric term projections
Karl Deisseroth (26:49.200)
which comes up all the time, which is we very often
Lex Fridman (26:54.120)
will look at our internal states
Lex Fridman (26:56.440)
and to understand somebody else,
Lex Fridman (26:57.720)
we'll project them onto somebody else.
Karl Deisseroth (27:00.520)
We'll try to understand someone else's behavior
Lex Fridman (27:02.840)
and make sense of it by projecting our own inner feelings,
Karl Deisseroth (27:06.440)
our own sort of narrative onto them
Lex Fridman (27:10.880)
and use that as a way to help us understand them better.
Lex Fridman (27:15.040)
And we'll do the reverse too.
Lex Fridman (27:16.140)
We'll take things we see in the outside world
Lex Fridman (27:18.400)
and we'll bring them into ourselves
Lex Fridman (27:19.660)
and see how well they map, how well they align.
Karl Deisseroth (27:21.480)
That's called introjection.
Lex Fridman (27:23.220)
So projections turns out to be a really rich word.
Lex Fridman (27:25.840)
And then finally, of course, there's the very common
Lex Fridman (27:28.320)
sense of it as a projector that illuminates
Karl Deisseroth (27:31.940)
by conveying information across space with light.
Lex Fridman (27:35.920)
So for English, for English language,
Karl Deisseroth (27:38.280)
perfect word to use for this book.
Lex Fridman (27:40.200)
But what's funny is not every,
Karl Deisseroth (27:43.260)
there are a lot of international translations now
Lex Fridman (27:45.000)
and all those rich connotations
Karl Deisseroth (27:46.760)
aren't captured in other languages.
Lex Fridman (27:48.660)
And so for some translations, connections is used
Karl Deisseroth (27:53.400)
instead of projections.
Lex Fridman (27:54.400)
In fact, even in England,
Karl Deisseroth (27:56.120)
the British version is connections instead of projections
Lex Fridman (27:58.320)
because apparently projections
Karl Deisseroth (28:00.040)
doesn't have the full connotation, I was told.
Lex Fridman (28:02.600)
So you have to sacrifice some of the rich ambiguity
Karl Deisseroth (28:06.560)
of meaning with connections, that's interesting.
Lex Fridman (28:09.920)
I mean, connect, man, words are so interesting.
Karl Deisseroth (28:12.680)
They have so many meaning.
Lex Fridman (28:14.000)
I love language and how much is lost in translation.
Karl Deisseroth (28:16.960)
I'm very fortunate enough to be able to speak.
Lex Fridman (28:19.760)
I'm not good at languages.
Karl Deisseroth (28:20.760)
I was just, I guess, forced to by life's circumstance
Lex Fridman (28:24.520)
to learn two languages, Russian and English.
Lex Fridman (28:27.720)
And it's just so interesting to watch
Lex Fridman (28:29.640)
how much of culture, how much of people,
Lex Fridman (28:31.420)
how much of history is lost in translation.
Lex Fridman (28:35.240)
The poetry, the music, the history, the pain,
Karl Deisseroth (28:39.960)
the way the scientists actually express themselves,
Lex Fridman (28:41.880)
which is funny.
Karl Deisseroth (28:43.000)
I mean, it's so sad to see how much brilliant work
Lex Fridman (28:52.000)
that was written in Russian.
Karl Deisseroth (28:53.440)
There's a whole culture of science in the Soviet Union
Lex Fridman (28:56.960)
that is now lost.
Karl Deisseroth (28:58.000)
It makes me wonder, in the modern day,
Lex Fridman (29:01.120)
how much incredible science is going on in China
Karl Deisseroth (29:05.160)
that is lost in translation.
Lex Fridman (29:07.000)
And I'll never, I mean, that makes me very sad
Karl Deisseroth (29:09.040)
because I'll never learn Chinese in the same way
Lex Fridman (29:13.360)
that I've learned English and Russian.
Karl Deisseroth (29:15.800)
Maybe, whenever I say stuff like that,
Lex Fridman (29:17.900)
people are like, well, there's still time.
Karl Deisseroth (29:19.800)
But, you know, yeah, that's actually fair,
Lex Fridman (29:23.820)
that I think the 21st century, both China and U.S.
Karl Deisseroth (29:29.880)
will have very important roles in the scientific development
Lex Fridman (29:33.640)
and we should actually bridge the gap through language.
Lex Fridman (29:36.880)
And that doesn't just mean convincing Chinese
Lex Fridman (29:39.440)
to speak English.
Karl Deisseroth (29:40.680)
That means also learning Chinese.
Lex Fridman (29:43.240)
Well, we need these bridge people who can do both.
Karl Deisseroth (29:45.440)
You know, Nabokov, for example, writing in English
Lex Fridman (29:50.120)
beautifully, one of my favorite poets, Borges,
Karl Deisseroth (29:53.600)
who I mentioned earlier, he wrote both in English
Lex Fridman (29:56.960)
and in Spanish, I think beautifully in both.
Karl Deisseroth (2:00:02.220)
You've never held your best friend's head on your lap
Lex Fridman (2:00:05.060)
and watched him gasp his last breath,
Karl Deisseroth (2:00:07.060)
looking to you for help.
Lex Fridman (2:00:09.300)
If I asked you about love,
Karl Deisseroth (2:00:11.420)
you'd probably quote me a sonnet.
Lex Fridman (2:00:14.420)
But you've never looked at a woman
Lex Fridman (2:00:16.140)
and be truly vulnerable,
Lex Fridman (2:00:18.540)
known someone who can level you with their eyes,
Karl Deisseroth (2:00:21.780)
feeling like God put an angel on earth just for you,
Lex Fridman (2:00:25.420)
who could rescue you from the depths of hell
Lex Fridman (2:00:27.780)
and you wouldn't know what it's like to be her angel.
Lex Fridman (2:00:32.340)
To have that love for her,
Karl Deisseroth (2:00:34.300)
be there forever, through anything, through cancer.
Lex Fridman (2:00:38.340)
And you wouldn't know about sleeping,
Karl Deisseroth (2:00:40.260)
sitting up in a hospital room for two months,
Lex Fridman (2:00:42.620)
holding her hand because the doctors could see in your eyes
Karl Deisseroth (2:00:46.260)
the terms visiting hours don't apply to you.
Lex Fridman (2:00:49.220)
You don't know about real loss
Karl Deisseroth (2:00:51.260)
because that only occurs when you love something
Lex Fridman (2:00:55.180)
more than you love yourself.
Karl Deisseroth (2:00:57.860)
I doubt you've ever dared to love anybody that much.
Lex Fridman (2:01:01.860)
I look at you.
Karl Deisseroth (2:01:03.260)
I don't see an intelligent, confident man.
Lex Fridman (2:01:05.700)
I see a cocky, scared, shitless kid.
Lex Fridman (2:01:08.900)
But you're a genius, Will.
Lex Fridman (2:01:10.380)
No one denies that.
Karl Deisseroth (2:01:12.060)
No one can possibly understand the depths of you.
Lex Fridman (2:01:14.820)
But you presume to know everything about me
Karl Deisseroth (2:01:16.700)
because you saw a painting of mine
Lex Fridman (2:01:18.740)
you ripped my fucking life apart.
Lex Fridman (2:01:21.660)
You're an orphan, right?
Lex Fridman (2:01:23.860)
Do you think I know the first thing
Karl Deisseroth (2:01:25.300)
about how hard your life has been,
Lex Fridman (2:01:27.620)
how you feel, who you are because I read Oliver Twist?
Lex Fridman (2:01:31.740)
Does that encapsulate you?
Lex Fridman (2:01:33.980)
Personally, I don't give a shit about all that
Lex Fridman (2:01:36.020)
because you know what?
Lex Fridman (2:01:37.540)
I can't learn anything from you
Karl Deisseroth (2:01:39.220)
that I can't read in some fucking book
Lex Fridman (2:01:41.740)
unless you want to talk about you, who you are.
Lex Fridman (2:01:45.260)
And I'm fascinated, I'm in.
Lex Fridman (2:01:47.540)
But you don't want to do that, do you, sport?
Karl Deisseroth (2:01:50.380)
You're terrified of what you might say.
Lex Fridman (2:01:53.660)
Your move, chief.
Karl Deisseroth (2:01:55.820)
Well done, sir, I know it's a movie.
Lex Fridman (2:01:57.500)
It's interesting, right?
Lex Fridman (2:01:58.820)
So some of that conversation
Lex Fridman (2:02:00.140)
is at some intellectual level, too.
Karl Deisseroth (2:02:03.140)
It's not just emotional, it's something,
Lex Fridman (2:02:06.060)
it's like, the reason I kind of connect with that is
Karl Deisseroth (2:02:10.700)
that's a lot of work for a therapist.
Lex Fridman (2:02:14.300)
Like, to really understand another,
Karl Deisseroth (2:02:16.180)
because he's, I mean, from, okay, I know this is fictional,
Lex Fridman (2:02:19.520)
but just, there's calculation happening.
Karl Deisseroth (2:02:22.900)
He deeply cares to say the words
Lex Fridman (2:02:26.020)
that the other person needs to hear,
Lex Fridman (2:02:27.960)
but also a little bit loses himself in the pride,
Lex Fridman (2:02:32.620)
but then catches himself again,
Karl Deisseroth (2:02:35.220)
switches from anger to connection.
Lex Fridman (2:02:38.620)
Yeah.
Karl Deisseroth (2:02:39.500)
A lot is brought up there.
Lex Fridman (2:02:40.900)
You're right, there has to be some emotion
Karl Deisseroth (2:02:42.900)
in the therapist to care enough to keep going,
Lex Fridman (2:02:46.140)
to keep probing, to open up as he's doing so, right?
Karl Deisseroth (2:02:51.140)
He revealed a lot about himself, his own vulnerabilities,
Lex Fridman (2:02:53.940)
but that gave him authenticity.
Karl Deisseroth (2:02:56.780)
He had to open himself up
Lex Fridman (2:02:58.060)
so that the kid would see the authenticity
Lex Fridman (2:03:01.780)
and open himself up in return.
Lex Fridman (2:03:05.100)
So how do you do that as a psychiatrist, as a therapist?
Karl Deisseroth (2:03:10.020)
You have to be careful.
Lex Fridman (2:03:11.140)
You don't wanna do too much,
Lex Fridman (2:03:13.740)
but opening up a little bit does help.
Lex Fridman (2:03:17.540)
It does create a chance.
Karl Deisseroth (2:03:20.260)
You're offering up something
Lex Fridman (2:03:21.420)
and that helps the patient come back in return,
Lex Fridman (2:03:24.740)
and it gives you that believability and authenticity.
Lex Fridman (2:03:28.740)
Do you pay the price for that, for opening it up?
Karl Deisseroth (2:03:31.380)
You can.
Lex Fridman (2:03:32.900)
You have a family.
Karl Deisseroth (2:03:33.820)
You have an incredibly difficult research.
Lex Fridman (2:03:38.220)
You're doing a lot of things in your world.
Karl Deisseroth (2:03:40.380)
I mean, it's the price you pay for like.
Lex Fridman (2:03:43.900)
Well, this was one of the terrifying things
Karl Deisseroth (2:03:45.740)
about writing the book was I do open up
Lex Fridman (2:03:50.100)
in a little bit about my own personal life,
Karl Deisseroth (2:03:52.620)
my own personal challenges,
Lex Fridman (2:03:53.820)
and that was a considered decision
Karl Deisseroth (2:03:55.540)
because I could have done the patient work
Lex Fridman (2:04:01.360)
and the science work
Lex Fridman (2:04:02.200)
and the history of the human family work
Lex Fridman (2:04:04.900)
and tied it all together,
Lex Fridman (2:04:07.860)
but it wasn't, and in an early draft, it was like that,
Lex Fridman (2:04:13.260)
but it wasn't real yet.
Karl Deisseroth (2:04:15.540)
It wasn't something that everybody could connect with,
Lex Fridman (2:04:19.540)
and I said, then I realized, look, if I'm gonna do this,
Karl Deisseroth (2:04:23.180)
I've gotta open up myself,
Lex Fridman (2:04:26.380)
and then people can connect with me
Lex Fridman (2:04:28.140)
and see what I'm really saying, and so I did,
Lex Fridman (2:04:31.780)
and that was not something that I'd gone in planning to do.
Karl Deisseroth (2:04:37.500)
In retrospect, I learned a lot about myself.
Lex Fridman (2:04:39.360)
It was actually really, I think, a good thing that I did,
Lex Fridman (2:04:42.300)
but it was scary.
Lex Fridman (2:04:43.820)
Where are the darkest places you've ever gone in your life?
Karl Deisseroth (2:04:51.300)
You know, I had, things haven't always been easy,
Lex Fridman (2:04:55.500)
personally or professionally.
Karl Deisseroth (2:04:57.300)
I had moments, you know, I was effectively a single dad
Lex Fridman (2:05:00.820)
for a while, a number of years,
Lex Fridman (2:05:03.180)
and these came at probably the hardest,
Lex Fridman (2:05:05.300)
also, professional lifetimes for me, too,
Karl Deisseroth (2:05:09.440)
the absolute hardest days of late medical school,
Lex Fridman (2:05:13.380)
internship, taking call, getting up at 3 a.m.,
Karl Deisseroth (2:05:18.300)
surgery, medicine, rounds, unforgiving environments,
Lex Fridman (2:05:24.380)
and then all the while, personal life,
Karl Deisseroth (2:05:28.400)
stripped down to the bare, and these were low moments,
Lex Fridman (2:05:32.500)
and then I was hit particularly hard by
Karl Deisseroth (2:05:35.740)
just experiences on the clinical ward,
Lex Fridman (2:05:39.420)
connecting too deeply with patients,
Karl Deisseroth (2:05:42.020)
like a child with a brain tumor,
Lex Fridman (2:05:44.020)
and feeling it too strongly, and those things,
Karl Deisseroth (2:05:49.400)
when you get down to those lowest of the low moments,
Lex Fridman (2:05:51.760)
when everything is stripped away,
Lex Fridman (2:05:53.580)
and there's only this raw core,
Lex Fridman (2:05:58.160)
well, that's pretty hard.
Karl Deisseroth (2:06:00.260)
That was probably the lowest moment,
Lex Fridman (2:06:02.060)
and you learn a lot about yourself in those moments,
Karl Deisseroth (2:06:04.180)
you know, what's left, and then what are the roots out
Lex Fridman (2:06:09.180)
from there, and that can be powerful to see in yourself.
Lex Fridman (2:06:15.420)
Have you thought about killing yourself?
Lex Fridman (2:06:18.860)
I have not.
Karl Deisseroth (2:06:20.260)
I have not.
Lex Fridman (2:06:21.100)
Have you seen that thought in the distance?
Karl Deisseroth (2:06:25.140)
I am fortunate that that has not come to my mind,
Lex Fridman (2:06:28.940)
and I have not seen it, even in the distance,
Lex Fridman (2:06:32.020)
and in some ways, I've wondered if that's made me,
Lex Fridman (2:06:36.900)
am I a less effective psychiatrist because of that?
Karl Deisseroth (2:06:40.620)
I've been, I've felt everything stripped away.
Lex Fridman (2:06:44.060)
I've been at the lowest of the low, and yet, that.
Karl Deisseroth (2:06:48.220)
There's still hope.
Lex Fridman (2:06:49.060)
There's a light of hope still at the end of the tunnel.
Lex Fridman (2:06:52.420)
So you never lost, even for brief moments, that.
Lex Fridman (2:06:56.780)
Never did.
Karl Deisseroth (2:06:57.780)
I don't know why.
Lex Fridman (2:06:59.020)
You don't know why.
Karl Deisseroth (2:06:59.860)
There was no reason.
Lex Fridman (2:07:00.820)
You don't know why.
Karl Deisseroth (2:07:01.660)
No reason to feel hope at that moment, honestly.
Lex Fridman (2:07:03.900)
Uh, so it was just the light without reason.
Karl Deisseroth (2:07:07.700)
Yeah, that's right.
Lex Fridman (2:07:10.940)
What wisdom do you draw from that time?
Karl Deisseroth (2:07:15.060)
About, so first of all, you said something funny,
Lex Fridman (2:07:19.460)
which is, I wonder if it, that it's somehow
Karl Deisseroth (2:07:23.140)
not having thoughts of suicide limits your capacity
Lex Fridman (2:07:28.140)
to truly understand somebody who is having those thoughts.
Lex Fridman (2:07:34.780)
So how many demons must a psychiatrist have
Lex Fridman (2:07:39.380)
in order to be a good psychiatrist?
Karl Deisseroth (2:07:42.940)
You know, this is a really interesting question.
Lex Fridman (2:07:45.420)
I think everybody knows, and I can say this,
Karl Deisseroth (2:07:47.580)
that psychiatrists can be a little unusual.
Lex Fridman (2:07:50.820)
We think about ourselves, right?
Karl Deisseroth (2:07:53.700)
We think about our brains.
Lex Fridman (2:07:54.780)
That may be one reason why we become psychiatrists
Karl Deisseroth (2:07:56.940)
is we think, oh, that's interesting going on in there.
Lex Fridman (2:07:59.340)
What's that about?
Lex Fridman (2:08:00.660)
So a little introspective, a little introverted maybe,
Lex Fridman (2:08:03.940)
and that's what can make us good when we're good.
Karl Deisseroth (2:08:07.720)
And, but also that may select for people
Lex Fridman (2:08:12.720)
who have some unusual aspects,
Lex Fridman (2:08:14.740)
but you don't have to have all of them.
Lex Fridman (2:08:17.140)
There's a lot that can go wrong in the psychiatric realm.
Karl Deisseroth (2:08:21.100)
I think having some of those, some of it,
Lex Fridman (2:08:24.860)
but not all of it is enough.
Karl Deisseroth (2:08:26.140)
You get to see how low things can get.
Lex Fridman (2:08:29.580)
You can get, you get empathy from that,
Karl Deisseroth (2:08:35.660)
even if the symptoms are not the same.
Lex Fridman (2:08:38.440)
Just empathy for struggle, for suffering.
Karl Deisseroth (2:08:41.060)
That's right, that's right.
Lex Fridman (2:08:42.820)
Do you yourself have to practice observing triggers
Lex Fridman (2:08:46.820)
just as a human operating in this world?
Lex Fridman (2:08:49.480)
I've definitely, those skills that have come from therapy,
Karl Deisseroth (2:08:53.200)
I've found them useful, yeah.
Lex Fridman (2:08:55.940)
If I noticed that, we've all been through experiences
Karl Deisseroth (2:09:00.020)
where we wonder, oh, I got really mad in that interaction.
Lex Fridman (2:09:03.380)
Why did I get that mad?
Karl Deisseroth (2:09:05.300)
Yeah, sure, maybe I could have been irritated,
Lex Fridman (2:09:06.980)
but man, why did I?
Lex Fridman (2:09:08.660)
And then thinking about it and realizing,
Lex Fridman (2:09:12.140)
okay, back up here, think about the broader context.
Karl Deisseroth (2:09:18.740)
Think about how that relates to prior events in my life.
Lex Fridman (2:09:23.140)
Okay, yeah, so this is a thing for me
Karl Deisseroth (2:09:25.940)
when something of this class happens, then it triggers me.
Lex Fridman (2:09:30.140)
So going forward, I'm gonna be aware of that.
Lex Fridman (2:09:33.980)
And I've definitely used that
Lex Fridman (2:09:35.100)
because you don't wanna be out of control of those emotions.
Karl Deisseroth (2:09:40.420)
You wanna identify them.
Lex Fridman (2:09:41.460)
You wanna know where they come from
Lex Fridman (2:09:42.860)
and you wanna head them off
Lex Fridman (2:09:44.780)
as a civilized human being living on this earth,
Karl Deisseroth (2:09:48.300)
trying to get along with other people.
Lex Fridman (2:09:50.060)
You wanna understand those moments.
Karl Deisseroth (2:09:51.980)
Let me return to Robin Williams for a second
Lex Fridman (2:09:56.880)
and looking at Robin Williams, the actor,
Karl Deisseroth (2:10:00.820)
sorry, the human,
Lex Fridman (2:10:03.140)
because you mentioned for depression,
Karl Deisseroth (2:10:06.320)
you can have everything going well.
Lex Fridman (2:10:08.220)
And I think there's just famous cases of just public figures
Karl Deisseroth (2:10:12.940)
because a lot of people know them,
Lex Fridman (2:10:15.120)
where they suffer quietly
Lex Fridman (2:10:19.700)
and it seems like from the outside perspective
Lex Fridman (2:10:22.620)
that they have everything going for them,
Karl Deisseroth (2:10:24.820)
that they're at the top of their career.
Lex Fridman (2:10:27.180)
Two people that come to mind
Karl Deisseroth (2:10:28.580)
are Robin Williams and Anthony Bourdain.
Lex Fridman (2:10:32.300)
What insight do you have in why either of those have taken,
Lex Fridman (2:10:36.540)
why Robin Williams, a comedian,
Lex Fridman (2:10:39.860)
one of sort of the most jolly humans?
Karl Deisseroth (2:10:42.340)
Obviously, there was always the darkness
Lex Fridman (2:10:43.820)
that he was channeling in order to present the happiness,
Lex Fridman (2:10:50.340)
but it feels like that realness is only possible
Lex Fridman (2:10:53.180)
when you're deeply self honest and analytical
Lex Fridman (2:10:56.340)
and then if you're deeply self honest,
Lex Fridman (2:10:59.460)
you're going to realize that there's a lot
Karl Deisseroth (2:11:00.920)
of beautiful things about life that you can discover
Lex Fridman (2:11:03.620)
and if you do that,
Lex Fridman (2:11:05.240)
how can you possibly then take your own life?
Lex Fridman (2:11:07.820)
I mean, you go through all of these thoughts
Lex Fridman (2:11:10.180)
and I think a lot of people really loved Robin Williams,
Lex Fridman (2:11:16.100)
which is why it was really difficult to see
Lex Fridman (2:11:18.020)
how can even him, how can even Robin Williams
Lex Fridman (2:11:21.420)
take his own life?
Lex Fridman (2:11:22.260)
So I don't know if there's something to be said
Lex Fridman (2:11:24.620)
about the nature of depression
Karl Deisseroth (2:11:25.960)
from just looking at his case.
Lex Fridman (2:11:29.120)
I think the action of suicide is not well understood.
Karl Deisseroth (2:11:33.380)
It doesn't always, although often,
Lex Fridman (2:11:35.540)
is correlated with depression.
Karl Deisseroth (2:11:37.660)
There are cases of suicide where there is not
Lex Fridman (2:11:40.420)
clear depression, that's in the minority.
Karl Deisseroth (2:11:42.900)
By the way, if I just,
Lex Fridman (2:11:44.260)
because you said it so interesting,
Karl Deisseroth (2:11:46.120)
action of suicide, because there's also thoughts of suicide
Lex Fridman (2:11:49.820)
and probably those, they're probably somewhat understood,
Lex Fridman (2:11:54.580)
but it's an interesting, because you can think of suicide,
Lex Fridman (2:11:59.300)
if you have suicidal ideation,
Karl Deisseroth (2:12:00.940)
you can think of that for so many reasons.
Lex Fridman (2:12:04.020)
That's right.
Lex Fridman (2:12:04.940)
And I mean, thoughts sometimes, like painful thoughts,
Lex Fridman (2:12:16.380)
angry thoughts, or thoughts in general,
Karl Deisseroth (2:12:19.260)
can be very different, like fantasies, for example.
Lex Fridman (2:12:21.340)
You can fantasize, like sexual fantasies.
Karl Deisseroth (2:12:24.440)
You can fantasize, I was just for humor's sake
Lex Fridman (2:12:28.480)
wanted to mention stuff, but then people think I'm serious,
Lex Fridman (2:12:30.780)
so I'm not gonna mention anything.
Lex Fridman (2:12:32.380)
But sexual fantasies, and then there's,
Karl Deisseroth (2:12:34.900)
I know there's people that have sexual fantasies
Lex Fridman (2:12:36.420)
and they don't wanna actually do that in real life.
Karl Deisseroth (2:12:38.580)
That sexual fantasy serves some kind of purpose
Lex Fridman (2:12:41.400)
in imagination only, and in that same way,
Karl Deisseroth (2:12:44.340)
suicide might serve a purpose in imagination only,
Lex Fridman (2:12:46.940)
is very unlikely to lead to action.
Lex Fridman (2:12:48.800)
And yet there's other thoughts that maybe are more amorphous
Lex Fridman (2:12:52.500)
that do lead to action, and that leap,
Karl Deisseroth (2:12:56.300)
yeah, that, oh boy, that's a fascinating,
Lex Fridman (2:12:58.420)
and that's such a philosophically powerful thought
Karl Deisseroth (2:13:02.140)
to not exist, like that question, that's the,
Lex Fridman (2:13:05.680)
is it Sarcher or Camus, Camus?
Karl Deisseroth (2:13:08.680)
Well, the myth is Sisyphus, Camus, who says,
Lex Fridman (2:13:11.700)
like basic question of why live?
Karl Deisseroth (2:13:15.500)
Good question.
Lex Fridman (2:13:16.500)
Yeah, right.
Lex Fridman (2:13:18.100)
So that's a great question, actually,
Lex Fridman (2:13:20.820)
and there are other related questions.
Karl Deisseroth (2:13:22.860)
Some people may have the thought of suicide
Lex Fridman (2:13:26.340)
because there seems no point, there's no joy in life.
Karl Deisseroth (2:13:33.180)
That's one reason that some people can put forward.
Lex Fridman (2:13:36.780)
Sometimes there's an, it's not just the absence of joy,
Karl Deisseroth (2:13:39.900)
there's an active pain, an active psychic pain
Lex Fridman (2:13:43.140)
in some people, and that, the inescapability of that
Karl Deisseroth (2:13:47.500)
is enough to drive the thoughts of suicide.
Lex Fridman (2:13:50.500)
And then there are interpersonal and cultural reasons
Karl Deisseroth (2:13:53.260)
as well that can show up.
Lex Fridman (2:13:54.660)
But the act, this act of ending of the self is,
Karl Deisseroth (2:14:00.060)
in all these cases, there's no real way to study this
Lex Fridman (2:14:02.500)
in animals, no other animal as far as we know
Karl Deisseroth (2:14:05.300)
that we can study has this concept of this is myself,
Lex Fridman (2:14:10.780)
the situation is not tolerable, therefore,
Karl Deisseroth (2:14:13.620)
I will end the self.
Lex Fridman (2:14:15.400)
To our knowledge, this is not something
Karl Deisseroth (2:14:16.780)
that can be studied in other animals.
Lex Fridman (2:14:18.740)
So it remains this very poorly understood action.
Lex Fridman (2:14:26.260)
And in predicting it, so what do we do as psychiatrists?
Lex Fridman (2:14:29.860)
We have this challenge.
Karl Deisseroth (2:14:30.700)
People come to the emergency room, they say they're suicidal
Lex Fridman (2:14:33.980)
or their friends say they're suicidal
Karl Deisseroth (2:14:35.380)
or they've taken some action that didn't lead to death.
Lex Fridman (2:14:40.220)
What do we do?
Karl Deisseroth (2:14:41.060)
Well, there's a whole range of options.
Lex Fridman (2:14:43.980)
Was it a suicidal gesture in the sense
Lex Fridman (2:14:46.120)
of not intending death or was the intent death?
Lex Fridman (2:14:51.940)
And if it was the intent was death,
Lex Fridman (2:14:53.620)
what were the reasons?
Lex Fridman (2:14:54.440)
Are the reasons transient?
Lex Fridman (2:14:55.500)
Are they gone now?
Lex Fridman (2:14:56.980)
What's the probability that it'll be repeated?
Lex Fridman (2:15:00.220)
So we do all these things just to decide
Lex Fridman (2:15:02.980)
what sort of treatment should be carried out,
Lex Fridman (2:15:04.300)
but nowhere is there a deep understanding of the biology,
Lex Fridman (2:15:09.060)
of the cells and circuits and activity patterns
Karl Deisseroth (2:15:12.520)
that underlie the action to end the self.
Lex Fridman (2:15:16.860)
It's a very, it's this frustrating thing.
Karl Deisseroth (2:15:21.700)
It's so timely, it's so common, it shows up in veterans,
Lex Fridman (2:15:26.460)
it shows up in kids, it shows up in people
Karl Deisseroth (2:15:29.420)
at every stage of life, and yet we're very bad
Lex Fridman (2:15:33.580)
at understanding it and we're relatively poor
Karl Deisseroth (2:15:36.380)
at predicting it and our tools are not very powerful.
Lex Fridman (2:15:40.820)
We can put people in a locked unit,
Karl Deisseroth (2:15:42.740)
we can give them care, therapy for a while.
Lex Fridman (2:15:44.900)
At some point, we release them
Lex Fridman (2:15:47.140)
and there's only so much we can do.
Lex Fridman (2:15:48.660)
It's one of the most frustrating things,
Karl Deisseroth (2:15:50.860)
the suffering that is linked to suicidality.
Lex Fridman (2:15:53.600)
But it is a decision and it is an action
Lex Fridman (2:15:56.700)
and if you look at optogenetics,
Lex Fridman (2:15:58.380)
you should be able to one day sort of understand
Karl Deisseroth (2:16:01.780)
the dynamics of such weighty decisions.
Lex Fridman (2:16:05.460)
The individual causes then, if someone is anhedonic,
Karl Deisseroth (2:16:07.600)
if there is no joy in life, that very likely
Lex Fridman (2:16:11.300)
is addressable by optogenetics.
Karl Deisseroth (2:16:12.740)
We know how to turn that dial very robustly in animals.
Lex Fridman (2:16:17.780)
The motivation to overcome challenges,
Karl Deisseroth (2:16:20.660)
that we have some hope of understanding.
Lex Fridman (2:16:25.780)
Psychic pain, internal negative states,
Karl Deisseroth (2:16:28.380)
we have actually a handle on that as well.
Lex Fridman (2:16:30.360)
There's a structure in the brain called the habenula
Lex Fridman (2:16:32.980)
and some linked structures around it
Lex Fridman (2:16:35.440)
that seems to generate this negative internal state.
Karl Deisseroth (2:16:39.100)
It's active when a state of acute disappointment,
Lex Fridman (2:16:42.500)
acute outcomes that go wrong, not as expected.
Karl Deisseroth (2:16:49.940)
Moments of unexpected pain.
Lex Fridman (2:16:52.240)
The habenula is there, it seems,
Karl Deisseroth (2:16:54.220)
it's active to report on internal negativity
Lex Fridman (2:16:59.100)
with its action.
Lex Fridman (2:17:00.940)
And so you could imagine strategies
Lex Fridman (2:17:02.680)
to target this brain structure
Karl Deisseroth (2:17:03.900)
that might have the effect of reducing psychic pain,
Lex Fridman (2:17:07.260)
reducing the negativity of internal states.
Karl Deisseroth (2:17:09.760)
That is a very concrete hope.
Lex Fridman (2:17:11.940)
It's precise, it's anatomical.
Karl Deisseroth (2:17:14.180)
Optogenetics has given us all the firm foundation we need
Lex Fridman (2:17:17.420)
to go after that question.
Lex Fridman (2:17:19.740)
So I think there is hope.
Lex Fridman (2:17:21.460)
If you look at the individual causes,
Karl Deisseroth (2:17:22.960)
the individual symptoms relating to suicide,
Lex Fridman (2:17:25.940)
and then it's like a puzzle,
Karl Deisseroth (2:17:26.980)
you put together the puzzle pieces.
Lex Fridman (2:17:29.340)
By the way, I do think my habenula is
Karl Deisseroth (2:17:34.940)
very functioning, very actively.
Lex Fridman (2:17:37.420)
And I wonder if it's like,
Lex Fridman (2:17:39.940)
because you can also learn to channel these things, right?
Lex Fridman (2:17:43.180)
Some of the things we suffer from,
Karl Deisseroth (2:17:45.940)
I mean, there's degrees of suffering,
Lex Fridman (2:17:48.220)
can be a source of progress and personal growth
Lex Fridman (2:17:54.580)
and development and all those kinds of things.
Lex Fridman (2:17:57.020)
I mean, I, what is it?
Karl Deisseroth (2:18:01.140)
Nietzsche suffered from stomach issues.
Lex Fridman (2:18:07.300)
I wonder if he's written some of those things
Karl Deisseroth (2:18:09.140)
if his stomach was all great.
Lex Fridman (2:18:12.700)
I mean, there's, I kind of think that
Karl Deisseroth (2:18:18.060)
a difficult life in some form,
Lex Fridman (2:18:19.460)
you can get, you get to choose in some regard
Lex Fridman (2:18:21.740)
and some of you don't.
Lex Fridman (2:18:22.820)
The difficulties you have and the ones you do have,
Karl Deisseroth (2:18:25.340)
it's nice to use if possible.
Lex Fridman (2:18:27.420)
Sometimes it's nice to treat,
Karl Deisseroth (2:18:28.760)
sometimes it's nice to use.
Lex Fridman (2:18:31.460)
Well, the way you phrase it, I think you're using it.
Karl Deisseroth (2:18:33.580)
I could be wrong, but if you,
Lex Fridman (2:18:35.780)
you phrased in this semi humorous way about your habenula,
Karl Deisseroth (2:18:39.180)
it seems to me that you're using that to good effect.
Lex Fridman (2:18:43.780)
Now, but one never really knows
Lex Fridman (2:18:46.300)
what someone else's internal state is.
Lex Fridman (2:18:48.100)
As I look at you, I don't know the depths of what's going on
Lex Fridman (2:18:51.860)
and it's possible that it's a much harder situation
Lex Fridman (2:18:56.780)
in there.
Karl Deisseroth (2:18:57.820)
Yes.
Lex Fridman (2:18:58.700)
So that's, I actually worry about this a lot.
Lex Fridman (2:19:00.400)
So I'm extremely self critical,
Lex Fridman (2:19:02.120)
like in the privacy of my own mind,
Karl Deisseroth (2:19:04.420)
which is an interesting thing
Lex Fridman (2:19:05.900)
when you get to meet the internet
Lex Fridman (2:19:07.780)
and the internet will tell you you suck.
Lex Fridman (2:19:11.580)
But for now, now this is what I worry about
Lex Fridman (2:19:15.100)
and I'm very paying attention.
Lex Fridman (2:19:16.820)
For now it's really, I just have this like very negative
Karl Deisseroth (2:19:19.280)
voice, but that voice seems to be very useful
Lex Fridman (2:19:23.620)
for productivity and so I channel it.
Karl Deisseroth (2:19:26.320)
I just put it on the table and let that voice like
Lex Fridman (2:19:29.060)
talk to me, but I'm very, I'm like monitoring that voice
Karl Deisseroth (2:19:33.980)
because looking at Robin Williams, you know,
Lex Fridman (2:19:35.780)
you get older, your brain changes or like you're,
Lex Fridman (2:19:38.940)
and then that voice can now all of a sudden grow, right?
Lex Fridman (2:19:43.540)
And then where you can't control as much,
Karl Deisseroth (2:19:45.260)
you have to be very careful with these kinds of things.
Lex Fridman (2:19:47.900)
You're very right about that.
Lex Fridman (2:19:50.180)
So my negativity, I have this,
Lex Fridman (2:19:53.060)
I never think I've done enough is sort of where my
Karl Deisseroth (2:19:56.020)
negativity comes from inside.
Lex Fridman (2:19:57.460)
I never think that I've met the potential of the moment.
Karl Deisseroth (2:20:04.520)
I haven't done, I haven't, you know,
Lex Fridman (2:20:08.780)
made the most of the opportunities that are available.
Karl Deisseroth (2:20:12.180)
Still early, I haven't, you know,
Lex Fridman (2:20:15.100)
progressed as far as I should.
Lex Fridman (2:20:16.660)
And exactly as you're saying, that works for a while.
Lex Fridman (2:20:20.940)
But then what happens as you get later in life
Lex Fridman (2:20:23.660)
and there's less runway to, you know, fix that.
Lex Fridman (2:20:28.940)
And then maybe then that negative voice is a problem.
Lex Fridman (2:20:33.020)
But also at that point, the negative voice
Lex Fridman (2:20:34.940)
starts having more and more of a point.
Karl Deisseroth (2:20:36.820)
When you're being very successful,
Lex Fridman (2:20:39.900)
it's easy to be like, no, okay, well,
Karl Deisseroth (2:20:43.680)
like because later in life, you're really literally
Lex Fridman (2:20:46.100)
just sitting there on a rocking chair doing nothing.
Lex Fridman (2:20:49.700)
And then it's, or maybe any kind of tragedy happens.
Lex Fridman (2:20:53.640)
Loss of a loved one, loss of a job,
Karl Deisseroth (2:20:57.140)
loss or you get screwed over in some kind of way.
Lex Fridman (2:21:01.480)
I don't know.
Lex Fridman (2:21:02.540)
And then all of a sudden the negative voice
Lex Fridman (2:21:04.180)
is just you and the negative voice
Karl Deisseroth (2:21:05.660)
for days and days and days.
Lex Fridman (2:21:07.940)
And so I don't know, to go back to your example
Karl Deisseroth (2:21:10.380)
of Robin Williams, I don't know what was going on inside him.
Lex Fridman (2:21:13.420)
I don't know the nature of his internal state.
Lex Fridman (2:21:15.460)
Was it active psychic pain that?
Lex Fridman (2:21:18.540)
May I mention, may I interrupt to just say
Karl Deisseroth (2:21:20.240)
that Sergei posted an examination of Robin Williams.
Lex Fridman (2:21:23.580)
His brain tissue suggested that he suffered from quote,
Karl Deisseroth (2:21:27.380)
diffuse LEWY, Lewy body dementia, LBD.
Lex Fridman (2:21:33.840)
Depression is a symptom of LBD and it's not about psychology.
Karl Deisseroth (2:21:38.300)
It's rooted in urology.
Lex Fridman (2:21:40.460)
This is words from Sergei.
Karl Deisseroth (2:21:42.020)
His brain was falling apart.
Lex Fridman (2:21:43.660)
Yeah, Lewy body dementia.
Karl Deisseroth (2:21:45.340)
This is a very interesting neurological disorder
Lex Fridman (2:21:47.660)
where among other things, there's neuron death indeed.
Lex Fridman (2:21:51.900)
So you've got frank neuron loss.
Lex Fridman (2:21:54.540)
It's not just a matter of some longstanding psychic pain,
Lex Fridman (2:21:58.280)
but you've got a progressive loss.
Lex Fridman (2:22:00.940)
And so clearly you've got a situation
Karl Deisseroth (2:22:03.020)
where he could have finally reached a point
Lex Fridman (2:22:04.500)
where the balance that he'd worked out
Karl Deisseroth (2:22:07.540)
between negativity and positivity was disrupted due to loss.
Lex Fridman (2:22:12.460)
The wrong cells died, the wrong projections were cut.
Karl Deisseroth (2:22:15.140)
By the Lewy body dementia.
Lex Fridman (2:22:16.920)
Certainly dopamine neurons die in Lewy body dementia.
Karl Deisseroth (2:22:19.620)
Those are neurons that give rise to much of the feelings
Lex Fridman (2:22:23.440)
of reward and pleasure that we experience among other roles.
Lex Fridman (2:22:27.380)
So clearly in his case, there could have been
Lex Fridman (2:22:30.700)
a very concrete cellular neurological issue
Karl Deisseroth (2:22:34.360)
that was progressive and pushed him to that point.
Lex Fridman (2:22:37.740)
But were you about to make a point about broader
Lex Fridman (2:22:41.720)
that if there is not a neurological degeneration?
Lex Fridman (2:22:45.020)
Yeah, so in his case, not knowing that,
Karl Deisseroth (2:22:48.340)
it could have been simply that,
Lex Fridman (2:22:49.660)
let's say he had an internal psychic pain state
Lex Fridman (2:22:52.780)
and he was in sort of a compensated mode
Lex Fridman (2:22:56.660)
for much of his life, able to generate enough joy
Karl Deisseroth (2:22:58.740)
from his comedy and his social interactions.
Lex Fridman (2:23:02.660)
But eventually later in life, those things drop away,
Karl Deisseroth (2:23:06.860)
the balance shifts.
Lex Fridman (2:23:08.180)
You get tired of fighting the pain for that long.
Lex Fridman (2:23:10.780)
So you've got this time dependent non stationarity
Lex Fridman (2:23:14.160)
that happens and then the same symptom
Karl Deisseroth (2:23:18.260)
becomes no longer tolerable in the end.
Lex Fridman (2:23:21.180)
What is autism?
Lex Fridman (2:23:22.660)
What do we know about autism?
Lex Fridman (2:23:25.420)
Human beings exist on a spectrum of how social we can be.
Lex Fridman (2:23:30.700)
And this is pretty interesting actually, scientifically,
Lex Fridman (2:23:34.640)
but also very important clinically.
Karl Deisseroth (2:23:38.240)
There are hyper social states where people
Lex Fridman (2:23:40.420)
are almost too social.
Karl Deisseroth (2:23:42.800)
There are chromosomal deletion states
Lex Fridman (2:23:44.740)
where people have instant affinity and bonding
Lex Fridman (2:23:47.740)
and rich deep seeming connections with people, very verbal.
Lex Fridman (2:23:52.740)
On the other end, people with autism spectrum disorder
Karl Deisseroth (2:23:57.620)
are not able to keep up with social interactions
Lex Fridman (2:24:05.300)
and it's a spectrum.
Karl Deisseroth (2:24:06.540)
Some have mild to moderate difficulties.
Lex Fridman (2:24:09.500)
They may have inability to understand
Lex Fridman (2:24:13.800)
what the next thing to do in a social situation is,
Lex Fridman (2:24:16.140)
but may have perfectly good language abilities.
Lex Fridman (2:24:19.820)
And as you progress further along the spectrum,
Lex Fridman (2:24:21.860)
that gets more and more severe
Lex Fridman (2:24:23.180)
so they can't make eye contact because it's too overwhelming
Lex Fridman (2:24:28.100)
to think about what has to be done next
Karl Deisseroth (2:24:29.780)
if a person looks in a particular way.
Lex Fridman (2:24:32.260)
And then as you go farther,
Karl Deisseroth (2:24:33.460)
then language and social communication themselves break down
Lex Fridman (2:24:38.020)
so there's no reciprocity, there's no shared enjoyment.
Lex Fridman (2:24:41.980)
And that this gets very hard then
Lex Fridman (2:24:43.500)
as you get to this far end of the spectrum
Karl Deisseroth (2:24:45.340)
where there's really an absence of social cognition at all
Lex Fridman (2:24:50.060)
and social bonding.
Lex Fridman (2:24:52.820)
So why does this exist?
Lex Fridman (2:24:54.580)
What is it?
Karl Deisseroth (2:24:55.620)
It's very genetic.
Lex Fridman (2:24:56.860)
As I mentioned, it's one of the top three or four
Karl Deisseroth (2:25:00.020)
most biological in the sense of most genetically determined
Lex Fridman (2:25:03.820)
of the psychiatric illnesses.
Karl Deisseroth (2:25:05.400)
It does have these interesting positive correlations,
Lex Fridman (2:25:08.020)
slight positive correlations
Karl Deisseroth (2:25:09.240)
with intelligence and education.
Lex Fridman (2:25:13.420)
And the reason for that
Karl Deisseroth (2:25:16.140)
is kind of interesting to think about.
Lex Fridman (2:25:18.300)
Is there something good about it?
Karl Deisseroth (2:25:19.480)
Just like, or at least with at least part of the spectrum,
Lex Fridman (2:25:23.020)
is there something good about it?
Karl Deisseroth (2:25:23.980)
Just as we were talking about for depression,
Lex Fridman (2:25:26.220)
as you could say for mania,
Karl Deisseroth (2:25:27.460)
as you could say for schizophrenia.
Lex Fridman (2:25:30.340)
And here it's kind of interesting
Karl Deisseroth (2:25:33.660)
to think about the underlying science
Lex Fridman (2:25:37.380)
of what it means to be good at a social interaction.
Karl Deisseroth (2:25:41.840)
Someone who's very good at a social interaction
Lex Fridman (2:25:44.020)
is incredibly good at dealing
Karl Deisseroth (2:25:45.220)
with unpredictable information,
Lex Fridman (2:25:48.420)
is able to handle this torrent of information
Karl Deisseroth (2:25:51.420)
coming through rapidly changing
Lex Fridman (2:25:56.020)
model of the other person and of the interaction
Lex Fridman (2:25:58.540)
and their model of you, your model of them.
Lex Fridman (2:26:02.540)
With each word that changes,
Karl Deisseroth (2:26:03.940)
with each new bit of information
Lex Fridman (2:26:05.580)
that comes in through the conversation,
Karl Deisseroth (2:26:06.940)
each bit of body language, all this is rapidly changing.
Lex Fridman (2:26:09.740)
And some people are able to keep up
Karl Deisseroth (2:26:12.400)
with that firehose of information perfectly well.
Lex Fridman (2:26:15.640)
But that's a special brain state to be in.
Karl Deisseroth (2:26:17.300)
That's working with unpredictability.
Lex Fridman (2:26:20.420)
That's the only way that can be done
Karl Deisseroth (2:26:24.500)
is most likely by constantly running models
Lex Fridman (2:26:29.100)
of what the other person might be about to say.
Lex Fridman (2:26:32.200)
So you can't stop and think, oh, what did that word mean?
Lex Fridman (2:26:34.360)
What did that shift in eye contact mean?
Lex Fridman (2:26:37.660)
What do they mean together?
Lex Fridman (2:26:38.800)
There has to be some advanced work going on
Karl Deisseroth (2:26:41.180)
where you're predicting what's going on
Lex Fridman (2:26:42.440)
if you're to keep up with a rich
Lex Fridman (2:26:43.840)
and fast social interaction.
Lex Fridman (2:26:46.620)
Now, on the flip side, there are brain states
Karl Deisseroth (2:26:51.700)
that maybe don't have to work so fast
Lex Fridman (2:26:53.580)
but that are extremely important still.
Karl Deisseroth (2:26:54.940)
Dealing with something that's not moving
Lex Fridman (2:26:57.100)
or that's predictable, still complex,
Karl Deisseroth (2:27:00.220)
like mathematical proof or a very complex arrangement
Lex Fridman (2:27:05.500)
of geometrical shapes, a large number
Karl Deisseroth (2:27:08.740)
of individual nonmoving things.
Lex Fridman (2:27:11.100)
There's possibly a way of being that's particularly good
Karl Deisseroth (2:27:14.420)
at dealing with these static, unmoving,
Lex Fridman (2:27:16.460)
or predictable situations and less so
Karl Deisseroth (2:27:19.980)
with these rapidly changing social situations.
Lex Fridman (2:27:22.940)
And so the way I conceptualize autism
Karl Deisseroth (2:27:25.940)
is these are people whose brains are not so good
Lex Fridman (2:27:31.020)
with the high bit rate, unpredictable information,
Lex Fridman (2:27:34.500)
but may be quite good at given enough time,
Lex Fridman (2:27:38.060)
given the grace to work with the system,
Karl Deisseroth (2:27:45.140)
to look at it from different angles,
Lex Fridman (2:27:47.860)
to take different perspectives with a confidence
Karl Deisseroth (2:27:49.740)
that it's not changing in between perspectives.
Lex Fridman (2:27:53.980)
That's a brain state that's valuable.
Karl Deisseroth (2:27:55.680)
It's something that has probably contributed
Lex Fridman (2:27:59.540)
to a lot of the success of the human family,
Karl Deisseroth (2:28:01.140)
being able to design something,
Lex Fridman (2:28:02.340)
being able to consider all the different contributions
Karl Deisseroth (2:28:09.060)
to a static, predictable system.
Lex Fridman (2:28:13.300)
So autism, in a sense, is a spectrum
Karl Deisseroth (2:28:17.820)
that has identifiable characteristics
Lex Fridman (2:28:21.140)
about the way people deal with dynamic information,
Karl Deisseroth (2:28:25.100)
often expressed itself as like social dynamic information.
Lex Fridman (2:28:29.100)
But you critically, your use of the word often there
Karl Deisseroth (2:28:31.180)
is really, I think, smart,
Lex Fridman (2:28:32.700)
because it's not just social interaction
Karl Deisseroth (2:28:35.900)
that is a challenge in autism.
Lex Fridman (2:28:37.220)
And so many people conceptualize it purely
Karl Deisseroth (2:28:39.980)
as a social dysfunction disorder.
Lex Fridman (2:28:44.820)
But it's really any unpredictable information
Karl Deisseroth (2:28:47.560)
that's a problem, that's a challenge
Lex Fridman (2:28:49.500)
for people on the spectrum.
Karl Deisseroth (2:28:50.880)
They react very negatively to unexpected sounds,
Lex Fridman (2:28:56.260)
even if not social sounds, unexpected lights,
Karl Deisseroth (2:28:59.300)
unexpected touches, and so it's really
Lex Fridman (2:29:02.300)
unpredictable information that is, in my view,
Karl Deisseroth (2:29:05.060)
the core problem with the processing in autism,
Lex Fridman (2:29:08.380)
not just social.
Karl Deisseroth (2:29:09.220)
Social just shows up because it's so unpredictable.
Lex Fridman (2:29:11.500)
Yeah, it's so interesting.
Karl Deisseroth (2:29:12.940)
I mean, I try to not to think about that stuff.
Lex Fridman (2:29:16.780)
I'm afraid of thinking about disorders
Lex Fridman (2:29:22.580)
and things like that because just like I don't like
Lex Fridman (2:29:25.440)
sort of economics or game theory,
Karl Deisseroth (2:29:28.500)
I want to be careful with it because it,
Lex Fridman (2:29:32.260)
whenever you have a category or a model,
Karl Deisseroth (2:29:34.300)
it's too easy to just, for everything,
Lex Fridman (2:29:37.620)
I mean, it's the OCD thing.
Karl Deisseroth (2:29:39.400)
I like models too much.
Lex Fridman (2:29:40.860)
I like categories too much.
Karl Deisseroth (2:29:42.220)
The moment you acknowledge yourself,
Lex Fridman (2:29:44.200)
well, I have an eating disorder, for example,
Karl Deisseroth (2:29:46.340)
or something like that, as opposed to just being a,
Lex Fridman (2:29:49.180)
well, I'll just leave it at that
Karl Deisseroth (2:29:51.340)
from my own critical understanding of myself.
Lex Fridman (2:29:54.520)
Let's just say I don't know how to moderate eating fruit.
Karl Deisseroth (2:29:56.940)
People make fun of me.
Lex Fridman (2:29:57.780)
They think all fruit is healthy.
Karl Deisseroth (2:30:00.780)
I know.
Lex Fridman (2:30:03.100)
I don't know how to moderate anything,
Lex Fridman (2:30:05.200)
but even fruit, apples and cherries, is a nightmare.
Lex Fridman (2:30:10.260)
Anyway, that's such a psychiatrist thing to say.
Karl Deisseroth (2:30:14.380)
Very interesting.
Lex Fridman (2:30:15.220)
Thank you.
Lex Fridman (2:30:18.340)
But there's characteristics and it's interesting
Lex Fridman (2:30:22.680)
to think about, like for example,
Karl Deisseroth (2:30:24.300)
I have trouble making eye contact,
Lex Fridman (2:30:26.580)
but I actually, as you said it now,
Karl Deisseroth (2:30:29.020)
it's not that I'm shy at all in that sense.
Lex Fridman (2:30:35.140)
It's literally, I'm getting way too much information
Lex Fridman (2:30:38.540)
and it's distracting me.
Lex Fridman (2:30:40.180)
Like I need to just close my eyes so I can,
Karl Deisseroth (2:30:44.020)
like all the things that people seem to be able to do
Lex Fridman (2:30:46.580)
in parallel, it's just, you just asked me a question.
Karl Deisseroth (2:30:51.020)
For me to think about the answer to that question,
Lex Fridman (2:30:53.300)
I can't have all this cool, rich visual information
Karl Deisseroth (2:30:56.120)
coming my way.
Lex Fridman (2:30:57.180)
That's literally, because I often close my eyes to think.
Karl Deisseroth (2:31:01.020)
It's not because I'm afraid of something, whatever.
Lex Fridman (2:31:04.060)
It's just like too much information happening here.
Karl Deisseroth (2:31:06.940)
Well, that's a beautiful description.
Lex Fridman (2:31:08.980)
It's amazing that that is how you experience
Karl Deisseroth (2:31:12.300)
the eye contact aspect.
Lex Fridman (2:31:15.620)
I think that's, I mean, you've articulated
Lex Fridman (2:31:18.340)
what captures it for so many people,
Lex Fridman (2:31:22.620)
which is that it's overwhelming.
Karl Deisseroth (2:31:23.720)
There's just too much information just coming in
Lex Fridman (2:31:26.020)
through the eyes and to keep up with it,
Karl Deisseroth (2:31:30.740)
to know you're gonna be expected to keep up with it,
Lex Fridman (2:31:33.460)
first of all, so there's that aspect.
Karl Deisseroth (2:31:35.140)
You know, you've learned socially
Lex Fridman (2:31:37.200)
that there's gonna be an expectation
Karl Deisseroth (2:31:38.900)
if you're making eye contact.
Lex Fridman (2:31:40.740)
People are gonna think you're keeping up with it,
Lex Fridman (2:31:42.740)
and you don't want to because you wanna focus
Lex Fridman (2:31:45.660)
on other things and make progress in other dimensions.
Karl Deisseroth (2:31:50.200)
Yeah, and so then there's a strong desire
Lex Fridman (2:31:52.220)
to look away or to close the eyes
Karl Deisseroth (2:31:53.580)
because it's overwhelming, it's a distraction,
Lex Fridman (2:31:57.860)
and it's gonna cause errors of understanding.
Lex Fridman (2:32:00.180)
And of course, our eyes, that's part,
Lex Fridman (2:32:02.020)
the way we use our eyes is part of the human communication,
Lex Fridman (2:32:04.540)
so you have to kind of be aware of that,
Lex Fridman (2:32:07.180)
of that element of it.
Lex Fridman (2:32:10.580)
So yeah, I mean, but it's fascinating.
Lex Fridman (2:32:12.140)
You should be aware of your own self
Karl Deisseroth (2:32:13.940)
in those little characteristics,
Lex Fridman (2:32:16.180)
whether it's classified on some aspect
Karl Deisseroth (2:32:19.580)
of the autism spectrum or just in general,
Lex Fridman (2:32:22.860)
whether it's eating, whether it's depression,
Karl Deisseroth (2:32:26.220)
whether it's even like schizophrenia
Lex Fridman (2:32:29.180)
that I hope we get a chance to talk to a little bit.
Karl Deisseroth (2:32:32.980)
Yeah, but those things are all made up
Lex Fridman (2:32:35.420)
of different symptoms and characteristics,
Lex Fridman (2:32:40.100)
and use them as a superpower, I suppose,
Lex Fridman (2:32:43.380)
is the best we can hope for in mild cases, I guess.
Karl Deisseroth (2:32:47.900)
I do think both brain states can't coexist
Lex Fridman (2:32:50.300)
at the same time.
Karl Deisseroth (2:32:51.140)
The way of dealing with something unpredictable
Lex Fridman (2:32:52.820)
and dealing with something predictable,
Karl Deisseroth (2:32:55.140)
those are different ways of being,
Lex Fridman (2:32:56.500)
here's a huge opportunity for very creative
Karl Deisseroth (2:33:01.100)
model building in theoretical neuroscience
Lex Fridman (2:33:04.540)
and linking that to these data streams
Karl Deisseroth (2:33:07.180)
we're getting across the brain that we talked about earlier,
Lex Fridman (2:33:11.060)
these immense data sets of activity across the brain.
Karl Deisseroth (2:33:15.300)
Here's where I think there could be
Lex Fridman (2:33:17.300)
a real convergence of theoreticians and experimentalists
Karl Deisseroth (2:33:19.860)
to say, okay, given what we know about wiring of the brain,
Lex Fridman (2:33:24.420)
here is what the brain state is likely to be
Karl Deisseroth (2:33:27.900)
that deals well with unpredictable information,
Lex Fridman (2:33:30.980)
and here's the brain state
Karl Deisseroth (2:33:31.860)
that deals with predictable information.
Lex Fridman (2:33:33.740)
Here's why they're incompatible, at least at the same time.
Karl Deisseroth (2:33:36.580)
Here's why you've gotta be able to detect
Lex Fridman (2:33:39.100)
which state you should be in.
Karl Deisseroth (2:33:40.140)
Here's how you could switch between them.
Lex Fridman (2:33:42.140)
Here's the kind of cells that you would predict,
Karl Deisseroth (2:33:44.700)
almost like predicting the Higgs boson.
Lex Fridman (2:33:46.540)
Here's the kind of circuitry that I would predict
Karl Deisseroth (2:33:49.540)
should govern the switching,
Lex Fridman (2:33:51.820)
or might make one state too sticky, too hard to get out of.
Karl Deisseroth (2:33:58.300)
That is a huge opportunity for an interaction
Lex Fridman (2:34:01.100)
from the theoretical and experimental side together.
Karl Deisseroth (2:34:04.300)
Make one state too sticky.
Lex Fridman (2:34:07.900)
The sort of measure the stickiness of the state
Lex Fridman (2:34:12.580)
and how to lessen the stickiness.
Lex Fridman (2:34:14.980)
Get some oil in the machine.
Karl Deisseroth (2:34:16.500)
Yes, yeah, what would predict the kind of oil
Lex Fridman (2:34:19.460)
that would work well.
Karl Deisseroth (2:34:21.900)
What, in your practice, is treatment or advice
Lex Fridman (2:34:27.940)
for the people on the autism spectrum?
Lex Fridman (2:34:31.340)
So right now, there's no real medical treatment.
Lex Fridman (2:34:34.460)
There are behavioral treatments
Karl Deisseroth (2:34:36.580)
that are most effective early in life.
Lex Fridman (2:34:38.860)
They make sure people don't fall too far behind.
Karl Deisseroth (2:34:42.140)
If you're not interacting socially,
Lex Fridman (2:34:43.780)
you create this vicious cycle
Karl Deisseroth (2:34:46.900)
where you fall farther and farther behind
Lex Fridman (2:34:48.580)
because you're not interacting.
Lex Fridman (2:34:49.700)
And these therapies which are applied early in life,
Lex Fridman (2:34:52.700)
therapists work with the kids,
Karl Deisseroth (2:34:55.860)
train them to deal with these things
Lex Fridman (2:34:57.860)
that otherwise would be aversive to them,
Karl Deisseroth (2:34:59.860)
teach them how to predict things and interact,
Lex Fridman (2:35:02.660)
and that has a big effect.
Lex Fridman (2:35:04.820)
But it's behavioral therapy.
Lex Fridman (2:35:06.820)
There's no medicine that works.
Karl Deisseroth (2:35:08.820)
There are ways of reducing individual symptoms though
Lex Fridman (2:35:12.020)
that sometimes come along with autism
Lex Fridman (2:35:13.980)
and those do respond to medications.
Lex Fridman (2:35:15.700)
So you can, one thing, very often,
Karl Deisseroth (2:35:18.660)
my patients with autism are very anxious
Lex Fridman (2:35:21.380)
because they live in a world
Karl Deisseroth (2:35:23.820)
that they have a really hard time
Lex Fridman (2:35:25.500)
predicting what's gonna happen.
Lex Fridman (2:35:26.540)
And so they find, and some of these are high functioning,
Lex Fridman (2:35:29.380)
Silicon Valley types who they may make great livings
Lex Fridman (2:35:33.820)
but they're very unhappy because they're on the spectrum.
Lex Fridman (2:35:38.100)
They don't understand how social interactions really work.
Karl Deisseroth (2:35:43.220)
They're very anxiety provoking
Lex Fridman (2:35:46.180)
because they don't know what to say.
Karl Deisseroth (2:35:47.180)
They don't have any clue how anybody else knows what to say.
Lex Fridman (2:35:50.900)
They're constantly worried they're gonna say something
Karl Deisseroth (2:35:52.700)
that's completely inappropriate
Lex Fridman (2:35:54.540)
and so they're very anxious.
Lex Fridman (2:35:55.580)
And I can treat their anxiety.
Lex Fridman (2:35:57.420)
It doesn't touch the autism per se
Lex Fridman (2:35:59.700)
but I can help them with their anxiety.
Lex Fridman (2:36:02.500)
What I just talked about, eye contact.
Karl Deisseroth (2:36:05.220)
I am richly, even with eyes closed
Lex Fridman (2:36:08.260)
and all those kinds of things,
Karl Deisseroth (2:36:09.340)
I'm richly experiencing the world.
Lex Fridman (2:36:12.220)
And it's not like you're afraid of the world
Karl Deisseroth (2:36:14.420)
or you're not able, I don't know what to do.
Lex Fridman (2:36:16.100)
No, I know everything.
Karl Deisseroth (2:36:17.420)
In fact, I know way too much.
Lex Fridman (2:36:19.140)
There's so many cool options.
Karl Deisseroth (2:36:20.820)
Like at any one moment, there's all the stuff happening
Lex Fridman (2:36:24.540)
and it's all beautiful.
Lex Fridman (2:36:26.180)
And at any one moment, you can do anything you want.
Lex Fridman (2:36:28.620)
You can take off your clothes.
Karl Deisseroth (2:36:29.780)
You can punch that guy over there.
Lex Fridman (2:36:31.740)
You can run away.
Karl Deisseroth (2:36:33.820)
You can go in for a hug.
Lex Fridman (2:36:35.820)
You can say something profound and deep
Karl Deisseroth (2:36:38.380)
or you can say something generic
Lex Fridman (2:36:39.980)
or you can do so many things you can say.
Lex Fridman (2:36:42.260)
And then it'll go, it'll unravel in all these kinds of ways
Lex Fridman (2:36:46.380)
and this moment could be completely life changing
Karl Deisseroth (2:36:48.900)
or it can be mundane and meaningless.
Lex Fridman (2:36:51.300)
And all of those options are before you at any one moment.
Lex Fridman (2:36:54.540)
And so it's like, it's amazing and overwhelming
Lex Fridman (2:36:59.820)
if you allow yourself to think about it,
Karl Deisseroth (2:37:02.100)
which whatever, exactly.
Lex Fridman (2:37:04.660)
Like, well, I'm fortunate with chess,
Karl Deisseroth (2:37:06.340)
you have a few set options.
Lex Fridman (2:37:08.460)
Two dimensional, at least dimensional is constraints.
Karl Deisseroth (2:37:11.860)
There is unlimited possibilities
Lex Fridman (2:37:15.140)
and unlimited beautiful things happening all around you.
Lex Fridman (2:37:18.420)
So I don't think there's a kind of sense
Lex Fridman (2:37:20.540)
that somehow you're limited in the places of,
Karl Deisseroth (2:37:28.140)
in the way you can see the world
Lex Fridman (2:37:29.820)
and how you can interact with that world.
Karl Deisseroth (2:37:31.860)
I am overwhelmed by the lack of limit.
Lex Fridman (2:37:36.300)
That all of us should be, have you looked around?
Karl Deisseroth (2:37:38.540)
You can do whatever the hell you want.
Lex Fridman (2:37:40.180)
Nobody will remember you anyway.
Karl Deisseroth (2:37:42.180)
All of us will be dead one day.
Lex Fridman (2:37:44.100)
You could do anything.
Karl Deisseroth (2:37:45.820)
You can, I don't know, you can get naked
Lex Fridman (2:37:49.700)
and run around the city,
Karl Deisseroth (2:37:50.900)
as long as you're not hurting anybody,
Lex Fridman (2:37:52.700)
and it doesn't matter.
Lex Fridman (2:37:54.580)
So it's Austin, anyway.
Lex Fridman (2:37:55.580)
Austin, yeah, exactly.
Karl Deisseroth (2:37:59.060)
Seems like a to do item for anybody living in Austin,
Lex Fridman (2:38:03.100)
for sure.
Lex Fridman (2:38:04.540)
But the spectrum is an interesting concept
Lex Fridman (2:38:07.220)
because that is, when I say,
Karl Deisseroth (2:38:10.420)
when I refer to the spectrum,
Lex Fridman (2:38:12.460)
I'm actually referring to, it's a precise clinical term,
Lex Fridman (2:38:15.320)
but you're right, it's been coopted more broadly
Lex Fridman (2:38:17.900)
and it is widely used and it can be
Karl Deisseroth (2:38:20.900)
an unfair categorization of someone
Lex Fridman (2:38:22.500)
who's socially and occupationally very healthy.
Lex Fridman (2:38:25.860)
And that is critical
Lex Fridman (2:38:29.740)
because we don't define a disorder
Karl Deisseroth (2:38:32.260)
unless there's social or occupational dysfunction.
Lex Fridman (2:38:34.740)
It doesn't matter what the symptoms are.
Karl Deisseroth (2:38:36.820)
I've had patients who are pleasantly hallucinating,
Lex Fridman (2:38:39.740)
so frankly, psychotic, but doesn't affect their lives,
Lex Fridman (2:38:43.140)
so I don't give that person a diagnosis
Lex Fridman (2:38:46.400)
because there's not social or occupational dysfunction.
Karl Deisseroth (2:38:49.980)
Same with anything on this,
Lex Fridman (2:38:53.620)
any of the diverse symptoms of autism spectrum disorder.
Karl Deisseroth (2:38:58.580)
If someone has them,
Lex Fridman (2:38:59.980)
but they're successful socially and occupationally,
Karl Deisseroth (2:39:03.140)
we don't say that there's a disorder.
Lex Fridman (2:39:05.620)
But then you're right, that the concept of the spectrum
Karl Deisseroth (2:39:07.700)
does become a useful pigeonholing device,
Lex Fridman (2:39:12.720)
which is maybe not the best thing.
Karl Deisseroth (2:39:15.500)
Yeah, and the eye contact is an interesting one,
Lex Fridman (2:39:19.980)
is an interesting one.
Karl Deisseroth (2:39:21.180)
I'm torn on it.
Lex Fridman (2:39:23.780)
I'm torn about the usefulness of eye contact
Karl Deisseroth (2:39:25.900)
because people kind of make fun of it,
Lex Fridman (2:39:27.460)
but let me just say one thing about eye contact
Lex Fridman (2:39:31.660)
and about life in general.
Lex Fridman (2:39:33.180)
It's okay to be weird,
Lex Fridman (2:39:36.900)
but like some people, when you have your eyes closed
Lex Fridman (2:39:39.420)
and there's that weird, what is happening to this creature?
Karl Deisseroth (2:39:41.740)
Like you see a weird creature on the side of the road.
Lex Fridman (2:39:44.860)
It's interesting.
Lex Fridman (2:39:46.340)
And you wanna, I mean, the weird stuff,
Lex Fridman (2:39:49.120)
I'm gonna go back to Robin Williams with the,
Lex Fridman (2:39:51.580)
that's the good stuff, right?
Lex Fridman (2:39:53.780)
He has that whole speech about him and his wife
Lex Fridman (2:39:56.380)
and what he loves all the little peculiarities,
Lex Fridman (2:39:59.280)
all the weird stuff.
Lex Fridman (2:40:00.180)
And that, like let those flourish.
Lex Fridman (2:40:04.220)
Let those, like celebrate those in yourself
Lex Fridman (2:40:06.420)
and not in some kind of woke way,
Lex Fridman (2:40:08.580)
but in some like very human way.
Karl Deisseroth (2:40:10.940)
This is what makes us, this is the weirdness.
Lex Fridman (2:40:13.060)
Yeah, I'm 100% on board with that.
Lex Fridman (2:40:17.380)
And I don't think, you know, people who are happy
Lex Fridman (2:40:22.500)
and who have people in their lives who are happy with them,
Karl Deisseroth (2:40:27.140)
these are, I think, let the weirdness flourish.
Lex Fridman (2:40:30.500)
Let the, all the different ways members
Karl Deisseroth (2:40:33.620)
of the human family can be different.
Lex Fridman (2:40:35.220)
Let's see them all.
Karl Deisseroth (2:40:36.140)
That's one of our, that's one of the joys of being alive
Lex Fridman (2:40:38.840)
is seeing all the ways we can be human.
Lex Fridman (2:40:41.140)
And I think about it all the time.
Lex Fridman (2:40:43.960)
Why do we have all these ways of being human?
Lex Fridman (2:40:49.880)
And even within one individual,
Lex Fridman (2:40:53.000)
you go through phases of life
Karl Deisseroth (2:40:54.220)
where you express different sides of your way of being,
Lex Fridman (2:40:57.160)
which is also a pretty fun opportunity, right?
Karl Deisseroth (2:40:59.280)
You can go through phases where you're in one mode
Lex Fridman (2:41:02.880)
and phases when you're in another mode.
Lex Fridman (2:41:05.300)
And let that, you know, just let that flourish too.
Lex Fridman (2:41:09.720)
Let the ways that you can be you vary as well.
Karl Deisseroth (2:41:13.360)
I think that's important for people to explore.
Lex Fridman (2:41:15.720)
And I should, like, as if you can address the internet,
Lex Fridman (2:41:22.560)
but I would like to sort of ask the internet
Lex Fridman (2:41:27.080)
to celebrate the weirdness of people.
Karl Deisseroth (2:41:31.400)
Like, that's, it's the Robin Williams,
Lex Fridman (2:41:37.580)
people call these imperfections,
Lex Fridman (2:41:39.160)
but they're not, that's the good stuff.
Lex Fridman (2:41:40.800)
For any one individual person,
Karl Deisseroth (2:41:43.800)
find the weird stuff and celebrate it,
Lex Fridman (2:41:47.680)
as opposed to what the internet often does,
Karl Deisseroth (2:41:50.480)
which is find the weird stuff and criticize it.
Lex Fridman (2:41:55.000)
Because when you criticize the weird stuff,
Karl Deisseroth (2:41:57.580)
you're creating conformity, which is another human thing.
Lex Fridman (2:42:01.700)
But that conformity creates a boring world.
Karl Deisseroth (2:42:05.700)
You want the weird, you want the crazy.
Lex Fridman (2:42:10.780)
That's what fun is made of.
Karl Deisseroth (2:42:12.580)
That's the foundation of humor
Lex Fridman (2:42:16.220)
and all of the ways in which we deal
Karl Deisseroth (2:42:19.020)
with the suffering in the world,
Lex Fridman (2:42:21.620)
with the injustices in the world,
Karl Deisseroth (2:42:23.500)
is like this like huge variety of weird.
Lex Fridman (2:42:30.900)
Yeah, I don't know.
Lex Fridman (2:42:32.600)
And that's what, at the depth of psychiatry,
Lex Fridman (2:42:34.980)
is like you wanna acknowledge the weird,
Karl Deisseroth (2:42:38.780)
celebrate the weird, like step around it
Lex Fridman (2:42:41.860)
to find the particular aspects of weird
Karl Deisseroth (2:42:44.980)
that are debilitating, like you said.
Lex Fridman (2:42:47.260)
They're somehow negatively affecting your ability
Karl Deisseroth (2:42:49.620)
to function in the world,
Lex Fridman (2:42:51.100)
as opposed to trying to shut it all down.
Karl Deisseroth (2:42:54.700)
That's right.
Lex Fridman (2:42:56.580)
Well, on that topic, I mean,
Karl Deisseroth (2:42:58.420)
I'd love to talk to you about schizophrenia.
Lex Fridman (2:43:00.700)
What is schizophrenia?
Karl Deisseroth (2:43:04.900)
From your research and from your general understanding,
Lex Fridman (2:43:07.500)
and what is the full landscape of suffering
Lex Fridman (2:43:10.700)
and wisdom that schizophrenia explores?
Lex Fridman (2:43:15.900)
Schizophrenia is a state where
Karl Deisseroth (2:43:19.420)
there is a break from reality.
Lex Fridman (2:43:22.300)
And so this can show up, as we call them,
Karl Deisseroth (2:43:25.020)
the positive symptoms of schizophrenia.
Lex Fridman (2:43:27.700)
These include hallucinations,
Karl Deisseroth (2:43:29.780)
hearing something or seeing something that's not there,
Lex Fridman (2:43:32.020)
usually auditory hallucinations.
Karl Deisseroth (2:43:34.660)
Paranoia, people can have complex fears.
Lex Fridman (2:43:38.500)
Delusions, which we call fixed false beliefs,
Karl Deisseroth (2:43:41.200)
people get an extremely unshakable
Lex Fridman (2:43:43.380)
but completely implausible idea about something.
Karl Deisseroth (2:43:46.580)
Sometimes it relates to themself, sometimes to the world.
Lex Fridman (2:43:49.880)
These we call the positive symptoms,
Karl Deisseroth (2:43:51.500)
break from reality as we know it.
Lex Fridman (2:43:54.640)
Then there are the negative symptoms that come with it,
Lex Fridman (2:43:57.020)
and these are progressive.
Lex Fridman (2:43:59.820)
These are flattening of emotion, as we call it,
Lex Fridman (2:44:04.460)
so starting to express less and less positive emotion,
Lex Fridman (2:44:07.540)
ending more in a neutral or flat state.
Karl Deisseroth (2:44:12.040)
Thought disorder, inability to work with complex patterns
Lex Fridman (2:44:16.520)
of planning or thinking, so you can't make plans,
Karl Deisseroth (2:44:19.580)
you'd have poor working memory,
Lex Fridman (2:44:21.200)
you can't keep track of where you were in a conversation,
Karl Deisseroth (2:44:25.420)
in a sequence of actions.
Lex Fridman (2:44:27.820)
So poor and impaired working with the thoughts of oneself
Lex Fridman (2:44:34.620)
and then these positive symptoms of break from reality.
Lex Fridman (2:44:37.980)
Okay, now why do these come together?
Lex Fridman (2:44:42.160)
What's the neurobiology of it?
Lex Fridman (2:44:44.060)
Again, we don't know.
Karl Deisseroth (2:44:45.380)
Schizophrenia, extremely genetically determined.
Lex Fridman (2:44:48.020)
If you look at the numbers,
Karl Deisseroth (2:44:48.860)
could be upwards of 80% genetically determined.
Lex Fridman (2:44:51.920)
1% of the human population around the world,
Lex Fridman (2:44:57.240)
it's universal, okay?
Lex Fridman (2:44:58.840)
It's not confined to any one culture,
Karl Deisseroth (2:45:00.880)
not even really biased in one culture or another,
Lex Fridman (2:45:04.640)
about 1% around the world.
Lex Fridman (2:45:07.360)
And has this progressive quality to it, untreated,
Lex Fridman (2:45:12.480)
so it's very interesting.
Karl Deisseroth (2:45:13.560)
There's a break that happens, we call it first break,
Lex Fridman (2:45:17.080)
when someone experiences their first disruption of reality,
Karl Deisseroth (2:45:22.680)
they can have a completely typical life up until that point.
Lex Fridman (2:45:25.160)
So you might have a, and I've seen just heartbreaking cases
Karl Deisseroth (2:45:28.200)
of like this in the Stanford emergency room
Lex Fridman (2:45:31.560)
where a kid has come there,
Karl Deisseroth (2:45:33.160)
who's been extremely high functioning in that sense
Lex Fridman (2:45:37.660)
of academic achievement and athletic and interpersonal,
Lex Fridman (2:45:41.720)
and then comes to college.
Lex Fridman (2:45:43.360)
Usually in men, it's around 18, 19 when the first break
Karl Deisseroth (2:45:47.600)
happens, some terrifying paranoia hits
Lex Fridman (2:45:52.520)
or some auditory hallucinations start.
Karl Deisseroth (2:45:55.240)
They're getting screamed at by a voice in their head.
Lex Fridman (2:45:57.760)
So devastating.
Karl Deisseroth (2:45:59.520)
With women, comes on also often a little later,
Lex Fridman (2:46:02.800)
sometimes in the 20s, and it can be progressive.
Karl Deisseroth (2:46:06.120)
If it's not treated, it just progresses and progresses.
Lex Fridman (2:46:09.640)
The voices become overwhelming, the delusions
Lex Fridman (2:46:14.120)
and paranoia extend and expand.
Lex Fridman (2:46:16.740)
The thought, the negative symptoms particularly
Karl Deisseroth (2:46:18.360)
become more and more severe.
Lex Fridman (2:46:20.360)
So one can't even maintain thoughts
Karl Deisseroth (2:46:23.120)
in any sort of ordered fashion.
Lex Fridman (2:46:26.360)
And then eventually, it can be fatal,
Karl Deisseroth (2:46:30.040)
it can lead to suicide, it can lead to erratic behavior
Lex Fridman (2:46:33.720)
that leads to accidents.
Karl Deisseroth (2:46:35.480)
Now, it can be treated.
Lex Fridman (2:46:38.840)
There are medications that help, fortunately.
Karl Deisseroth (2:46:42.200)
They have side effects, so they're not perfect.
Lex Fridman (2:46:44.040)
You can have movement problems and actually a whole host
Karl Deisseroth (2:46:49.680)
of different side effects that come from the medications.
Lex Fridman (2:46:51.600)
But we can help people now with schizophrenia
Karl Deisseroth (2:46:55.160)
very, very significantly.
Lex Fridman (2:46:58.040)
But the amazing thing, and this is emblematic
Karl Deisseroth (2:47:00.460)
of where psychiatry stands, we don't have
Lex Fridman (2:47:03.260)
the deep understanding, just like with depression,
Karl Deisseroth (2:47:05.760)
we don't have that heart as a pump level of understanding
Lex Fridman (2:47:09.600)
that we'd like to have with schizophrenia,
Karl Deisseroth (2:47:11.440)
despite it being so biological, so genetic in its nature.
Lex Fridman (2:47:15.360)
So is there a way to return to the other side
Lex Fridman (2:47:20.720)
of the first break?
Lex Fridman (2:47:22.360)
So when you have a break with reality,
Lex Fridman (2:47:24.040)
is there a way to kind of stitch it together?
Lex Fridman (2:47:27.480)
So some people, that works, but we don't really know how.
Lex Fridman (2:47:32.360)
So medications, antipsychotic medications, we call them,
Lex Fridman (2:47:36.120)
they block a particular neurotransmitter receptor
Karl Deisseroth (2:47:39.220)
called the serotonin 2A receptor,
Lex Fridman (2:47:44.240)
and they modulate dopamine as well
Lex Fridman (2:47:46.440)
and other neurotransmitters.
Lex Fridman (2:47:49.640)
These can take someone who's actively hallucinating,
Karl Deisseroth (2:47:53.700)
actively paranoid, put them back in a completely normal
Lex Fridman (2:47:56.720)
state, and some people stay that way indefinitely.
Lex Fridman (2:48:01.280)
So you can bring people back from that,
Lex Fridman (2:48:04.240)
back to the other side, have it stitched together.
Karl Deisseroth (2:48:07.240)
More typically, you'll end up in some intermediate state
Lex Fridman (2:48:11.920)
where symptoms are reduced powerfully,
Lex Fridman (2:48:15.440)
but there might be still something there
Lex Fridman (2:48:16.960)
and you've got a drop down in functioning
Karl Deisseroth (2:48:19.480)
that may be persistent for a while.
Lex Fridman (2:48:22.020)
But concepts, what physically is going on?
Karl Deisseroth (2:48:26.080)
One idea is that it's communication within the brain.
Lex Fridman (2:48:31.680)
One part of the brain is not able to tell
Karl Deisseroth (2:48:34.800)
other parts of the brain what it's doing.
Lex Fridman (2:48:36.400)
And so the auditory hallucinations
Karl Deisseroth (2:48:38.020)
are very interesting in this regard.
Lex Fridman (2:48:40.240)
They often have this conversational,
Karl Deisseroth (2:48:42.080)
inner monologue like quality.
Lex Fridman (2:48:44.280)
As we're walking along the street,
Karl Deisseroth (2:48:45.440)
we may have an inner monologue,
Lex Fridman (2:48:47.180)
thoughts about what's going on.
Karl Deisseroth (2:48:49.200)
If we see somebody we don't like,
Lex Fridman (2:48:50.680)
we may have a thought,
Karl Deisseroth (2:48:52.080)
wish somebody would punch that guy, something like that,
Lex Fridman (2:48:54.160)
or maybe I should punch that guy.
Lex Fridman (2:48:55.300)
But these are so far below where we would ever act
Lex Fridman (2:48:59.920)
or even think of acting,
Lex Fridman (2:49:02.320)
but they're just things that come up.
Lex Fridman (2:49:03.800)
And in people with schizophrenia,
Karl Deisseroth (2:49:07.720)
those inner thoughts, that inner monologue,
Lex Fridman (2:49:09.920)
is not recognized as the inner monologue of the self.
Lex Fridman (2:49:15.200)
And so it's perceived as something coming from the outside
Lex Fridman (2:49:20.840)
or from inside, but from another entity.
Karl Deisseroth (2:49:23.360)
Another, oh, another, I thought you meant
Lex Fridman (2:49:26.000)
like another room inside the same building.
Karl Deisseroth (2:49:29.240)
Another room inside there, yeah.
Lex Fridman (2:49:31.880)
And so that's, so it could be conceptualized
Karl Deisseroth (2:49:35.280)
as a communication within the brain problem,
Lex Fridman (2:49:38.320)
notifying another part of the brain what's going on.
Lex Fridman (2:49:40.880)
And there's some evidence consistent with that.
Lex Fridman (2:49:44.280)
I don't know if you can help with this,
Lex Fridman (2:49:45.760)
but I sometimes, so I've been talking
Lex Fridman (2:49:48.320)
to quite a few homeless folks recently,
Karl Deisseroth (2:49:50.280)
just, so what I do is I hang out at night
Lex Fridman (2:49:56.080)
and talk to interesting people.
Lex Fridman (2:49:59.800)
And some of them, and I've known people in the past
Lex Fridman (2:50:02.560)
who suffer from schizophrenia,
Lex Fridman (2:50:03.920)
and some of them, like self, will describe
Lex Fridman (2:50:07.880)
as that as something they suffer from.
Lex Fridman (2:50:12.440)
And they seem to understand something deeply
Lex Fridman (2:50:14.400)
about this world.
Karl Deisseroth (2:50:15.880)
I don't know if it's correlated
Lex Fridman (2:50:17.960)
or maybe it's another aspect of like depression,
Karl Deisseroth (2:50:23.440)
all those things that I've encountered in my own life
Lex Fridman (2:50:27.720)
is maybe just the struggle and the suffering
Karl Deisseroth (2:50:31.580)
has taken you through a life
Lex Fridman (2:50:33.180)
where you think deeply about life.
Karl Deisseroth (2:50:35.280)
Like there's like self reflection
Lex Fridman (2:50:37.500)
that society forces on you
Karl Deisseroth (2:50:39.520)
because it's a disorder of some kind.
Lex Fridman (2:50:43.320)
It's interesting, I guess my only sort
Karl Deisseroth (2:50:46.240)
of anecdotal observation is people who suffer
Lex Fridman (2:50:48.480)
from schizophrenia seem to be very interesting
Lex Fridman (2:50:53.040)
and very thoughtful in a nonlinear way about the world.
Lex Fridman (2:51:00.080)
I've noticed that it's not always positive.
Karl Deisseroth (2:51:04.040)
There are unusual ways they view the world.
Lex Fridman (2:51:06.560)
It was, but it's always interesting.
Karl Deisseroth (2:51:10.000)
That could be conspiratorial thinking too.
Lex Fridman (2:51:12.680)
Like, but like the theories they have
Karl Deisseroth (2:51:15.040)
about the way the world functions,
Lex Fridman (2:51:17.080)
often very well read, which is also interesting
Karl Deisseroth (2:51:20.480)
because they're almost like looking
Lex Fridman (2:51:21.620)
for helpful answers from somewhere.
Karl Deisseroth (2:51:23.640)
Absolutely there.
Lex Fridman (2:51:24.540)
And so they're, they might be citing
Karl Deisseroth (2:51:26.440)
some very interesting literature
Lex Fridman (2:51:27.920)
and then using that to, there's a stickiness
Karl Deisseroth (2:51:32.760)
in their mind to different models of the world
Lex Fridman (2:51:34.800)
and trying to make sense of that world.
Lex Fridman (2:51:36.640)
And those models could include conspiracy theories.
Lex Fridman (2:51:39.080)
Yeah, they're very attuned to complexity
Lex Fridman (2:51:42.400)
and they come up with unlikely explanations,
Lex Fridman (2:51:46.180)
which is one of the things that makes them,
Karl Deisseroth (2:51:48.440)
it makes it hard for them to function in the world
Lex Fridman (2:51:50.520)
is how unlikely their explanations are.
Lex Fridman (2:51:53.040)
But you're right, there's a depth of consideration
Lex Fridman (2:51:55.800)
of the complexity of the world and a concern about it
Lex Fridman (2:52:00.400)
and a work, an impulse to work to understand it
Lex Fridman (2:52:04.640)
that is actually quite refreshing.
Lex Fridman (2:52:07.080)
But the first case in the medical literature,
Lex Fridman (2:52:11.120)
there was a classical schizophrenia.
Karl Deisseroth (2:52:15.280)
There was a patient named James Tilly Matthews
Lex Fridman (2:52:17.880)
who had this, he sketched out for his doctor
Karl Deisseroth (2:52:22.380)
the experiences he was sensing
Lex Fridman (2:52:26.560)
and he drew himself as a cowering figure
Karl Deisseroth (2:52:31.080)
on the ground controlled by a loom,
Lex Fridman (2:52:34.600)
a weaving device that was sending threads,
Karl Deisseroth (2:52:37.840)
long threads, projections across space
Lex Fridman (2:52:40.840)
from the loom to him, to his arms and to his body
Lex Fridman (2:52:44.080)
and controlling him from afar.
Lex Fridman (2:52:47.760)
And he called this the air loom, a loom in the air.
Lex Fridman (2:52:51.720)
And it was such an evocative thing
Lex Fridman (2:52:54.200)
because this was the start of the Industrial Revolution
Karl Deisseroth (2:52:56.640)
or mid and it was where really industrial strength,
Lex Fridman (2:53:01.280)
looms and weaving devices were really kind of the emblematic
Karl Deisseroth (2:53:05.840)
of the most complex, powerful technological achievements
Lex Fridman (2:53:10.280)
of the time and so that was the explanation available
Karl Deisseroth (2:53:13.280)
to him to explain how his body was seemingly moved
Lex Fridman (2:53:18.040)
without his volition and these days, of course,
Karl Deisseroth (2:53:22.040)
people with schizophrenia will have more technology
Lex Fridman (2:53:25.040)
appropriate interpretations, they'll have delusions
Karl Deisseroth (2:53:29.020)
of satellite or alien control or beamed information,
Lex Fridman (2:53:32.920)
very, very common to have this delusion
Karl Deisseroth (2:53:35.060)
of a government agency sending electromagnetic
Lex Fridman (2:53:39.640)
or radio frequency information to control their limbs.
Lex Fridman (2:53:43.360)
But it's the same thing, whether it's a thread
Lex Fridman (2:53:45.760)
from an Industrial Revolution loom
Karl Deisseroth (2:53:48.280)
or RF radiation, it's the same thing just adapted
Lex Fridman (2:53:53.480)
to the moment explaining, trying to explain
Karl Deisseroth (2:53:56.400)
the world they live in and their relationship to the world.
Lex Fridman (2:53:58.520)
But unconstrained by sort of the thing
Karl Deisseroth (2:54:01.160)
that's socially acceptable,
Lex Fridman (2:54:02.720)
which is both refreshing and dangerous.
Karl Deisseroth (2:54:05.320)
Yes.
Lex Fridman (2:54:08.640)
I wrote down a question.
Lex Fridman (2:54:10.880)
Why do we cry?
Lex Fridman (2:54:13.240)
Are tears a window to some depths
Lex Fridman (2:54:15.200)
that we ourselves don't know?
Lex Fridman (2:54:17.500)
I almost wanna make fun of myself for that question,
Lex Fridman (2:54:19.620)
but you do talk seriously about crying in the book.
Lex Fridman (2:54:22.600)
In fact, the whole first chapter really tussles
Karl Deisseroth (2:54:26.280)
with crying as why do we do it, what does it mean,
Lex Fridman (2:54:29.240)
why is it involuntary?
Lex Fridman (2:54:31.000)
It seems like a weakness, right?
Lex Fridman (2:54:32.560)
Because it's so involuntary and it's reflecting
Karl Deisseroth (2:54:35.240)
something true and inside.
Lex Fridman (2:54:37.760)
At the level of the individual,
Lex Fridman (2:54:39.120)
that seems like a problem, right?
Lex Fridman (2:54:40.480)
Wouldn't it be better if we could control it,
Karl Deisseroth (2:54:42.560)
if we could not show that emotion when it's not useful,
Lex Fridman (2:54:48.600)
show it when it's useful?
Lex Fridman (2:54:49.480)
But it's not, it's largely involuntary.
Lex Fridman (2:54:52.880)
And so there's a value to it, I think,
Karl Deisseroth (2:54:55.540)
as an honest reporter of a need,
Lex Fridman (2:54:59.040)
of hope and frailty at the same time.
Karl Deisseroth (2:55:03.520)
I am a human being, there's a frailty to myself
Lex Fridman (2:55:10.120)
or my situation where I need social help,
Karl Deisseroth (2:55:12.280)
I need help from my community.
Lex Fridman (2:55:14.680)
I have hope that that is possible,
Lex Fridman (2:55:18.360)
but I'm not enough for myself, I need the community.
Lex Fridman (2:55:21.520)
That I think is what the social signal of crying is.
Karl Deisseroth (2:55:25.400)
Now people have studied crying, it's an extreme,
Lex Fridman (2:55:29.280)
you can quantify the extent to which the presence of tears
Karl Deisseroth (2:55:33.240)
on a face triggers reactions in onlookers.
Lex Fridman (2:55:37.920)
And you can show the same face in the presence
Karl Deisseroth (2:55:41.040)
or absence of tears and show that to people
Lex Fridman (2:55:44.320)
under quantifiable and rigorous psychological conditions.
Lex Fridman (2:55:49.360)
And tears are much more powerful at stirring
Lex Fridman (2:55:53.280)
the desire to help in viewers
Karl Deisseroth (2:55:57.040)
than any other facial feature.
Lex Fridman (2:56:01.120)
Which is pretty interesting that it's the honest one
Lex Fridman (2:56:04.000)
that's also the most powerful, right?
Lex Fridman (2:56:05.640)
It kind of indicates there's a certain logic
Karl Deisseroth (2:56:07.720)
to our design as social beings
Lex Fridman (2:56:11.240)
that we have an honest report.
Karl Deisseroth (2:56:14.560)
That's hard to control.
Lex Fridman (2:56:17.160)
But is it well understood how that connects
Lex Fridman (2:56:21.520)
to the internal state of emotion?
Lex Fridman (2:56:26.360)
Yeah, there are long range projections that come,
Lex Fridman (2:56:30.480)
so where is crying generated?
Lex Fridman (2:56:31.840)
This is the confusing thing about it.
Lex Fridman (2:56:33.200)
So that we have a little tear duct, the lacrimal gland
Lex Fridman (2:56:36.600)
that leads to the release of fluid,
Karl Deisseroth (2:56:38.080)
it ejects fluid and it comes out.
Lex Fridman (2:56:40.360)
And those of course, that whole system was designed
Karl Deisseroth (2:56:43.440)
to keep the eye clean, to wash out particulate irritants.
Lex Fridman (2:56:47.040)
So it's a long standing, as long as we've had eyes
Lex Fridman (2:56:49.760)
and have been out of the water in our evolution,
Lex Fridman (2:56:52.840)
we've needed this sort of thing.
Lex Fridman (2:56:53.960)
So long standing biological structure,
Lex Fridman (2:56:56.120)
recently co opted it seems by our evolution
Karl Deisseroth (2:56:59.960)
as social primates.
Lex Fridman (2:57:02.920)
Now, how could that happen?
Karl Deisseroth (2:57:03.880)
Well, the lacrimal gland is controlled by structures
Lex Fridman (2:57:07.560)
in the pons, which is a structure deep in our,
Karl Deisseroth (2:57:11.200)
just above our neck, between our neck and our head.
Lex Fridman (2:57:14.120)
And reflecting its ancient origin, right?
Karl Deisseroth (2:57:16.760)
As you go farther down toward the spinal cord,
Lex Fridman (2:57:18.560)
these are the more basic early evolved structures.
Lex Fridman (2:57:21.840)
And in the pons, that's where breathing is controlled,
Lex Fridman (2:57:25.240)
tear duct contraction.
Lex Fridman (2:57:30.480)
And what we found and with optogenetics,
Lex Fridman (2:57:34.000)
we helped sort this out,
Karl Deisseroth (2:57:35.360)
there are long range projections
Lex Fridman (2:57:36.760)
from fear and anxiety regions in the forebrain
Karl Deisseroth (2:57:40.960)
that project all the way to the pons
Lex Fridman (2:57:43.360)
in and around those areas.
Karl Deisseroth (2:57:45.360)
The reason those are there,
Lex Fridman (2:57:47.280)
we think is to regulate the respiratory rate changes,
Karl Deisseroth (2:57:50.720)
the breathing changes of fear and anxiety.
Lex Fridman (2:57:52.960)
So we know when we're in a state of fear and anxiety,
Karl Deisseroth (2:57:55.720)
we need, we cope better if we have elevated heart rate,
Lex Fridman (2:57:58.840)
elevated respiratory rate, more blood pumping around,
Karl Deisseroth (2:58:01.480)
more oxygenated blood,
Lex Fridman (2:58:02.440)
we're ready to meet the threat if it happens.
Karl Deisseroth (2:58:05.040)
All those cells are down there in the pons too,
Lex Fridman (2:58:07.480)
right next to the lacrimal duct, the tear gland neurons.
Lex Fridman (2:58:12.480)
And so almost certainly this fear anxiety induced crying
Lex Fridman (2:58:17.480)
arose from a very slightly misdirected long range projection
Karl Deisseroth (2:58:23.560)
that was there to regulate breathing.
Lex Fridman (2:58:27.520)
And a little twist, just a little misdirection,
Karl Deisseroth (2:58:29.800)
a little missing of one sign post to stop here,
Lex Fridman (2:58:33.640)
going on a little farther,
Karl Deisseroth (2:58:35.320)
getting to the lacrimal gland neurons gave us crying.
Lex Fridman (2:58:38.920)
And that's, and we just have it,
Karl Deisseroth (2:58:40.400)
that peculiar sort of structure, neuronal structure
Lex Fridman (2:58:43.680)
that resulted in that, that's what we're stuck with.
Lex Fridman (2:58:46.680)
And that ends up being, in terms of social interaction,
Lex Fridman (2:58:50.000)
one of the more important, authentic,
Karl Deisseroth (2:58:53.880)
involuntary displays of interstate.
Lex Fridman (2:58:57.040)
That's right.
Lex Fridman (2:58:57.880)
And social communication.
Lex Fridman (2:58:58.920)
Yeah.
Lex Fridman (2:58:59.760)
Oh, yeah, is there other stuff like that?
Lex Fridman (2:59:04.000)
I mean, do you, yeah, I mean, the human face is fascinating
Karl Deisseroth (2:59:08.160)
as a display of emotion, as a display of truth and lying
Lex Fridman (2:59:12.280)
and all those kinds of things.
Karl Deisseroth (2:59:13.880)
I personally, I mean, we're all, I suppose,
Lex Fridman (2:59:19.560)
have different sensors that are sensitive
Karl Deisseroth (2:59:24.160)
to certain aspects of the human face.
Lex Fridman (2:59:25.720)
But to me, it seems like the eyes
Karl Deisseroth (2:59:28.320)
are really important communication or something.
Lex Fridman (2:59:31.240)
You know, I've talked to a few sort of girls
Karl Deisseroth (2:59:33.160)
about like Botox and stuff like that.
Lex Fridman (2:59:35.320)
And it always bothers me when,
Karl Deisseroth (2:59:37.560)
I guess guys can do this too,
Lex Fridman (2:59:38.800)
but like when women speak negatively
Karl Deisseroth (2:59:43.440)
of, I guess you can call them wrinkles,
Lex Fridman (2:59:46.280)
at the tips of an eye.
Lex Fridman (2:59:49.760)
But like to me, when you smile, when you wink,
Lex Fridman (2:59:54.440)
not wink, but like narrow the eyes,
Karl Deisseroth (2:59:58.040)
something is communicated and those,
Lex Fridman (30:00.760)
We need those people who can serve as bridges
Karl Deisseroth (30:03.600)
across cultures who really can do both.
Lex Fridman (30:06.960)
You mentioned Borges, so you open your book
Karl Deisseroth (30:10.400)
with a few lines from a poem by Jorge Luis Borges,
Lex Fridman (30:14.720)
a love poem.
Karl Deisseroth (30:15.880)
I'm gonna read parts of it because it's a damn good poem.
Lex Fridman (30:18.660)
It's called Two English Poems.
Karl Deisseroth (30:20.380)
I mean, there's, I'd like to understand why you used it
Lex Fridman (30:24.080)
and the specific parts you used, which is interesting.
Lex Fridman (30:27.480)
But then when I read the full thing,
Lex Fridman (30:30.440)
so I think you used it as a sort of beautiful description
Karl Deisseroth (30:36.340)
of what it means to delve deep into understanding,
Lex Fridman (30:40.080)
offering yourself to the task of understanding
Karl Deisseroth (30:42.440)
another human being.
Lex Fridman (30:43.960)
But if you look at the full context of the poem,
Karl Deisseroth (30:46.000)
it's also a damn good description of being hit by love
Lex Fridman (30:49.080)
and overtaken by it and sort of,
Lex Fridman (30:52.760)
and trying to figure out how to make sense of the world
Lex Fridman (30:56.560)
now that you've been stricken by it.
Karl Deisseroth (30:59.320)
It says a bunch of things about chatting
Lex Fridman (31:03.800)
and significantly with friends and all those kinds of things
Lex Fridman (31:06.020)
and then the poem reads, the big wave brought you.
Lex Fridman (31:10.600)
I get, this is the moment, I guess, of the universe
Karl Deisseroth (31:14.160)
where the two people you fall in love.
Lex Fridman (31:16.720)
Maybe I'm totally misreading this poem, by the way.
Karl Deisseroth (31:18.800)
Doesn't matter, you can't misread a poem.
Lex Fridman (31:20.720)
So it goes on, words, any words, your laughter,
Lex Fridman (31:25.880)
and you're so lazily and incessantly beautiful.
Lex Fridman (31:28.900)
We talked and you have forgotten the words.
Karl Deisseroth (31:31.880)
The shattering dawn finds me in a deserted street
Lex Fridman (31:34.600)
of my city, your profile turned away.
Karl Deisseroth (31:37.720)
The sounds that go to make your name.
Lex Fridman (31:40.280)
The lilt of your laughter.
Karl Deisseroth (31:42.120)
These are the illustrious toys you have left me.
Lex Fridman (31:45.240)
So these little memories of these peculiar little details,
Karl Deisseroth (31:48.280)
he remembers, those are the illustrious toys.
Lex Fridman (31:51.040)
I apologize to mix my own words with the poem,
Lex Fridman (31:53.160)
but you should definitely read it.
Lex Fridman (31:55.640)
I turn them over in the dawn, I lose them.
Karl Deisseroth (31:58.640)
I find them.
Lex Fridman (31:59.840)
I tell them to the few stray dogs
Lex Fridman (32:01.760)
and to the few stray stars of the dawn.
Lex Fridman (32:05.360)
Your dark, rich life.
Karl Deisseroth (32:09.080)
I must get at you somehow.
Lex Fridman (32:11.620)
I put away those illustrious toys you have left me.
Karl Deisseroth (32:14.500)
I want your hidden look, your real smile.
Lex Fridman (32:18.000)
That lonely, mocking smile your cool mirror knows.
Karl Deisseroth (32:22.080)
I want your hidden look, your real smile.
Lex Fridman (32:26.000)
So this is the first part of the poem,
Lex Fridman (32:28.060)
and then it goes on, which is some of the parts
Lex Fridman (32:30.740)
that you reference.
Lex Fridman (32:33.040)
Second part is, what can I hold you with?
Lex Fridman (32:36.000)
I offer you lean streets, desperate sunsets,
Karl Deisseroth (32:38.500)
the moon of the jagged suburbs.
Lex Fridman (32:40.320)
I offer you the bitterness of a man
Karl Deisseroth (32:42.080)
who has looked long and long at a lonely moon.
Lex Fridman (32:45.220)
I offer you my ancestors, my dead men,
Karl Deisseroth (32:48.440)
the ghosts that living men have honored in bronze.
Lex Fridman (32:51.340)
My father's father killed in the frontier of Buenos Aires,
Karl Deisseroth (32:55.200)
two bullets through his lungs, and so on, so on.
Lex Fridman (32:57.780)
I offer you whatever insights my books may hold,
Karl Deisseroth (33:00.480)
whatever manliness or humor in my life.
Lex Fridman (33:02.580)
I offer you the loyalty of a man who has never been loyal.
Karl Deisseroth (33:05.800)
I offer you that carnival of myself
Lex Fridman (33:08.040)
that I have saved somehow, the central heart
Karl Deisseroth (33:10.080)
that deals not in words, traffics, not with dreams,
Lex Fridman (33:14.120)
and is untouched by time, my joy, and adversities.
Lex Fridman (33:18.560)
And I think this is the part that you include in the book.
Lex Fridman (33:22.080)
I offer you the memory of a yellow rose seen at sunset,
Karl Deisseroth (33:25.600)
years before you were born, I, damn, that's a good line.
Lex Fridman (33:30.680)
Okay, I offer you explanations of yourself,
Karl Deisseroth (33:35.280)
theories about yourself,
Lex Fridman (33:36.520)
authentic and surprising news of yourself.
Karl Deisseroth (33:39.080)
I can give you my loneliness, my darkness,
Lex Fridman (33:42.000)
the hunger of my heart.
Karl Deisseroth (33:43.560)
I'm trying to bribe you with uncertainty,
Lex Fridman (33:45.640)
with danger, with defeat.
Karl Deisseroth (33:47.720)
That is a man who's in love and longing.
Lex Fridman (33:49.980)
If I've taken, but I just wanna go back to,
Karl Deisseroth (33:52.960)
maybe you could say why you wanted to include that poem,
Lex Fridman (33:55.120)
but also your dark, rich life, I must get at you somehow.
Karl Deisseroth (34:00.080)
I put away those illustrious toys you have left me at.
Lex Fridman (34:03.440)
I want your hidden look, your real smile,
Karl Deisseroth (34:06.080)
that lonely, mocking smile, your cool mirror nose.
Lex Fridman (34:09.040)
Sometimes I meet a stranger, and I just,
Karl Deisseroth (34:13.320)
it's like a double take.
Lex Fridman (34:15.920)
It's like, who are you?
Lex Fridman (34:17.820)
Have we met before somewhere?
Lex Fridman (34:19.480)
Who's that person behind there?
Lex Fridman (34:22.320)
And I wanna get at that, whatever that is.
Lex Fridman (34:25.000)
And of course, maybe that's what love is,
Karl Deisseroth (34:27.000)
because maybe that's the whole pursuit,
Lex Fridman (34:30.200)
like a lifelong pursuit of getting at that person.
Karl Deisseroth (34:32.360)
Maybe that's what that is,
Lex Fridman (34:33.640)
and like that insatiable sort of curiosity to keep getting.
Lex Fridman (34:37.960)
Like, well, who is that person in your own private life?
Lex Fridman (34:40.400)
Yeah, so that, absolutely, I think that,
Karl Deisseroth (34:42.680)
it was a beautiful description of what you just said,
Lex Fridman (34:44.900)
when there's that first moment,
Lex Fridman (34:46.840)
and then you wanna dive deeper.
Lex Fridman (34:48.880)
You want to know what the hidden mysteries are.
Karl Deisseroth (34:52.160)
In a way, it's a love poem.
Lex Fridman (34:55.280)
As a scientist, though, it also,
Karl Deisseroth (34:58.480)
it's a bit of how a scientist can love science,
Lex Fridman (35:01.120)
and that wanting to dive deeper is,
Karl Deisseroth (35:07.560)
it's almost like, again, where the,
Lex Fridman (35:09.760)
it could be a love affair
Karl Deisseroth (35:10.840)
with investigating the human mind, for example.
Lex Fridman (35:13.320)
And that was one reason it spoke to me also.
Karl Deisseroth (35:16.600)
Again, thinking about the broader sweep
Lex Fridman (35:19.160)
of where the human mind came from,
Lex Fridman (35:20.860)
and the steps it took to get where it is today,
Lex Fridman (35:25.020)
what was given up along the way,
Lex Fridman (35:26.940)
what compromises were made.
Lex Fridman (35:28.180)
And here's where the darkness of the poem
Karl Deisseroth (35:29.780)
starts to come in a little bit, too.
Lex Fridman (35:31.500)
It doesn't shy away from the negativity,
Karl Deisseroth (35:35.060)
from the confusion, from the danger.
Lex Fridman (35:39.100)
And then at the very end,
Karl Deisseroth (35:42.120)
the boardface is offering up scenes from his life,
Lex Fridman (35:46.540)
parts of himself, and this is how we connect with people.
Karl Deisseroth (35:49.540)
We offer up parts of ourselves, just here it is,
Lex Fridman (35:51.940)
and then we see how well does that map onto what you have.
Lex Fridman (35:54.640)
And it's that offering up that I liked,
Lex Fridman (35:57.780)
and not the good stuff, or not only the good stuff.
Karl Deisseroth (36:00.380)
The yellow rose is nice,
Lex Fridman (36:01.380)
but he's offering up the bad stuff, too.
Lex Fridman (36:03.660)
And that, to me, was important for the book,
Lex Fridman (36:06.260)
because I'm offering up hard stuff, too.
Karl Deisseroth (36:10.000)
In fact, a lot of it.
Lex Fridman (36:11.220)
And also, hard stuff from within me,
Karl Deisseroth (36:13.420)
from my own personal side, too.
Lex Fridman (36:15.080)
And that was, there's a lot of vulnerability
Karl Deisseroth (36:17.460)
that comes with that, but that comes with love,
Lex Fridman (36:20.180)
that comes with writing.
Karl Deisseroth (36:21.300)
You have to be open, you have to be vulnerable.
Lex Fridman (36:23.540)
And so, I thought that reflected what I was trying to do,
Lex Fridman (36:28.180)
and I thought it was, as an epigraph,
Lex Fridman (36:29.740)
it kind of made it clear how vulnerable I was
Karl Deisseroth (36:33.740)
in taking this step, but also what could come out of it.
Lex Fridman (36:38.260)
And also, in a meta way,
Karl Deisseroth (36:39.620)
because I was not familiar with this poem,
Lex Fridman (36:41.820)
it made me curious of the poem itself
Karl Deisseroth (36:47.620)
to pull at that thread of finding out more.
Lex Fridman (36:51.260)
You picked a very particular part
Karl Deisseroth (36:53.300)
that kind of made you want to pull at that thread,
Lex Fridman (36:57.660)
and see where did these few lines come from?
Karl Deisseroth (37:02.940)
Because I read it as a curiosity of a scientist,
Lex Fridman (37:05.780)
those lines alone.
Lex Fridman (37:08.380)
And also, as a desperate human being,
Lex Fridman (37:13.300)
searching, like offering himself for an understanding,
Karl Deisseroth (37:17.340)
or connection with another human being.
Lex Fridman (37:19.500)
And then, because I wasn't sure if it's a love poem or not,
Karl Deisseroth (37:21.980)
or if it's desperation, or if it's curiosity,
Lex Fridman (37:23.700)
whatever it is, and then you see the love poem.
Karl Deisseroth (37:26.220)
I mean, I don't know, that's gonna stick with me
Lex Fridman (37:28.300)
for a while, your dark, rich life.
Lex Fridman (37:32.180)
And then a few lines in here are just,
Lex Fridman (37:35.340)
I mean, those are, I'm gonna just use them
Karl Deisseroth (37:38.500)
as pickup lines at a bar.
Lex Fridman (37:40.260)
I offer you the memory of a yellow rose
Karl Deisseroth (37:42.420)
seen at sunset years before you were born.
Lex Fridman (37:47.380)
No, that's a pickup line I've never heard,
Karl Deisseroth (37:48.900)
if I've ever heard one, anyway, sorry.
Lex Fridman (37:51.460)
But this is universal.
Karl Deisseroth (37:52.300)
You see it in so many forms of art.
Lex Fridman (37:55.500)
Like, we're in Texas now,
Karl Deisseroth (37:57.340)
you see this in country and western songs.
Lex Fridman (38:00.020)
It's often a list of things.
Karl Deisseroth (38:02.100)
Like, here's how I describe myself.
Lex Fridman (38:03.620)
There's this, and there's that,
Lex Fridman (38:04.460)
and there's the other thing, and here you are.
Lex Fridman (38:06.300)
These things matter to me,
Lex Fridman (38:07.900)
and I hope they matter to you, too.
Lex Fridman (38:09.260)
It's a pretty universal form,
Lex Fridman (38:11.060)
but he did it in this very artful
Lex Fridman (38:14.700)
and very vulnerable way.
Karl Deisseroth (38:16.780)
It was both beautiful, and you could feel the hurt
Lex Fridman (38:20.580)
coming from him, too, and that was important.
Karl Deisseroth (38:22.960)
The dark stuff, too.
Lex Fridman (38:24.300)
I offer you my ancestors, my dead men,
Karl Deisseroth (38:26.820)
the ghosts that living men have honored in bronze,
Lex Fridman (38:29.460)
and talking about two bullets through his lungs,
Karl Deisseroth (38:32.300)
bearded and dead, wrapped by his soldiers
Lex Fridman (38:36.620)
in the hide of a cow,
Karl Deisseroth (38:37.980)
a mother's grandfather just 24,
Lex Fridman (38:40.320)
heading a charge of 300 men in Peru,
Karl Deisseroth (38:43.620)
now ghosts on vanished horses.
Lex Fridman (38:46.980)
So all of it, the whole history of it.
Lex Fridman (38:50.320)
Since it is a love poem, what do you think about love?
Lex Fridman (38:55.100)
Carl, what's the role of love in the human condition?
Karl Deisseroth (38:58.620)
We'll talk about the dark stuff.
Lex Fridman (39:00.660)
But maybe love is the dark stuff, too.
Karl Deisseroth (39:02.940)
I mean, it's the most powerful connection we can form,
Lex Fridman (39:06.980)
and that's what makes it so important to us.
Karl Deisseroth (39:11.280)
It's the strongest and most stable connection
Lex Fridman (39:16.300)
that we can form with another person,
Lex Fridman (39:17.700)
and that matters immensely.
Lex Fridman (39:19.900)
It matters for the human family to have evolved
Karl Deisseroth (39:24.420)
to be something that could survive against the odds
Lex Fridman (39:27.220)
that we've faced over the years.
Karl Deisseroth (39:29.740)
That unreasonable bond that becomes reasonable
Lex Fridman (39:35.580)
by virtue of its own existence.
Lex Fridman (39:38.580)
And of course, that joy, the wild, raw joy of love,
Lex Fridman (39:45.060)
is not a bad thing, either.
Lex Fridman (39:46.660)
So you put these together,
Lex Fridman (39:48.540)
the strongest bridge we can form,
Lex Fridman (39:51.580)
and the reward and the joy that it brings.
Lex Fridman (39:54.340)
That's what love is to me,
Lex Fridman (39:56.820)
and from my perspective, this is something that,
Lex Fridman (3:00:00.320)
that stuff is really useful, the human face.
Lex Fridman (3:00:03.120)
And when it's gone, something is missing.
Lex Fridman (3:00:05.400)
And a lot of little stuff, it feels like it really,
Karl Deisseroth (3:00:08.560)
it's almost involuntary, I guess,
Lex Fridman (3:00:10.680)
but it's harder to describe as the presence
Karl Deisseroth (3:00:12.860)
or absence of tears.
Lex Fridman (3:00:13.920)
It's like something about this person,
Karl Deisseroth (3:00:16.600)
you can tell they're not bullshitting you.
Lex Fridman (3:00:18.840)
Yeah, yeah.
Lex Fridman (3:00:19.680)
And so that was what made, presumably,
Lex Fridman (3:00:21.940)
that tear recruitment so powerful,
Karl Deisseroth (3:00:24.840)
is it just landed in this very high value real estate
Lex Fridman (3:00:28.420)
for social communication.
Karl Deisseroth (3:00:29.780)
If it had gone to, you know,
Lex Fridman (3:00:31.640)
there's a lot of neurons in the pons
Karl Deisseroth (3:00:34.000)
that control movement of large muscles elsewhere,
Lex Fridman (3:00:40.180)
that would have been much less effective
Karl Deisseroth (3:00:41.620)
as a social signal than something around the eye.
Lex Fridman (3:00:43.440)
So it was, however that little misdirection happened,
Karl Deisseroth (3:00:46.800)
it landed in a great area for social communication.
Lex Fridman (3:00:50.420)
And because it was coming from the fear and anxiety circuits
Karl Deisseroth (3:00:53.400)
that regulate that necessary involuntary change
Lex Fridman (3:00:57.000)
in heart rate and respiratory rate,
Karl Deisseroth (3:00:59.640)
it also was involuntary and that became valuable
Lex Fridman (3:01:02.440)
as a truth signal, as social beings.
Lex Fridman (3:01:05.880)
So very interesting when you think about
Lex Fridman (3:01:08.480)
the origins of the human family,
Karl Deisseroth (3:01:09.680)
the origins of social structures
Lex Fridman (3:01:12.480)
and our ability and need to call for help
Karl Deisseroth (3:01:14.920)
when there's hope, but need at the same time.
Lex Fridman (3:01:20.520)
What is consciousness, Carl?
Lex Fridman (3:01:23.080)
So you're actually using techniques.
Lex Fridman (3:01:26.560)
I mean, even putting psychiatry aside,
Karl Deisseroth (3:01:28.360)
just looking at optogenetics,
Lex Fridman (3:01:31.760)
you're trying to understand some of these deep aspects
Karl Deisseroth (3:01:34.440)
of the human mind.
Lex Fridman (3:01:36.040)
And maybe this is a good time to return to a question
Karl Deisseroth (3:01:38.380)
you mentioned you might have an opinion on
Lex Fridman (3:01:41.160)
if there's such a thing as a theory of everything
Karl Deisseroth (3:01:43.260)
for the human mind.
Lex Fridman (3:01:44.920)
Because surely answering of what is consciousness
Karl Deisseroth (3:01:47.800)
is as, well, that's not sure.
Lex Fridman (3:01:50.920)
But it seems like it's a fundamental part
Karl Deisseroth (3:01:53.480)
of the human experience in the human mind
Lex Fridman (3:01:56.160)
and solving that question will result in solving
Karl Deisseroth (3:02:00.680)
the bigger thing about the human mind.
Lex Fridman (3:02:02.620)
The flip side could be consciousness
Karl Deisseroth (3:02:05.000)
is just the few neurons that are generating
Lex Fridman (3:02:07.680)
some useful thing that make us,
Karl Deisseroth (3:02:10.080)
it's like the sense of self
Lex Fridman (3:02:12.920)
that you talked about in the mice.
Karl Deisseroth (3:02:16.280)
Maybe it's a subset of those cells
Lex Fridman (3:02:18.620)
that are just creating a richer sense of self
Lex Fridman (3:02:21.080)
and that's it.
Lex Fridman (3:02:22.900)
So this is a great question.
Karl Deisseroth (3:02:26.240)
All neuroscientists think about this
Lex Fridman (3:02:28.080)
and a lot of non neuroscientists too.
Karl Deisseroth (3:02:29.840)
It's the reason a lot of people came to the study
Lex Fridman (3:02:34.040)
of the brain is to think about consciousness
Lex Fridman (3:02:36.080)
and not just being awake or alert
Lex Fridman (3:02:38.360)
but really what's sometimes called
Karl Deisseroth (3:02:40.480)
the hard problem of consciousness
Lex Fridman (3:02:42.240)
which is what is that nature of that inner
Lex Fridman (3:02:45.880)
subjective sense we have?
Lex Fridman (3:02:47.800)
Not just information processing
Lex Fridman (3:02:51.800)
but feeling something about the information.
Lex Fridman (3:02:54.960)
What is that inner state of subjectivity physically?
Lex Fridman (3:02:59.120)
What is it?
Lex Fridman (3:03:00.880)
And that's called the hard problem of consciousness
Lex Fridman (3:03:03.320)
and it's not a extremely well defined question.
Lex Fridman (3:03:08.560)
Everybody has sort of a sense of what it means
Lex Fridman (3:03:11.340)
but it's such a hard problem
Lex Fridman (3:03:14.200)
because you run into paradoxes quite quickly
Karl Deisseroth (3:03:17.120)
the more you think about it
Lex Fridman (3:03:18.440)
and that is exciting also
Karl Deisseroth (3:03:21.800)
because it makes us think
Lex Fridman (3:03:23.320)
actually there's some fundamental,
Karl Deisseroth (3:03:25.960)
there's a big thing that we're missing.
Lex Fridman (3:03:28.120)
The brain is not just a collection of little tricks.
Karl Deisseroth (3:03:30.880)
There is a big, big concept.
Lex Fridman (3:03:32.760)
So that's your sense of the big
Karl Deisseroth (3:03:34.000)
because a flip side could be with optogenetics.
Lex Fridman (3:03:37.600)
You can, there's an engineering question.
Lex Fridman (3:03:40.320)
Can you turn consciousness on and off like a light switch?
Lex Fridman (3:03:43.920)
Okay, so here's where exactly consciousness
Karl Deisseroth (3:03:47.200)
frames the problem extremely well
Lex Fridman (3:03:48.920)
and it frames it the following way.
Lex Fridman (3:03:50.580)
So I told you earlier that we can stimulate
Lex Fridman (3:03:54.680)
20 or 25 cells in the visual cortex of a mouse
Lex Fridman (3:03:59.600)
and we can make it behave and we can make its brain act
Lex Fridman (3:04:03.520)
as if it's seeing something that isn't there.
Karl Deisseroth (3:04:06.040)
We have that level of control now.
Lex Fridman (3:04:07.240)
We can pick out 25 neurons, play in activity
Lex Fridman (3:04:10.920)
and both behavior and in the brain,
Lex Fridman (3:04:13.080)
it's as if it's seeing something specific.
Karl Deisseroth (3:04:16.120)
Okay, now let's do a thought experiment,
Lex Fridman (3:04:18.600)
you know, a Gedanken experiment and let's play this out.
Karl Deisseroth (3:04:22.760)
Let's say we could do the same thing
Lex Fridman (3:04:24.380)
for every single neuron in the brain of a human being.
Karl Deisseroth (3:04:27.880)
Let's say we had total control
Lex Fridman (3:04:30.120)
and I could do something like,
Karl Deisseroth (3:04:31.520)
I could show you a rich deep color red
Lex Fridman (3:04:34.800)
and you could look at it and you would be aware
Karl Deisseroth (3:04:36.480)
that it's red, but also you might have some feelings
Lex Fridman (3:04:38.240)
about it, something would be stirred in you,
Karl Deisseroth (3:04:40.320)
some subjective sense as you looked at that rich color red
Lex Fridman (3:04:44.720)
and then I would take away the visual stimulus
Lex Fridman (3:04:48.880)
and I would, in this thought experiment,
Lex Fridman (3:04:50.340)
I would, using some hyperoptogenetics,
Karl Deisseroth (3:04:53.300)
I would play in exactly the same pattern of activity
Lex Fridman (3:04:57.000)
in every cell in your brain for as long as was needed,
Karl Deisseroth (3:05:00.360)
whatever, 15 seconds, something like that,
Lex Fridman (3:05:03.360)
that exactly matched what was going on
Karl Deisseroth (3:05:06.880)
when you were feeling that inner subjective sense.
Lex Fridman (3:05:10.320)
Okay, so in that thought experiment,
Karl Deisseroth (3:05:12.160)
a question for you is would you be feeling
Lex Fridman (3:05:16.320)
that same inner subjective sense?
Karl Deisseroth (3:05:18.080)
Stimulus is gone, every neuron's doing the same thing
Lex Fridman (3:05:20.560)
because I'm controlling it.
Karl Deisseroth (3:05:23.040)
There's a philosophical question there.
Lex Fridman (3:05:25.800)
If you ask me specifically, I would say yes.
Karl Deisseroth (3:05:29.360)
Okay, good, most people would say that
Lex Fridman (3:05:31.400)
because it's hard to say no, right?
Karl Deisseroth (3:05:33.740)
It's very hard to say no.
Lex Fridman (3:05:34.800)
If every cell in your brain is doing what it was doing,
Lex Fridman (3:05:38.240)
what else could be different?
Lex Fridman (3:05:39.560)
How could? Well, most normal people would say yes.
Karl Deisseroth (3:05:42.720)
Of course, philosophers would then start saying no.
Lex Fridman (3:05:46.320)
They're the ones that say,
Karl Deisseroth (3:05:50.460)
I'm in sort of parallel and sorry
Lex Fridman (3:05:53.040)
if it's a bit of an interruption,
Lex Fridman (3:05:54.240)
but if there's a robot that's conscious in front of you,
Lex Fridman (3:05:58.400)
if it appears conscious, then it's conscious.
Karl Deisseroth (3:06:02.900)
Like to me, of course, philosophers again speak up
Lex Fridman (3:06:07.300)
and say, well, no, how do you know it's conscious?
Lex Fridman (3:06:10.040)
Well, how do you know anything is conscious?
Lex Fridman (3:06:12.360)
And sort of as normal humans,
Karl Deisseroth (3:06:15.460)
we tend to lean on the experience
Lex Fridman (3:06:19.160)
versus some kind of philosophical concept.
Lex Fridman (3:06:22.640)
So the great thing about what you just said,
Lex Fridman (3:06:25.320)
the Turing test is it's very practical.
Karl Deisseroth (3:06:28.400)
If it acts conscious, it is conscious.
Lex Fridman (3:06:31.000)
But I think that's limiting.
Karl Deisseroth (3:06:32.880)
I like the thought experiment.
Lex Fridman (3:06:34.760)
I think it's actually more informative.
Lex Fridman (3:06:36.240)
And so I'm halfway to the conclusion there,
Lex Fridman (3:06:39.760)
but let's take it as your answer was yes,
Karl Deisseroth (3:06:43.240)
that you would be feeling the same thing.
Lex Fridman (3:06:44.920)
Okay, now here's where it gets fun.
Karl Deisseroth (3:06:47.120)
Now that every cell in your brain knows what it has to do
Lex Fridman (3:06:55.480)
in the sense that we know it and we're providing it,
Karl Deisseroth (3:07:00.360)
your brain cells don't need to be in your head
Lex Fridman (3:07:02.600)
anymore at all, right?
Karl Deisseroth (3:07:04.680)
The only reason they're next to each other,
Lex Fridman (3:07:06.440)
the only reason they're wired together
Karl Deisseroth (3:07:08.120)
is to affect each other, to stimulate or inhibit each other.
Lex Fridman (3:07:12.200)
But we don't need that anymore
Karl Deisseroth (3:07:13.580)
because optogenetically,
Lex Fridman (3:07:15.280)
we're providing that activity pattern
Karl Deisseroth (3:07:17.280)
for as long as needed.
Lex Fridman (3:07:18.120)
We're providing the effect of the communication.
Karl Deisseroth (3:07:20.000)
They don't need to be connected anymore.
Lex Fridman (3:07:22.600)
They don't even need to be in your head.
Karl Deisseroth (3:07:24.480)
I could spread your neurons all over the continent,
Lex Fridman (3:07:28.040)
all over the galaxy,
Lex Fridman (3:07:30.200)
and I could still provide the same stimulus pattern
Lex Fridman (3:07:34.040)
over 10 or 15 seconds to all those neurons.
Lex Fridman (3:07:36.760)
And somewhere Lex Friedman would have to be,
Lex Fridman (3:07:41.560)
even though no longer existing as a physical object anymore,
Karl Deisseroth (3:07:45.280)
would be feeling that subjective feeling.
Lex Fridman (3:07:48.240)
And it's inescapable
Karl Deisseroth (3:07:49.080)
because it's exactly the same as the previous situation.
Lex Fridman (3:07:52.040)
All the neurons have to be spatially,
Karl Deisseroth (3:07:55.320)
like the locality constraint,
Lex Fridman (3:07:56.840)
they have to be spatially close to each other.
Lex Fridman (3:08:01.080)
And you talk about light opto,
Lex Fridman (3:08:03.680)
which is funny because light is the fastest traveling thing
Karl Deisseroth (3:08:09.280)
that we know of.
Lex Fridman (3:08:10.320)
Maybe let's not put them all over the universe
Karl Deisseroth (3:08:13.080)
because we might get relativistic problems then.
Lex Fridman (3:08:14.680)
Let's just keep them out.
Karl Deisseroth (3:08:15.800)
Let's keep all your neurons.
Lex Fridman (3:08:17.000)
Let's spread them over North America, okay?
Lex Fridman (3:08:19.240)
And let's play them out, same pattern of activity.
Lex Fridman (3:08:22.720)
And right, it seems absurd, right?
Karl Deisseroth (3:08:24.200)
There's no way that could be true.
Lex Fridman (3:08:25.960)
There's no way that Lex would be feeling
Karl Deisseroth (3:08:28.720)
that internal sense
Lex Fridman (3:08:29.760)
if his neurons were spread all over North America.
Lex Fridman (3:08:32.800)
And yet it's exactly the same as the previous situation
Lex Fridman (3:08:35.200)
where you said, sure.
Lex Fridman (3:08:37.000)
So we've got a paradox.
Lex Fridman (3:08:38.000)
And this is what makes people think.
Lex Fridman (3:08:39.320)
Is it a paradox though, sorry?
Lex Fridman (3:08:40.880)
Well, maybe paradox is the wrong word.
Karl Deisseroth (3:08:42.600)
We got a problem.
Lex Fridman (3:08:44.000)
We got a problem because it reveals
Karl Deisseroth (3:08:46.120)
that there's something big about those,
Lex Fridman (3:08:49.840)
that internal subjective state that we're not explaining.
Lex Fridman (3:08:53.100)
And we don't really have a hope of explaining
Lex Fridman (3:08:54.680)
in the near future.
Lex Fridman (3:08:55.720)
But don't you think we would still have that?
Lex Fridman (3:08:58.680)
It's just the word internal loses meaning,
Lex Fridman (3:09:00.580)
but don't you think we still have
Lex Fridman (3:09:02.200)
that internal subjective state?
Lex Fridman (3:09:04.360)
Or if not, then where the heck is the magic coming from?
Lex Fridman (3:09:10.760)
Okay, well, I just think,
Karl Deisseroth (3:09:13.440)
I think one of the problems
Lex Fridman (3:09:16.840)
that I think we need to let go of
Karl Deisseroth (3:09:19.160)
is we tend to, outside of the experience of consciousness,
Lex Fridman (3:09:23.460)
the hard problem of consciousness,
Karl Deisseroth (3:09:25.720)
we tend to think that we individual humans
Lex Fridman (3:09:27.940)
are really special.
Karl Deisseroth (3:09:30.400)
Not the subjective experience,
Lex Fridman (3:09:32.360)
but the entirety of it, like the body
Karl Deisseroth (3:09:34.840)
that contains the thing.
Lex Fridman (3:09:35.800)
So the local, the constraint of all the stuff
Karl Deisseroth (3:09:40.800)
has to be together, and it's all mine.
Lex Fridman (3:09:45.320)
That's a very, I don't know if that has anything to do
Karl Deisseroth (3:09:48.640)
with the mechanisms that are creating this.
Lex Fridman (3:09:52.000)
So in fact, one really nice way to break through that
Karl Deisseroth (3:09:56.960)
is to either observe or create consciousness
Lex Fridman (3:10:02.960)
that spans multiple organisms.
Karl Deisseroth (3:10:07.400)
Sort of like, let's say it's not an organism dependent
Lex Fridman (3:10:14.340)
phenomena, that the phenomena can,
Karl Deisseroth (3:10:17.540)
that's just a peculiar way it has evolved on Earth,
Lex Fridman (3:10:22.160)
but it's a phenomena that doesn't have anything to do
Karl Deisseroth (3:10:26.320)
with a specific biological system.
Lex Fridman (3:10:31.640)
Right, so and we have different parts of our brain exist
Lex Fridman (3:10:35.760)
and sometimes create complex awarenesses of things
Lex Fridman (3:10:41.360)
that involve different neurons that are distributed widely
Lex Fridman (3:10:47.400)
and that need to communicate with each other
Lex Fridman (3:10:49.040)
to form this joint representation,
Karl Deisseroth (3:10:51.240)
this state of consciousness.
Lex Fridman (3:10:53.120)
But indeed, why do they have to be in the same head?
Karl Deisseroth (3:10:57.280)
We don't know why that would be the case that they do.
Lex Fridman (3:11:02.160)
And so that's a huge unanswered question in the field
Karl Deisseroth (3:11:06.640)
is what is it that binds the activity of neurons together
Lex Fridman (3:11:11.760)
so they can form a joint representation?
Lex Fridman (3:11:14.440)
And actually this comes back to the dissociation experiment
Lex Fridman (3:11:16.840)
we talked about before, where your sense of self
Karl Deisseroth (3:11:19.360)
becomes separated from your body.
Lex Fridman (3:11:23.480)
Those things that were fused in a joint representation,
Karl Deisseroth (3:11:26.600)
the same concept, unitary, are now separate.
Lex Fridman (3:11:31.400)
And in late 2020, we published a paper in Nature
Karl Deisseroth (3:11:35.440)
showing how this could be.
Lex Fridman (3:11:37.160)
We used optogenetics to drive this rhythm
Karl Deisseroth (3:11:41.000)
that ketamine and PCP cause in retrosplenial cortex
Lex Fridman (3:11:44.000)
and we got different parts of the brain to be out of sync
Lex Fridman (3:11:47.520)
and when they were active, never able to be active
Lex Fridman (3:11:50.440)
at the same time, never able to form
Karl Deisseroth (3:11:53.680)
a joint representation at the same time.
Lex Fridman (3:11:56.120)
And so we've got a toehold into these questions.
Karl Deisseroth (3:11:58.080)
We don't have the answers, but.
Lex Fridman (3:11:59.920)
And that mimics the dynamics of ketamine effects.
Karl Deisseroth (3:12:02.600)
Exactly, exactly.
Lex Fridman (3:12:04.280)
And you're able to find that kind of oscillation.
Karl Deisseroth (3:12:08.280)
Wow, wow, wow.
Lex Fridman (3:12:09.920)
I see if you get even greater and greater control
Karl Deisseroth (3:12:13.520)
with more control over individual neurons
Lex Fridman (3:12:16.000)
and understanding, like if you think of certain neurons
Karl Deisseroth (3:12:19.840)
that having some role to play in the sense of self,
Lex Fridman (3:12:24.500)
you can play like an orchestra.
Karl Deisseroth (3:12:27.760)
That, to create certain degrees of consciousness,
Lex Fridman (3:12:31.720)
degrees of subjectivity, and thereby understand
Lex Fridman (3:12:35.500)
what is consciousness.
Lex Fridman (3:12:37.480)
But by having a very complicated light switch essentially.
Lex Fridman (3:12:41.960)
And here's the challenge is the nice thing
Lex Fridman (3:12:44.780)
about the thought experiment is it kind of highlights
Karl Deisseroth (3:12:50.000)
that we're gonna hit a point where
Lex Fridman (3:12:53.880)
we're addressing some very, very fundamental questions.
Lex Fridman (3:12:57.380)
What allows the activity of two sets of neurons
Lex Fridman (3:13:03.640)
to become mutually relevant to each other?
Karl Deisseroth (3:13:07.080)
This is in some ways maybe one of the deepest
Lex Fridman (3:13:11.560)
remaining questions in neuroscience is what allows
Lex Fridman (3:13:14.600)
activity patterns to become relevant to each other?
Lex Fridman (3:13:18.900)
Do they have to be in sync temporarily?
Karl Deisseroth (3:13:21.200)
Do they need to be, is there some other quality
Lex Fridman (3:13:25.920)
that we don't know about that also needs to be present
Lex Fridman (3:13:28.440)
to allow cells to fuse together into a joint representation?
Lex Fridman (3:13:32.140)
Just so I understand, because it feels close
Karl Deisseroth (3:13:37.520)
to some very, very deep idea.
Lex Fridman (3:13:41.080)
So there's a bunch of semi distributed signals
Karl Deisseroth (3:13:43.600)
going on in the brain.
Lex Fridman (3:13:46.120)
And you're saying there could be something
Karl Deisseroth (3:13:50.680)
like a theory of everything if one to exist
Lex Fridman (3:13:53.800)
is to understand why, how and why signals
Karl Deisseroth (3:13:58.240)
close to each other start becoming relevant to each other
Lex Fridman (3:14:07.040)
as part of some very much bigger signal
Karl Deisseroth (3:14:10.900)
that they're producing.
Lex Fridman (3:14:12.420)
How they coordinate, essentially.
Karl Deisseroth (3:14:16.880)
Because it's very distributed.
Lex Fridman (3:14:18.440)
I mean that's a kind of, within a distributed system,
Lex Fridman (3:14:22.440)
how is order achieved?
Lex Fridman (3:14:25.800)
And this is a very specific kind of distributed system
Karl Deisseroth (3:14:28.840)
that is one of the most intelligent that we're aware of
Lex Fridman (3:14:32.400)
in the known universe.
Karl Deisseroth (3:14:34.760)
In that would maybe be something also,
Lex Fridman (3:14:38.280)
an understanding of the full conscious experience too.
Karl Deisseroth (3:14:42.400)
That this kind of coordination.
Lex Fridman (3:14:44.440)
How does the coordination between different neurons
Karl Deisseroth (3:14:46.640)
that are responsible for sense of self,
Lex Fridman (3:14:49.060)
how do they begin to form a big picture
Lex Fridman (3:14:51.740)
that we see as a human experience?
Lex Fridman (3:14:54.080)
That's really, really interesting.
Lex Fridman (3:14:55.520)
So uniting the small and the,
Lex Fridman (3:14:57.160)
I mean that's actually literally theory of everything.
Karl Deisseroth (3:15:00.960)
Uniting the small, the sort of the theory of the neuron.
Lex Fridman (3:15:05.320)
The functioning of the neuron with the big.
Karl Deisseroth (3:15:07.800)
Just the functioning of the entire mind.
Lex Fridman (3:15:12.060)
That's right.
Lex Fridman (3:15:12.900)
And I think keeping a toehold in both
Lex Fridman (3:15:14.920)
at the cellular level of resolution
Lex Fridman (3:15:17.820)
and the brain wide resolution will be critical.
Lex Fridman (3:15:19.720)
If you lose touch with either,
Karl Deisseroth (3:15:21.320)
I think you'll miss the big insight.
Lex Fridman (3:15:23.580)
So that's what we're trying to do.
Karl Deisseroth (3:15:25.380)
Keeping grounded in the cellular resolution.
Lex Fridman (3:15:29.200)
Trying to keep the broadest brain wide perspective
Lex Fridman (3:15:32.200)
and meet in the middle.
Lex Fridman (3:15:35.000)
Do you think you'll see it in your lifetime?
Karl Deisseroth (3:15:36.920)
A major breakthrough in that dimension.
Lex Fridman (3:15:39.560)
I have hope.
Karl Deisseroth (3:15:40.400)
I have hope.
Lex Fridman (3:15:42.020)
It's very hard to predict what will happen
Karl Deisseroth (3:15:43.760)
with big things like this.
Lex Fridman (3:15:45.480)
If we don't get there,
Karl Deisseroth (3:15:46.800)
there'll be plenty of other exciting stuff.
Lex Fridman (3:15:48.560)
So it's okay.
Lex Fridman (3:15:50.760)
But the other aspect of this whole thing
Lex Fridman (3:15:52.920)
is that your life is pretty short.
Karl Deisseroth (3:15:55.240)
Yeah, that's true.
Lex Fridman (3:15:56.640)
So first of all, you can die any day.
Karl Deisseroth (3:15:59.440)
I tend to try to think about that,
Lex Fridman (3:16:01.360)
that it ends, it can end any moment
Karl Deisseroth (3:16:03.900)
because it really, really can.
Lex Fridman (3:16:05.640)
And if not, it'll be soon anyway.
Lex Fridman (3:16:08.760)
Do you think about that?
Lex Fridman (3:16:09.960)
Do you think about your mortality?
Karl Deisseroth (3:16:12.260)
I do, yeah.
Lex Fridman (3:16:13.100)
It comes back to what we talked about earlier.
Karl Deisseroth (3:16:16.920)
I never think I've done enough
Lex Fridman (3:16:18.480)
and it's relevant to that for sure.
Karl Deisseroth (3:16:20.880)
There's a deadline.
Lex Fridman (3:16:25.060)
Do you think there's ever going to be a feeling
Lex Fridman (3:16:27.180)
where you sit back and you're really proud of yourself?
Lex Fridman (3:16:34.200)
I hope so.
Karl Deisseroth (3:16:35.320)
Like, I've done enough.
Lex Fridman (3:16:36.680)
I've done everything there is.
Karl Deisseroth (3:16:39.560)
Because the thing is,
Lex Fridman (3:16:41.080)
a warrior has some number of battles in them.
Lex Fridman (3:16:44.800)
And at a certain point, if you're deeply honest,
Lex Fridman (3:16:47.000)
it's like, well, that was a pretty good run.
Karl Deisseroth (3:16:50.240)
As far as runs goes, that was pretty good.
Lex Fridman (3:16:53.040)
And you can hang up your helmet
Lex Fridman (3:16:55.240)
and then go sort of drink some ale,
Lex Fridman (3:17:00.240)
listen to some music with the old lady,
Lex Fridman (3:17:03.600)
and say, I did pretty good.
Lex Fridman (3:17:04.920)
You think you'll get there?
Karl Deisseroth (3:17:08.600)
You know, with something,
Lex Fridman (3:17:10.320)
nature always has surprises for us.
Karl Deisseroth (3:17:12.960)
The curious mind is always after more.
Lex Fridman (3:17:17.400)
But biology gives us other rewards.
Karl Deisseroth (3:17:22.120)
Children and family, community.
Lex Fridman (3:17:26.040)
And one can feel good about those things.
Karl Deisseroth (3:17:30.340)
Biology is full of rewards.
Lex Fridman (3:17:31.740)
But do you think about those rewards?
Lex Fridman (3:17:34.780)
What do you think is the why of those rewards?
Lex Fridman (3:17:37.040)
What's the meaning of life and this existence?
Lex Fridman (3:17:40.200)
What's the why of biology?
Lex Fridman (3:17:44.520)
What does it want from us?
Lex Fridman (3:17:45.460)
Why are all these cells very busy
Lex Fridman (3:17:47.980)
putting together an organism
Karl Deisseroth (3:17:49.320)
that seems to want to just be in a hurry to do stuff
Lex Fridman (3:17:53.660)
and survive, but it's not happy being survived.
Karl Deisseroth (3:17:57.560)
Like you said, it's curious.
Lex Fridman (3:17:59.240)
It keeps wanting to get into more trouble.
Lex Fridman (3:18:01.640)
Why?
Lex Fridman (3:18:02.960)
Yeah, you know, we're clearly designed for that, right?
Karl Deisseroth (3:18:07.360)
We're clearly designed to ask why and to answer.
Lex Fridman (3:18:10.680)
And that, I think, is,
Karl Deisseroth (3:18:12.920)
I don't know the meaning of all life.
Lex Fridman (3:18:15.320)
I think a meaning of our lives is that.
Lex Fridman (3:18:17.920)
And this is the Aristotelian happiness.
Lex Fridman (3:18:22.480)
An organism is happy, an animal's happy
Lex Fridman (3:18:24.320)
if it's performing to its design, right?
Lex Fridman (3:18:26.440)
If it's doing what it was made for.
Lex Fridman (3:18:29.760)
Yeah, well, you have to understand, what's the design?
Lex Fridman (3:18:33.680)
And, you know, who is the designer
Lex Fridman (3:18:39.040)
and what were they up to and how hard is it?
Lex Fridman (3:18:43.840)
Do you have to build the whole universe?
Lex Fridman (3:18:45.180)
And does the design even know what the hell they're doing?
Lex Fridman (3:18:47.640)
Because, you know, maybe the designer built humans
Karl Deisseroth (3:18:51.720)
to find out about themselves.
Lex Fridman (3:18:56.480)
That's what I would do.
Karl Deisseroth (3:18:57.520)
Like, if I had the power to build clones,
Lex Fridman (3:19:00.720)
I would build a lot of clones
Lex Fridman (3:19:02.480)
and I would get them into different trouble
Lex Fridman (3:19:04.840)
to understand, like, what am I designed,
Lex Fridman (3:19:08.560)
what's this body designed to do?
Lex Fridman (3:19:10.440)
How far can I go that way?
Karl Deisseroth (3:19:11.680)
Exactly.
Lex Fridman (3:19:12.880)
And then, and I dissociate myself completely
Karl Deisseroth (3:19:15.640)
from having any way to know, like, that I know that person.
Lex Fridman (3:19:19.000)
Oh, that's good.
Karl Deisseroth (3:19:19.980)
I mean, I suppose you could do that
Lex Fridman (3:19:21.280)
in a single person's body, but dissociation, you could.
Karl Deisseroth (3:19:26.200)
Yeah, but I do wonder what,
Lex Fridman (3:19:30.200)
if you look at Earth as a collection of humans,
Karl Deisseroth (3:19:33.800)
as a collection of biological organisms,
Lex Fridman (3:19:35.940)
it seems that we're busy doing something
Lex Fridman (3:19:40.520)
and it just seems too beautiful and too special
Lex Fridman (3:19:45.440)
to be a random, a random experiment.
Karl Deisseroth (3:19:50.440)
It seems like it's an experiment that's cleverly designed
Lex Fridman (3:19:57.080)
That's right.
Karl Deisseroth (3:19:58.760)
by some forces of nature
Lex Fridman (3:20:00.640)
that are beyond our current understanding.
Lex Fridman (3:20:03.560)
And maybe that's part of our design,
Lex Fridman (3:20:05.520)
is to keep asking why.
Karl Deisseroth (3:20:06.560)
You said answer.
Lex Fridman (3:20:07.380)
I'm not sure that's part of the design, the answer.
Karl Deisseroth (3:20:11.800)
I think we're given just the sufficiently limited
Lex Fridman (3:20:15.080)
cognitive capability that we know how to long
Karl Deisseroth (3:20:19.020)
to find the answer and we lack the ability
Lex Fridman (3:20:22.520)
to find the answer.
Karl Deisseroth (3:20:24.120)
That's basically a summary of your career.
Lex Fridman (3:20:26.460)
No, I'm just kidding.
Lex Fridman (3:20:27.800)
And then we give each other Nobel Prizes
Lex Fridman (3:20:29.480)
for having even an inkling of a good step
Karl Deisseroth (3:20:33.200)
towards the right direction.
Lex Fridman (3:20:35.120)
Carl, you're an incredible human being.
Karl Deisseroth (3:20:38.580)
I'm a huge fan of who you are as a person,
Lex Fridman (3:20:41.000)
who you are as a scientist, who you are as a writer.
Karl Deisseroth (3:20:43.520)
I just thank you so much.
Lex Fridman (3:20:45.300)
I'm so honored that you would sit down
Lex Fridman (3:20:46.720)
and talk to me today.
Lex Fridman (3:20:47.560)
It was amazing.
Karl Deisseroth (3:20:48.380)
It's been incredibly fun.
Lex Fridman (3:20:49.840)
Let's do it again sometime.
Karl Deisseroth (3:20:50.740)
Let's do it again.
Lex Fridman (3:20:51.580)
It's been really great.
Karl Deisseroth (3:20:52.400)
Your insights and wit and modesty
Lex Fridman (3:20:55.600)
are really quite rewarding.
Karl Deisseroth (3:20:58.260)
Thank you so much, man.
Lex Fridman (3:21:00.520)
Thanks for listening to this conversation
Karl Deisseroth (3:21:02.040)
with Carl Diceroth.
Lex Fridman (3:21:03.680)
To support this podcast,
Karl Deisseroth (3:21:04.920)
please check out our sponsors in the description.
Lex Fridman (3:21:07.480)
And now, let me leave you with some words from Carl Jung.
Karl Deisseroth (3:21:11.500)
Knowing your own darkness is the best method
Lex Fridman (3:21:13.960)
for dealing with the darkness of other people.
Karl Deisseroth (3:21:16.360)
Thank you for listening and hope to see you next time.
Lex Fridman (40:02.740)
it can be hard to capture fairly,
Karl Deisseroth (40:05.040)
because you wanna talk about the positive
Lex Fridman (40:07.220)
and the negative sides at once.
Karl Deisseroth (40:09.100)
They need to be wrapped up together
Lex Fridman (40:10.360)
for a full, honest description of what it is,
Lex Fridman (40:13.700)
and that's hard to do in a compact form.
Lex Fridman (40:16.660)
And so you have to take time to talk about love.
Karl Deisseroth (40:19.380)
You have to take time to do it justice.
Lex Fridman (40:23.580)
It takes a book, or at least a poem.
Karl Deisseroth (40:25.500)
Or several thousands of them.
Lex Fridman (40:28.420)
I don't know, could you pull up,
Karl Deisseroth (40:30.620)
there's a video I saw, yeah, like right here.
Lex Fridman (40:33.980)
So can you pause for a second?
Lex Fridman (40:37.380)
So there's March of the Penguins.
Lex Fridman (40:39.220)
So you always see penguins huddling together against,
Karl Deisseroth (40:44.140)
I mean, sorry if I say just metaphors and everything,
Lex Fridman (40:46.340)
but them huddling together against the harshness
Karl Deisseroth (40:50.820)
of the conditions around them.
Lex Fridman (40:52.180)
That's very kind of, that's like a metaphor for life,
Karl Deisseroth (40:55.680)
like finding this connection.
Lex Fridman (40:57.500)
That's kind of what love is.
Karl Deisseroth (40:59.220)
It's like it allows you to forget whatever the absurdity,
Lex Fridman (41:02.140)
whatever the suffering of life is,
Karl Deisseroth (41:03.740)
together you get to like huddle for warmth.
Lex Fridman (41:06.720)
And that's why I love sort of just the honesty
Lex Fridman (41:11.500)
and the intensity of the way penguins,
Lex Fridman (41:13.100)
just in the middle of like the cold do this.
Lex Fridman (41:15.180)
And then this video I saw, a lonely,
Lex Fridman (41:18.900)
this is misinformation.
Lex Fridman (41:20.940)
So the name of the video is Lonely Deranged Penguin.
Lex Fridman (41:23.900)
I don't know if he's deranged.
Lex Fridman (41:26.060)
So if you play it.
Lex Fridman (41:27.740)
So he left his pack and there's a nice like voiceover
Lex Fridman (41:34.540)
and you don't need to play it,
Lex Fridman (41:36.040)
but he for some reason left the pack
Lex Fridman (41:38.940)
and journeyed out into the mountains.
Lex Fridman (41:41.820)
And so the narrator says that he's deranged,
Karl Deisseroth (41:44.740)
he's lost his mind.
Lex Fridman (41:46.500)
Now I'd like to project the idea that he's actually,
Karl Deisseroth (41:50.700)
there's so many stories you could think of.
Lex Fridman (41:52.940)
He's returning to his homeland.
Karl Deisseroth (41:55.100)
He's an outsider thinking,
Lex Fridman (41:56.740)
journeying out into the unknown,
Karl Deisseroth (41:58.340)
thinking he may be able to discover
Lex Fridman (42:00.180)
something greater than the tribe.
Karl Deisseroth (42:02.100)
He might be looking for a lost love.
Lex Fridman (42:04.640)
Why is he deranged immediately?
Lex Fridman (42:06.660)
Why has he lost his mind?
Lex Fridman (42:07.980)
Anyway, but this, people should look up this video
Karl Deisseroth (42:10.980)
because to me, I might be the only one
Lex Fridman (42:12.940)
who romanticizes this, but it's such a nice kind of,
Karl Deisseroth (42:17.940)
it's both a picture of perhaps a mental disorder,
Lex Fridman (42:21.820)
which is what the video kind of describes.
Lex Fridman (42:23.900)
And it may be some deeper explanation
Lex Fridman (42:25.900)
that's not, that has to do with the motivation of a mind.
Lex Fridman (42:32.620)
But yeah, I don't know if you have a deeper analysis
Lex Fridman (42:35.500)
on this penguin.
Karl Deisseroth (42:36.340)
Well, I, like you as a psychiatrist,
Lex Fridman (42:40.100)
I would want to sit down with a penguin and go through,
Karl Deisseroth (42:44.600)
I want to see the notes from his prior therapist.
Lex Fridman (42:47.680)
But this actually is relevant,
Karl Deisseroth (42:51.620)
not knowing what was that penguin's motivation.
Lex Fridman (42:54.620)
We have very clear situations
Karl Deisseroth (42:57.740)
where there are both within an individual,
Lex Fridman (42:59.620)
we go through periods of time when we stay in one place
Lex Fridman (43:03.700)
and we reap the benefits from what we've built.
Lex Fridman (43:06.580)
And then we go through periods of foraging, of wandering.
Karl Deisseroth (43:11.300)
Even if there may be resources where we are,
Lex Fridman (43:15.180)
we have periods of time in our lives
Karl Deisseroth (43:17.700)
where we wander, where we go in an exploratory mode.
Lex Fridman (43:22.700)
And different people express that trait in different ways.
Karl Deisseroth (43:26.500)
This is not a human specific trait.
Lex Fridman (43:27.860)
If you go down to the tiny little nematode worm,
Karl Deisseroth (43:31.540)
C. elegans with 302 nervous system cells,
Lex Fridman (43:34.740)
they go through these phases of foraging and rest
Lex Fridman (43:37.180)
and different individuals have different propensity
Lex Fridman (43:39.540)
to forage or to rest and stay in one place.
Karl Deisseroth (43:42.900)
At the level of the species, that's really good
Lex Fridman (43:45.540)
that there's that diversity in their willingness to forage.
Karl Deisseroth (43:51.060)
Some stay where they are,
Lex Fridman (43:52.980)
the species is somewhat on a firm footing then,
Lex Fridman (43:56.660)
but some carry a burden, a risk for themselves,
Lex Fridman (44:00.340)
but it's good for the species that they're explorers
Lex Fridman (44:03.340)
and they will venture out.
Lex Fridman (44:05.500)
The migration patterns that different species blunder into
Lex Fridman (44:09.180)
and that turned out to be really good,
Lex Fridman (44:10.760)
they weren't logically derived.
Karl Deisseroth (44:13.300)
They most certainly started
Lex Fridman (44:15.260)
from something like this, an exploration.
Lex Fridman (44:18.220)
And humans do this too, you think?
Lex Fridman (44:19.340)
And we do it too.
Karl Deisseroth (44:20.460)
In fact, it's something we do extremely well.
Lex Fridman (44:23.860)
Let's talk about psychiatry a little bit.
Lex Fridman (44:28.900)
So in my book, you're a rockstar.
Lex Fridman (44:30.940)
First of all, for people who don't know,
Karl Deisseroth (44:33.100)
aside from sort of the neurological view of the brain
Lex Fridman (44:38.320)
and neuroscience view of the brain,
Karl Deisseroth (44:40.200)
you're also one of the great psychiatrists of our time.
Lex Fridman (44:43.200)
I've always, not always, but when I was younger,
Karl Deisseroth (44:45.780)
I dreamed about being a psychiatrist.
Lex Fridman (44:49.860)
So it's like getting to meet your heroes
Lex Fridman (44:53.380)
and also getting to meet the people who,
Lex Fridman (44:59.020)
the best at the top of the world
Karl Deisseroth (45:01.500)
at the thing you've failed to pursue.
Lex Fridman (45:03.580)
So I'm getting a free therapy session on top of that.
Karl Deisseroth (45:07.220)
Okay, so what big picture, what is the practice,
Lex Fridman (45:11.460)
the goal, the hope of modern psychiatry?
Karl Deisseroth (45:13.860)
If you could try to describe the discipline
Lex Fridman (45:17.380)
as you see it, maybe historically
Karl Deisseroth (45:20.700)
throughout the 20th century,
Lex Fridman (45:23.060)
in contrasting to what it is today.
Karl Deisseroth (45:25.500)
Or maybe if you want to describe
Lex Fridman (45:27.460)
to what you hope psychiatry becomes
Karl Deisseroth (45:29.580)
or longs to become in the 21st century.
Lex Fridman (45:34.180)
It's been an interesting journey.
Karl Deisseroth (45:36.340)
Psychiatry started out pretty firmly grounded
Lex Fridman (45:39.380)
in neurology and pathology.
Karl Deisseroth (45:40.980)
Some of the initial founders effectively of the field
Lex Fridman (45:44.260)
were very well grounded in microscopy, looking at cells,
Karl Deisseroth (45:49.580)
working with patients, particularly on the neurological side,
Lex Fridman (45:52.540)
and this certainly included Freud
Lex Fridman (45:54.460)
and some of his contemporaries.
Lex Fridman (45:58.340)
But they rapidly discovered that what they could work with
Karl Deisseroth (46:03.100)
at the level of cells and microscopy
Lex Fridman (46:05.700)
was so far from the realm of what they could get
Karl Deisseroth (46:09.620)
from a human being and what they were getting
Lex Fridman (46:12.380)
from the human being was so much more interesting
Lex Fridman (46:14.660)
and was so mysterious and so unknown
Lex Fridman (46:17.260)
that many of them just said,
Karl Deisseroth (46:18.880)
we're gonna inhabit this domain
Lex Fridman (46:20.180)
and we're gonna work with the people with their words
Lex Fridman (46:23.220)
and understand what we can based on verbal communication,
Lex Fridman (46:27.060)
because that was the only tool that people really had.
Lex Fridman (46:30.520)
And that was a very important step for the field.
Lex Fridman (46:37.220)
I would say one of the interesting things
Karl Deisseroth (46:39.180)
that came from the early decades of psychiatry
Lex Fridman (46:42.620)
really was this distinction
Karl Deisseroth (46:44.020)
between the conscious and the unconscious mind
Lex Fridman (46:47.220)
and paying particular attention to the unconscious mind
Karl Deisseroth (46:51.440)
as something that was worthy of consideration
Lex Fridman (46:54.020)
that might be important in explaining people's actions
Lex Fridman (46:58.620)
and that perhaps even insight into that was valuable
Lex Fridman (47:01.140)
in its own right.
Lex Fridman (47:02.620)
And out of that, psychoanalysis became a practice
Lex Fridman (47:07.580)
that was not always focused on cures or treatments,
Lex Fridman (47:12.840)
but was more focused on insight.
Lex Fridman (47:14.220)
What does it mean?
Lex Fridman (47:15.380)
How can we help people understand
Lex Fridman (47:17.340)
why they're feeling something or thinking something
Lex Fridman (47:19.900)
or dreaming something?
Lex Fridman (47:22.260)
And that insight separate even from treatment
Karl Deisseroth (47:24.700)
was an interesting thing.
Lex Fridman (47:26.540)
As long as one was honest about that
Lex Fridman (47:28.940)
and said we're going for understanding,
Lex Fridman (47:31.160)
we're going for insight.
Karl Deisseroth (47:32.400)
Maybe it's useful to just pause on that.
Lex Fridman (47:34.820)
If we look at the father of psychoanalysis, Zygmunt Freud,
Lex Fridman (47:40.780)
what do you make of the ideas that he had?
Lex Fridman (47:43.340)
So you mentioned taking the unconscious,
Karl Deisseroth (47:46.860)
the subconscious seriously.
Lex Fridman (47:49.380)
That's like step one,
Karl Deisseroth (47:50.900)
like that there could be worlds
Lex Fridman (47:52.220)
we do not have direct access for
Lex Fridman (47:53.900)
and we probe at them through conversation
Lex Fridman (47:57.820)
or is that too simplistic
Lex Fridman (48:00.900)
to call psychoanalysis conversation?
Lex Fridman (48:03.100)
That's not too simplistic, but that's right.
Lex Fridman (48:05.220)
And I think that was valuable.
Lex Fridman (48:06.660)
Where Freud ended up breaking
Karl Deisseroth (48:09.040)
from some of his contemporaries,
Lex Fridman (48:10.300)
he was very focused on this unconscious
Karl Deisseroth (48:13.300)
as being so tightly linked to libido.
Lex Fridman (48:15.700)
And really from his perspective,
Karl Deisseroth (48:18.860)
you couldn't really separate the operation
Lex Fridman (48:20.820)
of the unconscious mind from these aspects
Karl Deisseroth (48:22.720)
of the libidinous aspects.
Lex Fridman (48:24.180)
And that was one reason.
Lex Fridman (48:25.020)
What's a libidinous aspect?
Lex Fridman (48:25.860)
You know, sexually related drives.
Karl Deisseroth (48:29.140)
Carl Jung, who was his contemporary,
Lex Fridman (48:33.100)
that's one factor that led to them separating
Karl Deisseroth (48:36.220)
was Carl Jung felt there was a lot more
Lex Fridman (48:39.540)
to the unconscious than this libidinous aspect of it.
Lex Fridman (48:42.700)
And he saw it as a much more complete
Lex Fridman (48:47.500)
alternate representation of the conscious self,
Karl Deisseroth (48:50.900)
one that maybe reflected a whole range
Lex Fridman (48:53.460)
of different motivations and desires.
Lex Fridman (49:00.020)
And to properly treat it one had to consider all of them
Lex Fridman (49:04.780)
rather than the ones that Freud was focused on.
Karl Deisseroth (49:06.420)
Carl Jung, shut your mouth.
Lex Fridman (49:08.340)
Thank you.
Karl Deisseroth (49:09.780)
Thank you for the high level of images
Lex Fridman (49:13.300)
that Sergei's pulling up.
Karl Deisseroth (49:14.340)
For people who are just listening,
Lex Fridman (49:15.500)
he pulled up a quote from Sigmund Freud's meme,
Karl Deisseroth (49:19.860)
your mom quote Freud.
Lex Fridman (49:23.380)
So the shadow, the Carl Jung shadow encompasses everything,
Karl Deisseroth (49:28.780)
not just the desire to have sex with your mother
Lex Fridman (49:31.260)
or sex period.
Karl Deisseroth (49:32.580)
That's right, that's right.
Lex Fridman (49:34.320)
If you look at those two folks en masse,
Karl Deisseroth (49:38.100)
I mean, there's a kind of,
Lex Fridman (49:39.980)
it's almost like a technique for philosophical exploration
Karl Deisseroth (49:44.140)
of human mind, human motivations.
Lex Fridman (49:47.320)
So it's not even like necessarily,
Karl Deisseroth (49:49.980)
it's also doubles as a methodology for helping people,
Lex Fridman (49:53.720)
but it's almost like a,
Karl Deisseroth (49:56.420)
it's a kind of philosophical method.
Lex Fridman (49:59.940)
Right, this is the fascinating thing about psychoanalysis.
Lex Fridman (50:03.740)
And even though it's, I would say,
Lex Fridman (50:06.860)
mostly not considered a treatment today,
Karl Deisseroth (50:10.340)
it persists for a couple of reasons.
Lex Fridman (50:11.740)
One is it's thought that it gives people some insight.
Lex Fridman (50:15.820)
But second, there's been a huge influence on literature,
Lex Fridman (50:19.940)
on philosophy, on art.
Lex Fridman (50:22.060)
And the opening up of discussion
Lex Fridman (50:24.500)
about what was below our conscious mind
Karl Deisseroth (50:27.580)
was so fertile in the implications
Lex Fridman (50:31.700)
that it sort of reverberated and still does
Karl Deisseroth (50:34.700)
throughout all these different realms of human endeavor
Lex Fridman (50:37.100)
from different artistic experiences that people have
Karl Deisseroth (50:42.100)
that can be colored by this concept of the unconscious.
Lex Fridman (50:50.000)
Now, the other thing that was interesting
Karl Deisseroth (50:51.760)
is this distinction,
Lex Fridman (50:55.320)
you know, what are the parts of the unconscious?
Lex Fridman (50:57.760)
And so there were these id and ego
Lex Fridman (51:00.680)
and superego subdivisions that,
Karl Deisseroth (51:05.920)
you know, that Freud, for example, would talk about them.
Lex Fridman (51:09.120)
And the id was the primary, the primal drives
Karl Deisseroth (51:13.080)
that an infant would have or that a very young child
Lex Fridman (51:16.480)
just warmth and feeding and then later
Karl Deisseroth (51:19.840)
the sexual or libidinous aspects.
Lex Fridman (51:22.520)
And for Freud, the later happened very quickly.
Karl Deisseroth (51:25.160)
That's the controversial thing about him, I think.
Lex Fridman (51:29.400)
I guess he thought like even children had sexual desires,
Karl Deisseroth (51:32.520)
that they're like dealing with, contending with.
Lex Fridman (51:35.120)
So it's the full thing.
Karl Deisseroth (51:36.360)
Hungry, wanting to eat, wanting to poop,
Lex Fridman (51:38.640)
wanting to have sex.
Karl Deisseroth (51:39.920)
Yeah, and he was extremely focused on that aspect.
Lex Fridman (51:43.680)
But then there was the superego,
Karl Deisseroth (51:46.280)
which brought on these later sort of moralistic
Lex Fridman (51:51.080)
sort of codes of conduct.
Lex Fridman (51:52.840)
And that, of course, was very often in tension,
Lex Fridman (51:56.200)
but all this could play out subconsciously.
Lex Fridman (51:58.560)
And then the ego, this third aspect was mediating,
Lex Fridman (52:01.800)
and Freud's conception mediated this tension
Karl Deisseroth (52:04.680)
between the different parts.
Lex Fridman (52:06.300)
Now, I think that's interesting.
Karl Deisseroth (52:08.500)
I will say that in some ways, it's maybe unnecessary
Lex Fridman (52:14.380)
from the perspective of modern neuroscience
Karl Deisseroth (52:16.260)
to divide things up that way from the moralistic drives
Lex Fridman (52:23.100)
and the primal gratification drives.
Karl Deisseroth (52:27.300)
In some ways, they're all drives,
Lex Fridman (52:29.260)
and maybe they're even all primal drives.
Karl Deisseroth (52:31.660)
The moralistic drives, they're taught,
Lex Fridman (52:34.540)
and they're taught in ways that ultimately relate
Karl Deisseroth (52:37.900)
back to survival, and you could even say,
Lex Fridman (52:42.340)
selfish aspects of health and life
Karl Deisseroth (52:46.260)
for the self and family.
Lex Fridman (52:47.540)
And so this is, I think it's maybe an artificial distinction.
Karl Deisseroth (52:53.500)
The concept of the unconscious is very valuable
Lex Fridman (52:56.300)
and very interesting, but these categorizations
Karl Deisseroth (52:59.820)
of id and superego may not map onto neurobiology
Lex Fridman (53:05.900)
in any particular way.
Karl Deisseroth (53:07.300)
If there's a town hall of competing drives and desires,
Lex Fridman (53:10.540)
and they interrelate to each other,
Karl Deisseroth (53:13.700)
they involve different aspects of the brain
Lex Fridman (53:16.060)
and the history of the person,
Lex Fridman (53:18.740)
and actions and choices come out of the result
Lex Fridman (53:22.140)
of that overall shouting in the town hall.
Lex Fridman (53:25.420)
So in some sense, Carl Jung was a step into the direction
Lex Fridman (53:27.940)
of liberating yourself from such harsh categorizations.
Lex Fridman (53:32.300)
Do you think, I mean, you have Daniel Kahneman
Lex Fridman (53:35.260)
with System One and System Two.
Karl Deisseroth (53:37.420)
There's just these very compelling categorizations
Lex Fridman (53:40.500)
of the human mind that seem to be sticky
Karl Deisseroth (53:46.940)
in the superego, no, in how we talk about these ideas
Lex Fridman (53:51.300)
and so on.
Lex Fridman (53:52.740)
Do you think those are helpful or do they get in the way?
Lex Fridman (53:55.500)
Is it some kind of balance in terms of deeper understanding
Lex Fridman (53:57.900)
of how the mind actually works?
Lex Fridman (53:59.380)
You know, it's from modern neuroscience,
Karl Deisseroth (54:02.940)
whenever we seem to get closer to addressing a question
Lex Fridman (54:08.220)
like this at the level of cells,
Karl Deisseroth (54:10.900)
it seems to get farther away.
Lex Fridman (54:12.340)
And I'll give you an example of what I mean by that.
Lex Fridman (54:14.780)
So one thing I'm doing in my laboratory
Lex Fridman (54:16.820)
and many people are doing is we are listening in
Karl Deisseroth (54:20.740)
on the activity of cells, neurons in the brain
Lex Fridman (54:24.420)
of mice or rats or fish or monkeys.
Karl Deisseroth (54:27.700)
Individual cells.
Lex Fridman (54:28.540)
Individual cells, exactly.
Karl Deisseroth (54:29.940)
Of which there are, in our brain, many billions.
Lex Fridman (54:33.220)
And when we do and we try to predict
Lex Fridman (54:37.260)
what action will be taken by an animal
Lex Fridman (54:40.500)
to address this question, where does the choice arise?
Karl Deisseroth (54:43.660)
Where does the impetus to make a particular selection
Lex Fridman (54:47.060)
of one action versus another action,
Lex Fridman (54:48.780)
where does that start in the brain?
Lex Fridman (54:50.060)
If you're recording, listening in on the activity of cells
Karl Deisseroth (54:52.940)
all across the brain, where's the earliest spot
Lex Fridman (54:56.660)
you can pick up a choice being made?
Lex Fridman (55:00.620)
Well?
Lex Fridman (55:01.460)
That's so awesome.
Karl Deisseroth (55:02.300)
Yeah, at one level, you might think,
Lex Fridman (55:04.180)
how excited would Jung have been to see this
Karl Deisseroth (55:07.340)
or Freud or the early psychoanalyst
Lex Fridman (55:10.340)
to see where this starts.
Lex Fridman (55:12.500)
But it's not so simple because an emerging theme
Lex Fridman (55:15.820)
in very recent neuroscience,
Karl Deisseroth (55:17.140)
literally over the last few years,
Lex Fridman (55:19.620)
is that things sort of all start together
Karl Deisseroth (55:23.220)
all across the brain.
Lex Fridman (55:24.380)
And so you can be recording from the cortex,
Karl Deisseroth (55:27.060)
this rim of cells at the surface of the brain,
Lex Fridman (55:29.900)
or you can be recording deeper
Karl Deisseroth (55:31.860)
in a structure called the striatum,
Lex Fridman (55:33.220)
which is a little older.
Karl Deisseroth (55:34.940)
It's more tightly linked to action.
Lex Fridman (55:38.380)
And then structures called the thalamus,
Karl Deisseroth (55:40.300)
other parts of the brain.
Lex Fridman (55:41.660)
And if you record from these,
Karl Deisseroth (55:43.020)
these all sort of represent the action and the choice
Lex Fridman (55:48.820)
more or less all at about the same time, very close.
Lex Fridman (55:51.300)
And so you can't point to a particular spot and say,
Lex Fridman (55:56.020)
here's where the choice or the action originates.
Karl Deisseroth (55:59.180)
It's a group.
Lex Fridman (56:00.620)
Finding the free will neuron.
Karl Deisseroth (56:03.820)
It's relevant to that question.
Lex Fridman (56:05.140)
Nobody is close to being able to point to such a thing.
Karl Deisseroth (56:08.100)
Well, close is a relative term.
Lex Fridman (56:11.820)
And nobody, what I tweet today,
Karl Deisseroth (56:16.180)
all generalizations are wrong.
Lex Fridman (56:19.820)
So including this one.
Karl Deisseroth (56:21.180)
Let's actually talk about that.
Lex Fridman (56:22.260)
So the study of individual cells.
Karl Deisseroth (56:25.300)
If you could linger on your sense
Lex Fridman (56:27.900)
that as you get closer to that understanding,
Karl Deisseroth (56:30.460)
it feels like you're getting farther away.
Lex Fridman (56:33.100)
Why is that?
Karl Deisseroth (56:34.020)
Because that often is the feeling
Lex Fridman (56:36.020)
until you're actually there.
Lex Fridman (56:38.460)
So like, you know, see that's when I'm running
Lex Fridman (56:42.860)
and I know there's only a mile left,
Karl Deisseroth (56:44.940)
it just feels like that mile
Lex Fridman (56:46.940)
is just getting longer and longer,
Lex Fridman (56:49.020)
but eventually you finish.
Lex Fridman (56:50.140)
So maybe we're getting close
Karl Deisseroth (56:51.820)
to cracking open these beginnings of a sense,
Lex Fridman (56:54.540)
like we'll talk about consciousness
Karl Deisseroth (56:56.180)
or these very difficult, big questions
Lex Fridman (56:59.580)
about the human mind.
Lex Fridman (57:00.900)
Where do they start?
Lex Fridman (57:02.380)
You're right to say we shouldn't generalize
Karl Deisseroth (57:04.700)
or make absolutist statements,
Lex Fridman (57:06.420)
but I would say right now,
Karl Deisseroth (57:09.180)
the reason things are looking even harder to crack
Lex Fridman (57:12.900)
than we had initially thought,
Karl Deisseroth (57:14.740)
we now have the data streams
Lex Fridman (57:16.460)
that we've wanted for so long
Karl Deisseroth (57:18.220)
in terms of activity patterns all across the brain
Lex Fridman (57:22.260)
at the level of cells.
Karl Deisseroth (57:23.260)
We can literally see what the cells are doing.
Lex Fridman (57:26.660)
Immense data sets.
Karl Deisseroth (57:27.820)
You know, we get, these are time series
Lex Fridman (57:30.780)
of one individual cell with sub second resolution
Lex Fridman (57:34.080)
and you can collect this from enormous numbers of cells
Lex Fridman (57:36.740)
across the brain.
Lex Fridman (57:38.080)
So very rich data sets that we've wanted for a long time
Lex Fridman (57:40.860)
and yet having these has not led
Karl Deisseroth (57:44.580)
to an understanding of truly where actions
Lex Fridman (57:48.140)
initiate in terms of regions or locations.
Lex Fridman (57:51.980)
And let's get a few questions on that.
Lex Fridman (57:54.180)
Is the answer, high level question by your intuition,
Lex Fridman (57:59.660)
is the answer within the data?
Lex Fridman (58:01.660)
Or do we need different kind of data?
Lex Fridman (58:04.620)
So we should also say that when you collect data
Lex Fridman (58:07.900)
about the brain, there's like the richness
Karl Deisseroth (58:10.700)
of information you're collecting,
Lex Fridman (58:12.620)
but there's also human doing stuff.
Lex Fridman (58:14.760)
And information, so static information about the human
Lex Fridman (58:20.960)
and dynamic information about the human
Lex Fridman (58:23.480)
and you can get them to do different stuff
Lex Fridman (58:25.300)
and you can select different humans
Lex Fridman (58:27.400)
and that's part of the collection of data aspect.
Lex Fridman (58:30.680)
So like when you're collecting data about the brain,
Karl Deisseroth (58:33.420)
there's some truths that you can,
Lex Fridman (58:36.360)
you know, in machine learning is like annotations,
Karl Deisseroth (58:38.200)
like supervised learning.
Lex Fridman (58:39.680)
There's some true things you can hold on to
Karl Deisseroth (58:42.080)
before you look at the full rich mess complexity
Lex Fridman (58:46.040)
of the human mind.
Lex Fridman (58:47.600)
So given the data you've looked at,
Lex Fridman (58:50.040)
do you think the answer for the origin of free will
Lex Fridman (58:54.040)
in the human mind can be found?
Lex Fridman (58:58.120)
Well, one amazing thing is that nobody's found it,
Lex Fridman (59:04.340)
but we have these rich data sets
Lex Fridman (59:05.860)
and then there's a conundrum which is,
Karl Deisseroth (59:09.800)
is it in the data and we just don't know
Lex Fridman (59:11.520)
how to look at it.
Karl Deisseroth (59:12.360)
Maybe we don't know the right scale,
Lex Fridman (59:13.760)
the right projection to make of the data,
Karl Deisseroth (59:15.800)
the right way to interpret it.
Lex Fridman (59:17.760)
And here's where causal testing becomes very valuable
Karl Deisseroth (59:21.280)
because then instead of just passively observing,
Lex Fridman (59:25.200)
well, here are the activity patterns
Lex Fridman (59:28.380)
and then here's the choice made by the animal.
Lex Fridman (59:32.240)
As we've gotten more powerful at reaching in
Lex Fridman (59:36.040)
and causing things to happen in the brain,
Lex Fridman (59:38.000)
turning up or down the activity
Karl Deisseroth (59:40.680)
of certain types of cells or defined populations of cells
Lex Fridman (59:44.440)
and seeing how that affects actions,
Karl Deisseroth (59:46.400)
these causal perturbations have turned out
Lex Fridman (59:48.920)
to be very valuable.
Karl Deisseroth (59:50.480)
We're just now getting to the point
Lex Fridman (59:52.240)
where we can apply these in very wide swaths of the brain
Karl Deisseroth (59:58.440)
at cellular resolution and so we're gonna be able,
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