Invest Like the Best with Patrick O'Shaughnessy
00:49:33 · Patrick O'Shaughnessy
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00:50:59 · Andrew Huberman
[00:50:59] S1: 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 orbital frontal cortex does? It's involved in morality? No, it's involved in contextual decision making strategy. That's Phineas Gage. Certainly not the whole story, but it goes to He's got lesions in his hippocampus. Can't remember new things. 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, using light, using sound. I mean, we only have so many different ways to manipulate neurons, but in the health realm, love that you bring this up because it really bridges the two areas that we've been talking about, public health discourse and neuroscience, reading and writing to the nervous system. And it bridges the two because what are we talking about? Get morning sunlight. Why? To set your circadian rhythm, spike your cortisol. 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, believe it or not, helped so many people with true clinical grade OCD. They were over prescribed 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, allows you to form new associations in a very condensed timeframe. Sometimes it works great, sometimes not. But it's interesting. Same thing with MDMA. Create really massive increases in neuromodulators in a specific context that 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 lathing away at the problem through talking about it day in, day out.
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...