Andrew Huberman - The Frontier of Neurotechnology - [Invest Like the Best, EP.494]

There's a very interesting thing happening that relates to a piece of your work, which I haven't seen you talk about as much, and so maybe it's a fun place to begin. It feels like we're now bandwidth-limited on the most talented people's ability to do work. It used to be that the rest of the world couldn't keep up with the most talented people, and they would get frustrated that no one was moving as fast or as efficiently as they were.

There seems to be something flipping, which is that some of these people would earn a really high return if they could generate more energy, maintain more energy, and not burn out. I heard this from several great entrepreneurs this summer. I think maybe Elon has just gotten into everyone's head, that the real greats are going to run multiple companies.

Technology unlocks so much potential for the most talented people, and so this seems like an actual bottleneck: these people's energy. I'd be curious, in all your research and study, what you've learned about the component parts of this—generating energy, maintaining it, clean versus dirty fuel, and long-term performance. All of these things are fascinating, and I think they're actually important to the degree of progress, so I would love you to just riff on all that for a while.

1. The Energy Bottleneck

With the caveat that Elon represents the apex of being able to do multiple huge things simultaneously, I don't think he has any peers in that regard. In fact, one of the best multibillionaire investors from the Bay Area, who may have gone to Stanford and may have been part of the early PayPal team, has asked me, "How is it that Elon does this?" I'm like, "I can't tell you."

Physiologically?

Physiologically. I mean, there are examples throughout history of people who seem to require less sleep. They just have more energy, and most people can get their energy up. There are a lot of healthy ways to do that now, and I think we've undergone this huge shift whereby everyone understands you have to sleep eventually, and you have to know your own sleep requirements.

So to delude oneself into thinking you only need 4 or 5 hours because Elon only needs 4 or 5 hours, that's ridiculous. An honest self-assessment about how much sleep one actually needs to perform well, and perhaps best, and what you can get by on if you can't get that—that's an important thing to understand.

But most people know. For me, it's 7 hours; I feel great. 8 probably puts me into the day a little bit groggy. 6, I can manage just fine. 5 for 1 day, or a sleepless night, I'm good. 2 nights like that, of 4 to 0 hours of sleep, and I'm cratered. I think most people are similar.

What's really changed is that we have effective, healthy ways to build our energy up. We know to sleep. We can talk about exercise and caffeine. Some people are using nicotine. Yes, it's addictive, and it raises blood pressure, but it does put people into that focused but relaxed mode.

I always say, if you really want the benefits of nicotine, don't use it very often. If you want the actual cognitive-enhancing effects, or the focus-enhancing effects, then you have to not be a chronic user and instead spike your system with nicotine at low amounts every once in a while.

Setting Elon aside, with the understanding that he represents that extreme in terms of energy and sleep requirements being very low, I think what's really happening now is that people are hopefully doing this self-assessment. I would hope people would have an honest conversation with themselves and say, "At this point in my life, with or 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 that it's not enough?"

And I think most people know that. Okay, so that's step 1.

The next one is something most people don't ever talk about, which is that some people actually just have more energy. They can focus for long, long periods of time. They have a ton of energy to run, and they have a ton of energy to then go work.

But what we never ask is, what is that person's internal state? I know people who can do all of that, but they're kind of redlining and using a lot of stimulants to do it. Or they're not using stimulants to do it, but they're redlining. Then at night, they're having a hard time switching it off, and so they're not resetting their system.

Some people, however, wake up at 4:00 a.m., work out, handle business, deal with family, go off to work, get back to business, come home, and pivot and task-switch really fast. I don't think these things are necessarily stable features throughout our entire life.

A lot of young guys come up to me and ask, "What should I do?" The Oracle said it best: know thyself. You really have to be honest with yourself about what you need in order to do something for a long period of time.

Now, that said, I do recall working 80, even 100-hour weeks in graduate school, and that served me well. I mean, it eventually led me to tenure at Stanford, et cetera. I do think that if you can pull it off, from 0 to maybe the first 4 years of starting a company, or if you're in medical school, the goal is: don't die. Get as much done as you can, and don't impair yourself with an injury or chronic disease.

We don't really define this thing, optimization. Then you start to pivot into, how can I insert components of rest along the way, maybe during the day or across the week or the month, that really allow me to access my best levels of focus and creativity?

But I'd be naive, and I'd be lying, if I said somebody starting a company in the AI realm in the Bay Area or elsewhere these days is going to sit down and hear, "Listen, you really need 8 hours of sleep. You have to do your resistance training. You should do some breathwork." No, none of that.

What they should determine is how much energy they actually have. And you've met these people, right? Occasionally, you'll run into someone like Jimmy Iovine or some of the folks doing AI at Meta, and they just seem to have an extra gear. Some people have this extra gear.

Now, there's one other component—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.

2. Learning To Switch Off

Yeah, can we go deeper into that one? To be very selfish about it, if I were to self-diagnose, the biggest problem I have is downshifting. Sometimes it'll take literally 4 hours to go from a crazy, exciting, awesome day to being able to fall asleep, or just to stop the mind. If I could bestow myself with any gift, it would be what you're describing. So what is the research on how to do that?

In terms of sleep, there are a couple of prerequisites for sleep. There are a bunch of don'ts, so obviously you don't want to drink caffeine too late. Being under too much bright light late in the day can make it difficult, but a lot of us can't control that. Alcohol and cannabis impair the quality of your sleep, but help you get to sleep. We all know that by now.

But in terms of being able to turn your thoughts off, this is a very, very difficult thing for people, for good reasons. The brain wants to think, plan, remember, and organize itself around what's coming next because such a huge aspect of brain function is predicting what's happening next.

The first requirement is to turn your thoughts off. The second requirement is to slow your heart rate down. That's purely of the body. The third is that you need to forget about the position of your limbs in space.

So let's work through each one systematically. For the first one, turning your thoughts off is a skill. We can think, predict, and remember, but we also can get into pure sensation, and that's the gateway to turning off your thoughts.

This doesn't come from Eastern tradition per se, although 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? You have to focus on pure sensation. You start by focusing on the surface of your body.

If you can detect your heart rate, some people are very good at what's called interoception. They can get pretty accurate measurements of their heart rate without pressing on a vein or artery, and they're just listening to their own breathing. They're listening to the sounds in the room. They're bringing their conscious awareness to the body, and it generally helps. This relates to the second thing: slowing the heart rate down by doing long exhales.

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. Meditation has you focus all of your attention on your breathing, or all of your attention on some region behind your forehead or your hands or whatever. In this sort of practice, what you do is migrate your attention to your feet, to your legs, to your breathing, to sounds in the room, then back again. This might sound really squishy, but you're moving away from thinking and planning to pure sensation and perception, and you're literally bringing your perception into the present.

Remember, this is one door in front of turning off your thoughts. To actually turn off your thoughts, your heart rate has to drop a certain amount. Those long exhales drop your heart rate through something called respiratory sinus arrhythmia. Arrhythmia makes it sound dangerous or bad, but it's actually very good.

As you're breathing, the size of your heart is literally changing based on the amount of space it has because of the movement of the diaphragm and the filling of the lungs. When we inhale, our heart rate actually speeds up a bit. When we exhale, the heart gets a little bit smaller volume-wise, and the blood that's in it therefore moves a little bit quicker per unit volume, and the brain sends a signal to slow the heart down. So when you exhale, you're slowing the heart rate down through this thing that we call the vagus nerve.

If you want to slow your heart rate down anytime you're awake, 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 your lungs are empty, and then just passive inhales. Normally, when we're really activated, we're doing a lot of inhaling and passively exhaling.

The last piece is being able to turn off your perception of your limbs relative to you. That's something we call proprioception. There are 3 ways to do this: one is old school and everyone accepts it, one sounds pretty wacky, and then there's a new technology that's coming out that I wish I had developed, which I think is going to make people more comfortable with the second one.

Believe it or not, there have been studies of what puts babies to sleep and what puts adults to sleep without pharmacology. It turns out that the rocking and pacing we do with babies at a certain rate—parents figure this out on their own—puts them to sleep. It turns out that you can build a bed that rocks at a certain frequency, and adults will fall asleep very quickly. What it has to do with is the fact that when you're moving side to side, your eyes are generating compensatory eye movements under your closed eyelids.

Our eye movements, all the time, are communicating through our brain stem to our cerebellum to control balance and proprioception. So when people are rocked this way, somehow they fall asleep more quickly. That's interesting, actually, and the frequency at which that works best and fastest is known.

I don't have a rocking bed. I don't know anyone large enough to rock me and hold me, and if they did, I'm not sure I'd feel comfortable with that. I can't imagine you would either. So there are 2 ways to approach this. 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.

I've been talking about this a lot in public education recently, and I confess it makes me feel really weird as a neuroscientist. So I'm going to preface this by saying, please don't just put the eye-movement thing out into the world without allowing me to first say that this confuses the circuit between—for the aficionados—the direction-selective cells in the retina, the accessory optic nuclei of the brain stem, and the cerebellum, and you forget about body position.

Basically, what you do is, under closed eyelids, move your eyes to one side, then the other, slowly or fast—it doesn't really matter—then up, then down. You can roll them counterclockwise and clockwise. You can do a long exhale. But really, what you're doing is confusing this system.

The reason I got so interested in this, and the reason I went to the literature on rocking babies and adults to fall asleep, is because a group out of MIT approached me and said, "We'd like you to try this eye mask." The eyes are 2 pieces of the brain; they're just not in the cranial vault, which makes them unusual in terms of parts of the brain. So the eyes are an amazing gateway to the rest of the brain.

Everyone knows about eye masks to keep the darkness out. This group has developed eye masks that measure rapid eye movement, because right now your WHOOP, your Oura, and your Eight Sleep aren't measuring REM directly. This can measure REM directly, but they designed this mask specifically to make people fall asleep faster. I thought, "I want that thing."

So I got to try it, and it works very well in the daytime or at night. What does it do? It generates these slow, back-and-forth, up-and-down eye movements through a small amount of stimulation behind your ears, because it turns out you can access the extraocular muscles well enough from that location. It's just an eye mask with some straps. You sometimes feel a little bit of the stimulation, and you're out.

Once REM sleep starts, it actually helps amplify the REM stage, and you get much more REM. I wish I had a stake in this company. I don't. These technologies are about 7 to 12 months from release, and I'm super excited about them. I'm also super excited about the fact that people can just do this on their own, and obviously babies get rocked. You could do the non-mask tool approach, or you could use the mask.

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. Of course, I'm also interested in reading from and writing to the nervous system in waking states.

You can imagine that within 12 months, or a year, of the release of the technology I just described, somebody could develop eyeglasses like this that are stimulating some component of the autonomic nervous system, so that I'm exceptionally focused at certain times of day, and then when I'm walking home, I'm in a slightly more relaxed state to capture some more of that energy.

We're going to start shifting brain states into focus, into modes for learning, and we're going to start doing it with technologies. Right now, we're doing cold showers, caffeine, and exercise. We're doing inhale-emphasized breathing versus exhale-emphasized breathing to get more alert or calm. If you think about it, all breathing exercises can be summarized as inhale-emphasized or exhale-emphasized.

Yes, we can do that stuff deliberately, but you can imagine that pretty soon there will be noninvasive stimulation devices that will allow people to do this. It will start in sleep, because we're all kind of comfortable with the idea now of measuring our physiology in sleep, and a little bit in waking states, but this is where this is going.

To return to this in sequence, you need to learn to turn your thoughts off. You need to forget about your body position and slow your heart rate down. The order in which you do that doesn't really matter. Ideally, you want to combine all 3, but I think that's going to be a significant achievement for humanity.

If you look at recovery from illness, healing, learning, stress control, and burnout—if you're going through grief or psychological stress or trauma healing, if you're trying to start a company and you've got kids, or even if you're just trying to work the maximum number of hours and you've got 4 hours to sleep and you're somebody who needs 6—you want to be able to hit the pillow and shut it off. We don't have good ways to do that except for the tools I described.

I think we are starting to go about things in a more healthy way. But what I'm talking about is people doing a thorough self-assessment of sleep need and the ability to turn off thoughts, and then training those things.

In fact, a lot of hard-driving people will come to me and say, "What workout should I do?" And I'm like, "Look, how much time do you have?" In graduate school, I worked out twice a week. I don't talk about this, but I lifted weights and ran really far because I just wanted to maintain while I worked my ass off publishing as many great papers as I could.

Later, I was doing 3 workouts a week with the weights. I do cardio 3 times a week—long, medium, and short. Take a day off. Maybe do some sauna and cold. My life's a little bit different now, or a lot different, but I do think those first years you're trying to just not die while you create this thing.

Then you start moving into some, quote-unquote, "balance and optimization." Then you get the people who have really achieved some level of mastery or virtuosity in their craft, and you get a real assessment of how accurately their schedule matched who they really were at a physiological level by looking at them and going, "They look like shit. They have a chronic illness. They look 10 years older than they were supposed to."

Or there are certain people who are phenoms, like an Elon, or you look at some people and you just go, "Holy crap, they just got an extra gear." I'm speculating here, but I'm guessing that Jack Dorsey was always a pretty calm, thoughtful guy.

That's what people tell me of him, and that's how I experience him too. But I'm guessing he's also put some work into it. 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.

3. The Health Discourse Disaster

Since you've been covering it for so long, I'm curious what you think the biggest challenge, problem, or issue is facing your whole field. 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, what is the biggest challenge facing the field today, do you think?

I feel like the public discourse around health and longevity is a fucking disaster. It is a bunch of clowns, and people are doubling and tripling down on the theatrics. I'm not saying I get everything right or that I have all the answers. I'm definitely not saying that.

I got into this at the right time, but the downside is that it was so devoid of anyone else. There were people talking about health only in the area they worked on in their lab, but not broadly. The bar for entry in public discourse around health is basically zero. You show your abs and admit you're on steroids, and you have a following. Some dude shows his abs, or some woman shows her glutes and claims to be all natural, and we believe them, and suddenly they have a following.

If that's the bar for entry, I come from a field where having a PhD isn't even nearly sufficient. It's necessary, but not even nearly sufficient to say that you've contributed something to the understanding of the brain. Tim Ferriss was talking about a lot of this stuff early on: biohacking and self-optimization. What I love about Tim is that he's remained Tim.

There was a period where he experimented. He had some things that he felt probably weren't a good idea. He talks about those—things that he wishes he hadn't done and things that he's happy he did. He's also into investing and all these other things. I think Tim's fantastic because he's being Tim.

I'm not referring to that. Then you started getting these more and more extreme versions, where people were coming in with basically no science or health training and saying, "Here's how you optimize the mind and body, and I know this because I'm doing all these things. I used to be fat, and I'm not fat anymore." I think that's fine in principle, but then it just keeps getting crazier and crazier.

What you've seen now is a big gap between, if I'm just honest, the A-tier public health educators and what used to be the B-tier public educators. It's getting bigger and bigger and bigger because one has to be true to oneself, but you also have to take the endeavor seriously. It's very easy to get attention. It's very hard to keep respect.

I do think that public health discourse is harmed when it becomes about the theatrics, and I'm not trying to avoid naming names here. I think everyone can look out on the landscape of people from Bryan Johnson to me to Gary Brecka to Dave Asprey and everyone else—there are a lot of people in the space—and ask, "Whose persona resonates?" Not just what captures the entertainment value.

What I would expect will happen next, now that we've gone from high amounts of interest in this to optimization, optimization, is that it will turn into, "Are we over-optimizing?" I think we're going to see a downturn in the number of things that people are willing to do each day. They're going to say, "This is just too much." It's gotten kind of kooky.

Yeah.

It's kind of crazy. I need more serious peers. I need serious peers with training in either science or medicine, maybe pharmacology, and they're out there, but I think those people are going to rise to the surface. We haven't seen them yet. I look forward to having colleagues like that.

I think what's going to happen is that we're going to get many, many more people trained as PhDs and MDs who will be doing serious science and health discourse—not regressing to the TikTok dance model or the focus-on-me model, but really educating people in a way that's unique, a way that I'm certain I haven't even tapped into. Someone's going to come along who's better than me.

I think this field is going into a downturn now. Public education around health, optimization, longevity, et cetera, 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. Then it will be where I would like to see it.

4. The Brain Writing Frontier

How about on the research side? What's the biggest problem facing the field?

I think the coolest problem, which is also the biggest problem, is how we can noninvasively write to the nervous system in sleep and waking states. My best friend from childhood, Eddie Chang, is chair of neurosurgery at UCSF. He's a bioengineer. He's doing things similar-ish to what Neuralink is doing, but removing brain tumors and this kind of thing.

I've been with him to surgeries, right up there next to the tumors. The patient is awake. He's probing areas of the brain. He has permission to map areas related to speech and language, et cetera. Breaching the skull is a big deal.

The neurosurgeons say, "A titanium plate would be better. It's stronger, and it lasts longer." But most people don't want to have to do that. They do it because they need something taken out, like a tumor or an epileptic focus.

I think the big one now is who can develop a noninvasive way—probably ultrasound—of selectively activating or quieting brain areas with high temporal precision. Getting people who are in locked-in syndrome to speak, as Eddie has done, or getting people who have a spinal cord injury to walk, which Neuralink, Eddie, and others are trying to develop technologies to do, is heroic.

Ultimately, and I'll go on record saying this, anyone who thinks that Meta, OpenAI, Anthropic, or Elon, whose stated neural interest is Neuralink, are LLM AI companies is perhaps going to be surprised by this prediction. Every single one of them is going to be a biotech company. They're all interested in the brain.

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, "Here's the goal." The goal is to be able to read and write from your brain noninvasively, and there are straightforward ways to do that.

The big thing is: How can you stimulate a brain area with temporal and spatial precision? How can you quiet that brain area with spatial and temporal precision? How can you dial up or down the level of quieting? It's one thing to say silent versus activated, but the nervous system has a lot of graded signals in it.

We don't think about those signals, but the communication between areas is gated and graded. Thresholds for activation change, even for things like drive and motivation. A noninvasive device where you could literally crank up your level of motivation by stimulating the nucleus accumbens and related pathways while engaging in a particular learning task or in hard work, and then turn it off so that you can capture more energy and have more of a square-wave function in your energy output—that's coming. Those companies are all about that.

That's what the real arms race of AI is about. I chuckle when I think, "The LLMs are great or terrible, depending on who you are," and I believe they're great. I'm a big fan of AI, but I'm talking about the dynamic modulation of your own neural activity using noninvasive technologies, not pharmacology.

Then, using AI, you could understand, "This level of activation in this brain area for you, Patrick, is related to a hypermotivated brain state that makes it very hard for you to do anything else the rest of the day." It would just learn to titrate.

You say, "That sounds kind of science fiction. How far off is that?" My Eight Sleep changes the temperature throughout the night to give me more REM sleep or deep sleep. It's already doing that. We're just okay with these things in sleep, and it's doing that through a powerful but indirect method: temperature change.

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. That's what these companies want to do. My field of neuroscience has to embrace this, and it is.

The people who are trying to figure out what the natural signals are that occur in the brain when people think, when people see, and when people move their limbs in a particular way—that's been the last 30 or 40 years. That's all reading from the nervous system. Now it's about writing to the nervous system noninvasively.

5. Reading The Brain Precisely

I have a stupid, basic question. What is the method by which we can read, how precise is our ability to read activity, and what does activity even mean in different parts of the brain?

Great questions. It depends on how invasive you want to get. Most people understand—or, if you haven't, no big deal—that neurons communicate through action potentials, electrical signals. We were taught, and it's still in the textbooks, that they're always the same size and shape for a given neuron. It turns out that's not even true.

There's variability there, but we sort of have this all-or-none idea: a neuron either fires or it doesn't. But there are graded potentials. You get to a threshold, the neuron fires, and it communicates with the next neuron.

Depending on the milieu there—how many other inputs there are and what they're doing—the next neuron fires. You set off a chain or not. You can record from neurons by putting an electrode close to them: extracellular recordings.

You can put a bed of nails nearby and record lots of those extracellular signals. You can impale a neuron and record intracellularly. All of that requires breaching the skull and sticking wires basically down into the brain. The methods that are really exciting are things like ultrasound and transcranial magnetic stimulation, which is used for the treatment of depression and other things. The spatial control there for stimulation isn't great.

The recording from the nervous system can go from what I just described—intracellular recording at the most extreme—to extracellular recording, and then all the way to fMRI or EEG, where people see these heat maps of the brain. You really can only measure signals at the surface, like at the cortex, which is interesting, but you're not going to get to the deeper layers. A big problem now is how important it is to understand the natural patterns of activity in detail before we start poking around and stimulating with writing.

Obviously, there are at least 2 ways to write. You can use pharmacology. What does most pharmacology do? Whether it's alcohol, barbiturates, or sedatives of some kind, what are you doing? You're increasing the threshold for activation. You're quieting the brain just by increasing the threshold for activation. You're doing it indirectly by increasing inhibitory release, so there's less excitation overall.

You think about Adderall, caffeine, nicotine, speed, modafinil, and you're talking about lowering the threshold, because those generally work by increasing neuromodulators that increase the likelihood that neurons will fire. So you're just ramping up that baseline. You're creating higher RPM across the brain and body. That's why they lead to some shaking and agitation. Everything's primed to move, primed to fire, primed to think. It's hard to shut off your mind when you're under the influence of stimulants, and easier when you're under the influence of these other drugs that increase inhibition.

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 underneath the skin. I say skin because you don't necessarily have to go under the skull. Let's take vagal stimulation, for example. Most people think about vagal stimulation as a way to calm down, but most of the vagal pathways are excitatory. One common treatment for depression now, if somebody's willing, is to put a small stimulator—a little smaller than a penny—under the skin of the neck and stimulate the vagus in order to overcome this sort of sedation that accompanies depression.

So vagal stimulation increases alertness. Neuroscientists have known this for a long time, and a lot of people are getting pretty good results in their treatment of depression by increasing vagal stimulation. And it's dynamic. You can say, “How do you feel?” “I feel okay.” You can actually see this in real time. There's an amazing thing that my colleague Karl Deisseroth, one of the greatest bioengineers alive, has talked about, where he's talking to a patient and she's suicidally depressed. Then he starts increasing the stimulation on her vagus, and she starts moving from that to a discussion about how she feels willing enough to go out and apply for a job 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 and our perception of ourselves. So this would be very nice to have. The question is, are you willing to go under the skin? I am.

A guy who came up not mainly through my lab, but spent some time in my lab, is now the head neurosurgeon at Neuralink. Matt MacDougall is an amazing guy. He has a little receiver implanted under the skin of his hand between his thumb and his index finger, and his wife does too. It opens the door to their home without keys. I was like, “What are you doing?” He's like, “It's sort of biohacking, Bay Area-ish kind of stuff.” He's like, “Yeah, I'm just playing with the idea of what it's like to have a small device under your skin that can do stuff in the world for you.”

That's very Neuralink-ish, and obviously they have much bigger aspirations than that. But I think within 12 months, 20% of the entrepreneurial world will be asking, “If it's only as invasive as getting a piercing, maybe I want a little vagal stimulator.” And that's coming next. People are thinking about peptides and what we're going to do. I'm not worried about peptides. I'm thinking implantable devices are where it's going to go next.

The commercially available vagal stimulators—some have shown some promise—aren't super impressive to my neurosurgeon colleagues who like to get it under the skin and under the skull. But I will say there's some interesting results there, but we're not quite there. Think about 10 years ago, if I told you, “Listen, you're going to be wearing a ring or a band on your wrist that measures your sleep and HRV.” That's pretty out there.

I'm so fascinated by this. There's reading the underlying activity of the brain at different levels of fidelity. There's writing. You talked about ultrasound stimulation. I think there's electrical stimulation, and I think there's magnetic stimulation potentially of these areas of the brain. One central part that I don't really know much about is the model of the brain itself.

Yeah.

How far along are we in our understanding of that? I know there are some things that we can say—activation of this area produces this thing. But it feels like we need those 3 things: good input modalities, good reading methods, and a model.

Yeah. I'm glad you're asking. These are my favorite topics. Usually people are like, “What peptide should I take?”

Which peptide should we take, by the way?

It depends on what your pain points are.

At the periphery—the retina, the cochlea, the tongue, the olfactory system, the skin, neuromuscular control, which isn't at the periphery—I think we know pretty darn well how the nervous system works. We know how different wavelengths of light are transformed into visual images, not just at a first approximation, but in significant detail. We understand how motion is processed. We understand a fair amount about memories, although I want to put that on the shelf for a moment, because there's an important finding in the memory field that may make you feel like we're in a kind of Twilight Zone, perhaps in neuroscience. It worries me all the time.

The hypothalamus—circuits that are deep in the brain that control hunger, anger, sexual appetite, lack thereof, hormone secretion—those are switches. Do we understand those? Yes. Do we understand everything? No. But we understand them. One of the reasons the GLP-1s are so effective, and one of the reasons they gained so much velocity, is because we understand where they bind in the brain. They bind to these hypothalamic and other areas, of course, that activate neurons involved in the suppression of appetite. It's a very simple equation, really: ramp these GLP-1 levels up 1,000-fold, and people aren't as hungry.

It turns out they're not as driven for other things, too, if you get beyond a certain level. I think Sam Altman talked about his experience with that at one point, and why he decided to either back off the dosage or stop taking them.

As you move in from the periphery of the sensory organs, 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, your prefrontal cortex, we know, based on lesion studies in humans and activation studies, is really important for contextual learning, for strategy-setting in different environments, and for suppression of impulse, what we call top-down suppression.” So do we understand what the prefrontal cortex is doing? Yeah.

The place where it starts to get murky is at the level of memory—we'll talk about that in a moment—and at the level of thoughts. You won't find a chapter in a neuroscience textbook that says, “This is how thoughts are made.” We can talk about what's starting to emerge there: these dynamic attractor states. We'll get to those in a moment.

But here are the eerie results from the study of the hippocampus and memory that freak me out. 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 pharmacology—into a complicated place. It doesn't allow for clean matching of conceptual understanding of the brain from experiments to levers that actually allow us some control.

The experiments are like this. Mark Mayford's lab, down at Scripps, has done this. Susumu Tonegawa, who won a Nobel for his work on immunoglobulins but then became a very successful neuroscientist, has done these experiments too. They have an animal do some sort of learning task. It could learn that it gets shocked over here and not there, or that it gets a reward over here and not there. It could learn a maze, or a lever-press combination that gets it a reward. Mice can learn pretty sophisticated things. Monkeys can do this too. Humans can do this too.

Because methods for reading from the brain, including the hippocampus—a deep-ish brain structure—have gotten pretty good, you can say, “Okay, these are the patterns of signals that occurred as the animal learned, and here are the patterns of signals that occur every time the animal expresses this thing.” We imagine there's a correlate where every time somebody serves a tennis ball the way they perfected it, the same cluster of neurons is activated in the brain.

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, and you get the tennis serve. 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? And indeed, that’s what you find. Hypothetically, you serve the tennis ball. I’m able to measure, let’s just say with the highest degree of fidelity, the patterns of activation from start to finish that occur as you toss the ball in the air and serve.

Great. Now I stamp those neurons with a chemical tag. This has been done. Then I come back later and activate those neurons in the same sequence, and you do the serve perfectly, and I say, “Great.” But then they did the important control experiment. What if I activate those neurons in the opposite sequence? What if I activate all those neurons at once, like banging on the keys of the piano? It’s not the same as playing the song.

If I just say, “What are all the keys involved in this motif of music?” and instead bang on them all at once, you get a very different sound coming out of the piano. It turns out you get the exact same behavior. This is problematic for the field of neuroscience because what it says is that this notion of these circuits firing in a particular sequence, at least for memory, is probably not true.

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. That’s kind of cool, right? 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. First of all, it’s very hard to activate these select sets of neurons with high spatial and temporal fidelity to begin with. But the other problem is that these neurons, I didn’t tell you, are all also involved in lots of other perceptions and behaviors. So it’s not like you have a circuit for serving a tennis ball that isn’t also used for some aspect of thinking and remembering about something from your childhood. I mean, that’s one of the beauties of the nervous system: It repurposes different neurons to participate in different circuits depending on the perceptions and behaviors that you’re experiencing or engaging in.

Our model of the brain works at the level of the periphery and the deeper brain structures, 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, and every textbook says it does. The flow from the eyes to the thalamus and up to the cortex to create a visual perception—we know that direction of flow is critical. If you cut that off at the level of the deeper brain structure of the thalamus, there’s no perception. We know this from human patients.

But memory, thinking, and brain plasticity all rest on the assumption that the temporal order matters, and apparently it doesn’t. That’s one of the unspoken “Hmm” within our field, and people are trying to understand that and what it means, but it’s going to present a serious problem for the neurotechnologies. 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.

The other piece is that we don’t really understand what a thought is. So if you’re going to get in there and start stimulating neurons in even just motor cortex to generate movement, without the acknowledgement that these neurons are extensively interconnected with structures involved in thinking and planning, you could send the system into a state of chaos. That said, 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.

I mean, there are people working on brain-damaged patients who 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. That’s how my friend Eddie Chen gets people with locked-in syndrome to speak through a computer. He’s not measuring from the speech-production areas. He’s carefully characterized, for many years—decades—the signals coming out of the speech-planning areas.

Because the signals can’t get down to the pharynx and larynx—speech is just the pharynx and larynx controlling exhales—what he’s doing is transforming those signals into electrical signals so that the person can talk through a computer. So there are advantages and disadvantages to this nonspecificity. I think that’s the big one. That’s the really big one.

6. The Cyborg Threshold

What about all this excites you most and scares you most? Some of this feels like it strips me of my humanity or my identity in some weird way. If I knew that you could just play me like a piano with high-precision technology underneath the skull or something, that would be strange. The bigger question is, where do you actually think we’re going 5 or 10 years from now? What kinds of things do you think we’ll have? But I’m also just curious about the cyborg line here that we’re probably going to cross, which gets philosophically weird.

I have to acknowledge that I was born and raised in Palo Alto and had friends in the technology and medical sectors, so sometimes I get a little bit of blinders on.

Yeah.

Me too.

A lot of people are terrified of AI, and I’m told lately that I’m not scared enough.

Yeah.

I acknowledge that people are concerned and afraid because they don’t understand it, but I remember the same discussions about computers, which is not to say that we don’t need to be careful. But people are okay now with reading from the nervous system. People are okay now with the fact that our phones are recording everything that we’re saying.

Yeah.

We were like, “Is it really listening? How could it really know?” It’s a little bit like autonomous driving. In San Francisco, I got in a Waymo. I didn’t even think about it; I just got in. 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 cross.

Right now, we get heart rate, HRV, and a few other things, but mostly heart rate and HRV, and from that we’re told how stressed we are, how well recovered we are, and how well we are sleeping. None of that is a direct readout from the autonomic nervous system. I actually have a former postdoc who did her undergraduate work at Stanford, graduate work at Harvard, and was at Caltech briefly. Her name is Malisy Ylmaz. She’s a brilliant neuroscientist and now a biotechnologist.

She’s developing a tool. 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. I got to try it. It gives you a readout at the end of the day of how different activities and different patterns of speech and breathing in you relate to levels of distress versus eustress.

Right now, we just think all levels of increased heart rate and decreased levels of HRV are bad, 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 set you up for better sleep and more focus. The data have hinted in that direction for a while, but these devices are the sort that she’s developed, and she’s brought this to police departments and first responders. Eventually, this will be a broadly available technology.

Direct measurements from the nervous system: How stressed are you when you are stressed, or are you actually doing great? You’re just in a high-arousal state. That might change your perception of how stressed you are. I think accurate feedback about those things will have a real positive effect on our health metrics. 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.

You’ll also learn how long the tail on your stress is from a given stressful interaction—stress in air quotes. How well you’re focusing will probably need to be picked up from measurements of pupil-size changes. This is how it’s done in animals. This is why I think, confidently, it’ll be done from eyeglasses. So you need a lot of access from a wristband and eyeglasses, or an eye mask during sleep. I think people are going to be really comfortable with that.

The big one is how willing people are going to be to set up their entire brain for vulnerability to noninvasive control. We’re not going to drop wires into people’s brains for a while, unless they have a clinical issue. Maybe something under the skin, but you still don’t have access to all the neurons. What I want for myself is access to all the neurons so I can turn things up or turn them down, at least by brain structure, and have control over it.

There has to be some benevolence written into and, you know, hardwired into the device, right? We can’t have things where you just suddenly find yourself in a rage. You would hope that the companies building these things would put safeguards in place. They have them for vagal stimulators. Why wouldn’t they have them for brain stimulators?

The vulnerability—or let’s call it accessibility—that I’m talking about would be the following. In my lab, when I was running it, and in a lot of labs, people tickle neurons, write to neurons, and increase their activity a little, 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. Typically, these are genes that express channels that come from either algae or other nonhuman organisms.

Sounds scary, right? But the way this is done is you can do it locally by making 1 injection. Okay, problem: you have to breach the skull. Or what a lot of people do is inject an animal with an adeno-associated virus, or some sort of virus that can stably express genes in all the types of cells that you want.

You can direct them to neurons. You can direct them to immune cells. You do this by putting in specific promoters. It sounds fancy, but it’s straightforward in primates and mice and so on. You can do this in humans. They’ve done it in humans for other purposes, but it’s more localized, like into the eyes.

So here’s where we’re going. This is where we’re going to end up. 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. Everyone goes, “Oh my God, it’s going to make me sick.” No, it’s not going to make you sick. It’s not the active virus. The virus is just a vector. It’s just a carrier for some genetic cargo that puts into your brain a channel.

If you have a hat on—a wool cap or a baseball cap—it can direct stimulation of only those neurons because it will cast a nonspecific stimulus, like a cone of maybe light that can go through the skull, like long-wavelength light, which seems the most likely, or ultrasound in a nonspecific way. So it’s not illuminating or activating the whole brain, but it will send a beam of sound or light onto these neurons, which will be active if they express that tag.

You can increase the intensity of the light. You could flicker the light. We’ll work through all the different parameters that allow you to turn those neurons from inactive to active to more active to hyperactive, and dial it down. Most likely, through AI, you’re not going to be turning a knob. If you’re somebody who is suffering from severe motivational issues, or you have healthy levels of motivation and you want to ramp it up, we’ll just increase the stimulation.

Now, does this open up into people cranking the circuit for themselves?

Yeah, but we also have this thing called caffeine, and we also have this thing called methamphetamine. Methamphetamine’s a problem. 90% plus of the adult world’s population drinks caffeine every day, which increases excitability in the brain, basically.

Yeah.

I mean—

It’s like a blunt version of the same thing.

Yeah, it blocks the thing that shuts down excitation, but the net effect is more excitation. So you know how much coffee you can drink at a given time of day, given how much sleep you’ve had. You’ll decide how much alertness you want to have. 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 AND gate. Maybe you also have to take a pill, so you can’t just have the virus and the ultrasound. You need a third factor there. It could be an AND gate. It could have any number of different safeguards in there, but people who have vagal stimulators can unplug them, too.

I know it sounds scary, but it’s absolutely going to happen for the people who want to do it. I think not everyone’s going to want to do it, and right now the reading and measurement from the brain and body are freaking some people out. I put out a post on X a few weeks ago: “If the cost of whole-body MRI comes down, I can imagine most people would want it.” I know people who have told me they’ve saved patients’ lives because they went and got this done, saw a tumor, and we took it out. The neurosurgery community did not like that. I thought it would be, “More business for them,” but they did not like it.

The public gaining more access to their own health data is scaring some sectors of medicine. Dermatologists and ophthalmologists love AI, and they think more measurements are better. But I think The Wall Street Journal just put something out saying that whole-body MRI is basically bad. But you don’t have to do it. I’m assuming it’s safe if the cost is low enough or insurance covers it. I just don’t get the logic, but my friends in medicine tell me we all know that within 20 months—I don’t know why 20 and not 24—it’s going to be commonplace because the cost is coming down, just like blood testing.

Everyone was resistant to blood testing and to genetic testing. I’m old enough to remember the 1980s, when it was like, “Will you get your genome mapped?” It was, “What if you have the Huntington’s gene? What if you’re going to get—would you want to know?” They had episodes of 60 Minutes about this. Now it’s very simple. You want to know, you go take the test. You don’t want to know, you don’t take the test.

Yeah.

No one’s talking about whether or not getting your genetics done is worthwhile or scary. It’s up to you. Same thing with your blood.

It’s so interesting to me that through all this, so many of the things that you’ve written about or I’ve seen you talk about are indirect ways to affect these same end states, and it sounds like what you think the arc is is just away from the blunt tools and toward direct, highly precise tools through technology over time.

More and more specificity. That’s what you want as an experimental neurobiologist. 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 orbitofrontal cortex does? It’s involved in morality.” No, it’s involved in contextual decision-making and strategy. That’s Phineas Gage. Certainly not the whole story, but it got us through.

H.M. had lesions in his hippocampus and couldn’t remember new things. We are now at the level of tickling specific neurons that are involved in a particular memory or the expression of a particular behavior, using chemogenetic tags, light, and sound. We only have so many different ways to manipulate neurons.

In the health realm—I love that you’re bringing this up because it really bridges the 2 areas that we’ve been talking about, public health discourse and neuroscience, reading and writing to the nervous system—it bridges the 2 because what are we talking about? Get morning sunlight. Why? To set your circadian rhythm, spike your cortisol, and so on. It seems like a blunt tool, but there’s a circuit in place from your eye to your hypothalamus and on and on that is there for that purpose.

So it’s not biohacking, right? This is important. It’s not like using a paper clip to fix my glasses. That’s not what the paper clip was designed for. It’s not a good solution. It’s a temporary solution.

The problem with a lot of pharmacology, like SSRIs, is that, believe it or not, they helped so many people with true clinical-grade OCD. They were overprescribed for depression, and really what they do is increase serotonin, which allows for more neuroplasticity. Now everyone’s down on SSRIs, understandably so, although they have their place, but everyone’s really excited about psilocybin. What is psilocybin? It increases serotonin, and massively so. It unmasks lateral connections in the brain and allows you to form new associations in a very condensed timeframe. Sometimes it works great; sometimes it doesn’t, but it’s interesting.

Same thing with MDMA. It creates really massive increases in neuromodulators in a specific context. If we’re going to work on this thing—this pain, this issue, this trauma, this depression—you get more plasticity than you do if you’re just chipping away at the problem through talking about it day in, day out. You need the therapy, but what did you really do to create plasticity? 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.

Okay, TMS—or what I think will soon happen—is combining transcranial magnetic stimulation and pharmacology in order to work through a clinical issue involving emotions or the mind, like depression or PTSD. These 2 things are going to start to intersect. ADHD with stimulants: yep, it ramps up activity in the prefrontal cortex, and you can focus better on things that you normally wouldn’t be able to focus on. It’s just a nonspecific focus enhancer because it increases activity there.

You could also do sleep and creatine, in particular when sleep-deprived. Is it like Adderall? No. But those 2 things—a great night’s sleep plus some caffeine—give you pretty close to Adderall-level effects. It’s just that the people taking Adderall aren’t getting great sleep.

We’re really talking about tools of different types and different margins of safety, but they are all very blunt because all these receptors are expressed everywhere. So you get sexual side effects, weight gain or excessive weight loss with certain antidepressants, or hypersexuality with certain drugs, et cetera, because these receptors are all over the brain.

The same thing with electrical stimulation. You just want more spatial and temporal specificity. It has to go that way. Neuroscience went that way in terms of reading and understanding the nervous system.

You can talk about Dario’s work, for instance. He talks about his work in this realm, but he was recording in Mike Berry’s lab from retinas, usually a salamander retina or some other creature, and they recorded as many neurons as they could. You knew what visual signals you were giving the retina, so you knew the input. You knew the responses at the lower levels—the photoreceptors—and the output cells, what we call ganglion cells, the signals going off to the brain.

The goal was to get as much information as possible about the total collection of neurons responding to an image, so we could move from image to perception deep in the brain. Now, you’re still a few steps away from the actual perception, which takes place in the brain, but Dario and the people he was trained under—Markus Meister and others—were heroes of our field.

Dropping electrodes in an area and going, “Bzhh,” and buzzing, and the animal goes into a rage or starts mating or whatever—that’s super cool. But then you have to move to, “What’s the nature of the switch in real life?” 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 interaction? But these are all still very low-level behaviors and motivations, and we're just starting to understand those. So, the cyborg thing—can I increase your creativity? We're not even close to that. We don't even know what circuit—

Or IQ or something.

Yeah. You could imagine stimulating more memory capacity, but you might give up something. You want to hear something super creepy? This might freak out your audience, but it's true.

A few years back, there was a guy, He Jiankui. His first name is He—that's how you pronounce it, H-E. I can't pronounce his last name. He had done his postdoctoral 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 CRISPR in twin babies. He had deleted CCR5, the HIV receptor, and the story was—and I don't know if it's true or not—that the father of these children was HIV-positive and wanted to save these kids from getting HIV/AIDS.

There was this moment in the medical science community where no one knew how people would react. Were they going to give him a Nobel Prize or throw him in jail? He went ahead and did the experiment. We know how to do this now. The technologies exist, but he just did it.

There was this really weird sociology around this in the science community. People who had worked with him previously, who had exchanged emails with him, had their emails dug into, and it was clear that the communications from a lot of these people were sort of, “Hey, be careful,” but also, “Is it working? Is it working?” Everyone was waiting. If he got in trouble, people could say, “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 I knew the lab he worked in, but it was like, “Am I going to be a part of this? Was I important for this important discovery, or should I dissociate myself from this?”

It turns out the world decided, no, ethically, this is bad. The Chinese government came out and said that his lab would be taken away and that he would be punished in some way. I don't know how he was going to be punished. You know what—

Disappeared.

Yeah. Do you know what that guy's doing right now? He has a laboratory, purportedly, in Austin, Texas. I don't know if that's true or not, so my first reaction is, “How did that happen?” My second reaction is, “Wait, of course. He wasn't the only person doing this.” You know this is happening in labs all over the world. It's just no one's talking about it because he proved that it's dangerous to talk about.

I think it's very important to have the ethics and the committees set up for this kind of technology, but then you take a step back and say, “Where are we in the world of genetic engineering of humans?” You say, okay, they do testing of amniotic fluid in pregnant women and babies. It's commonplace. People can refuse it, I believe, but in general, that's done.

People are screening embryos for IVF. There are companies like Heracite and Orchid. Some are more focused on trying to see if there are any diseases. Some are trying to link certain genetic patterns of expression to autism, but also to IQ, height, et cetera. So you can see where this is going.

Then, of course, there's this thing that we call partner selection. People choose, in most cases—not always—but they choose who to get sperm from or eggs from in the context of a relationship, right? Or if people are using a sperm donor, they're choosing on the basis of—if you look at the criteria, the criteria are height, where they went to school, what they look like, you know? The lines between these haven't been cleanly defined, but you can see there's a gradation there.

I don't know if He Jiankui is actually in Austin, Texas, or if he's actually doing these experiments. I don't know that. I want to be very clear. But I find it fascinating and important to understand that people are going to run with these technologies. How fast they run and where they get implemented isn't clear.

What about memory? The CCR5 receptor supposedly is also linked to some aspects of neural-circuit formation that are linked to memory. So there was this other layer of those experiments that everyone knew in the neuroscience community but wasn't talking about: Was he actually trying to both render those kids immune to HIV infection and make them super smart?

No one's been able to answer that question conclusively, but there is this idea that maybe people are genetically engineering people who have some gene expression, or lack of gene expression, that renders them more cognitively or physically capable. You go, “Oh, that sounds crazy.” Yeah, and the follistatin gene has been mutated in animals, and there are people doing gene therapy for follistatin to try to build more muscle.

So if this was 15 years ago and you and I were having this conversation, you'd be like—

The guy's out of his mind.

“The guy's out of his mind.” Everything I just described has happened. 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, whether he's someplace else, or whether he's sitting in a prison someplace in China, I don't know. Okay? I think it'll be interesting. The internet will tell us.

Yeah.

I guess I'm more excited than concerned, provided people are talking about it and thinking about it really carefully. One of the beautiful things about social media is that nothing stays a secret for very long, if at all. Nothing stays a secret. There are no secrets anymore.

You can have a private conversation with somebody; that absolutely is true. But as soon as more than 2 people know about something, you can't exist in this world without leaving a digital footprint. Sooner or later, we'll hear.

7. Waking States Become The Frontier

It seems like the arc of all this is just control: control of genetics, control of brain states, control of all these things through technology over time. This is very much like a William Gibson “the future is here, just not evenly distributed yet” type of thing. These are all “the future is here” type things.

What excites you most about all this stuff? If you had to pinpoint it—if I forced you to go start a company or something and just focus on one thing.

I spend a lot of time thinking about media and culture and just humans generally. To me, the most exciting thing is that because of social media, we're all on the same campus. X is that campus. Instagram, to some degree. Those are the campuses for communication about these things.

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 we can't predict that are going to happen. 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 and really understands it, is going to move that space forward at tremendous velocity at some point.

The issue is that He Jiankui was a scientist just doing his thing, and he went rogue and did it. He didn't check with anybody. When I was coming up, you did experiments at night, and the goal was, “Don't kill yourself, don't burn down the lab, don't break protocol, but do experiments.” Now it's changed a little bit. Everyone's a little bit more paranoid.

I'm excited that somebody—and they're starting—will do this. I think that people are thinking about neurotechnologies to read from and write to the nervous system in awake states. My own interest right now is really understanding waking states.

We understand slow-wave sleep, deep sleep, N1, N2, and N3 sleep. I wrote a whole chapter in the book about sleep—its architecture and how temperature changes one or the other. Heat up the bed in the morning, or the room in the morning, and you get more REM. We know all that stuff.

We know so much about sleep and how to measure it, and now how to nudge and maybe even dial in sleep really precisely with these eye-mask-type tools. Changing the room temperature is pretty crude compared to that, but it's also helpful.

I want to understand waking brain states. I don't know how to describe the state that we're in. REM isn't language about how you feel in REM; it's rapid eye movements. There's something associated with the state that we're in right now: I'm alert, I'm focused, I'm enjoying our discussion. What is this state?

We need a much better understanding of waking states and which waking states lend themselves better to which activities. Then we can start writing to the nervous system to generate those states with a lot of temporal and spatial precision. That, to me, seems like the most important thing to resolve right now, and it's totally doable.

I'm not the person to do it because I'm no longer running a lab. The problem with neuroscience as a field is a little bit of a problem with academia, but even in the biotech sector related to neuroscience, people tend to work on things that are about 4 degrees off from what their training was.

Actually, even though I've never met him, I think Dario—even though I disagree with a lot of things I hear from him about AI—I think it's interesting that someone who came up through neuroscience is in this quite different but related field. Sam Altman, who I've spoken to, is extremely smart about the neuroscience, as are Mark Zuckerberg and Marc Andreessen. Elon Musk obviously understands what he's trying to achieve with Neuralink, and he's extremely savvy with respect to what can be done now and where we need to go.

In a lot of ways, the technologists who used to just engineer stuff are becoming neuroscientists, and I love that because neuroscience has always benefited from bringing people in from other fields.

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. It's something a whole lot more complicated. But bioengineers are getting very, very good. People like Eddie Chang—obviously, Neuralink is doing this—Matt MacDougall and the folks there, and Sam, Zuck, and Dario. That's a pretty killer lineup, and Elon. Those are the big four. Those are the athletes of brain exploration now.

I think most people don't realize that. I'm not sitting here like one of the kids saying, “I'm not trying to glaze it.” 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 I'm all excitement about it, frankly. But I think we need a better definition of waking brain states. I think that's the biggie.

And the reason I mention those different silos that I've touched into is that any time you see a field, whether it's action sports or science or medicine, take a big leap forward, there's always this thing that we talked about earlier where people get into it. Some people go public-facing; they push the margins a little bit, then it gets too crowded, people start getting wacky to get more signal-to-noise on them, and then the thing kind of dies down. Then there's this surge of really accessible, useful technologies and information.

Quality, yeah.

So I think 2027 and 2028 are going to be a low-level noise, in my estimation, around the health space. I mean, that's what the book Protocols was about. That's my thesis. We got it. I'm not going to keep talking about morning light. For God's sake, I'm starting to tire myself out.

Yeah. The reason I can move on from it is because I know it for certain. What's in the book are the things I know for certain. So now that my thesis is turned in and people can do with it what they will, I think it has things of value, certainly information, but hopefully things of value to people. Now it's time to move into some other realm, and you can probably tell from today's conversation—I didn't realize this was going to come up—I am very, very interested in reading and writing from the awake nervous system.

Eddie Chang and I talk three times a week for hours at a time. We take walks. Where is neuroscience? What's next? I'm just super excited. It's going to be great. I promise you, there are safeguards we need in place, but the best people are on these problems. The best people. And that's why it pisses me off when the traditional media tries to slow these people down. “Okay, everybody, make your public statement about how you're not going to blow up the world.” It's like, of course. You want them to do that. Also, by the way, it doesn't pacify anybody. Of course, we need the ethics, we need the safeguards in place, but I'm nothing but excitement about this. But then again, I'm born and raised in Palo Alto.

I did not exactly expect our discussion to focus so much on neurotech and waking brain states and things like this, but I honestly hope you and I can do this once a year to check in on the state of this stuff. It does seem like if you really think ahead from the current stuff in AI to where this is all going, of course, inevitably, the intimacy of technology into us is going to increase, and this is the final frontier. So incredibly fun to talk to you about.

8. Follow Your Genuine Curiosity

When I do this—and I hope it's the first of many—I ask the same traditional closing question. What is the kindest thing that someone's done for you?

The kindest thing. All right, this is a bit of a weird one, but I've carried the message that I got forward through basically everything. Once people hear it, if they thread it back through portions of today's conversation, I think they'll know how I've done that.

When I was in graduate school, I initially joined a different laboratory. You do rotations, and I joined a laboratory doing excellent work that was very popular at the time. It was really on the cutting edge of molecular genetic techniques for looking at neurons, and it was all the rage at the time. But I had this absolute love and obsession for the work that I had done in my second rotation, on stuff and in a field that was pretty crowded, and I found myself, having joined this other lab, sneaking into the lab that interested me more at night and doing experiments.

The woman who ran that lab, my graduate advisor, Barbara Chapman, came to me one day and just said, “Listen, I'm totally okay with the fact that you didn't join my lab.” Her lab was already very successful anyway, publishing papers in Science, et cetera. 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 you want to know the answers to the questions that you're working on.”

I was like, “Okay.” So I broke up with the other lab. I joined her lab. We published 8 first-author papers. But that was all the consequence of working on things to try and answer questions that I was most curious about.

That was an incredibly kind thing to do. It also required a lot of humility and boldness on her part because she was basically saying, “Dump them. Come back to me.” And I had to trust that it wasn't because of some sense of rejection in her, and it wasn't. She had an extremely strong ego. Honestly, I think that's the kindest thing anyone's ever done for me because it showed a belief in me. It showed that she understood that I didn't have enough self-understanding and, frankly, enough guts to just say, “I don't want to do the thing that everyone else is super excited about. I want to focus on the thing that I'm most excited about,” which takes a strong mind and is much easier to do once you've had some significant success in a field.

It's easy to do when you're like, “Oh yeah, everyone said that area was done. No one listens to that music,” but then we had 2 platinum albums. It's easy to just carry on. But when you're making the decision to go into this area that you know most people are saying, “Why would you go there? No one works on that anymore,” it turns out that the wheel of the field rotated, too, and I found myself exiting my PhD lab with the skills that were best suited to what was most important in the field next.

And I had to be very careful because the landscape matched my internal curiosity, and I had to make sure, yes, I'm going into this for the right reasons. And it was true. And likewise with starting a podcast, I loved running a lab. I truly did. I loved teaching at Stanford. I still do. But I just have this itch. I've got this knowledge in me that I know people can benefit from.

I did not anticipate what came with being public-facing. That was not anticipated. I had no training for that—for being in the media. And I'm like, “Fuck it. I want to do this,” and then I just pulled all the stops out and went for it.

Here we are. Can you say that line one more time? What was her phrasing of it?

Success is determined by how precisely you match your genuine curiosity to the work that you do. You do have to understand the field you're in and pay attention to it, because all experiments are so hard. Building any company is hard. Doing any podcast, if it's done right, is hard. So you have to make sure that it's really true to you.

And not to puff him up too much, but I think one of the reasons why Elon is admired by so many people—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. It's his ability to ignore what people say about what he should be doing.

I had a guy come on my podcast who I actually like and respect, and he was telling me all the things that Elon and the top technologists should be doing. They should be helping people this way and that way, and I'm like, “Wait, electric cars, and I do think OpenAI is heading toward some very interesting things that relate to medicine and benevolence there, and on and on.” And he's like, “Yeah, that's what they should be doing, not this other stuff, not Mars.”

That's like telling Metallica to play the Grateful Dead. Metallica are Metallica because that's what they love. That's the music they fucking love. And the Grateful Dead are the Grateful Dead because that's the music they love. You have to be yourself.

The big tragedy is when people don't go in the direction of their genuine curiosity because they're trying to “succeed.” 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.” And not doing that is kind of a slow death, frankly.

Hmm. A wonderful, awesome place to close, Andrew. Thank you so much for your time.

Thanks.