How Your Immune System Works & How to Improve It | Dr. Max Krummel

1. 0:00 – 2:18

   Max Krummel

   1. MKDr. Max Krummel0:00

      A famous, um, immunologist in the 1970s drew this parallel in wartime and said in World War II, submarines had two sets of books. One of them was a book that gave them the sound profile of all the US submarines, and so they could listen to the whir of the engines, and if they heard a whir of the engine that had the certain cycle of a general mo- you know, motors engine, they wouldn't fire. So that's the sort of like self, I know what self is. And then they had another book that was the engine sounds of the known diesel engines of whatever engines of the German submarines, and if they heard that, then they absolutely would fire, and that's a self versus non-self-discrimination problem, just like the immune system has to do. But what I bring you with it, aging, is this concept that as you get weirder and different and your, your body is getting, like, more complex, then as those books, you know, start to have every possible, possibly every possible permutation of every biomolecule could, could, could be made by your body at that point. And then a virus doesn't necessarily have anything unique about it.

   2. AHAndrew Huberman0:56

      [upbeat music] Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Max Krummel, a professor and leading expert in immunology and cancer biology at the University of California, San Francisco. Today, we discuss your immune system, how it works, what it needs to function at its best, and how things like aging, vaccines, sleep, and even your thoughts and emotions shape immune function. For instance, most everybody knows that being sleep-deprived makes you more prone to getting sick. But why? Meaning mechanistically why? Well, it turns out there's a specific set of cells that need to migrate in a particular way during sleep, and we talk about how you can reinforce that process in ways other than sleep. We also discuss incredible findings that certain brain states and memories can be associated with an immune system status you had when those memories formed, and evidence that just recalling those memories, thinking about where you were, what you were feeling at those times when the memories formed, can activate your immune system in the same way, which is remarkable. We also have a very candid discussion about vaccines and medications more broadly. You'll notice that Dr. Krummel is incredibly balanced throughout today's conversation, and yet he's also willing to state his views

2. 2:18 – 8:36

   Immune System, Immunotherapy

   1. AHAndrew Huberman2:18

      very clearly, so it provides a very rich discussion about vaccines and all the rest. Indeed, thanks to Max's incredible breadth of understanding of immunology and much more, and his ability to break down complex topics and make them accessible, plus his genuine care for public education and science, today's is a truly special and important episode to educate and inform you in actionable ways. I should also mention that Dr. Krummel has an incredible zero-cost Substack. It's called The Immune Beyond. You can access it by going to theimmunebeyond, all one word, .substack.com, and there he teaches about science and more. Again, it's awesome, it's free, so definitely check it out. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. Max Krummel. Dr. Max Krummel, welcome.

   2. MKDr. Max Krummel3:17

      Thanks.

   3. AHAndrew Huberman3:17

      Most everybody, including me, has heard of this thing we call the immune system, and most people just think, "Okay, this is the thing that when I'm rested, it keeps me from getting sick, and when I'm not as well rested, I tend to get more sick, and there are these airborne things, and we can get sick, and there's like funguses and viruses," and, and I think that's probably what most people understand, and they probably also understand that there are like cells and T cells and B cells. But if we wanna think about a little bit of the history of our understanding of the immune system and what we understand now, maybe you could orient us, because in reading your work prior to this discussion, I'm realizing that this is a very recent field, and also there's still a lot that we do not understand.

   4. MKDr. Max Krummel4:02

      When I started immunology, sort of thirty years ago, I was rotating in labs at Berkeley. I think you were at Berkeley as well. And, uh, one of the transcription factor biologists, you know, mentor said, uh, you know, "Why do you wanna work in immunology? It's not really a field." And so at the time, it was kinda true. You know, everything was about, um, DNAs, cloning. We still... You know, it's obviously still a lot about molecular biology, what we do. But, uh, you know, at the time, it was pretty simple. We thought of the immune system as something that, on the one hand, it had to come into play when you saw a virus or something foreign, um, and otherwise, it generally had to be quiescent and kinda leave you alone. I think cancer immunotherapy changed that a lot. That, that gave us the idea that you could tune its reactivity so that you could get to the point where if you gave an immunotherapy, what it was actually doing was raising the threshold of when a T cell would activate and allowing T cells that might be just letting the tumor get by get-- They'd, they'd be able to go and go after that tumor and, and, and kill it. I think that changed the spectrum a certain degree, where we suddenly thought, "Okay, this isn't just a, just a, you know, foreign versus self thing," because it's-- a tumor is kinda not exactly self, but it's al- it's actually, it's also not foreign. It was once you. It's a cell that's kind of evolved. So I think tumor immunology really changed our perspective on that, you know, to the point where we now think of it as a, as a tunable system. But then I think, you know, a lot has happened in the last twenty years. There's been a lot of excitement about cancer immunotherapy, because, well, we're, we're curing people with cancer, which really wasn't done before. You're now in the space where, um, the immune system is showing all these other roles. I mean, you know it in the, in the nervous system. In the brain, there's microglia that do various functions, cleaning up, et cetera. But it's in your gut. It's allowing microbes to live in you, but it's titrating them. It's keeping them there in the kinda like the right quantity. So it's kind of guarding yourself. It's, uh, you know, it sits in your liver Regulating how, how much you metabolize. There's a collection of cells there. Um, it's in your heart. It's, you know, re-regulating cardiomyocyte function. Uh, those are the, the muscle cells of your heart. Uh, they have to be cleaned up from time to time, so there's a set of immune cells that will help get rid of their byproducts in the, in the, in the heart. So it has all these additional functions that kind of before were, were lost in the, in the just, uh, you know, the foreign battle against the foreign, and now we have this kind of perspective of this system that measures us all the time. It measures everything about us, and it exists in some ways, I think it's to, to help us be who we are. You know, as, as... and that's hopefully that's you as a healthy person. You know, in chronic disease, unfortunately, it can be part of the problem where it becomes part of the things that's letting the chronic thing, whether that's a tumor or kidney disease or what have you, it can, it can actually help perpetuate it because, um, well, it's, you know, in some ways it's trying its best.

   5. AHAndrew Huberman6:49

      Mm-hmm.

   6. MKDr. Max Krummel6:49

      But it's applying the wrong program to the wrong situation. Um, so yeah, it's, it's changed a ton. I'll give you another little funny story, which is that, that, um, you know, when I first came into immunology, again, we had this story like, you know, you know, mentor who says, uh, you know, "This isn't really a field." The year was, like, I came into the field in nineteen eighty-nine, and that's right at the peak of AIDS. And, um, AIDS was like as, as a biologist was really interesting because, you know, the, the HIV virus af- infects T cells. So your body is filled with ten to the eleventh or so T cells, like a ton of different kinds of T cells. And, um, you had a, you have a subset of T cells that are called CD4 T cells. They're kind of a flavor of T cells. And, uh, the virus gets rid of those. So HIV virus will infect the CD4 T cells, and then, then you end up with not having them. And the, the manifestations of AIDS, for those that weren't around during it, was it was just a ton of different opportunistic infections. So like soil bacteria that you and I, you know, fight off without even thinking about it would, would, would kill people. But so too would you see-- you saw people with, uh, Kaposi sarcoma, you saw like a opportunistic vi- like where, you know, a, uh, cancer's emerging. Um, and you just saw all these kind of manifestations of where the immune system was important, dementias in, in people with HIV as well. You know, it was an early accent at the time on how many different things the immune system might be important for. So regardless of whether, you know, it was a f- a field or not, it was clearly important. And it was all these things we didn't know about it that like fueled the discoveries that have led to where we are right now. And some of those, I, you know, I think it's worth pointing out, were just these curiosity questions like, "What are these cells?" Like, they were hard to study at, in the beginning. You know, they're-- they don't live, you know... It's, it's sometimes hard to keep cells out of a, out of a h- out of a human body

3. 8:36 – 13:02

   Illness, Childhood & Immune System

   1. MKDr. Max Krummel8:36

      alive. So, you know, there's, there's issues about, you know, how do you keep these things alive in the very first place? And then, and then what, what kinds of things, you know, trigger them to do stuff? And you got to make reagents to test those, you know, ideas you might have about what they might do. It was a long haul, I think, to get ourselves together where we now have a pretty good understanding of all the molecules and the cell types and the, and the behaviors that they can engage in. And it just gets more compli-- you know, more, more complex and more like rich as we understand that they're basically every single T cell in your body is like a free agent, and they're part of a sensory system. Each one can measure the concentration of a, of a, of a set of biomolecules, proteins, in, in the form of peptides. They can measure that, and each one then can say that's out of range or that's in range. So it's like you have like ten to the eleventh little sensors going around you curating you, you know, making sure you're the right thing. And if they see something that's out of range, they can do something about it. You know, like the whole thing is magnificent.

   2. AHAndrew Huberman9:32

      It is magnificent. Do you mind if we take a developmental, um, perspective on this for a second? And then I have a basic health question.

   3. MKDr. Max Krummel9:40

      Yeah.

   4. AHAndrew Huberman9:40

      The developmental perspective is I think most of us either remember or have observed that when humans are young, they get sick a lot more. Presumably, that's because their immune system isn't as well developed. But kids tend to get sick and then get over being sick pretty quickly.

   5. MKDr. Max Krummel9:59

      Yeah.

   6. AHAndrew Huberman10:00

      Maybe you could describe what's going on there.

   7. MKDr. Max Krummel10:02

      Yeah.

   8. AHAndrew Huberman10:02

      And it also is the case that, you know, as we get older, much older, in fact, uh, last quarter of life, let's say, people tend to get sick more. Uh, what's going on, um, in terms of immune system function, um, or is there something more broadly happening at level of just kind of energetics, mitochondrial function?

   9. MKDr. Max Krummel10:24

      Yeah.

   10. AHAndrew Huberman10:24

       Very curious about this.

   11. MKDr. Max Krummel10:25

       If I can take a step even further back, I will ask you a question of like, who are you? And I don't mean that like in a personal sense, but I can, you know, talk about that too if you want. Uh, but the more the question is like at, at some point, where does your body end and where does the world outside start? And one of the things that, you know, you start to realize if you look in a microscope is that we're covered with microbes all over our surface. We're covered with microbes all the way in our gut. In fact, we can't-- you know, you can't digest... You've probably heard this before, but you can't digest animal fats if it weren't for the bugs, the bacteria in your gut. They make some of the key components of, of bioacids that allow you to digest animal fats. So you need this system that's around you. So you aren't just the cell like y- if you learn biology, you've got the-- again, again, we're going to go way back. There's the egg and the sperm, and they fertilize, and now you got this, this, this cell that starts to divide and gives rise to every other cell in our body. So you might say that your body is just that collection of cells. But in fact, it's, it's, it's, it's absorbed a lot of viruses and, and, um, bacteria from our environment. And, you know, to go into that really briefly, that's really important because we only have twenty thousand genes in our genome. So there's only so much in a given life that we can do with those genes. And so by absorbing all kinds of other species onto us, we get their genomes. So like, like you said, like I was saying, the, the bacteria in your gut can now help you absorb nutrients that you wouldn't otherwise. If you eat sushi, you know, you've heard this probably, right? You get, you get bacteria in your gut that can help you absorb the, the, the, uh, seaweed, you know, nutrients from seaweed. So, so taking this into your question, you know, when you're first born, you've never really seen anything. And so two things are, are, are think worth pointing out at the early phase of life. One of them is for the first six months or so, your immune system is pretty poor at being trained on things, and it's presumably-- we presume that for those six months that's because your body's developing so fast that if you were to have a super active immune system, you might actually find yourself attacking yourself. You might think that you're foreign because some genes turn on during development, and then all of a sudden your, you know, your, your immune system's like, "Oh, I, I see something different, and now I need to react." So that's well known, and that's just- that's one of the reasons why some childhood vaccinations that are really important to protect kids in long-- over life, why they aren't given until you're six months or, or, or older. But I think to your point, one of the things that's happening with kids is that they then, then as they go into their like until they're ten and you're talking about they get sick a lot, they just haven't seen a lot of these bugs before. So they don't have an immune system that knows what flu is 'cause they've never seen... It's-- the body's never-- that body, the kid's body has never seen flu before. So every single virus and pathogen that hits it is gonna elicit some am- you know, some amount of illness.

4. 13:02 – 18:36

   Aging & Immunity, DNA Mutations

   1. MKDr. Max Krummel13:02

      But then they have a very strong immune system. It reacts and, you know, gets rid of that, with the exception of the ones that, you know, are those, those certain viruses and bacterias, mumps, measles, rubella, that are, that are lethal, and that's why we immunize, as we said. And that's-- those are things that your immune system, if they get too much of those, kids will die. And so it's better to protect them with a vaccine. All right, so that's the front end, right? The front end has this initial, you know, immunosuppression, then just exposure to all these things that are in our environment, and you and I take on as part of our ge- genomes, but we have to get a-- we have to reach a detente with some of them. You know, we have to get to the point where the immune system can kind of like fire back when they show up if they're bad and, and, and allow them to live in us if they're good with us. And so I think that's what's happening a lot in those first years of life. And, you know, you can see that both in the form of, you know, kid getting sick a lot, but you'll also see that their guts develop way diverse microbiome. You know, they, they allow a whole bunch of things that come in from the outside and are acceptable and are quite good for you. So that's the front end. And the back end of life, it's a little bit more complicated, but I'll tell you, I'll tell you two things that I think are important. On the one hand is the idea that... is, is the, is the fact that a lot of your cells in general become less functional, including immune cells, and you get less cells produced. And, and that might just be because, you know, we were never selected as organisms to live as long as we do right now. That's one i- idea of aging, right? Yeah. Aging-

   2. AHAndrew Huberman14:20

      Do we know that? That we just were supposed to be dead by seventy?

   3. MKDr. Max Krummel14:23

      Well, no, but we do know that, that we can reproduce and, and, you know, pass on our genes successfully already when we're sixteen. So, you know, the, the, the selective pressure to pass on your genes, if you've-- you imagine that's how genetic evolution happens is that you pass on your genes as being successful, you can already do that at sixteen, and anything after that is just cream on the crop. But, um, you know, at some point, maybe there's no selection. So we don't know that, but it's, it's a reasonable hypothesis to say there wasn't any real selective pressure for passing on genes that do anything past when you're actually having kids.

   4. AHAndrew Huberman14:55

      The psychologists would tell us that, uh, the wisdom of people, you know, sixty, seventy, eighty and beyond is useful for, um, groups of humans that live in, you know, uh, you know, villages of one hundred or so people 'cause they can give information to younger-

   5. MKDr. Max Krummel15:10

      Right. Agreed

   6. AHAndrew Huberman15:11

      ... people that is on the periodicity of, like, every five to ten years, maybe every thirty years, but that's a just so story.

   7. MKDr. Max Krummel15:18

      Yeah.

   8. AHAndrew Huberman15:18

      Right? I mean, it's a nice just so story.

   9. MKDr. Max Krummel15:20

      I like it too, and, and the-- I think the geno- uh, geneticists will refer to that as like the grandfather effect, where genes may be selected for... and maybe they're mostly about s- you know, genes that make us social in the-- in the-- for, for, for the elderly that do, th- y- you know, they're gonna have effects on the fitness of their grandchildren, which is their genes.

   10. AHAndrew Huberman15:39

       Mm-hmm.

   11. MKDr. Max Krummel15:39

       And so there's... Yeah, I, I think there's something to be said for that in, in conceptual space. I don't know if I can prove it to you that that's-

   12. AHAndrew Huberman15:46

       It's a tough experiment to do [chuckles]

   13. MKDr. Max Krummel15:47

       It's a really tough experiment to have two villages where the, you know, the grandparents are eliminated or, like, kept, you know, s- n- both non-ethical and also not useful.

   14. AHAndrew Huberman15:55

       Right.

   15. MKDr. Max Krummel15:55

       But we're talking about the aging immune system, and I think, I think there's two things that, again, come to this question that I was asking, like, who are you? Um, and I was saying, okay, well, in aging, you have this issue that the immune system is, is tapering in its efficacy, its-- many of the cells that you, you know, you've been holding your whole life start to f- to literally they die off. But there's another thing, which is I think a lot of people don't realize when you say-- when the basic biology will say that sperm, you know, like, uh, uh, fertilizes the egg, so you've got your mom's genes and your dad's genes, so you've got twenty-three chromosomes from your mom, twenty-three chromosomes from your dad. And, and, and at least in when you're first born, every cell is a clone. It has exactly the same information. But DNA replication and, and DNA sort of like fidelity isn't perfect. Like they say that on your skin, the cells of your skin may have somewhere between ten and thirty thousand mutations per cell per day just from like by basic sun exposure. And it's... That, that's higher than some of the other organs, but the basic idea is that your DNA, you know, is, is su- susceptible to UV radiation. That's one of the reasons we put on sunscreen. But what it, what it practically means, no matter what number you put in there, whether it's ten thousand mutations per day or... Remember, the, the genomes are huge, right? So ten thousand mutations out of terabytes of mu- of, of, of information still is only a certain number, but do that over every-- over, over years. And the main thing is that-- w- that, that, that means is that every cell in your body is no longer identical to the one next to it because this one got different mutations on day one, this one got some mutations on day two, and slowly but surely, you are becoming like a mosaic. And I say mosaic, you know, because like the tile you see in, uh, Morocco, you know, very intricate designs, because if you actually, you know, start to look into tissue, you know, you'll find that certain clones, certain w- mutations do make certain cells more fit, and they're the ones that if you scratch yourself and a cell has to like-- some, some new has to-- cell has to form, they might be the fittest to fill that void.

   16. AHAndrew Huberman17:42

       Mm.

   17. MKDr. Max Krummel17:42

       And as one of the other clones over here that got a different mutation may not be fit to fill that clone in. So you, you end up with this pastiche of who you are. So now, again, I ask you, like, who are you now? So if I want to defend against something that looks different What if everything looks different? What if every cell is different from every other cell? It's, it's, it... Okay, you want, you want another analogy?

   18. AHAndrew Huberman18:04

       I would like another analogy. The only, um, exception that I can think of to this, and I could be wrong, is that our neurons, our central nervous system neurons, our brain and spinal cord, most all of them are the same ones that we were born with. Um-

   19. MKDr. Max Krummel18:19

       They're same cells, but the DNA-

   20. AHAndrew Huberman18:20

       Same cells, but they're, so you're saying mutations are constantly accruing in the neurons as well

   21. MKDr. Max Krummel18:23

       ... in the, in the DNA. So there, there's this, you, it is fascinating by the way that neurons live that long and, you know, hair cells, they s- they say that the, the proteins in, uh, in our hair, hair cells of our ear are the same exact molecules, atoms as we had when we

5. 18:36 – 21:14

   Sponsors: Joovv & Eight Sleep

   1. MKDr. Max Krummel18:36

      were born. So there's, there's some cells that are long liv- but in their nuclei, the DNA that's encoding who they are, who those cells are, is subject to mutation ongoing.

   2. AHAndrew Huberman18:44

      Mm-hmm.

   3. MKDr. Max Krummel18:44

      And it depends on how deep they are. Like the, we tend to think that one of the reasons that immune stem cells live in our bone marrows, you know, our long bones are hollow, and in there is the source of the immune system's, you know, revitalization. It's the stem cells that make more white blood cells. We'd like to think that they live in there because it protects them from radiation. They l- they, they, they, they hang out, and stem cells are, you know, the, the bone actually serves not only a structural purpose in our body, but they, it, it's a cavity in which things can live. And there's-

   4. AHAndrew Huberman19:11

      Keep it away from-

   5. MKDr. Max Krummel19:12

      From UV

   6. AHAndrew Huberman19:13

      ... solar radiation

   7. MKDr. Max Krummel19:13

      ... solar radiation.

   8. AHAndrew Huberman19:14

      Keep it away from chemical cues in the environment that can mutate.

   9. MKDr. Max Krummel19:17

      Exactly. Sequester your stem cells.

   10. AHAndrew Huberman19:19

       Mm-hmm.

   11. MKDr. Max Krummel19:19

       And, um-

   12. AHAndrew Huberman19:19

       Don't burn them.

   13. MKDr. Max Krummel19:20

       Yeah.

   14. AHAndrew Huberman19:21

       That kind of thing.

   15. MKDr. Max Krummel19:21

       Yeah.

   16. AHAndrew Huberman19:22

       Yeah. Likewise, the neurons in the, in the, uh, inside of the skull-

   17. MKDr. Max Krummel19:27

       Yeah

   18. AHAndrew Huberman19:27

       ... and the spinal cord-

   19. MKDr. Max Krummel19:28

       Are protected

   20. AHAndrew Huberman19:28

       ... um, they're protected.

   21. MKDr. Max Krummel19:29

       Yeah.

   22. AHAndrew Huberman19:30

       And, uh, that's interesting.

   23. MKDr. Max Krummel19:32

       Yeah.

   24. AHAndrew Huberman19:32

       Yeah. I would like to take a quick break and acknowledge one of our sponsors, Joovv. Joovv makes medical grade red light therapy devices. Now, if there's one thing that I have consistently emphasized on this podcast is the incredible impact that light can have on our biology and our health. Now, in addition to sunlight, which I've talked about a lot on this podcast, red light, near-infrared, and infrared light have been specifically shown to have positive effects on improving numerous aspects of cellular and organ health. These include faster muscle recovery, improved skin health, wound healing, improvements in acne, reduced pain and inflammation, improved mitochondrial function, and even improvements in vision. Nowadays, there are a lot of red light devices out there, but what sets Joovv lights apart and why they're my preferred red light therapy device is that they use clinically proven wavelengths, meaning they use the specific wavelengths of red light, near-infrared, and infrared light in combination to trigger the optimal cellular adaptations. Personally, I use the Joovv whole body panel about three to four times a week, usually for about 10 to 20 minutes per session, and I use the Joovv handheld light both at home and when I travel. If you would like to try Joovv, they're offering up to $400 off select products for listeners of this podcast. To learn more, visit Joovv, spelled J-O-O-V-V, .com/huberman. Again, that's J-O-O-V-V .com/huberman. Today's episode is also brought to us by Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity. One of the best ways to ensure you get a great night's sleep is to make sure that the temperature of your sleeping environment is correct, and that's because in order to fall asleep and stay deeply asleep, your body temperature actually has to drop by about one to three

6. 21:14 – 30:11

   Self vs Non-Self Recognition, Aging, Cancer; Immune Surveillance

   1. AHAndrew Huberman21:14

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   2. MKDr. Max Krummel22:11

      Sometimes I tend to send, think the immune system, you want to defend it like you want to defend a, a nation, and you want to defend it from outsiders. And I've just told you a story that's, if you want to take a political statement from it, it's pro-immigration because all these bacteria that live on us are actually bringing us goods, and they, they do a lot of work for us.

   3. AHAndrew Huberman22:26

      We just lost half the audience.

   4. MKDr. Max Krummel22:27

      I'm sorry.

   5. AHAndrew Huberman22:27

      No, I'm just kidding. I'm to- totally joking.

   6. MKDr. Max Krummel22:29

      I'm sorry. [laughs]

   7. AHAndrew Huberman22:29

      We, we're a bi- we're a bipartisan audience. [laughs]

   8. MKDr. Max Krummel22:31

      Well, you know, take it-

   9. AHAndrew Huberman22:32

      I'm, I'm totally joking

   10. MKDr. Max Krummel22:32

       ... take it how you want, but, uh-

   11. AHAndrew Huberman22:33

       I'm totally joking

   12. MKDr. Max Krummel22:33

       ... but by analogy-

   13. AHAndrew Huberman22:34

       I'm joking

   14. MKDr. Max Krummel22:35

       ... it's the argument for, you know, why s- why certain, um, in, you know, influx of, of, of, uh, in this case, organisms onto us are, you know, create a more robust, you know, person than we were before. But I want to give you the, uh, this story that one of, a famous, um, immunologist in the 1970s drew this parallel in wartime and said in, you know, World War II, submarines would be underneath the ocean and they'd be traveling around, and they would, if they could, if they heard another submarine, they would scuttle the missiles, the, you know, torpedoes, because that could be the enemy, and the enemy could fire at them. And so they had two sets of books that they used. Uh, one of them was a book that gave them the sound profile of all, let's say it's a US, of all the US submarines. And so they could listen to the whir of the engines, and if they heard a whir of the engine that had the certain cycle of a general mo- you know, motors engine, they wouldn't fire. So that's the sort of like self, I know what self is.

   15. AHAndrew Huberman23:31

       Mm-hmm.

   16. MKDr. Max Krummel23:33

       And then they had another book that was the engine sounds of the known diesel engines of whatever engines of the German, uh, you know, submarines. And if they heard that, then they absolutely would fire. And that's a self versus non-self-discrimination problem, just like the immune system has to do. But what I bring you with it aging is this concept that as you get weirder and different, and your, your body is getting, like, more complex then as those books, you know, start to have every possible, possibly every possible permutation of every biomolecule could, could, could be made by your body at that point. And then a virus doesn't necessarily have anything unique about it. A virus is also gonna make proteins, and that's your immune system can see the viral proteins and say, "Oh, a new thing has come in, and that's, you know, that's out of range, and now I need to mount that, a T cell response against this. I need to make the, you know, just bring in the troops." But with aging, we have this, this kind of, you know, us diverging problem so that this, you know, this system that's supposed to sense us-

   17. AHAndrew Huberman24:27

       Hmm

   18. MKDr. Max Krummel24:27

       ... is just, you know, s- it has a lot of cosmic background. It has a lot of noise in it. And so I think it, I think that's one of the reasons why we also have issue when we're aging, and it's-- I think it's also one of the issu- reasons why cancer is more prevalent in later life for... I mean, there's two parts to that. One is, of course, you've accumulated mutations in your cells that could be cancerous. But also the immune system has been seeing those and all the various different accumulations of them and ones like them, you know, over these years to the point where the weird doesn't look that weird anymore. You know, something like a cancer that is different than you, it's not that much different than, like, another cell over here that's gone, you know, like, and it's just happily making skin and isn't cancerous, but, you know, it's, it's, it's got some differences.

   19. AHAndrew Huberman25:07

       What about the argument that there's so much cellular turnover that, um, the cells that accumulate these, these mutations are being eliminated? You're saying because they're-

   20. MKDr. Max Krummel25:17

       Hmm

   21. AHAndrew Huberman25:17

       ... clonal, they're producing different-- They become different, they produce cells that are also different, then they die.

   22. MKDr. Max Krummel25:24

       Yeah.

   23. AHAndrew Huberman25:24

       Is this, is that the way it works?

   24. MKDr. Max Krummel25:26

       Yeah, and I think, I think you're, you are bringing something up that's also true, which is that all the time, I think, the immune system is defending us against, you know, mu-mu-mutations. So one example that everybody sees when they get to be about forty or, or fifty is, is little, these white spots under your skin. And we, we think that those are places where the immune system has sensed a collection of cells that were pre-cancerous, maybe they were even beginning of cancer, and has wiped them out. And, and so the, you know, the-- a lot of the origin of cancers in skin is, is melanin-producing cells like melano- you know, melanoma is skin, is what we call skin cancer. Um, those melanocytes, that, that white area, they've just been wiped of a whole collection of melanocytes, and that's why it's, you know, like it's, it's white instead of as dark as your, as the rest of your skin. So, you know, to that extent, the idea that the immune system is, is pruning you all the time is, you know, there's-- it looks like there's pretty good evidence for that.

   25. AHAndrew Huberman26:17

       Mm-hmm.

   26. MKDr. Max Krummel26:17

       Um, and the question is, when does something become dangerous? That's, that's, that's, and that, you know, that's fundamentally the question with cancer and these sorts of things. If, if you said, "I wanna actually have the fittest cells in my skin to, uh, fill in a gap if I scratch myself. I'd really like to have cells that quickly replicate, just like maybe in kids." Kids heal so ridiculously quickly, right?

   27. AHAndrew Huberman26:37

       Because they have an abundance of these cells that-

   28. MKDr. Max Krummel26:39

       I think, I think they're, they're, they're wound healing. I mean, there, there's a group out of Stanford that studies this, but essentially, you know, wound healing in, in, in young is quite, quite a bit faster and more efficient, and, and there's many levels of that.

   29. AHAndrew Huberman26:50

       It's remarkable.

   30. MKDr. Max Krummel26:50

       There's many levels of that.
7. 30:11 – 35:57

   Cancer, Immune System, Age & Measuring Change

   1. MKDr. Max Krummel30:11

      and when certain viruses are just sitting in us, we're perfectly fine. You know, we have new viruses sitting around and as long as they're laying dormant, our immune system can say, "Okay, I'm gonna just hang out here, and if anything bad happens, I'm gonna squelch that." But it's not like we've been purified.

   2. AHAndrew Huberman30:26

      Mm.

   3. MKDr. Max Krummel30:26

      You know, that's a reality that's a little bit too bad, but, you know, it's also one where you say, again, if, if the goal of us is to make it to 30, let's say you get a, a hepat- an early liver infection of a HCV or HPV. If the immune system can just let that be, you're not gonna destroy your own liver, and you'll live to produce, and your genes will get passed on. On the other hand, if you m- mounted a massive immune response, you know, you went all the way in the fuel gauge to the right, your, your immune system can kill you. It, it absolutely can. You know? It's, it's can, can kill any cell it wants. So, so that, that, that again, that idea that there's space in between is the one that we actually are starting to understand, that it has all these specialized roles that are not always about getting rid of things at all cost.

   4. AHAndrew Huberman31:08

      This raises a question for me, and obviously, I'm not an immunologist, but it seems like one-

   5. MKDr. Max Krummel31:12

      You're gonna be one by the end of today. [laughs]

   6. AHAndrew Huberman31:13

      Yeah, I hope so.

   7. MKDr. Max Krummel31:14

      You're gonna... [laughs]

   8. AHAndrew Huberman31:14

      I like the sound of that, um, as will the audience.

   9. MKDr. Max Krummel31:17

      [laughs]

   10. AHAndrew Huberman31:17

       One potentially useful strategy the immune system could have, perhaps, would be rather than to decide to launch an attack on a particular cell because it's mutated and different-

   11. MKDr. Max Krummel31:31

       Mm-hmm

   12. AHAndrew Huberman31:31

       ... um, enough to assess how many cells throughout the body or even just get a local average of how many cells have similar mutations or just are different, right?

   13. MKDr. Max Krummel31:42

       Yep.

   14. AHAndrew Huberman31:42

       So that if we are indeed born pure-

   15. MKDr. Max Krummel31:45

       Mm-hmm

   16. AHAndrew Huberman31:45

       ... um, in the biological sense.

   17. MKDr. Max Krummel31:46

       Yeah, yeah. [laughs]

   18. AHAndrew Huberman31:47

       Um, uh, let's just keep it there for sake of today's discussion.

   19. MKDr. Max Krummel31:50

       [laughs]

   20. AHAndrew Huberman31:50

       And, you know, by time we are, um, you know, 32 years old, we are a mosaic of mutations-

   21. MKDr. Max Krummel31:57

       Mm-hmm

   22. AHAndrew Huberman31:58

       ... as it's, it appears we are. If the immune system could surveil multiple regions in the body-

   23. MKDr. Max Krummel32:04

       Mm-hmm

   24. AHAndrew Huberman32:04

       ... maybe compare organs or maybe keep it within organ system and say, you know, the number of, of mutated cells, uh, or not pure me cells-

   25. MKDr. Max Krummel32:14

       Mm-hmm

   26. AHAndrew Huberman32:14

       ... would be one way to do it more simply perhaps, has exceeded a certain threshold measured, I don't know, like enough receptors have something in them that the cell goes, "Okay, you know what? I'm gonna fight."

   27. MKDr. Max Krummel32:24

       Yep.

   28. AHAndrew Huberman32:25

       Right? In the same way that, you know, soldiers, you know, they might hear a shot whiz by, but then do they necessarily reveal their location and launch an attack? No. But-

   29. MKDr. Max Krummel32:34

       Yeah

   30. AHAndrew Huberman32:34

       ... but if it's, uh, enough of an, of an attack, they'll, uh, fight back.
8. 35:57 – 42:13

   Thymus, T Cells; Aging & Cancer

   1. MKDr. Max Krummel35:57

      you have, like, these cues that I think the immune system-- and I say the immune system because it's some cells are gonna see the damage, and some cells are gonna see the, the additional proteins that come in, and then they exchange information just like your brain. You know, we, uh, you can talk about the fact that the brain has this wired, you know, set of cells that are wired in space. They're, you know, across your body from your brain all the way to a muscle, let's say. Immune system has this collection of cells that are-- they're literally crawling around us right now. In fact, we used to do... We still do a lot of imaging. If you look in a piece of skin, you can see the cells. The immune system are really, really surveying us. They're crawling around. But they get together like neurons, and they can form synapses, and one can say to another one, "This is what I saw." You know, he says, "Oh, you saw that? Well, I's, you know, I'm just seeing this." And, and they can, you know, form a cluster of cells that basically get together like a neural little m-mini brain in our tissue, and they can say, "This is bad. We gotta do something about that." But I think the slow burn doesn't do that. The slow burn is one of the ones where the cells are like, "Yeah, it's not that bad."

   2. AHAndrew Huberman36:54

      I realize this perhaps is not your immediate area of, uh, research, but recently I've been seeing a lot more interest, um, in the thymus.

   3. MKDr. Max Krummel37:01

      Hmm.

   4. AHAndrew Huberman37:02

      This organ that we have when we're young, and it disappears as we get older, and there's-

   5. MKDr. Max Krummel37:07

      Yeah

   6. AHAndrew Huberman37:07

      ... a lot of interest in the-

   7. MKDr. Max Krummel37:08

      Yeah

   8. AHAndrew Huberman37:08

      ... thymus. Maybe, um, because we've never covered the thymus on this podcast in any amount of detail, if you could just, uh, educate us a bit, uh, what it is, what it does, and why it might be interesting as a, as a, um-

   9. MKDr. Max Krummel37:19

      For-

   10. AHAndrew Huberman37:19

       ... therapeutic. I mean, maybe we sh-- in a few years, we'll all be banking our thymic cells.

   11. MKDr. Max Krummel37:23

       Hmm.

   12. AHAndrew Huberman37:23

       Um, maybe we will be... I know some people are already injecting non-FDA approved peptides that, uh, come from the thymus. I'm not recommending anyone do that.

   13. MKDr. Max Krummel37:32

       Hmm.

   14. AHAndrew Huberman37:32

       But people are already doing it.

   15. MKDr. Max Krummel37:33

       Hmm.

   16. AHAndrew Huberman37:33

       Um, 'cause that's the, the Internet in twenty twenty-six.

   17. MKDr. Max Krummel37:36

       That's the clouds, yeah.

   18. AHAndrew Huberman37:36

       But what's the thymus? What does it do? Wh-why this interest?

   19. MKDr. Max Krummel37:39

       Yeah. Well, I can back up one step, and I've, I've used the word T cell before.

   20. AHAndrew Huberman37:43

       Mm-hmm.

   21. MKDr. Max Krummel37:44

       And T cell originally was thymus cell. So for those that maybe don't, you know, have gone to have blood taken, you know, if you have blood taken in a hospital, whatever, you'll, you'll get red blood cells, and those are the cells that carry oxygen around your body, and then you have white blood cells that come in two flavors. Two main... Well, they come in multiple flavors, but we'll, for the moment, we'll talk about two. One, one are called B cells, and one are called T cells, and T cells were named because of the thymus. So the thymus is this funny organ, and it has a funny history. In fact, I'm, I'm writing these Substacks these days, and, and, and I'm writing one that's supposed to be released tomorrow about the thymus because it, you know, uh, it really should have gotten the Nobel Prize. There was a guy who's alive, he's like ninety-seven years old in, in Australia, who did this, saw th- did this remarkable kind of experiment. There was this time when kids that had heart issues would come in for surgeries, and they would discover this enormous white, whitish organ as a growth near the heart as they were taking the body, you know, as they were cutting open. And all the autopsies up to that point had been done mostly with adults. And in adults, there's only this small little thing there. And so they were like, "Oh my God, part of the heart thing is this overgrown thing." They, they didn't really know what it did. And so they would remove it. And, uh, the kids then go home, and it, it was usually exploratory heart surgery, but then kids would go home. And, uh, far from, you know, dying of heart disease, many of them would die from, like, opportunistic infections. They would get all these infections. They'd get flu and, and et cetera. And so there was this hint that maybe this removal had taken out a critical part of your immune system, had made it so you were super susceptible to bacteria. And so this guy named Jacques Miller, who's this, this ninety-seven-year-old codger in, in Australia, at the time, he was in, in England, and he basically took a bunch of mice, and then when they were newborn, he'd removed their thymus, the same, same little whitish organ. And sure enough, the, those mice were, they, they basically grew up, you know, okay, but then they all would succumb to bacterial infections. And in fact, a few of them even got tumors, which was kinda noted at the time but forgot. And the reason why that is, is because the thymus is the place that makes all your T cells. And it, and it comes from a kind of a convoluted path, but you remember how we were talking about how the stem cells of your immune s-system lives in your bone? Well, there are stem cells that live in their bone, and they travel through your bo-- through your blood to the thymus and become T cells. And the, the reason they need to do that is that the thymus is this kind of s-super special place that is able to present to them, to show them all of the genes in your genome in various different ways. And so the T cells that come in there, the T cells are developing, and they each have a possible ten to the eleventh different kinds of receptors that smell different things, and you don't want any of these to come out that are too reactive to you. So you don't want to, you don't want to produce T cells that are gonna go off and kill your pancreas or, you know, kill your big toe or anything, right? You, you wanna, you wanna maintain, like, tolerance, so you wanna make sure that you don't make the immune system that's too harsh. So the, this thymus has the, the role of producing T cells but also of educating them in some ways, of only letting the ones that come out have, that have sensors that are correctly tuned to, to let you be you in that way. Now, to the point about the, uh, the story, and you were asking about aging is that, is that in kids, those are really big because at that point, we were talking about the developing immune system. It has to go from, like, you know, living under the veil of your mother's immunity, and then it needs to let some development happen, and then it needs to burst out and start to be able to react against whatever bacteria and viruses you're gonna see over life. So your thymus has this huge output. So as, like, between really from, you know, three to six months old and, you know, into your, into your four or five years of age but tapering, your body makes tons of T cells. And it's because probably what you're talking about, you're getting exposed to all kinds of different bac-bacteria and viruses, and so you need to make that, make that collection of immune cells that both some of them, you know, see self at low levels, but then they also can maybe react against different things in the environment, including the ones you need to defend against. Then what happens is, because again, I think we're not needing that later, and maybe we don't even want that, the thymus involutes. It gets super, super small, so that in aged people it's, like, tiny. And, um, and so it's not putting out new T cells. And so the reason why there's interest in, like, these peptides but all these other approaches to, like, revitalize the thymus is that, like, in cancer, for example, wouldn't you like to have a whole bunch of new T cells that could come into, in, into you, flood in there with exactly the specificity for the, for the tumor? The tumor has managed to teach all your normal cell, your other T cells in your body that it's normal. Maybe

9. 42:13 – 47:28

   Reproduction, Aging & Immune System; Basic Research

   1. MKDr. Max Krummel42:13

      you need a source of new material to come in and do that. And there's really two ways. I think you, you mentioned you talked to Alex Marson not too long ago, and he, I'm sure he would've talked about engineering cells that you can engineer on the outside and give them specificity. But the sort of like, if you will, the more natural route to that might be to, to let the thymus make use of more T cells and, and make sure that as they come out, you make sure that they can react against this tumor or whatever it is you need to defend against. It's always been a fascinating organ from the sense that it's the origin of all the cell types that we care about, uh, the T cells in that case. But it does have this, like, aging hit, you know, this sort of aging effect that seems to make us a little bit more susceptible to things later in life. And, you know, again, we could argue about what, whether there was a big evolutionary design behind doing that or whether it just wasn't needed because if so you got, you get to 30 and you died of an arrow wound, you know, you know, uh, and but you've given them your genes. You're, you're a winner in the evolutionary sense, you know? [laughs]

   2. AHAndrew Huberman43:09

      I love this, uh, uh, this stance on, well, if you've already reproduced. I'll, I'll just, uh, give a brief, uh, vignette. Uh, we were introduced by our, uh, mutual friend, uh, David Feldheim, who's a, a phenomenal developmental biologist from-

   3. MKDr. Max Krummel43:24

      He is

   4. AHAndrew Huberman43:24

      ... UC Santa Cruz, and his wife, Sophie Salama, is also a phenomenal biologist, a mutual friend. And years ago, I was in Dave's lab b- because we are longtime collaborators and published a bunch of papers together, and, uh, he was doing some injections. I'm gonna get you in trouble, Dave.

   5. MKDr. Max Krummel43:38

      Uh-huh.

   6. AHAndrew Huberman43:38

      He doesn't do this any longer.

   7. MKDr. Max Krummel43:40

      Yeah, I'm gonna, I'm gonna join him to get you in trouble 'cause we-

   8. AHAndrew Huberman43:42

      He was doing some injections

   9. MKDr. Max Krummel43:43

      ... we both love you a lot

   10. AHAndrew Huberman43:43

       ... and he might've been using, might have been using carbocyanine dyes. This was kind of a conventional tool back. You put a little crystal in a piece of tissue that's fixed tissue so it's not a live animal or anything, and then you put it in the fridge, and then the fluorescent dye would label a, a set of neurons in a pathway. And, um, and I walked over and I, I saw Dave doing this, and he wasn't wearing any gloves. And I thought, "These are carbocyanine dyes."

   11. MKDr. Max Krummel44:07

       With cyanide being the-

   12. AHAndrew Huberman44:08

       Cyanide being the-

   13. MKDr. Max Krummel44:08

       Being the, yeah

   14. AHAndrew Huberman44:09

       ... being the, uh-

   15. MKDr. Max Krummel44:09

       The key

   16. AHAndrew Huberman44:09

       ... and I said, um, "Dave, uh, don't you wanna put on gloves?" And he literally looked up from the microscope at me, I'll never forget, and he said, "I've already successfully reproduced."

   17. MKDr. Max Krummel44:20

       [laughs]

   18. AHAndrew Huberman44:21

       And he went back to doing it. And it's his lab, so, and everyone else was following safety protocol. Don't go after him. He doesn't do this any longer, folks.

   19. MKDr. Max Krummel44:27

       [laughs]

   20. AHAndrew Huberman44:27

       But, um, there's an interesting mindset-

   21. MKDr. Max Krummel44:30

       Hmm

   22. AHAndrew Huberman44:30

       ... among you, because he comes from cell biology-

   23. MKDr. Max Krummel44:32

       Yeah, yeah

   24. AHAndrew Huberman44:33

       ... Randy Schekman's lab.

   25. MKDr. Max Krummel44:33

       Yeah.

   26. AHAndrew Huberman44:33

       You both trained in Nobel Prize-winning laboratories as graduate students. So I, I find it remarkable that this, this stance of, uh, well, if you've already successfully reproduced, you really aren't needed. But, um, his kids are now graduated or in college. So there is this thing about raising the young, too-

   27. MKDr. Max Krummel44:49

       Yeah

   28. AHAndrew Huberman44:49

       ... and not just creating them and then dying.

   29. MKDr. Max Krummel44:51

       Agreed.

   30. AHAndrew Huberman44:51

       Yeah.
10. 47:28 – 52:55

    Sleep & Illness Susceptibility

    1. MKDr. Max Krummel47:28

       or more importantly, try to prove that it's not true. And so the better experiments, the kind of, we, we call them killer experiments, right? The ones that kinda kill the, kill the idea if they're wrong, if the idea is wrong. But it's killer because it, if it's, turns out the way you hope it will- You know, again, when we get to some of these aging things, there's a lot of in-- there's a lot of intuition that we all can put into this, whether we're like professional scientists or at home scientists. But it's really hard to say that intuition, like your idea about how the way the world should work, is in fact the way the world does work. You know, that, that I, I wish that because of your age, certain things would happen. That's, that's a, that's lovely, but it could be super-

    2. AHAndrew Huberman48:06

       Mm-hmm

    3. MKDr. Max Krummel48:06

       ... the word was baroque, you know, like-

    4. AHAndrew Huberman48:08

       Mm-hmm

    5. MKDr. Max Krummel48:08

       ... it should... The whole system could be, you know, configured in a completely weird way that doesn't really initially make intuitive sense to us. And that's also why some of those discoveries are so big to us. We're like, "Oh my God, I didn't realize that this system that seems like it might be quite simple is so complicated. The world is so strange."

    6. AHAndrew Huberman48:25

       Well, when I started in neurobiology, the brain, the-- actually, the entire central nervous system was considered an immune privileged organ.

    7. MKDr. Max Krummel48:32

       Yes.

    8. AHAndrew Huberman48:33

       There weren't supposed to be immune cells there.

    9. MKDr. Max Krummel48:34

       Mm-hmm.

    10. AHAndrew Huberman48:34

        And thanks to the beautiful work of Carla Shatz-

    11. MKDr. Max Krummel48:37

        Mm-hmm

    12. AHAndrew Huberman48:37

        ... with the, uh, major histocompatibility complex work-

    13. MKDr. Max Krummel48:40

        Mm-hmm

    14. AHAndrew Huberman48:41

        ... and, um, Ben Barres-

    15. MKDr. Max Krummel48:42

        And Ben Barres

    16. AHAndrew Huberman48:43

        ... and I'm failing to mention all their scientific offspring, but Beth Stevens, Cagla Ergil, like-

    17. MKDr. Max Krummel48:48

        Sure

    18. AHAndrew Huberman48:48

        ... and on and on.

    19. MKDr. Max Krummel48:49

        Yeah.

    20. AHAndrew Huberman48:49

        Um, it would take the rest of the episode to name all, all of Ben's scientific offspring.

    21. MKDr. Max Krummel48:52

        Sure.

    22. AHAndrew Huberman48:53

        And Carla's too. Uh-

    23. MKDr. Max Krummel48:54

        And your-- and being you one of them.

    24. AHAndrew Huberman48:55

        Right. I didn't work on those issues, but, um, but I was in those labs when it was happening. We now know that the immune system is active-

    25. MKDr. Max Krummel49:02

        Definitely

    26. AHAndrew Huberman49:02

        ... and alive in the central nervous system throughout the whole lifespan, serving critical roles.

    27. MKDr. Max Krummel49:05

        Yeah.

    28. AHAndrew Huberman49:06

        There are two things that, well, three really, that, that are somewhat practical questions. I'll start with the most basic one. Why is it at a mechanistic level that if you miss a night or two of sleep that your immune system seems so less effective in fighting off, off infections? Do we know what's happening? Is it like you've got so much adenosine, which is the sleepy molecule-

    29. MKDr. Max Krummel49:26

        Mm

    30. AHAndrew Huberman49:27

        ... and, and, uh, like that the adenosine inhibits T cell function or something? Do we actually know?
11. 52:55 – 54:08

    Sponsor: AG1

    1. MKDr. Max Krummel52:55

       that the, um, there's macrophages, immune cells in your eye that are basically clearing the, clearing the lens.

    2. AHAndrew Huberman53:00

       Mm-hmm.

    3. MKDr. Max Krummel53:01

       You know, so there's, there's all these like places where it's doing little cleanup that you can imagine that if the, the thing it's trying to get rid of is granularity, that, that you need to have sleep where you just aren't making more granularity so that it can, you know, sort of like when you wash your car windshield, you do it completely at that point and you... but you can't be driving with flys hitting you and everyone, right? [laughs]

    4. AHAndrew Huberman53:22

       [laughs] Yeah, exactly.

    5. MKDr. Max Krummel53:22

       Or you'll never clear it.

    6. AHAndrew Huberman53:23

       That's a great analogy.

    7. MKDr. Max Krummel53:24

       You know, so I think there's certain elements of some of these cleanup processes that happen best when you're not getting things, you know, you know, dirty or, again, I think a lot of what we're talking about is byproducts of our energetics that leave, you know, some damage behind it. I, I think we just use a lot of ATP and we do a lot of stuff as our bodies and the, and the sleep is this time where you can not be, you know, you know, producing more of that and get ahead of the curve on cleaning things up a bit.

    8. AHAndrew Huberman53:48

       Mm-hmm.

    9. MKDr. Max Krummel53:48

       Um, like pulling into a gas station, cleaning off your windshield.

    10. AHAndrew Huberman53:51

        I'd like to take a quick break and acknowledge our sponsor, AG1. I'm excited to share that AG1 has just launched their newest formulation, AG1 Pro. AG1 Pro takes the clinically backed AG1 formula, which is a blend of vitamins, minerals, probiotics, and adaptogens, and adds three important

12. 54:08 – 1:02:57

    Umbilical Cord Banking; Organoids, CAR T Cells, Thymus

    1. AHAndrew Huberman54:08

       new ingredients: creatine monohydrate, calcium HMB, and zinc carnosine. Each serving has five grams of creatine monohydrate to support muscle strength and performance, as well as brain health, calcium HMB to support muscle recovery and reduce muscle breakdown, and zinc carnosine to support and improve the lining of your gut. All three of these ingredients have compelling science to support them, and therefore, I love seeing them added to the existing AG1 formula. As most of you know, I've been taking AG1 every day for nearly 14 years now. I started taking it long before I even knew what a podcast was. It's a great product, and it's now made even better with the new AG1 Pro formula. If you would like to try AG1 Pro, you can go to drinkag1.com/huberman to get a special offer. AG1 is giving away a free bottle of omega-3 coenzyme Q10 with your first subscription. Again, go to drinkag1.com/huberman to get a free bottle of omega-3 coenzyme Q10 with your first AG1 subscription. This thymus thing is really intriguing, and, uh, I know a lot of people who, um, opted to bank their child's umbilical cord-

    2. MKDr. Max Krummel55:13

       Yeah

    3. AHAndrew Huberman55:13

       ... in the hopes that the stem cells from the umbilical cord will someday be useful.

    4. MKDr. Max Krummel55:16

       Yeah.

    5. AHAndrew Huberman55:17

       How invasive is it and/or should we be, uh, banking thymic cells?

    6. MKDr. Max Krummel55:22

       Mm.

    7. AHAndrew Huberman55:22

       Uh, because these seem like incredibly valuable cells for their ability to, uh, immune surveil and create kind of the perfect situation using our own endogenous T cells to battle infections. I mean, I kinda wish I had a little, little chunk of my thymus-

    8. MKDr. Max Krummel55:37

       Yeah

    9. AHAndrew Huberman55:37

       ... um, in a minus 80 freezer someplace so that when I'm 85 years old-

    10. MKDr. Max Krummel55:42

        You might be able to expand that

    11. AHAndrew Huberman55:43

        ... um, I might be able to exploit that.

    12. MKDr. Max Krummel55:44

        Yeah. Well, I'll, I, I'll say that the umbilical cord one is, is pretty straightforward. It's, you know, the umbilical cord is being essentially discarded anyway, and it contains a lot of, as you know, bone marrow stem cells that, um, the utility of those is a little different than the thymus. The utility of, of banking that material, and banking just means you put it into a vial, small little, you know, small little vial with the right media, and you set it in a very, very cold environment for whenever you might need it. Is that if you need to have a bone marrow transplant, so for example, if you have a tumor of the bone marrow system, you can subject yourself to radiation and wipe out all that tumor cells, but you'll wipe out all the stem cells, but if you got this vial here, you got a little replacement.

    13. AHAndrew Huberman56:27

        Has that ever been done successfully?

    14. MKDr. Max Krummel56:29

        Yeah, yeah. You can do-

    15. AHAndrew Huberman56:30

        So are there, are there, are there kids that s-

    16. MKDr. Max Krummel56:31

        You can do autologous, autologous, you can do-

    17. AHAndrew Huberman56:32

        Are there kids or adults that are alive today because they banked their umbilical cords?

    18. MKDr. Max Krummel56:36

        But certainly companies sell access to that. So whether that's how you're-

    19. AHAndrew Huberman56:37

        Well, and somebody has to pay to keep the freezers-

    20. MKDr. Max Krummel56:39

        Freezer

    21. AHAndrew Huberman56:39

        ... on backup generators-

    22. MKDr. Max Krummel56:41

        Yeah

    23. AHAndrew Huberman56:41

        ... and things like that. So people invest time and money into this idea.

    24. MKDr. Max Krummel56:44

        Yeah.

    25. AHAndrew Huberman56:44

        Is, is there a walking, talking, breathing human who would be otherwise dead, would otherwise be dead, excuse me, because they, they paid money to bank their, their umbilical cord?

    26. MKDr. Max Krummel56:54

        It's a really good question. I don't know the answer to that question.

    27. AHAndrew Huberman56:56

        I guess the parents paid.

    28. MKDr. Max Krummel56:57

        The, I can tell you, and this will be just like, this is, this is the depths of to which you're, you're describing, uh, Dave Alltime injecting a, you know, like mouse, [laughs] is that in mice this is true. That if you take, you know, bone marrow stem cells, you can reconstitute a mouse with a blood ca- blood cancer, and you can do that. I'm sure you can do it in humans, too. I have zero doubt that it also works. I don't know whether those companies have done that. That's, that's just actually something where I-

    29. AHAndrew Huberman57:22

        'Cause this-

    30. MKDr. Max Krummel57:22

        ... all of my knowledge-
13. 1:02:57 – 1:13:14

    Scientific Curiosity, Failures, & Discovery

    1. MKDr. Max Krummel1:02:57

       it's, it's intuitive and it's almost certainly true that we will have some of these things. Whether we'll have them in time for like you or me, I, I don't know.

    2. AHAndrew Huberman1:03:05

       Mm-hmm.

    3. MKDr. Max Krummel1:03:06

       I, I just don't know, and I, I think that's true of a lot of these things. They say, "Oh, you know, we're, we seem to be right on the cusp right now," for example, in, in cancer therapy we've been on the cusp for 10 or 15 years of these things called CAR Ts, uh, uh, Alex will have told you about these, where you engineer your T cells and give, you give them special receptors that can get them to go into to eliminate tumors. But for whatever reason, they haven't worked in patients. They haven't worked, they haven't worked, they haven't worked. And T cell, the immune system gets turned off. These cells don't make it. They don't... They, they fail to eliminate the tumor. We will figure that out, but we've been thinking we'd figure it out, you know, sort of for five or 10 years and it's, it's, you know, that gets frustrating and I think it gets frustrating for people that are like waiting for it to, um, on the outside like, "Why can't you solve this?" And you're like, "Well, because the universe isn't always configured how we think it is," and that's discovery. That's the problem with discovery. If we knew-

    4. AHAndrew Huberman1:03:51

       Yeah

    5. MKDr. Max Krummel1:03:51

       ... what we needed to do, we would engineer it and it would work.

    6. AHAndrew Huberman1:03:54

       Yeah, um-

    7. MKDr. Max Krummel1:03:54

       But we don't

    8. AHAndrew Huberman1:03:55

       ... th- this is an important discussion that we haven't spent enough time on in this podcast that I think is, it very important for people to hear, and I have some thoughts about it, but I'd, I'd love for any disagreements. I'm not looking for, um, just agreements, but-

    9. MKDr. Max Krummel1:04:08

       Yeah

    10. AHAndrew Huberman1:04:08

        ... so my observation from a couple decades or more doing science and then mainly shifting to podcasting, but this is what I do. I talk with great scientists.

    11. MKDr. Max Krummel1:04:17

        Mm.

    12. AHAndrew Huberman1:04:17

        So that's the podcast, so I'm very immersed in like what's happening right at the cutting edge and, um, because of great guests like you. You know, my, my sense is that in every field there's been like this kind of steady pressure like r- water on rock pressure. Like okay, we're gonna understand, like salamanders regenerate. Wouldn't it be great if we could do that too?

    13. MKDr. Max Krummel1:04:35

        Mm-hmm.

    14. AHAndrew Huberman1:04:35

        Cut off a limb, it could grow back. Okay, amazing. Uh, I think it's like Ellie Tanaka's work has just shown that and you're like, "Wow, this would be incredible for amputees and brain regeneration and-"

    15. MKDr. Max Krummel1:04:44

        Right

    16. AHAndrew Huberman1:04:44

        ... but then it never really transfers or like, "Oh, we're gonna figure out ways to get genes into cells. We're gonna electroporate liposomes. Uh, we're gonna use, uh, calcium phosphate," like great research tools, tons of things happen. And it's like we're gonna modify genes, zinc finger nuclease, all this. Okay, CRISPR, boom. And one thing just breaks through and goes so much further.

    17. MKDr. Max Krummel1:05:03

        Mm-hmm.

    18. AHAndrew Huberman1:05:04

        And even though, you know, the ethics are questionable, there are babies that have deliberately induced, uh, gene alterations for, with CRISPR, uh, sickle cell anemia treatments as well-

    19. MKDr. Max Krummel1:05:14

        Mm-hmm

    20. AHAndrew Huberman1:05:14

        ... is a more benevolent example, but then the person who went rogue and just kinda did this in humans in China. But CRISPR just kinda broke through it all.

    21. MKDr. Max Krummel1:05:22

        Hmm.

    22. AHAndrew Huberman1:05:23

        The s- the excitement about stem cells led to like, yeah, I mean, even initiatives at the legislative level and like all these labs working on things. And then, as you said, it's kinda like run up against the dam.

    23. MKDr. Max Krummel1:05:33

        Yeah.

    24. AHAndrew Huberman1:05:34

        But I feel like in 10 years some or all of that information will be extremely relevant when boom, one thing will just like leap out of bacteria or like grasshoppers, no pun intended, with the grasshoppers. But the, the last example would be, you know, for years it was like the country's getting fatter, the cou- the country's getting obese. What are we gonna do? Do calories matter? Of course calories matter, this kind of thing. Ener- you know, laws of thermodynamics still apply. And then all of a sudden This freaking Gila monster biologist-

    25. MKDr. Max Krummel1:06:03

        Yeah, yeah

    26. AHAndrew Huberman1:06:03

        ... tells people what they already knew because the GLPs were already being used as a drug, just not at significantly high levels.

    27. MKDr. Max Krummel1:06:11

        Yeah.

    28. AHAndrew Huberman1:06:11

        And all of a sudden we have a imperfect but very important, more or less dare I say, cure-

    29. MKDr. Max Krummel1:06:18

        Yeah

    30. AHAndrew Huberman1:06:19

        ... for obesity.
14. 1:13:14 – 1:25:00

    Spatial Biology & Immune Cells; Memory & Immune State; Stress, Meditation

    1. MKDr. Max Krummel1:13:14

       Yeah, yeah.

    2. AHAndrew Huberman1:13:14

       It's like anyone that's, like, done a triathlon or-

    3. MKDr. Max Krummel1:13:18

       Well, yeah

    4. AHAndrew Huberman1:13:18

       ... you know, raised, raised a kid or done anything, you're like, "Oh, my goodness." Like-

    5. MKDr. Max Krummel1:13:21

       Yeah, yeah

    6. AHAndrew Huberman1:13:21

       ... and that never ends, right?

    7. MKDr. Max Krummel1:13:22

       Yeah, yeah.

    8. AHAndrew Huberman1:13:23

       There's nothing better than these long-term investments.

    9. MKDr. Max Krummel1:13:26

       Yeah.

    10. AHAndrew Huberman1:13:27

        Nothing.

    11. MKDr. Max Krummel1:13:27

        Yeah. When they break through the... Wait, your, like your analogy. When you break through that dam, or when you realize sometimes that you've broken through the dam, that's, that's one of the funny things about, I think science and maybe it's true in triathlons and stuff too, where you've realized that you've all of a sudden got somewhere. You've made it.

    12. AHAndrew Huberman1:13:41

        I haven't done a triathlon, so I have to be fair.

    13. MKDr. Max Krummel1:13:43

        Yeah.

    14. AHAndrew Huberman1:13:43

        Rob, uh, our producer sitting-

    15. MKDr. Max Krummel1:13:45

        He has done it

    16. AHAndrew Huberman1:13:45

        ... to our left, has, uh, he has done many Ironmans.

    17. MKDr. Max Krummel1:13:48

        Yeah.

    18. AHAndrew Huberman1:13:48

        Um, and he has that mindset-

    19. MKDr. Max Krummel1:13:49

        Yeah

    20. AHAndrew Huberman1:13:50

        ... of just steady pressure. I mean, his relationship to work and effort is remarkable because he burns so little energy worrying about things that we refer to as in the left column, like the stuff you can't impact-

    21. MKDr. Max Krummel1:13:59

        Yeah

    22. AHAndrew Huberman1:13:59

        ... and just focusing on what you can impact.

    23. MKDr. Max Krummel1:14:01

        Yeah.

    24. AHAndrew Huberman1:14:01

        I mean, so a lot of it is about learning energetic control.

    25. MKDr. Max Krummel1:14:04

        Yeah.

    26. AHAndrew Huberman1:14:04

        Like doing science, that is, or anything, is about what not to think about, what n- what to force yourself not to do [laughs] -

    27. MKDr. Max Krummel1:14:09

        Yeah

    28. AHAndrew Huberman1:14:09

        ... or think about.

    29. MKDr. Max Krummel1:14:10

        Yeah.

    30. AHAndrew Huberman1:14:10

        If I may, I'd like to shift us to this very interesting area of immunology and biology, which you refer to as spatial biology.
15. 1:25:00 – 1:26:37

    Sponsor: Function

    1. AHAndrew Huberman1:25:00

       autonomous nervous system is through, is through your breath. Mm-hmm. Um, that happens with meditation. I think that, to me, there's something intuitive about that. But, you know, I, I just an hour ago warned you about the problem of science being intuitive- Mm-hmm ... that some things that make the, they sort of make a great story in our minds, then don't turn out to be true. But the, the data on this insular cortex thing is starting to look like it's a real thing. Like, it's, there's a real- Mm-hmm ... connection between some of the peripheral states and, and, like, uh, regions of the brain. And however those are triggered, now maybe, you know, again, I've, I've always thought, "Well, maybe when you're healthy, you should smell, like, mint, and then when you wanna be healthy again," like, you know, there's, it's, it's those kind of crazy thoughts. But, but again, there's an element of that that's intuitive, too, where we say, "Oh, that seems to be the case. My mom makes me a comfort meal. Is it really the meal settling in, or is it just the, that, the sensations that make me feel like, you know, less, you know, well, stressed in one sense?" Mm-hmm. But maybe also, uh, to this point in literally s-resetting your tissue. I'd like to take a quick break and acknowledge our sponsor, Function. Function provides over 160 advanced lab tests to give you a clear snapshot of your bodily health. This snapshot gives you insights into your heart health, your hormone health, autoimmune function, nutrient levels, and much more. They've also recently added access to advanced MRI and CT scans. Function not only provides testing of over 160 biomarkers key to your physical and mental health, it also analyzes these results and provides recommendations for improving your health from top doctors. For example, in a recent test with Function, I learned that some of my blood lipids were slightly out of range. As a result, I decided to start supplementing with nattokinase,

16. 1:26:37 – 1:34:25

    Mindset; Tissue Engineering, Peptides, Systems Biology

    1. AHAndrew Huberman1:26:37

       which can naturally help reduce LDL cholesterol, and it did. In a follow-up test, I could confirm that this strategy worked. My blood lipids are now back exactly where I want them. Comprehensive lab testing of the sort that Function offers is just so important for health. I mean, how else are you gonna know what's going on under the hood? And while I've been doing blood work for years, it used to be time-consuming, complicated, and expensive. In fact, I used to spend thousands of dollars per year trying to get this kind of data, and the data, frankly, were not all that good. But now with Function, it's extremely easy and affordable. A Function membership is only a dollar a day, $365 a year. And if you think about the information it provides and the health challenges it helps you avoid and the proactive things that it can do for you to enhance your health, I truly look at it as a savings. To learn more, visit functionhealth.com/huberman and use the code Huberman for a $50 credit towards your membership. Again, that's functionhealth.com/huberman. I'm always struck by, um, extremes of personality, but in both directions. Hmm. So there are these people who just say, like, "I don't get sick." Hmm. And they don't get sick, and it's super frustrating. Hmm. Because I'm not one of these people that's very sickly, but I occasionally get, like, a sniffle or a cold or something, you know, less and less with each year because I do feel I pay more attention to the sleep piece- Mm-hmm, mm-hmm ... um, than I, certainly than I did when I was a graduate student, postdoc, or junior professor. [chuckles] Yeah. But there does seem to be this quote unquote "positive" or let's just call it a reinforced mindset- Mm-hmm ... as opposed, like an immune reinforcement associated with the mindset. Because, um, some people will say, like, "I, I just always get sick," and I believe them. They always seem sick. But it could be that, um, you get sick in o- in a given environment once, and then you, you just decide that you're sickly. So then y- you know, it could be that the immune system is listening to these thoughts, but not in the form of words. I think this is where, like, it gets hokey for people. Like real- Yeah ... biologists and peop- and physicians are like, "Yeah, you gotta be kidding me." Like, but 'cause immune cells don't listen to thoughts, they listen to brain states. Triggers of some sort. Triggers of some sort, right? Yeah. Um, and then there's, like, as humans, we have this obsession with language that makes it seem like you can, you know, write affirmations, and then it's the word content. Mm-hmm. But it's the feeling state associated with that that- Probably does ... at a biological level makes total sense. Yeah. So s- we were talking about spatial biology and the fact that- Yeah ... you can tuck some pancreas in the kidney, and unless they, someone has Type 1 diabetes- Hmm ... a lot of the functions of the pancreas can, um- Can still function ... can persist or transplantation of these clock neurons. And, you know, clearly there are limits to this, but in the context of the immune system, I'm wondering, can we take a little bit of thymic tissue, bank it, and then just later, like, put it in a slow-release capsule under our skin of our hand? You know, like, and that might sound crazy, but I- Hmm ... have friends, one of whom might be at Neuralink now, who actually embedded a little radio receiver under his hand to be able to- Yeah ... open his, um, hi- locks at his home- Yeah ... and his car, and his wife might have one also. And, like, that might sound really like Bay Area, like future tech, kind of wacky biohacking. Yeah. But, uh, if I knew that I could be much healthier by taking a few thymic cells in, in a, you know, a sterile capsule and sliding it under the skin, you know? People get their ears pierced with, you know- Right, right, right ... less, less invasive, uh, procedures. Why not? Well, I mean, the question is w- why would that... You know, is that likely to work? Um, you're basically... Remember how we were just talking about if I do 10 experiments, one might work. Yours isn't a bad idea, but-

    2. MKDr. Max Krummel1:30:14

       You know, is there... It's, it's more than likely one of the nine out of 10, I would guess.

    3. AHAndrew Huberman1:30:18

       Sure.

    4. MKDr. Max Krummel1:30:18

       But then-

    5. AHAndrew Huberman1:30:18

       Is there a correlate from any studies on animals? Um, I mean, we know that-

    6. MKDr. Max Krummel1:30:22

       Mm

    7. AHAndrew Huberman1:30:22

       ... in a lot of studies of cancer and tumors, I used to see these mice down in the vivarium, they would slide tumors under the skin-

    8. MKDr. Max Krummel1:30:29

       Yep, yeah

    9. AHAndrew Huberman1:30:29

       ... and study 'em.

    10. MKDr. Max Krummel1:30:30

        Yeah, yeah.

    11. AHAndrew Huberman1:30:30

        And give animals drugs or give animals stuff.

    12. MKDr. Max Krummel1:30:32

        Very, very common, yeah.

    13. AHAndrew Huberman1:30:34

        Yeah. Uh, tumors are happy to thrive in novel environments.

    14. MKDr. Max Krummel1:30:37

        Sure. Yeah.

    15. AHAndrew Huberman1:30:37

        So why wouldn't healthy cells?

    16. MKDr. Max Krummel1:30:38

        No, I think you can. I think one of the things that comes into play a little bit about that that's more about, you know, um, replacing an organ with one that might be better is that at some point if you come in... So one of the, the challenges of tissue engineering is if you wanna bring in new genes, the vector, the material that the, the, the, the surrounding, whether you're bringing it using a virus to, and, you know, to bring it into those cells that you're gonna now put into the person, whether it's a virus or a, a small piece of DNA called plasmid, you and... You effectively are giving that a new bit of identity and when that... When you go to transplant that organ back in, it's seen as foreign.

    17. AHAndrew Huberman1:31:16

        Mm-hmm.

    18. MKDr. Max Krummel1:31:16

        And it's, it's just like you just put an infected cell in you. You know, as far as the immune system knows, all of a sudden there's a s- cell with a huge number of new things being expressed, and some of them viral literally. So, you know, that's a... That represents an issue, I think, when we talk about any kind of, you know, sort of engineering at the pr- and, you know, at the moment is, is if you engineer a, a system to be maybe better, the immune system isn't necessarily gonna want better. And, and so you have to overcome this issue of tolerance maybe at the same time. And, and, and again, that's why that particular experiment, depending on what you're putting under the kidney capsule or whatever, it matters what the immune state is and what that thing is as to whether your immune system's gonna let it fly.

    19. AHAndrew Huberman1:31:54

        Mm-hmm. I'm not considering doing this.

    20. MKDr. Max Krummel1:31:56

        Yeah.

    21. AHAndrew Huberman1:31:56

        I just, I, I think we are at a-

    22. MKDr. Max Krummel1:31:58

        It's... Yeah

    23. AHAndrew Huberman1:31:58

        ... I don't know how old you are, but I, I can guess based on some mutual friends we have, but I'm guessing that a lot of people who are able to understand speech, they're old enough to understand speech, are thinking that in our lifetime we are going to be able to use our own cells or peptides or synthetic versions of peptides from our own cells and, and so forth to, to overcome a lot of the issues that our parents and grandparents were not able to overcome.

    24. MKDr. Max Krummel1:32:25

        You know, with regards to, like, the peptide side of things, and even the cells, and this is maybe where you're going with space, is that context does matter for the immune system. So... And, and it matters for all biological systems. I'll just give you an example. We did a study of, of wound healing, uh, some years ago, and if you have a wound in a mouse that's maybe just a... Like, you know, if you ever have a melanoma removed, they do a punch biopsy. It's a little circle. So you can do that in the back of a mouse, and then you can watch the wound healing happen. The... There's zones within there where certain biology is really important to be happening, and then... So, so, so imagine the, the wound is like this and it's open. The cells, like one layer back, are doing certain things, but the other ones behind that are also induced to do something. The wound isn't just this area. It's, it's actually sensed all, like a gradient almost like in the neurons.

    25. AHAndrew Huberman1:33:15

        Mm-hmm.

    26. MKDr. Max Krummel1:33:15

        And so these cells need to do different things than these cells. So if you wanted to administer some, you know, like, like a peptide or a, even just a cell type, you have to be a little bit conscious of, like, where it's gonna do the work you want it to do, and the natural system does that naturally. Like, the cells on the inside actually instruct the cells one layer back. But you don't necessarily want everybody getting the same signal.

    27. AHAndrew Huberman1:33:35

        Mm-hmm.

    28. MKDr. Max Krummel1:33:35

        So, like, development happens that way. You know about gradients, and we were talking-

    29. AHAndrew Huberman1:33:38

        Sure

    30. MKDr. Max Krummel1:33:38

        ... about this earlier that there's gradients. So, so I think one of the tricks that we don't really understand about this is when is something good, uh, for a process, and when is it only good when it's given in the right dose at the right time?
17. 1:34:25 – 1:39:37

    Immunizations in Childhood and Beyond

    1. MKDr. Max Krummel1:34:25

       to do with the drink, right?

    2. AHAndrew Huberman1:34:25

       Mm-hmm.

    3. MKDr. Max Krummel1:34:26

       You know, that, that issue is one that I think is really, um, is really critical in, in this, in this window of time right now. And honestly, I don't know what to think about the idea that p- people, you know, do experiments on themselves. I, I think we all wanna improve ourselves. We're all do- all, all do some kind of experiments on ourself. You're like, you read a book, you're trying to improve yourself, right? Um, the physical one gets a bit tricky when, uh, you know, you're not sure whether something's gonna be dangerous or not, but-

    4. AHAndrew Huberman1:34:48

       Oh, yeah. I'm not-

    5. MKDr. Max Krummel1:34:48

       Yeah

    6. AHAndrew Huberman1:34:48

       ... and I'm not promoting that people do this.

    7. MKDr. Max Krummel1:34:50

       Yeah.

    8. AHAndrew Huberman1:34:50

       I think that o- of course you wouldn't, would wanna see preclinical, clinical, and, and other, um, trials for this.

    9. MKDr. Max Krummel1:34:57

       I think I would personally. I mean, just-

    10. AHAndrew Huberman1:34:58

        Yeah. I mean, I'm, I... There are a few ar- areas well, where I am, um, a bit more adventurous, but for the most part I'm, uh, like, you know-

    11. MKDr. Max Krummel1:35:07

        Yeah

    12. AHAndrew Huberman1:35:07

        ... based on my training and background, I have to orient toward, you know, I, I'd like a bunch of o- Let me put it this way. I'd like to a bunch of other people to do it first.

    13. MKDr. Max Krummel1:35:14

        Yeah, yeah.

    14. AHAndrew Huberman1:35:15

        Like who wouldn't?

    15. MKDr. Max Krummel1:35:16

        Yep, yeah.

    16. AHAndrew Huberman1:35:16

        It's fun to be first unless you're doing something really stupid and that can get you killed.

    17. MKDr. Max Krummel1:35:20

        Oh, yeah.

    18. AHAndrew Huberman1:35:20

        In which case, like, let other people go first.

    19. MKDr. Max Krummel1:35:21

        Yeah.

    20. AHAndrew Huberman1:35:22

        Yeah.

    21. MKDr. Max Krummel1:35:22

        Well, the, I think a good example of that right now is, and this is, you know, sort of nationwide or even international, is vaccine hesitancy. And I know this is a touchy topic, so we can-

    22. AHAndrew Huberman1:35:30

        No, but you can be-

    23. MKDr. Max Krummel1:35:31

        ... if you guys are open. Well, I'll just point out that, that the, uh, one group that's completely, no matter whether they're hesitant against childhood vaccines and the number of them we get and the, the fact that the government makes you take them and these sorts of things, the, the... If those people have cancer, they're very interested in vaccines 'cause it's a... There, there's really good data that you can promote more immune cells against the, um, tumor by making a vaccine that consists of some of the proteins and peptides that are unique to the tumor and d- not different from you, and you introduce those as if you would introduce a virus or anything in a, in a childhood vaccine on similar concept, um, just different peptides. They're peptides from the tumor. And, and in those situations it's context, right? So if, if you and I had cancer and we don't have the, the conventional cures are not gonna work on us, we know, there we know statistics really well. Chemo is not very good for a lot of chem, you know, cancers, and so that's the only thing we got. But if you have access to something that's relatively new, and particularly vaccines, despite what, you know, some people worry about, they're Pretty safe. Um, and so the, the certain die versus try out a vaccine drives a lot of people to be interested in vaccines, and I would say, yeah, in that case, it's a really, you know... You can see where people's, their, their, their question about whether they're gonna try something or not is very context-dependent.

    24. AHAndrew Huberman1:36:46

        Very. I think, uh, I don't wanna go too deep into the vaccine debate, and I don't wanna be a spokesperson for either side because that's not my role today, but-

    25. MKDr. Max Krummel1:36:53

        Yeah

    26. AHAndrew Huberman1:36:54

        ... I think that the, um, the what you refer to as vaccine hesitancy actually comes back to an earlier issue that maybe you'd be willing to comment on.

    27. MKDr. Max Krummel1:37:02

        Sure.

    28. AHAndrew Huberman1:37:03

        Um, which is I think there are a very large number of people for whom they are neither anti-vaccine nor super pro, but they are, um, they're asking about timing-

    29. MKDr. Max Krummel1:37:14

        Mm

    30. AHAndrew Huberman1:37:14

        ... and combinations.
18. 1:39:37 – 1:49:22

    Pharmaceutical Companies, Public Distrust

    1. MKDr. Max Krummel1:39:37

       been feeling well, just straight up. And it is true, you know. And I'd say that a couple of the vaccines that have come out that I've had recently, the shingles one is a good example. I had it. It just knocked me completely out, and it, you know, it's very, very heavily adjuvanted, so it's clearly that it's, you know, it's having a... Um, does it, does it need to be? You know, I actually don't know. I don't know what studies were done. And, and there's kind of an, an aspect to which we, you know, I don't know that we're all, um, being shielded from the information, but I don't know that we all know how to read the information about how these regimens were chosen.

    2. AHAndrew Huberman1:40:05

       Mm-hmm.

    3. MKDr. Max Krummel1:40:06

       Um, some of them were chosen by competing pharma, pharma companies that each make their own, you know, materials. And, you know, again, I think there's a, there's a lot in this question. I don't know how much of it also represents the one problem with science that I could talk about is this, um, this issue that's a lot of science treat science as a kind of a papacy. Like, we know the language, we know the facts, and, and we probably don't have time to tell you why we think this and where we're, where the holes are.

    4. AHAndrew Huberman1:40:33

       Excuse me for interrupting, but, uh, you know, a huge basis of this podcast is to counter exactly that.

    5. MKDr. Max Krummel1:40:40

       I know. I know.

    6. AHAndrew Huberman1:40:41

       I mean, I know all these incredibly smart, incredibly well-meaning people who have lives of their own, health lives of their own, health challenges of their own, kids of their own, and on and on, and no one was hearing from them.

    7. MKDr. Max Krummel1:40:54

       Yeah.

    8. AHAndrew Huberman1:40:54

       It, it was... And as things get more politicized, there's less incentive to give nuance. I actually really appreciate you providing some nuance on the... I mean, it's clear where you stand on vaccines generally based on what you've said-

    9. MKDr. Max Krummel1:41:05

       Yeah, yeah

    10. AHAndrew Huberman1:41:06

        ... but you're, you're offering, um, perhaps the opportunity for, for better understanding and certainly delivery of the information.

    11. MKDr. Max Krummel1:41:12

        Yeah.

    12. AHAndrew Huberman1:41:13

        Yeah. I mean, it's a, it's a huge problem.

    13. MKDr. Max Krummel1:41:15

        Yeah. Well, I guess it's, it's one of those ones that I can only speak about what I did, right, as a, as a, as a human. When I had kids and I looked at the data, and I have probably better capacity than some anyways to read it and look at risk versus harm, you know, the percentages of these things, I absolutely has... You know, vaccinated kids, and that was, it seemed like, it seems even now like a, a reasonable no-brainer. But I just told you too that I, I asked to go off protocol because at some point I know these protocols have a little bit of like, again, they were designed on a one study. It doesn't mean that it doesn't work if you wait another month. In fact, if you do, if you've done enough mouse experiments as I have, you know that when you vaccinate on a slightly different schedule, you can still end up with the same outcome, you know, that is protection, you know, with slightly different schedules. It's not that convenient for doctors and hospitals and, and even sometimes for patients to get off on, you know, like, weird schedule, and then you forget a dose, and then it isn't as effective, right? So there's, there's efficacy that comes with, you know, trying to follow the protocol, and because the protocol has some convenience built into it, that means you're gonna do it. It's, um, it's like, it's like brushing your teeth in the morning. You do it in the morning, the evening, it's like it's when you do it, and so you'll do it twice a day. So there's a lot in this. I mean, like, you know, there's a lot of politics I think involved in, in vaccine too that relates to the question of like wh- at what point can the government do tell you what to do, which is, you know, it's, it's a, it's a surrogate question to the vaccine one, where a vaccine is, you know, if there's a harm, do, who gets to choose with the harm benefit and then How resources are given out for, like, schools and, you know, we know all these, we know all these sort of nuances. From the science standpoint, I don't think you wanna wipe out the baby with the bathwater. I don't think you... Personally, like, I wouldn't not immunize my kids. Could there be additional studies about the combination of these into, like, m- fewer shots? I think so. I don't see why not. Here's where you get the financial rise. What's the benefit to any pharma company of doing that?

    14. AHAndrew Huberman1:43:06

        Well, I think this is-

    15. MKDr. Max Krummel1:43:07

        Yeah. Yeah

    16. AHAndrew Huberman1:43:07

        ... again, I, I have to be careful that I don't place myself into an advocacy group that I'm not.

    17. MKDr. Max Krummel1:43:12

        Yeah.

    18. AHAndrew Huberman1:43:12

        I, I'm, I look at everything-

    19. MKDr. Max Krummel1:43:14

        Yeah

    20. AHAndrew Huberman1:43:14

        ... on a case-by-case basis.

    21. MKDr. Max Krummel1:43:16

        I, I try to do the same.

    22. AHAndrew Huberman1:43:16

        I, I really try to do that. But the, you know, and I've tried to be in recent years more open to the, to at least understanding what the anti-big pharma stance is really about.

    23. MKDr. Max Krummel1:43:29

        Mm.

    24. AHAndrew Huberman1:43:29

        You know, it comes up a lot around SSRIs, but you talk to somebody with clinical grade OCD, and they will tell you that SSRIs saved their life.

    25. MKDr. Max Krummel1:43:36

        Mm.

    26. AHAndrew Huberman1:43:37

        So there you go. Okay. Well, you know, so we can say all we want about pharma. Are you talking about people getting in-- taking insulin or, you know, until recently, the GLPs were mostly available through pharma. Now, they're sort of-- it's kinda the Wild West. People are m- microdosing them from all sorts of compounding pharmacies as their own issues and so on.

    27. MKDr. Max Krummel1:43:53

        Yep. Yep.

    28. AHAndrew Huberman1:43:53

        But my sense is that the frustration around the kind of dictatorial, like, "You're gonna do this at this point because this or else," like, "you're persona non grata."

    29. MKDr. Max Krummel1:44:04

        Mm-hmm.

    30. AHAndrew Huberman1:44:04

        That kind of... Like, people not, people being shunned in both directions, in either direction, rather. That's, you know, that, that's really the source of the problem. There, there really hasn't ever been a conversation quite like this.
19. 1:49:22 – 1:58:56

    Disease Risk, Immunity; Autism, Flu,

    1. MKDr. Max Krummel1:49:22

       knowledge is, is freer and knowledge is better communicated and that, and that, um, and that you do watch out for those situations where there should be, you know, a, a... And maybe vaccines are one wh- we, we, we, you know, we just need to do something sensible like what you're describing and just to do a study and say, let's do that study and, and make that very public that we do it and say that we're gonna do that and, and, and obviously people can sign up for, you know, via... You can have this regimen or you can have the old regimen or the new regimen and we... And, and you know, again, I, I, I may be speaking out. I don't do vaccines. I... It's not what my lab studies, but there could be some sense to saying, well, maybe science as a whole could take this on and say, what would be... Maybe the, maybe the answer isn't just say no vaccines and we, we think they do... There's good evidence that they're protective, but to the extent that you're coming at it, could we make it less... And, you know, let's, let's do it and let's just do it. Let's do that experiment. But I don't see that... That's one of the things that's not happening right now is that nobody's actually ch- describing an experiment.

    2. AHAndrew Huberman1:50:17

       Mm.

    3. MKDr. Max Krummel1:50:17

       What would be the experiment?

    4. AHAndrew Huberman1:50:19

       Yeah. Well, the discussions haven't happened, and I should say a couple of things. Um, first of all, thank you for being willing to venture into this area. I seriously doubt that any of your colleagues are going to be upset that you're having this conversation. I will make sure that anything we put out is in context. And if anyone cuts a clip, I will be the first to dive in there and say, "This is taken out of context." Uh, it, um, but, uh, to any people, colleagues or otherwise, that would say, "Hey, actually, this is the wrong stance. You don't wanna be talking about nuance in a time when there's so much threat to, uh, traditional medicine and vaccines, et cetera," I will say this: The idea that you need to push back with a, with just a fire hose of do this or else-

    5. MKDr. Max Krummel1:50:59

       Mm

    6. AHAndrew Huberman1:50:59

       ... did not work.

    7. MKDr. Max Krummel1:51:01

       Mm.

    8. AHAndrew Huberman1:51:01

       The pandemic proved that.

    9. MKDr. Max Krummel1:51:03

       Mm.

    10. AHAndrew Huberman1:51:03

        The... In fact, I think one of the biggest mistakes was to have one individual as opposed to a panel of people with more nuance communicating public health information at that time.

    11. MKDr. Max Krummel1:51:12

        Mm.

    12. AHAndrew Huberman1:51:13

        Any person, scientist, doctor, or otherwise, who thinks that the way to convince people to change their behavior around vaccines or anything else is to just ram it down the public's throat and say, "Or else you're whatever. You're political this or you're a fascist or whatever," okay? That is proven to be wrong.

    13. MKDr. Max Krummel1:51:32

        Mm.

    14. AHAndrew Huberman1:51:33

        And the path forward is really this kind of conversation.

    15. MKDr. Max Krummel1:51:36

        Mm.

    16. AHAndrew Huberman1:51:37

        It's highly educated people like yourself in the-- educated in the immune system who understand this, who have children, who've made certain choices saying, "Yes, and I can understand why you would be considering the following, um, questions, and we should do a study."

    17. MKDr. Max Krummel1:51:52

        Mm.

    18. AHAndrew Huberman1:51:52

        And, and in the meantime, you're not preventing anyone from getting vaccines. There's now a hunger for more nuanced conversation around these things.

    19. MKDr. Max Krummel1:51:59

        Mm.

    20. AHAndrew Huberman1:52:00

        I think it's the right time to have it when we're not in the throes of a pandemic. [chuckles]

    21. MKDr. Max Krummel1:52:03

        Yeah.

    22. AHAndrew Huberman1:52:04

        Yet.

    23. MKDr. Max Krummel1:52:04

        Yeah.

    24. AHAndrew Huberman1:52:05

        Yet. I mean, there's some things that are on the rise. It is scary. I'll, I'll be quite blunt that, um, you know, the, the rise in measles is scary. People say, "Well, measles, they used to have measles parties." Talk to somebody who had massive inflammation-

    25. MKDr. Max Krummel1:52:16

        Mm

    26. AHAndrew Huberman1:52:17

        ... and brain inflammation from measles. Not a pretty picture.

    27. MKDr. Max Krummel1:52:20

        No.

    28. AHAndrew Huberman1:52:21

        Not a pretty picture.

    29. MKDr. Max Krummel1:52:22

        Yeah.

    30. AHAndrew Huberman1:52:22

        So I think it's great that these conversations are starting, and it won't be taken out of context.
20. 1:58:56 – 2:08:02

    Biological Resilience, Cancer; Computational Research

    1. AHAndrew Huberman1:58:56

       and autism and other issues. But then the pushback is, well, this vaccine, et cetera, was directionally guided by sparse information to begin with-

    2. MKDr. Max Krummel1:59:05

       Mm

    3. AHAndrew Huberman1:59:05

       ... under times of pressure. There's financial incentives. So it's just this ping pong that goes back and forth. But many thousands of parents write to me and say, "Should I wait on certain vaccines?" And I'm like, "Listen, I am not the person to answer that question." [chuckles]

    4. MKDr. Max Krummel1:59:18

       Yeah.

    5. AHAndrew Huberman1:59:18

       Um, but you have every right to ask your doctor.

    6. MKDr. Max Krummel1:59:20

       Yeah.

    7. AHAndrew Huberman1:59:21

       Right? But they're not asking because they're extremists. They're not anti-vaxxers. They're asking because they love their kids-

    8. MKDr. Max Krummel1:59:26

       Right

    9. AHAndrew Huberman1:59:26

       ... and they've seen enough things to call into question the incentives, and they just know that the conversation cannot be as polarized as it's presented to them in re- in reality. The, the data cannot be as polarized as it's been presented.

    10. MKDr. Max Krummel1:59:37

        Yeah, certainly, certainly in media some of these things get presented quite, quite, um, you know, inflammatory. And again, if, if newspapers want to sell a newspaper, they show a plane crash, you know?

    11. AHAndrew Huberman1:59:47

        Right.

    12. MKDr. Max Krummel1:59:47

        So it's not happening every day, but-

    13. AHAndrew Huberman1:59:49

        But they'll show you an airline ad in the same issue.

    14. MKDr. Max Krummel1:59:51

        [chuckles] Well, there's that too.

    15. AHAndrew Huberman1:59:52

        Yeah. You know, so. [chuckles]

    16. MKDr. Max Krummel1:59:53

        I think one of the interesting things that, that we could get into to is, is that in u- in a lot of these studies, scientists are, there's a motivation to, to make the most of your result, and we've talked about why that's important, is that if you find something orthogonal, CRISPR, checkpoint blockade, uh, you know, X-rays, you look for that orthogonal use for it, right? And you... Or that, that orthogonal meaning. That ex- Sometimes we call it extensibility. Like, I see that if I, if I drop a coffee cup on the thing, that gravity pulls it down. Well, then I can learn that, uh, eh, I can drop all kinds of things. I can make gravity work for me. You know, it becomes a tool. And, and I think one of the things that's, that p- that, that is lost sometimes is that some things are not extensible. So, you know, you can imagine that, like, if I, if I had something that move-- makes a cell move, that that might screw up the whole system forever. But humans and our bodies turn out to be remarkably resilient. I mean, we can go from minus twenty degrees to f- you know, a hundred and ten degrees. We can not eat for a long time. You know, we can... You know, all these things don't cause us to fall apart. So if we didn't have resilience, I think our species wouldn't exist because there's all these pressures and all these varieties of life under which we lead. And I think a lot of science sometimes doesn't, you know, it, it... And, and, and From the outsider, even as an insider, you can read a paper and they, they, they point to why it might be important. But they're really doing that to, to, to, to ga- garner interest for their story, you know, and then say, "This might be important for this, but I haven't shown that it's important for it." They, they don't say that it's important, they say it might be im- important, and they're trying to look for that orthog- that, that orthogonal or that extensibility of it. And I think that's kind of important also just to go a little bit off this topic for a moment in how we think about drugging diseases as we go forward. And that is to say, we've looked for these one and done drugs that are you, you, you take a pill and it cures everything, you know, forever, and that's sort of found of youth-ish. And, um, you know, we found a few of those. I would say checkpoint blockade is one of those, that you can take it and, you know, in 50% of melanomas, everything, the tumor goes away and everything's great. But most biological systems, if you have one button to push, they're super non-resilient. A virus can exploit that button, uh, you know, it, it, that, that can cause, you know, it collapse. And so most things are wired, like, in these really complicated ways. And I think what a few of us are thinking, this is for cancer in particular, where you wanna get the immune state from like, remember we had our little concept of a fuel gauge, you wanna get it from one position to another position. It may not just be about a push here. You may have to push some cells that way, create some new environment that looks like development. You know, your cells develop through states and, and you push the, the, the biological systems to reach this new state in a way that doesn't look like they're linear between, like, low immune reactivity and high reactivity. You might have to push it in a serious way because resiliency, the resi- the, the, the systems, like even in chronic disease but even in health, we're pretty resilient. You know, we, you can stand up to a lot of stuff.

    17. AHAndrew Huberman2:02:40

        Can humans do that even in the context of abundant funding for basic research?

    18. MKDr. Max Krummel2:02:45

        Mm.

    19. AHAndrew Huberman2:02:45

        Can what you just described actually be tested to the point where we can develop things? Uh, and the analogy here is I had my dad on the podcast, he's a theoretical physicist, and he explained to me that one of the most important things you learn in physics is that you can't really understand quantum mechanics using your logical brain.

    20. MKDr. Max Krummel2:03:05

        Okay.

    21. AHAndrew Huberman2:03:05

        You, you need the math to prove it.

    22. MKDr. Max Krummel2:03:06

        Mm.

    23. AHAndrew Huberman2:03:07

        And this is when whenever somebody-- he also warned whenever somebody says they understand quantum stuff, you, you have to ask them to demonstrate it for you.

    24. MKDr. Max Krummel2:03:14

        To leave. Yeah, yeah.

    25. AHAndrew Huberman2:03:14

        Because these people talk quantum because-

    26. MKDr. Max Krummel2:03:16

        Yeah

    27. AHAndrew Huberman2:03:17

        ... and, and we make all these assumptions about quantum, they talk about quantum fields, so we think they're smart.

    28. MKDr. Max Krummel2:03:21

        Mm-hmm.

    29. AHAndrew Huberman2:03:21

        But, but the theoretical physicists and therefore engineers get, you know, develop all sorts of incredible, uh, theorems and real experiments and then technologies based on all of that-

    30. MKDr. Max Krummel2:03:33

        Mm-hmm, mm-hmm
21. 2:08:02 – 2:13:34

    Autoimmune Conditions, Asthma, IBD

    1. MKDr. Max Krummel2:08:02

       wanna like hammer to get the system to go to that, but then it might be conli- connected to another one. And we all wanna find the one thing that like, you know, the fountain of youth, the thing that cures a disease and, and, and it's been forever that we've been looked for a single, you know, single hits, one, one and done. But it may be a collection of... And, you know, this is probably, this is how I live my life for health too, is there's collet- con- collection of behaviors and food you eat and sleep you get, and-

    2. AHAndrew Huberman2:08:25

       Mm-hmm

    3. MKDr. Max Krummel2:08:25

       ... all these things create, and partners, you know, the, the, you know, your loves of your life, the, the friends you have. They, they're all part of, I think, this, this... And, and that's getting a little away from immunology, obviously, but it-

    4. AHAndrew Huberman2:08:37

       No, but not-

    5. MKDr. Max Krummel2:08:38

       It's an analogy

    6. AHAndrew Huberman2:08:38

       ... well, we're talking about the insula, you know, not so much-

    7. MKDr. Max Krummel2:08:41

       Yeah

    8. AHAndrew Huberman2:08:41

       ... a good friend of mine who's a physician in the Bay Area says, uh, you know, "Better living through chemistry still requires better living."

    9. MKDr. Max Krummel2:08:46

       Yeah. [chuckles]

    10. AHAndrew Huberman2:08:47

        Which I love because it says you should never abandon as much as one can the foundational stuff of sleep, exercise, nutrition-

    11. MKDr. Max Krummel2:08:53

        Mm-hmm

    12. AHAndrew Huberman2:08:53

        ... circadian rhythm, light-

    13. MKDr. Max Krummel2:08:55

        Mm-hmm

    14. AHAndrew Huberman2:08:55

        ... social connection, you know-

    15. MKDr. Max Krummel2:08:57

        Mm-hmm

    16. AHAndrew Huberman2:08:57

        ... stress mitigation, and on and on.

    17. MKDr. Max Krummel2:08:58

        Right.

    18. AHAndrew Huberman2:08:58

        Could I ask you a couple of additional questions about the immune system-

    19. MKDr. Max Krummel2:09:01

        Yeah, please

    20. AHAndrew Huberman2:09:02

        ... um, before we wrap? Because I know, um, many people are curious about autoimmune-

    21. MKDr. Max Krummel2:09:08

        Hmm

    22. AHAndrew Huberman2:09:08

        ... issues. More and more, I hear about, you know... I don't know if it's chronic fatigue considered an autoimmune issue by most. Uh, uh, a lot of people seem to have chronic fatigue. There was a debate, does it really exist? For someone who believes they have it, uh, they, it absolutely exists.

    23. MKDr. Max Krummel2:09:23

        Yeah. [chuckles]

    24. AHAndrew Huberman2:09:23

        Um, they're tired. I believe them.

    25. MKDr. Max Krummel2:09:24

        Mm-hmm.

    26. AHAndrew Huberman2:09:25

        I know someone who had a myalgia-

    27. MKDr. Max Krummel2:09:27

        Hmm

    28. AHAndrew Huberman2:09:28

        ... uh, recently. Um, psoriasis is something that I maybe, uh, have known, uh, to be now autoimmune.

    29. MKDr. Max Krummel2:09:37

        Hmm.

    30. AHAndrew Huberman2:09:37

        Um, asthma.

Episode duration: 2:27:40