Invest Like the Best with Patrick O'Shaughnessy
00:53:02 · Andrew Huberman
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 combined transcranial magnetic stimulation and pharmacology in order to work through a clinical issue that is of, you know, emotions or mind like depression, like PTSD. So these two things are going to start to intersect. ADHD with stimulants. Yep. 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 creatine in particular when sleep deprived. Is it like Adderall? No. But those two things, great night's sleep plus some caffeine, you're pretty close to Adderall level effects. It's just that the people taking Adderall aren't getting great sleep. And so, we'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. So you get sexual side effects, weight gain or excessive weight loss with certain antidepressants, or hypersexuality with certain drugs, etcetera, 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, no one talks about his work in this realm, but he was recording in Mike Berry's lab from retina is 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. So you knew the input, you knew the responses at the lower photoreceptors, the output cells, what we call ganglion cells, the signals going off to the brain. The goal was get as much information about the total collection of neurons responding to an image so we can move from image to perception deep in the brain.
00:54:58 · Andrew Huberman, Patrick O'Shaughnessy
Now you're still a few steps away from the actual perception, which takes place in the brain, but those, and the guys that they were trained under, Markus Meister, those were heroes of our field, because dropping electrodes in an area and buzzing in like the animal goes into a rage or starts mating or whatever. That's super cool. But then you have to move to like, what's the nature of the switch in real 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 interaction? But these are all still very low level behaviors and motivations. And we're just starting to understand those. So the cyborg thing, like, can I increase your creativity? We're not even close to that. We don't even know what circuit... [00:55:43] S0: Or IQ or something.
00:55:44 · Andrew Huberman
[00:55:44] S1: Yeah. I mean, you you could imagine stimulating more memory capacity, but you might give up something. You wanna hear something super creepy? This might freak out your audience, but it's true. So a few years back, there was a guy, his first name is He, that's how you pronounce it, H E, I can't pronounce his last name. He actually 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 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 he 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 them a Nobel Prize or throw them in jail? He went to, like, the end experiment. We know how to do this now. The technologies exist, but 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, their emails now were like, who 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, but like, is it working? Is it working? But everyone was waiting, like if he gets in trouble, 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, but it's like, am I gonna be a part of this? Like, was I important for this important discovery, or should I dissociate myself from this? And it turns out the world decided, like, no, ethically this is bad. The Chinese government came out and said that his lab would be taken away, and he'll be punished in some way. I don't know how he was going to be punished. -Disappeared. -Do you know what that guy's doing right now? He has a laboratory purportedly in Austin, Texas. Okay? Now, I don't know if that's true or not. So my first reaction is like, how did that happen? My second reaction is, wait, of course he wasn't the only person doing this. Like, 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.
00:57:48 · Andrew Huberman
Now, 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, like, where are we in the world of genetic engineering humans? And you say, okay, well, they do testing of amniotic fluid in pregnant women 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 Heracyte 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, to height, etcetera. So you can see where this is going. And 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, and they're choosing on the basis of, like, look at the criteria, and the criteria are like height, where they go to school, what do they look like, you know? So the lines between these haven't been cleanly defined, but you can see there's a gradation there. Now, I don't know if he's 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, where they get implemented isn't clear. What about memory? The HIV 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, 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, but there is this idea that maybe people are genetically engineering people that have some gene expression or lack of gene expression, which renders them more cognitively or physically capable. And you go, Oh, that sounds crazy. Yeah, and the folestatin gene has been mutated in animals, and there are people doing gene therapy for follistatin to try and build more muscle. So if this was fifteen years ago, and you and I were having this conversation, he'd be like...
00:59:53 · Patrick O'Shaughnessy, Andrew Huberman
[00:59:53] S0: -Guys out of his mind. [00:59:54] S1: -Guys 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 or he's someplace else or 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 people are thinking about it really carefully. One of the beautiful things about social media is nothing stays a secret for very long, if at all. Nothing stays a secret. There are no secrets anymore. You can have a vaulted conversation with somebody, that absolutely is true. But as soon as more than two people know about something, like, you can't exist in this world without leaving a digital footprint. So sooner or later, we'll hear. It seems like the arc [01:00:42] S0: of all this is just control, like control of genetics, control of brain states, control of all these things through technology over time. And this is very much like a William Gibson future is here, just not evenly distributed yet. And these are all the future is here type things. What excites you most of all this stuff? If you had to pinpoint, like if I forced you to go start a company or something and just focus on one thing.
01:01:06 · Andrew Huberman
[01:01:06] S1: I spent a lot of time thinking about media and culture and just humans generally. 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. 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. Like someone in the human gene therapy space, who's 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. The issue is that here was a scientist, just like doing his thing, and he just kind of 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 like, Don't kill yourself, don't burn down the lab, don't break protocol, but like, 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. I think that people are thinking about neurotechnologies to read and write from the nervous system in awake states. My own interest right now is really understanding the waking states. We understand slow wave sleep, deep sleep, N1, N2, N3 sleep. I wrote a whole chapter in the book about sleep, its architecture, how temperature changes one or the other, heat up the bed in the morning or the room in the morning, you get more REM. We know all that stuff. We know so much about sleep and how to measure and now nudge and maybe even dial in sleep really precisely with these eye mask type tools. Changing the room temp 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 is not 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. Like, I'm alert, I'm focused, I'm enjoying our discussion. What is this state? We need much better understanding of waking states and which waking states lend themselves better to which activities.