The guest
Karl Deisseroth: Professor of bioengineering, psychiatry, and behavioral sciences at Stanford, widely regarded as one of the world's great living psychiatrists and neuroscientists. He pioneered optogenetics and authored the book Projections: A Story of Human Emotions.
What this episode covers
Lex Fridman talks with Stanford psychiatrist and neuroscientist Karl Deisseroth about how mental disorders sit on a spectrum and how studying dysfunction reveals normal brain function. They explore optogenetics, the light-based technique Deisseroth pioneered to control individual neurons, and what it reveals about depression, schizophrenia, autism, dissociation, and religiosity. Deisseroth opens up about his own clinical work treating treatment-resistant depression, the act of suicide, and his personal darkest moments. The conversation closes on consciousness, using a thought experiment about spreading neurons across a continent to expose how little we understand subjective experience.
Recommended on this episode
BookRecommended
Projections: A Story of Human Emotions
Karl Deisseroth
“i highly recommend it it's written masterfully”
“i highly recommend it it's written masterfully this is the lex friedman podcast”— Lex Fridman
MediaRecommended
Good Will Hunting
Gus Van Sant
“one of my favorite movies is goodwill hunting”
“one of my favorite movies is goodwill hunting i don't know if you've seen it with robin williams”— Lex Fridman
The guest's own work
BookBy the guest
Projections: A Story of Human Emotions
Karl Deisseroth
“he explores this in his book called projections a story of human emotions”— Karl Deisseroth
Also referenced (named, not recommended)
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Finnegans Wake
James Joyce
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The Idiot
Fyodor Dostoevsky
“i'm a big fan of prince michigan from the idiot and um i learned from brother karmazov”— Lex Fridman
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The Brothers Karamazov
Fyodor Dostoevsky
“from the idiot and um i learned from brother karmazov optimism can be seen as naivete and dumbness”— Lex Fridman
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Dubliners ("The Dead")
James Joyce
“the only thing i understood and really enjoyed is the short stories the dead”— Lex Fridman
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Ulysses
James Joyce
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A Portrait of the Artist as a Young Man
James Joyce
“i learned a lot about irish history from you know portrait of the artist as a young man”— Karl Deisseroth
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The Secret
Rhonda Byrne
“like the books or whatever i don't even know if it's a book the secret plugs into uh they kind of make a whole industry out of it”— Lex Fridman
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Two English Poems
Jorge Luis Borges
“you open your book with a few lines from a poem by jorge luez borges a love poem i'm going to read parts of it”— Lex Fridman
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March of the Penguins
Luc Jacquet
“so so there's march of the penguins so you always see like penguins huddling together against”— Lex Fridman
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The Lord of the Rings
Peter Jackson
“this is the i guess the ring scene from uh lord of the rings religion spirituality freud says cast it into the fire”— Lex Fridman
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Oliver Twist
Charles Dickens
“how hard your life has been how you feel who you are because i read oliver twist”— Lex Fridman
Big reveals from this episode
- Autism, anorexia, and bipolar disorder are all heavily genetic yet positively correlated with intelligence, education, and even income.
- Deisseroth's collaborator Botond Roska used optogenetics to partially restore sight in a blind human, published in Nature Medicine.
- By 2019 his lab could control 20-50 individually specified neurons to make a mouse behave as if it saw a stimulus that wasn't there.
- Deisseroth admits he chose to reveal his own personal struggles and darkest moments in the book because it wasn't 'real yet' without vulnerability.
- When asked if he has ever thought about killing himself, Deisseroth says no and wonders whether that makes him a less effective psychiatrist.
- Robin Williams' suicide is reframed via his diagnosed Lewy body dementia, with neuron and dopamine loss as a concrete neurological driver.
- The consciousness thought experiment: if every neuron got the same activity pattern, your neurons could be spread across North America and you'd still feel it.
- Lex recounts catching COVID and feeling 'greater clarity' afterward, prompting speculation about possible benefits of recovering from illness.
Worth remembering
- Lifetime prevalence of having a psychiatric disorder approaches roughly 25 percent of people.
- Optogenetics traces to an 1866 paper by St. Petersburg botanist Andrei Famintsyn on single-celled green algae that move toward light.
- Optogenetics works by inserting microbial opsin genes from algae that turn light into the electrical ion flow neurons use.
- Crying likely arose from a slightly misdirected long-range projection meant to regulate breathing during fear and anxiety.
- Tears on a face are far more powerful at triggering the desire to help in onlookers than any other facial feature.
- Deisseroth frames autism as difficulty processing unpredictable high-bit-rate information, not just social dysfunction.
- A brain structure called the habenula generates negative internal states and is a concrete target for reducing psychic pain.
- Schizophrenia is up to roughly 80 percent genetically determined and affects about one percent of people worldwide across all cultures.
- Religious experiences during epileptic seizures often originate in the temporal lobe, an early clue to where religiosity arises.
- Just 10-12 sessions of cognitive behavioral therapy can be very effective for mild to moderate depression.
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