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I'll go on record saying this.
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Anyone who thinks that Meta, Open AI, Anthropic, anyone that thinks that those are LLM AI companies is perhaps going to be surprised at this prediction.
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Every single one of those is going to be a biotech company.
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They're all interested in the brain.
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You talk to any of those guys, they may not have formal training in it, but they understand a lot of neuroscience, and they will all tell you the goal is to be able to read and write from your brain non-invasively.
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There's a very interesting thing happening that relates to a piece of your work which I I haven't seen you talk about as much and so maybe it's a fun place to begin which is that it feels like we're now bandwidth limited on the most talented people's ability to do work.
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Like it used to be that the rest of the world couldn't keep up with the most talented people and so they would get frustrated that no one was moving as fast or as efficiently as they were.
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There seems to be something flipping which is actually some of these people would earn a really high return if they could generate more energy, maintain more energy, not burn out.
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maintain more energy, not burn out. I heard this from several great entrepreneurs this summer that there's this expectation that the real greats kind of like I think maybe Elon has just gotten into everyone's head that the real greats are going to run multiple companies and and there's just this like this technology unlocks so much potential for the most talented people
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and so it seems like an actual bottleneck is like these people's energy and I'd be curious in your in all your research and and and study what you've learned about the component parts of this like generating energy maintaining it clean versus dirty fuel, long-term performance, like all of these things are fascinating and I think actually important to the degree of progress. And
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And so I would love you to just riff on on all that for a while with the caveat that you know Elon represents the apex of being able to do multiple huge things uh simultaneously and I don't think he has any peers in that in that regard.
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In fact, one of the best multi-billionaire investors from the Bay Area who may have gone to Stanford and may have been part of the PayPal early team has asked me, we're friends, um, how is it that Elon does this?
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I'm like, I I can't tell you >> like physiologically.
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>> Physiologically, I mean, there are examples throughout history of people who seem to require less sleep.
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They just have more energy.
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And most people can get their energy up.
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There are a lot of healthy ways to do that now.
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And I think now we've undergone this huge shift whereby everyone understands you have to sleep eventually and you have to know your own sleep requirements.
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So to delude oneself into thinking you only need four or five hours because Elon only needs four or five hours, that's that's ridiculous.
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We know where that leads.
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leads. So I think a an honest self assessment about how much sleep one actually needs to perform well and perhaps best and what you can get by on you know if you can't get that that's an important thing to understand but most people know like for me it's 7 hours I
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feel great eight I'm probably puts me into the day a little bit groggy six I can manage just fine for one day or or a sleepless night I'm good two nights like that of four to zero hours of sleep and I'm cratered and I Most people are similar. What's really changed is that
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What's really changed is that we have effective healthy ways to build our energy up. We know to sleep.
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We can talk about exercise, caffeine.
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Some people are using nicotine. Yes, it's addictive.
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It raises blood pressure, but it does put people into that, you know, focused but relaxed mode.
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I always say if you really want the benefits of nicotine, don't use it very often.
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If you want the actual cognitive enhancing effects or the focus enhancing effects, then you have to not be a chronic user and then you know spike your system with nicotine at low amounts every once in a while.
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But setting Elon aside is the with the understanding that he represents that ex extreme uh in terms of energy and and sleep requirements being very low.
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I think what's really happening now is people are hopefully doing this self assessment.
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Like I would hope people would have an honest conversation about themselves and say, you know, at this point in my life with or without without kids, at this stage of my company, at this stage of my career, whatever it is, at this age, how much sleep do I need in order to feel awesome, good enough, or it's not enough?
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And I think most people know that.
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Okay, so that's step number one.
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The next one is something most people don't ever talk about, which is some people actually just have more energy, right?
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they can focus for long long periods of time.
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They have a ton of energy to run.
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They have a ton of energy to then go work.
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But what we never ask is what is that person's internal state.
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So I know people that can do all of that, but they're kind of redlinining and they're using a lot of stimulants to do it or they're not using stimulants to do it, but they're redlinining and then at night they're having a hard time switching it off and so they're not resetting their system.
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Some people, however, are these like wake up at 4:00 a. m.
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, work out, handle business, deal with family, go off to work, back to business, come home, and they pivot and task switch really fast.
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I don't think these things are necessarily stable features throughout our entire life.
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But whenever, you know, it seems to be a lot of young guys come up to me and they're like, "What should I do?"
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The Oracle said it best, like know thyself.
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You really have to be honest with yourself about what you need in order to do something for a long period of time.
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Now that said, I do recall working 80 even 100 hour weeks in graduate school and that served me well.
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I mean eventually led me to tenure at Stanford etc.
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led me to tenure at Stanford etc. I do think that for the if you can pull it off I think from zero to maybe first four years of starting a company or if you're in medical school you know the goal is don't die get as much as done as you can and don't impair yourself with
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an injury or chronic disease and then you start to pivot into okay how you know we don't really define this thing optimization then it's how can I insert kind of components of rest along the way maybe during the day or across the week or the month that really allow me to access my, you know, my best levels of focus and creativity. But I'd be naive
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But I'd be naive and I'd be lying if I said, "Okay, you know, somebody's starting a company in the AI realm in the Bay Area or elsewhere these days, you're going to sit them down.
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You go, listen, you really need 8 hours of sleep.
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You got to do your resistance training.
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You should do some breath work." Like, no, none of that.
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What they should determine is how much energy they actually have.
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And you've met these people, right?
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Occasionally you'll run into, you know, like a Jimmy Ivine or a um there's some of the I've met some of the folks doing AI at Meta um and they just seem to have an extra gear.
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Some people have this extra gear.
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Now, there's one other component we can we can deep dive into any of these that nobody talks about and that's the ability to switch off your thoughts, your planning, and your concerns at the end of your day and drop into sleep. >> Yeah.
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Can we go deeper in that one?
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Because the the to be very selfish about it, like if I was to self diagnose, the biggest problem I have is downshifting.
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Like so sometimes where it'll take four like literally four hours to go from a crazy exciting awesome day to literally even be able to fall asleep or just like stop the mind and if I could bestow myself with any gift it would be what you're describing.
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So what what is the research there of how to do that?
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>> There are a couple of prerequisites for sleep.
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There are a bunch of don'ts.
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So obviously you don't want to drink caffeine too late.
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Um you know being under too much bright light late late in the day can make it difficult but a lot of us can't control that.
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um alcohol, cannabis, these things impair the quality of your sleep, help you get to sleep. We all know that by now.
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But in terms of being able to turn your thoughts off, this is a very very difficult thing for people um for, you know, good reasons, right?
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The brain wants to think, plan, remember, and organize itself around what's coming next because such a huge aspect of brain function is prediction of what's happening next.
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So, first requirement, turn your thoughts off.
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Second requirement is slow your heart rate down.
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Okay, so that's purely of body.
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And then third is you need to forget about the position of your limbs in space.
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Okay, so let's work through each one systematically.
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For the first one, turning your thoughts off is a skill. It's a skill. How what do you do?
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Okay, we can think, we can predict, we can remember, but we also can get into pure sensation.
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And that's the gateway to turning off your thoughts. Okay.
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And this doesn't come from eastern tradition per se.
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Although there this has been discussed for a long time in those traditions, but there's a neuroscience correlate to all of this of course and we can talk about those. So how do you do that?
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You have to focus on pure sensation.
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So you start focusing on the surface of your body.
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If you can detect your heart rate, some people are very good at what's called interosception.
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can actually get pretty accurate measurements of their heart rate just without, you know, pressing on a on a vein or artery and they're just listening to their own breathing.
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They're listening to the sounds in the room.
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They're bringing their conscious awareness just to the body and it generally helps and this relates to the second thing to slow the heart rate down by just doing long exhales.
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Now, this might sound very woo, but I want to be very clear this is not meditation because meditation has you do something very different.
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Meditation has you focus all of your attention on your breathing or all of your attention on, you know, some region behind your forehead or your hands or whatever.
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In this sort of practice, what you do is you actually migrate your attention to your feet, to your legs, to your breathing, to sounds in the room, then back again.
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Now, this might sound really squishy, but you're moving away from thinking and planning to pure sensation and perception.
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And you're literally bringing your perception into the present.
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Remember, this is one door in front of turning off your thoughts.
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To actually turn off your thoughts, your heart rate actually has to drop a certain amount.
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Those long exhales drop your heart rate through something called respiratory sinus arrhythmia.
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Arrhythmia makes it sound dangerous or bad, but it's actually very good.
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As you're breathing, the size of your heart is literally changing based on the amount of space it has because the movement of the diaphragm and the filling of the lungs.
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And when we inhale, our heart rate actually speeds up a bit.
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When we exhale, the heart actually gets a little bit smaller volume-wise and the blood therefore that's in it moves a little bit quicker per unit volume and the brain sends a signal to slow the heart down.
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So when you exhale, you're slowing the heart rate down through this thing that we call the vagus nerve.
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So, if you want to slow your heart rate down anytime in waking to de-stress or just bring your level of activation down or if you want to fall asleep, it really helps to do some long exhales until lungs are empty and then just passive inhales.
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Normally, when we're really activated, we're doing a lot of inhaling.
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We're passively exhaling.
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And then the last piece is to be able to turn off your perception of your limbs relative to you.
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This thing that we call propriception.
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And there are two ways to Well, there are three ways to do this.
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Okay, one is old school, everyone accepts it.
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One is pretty wacky sounding and then there's a new technology that's coming out that I wish I had developed that I think is going to make people more comfortable with the second one. So here here goes.
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So there, believe it or not, there have been studies of what puts babies to sleep and what puts adults to sleep without pharmarmacology.
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And it turns out that the rocking pacing that we do with babies at a certain rate, parents figure this out on their own, puts them to sleep.
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Turns out that you can build, and they've done this for studies, a bed that rocks at a certain frequency and adults will fall asleep very quickly.
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What it has to do with is the fact that when you're moving side to side, your eyes are generating under your closed eyelids compensatory eye movements.
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Our our eye movements all the time are communicating through our brain stem to our cerebellum to control balance and propriception.
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So when people are rocked this way, somehow they fall asleep more quickly.
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That's interesting actually.
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And the frequency that at which that works best and fastest is known.
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Now I don't have a rocking bed.
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I don't know anyone large enough to rock me and hold me.
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And if they did, I'm not sure I'd feel comfortable with that.
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Can't imagine you would either.
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So there are two ways to approach this.
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One is something that looks kind of wacky but works, which is to mimic the eye movements under closed eyelids that help you forget about your limb position.
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I've been talking about this a lot in public education recently, and I confess it makes me feel really weird as a neuroscientist.
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weird as a neuroscientist. So I'm going to just preface this by saying please don't just put the part out into the world about the eye movement thing without just allowing me to first say that this confuses the circuit between for the ficinados these direction selective cells in the retina the accessory optic nuclei of the brain stem
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and the cerebellum and you forget about body position and basically what you do is under closed eyelids you move your eyes to one side then the other slowly or fast doesn't really matter then up then down you can roll them counterclockwise and clockwise you can do a long exit But really what you're doing is confusing this system. The
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The reason I got so interested in this and the reason I went to the literature on rocking of babies and adults to fall asleep is because a group out of MIT approached me and they said, "We'd like you to try this eye mask."
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The eyes are two pieces of brain.
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They're just not in the cranial vault, which makes them unusual in terms of parts of brain.
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And so the eyes are an amazing gateway to the rest of the brain.
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Everyone knows about eye masks to get the darkness out.
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These guys have developed eye masks that measure rapid eye movement because right now your your whoop, your aura, your eight sleep.
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They're not measuring REM directly.
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This can measure REM directly, but they designed this mask specifically to make people fall asleep faster. Like I want that thing.
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So I got to try it and it works very well in the daytime or at night. And what does it do?
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It generates these slow back and forth up and down eye movements through a like small amount of stimulation behind your ears because it turns out you can access the extraocular muscles well enough from that location.
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So just an eye mask with some straps.
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You sometimes feel a little bit of the stimulation and you're out and then once REM sleep starts it actually helps amplify those the REM stage. You get much more REM.
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So I wish I had a stake in this company. I don't.
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These technologies are about I would say 7 to 12 months from release.
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I'm super excited about them.
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I'm also super excited about the fact that people can just do this on their own and obviously babies get rocked.
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You could do you know the non-mask tool approach or you could use the mask.
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I will say and I don't want to take us too far off course but for those interested in emerging technologies and AI in particular neural technologies I do think that in sleep reading from and writing to the brain is going to be a huge area but of course I'm most interested or I should say also interested in reading from and writing to the nervous system in waking states.
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You could imagine like within 12 months to a year of the release of the technology that I just described, you could imagine somebody developing eyeglasses like this that are stimulating some component of the autonomic nervous system so that I'm exceptionally focused at certain times a day and then when I'm walking home, I'm sort of in a slightly more relaxed state to capture some more of that energy.
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We're going to start shifting brain states into focus into modes for learning and we're going to start doing it with technologies.
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Right now we're doing cold showers, caffeine exercise.
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We're doing inhale emphasized breathing versus exhale emphasized breathing to get more alert or calm.
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If you think about it, all breathing exercises can be summarized as inhale emphasized or exhale emphasized.
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So yes, we can do that stuff deliberately, but you can imagine that pretty soon there will be non-invasive stimulation devices that will allow people to do this, but it will start in sleep because we're all kind of comfortable with the idea now of measuring our physiology in sleep little bit in waking states, but this is where this is going.
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So to return to this in sequence, you need to learn to turn your thoughts off.
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You need to forget about your body position and and slow your heart rate down.
15:59
And the order in which you do that doesn't really matter.
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You ideally want to combine all three.
16:02
But I think that's going to be a significant achievement for humanity because if you look at recovery from illness, healing, learning, um stress control, burnout, right?
16:16
If you're going through grief or psychological stress or trauma healing, if you're trying to start a company and you got kids or even if you're just trying to work the maximum number of hours and you have four hours to sleep and you're somebody who needs six, you want to be able to hit the pillow and shut it off.
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And we don't have good ways to do that except the tools I described.
16:35
So, I think we are starting to go about things in a more healthy way.
16:38
But what I'm talking about is people doing a a thorough self assessment of sleep need, ability to turn off thoughts, and then training those things.
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In fact, a lot of hard driving people will come to me and say like, "What workout should I do?"
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I'm like, "Look, how much time do you have?"
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In graduate school, I worked out twice a week.
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I don't talk about this, but I lifted weights and I ran really far because I just wanted to maintain while I worked my ass off publishing as many great papers as I could.
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And then later, I'm doing, you know, three workouts a week with the weights.
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I do cardio three times a week, long, medium, and short.
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You know, take a day off, maybe do some sauna, and cold.
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My life's a little bit different now, or a lot different.
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But I do think those first years, you're trying to just not die while you create your this thing.
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Then you start moving into some quote unquote balance and optimization.
17:23
And then you get the the people who have really achieved some level of mastery or virtuosity in their craft.
17:30
And you really get an assessment of how accurately their schedule matched who they really were at a physiological level by looking at them and going like they look like [ __ ] They have a chronic illness.
17:43
They look 10 years older than they were supposed to or there there are certain people who like phenoms, right?
17:48
Like Elon or you look at some people and you just go, "Holy crap, they just got an extra gear."
17:52
But I think and I'm speculating here, but I'm guessing that Jack Dorsey was always a pretty calm, thoughtful guy, right?
17:59
And that's what people tell me of him and that's how I experience him, too.
18:03
But I'm guessing he's also put some work into it.
18:06
He's figured out that staying alert and calm all day and sleeping well at night is the key to having a really long successful arc.
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19:47
Since you've been covering it for so long, I'm curious what you think the biggest challenge or problem or issue is facing your whole field.
19:52
Like if I think about this as the quest to learn and teach to understand our health and our well-being and ways of making it better.
20:02
What is the biggest challenge facing the field today?
20:05
I mean, I feel like the public discourse around health and longevity is a [ __ ] disaster.
20:07
This is a bunch of clowns and people are like doubling and tripling down on on the theatrics, right?
20:15
I'm not saying I get everything right or that I have all the answers.
20:18
I'm definitely not saying that.
20:20
I got into this at the right time, but the downside is that it was so devoid of anyone else, right?
20:28
anyone else, right? there were people talking about health only in their area that they worked on in their lab but not broadly that that you know the bar for entry in public discourse around health is basically like zero >> you know it's like you show your abs and you admit you're on steroids you have a
20:44
following you you show some dude shows his abs or some woman like shows her glutes and um and she claims to be all natural and we believe them then and suddenly they have a following so I mean if that's the the bar for entry I come from a field where it having a PhD isn't even nearly sufficient, right? It's
20:59
It's necessary, but not even nearly sufficient to say that you've contributed something to the understanding of the brain, right?
21:05
Like we could take somebody like Tim Ferrris was talking about a lot of this stuff early on that, you know, biohacking, self optimization.
21:11
And what I love about Tim is he's remained Tim.
21:13
There was this period where he experimented.
21:15
He had some things that like he felt like probably weren't a good idea.
21:19
You know, he talks about those like things that he wishes he hadn't done and things that he's happy he did.
21:24
And then you, you know, he's also in investing and all these other things.
21:28
I think Tim's fantastic because he's being Tim, so I'm not referring to that, right?
21:32
And then you started getting these more and more extreme versions where people were coming in with basically no science or health training and saying, "Hey, like here's how you optimize the mind and body."
21:42
And I know this because I'm doing all these things and I used to be fat and I'm not fat anymore.
21:45
And I think that's fine in principle, but then it just keeps getting crazier and crazier.
21:53
And so what you've seen now is there's a big gap between, if I'm just honest, between the A tier public health educators and what used to be the B tier public educators.
22:01
And it's just it's just getting bigger and bigger and bigger because one has to be true to self, but you also have to take the endeavor seriously.
22:08
It's very easy to get attention.
22:10
It's very hard to keep respect.
22:12
So I do think that the public health discourse is harmed when it becomes about the theatrics.
22:16
And I'm not trying to not name names here.
22:18
I mean, I think everyone can look out on the landscape of everyone from Brian to me to Gary Brea to to Asprey to anyone else.
22:26
They're a lot in the space and just go like what do like who whose sort of persona resonates not just what captures the entertainment value.
22:34
So, what I would expect will happen next now that we've gone from high amounts of interest in this to this optimization optimization now it's turned into are we overoptimizing?
22:45
We're I think we're gonna see a downturn in the number of things that people are willing to do each day.
22:50
They're like this just too much.
22:51
It's gotten kind of kooky. It's kind of crazy. Okay.
22:53
And the characters like I need more serious peers.
22:56
I need serious peers with training in either health or in either science or medicine, maybe pharmarmacology, and they're out there.
23:05
But I think those people are going to rise to the surface.
23:06
We haven't seen them yet.
23:08
So I look forward to having colleagues like that.
23:09
And then I think what's going to happen is we're going to get many many more people trained as PhDs, trained as MDs, who are going to be doing serious science health discourse, not just trying to go like like regressing to the tick- tock dance model, the focus on me model and really educating people in a way that's unique that I I'm certain I probably well I'm certain I haven't even tapped into, right?
23:33
Someone's going to come along that's better than me.
23:34
So I think this field is going to go into a downturn now.
23:39
the public education around um you know health and optimization longevity etc is going to go into a bit of a downturn and then I think we're going to get an influx of a lot of great people and then it will be where I would like to see it.
23:51
>> How about on the research side?
23:51
Biggest biggest problem facing the field.
23:54
>> Well, I think the coolest problem that's also the biggest problem is how we can non-invasively write to the nervous system in sleep and waking states.
23:59
So I mean my best friend from childhood Eddie Chang is chair of neurosurgery at UCSF. He's a bioengineer.
24:05
He's doing things I guess you know similarish to what Neurolink is doing but removing brain tumors and this kind of thing.
24:13
I've been with him to surgeries like right up there next to the tumors. Patient is awake.
24:18
He's probing areas of the brain.
24:19
He has permission to map areas related to speech and language etc.
24:21
So breaching the skull is a big deal.
24:24
The neurosurgeons say well you know a titanium plate would be better. It's stronger. It lasts longer.
24:28
But most people don't want to have to do that.
24:31
They do it because they need something taken out like a tumor or an epileptic fosi.
24:37
I think the big one now is who can develop it will probably be ultrasound but a non-invasive way of selectively activating or quieting brain areas with high amounts of temporal precision like getting people who are in in lockin syndrome to speak as Eddie has done or getting people who have a spinal injury
24:56
to walk which neural link and Eddie and others are trying to develop technologies to do that is you know that's heroic right but ultimately and I'll go on record saying this anyone who thinks that Meta, Open AI, Anthropic, or well, Elon's got Neuralink as his stated neural interest. Anyone that thinks that
25:15
Anyone that thinks that those are LLM AI companies is perhaps going to be surprised at this prediction.
25:23
Every single one of those is going to be a biotech company.
25:25
They're all interested in the brain.
25:27
You talk to any of those guys, they may not have formal training in it, but they understand a lot of neuroscience.
25:32
And they will all tell you, okay, here here's the goal, right?
25:36
The goal is to be able to read and write from your brain non-invasively.
25:38
And there are straightforward ways to do that.
25:41
So, the big thing is, how can you stimulate a brain area with temporal and spatial precision?
25:46
How can you quiet that brain area with spatial and temporal precision?
25:49
How can you dial up or down the level of quieting?
25:51
Because it's one thing to say silent versus activated, but the nervous system has a lot of graded signals in it.
25:57
I mean, we don't think about those signals, but the communication between areas is gated. It's graded.
26:02
Thresh thresholds for activation change.
26:04
I mean even just for things like drive and motivation a non-invasive device where you could literally turn up crank up your level of motivation by stimulating the nucleus incumbent while and related pathways while engaging in a particular learning task or or in hard work and then turning it off so that you can capture more energy.
26:24
You have more of a square wave function on your energy output that's coming and those companies are all about that.
26:31
That's what the real arms race of AI is about.
26:33
So I sort of chuckle when I think like okay like the LLMs are great or terrible depending on who you are and I believe they're great.
26:40
Um, I'm a big fan of AI, but the dynamic modulation of your own neural activity using non non-invasive technologies, not pharmarmacology, but then using AI to be able to understand, okay, this level of activation in this brain area for you, Patrick, is related to a hyperotivated brain state that makes it very hard for you to do anything else the rest of the day.
27:02
And it will just learn to titrate.
27:04
But you say, well, that sounds kind of science fiction. How far off is that?
27:05
I mean my eight sleep changes the temperature throughout the night to give me more REM sleep or deep sleep. It's already doing that.
27:14
It's just in we we're okay with these things in sleep and it's doing that through a you know a powerful but indirect method temperature change.
27:22
But it's no small thing to dynamically change and measure the degree of change in the nervous system in order to access a given state, sleep or otherwise better.
27:33
And that's what these companies want to do.
27:36
these companies want to do. So my field of neuroscience has to embrace this and they are that the people who are trying to figure out you know what are the natural signals in occurring in the brain when people think when people see when people move you know their limbs in a particular way that's been the last 30
27:51
40 years that's all reading from the nervous system now it's about writing to the nervous system non-invasive >> I have a stupid basic question what does it mean to like what is the method by which we can read and how precise is our ability to read activity and what does activity even mean in in different parts of the brain Great questions. So, it
28:06
So, it depends on how invasive you want to get.
28:10
So, most people understand that um or if you haven't, no big deal, that neurons communicate through action potentials, electrical signals, and we we were taught and it's still in the textbooks that they're always the same size and shape for a given neuron.
28:21
Okay, it turns out that's not even true.
28:22
So, there's variability there, but we sort of have this all or none like a neuron either fires or it doesn't, but there graded potentials.
28:28
You get to a threshold, the neuron fires, communicates with the next neuron, depending on the millu there, how many other inputs what they're doing, the next neuron fires.
28:35
you sort of set off a chain or not.
28:36
So you can record from neurons by putting an electrode close to the close to them extracellular recordings.
28:43
You can put a you know a sort of bed of nails nearby record lots of those extracellular signals.
28:48
You can impale a neuron record intracellularly.
28:51
All of that requires breaching the skull sticking wires basically down into the brain.
28:55
The methods that are really exciting are things like ultrasound transcranial magnetic stimulation which is used for the treatment of depression and other things.
29:05
The spatial control there of that's for stimulation is is not great.
29:11
The recording from the nervous system you can go from what I just described intracellular recording at the most extreme then extracellular recording and then you go all the way to like fMRI. Okay.
29:22
um or EEG, you know, when people see these like heat maps of the brain where you're really can only measure signals in the surface like at the at the cortex, which is interesting, but you're not going to get to the deeper layers.
29:32
A big problem now is how important is it to understand the natural patterns of activity in detail before we start poking around >> and stimulating with writing. Okay.
29:43
And obviously there are two ways to write. Well, at least two.
29:47
Let's let's off allow ourselves more than two.
29:50
You can use pharmarmacology.
29:51
So what does most pharmarmacology do?
29:53
Whether it's alcohol, um barbituates, sedatives of some kind, what are you doing?
29:59
You're increasing the threshold for activation.
30:00
You're quieting the brain by just increasing the threshold for activation.
30:03
You're doing it indirectly by increasing inhibitory release.
30:06
So there's less excitation overall.
30:08
You think about aderall, caffeine, nicotine, um speed, modafanil, and you're talking about lowering the threshold. Okay?
30:16
because those generally work by increasing neurom modulators that increase the likelihood that neurons will fire.
30:22
So you're just kind of ramping up that baseline.
30:23
You're sort of creating higher RPM across the brain and body.
30:27
That's why they lead to some shaking, some agitation.
30:29
Like everything's like primed to move, primed to fire, primed to think.
30:32
It's hard to shut off your mind under when you're under the influence of stimulants.
30:37
Easier when you're under the influence of these other drugs that increase inhibition.
30:40
So the real question for trying to get to better reading and writing to the nervous system is about spatial and temporal precision and how willing you are to put something under underneath the skin.
30:53
I say skin because you don't necessarily have to go under the skull.
30:58
Like let's take veagal stimulation for example.
31:00
Veagal stimulation most people think about as a way to calm down but most of the veagal pathways are excitatory.
31:06
And so common treatments for depression now if somebody's willing is to put a small you know it's a little smaller than a penny size stimulator some you know under the the skin of the neck and stimulate the vagus in order to overcome this sort of sedation depression that accompanies depression.
31:23
So veagal stimulation increases alertness.
31:28
Neuroscientists have known this for a long time and a lot of people are getting pretty good results in their treatment of their depression by increasing veagal stimulation and it's dynamic.
31:37
You can say how do you feel? I feel okay.
31:39
You can actually see this in real time.
31:41
There's an amazing thing that my colleague Carl Daiseroth, one of the greatest bio-engineers alive, u has talked about where he's talking to a patient and she's suicidally depressed and then he starts increasing the stimulation on her Vegas and she starts moving from that to a discussion about how she feels willing enough to go out and apply for a job. Right?
31:57
This is inc I mean in real time that just tells you that these excitatory mechanisms and these depressive mechanisms or inhibitory mechanisms are profound in terms of our perception of the outside world, our perception of ourel.
32:08
this would be very nice to have.
32:11
The question is, are you willing to go under the skin?
32:14
I am um a guy that came up not mainly through my lab, but he spent some time in my lab.
32:19
He's now the head neurosurgeon at Neurolink, Matt McDougall. Amazing guy.
32:22
He's has a little receiver uh under his skin, implanted under his the skin of his hand between his thumb and his and his index finger.
32:32
And his wife does too, and it opens their door to their home to keys like I was like, "What what are you doing?"
32:37
It's a sort of, you know, it's kind of biohacking Bay Areaish kind of stuff.
32:41
He's like, "Yeah, like I'm just he's just playing with the idea of what is it like to have a small device under your skin that can do stuff in the world for you?"
32:48
And that's very neural linkish.
32:50
And obviously they have much bigger aspirations than that.
32:51
But I think within 12 months 20% of the entrepreneurial world will be asking, "Huh, if it's only as invasive as getting a piercing, yeah, maybe I want a little veagal stimulator." And that's coming next.
33:13
People are thinking like, "Peptides, what are we going to do?"
33:14
I'm not worried about peptides.
33:15
I'm thinking implantable devices is where it's going to go next.
33:18
the commercially available veagal stimulators, some have shown some um some promise.
33:25
They're not super impressive to my neurosurgeon colleagues who like to get under the skin and under the skull.
33:29
But I will say there's some interesting results there and um but we're not quite there.
33:35
But think about 10 years ago if I told you, listen, you're going to be wearing a ring or a or a band on your wrist that measures your sleep and HRV, you know, and your sleep's going to be measured.
33:46
you feel like that's pretty out there.
33:49
>> I'm so fascinated by this.
33:49
So, in my mind, there's there's reading, the underlying activity of the brain at different levels of fidelity.
33:55
There's writing, you talked about um ultrasound stimulation.
33:59
I think there's electrical, I think there's magnetic stimulation potentially of these areas of the brain.
34:04
But one one central part that I don't really know much about is how much we actually like the model of the brain itself.
34:10
Like how far along in our understanding of that we even are.
34:13
understanding of that we even are. I know there's some things that we can say activation of this area produces this thing but like >> yeah what do we have a good it feels like we need those three things like good input modalities good reading good reading methods and and a model >> yeah I'm glad you're asking you I mean these are my favorite topics it's just
34:30
that usually people are like um you know what peptide should I take >> which peptide should we take by the way >> I mean depends on what what your what your pain points are depends on what your pain points are so at the periphery
34:42
the retina the cookia the tongue, the alactory system, the skin, neuromuscular control, which isn't, you know, at the periphery, but I think we know pretty darn well how the nervous system works. And we know how different
34:57
And we know how different wavelengths of light are transformed into visual images at a at a not even a first approximation, but you know, we understand that in significant detail how motion is processed.
35:07
We understand a fair amount about memories.
35:09
Although I want to put that on the shelf for a moment because there's an important finding in the memory field that will give you make you feel a little like it's in kind of twilight zone perhaps in neuroscience and um it worries me all the time.
35:22
The hypothalamus so circuits that are deep in the brain that control hunger like it anger, sexual appetite, lack thereof, hormone secretion, those are switches.
35:36
So do we understand those? Yes.
35:36
Do we understand everything? No. But we understand them.
35:41
I mean, one of the reasons the GLPs are so effective and one of the reasons they got so much velocity is because we understand where they bind in the brain and they bind to these hypothalamic and other areas of course that activate neurons that are involved in the suppression of appetite.
35:58
And so it's a very simple equation really.
36:01
Ramp these GLP levels up thousandfold, people aren't as hungry.
36:04
But turns out they're not as driven for other things too if you get beyond a certain level.
36:08
I think Sam has Alman talked about his experience with with that at one point.
36:12
Um and why he decided to either back off the dosage or stop taking them.
36:16
I would say as you move in from the periphery of the sensory organs, right?
36:19
Um and as you move up from the base of the brain, the deeper limbic structures and hypothalamic structures to the prefrontal cortex, we can say, yeah, like your prefrontal cortex, we know based on lesion studies in humans, activation studies, um is really important for contextual learning, for strate strategy setting in different environments, for suppression of impulse, what we call top down suppression.
36:43
So do we understand what the prefrontal cortex is doing? Yeah.
36:47
The place where it starts to get murky is at the level of memory.
36:50
Although we we'll talk about that in a moment.
36:53
And at the level of thoughts, you won't find a chapter in a neuroscience textbook that says this is how thoughts are made.
37:02
And we can talk about what's starting to emerge there.
37:04
These dynamic attractor states.
37:06
We'll get to those in a moment.
37:07
But here's the eerie study um results from the study of the hippocampus and memory that freak me out.
37:12
And a lot of neuroscientists don't want to talk about this because it throws all the read write stuff that we were talking about earlier all the technologies and pharmarmacology into a complicated place because it doesn't allow for clean matching of conceptual understanding of the brain from experiments to um levers that we could actually allow us some control and the the experiments are like this.
37:36
So Mark Mayfford's lab has done this.
37:38
So down at Scripps um Sus Susum Tonagawa who won a Nobel for his work on immunog globulins but then became a very successful neuroscientist.
37:45
They've done these experiments where they have an animal do some sort of learning task.
37:52
Could either learn that they get shocked over here and not there or they get a reward over here and not there or they learn a maze or they learn a lever pres lever press combination that gets them a reward.
38:01
You know, they can learn pretty sophisticated things for a mouse.
38:02
Um monkeys can do this too.
38:05
Um, humans can do this too because ways to read from the brain, including the hippocampus, a deepish brain structure, um, have gotten pretty good.
38:15
You can say, okay, these are the patterns of signals that happened as the animal learned.
38:18
And here are the patterns of signals that occur every time the animal expresses this thing.
38:25
We imagine this is that there's a coralate where every time uh, somebody serves a tenn tennis ball the way they perfected it, that the same cluster of neurons is activated in in the brain.
38:36
They're communicating with each other, the same circuit rather, and in a particular sequence, A leads to B leads to C, and so on, you get the tennis serve.
38:42
The data tell us that if you tag the neurons that were involved in this behavior and then reactivate them, you expect the behavior, right?
38:54
And indeed, that's what you find. Okay.
38:56
So, I let's let's hypothetically. Do you play tennis? >> A little. >> Okay. I play even less.
39:04
You serve the tennis ball.
39:04
I'm able to measure, let's just say, with the highest degree of fidelity that the the patterns of activation from start to finish that occur as you toss the ball in the air and you and you serve. Great.
39:13
Now I stamp those neurons with a chemical tag. This has been done.
39:15
Then I come back later and I activate those neurons in the same sequence and you do the exact and you do the serve perfectly and I say great.
39:23
But then they did the important control experiment.
39:26
What if I activate those neurons in the opposite sequence?
39:30
What if I activate all those neurons at once, like banging on the keys of the piano?
39:35
It's not the same as playing the song.
39:37
If I just say, what are all the keys involved in this motif of music and instead I just bang on them all at once, you get a very different sound coming out of the piano?
39:45
Turns out you get the exact same behavior.
39:47
This is problematic for the field of neuroscience because what it says is that this notion of the these circuits firing in a particular sequence, at least for memory, it's probably not true.
39:59
So now if I want to write to your nervous system, maybe I'm better off because all I have to do is activate these same neurons and it doesn't matter what sequence I activate them in.
40:08
That's kind of cool, right?
40:09
Like you want someone to walk, maybe you just need to activate the brain areas involved in walking and the body and the other brain circuits will figure it out. But here's the problem.
40:16
First of all, it's very hard to activate these select sets of neurons with high spatial and temporal fidelity to begin with.
40:23
But the other problem is these neurons I didn't tell you are all also involved in lots of other perceptions and behaviors.
40:31
So it's not like you have a circuit for serving a tennis racket that isn't also used for some aspect of thinking and remembering about something from your childhood.
40:40
I mean that's one of the beauties of the nervous system is it repurposes different neurons to participate in different circuits depending on the perceptions and behaviors that you're trying to ex that you're experiencing that you're engaging in.
40:51
So our our model of the brain works at the level of the periphery at the deeper brain structures.
40:57
But once you start getting into memory and thinking, it's complicated because we don't yet have a good model of whether or not the temporal ordering of firing of neurons matters.
41:13
And every textbook says it does.
41:13
And the flow from like eyes to the phalamus up to the cortex to create a visual perception.
41:20
We know that direction of flow is critical.
41:21
If you if you cut that off at the level of this deeper brain structure of the phalamus, there's no perception.
41:25
We know this from human patients.
41:28
But you know, memory, thinking, brain plasticity, these things all rest on the assumption that the temporal order matters.
41:34
And apparently it doesn't.
41:37
And that's one of the kind of um unspoken like within our field.
41:43
People are trying to understand that and what it means.
41:45
Um, but it's going to present a serious problem for the neurochnologies.
41:49
Again, it's going to alleviate some problems because maybe you don't need as much spatial fidelity, but in my mind, this is a huge gap in understanding.
41:58
And then the other piece is that we don't really understand what a thought is.
42:01
And so if you're going to get in there and start stimulating neurons in even just motor cortex to generate movement without the you know the acknowledgement the these neurons are extensively interconnected with structures involved in thinking and planning you could send the system into haywire.
42:18
That said you know if there's a goal in mind like drink the glass of water the brain generally figures it out and that's what's incredible.
42:27
I mean there are people working on brain damaged patients that are finding that if you just go to the areas of the brain where the signals are generated to inform the action output ends of the brain then you can do pretty well.
42:41
That's how my friend Eddie Chang gets people with lockedin syndrome to speak through a computer.
42:44
He's not measuring from the speech production areas.
42:47
He's me measuring he's he's carefully characterized for many years decades the signals coming out of the the speech planning areas.
42:54
And because the signals can't get down to the ferings and larynx because speech is just the fairings and larynx controlling exhales, what he's doing is he's it's just transforming those signals into electrical signals so that the person can talk through a computer.
43:07
So there's advantages and disadvantages to this non-specificity, but I would I think that's the big one.
43:16
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46:00
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46:20
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46:28
What about all this excites you most and scares you most?
46:30
Like some of this sounds like, oh, you could just literally pro it it feels to sort of strip me of my uh humanity or my identity in some weird way.
46:38
If if I knew that you could just like play me like a piano or something like this given high precision technology that's, you know, underneath the skull or something.
46:46
The bigger question is like where do you actually think we're going?
46:48
like 5 10 years from now, what do you what kinds of things you think we'll have?
46:53
>> But but I'm also just curious about like a cyborg line here that we're probably going to cross that gets kind of philosophically weird and I wonder what you think about it.
47:00
>> I have to acknowledge I was born and raised in Palo Alto and I have friends in the technology medical sector.
47:03
in the technology medical sector. So sometimes I get a little bit of the blinders on about how other you know a lot of people are terrified of AI and I'm I'm told lately that I'm not scared enough but I I acknowledge that people are concerned afraid they don't understand it but I remember the same discussions about computers
47:18
>> which is not to say that we don't need to be careful but >> people are okay now with reading from the nervous system right people are okay now with the fact that our phones are recording everything that we're saying remember while we're like is it really listening how could it really know it's a little bit like the autonomous driving >> like in San Francisco like I got in a Whimo. I didn't even think about it. I
47:37
I didn't even think about it. I just like got in.
47:39
I think measurement of the nervous system directly in waking states is the next mental hurdle and I think it's going to be a healthy one to to cross.
47:49
Right now we get heart rate, HRV and a few other things but mostly heart rate and HRV and from that we get told how stressed we are, how well recovered we are, how well how well we are sleeping.
48:00
None of that is direct readout from the autonomic nervous system.
48:03
actually have a former postoc of mine who did her undergraduate Stanford or graduate work at uh Harvard was at Caltech briefly. Her name is Melissa.
48:12
She's a brilliant neuroscientist and now biotechnologist.
48:15
She's developing a tool that it's like a little cuff that actually directly measures activity from the autonomic nervous system and then gives you a readout. This is so cool.
48:25
I've got I got to try it.
48:25
It gives you a readout at the end of the day of how different activities and different patterns of speech and breathing in you related to levels of of distress versus ustress.
48:38
Right now, we just think all levels of increased heart rate and decreased levels of HR RV are bad.
48:41
But she's discovering that there are certain things in your day like when you're stressed out doing things that you love that actually sets you up for better sleep, more focus.
48:50
that the data have kind of hinted in that direction for a while, but these devices of the sort that she's developed and she's um brought this to police departments, first responders, and eventually this will be a broadly available technology.
49:04
Direct measurements from the nervous system of yeah, how stressed are you when you are stressed or are you actually doing great?
49:10
You're just you just are in a high arousal state.
49:12
That might change your perception of how stressed you are.
49:16
I think accurate feedback about those things will have a real positive effect on our health metrics.
49:22
Um, maybe you'll discover that there are a lot of things in your day that really stress you out that you weren't aware of.
49:27
You'll also learn how long is the tail on your stress from a given stressful interaction. Stress in air quotes.
49:34
How well are you focusing will probably need to be picked up from measurements of um pupil size changes.
49:42
This is how it's done in animals.
49:42
This is why I think confidently this is it'll be done from eyeglasses.
49:46
So you can get a lot of access from a wristband and eyeglasses or an eye mask and sleep.
49:49
I think we're people are going to be really comfortable with that. Okay.
49:53
The big one is how willing are people going to be to set up their entire brain for a vulnerability to non-invasive control.
50:03
So we're not going to drop wires into people's brains, you know, for a while unless they have a clinical issue.
50:09
maybe something under the skin, but you still don't have access to all the neurons.
50:13
What I want for me is I want access to all the neurons where I can turn things up or turn them down, at least by brain structure.
50:20
And I have control over it, right?
50:22
There has to be some benevolence written into that, you know, and vaulted into the device, right?
50:26
We can't have things that just like and you just, you know, suddenly you're in a rage.
50:29
You would hope that the companies building these things would put safeguards in place.
50:34
They have them for veagal stimulators.
50:36
Why wouldn't they have them for brain stimulators?
50:37
And so the vulnerability or let's call it accessibility that I'm talking about would be the following.
50:42
My lab when I was running a lab and and a lot of people tickle neurons write to neurons increase their activity a little or a little bit more or a lot these days not through electrical stimulation but by putting some sort of gene in them that isn't normally expressed in them.
51:00
Typically, these are genes that express channels that come from either you know algae or you know other things like nonhuman little things. Sounds scary, right?
51:10
But the way this is done is you can do it locally by making one injection.
51:13
Okay, problem got to breach the skull.
51:15
Or what a lot of people do is they will inject an animal with an adnoassociated virus or some sort of virus that can stably express genes in all the the types of cells that you want.
51:28
You can direct them to neurons.
51:30
You can direct them to immune cells.
51:30
You do this by putting specific promoters.
51:33
Sounds fancy, but straightforward in in primates and mice and and so on.
51:35
You can do this in humans.
51:38
They've done it in humans for other purposes, but it's more localized, like into the eyes.
51:41
So, here's where we're going.
51:43
This is where we're going to end up.
51:44
I know it sounds scary, but at some point in the not too distant future, if you're willing and it can be done safely, you get an injection of a virus.
51:52
Everyone goes, "Oh my god, it's going to make me sick."
51:54
No, it's not going to make you sick.
51:55
It's not the active virus.
51:56
The virus is just a a vector.
51:58
vector. It's just a carrier from for some genetic cargo that puts into your brain a channel such that if you have a hat on, unless I'm making this up, like you have a like a think about like a wool cap or a or or baseball cap, that
52:11
it can direct stimulation of only those neurons because it will cast a non-specific stimulus like a cone of maybe light that can go through the skull like long wavelength light that seems the most likely or ultrasound in a non-specific way. So, not illuminating
52:25
So, not illuminating or activating the whole brain, but it'll sort of send a beam of sound or light onto these neurons that if they express that tag will be active.
52:33
You can increase the intensity of the light.
52:36
You could flicker the light.
52:37
You're going to we'll work through all the different parameters that allow you to turn those neurons from, you know, inactive to active to more active to hyperactive and and dial it down.
52:46
And then with most likely through AI, you're not going to be turning a knob.
52:49
you if you're somebody who is suffering from um severe uh motivational issues or you have healthy levels of motivation, you want to ramp it up, it'll just increase the stimulation.
53:01
Now, does this open up into people, you know, cranking the circuit for themselves? Yeah.
53:05
But we also have this thing called caffeine and we also have this thing called methamphetamine.
53:12
Now, methamphetamine is a problem.
53:12
Now, methamphetamine is a problem. 90% plus of the world's population adult world's population drinks caffeine every day which increases increases excitability in the brain basically it's like a blunt >> blocks the thing that's that shuts down excitation but you know the net effect is more excitation you know how much
53:29
coffee you can drink at a given time of day given how much sleep you've had >> you know you'll decide how much alertness you want to have but the what I guess I don't have a better word for it the opportunity or vulnerability of a given set of neurons will be set by some genetic thing that will be introduced through a virus. Maybe it's an ANDgate. Maybe you Maybe it's an ANDgate.
53:50
Maybe you also have to take a pill.
53:52
So, you can't just have the virus and the ultrasound.
53:56
You need a third factor there.
53:56
So, you know, it's it could be an ANDgate.
53:58
It could be um you can have any number of different safeguards in there.
54:02
But these people with veagal stimulators can unplug them, too.
54:04
So, I I know it sounds scary, but it's absolutely going to happen for the people that want to do it.
54:11
I think not everyone's going to want to do it.
54:13
And right now the reading and measurement from the brain and body are are freaking some people out.
54:18
You know, I put out a post on X a few weeks ago like, oh, if the cost of whole body MRI comes down, this is I can imagine most people would want it.
54:26
I know people who have, you know, told me they've saved patients lives because they went and got this done and saw a tumor and we took it out and the neurosurgery community did not like that.
54:37
I thought it'd be like, oh, more business for them, but they did not like it.
54:41
It's the public gaining more access to their own health data is scaring some sectors of medicine.
54:50
Dermatologists, opthalmologists love the AI and the more more measurements better, but you know, a lot of people are saying like I think the Wall Street Journal just put something out saying like whole body MRI is they basically said it's bad. You don't have to do it. I'm assuming it's safe.
55:04
I'm assuming it's safe. if the cost is low enough or insurance covers like I don't I I just don't get the logic but my friends in medicine tell me like we all know within 20 months I don't know why 20 and not 24 within 20 months it's going to be common place because the cost is coming down just like blood
55:21
testing everyone was resistant to blood testing and genetic testing >> I'm old enough to remember the 80s when it was like will you get your your your genome mapped it was like what if you have the Huntington's gene what if you're going to get would you want to know they had like episodes of 60 minutes about this. Now, it's very Now, it's very simple.
55:37
You want to know, you go take the test.
55:40
You don't want to know, you don't take the test.
55:41
No one's talking about whether or not getting your genetics done is worthwhile or not or scary or not. It's up to you.
55:46
Same thing with your blood.
55:48
>> It's so interesting to me that through all this, so many of the things that that you've written about or I've seen you talk about are indirect ways to affect these same end states.
55:56
And it sounds like what you think the arc is is just uh away from the blunt tools and towards direct highly precise tools through technology over time.
56:07
>> More and more specificity.
56:07
That's what you want as an experimental neurobiologist.
56:10
The early days of neurobiology were like lesion this or find a patient who had a spike through his head and oh that's what the orbital frontal cortex does.
56:16
It's involved in morality.
56:17
No, it's involved in contextual decision-making strategy. That's Phineas Gage.
56:21
Certainly not the whole story, but it got us through HM.
56:25
He's got lesions in his hippocampus, can't remember new things.
56:27
We now are at the level of tickling specific neurons that are involved in a particular memory or expression of a particular behavior using chemical genetic tags, um, using light, using sound.
56:39
I mean, we only have so many different ways to manipulate neurons.
56:43
But in the health realm, I love that you're bringing this up because it really bridges the two two areas that we've been talking about, public health discourse and neuroscience, right?
56:53
Reading and writing to the nervous system.
56:54
It bridges the two because what are we talking about? Get morning sunlight. Why?
56:57
To set your circadian rhythm, spike your cortisol.
56:59
It's very seems like a blunt tool, but there's a circuit in place from your eye to your hypothalamus and on and on that that is there for that purpose.
57:08
So, it's not biohacking, right? This is important.
57:12
It's not like using a paperclipip to fix my glasses.
57:13
That's not what the paper clip was designed for.
57:16
It's not a good solution.
57:17
It's a temporary solution.
57:17
The problem with a lot of pharmarmacology like SSRIs, believe it or not, are have helped so many people with true clinical grade OCD.
57:26
They were overprescribed for depression.
57:28
And really what they do is increase serotonin, which allows for more neuroplasticity.
57:32
Now everyone's down on SSRIs, understandably so, although they have their place, but everyone's really excited about psilocybin. What is psilocybin?
57:39
It increases serotonin massively.
57:41
So it unmasks lateral connections in the brain, allows you to form new associations in a very condensed time frame.
57:48
Sometimes it works great, sometimes not. But it's interesting. Same thing with MDMA.
57:51
Create really massive increases in neurom modulators in a specific context of we're going to work on this thing, this pain, this issue, this trauma, this depression, and you get more plasticity than you do if you're just, you know, lathing away at the problem through talking about it day in day out.
58:07
You need the therapy, but what did you really do to create plasticity?
58:12
you put serotonin through the roof with psilocybin or in the case of MDMA, you increase serotonin and dopamine and you have this heightened opportunity for plasticity.
58:20
Okay, TMS or what I think will soon happen is combine transcradial magnetic stimulation and pharmarmacology in order to work through a clinical issue that is of you know emotions or mind like depression like PTSD.
58:36
So these two things are going to start to intersect ADHD with stimulants. Yep.
58:40
Ramps up activity in the prefrontal cortex and you can focus better on things that you normally wouldn't be able to focus on.
58:49
It's just, you know, non-specific focus enhancer because it increases activity there.
58:52
You could also do sleep creatine in particular when sleep deprived. Is it like aderall? No.
58:57
But those two things, great night's sleep plus some caffeine, you know, you're pretty close to aderall level effects.
59:04
It's just that the people taking aderall aren't getting great sleep.
59:08
And so you're really talking about tools of different types, different margins of safety, but they are all very blunt because all these receptors are expressed everywhere.
59:17
So you get, you know, um sexual side effects, you know, weight gain or excessive weight loss with certain uh anti-depressants or hypersexuality with certain drugs, etc.
59:28
because these receptors are all over the brain.
59:30
The same thing with electrical stimulation.
59:33
You just want more spatial and temporal specificity.
59:35
And I it has to go that way. It has to go that way.
59:37
Neuroscience went that way in terms of reading and understanding the nervous system.
59:41
You can talk about Daario's work for instance.
59:44
No one talks about his work in this realm, but he was recording in Mike Barry's lab from retinas.
59:48
Usually a salamander retina or some other creature and they record as many neurons as you could and then you knew what visual signals you were giving the retina.
59:55
So you knew the input, you knew the responses at the lower photo receptors, the output cells, what we call ganglin cells, the signals going off to the brain.
1:00:02
And the goal was get as much information about about the total collection of neurons responding to an image so we can move from image to perception deep in the brain.
1:00:11
Now you're still a few steps away from the actual perception which takes place in the brain.
1:00:16
those and the guys that they were trained under Marcus Meister and other those were heroes of our field right because dropping electrodes in an area and going and buzzing and like the animal goes into a rage or it starts mating or whatever that's super cool but then you have to move to like what are what's the nature of the switch in real
1:00:35
life and people are studying those things what moves an animal from exploring mating to actual mating what moves an animal from exploring an aggressive interaction to an actual aggressive of interaction, but these are all still very lowlevel behaviors and motivations and we're just starting to understand those. So the
1:00:52
So the cyborg thing like can I increase your creativity?
1:00:57
We're not even close to that.
1:00:59
We don't even know what circuit >> or IQ or something. >> Yeah.
1:01:02
I mean you you could imagine stimulating more memory capacity, but you might give up something.
1:01:08
You want to hear something super creepy.
1:01:10
This might freak out your audience, but it's true.
1:01:14
So a few years back uh there was a guy his first name is he that's how you pronounce it h um I can't pronounce his last name he actually had done his post-docal training at Stanford and then he moved on to his own lab in China he announced to the world at a meeting that he had done crisper in um twin babies he
1:01:31
had deleted the HIV receptor and the story was and I don't know if it's true or not but that the father of these children was HIV positive and um he wanted to save these kids from getting HIV AIDS Okay, so there was this moment in the medical science community where no one knew how people would react. Were
1:01:48
Were they going to give him a Nobel Prize or or like throw him in jail?
1:01:51
He went to like the end experiment.
1:01:54
We know how to do this now.
1:01:55
The technologies exist, but he just did it.
1:01:57
he just did it. And there was this really weird sociology around this in the science community where people who had worked with him prior who had exchanged emails with him like their emails now were like people were digging into the emails and it was clear that the communications from a lot of these people were sort of the hey be careful
1:02:16
but like is it working is it working but everyone was waiting like if he's gets in trouble I don't want I didn't know the guy right and I didn't know the guy for the record I didn't know the guy I knew of him because you know I knew the lab he worked in Um, and I knew about this work, but it's like, am I going to be a part of this? Like, was I important
1:02:31
Like, was I important for this important discovery or or should I dissociate myself from this?
1:02:36
Cuz it turns out the world turn decide like, no, this is ethically this is bad.
1:02:40
The Chinese government came out and said that he would be his lab would be taken away and he would be punished in some way.
1:02:45
I don't know how he was going to be punished. >> Disappeared. >> Yeah.
1:02:48
Do you know what that guy's doing right now? >> No. >> Yeah. He has a laboratory. Do you know where?
1:02:52
Purportedly in Austin, Texas. >> Okay.
1:02:55
Now, I don't know if that's true or not. Okay.
1:02:57
So, what that means is that like like that just I'm like what does what does this mean?
1:03:05
So, my first reaction is like how did that happen? Okay.
1:03:08
My second reaction is wait of course he wasn't the only person doing this like you know this is happening in in labs all over the world.
1:03:16
It's just no one's talking about it because he proved that it's dangerous to talk about.
1:03:20
Now I think it's very important to have the ethics and the you know like the committee set up for this kind of technology.
1:03:26
But then you take a step back and you say like where are we in the world of genetic engineering humans and you say okay well you know they do um testing of amniotic fluid in you know baby you know pregnant women babies it's common place people can refuse it I believe but in general that's done.
1:03:42
People are screening embryos for IVF.
1:03:45
There are companies like Herasite and um Orchid.
1:03:47
Some are more focused on trying to see if there are any diseases.
1:03:50
Um, some are trying to link certain genetic patterns of expression to autism but also to IQ, to height, etc.
1:03:58
So, you can see where this is going, right?
1:04:00
And then, of course, there's this thing that we call partner selection, right?
1:04:02
People choose in most cases, not always, but they choose who to get sperm from or eggs from in the context of of a relationship, right?
1:04:12
or if people are using a sperm donors and that they're choosing on the basis of like you look at the criteria and the criteria like height, where they go to school, you know, what do they look like, you know, so there the lines between these haven't been cleanly defined, but you can see it's it's there's a gradation there.
1:04:29
Now, I don't know if he is actually in Austin, Texas, or if he's actually doing these experiments. I don't know that. I want to be very clear.
1:04:35
Um but I find it fascinating and important to understand that like people are going to run with these technologies.
1:04:43
How fast they run, where they get implemented isn't clear. Okay. What about memory?
1:04:50
The HIV receptor supposedly is also linked to some aspects of of neural circuit formation that are linked to memory.
1:04:57
So there was this other layer of those experiments that everyone knew in the neuroscience community but wasn't talking about which was was he actually trying to both render those kids immune from HIV infection but also make them super smart and no one's been able to answer that question conclusively.
1:05:15
But there is this idea that maybe pe people are genetically engineering people that have some gene expression or lack of gene expression which renders them more cognitively or physically capable.
1:05:27
You go, "Oh, that sounds crazy." Yeah.
1:05:29
And the folstatin gene has been mutated in animals and there are people doing gene therapy for folstatin to try and build more muscle.
1:05:36
If this was 15 years ago and you and I were having this conversation, you'd be like, >> "This guy's out of his mind.
1:05:43
>> Guy's out of his mind.
1:05:43
This stuff has everything I just described has happened.
1:05:47
Why it happened, exactly what they were trying to do, unclear whether or not it's still ongoing, whether or not this guy's actually in Austin, Texas doing these experiments or he's someplace else or he's sitting in a prison someplace in China, I don't know. Okay.
1:06:00
I think it'll be interesting.
1:06:00
The internet will tell us, right?
1:06:01
I guess I'm more excited than concerned provided people are talking about it and people are thinking about it really carefully.
1:06:10
One of the beautiful things about social media is nothing stays a secret for very long, if at all. Nothing stays a secret.
1:06:16
There are no secrets anymore.
1:06:16
You can have a vaulted conversation with somebody. That absolutely is true.
1:06:20
But as soon as more than two people know about something like you can't exist in this world without leaving a digital footprint.
1:06:29
So sooner or later we'll hear.
1:06:31
You know, >> it seems like the arc of all this is just control, like control of genetics, control of brain states, control of like all these things through technology over time.
1:06:42
And this is very much like a William Gibson future is here just not evenly distributed yet.
1:06:46
And these are all the, you know, future is here type things.
1:06:49
What excites you most of all this stuff?
1:06:51
Like if you had to pinpoint like this is the thing that like if I force you to go start a company or something and just focus on one thing.
1:06:57
I spent a lot of time thinking about media and culture and just humans generally.
1:07:03
So to me the most exciting thing is that because of social media we're all in the same campus X is that campus Instagram to some degree but those are the campuses for the communication about these things.
1:07:18
And so what I'm excited about is the idea that we've got so many more people learning about things in their field and adjacent to their field that there are a bunch of things that we can't predict that are going to happen.
1:07:31
Like someone in the human gene therapy space who is an amazing educator, has the charisma and the ability to talk about these things, but also has the chops, really understands it is going to move that space forward at tremendous velocity at some point.
1:07:45
The issue is that it was a scientist just like doing his thing and he just kind of went rogue and did it.
1:07:51
He didn't check with anybody.
1:07:52
You know, when I was coming up, you did experiments if at night like in the goal was like don't kill yourself, don't burn down the lab, like don't break protocol, but like do experiments.
1:08:02
Now it's changed a little bit.
1:08:03
Everyone's a little bit more paranoid.
1:08:04
I'm excited that somebody and they're starting.
1:08:07
I think that people are thinking about neurochnologies to read and write from the nervous system in awake states.
1:08:13
And I my own interest right now is really understanding the waking states.
1:08:19
We understand slowwave sleep, deep sleep, N1, N2, N3 sleep.
1:08:23
Wrote a whole chapter in the book about sleep, its architecture, how temperature changes one or the other.
1:08:26
Heat up the bed in the morning or the room in the morning. You get more REM. Why that?
1:08:30
Okay, we know all that stuff.
1:08:30
We know so much about sleep and how to measure and and now nudge and maybe even dial in sleep really precisely with these eye mask type tools.
1:08:39
Changing the room temp is pretty crude compared to that.
1:08:42
What's also helpful, I want to understand waking brain states.
1:08:47
I don't know how to describe the state that we're in.
1:08:49
And it's not a state like REM is is not language about how you feel in REM, right?
1:08:56
It's rapid eye movements.
1:08:56
There's something associated with the state that we're in right now.
1:08:58
Like I'm alert, I'm focused, I'm enjoying our discussion, you know, but we don't h like what is this state?
1:09:03
We need much better understanding of waking states and which waking states lend themselves better to which activities.
1:09:10
then we can start writing to the nervous system to generate those states with a lot of temporal and spatial precision.
1:09:16
That to me seems like the most important thing to resolve right now and it's totally doable.
1:09:22
I'm not the person to do it because I'm no longer running a lab.
1:09:23
The problem with neuroscience as a field.
1:09:29
There's a little bit of a problem with academia but even the biotech sector related to neuroscience is that people tend to work on things that are like four degrees off from what their training was.
1:09:38
Actually, even though I've never met him, I think Daario, even though I disagree with a lot of things I hear from him, but you know about AI, I think that it's interesting someone came up through neuroscience in this like quite different but related field, right?
1:09:51
Sam I've spoken to is extremely smart about the neuroscience.
1:09:54
Extremely smart as is Zuck. Okay? As is Andre, right?
1:10:00
you know and on and Elon obviously understands what he's trying to achieve with Neurolink and he's extremely savvy with respect to like what can be done now where we need to go.
1:10:09
So in a lot of ways the technologists who used to just engineer stuff like they're becoming neuroscientists and I love that because neuroscience has always benefited from bringing people in from other fields.
1:10:22
You can't give them the whole problem entirely because as soon as they sink their hands into a brain they realize this is not a computer.
1:10:28
this is not a computer. It's something a whole lot more complicated but we but bio-engineers are getting very very good and people like Eddie Chang obviously Neuralink's doing this Matt McDougall and the folks there and as are you know Sam Zuck and Dario like that's that's a pretty killer lineup >> you know and Elon those four right those
1:10:49
are the big four right those are the athletes of brain exploration now and I think most people don't realize that and I'm not sitting here like what do the kids say I'm not trying to like glaze I think it's just awesome You want people coming in who have outside expertise and can leverage the best minds like the best neuroscientists and engineers. So
1:11:04
So I'm all excitement about it frankly.
1:11:06
Um but I think we need better definition of waking brain states.
1:11:10
I think that's the biggie.
1:11:12
And the reason I mentioned those different silos that I've touched into is that anytime you see a field, whether or not it's action sports or it's science or it's medicine take a big leap forward, there's always this thing that we talked about earlier where people get into it.
1:11:24
Some people go public facing.
1:11:26
They kind of push the margins a little bit.
1:11:28
Then it gets like too crowded.
1:11:30
People start getting wacky to get more signal to noise on them and then the thing kind of dies down and then there's this surge of really accessible useful technologies and information.
1:11:39
2027 28 are going to be a kind of a a low-level noise in my estimation around the health space.
1:11:46
We kind of that's what the book protocols was about. That's my thesis. We got it.
1:11:50
I'm not going to keep talking about morning light.
1:11:51
For God's sake, I'm starting to tire myself out, you know.
1:11:55
So, but the reason I can move on from it is because I know it for certain.
1:11:57
What's in the book are the things I know for certain.
1:12:00
So, now that that my thesis is turned in and people can do with it what they will.
1:12:04
I think it has things of value.
1:12:06
Certainly information, but maybe hopefully things of value to people.
1:12:10
Now, it's time to move into some other realm.
1:12:12
And you can probably tell from today's conversation, I didn't realize this was going to come up.
1:12:14
I am very, very interested in reading and writing from the awake nervous system.
1:12:18
Eddie Chang and I talk three times a week for hours at a time. We take walks. Where is neuroscience? What's next?
1:12:25
Like I'm just super excited.
1:12:28
It's gonna it's going to be great.
1:12:29
I promise you there there safeguards we need in place.
1:12:31
But like the best people are on these problems. The best people.
1:12:36
And that's why it pisses me off when the traditional media tries to slow these people down.
1:12:39
Like okay everybody make your public statement about how you're not going to blow up the world.
1:12:43
It's like of course like you want them to do that.
1:12:45
It also by the way it doesn't pacify anybody.
1:12:49
But of course we need the ethics.
1:12:49
We need the safeguards in place.
1:12:51
But I'm nothing but excitement about this.
1:12:53
But then again, I'm born and raised in Palo Alto.
1:12:56
>> I did not exactly expect our discussion to focus so much on neuroch and waking brain states and things like this.
1:13:00
But I honestly hope you and I could do this once a year to get like check in on the state of this stuff.
1:13:05
It does seem like if you really think ahead from the current stuff in AI to where this is all going, of course, inevitably like the intimacy of technology into us is going to increase and this is sort of like the final frontier.
1:13:18
so incredibly fun to talk to you about.
1:13:20
When I do this, and I hope it's the first of many, I ask the same traditional closing question.
1:13:24
What is the kindest thing that someone's done for you?
1:13:28
>> The kindest thing, all right, this is a bit of a weird one, but I've carried the the message that I got forward through basically everything.
1:13:36
And if once people hear it, if they thread it back through portions of today's conversation, I think they'll they'll know how I've done that.
1:13:44
So, when I was in graduate school, I initially joined a different laboratory. you do rotations.
1:13:48
And I joined a laboratory doing excellent work, very popular at the time that was really on the cutting edge of molecular genetic techniques for looking at neurons.
1:13:58
And it was all the rage at the time.
1:14:01
But I had this like absolute love obsession for the work that I had done in my second rotation on stuff and in a field that was pretty crowded.
1:14:13
And I found myself having joined this other lab and sneaking into the the lab that interested me more at night and doing experiments.
1:14:24
And the woman who ran that lab, which is my graduate adviser, uh Barbara Chapman, she came to me one day and she just said, "Listen, I'm totally okay with the fact that you didn't join my lab."
1:14:32
Her lab was already very successful anyway, publishing papers in science, etc.
1:14:35
and she said, "But you just seem to really love this stuff, and the only thing that's really going to determine your success is how badly do you want to know the answers to the questions that you're working on." I was like, "Okay."
1:14:50
So, I broke up with the other lab. I joined her lab.
1:14:52
We published eight first author papers.
1:14:53
My career went, but that was all the consequence of working on things to try and answer questions that I was most curious about.
1:15:04
And that was an incredibly kind thing to do.
1:15:07
It also required a lot of humility and boldness on her part because she was basically saying like dump them come come back to me.
1:15:15
>> And I had to trust that it wasn't because of some sense of rejection in her. And it wasn't.
1:15:20
She had extremely strong ego.
1:15:22
And honestly, I think that's the kindest thing uh anyone's ever done for me because it showed a belief in me.
1:15:30
It showed that she understood that I didn't have enough self-standing and enough frankly enough guts to just say, "I don't want to do the thing that everyone else is super excited about.
1:15:37
I want to focus on the thing that I'm most excited about."
1:15:41
Which takes a strong mind and is much easier to do once you've had some significant success in a field.
1:15:47
It's easy to do when you're like, "Oh yeah, no one everyone said that that was done. That area was done.
1:15:50
No one listens to that music, but then we had like two platinum albums."
1:15:53
It's easy to just carry on.
1:15:54
But when you're making the decision, it's to go into this area that, you know, most people be like, why would you go there?
1:16:02
Like, no one works on that anymore.
1:16:04
And it turns out that that the wheel of the of the field rotated too.
1:16:09
And I found myself exiting my PhD lab with the skills that were best suited to what was most important in the field next.
1:16:18
And I had to be very careful because now the landscape matched my internal curiosity, right?
1:16:25
And now I had to make sure yes I'm going into this field because for the right reasons and it and it was true and likewise with starting a podcast I I would loved running a lab.
1:16:32
I truly did love teaching at Stanford. I still do.
1:16:37
But it was really I just have this itch.
1:16:39
I've got this knowledge in me that I know people can benefit from.
1:16:40
I did not anticipate what came with being public facing that was like not anticipated.
1:16:44
I had no training right in that in being media and like [ __ ] it I want to do this and I just you know like you know pulled all the stops out and just you know went for it. >> Here we are.
1:16:57
Can you say that line one more time?
1:16:58
What was the her phrasing of it?
1:17:01
>> Success is determined by how precisely you match your genuine curiosity to the work that you do.
1:17:06
You do have to understand the field you're in and pay attention to it because all experiments are so hard.
1:17:11
Building any company is hard.
1:17:13
doing any podcast if it's done right is hard.
1:17:15
So, you have to make sure that it's really true to you.
1:17:17
And not to puff him up too much, but I think one of the reasons why Elon is admired by so many people.
1:17:23
Yeah, some people dislike him, but I think one of the reasons why deep down people either greatly admire him or envy him is not his money.
1:17:29
It's his ability to ignore what pe people say about what he should be doing.
1:17:36
I had a guy come on my podcast who I actually like and respect and he he was telling me all the things that Elon and other the top technologist should be doing.
1:17:45
They should be helping the people this way and that way.
1:17:46
And I'm like wait but like electric cars and I do think open AI is heading to some very interesting things that relate to medicine and benevolence there and and on and on and he's like yeah that's what they should be doing not this other stuff not Mars.
1:17:59
And I'm thinking like that's like telling Metallica to play the Grateful Dead.
1:18:03
The Metallica are Metallica because that's what they love.
1:18:05
That's the music they [ __ ] love.
1:18:07
And the Grateful Dead are the Grateful Dead because that's the music they love.
1:18:12
Like, you have to be yourself.
1:18:12
The big tragedy is when people don't go in the direction of their genuine curiosity because they're trying to quote unquote succeed.
1:18:22
>> So, the kindest thing someone did for me was to gently but very clearly tell me, follow your curiosity, answer the question, solve the problems related to that, and you can't go wrong.
1:18:32
And to not do that is is a kind of a slow death frankly.
1:18:37
>> A wonderful awesome place to close.
1:18:39
Andrew, thank you so much for your time. >> Thanks.
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