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

Key Takeaway

Your immune system consists of 10 to the 11th T cells acting as individual sensors, constantly measuring biomolecules in your body to detect what's 'in range' versus 'out of range.' As you age, accumulated mutations make your cells increasingly diverse—like a complex mosaic—making it harder for your immune system to distinguish threats from normal variation. This is why older adults are more susceptible to both infections and cancer: the immune system struggles to identify what's truly dangerous when everything looks slightly different.

Episode Overview

Dr. Max Krummel, a leading immunologist from UCSF, explains how the immune system functions as a sophisticated sensory network that not only fights pathogens but regulates metabolism, brain function, gut health, and more. The discussion covers how immune function changes across the lifespan, why children get sick frequently but recover quickly, and how aging creates a 'mosaic' of cellular mutations that confuses immune surveillance.

Full Transcript

Transcript of How Your Immune System Works & How to Improve It | Dr. Max Krummel from Huberman Lab. Auto-generated from episode audio; may contain minor errors.

A famous 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 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. fire. 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.

Welcome to the Huberman Lab Podcast where we discuss science and science-based tools for everyday life. life. 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. Cromer is incredibly balanced throughout today's conversation, and yet he's also willing to state his views 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. Cromer has an incredible zero-cost Substack. It's called The Immune Beyond. You can access it by going to the immunebeyond all one word {dot} substack {dot} 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 Cromer. Cromer. Cromer. Dr. Max Cromer, welcome. Thanks. Thanks. Thanks. 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 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 want to 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.

understand. understand. When I started immunology, sort of 30 years ago, years ago, years ago, I was rotating in labs at Berkeley, where I think you were at Berkeley as well. well. well. And one of the transcription factor biologists, you know, mentor said, "You know, why do you want to work in immunology? It's not really a field." And so at the time it was kind of true, you know, everything was about DNAs, cloning. We still, you know, it's obviously still a lot about molecular biology what we do.

But 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. foreign. foreign. Um and otherwise it generally had to be quiescent and kind of 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 if when a T cell would activate, and allowing T cells that might be just letting the tumor get by, get they they'd be able to go and go after that tumor and and and kill it.

I think that changed the spectrum to 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 kind of not exactly self, but it's 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 20 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. And 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, the brain, there's microglia that do various functions, cleaning up, etc. 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 kind of like the right quantity. So, it's kind of guarding yourself.

It's uh you know, it sits in your liver your liver 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, regulating cardiomyocyte function. Uh those are the the muscle cells of your heart. heart. 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 where where lost in the in the just you know, the foreign battle against the foreign.

And now we have this kind of perspective of the 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, 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 it's a tumor or kidney disease or what have you. It can it can actually help perpetuate it because well, it's you know, in some ways it's trying its best.

But it's applying the wrong program to the wrong situation. situation. situation. Come on. Come on. Come on. So, yeah, it's it's changed a ton. I'll give you another little funny story which is that that you know, when I first came to immunology again we had the story like you know, you know, mentor who says you know, this isn't really a field. The year was like I came into the field in 1989 and that's right at the peak of AIDS. And um AIDS was like as as a biologist was really because you know, the the HIV virus infects T cells.

So, your body is filled with 10 to the 11th or so T cells. Like a ton of different kinds of T cells. T cells. T cells. And you had a subset of T And you had a subset of T cells that are called CD4 T cells. They're kind of a flavor of T cells. And 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. them. them. And the the manifestations of AIDS for those who 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 Kaposi's sarcoma. You saw like a opportunistic like where, you know, cancers emerging. cancers emerging. cancers emerging. Um, and you just saw all these kind of manifestations of where the immune system was important. Demencias in in people with HIV as well. You know, it was a really accent time on how many different things the immune system might be important for.

So, regardless of whether, you know, it was 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 it in the beginning, you know, they they don't live, you know, it's it's sometimes hard to keep cells out of out of a human cells out of out of a human body alive.

body alive. body 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 set of biomolecules, proteins. They 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 10 to the 11th little sensors going around you curating you.

curating 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. magnificent. magnificent. It is magnificent. Do you mind if we take a developmental perspective on this for a second and then I have a basic health question. 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.

Yeah. Yeah. Yeah. Maybe you could describe what's going on there. there. there. Yeah. Yeah. Yeah. And it also is the case that you know as we get older much older in fact, last quarter of life, let's say, people tend to get sick more. What's going on in terms of immune system function system function system function or is there something more broadly happening at level of just kind of energetics, mitochondrial function? Very curious about this. If I can take a step even further back I'll 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. But the more of 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 of 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 bile acids that allow you to digest animal fats. So you need this system that's around you. So you aren't just the cell like if you learn biology you've got the 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.

cells. cells. [snorts] [snorts] [snorts] But in fact it's it's it's it's absorbed a lot of viruses and and bacteria from our environment. our environment. our environment. And you know to go into that really briefly, that's really important because we only have 20,000 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 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 seaweed. seaweed. 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 I I think worth pointing out at the early phase of life. One of them is for the first 6 months or so, your immune system is pretty poor at being trained on things.

And it's presumably we presume that for those first 6 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 you're, you know, your your immune system's like, "Oh, I I see something different and now I need to react." react." react." So, that's well known and that's that's one of the reasons why some childhood vaccinations, they're really important to protect kids in long over life, why they aren't given until you're 6 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 into their 10 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. Cuz they've never seen it the body's never that body kids body has never seen flu before. So, every single virus and pathogen that hits it is going to elicit some of you know, some amount of illness.

illness. illness. But, then they have a very strong immune system it reacts and you know, gets rid of that. of that. of that. With the exception of the ones that are you know, are those those certain viruses and bacteria as mumps, measles, rubella that are they're 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 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 the one idea of aging right here. We know that that we just were supposed to be dead by 70. Well, no, but we do know that that we can reproduce and and you know, pass on our genes successfully already when we're 16. So, you know, the the selective pressure to pass on your genes if you imagine that's how genetic evolution happens is that you pass on your genes as being successful. You can already do that at 16 and anything after that is just cream of 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. The psychologist would tell us that uh the wisdom of people, you know, 60, 70, 80 and beyond is useful for um groups of humans that live in, you know, you know, villages of a hundred or so people cuz they can give information to younger people that is on the periodicity of like every 5 to 10 years, maybe every 30 years.

years. years. But that's a just-so story, right? That I mean I mean I mean It's a nice just-so story. I like I like I like too and I and the I think genome uh geneticist will refer to this as like the grandfather effect where genes may be selected for and maybe they're mostly about you know, genes that make us social in the and for for for the elderly that do you know, they're going to have effects on the fitness of their grandchildren, which is their genes.

Mhm. Mhm. Mhm. And so this yeah, 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 It's a tough experiment to do. It's a really tough experiment to have two villages where they you know, grandparents are eliminated or like kept you know, it's both non-ethical and also non-ethical. Right. Right. Right. 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. It's many of the cells that you you know, you've been holding your whole life start to 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 you you basic biology would say the sperm you know, like uh fertilize the egg so you got your mom's genes and your dad's genes. So you got 23 chromosomes from your mom, 23 chromosomes from your dad.

And and and at least in when you're first born, every cell is a clone that has the 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 10 and 30,000 mutations per cell per day. Just from like 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, it's susceptible to UV radiation.

That's one of the reasons we put on sunscreen. [gasps] [gasps] [gasps] But what it what it practically means and no matter what number you put in there, whether it's 10,000 mutations per day or remember the the genomes are huge, right? So 10,000 mutations out of terabytes of of of information still is only a certain number, but do that over every over over years. And the main thing is 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. a mosaic. a mosaic. And I say mosaic, you know, because like the tile you see in 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 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.

And there's one of the other clones over here that had got a different mutation may not be fit to fill that clone in. So you 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? other cell? other cell? It's it's it Okay, you want to you want another analogy? another analogy?

another analogy? I would like another analogy. The only exception that I can think of to this, and I could be wrong, is that our neurons, neurons, neurons, our central nervous system neurons, our brain and spinal cord, most all of them are the same ones that we were born with. with. with. Same cells, but they don't Same cells, but they're So you're saying mutations are constantly occurring in the neurons as well. So there's there's this It is fascinating, by the way, that neurons live that long. And, you know, hair cells, they they say that the the proteins in our in our hair hair cells over here are the same exact molecules, atoms, as we had when we were born.

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

radiation. radiation. They they they they they hang out in stem cells are, you know, the the bone actually serves not only a structural purpose in our body, but they it's a cavity in which things can live. Keep it away from from UV from UV from UV solar radiation solar radiation away from chemical cues in the environment that can mutate. Sequester your stem cells. And um And um And um Don't burn them. Yeah. Yeah. Yeah. That kind of thing. Yeah. Yeah. Yeah. Likewise, the neurons in the in the uh inside of the skull Yeah.

Yeah. Yeah. and the spinal cord are protected. are protected. are protected. Um they're protected. Yeah. Yeah. Yeah. And uh that's interesting. Yeah. Yeah. Yeah. I would like to take a quick break and acknowledge one of our sponsors, Joovv. Joovv makes medical-grade red light therapy devices. therapy devices. 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.

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Sometimes I tend to send to 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's pro-immigration because all these bacteria that live on us are actually bringing us goods. And they they do a lot of lot of lot of lost half the audience. I'm I'm I'm No, I'm just kidding. I'm totally joking. joking. joking. We we're a we're a bipartisan audience.

I'm I'm I'm totally joking. totally joking. totally joking. I'm totally joking. It's the argument for, you know, why why certain certain certain you know, influx of of of in this case organisms under us or you know, create a more robust, you know, person than we were before. But I want to give you this this story that one of a famous immunologist in the 1970s 1970s 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 and the torpedoes because that could be the enemy and the enemy could fire at them.

[snorts] [snorts] [snorts] 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 a certain cycle of a general you know motors engine, they wouldn't fire. So that's the sort of like self I know what self is. self is. self is.

And then they had another book that was the engine sounds of the known diesel engines of whatever engines of the German German 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 that 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 going to make proteins and that's your immune system can see the viral proteins and say say say 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 the 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 is just you know has a lot of cosmic background.

That's 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 issue 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. cancerous. 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 you 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. What about the argument that there's so much cellular turnover that um that um that um the cells that accumulate these mutations are being eliminated. You're saying because they're clonal, they're producing producing producing different they become different they produce cells that are also different and then they die.

Is this Is that the way it works? Yeah, and I think I think you're you are bringing something that's also true, which is that all the time I think the immune system is defending us against, you know, mutations. So, one example that everybody sees when they get to be about 40 or or 50 is is little these white spots on your skin. And we we think that those are places where the immune system has sensed a collection of cells that were precancerous, maybe they were even beginning of cancer, and has wiped them out.

And and so there you know, know, know, a lot of the origin of cancers in skin is is melan and then producing cells like melana, you know, melanoma is skin is what we call skin cancer. Um those melanocytes that that white area that's been wiped of a whole collection of melanocytes and that's why it's, you know, it's it's white [snorts] [snorts] [snorts] instead of as dark as your as your 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.

for that. for that. Um Um Um and the question is when does something become dangerous? become dangerous? become dangerous? As that's that's that you know, that's fundamentally the question with cancer and these sorts of things. If If you said, "I want to actually have the fittest cells in my skin to uh fill in a gap if I scratch myself." I would like to have cells that quickly replicate just like maybe in kids. Kids heal so ridiculously quickly, right? right? right? Because they have an abundance of these cells that cells that cells that I think I think they're they're they're wound healing.

I mean, there's 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. There's many levels of that, yeah. But um yeah, remarkably faster. And if you're a parent, you've seen this, you know, you know, you know, you cut yourself in the same day as a kid, your kid cut yourself and they're they're 3 days later they can't even find it on them.

And you know, like 4 weeks later you're still like kind of, you know, scabs or something. But I was just coming to the point that if you do that and and you want this do you want you maybe you want that to fill back in because you know, certainly out in the wild having an open wound is a bad thing. So you'd like to you know, quickly. quickly. quickly. Well, if a mutation has happened that fills that cell in quick more quickly, that is almost by definition a mutation that's let that cell divide faster.

Well, what is cancer? It's cells that divide faster. So in some sense, all these advances in your life were winners win by filling in the space left by cells that die is selecting for cells that get a little out of range with growth. And they may be a little bit better at growing. And then again, there's a quick question it's like, well, how much better do you want that? You want it to like help you, but at some point you don't want it to basically form a lesion and will grow grow grow grow grow and go other places and grow, which is called metastasis in cancer, which is how most people die.

To me, the the issue of self and non-self is one of the ones that's been with immunology for a very long time. And again, it's way richer than we thought about, I think, in the 1990s or 2000s. But you know, and then at the same time, the idea of what you can do with that information is also I call this kind of a new immunity. Immunity used to be like a fuel gauge. You'd say it was low for self, then it was really high against viruses and it was like a fuel gauge you know, now it's really hot.

And what we originally thought we were doing with cancer immunotherapy was making it just hotter generally. But now you realize that in between like the immune system not caring about something at all and and going and you know, like releasing all its fury on something are all these other things it can do with the information it gathers in there. And that's what I was saying, you know, it can it can like quarantine bacteria. It's not going to kill them. It's it's in that zone. The bacteria, as long as they're in the right zone, there's not too many of them, there's not too a of them.

Immune immune can actually help them be there. It can produce things that like either titrates them out of circulation or keeps them there. there. there. You know, in all these other studies, like I say, in the heart and the you could almost any organ and and you know, your immune system is consistently present and it's consistently measuring you. And the you again is this complex you. It's not just what came from the egg, it's the you that's you right now, including all the mutations that you might have accrued and all the bacteria and and the and the viruses, you know, we have a lot of viruses in our bodies that we tend to think that at the end of a of a illness that we've gone back to our pure state.

This may come from religion, you know, that we were born pure and if God had made us correctly, then we would be pure at the end of things. things. things. And you know, that would be pure immunity which would purify us of things. things. things. But the more we look, the more we find that every virus leaves a little evidence of a little bit of itself. And then there's a then there's the goal for the immune system to kind of quarantine that. To say this, you know, maybe we don't want to kill every one of our cells to get rid of every virus that's infected one of our cells.

We need to leave some of those alive. We don't like for example, in in herpes virus infection, it infects the nerves and when people have you know, emergence, they they get nerve pain and worse. A lot of that is caused by the immune system reacting to the virus trying to get out and then killing off neurons. So the the the it's immunopathology. The immune system is called causing as much of the damage and problem as the virus is. And it's the failure of that detente and when certain viruses are just sitting in us, we're perfectly fine.

You know, we have viruses in your RNA. As long as they're laying dormant, our immune system can say, "Okay, I'm going to just hang out here and if anything bad happens, I'm going to squelch that." But it's not like we've been purified. 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 bad or an early liver infection of a HCV or HBV.

or HBV. or HBV. If the immune system can just let that be, you're not going to destroy your own liver and you'll live to produce and your genes will get passed on. On the other hand, if you mount out a massive immune response, you know, you went all the way in the fuel gauge to the right, your immune system can kill you. It absolutely can. You know, it's can kill any cell it wants. So, so that that that again, that idea that the space in between is the one that we actually are starting to understand that has all these specialized roles that are not always about getting rid of things at all cost.

This raises a question for me and obviously I'm not an immunologist, but it seems like one You're going to be one by the end of today. today. today. I hope so. I like the sound of that. Um as will the audience. One potentially useful useful 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 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?

So that if we are indeed born pure um in the biological sense, um let's just keep it there for the sake of today's discussion. And, you know, by time we are um you know, 32 years old, we are a mosaic of mutations. As it it appears we are. If the immune system could surveil multiple regions in the body, maybe compare organs or maybe keep it within organ system and say, you know, know, know, the number of of mutated cells or not pure me cells 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 going to fight." Yeah. 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 but if it's uh of an of an attack, they'll uh fight back. Yeah. Yeah. Yeah. It seems like there should be some way to that the immune system could quantify either body wide or or local organ or or over some period of time they could integrate over time. I have to imagine that such a mechanism exists.

You're coming from neurobiology as I know, and so there is that in neurobiology of accommodation, right? If I always tell the story of I went to this little village in in France called Époisses. Époisses. Époisses. If you know the name, Époisses is a kind of a famous cheese that they make in this town, and it's super stinky. And they make it only in that town, and they make a lot of it in that town. And so when you drive into that town, it's like somebody has the worst foot odor.

It's striking. It really hits you. But after being in the town for like an hour, hour, hour, Mhm. Mhm. Mhm. you don't notice it. Yeah. Yeah. Yeah. And that's neuronal accommodation, where your nervous does the same kind of thing you're talking about, where the you know, the know, the know, the uh sensors in your nose can become They're like, okay, I've seen it, I've seen it. Now it's not anymore. And And so I'm going to tune that out because then your nose has the potential to smell other dangers or other stuff, right?

right? right? So that's the nervous system. And I I think you're exactly right where you're going with this is And we think this is true that the immune system is it you know, for danger, it's looking for something that you would call like a it's how it's seen the signal over time. So a virus may you know, the Let's Let's say your T cell recognize a virus. Well, you're looking for something that you've had nothing of before. And then all of a sudden the virus comes in and starts replicating, and you have a lot of it.

And then at some point, if you get rid of it, it'll come back down to next to nothing. And in that period you mounted a an immune response, [clears throat] and you learn it, and so the next time around you'll be faster to respond to it, and keep you from getting sick. sick. sick. That's one kind of signal. But self can have either one of two signals, I think. One of them is that you've had it your entire life. So that amount of protein, maybe it's a maybe it's insulin, you know, which we think in general, you know, it has a little bit of signal up and down as you have a sugar, but there's a range for that.

And so your body gets to used to that range, and the T cells that see insulin, they are very low. They're going to only be very very low reactive to that. And there's there's a whole story behind that. But basically, they're going to see that level. But you can also have things that the immune system is going to want to treat like self that maybe do a slow rise. They don't have this peak that you have with viruses. So like a a mutant cell, and maybe it's just a tiny tiny bit above normal above normal above normal for months.

And then it makes two copies of itself. And now it's a little bit higher than normal. The immune system is, you know, has I think one of the deficits with cancer is exactly that. That things that you do, and and this is sort of like I tried to live my life a little bit this way, but it's not validated by any, you know, any experimental stuff. It is the idea that whatever you are is what the immune system is going to help you be. If it if it's if it's a slow direction this way, it's going to be this way, it's going to be okay with that.

What it doesn't like is like big spikes. And and and and and that's maybe the signal that you're asking about. Like could you actually get to the point where you'd be reactive? The problem with cancer is that it is, you know, the slow and nefarious. It grows over time. And it and and I think we're made to absorb slow change. Mhm. Because if it's not causing us to be sick yesterday and a little bit more of it isn't causing us to be sick today, then it's probably just a developmental change.

Maybe it's a new bacteria. Maybe it's a new, you know, that that that's commensal. As as long as it doesn't accompany, again, viruses have two features in common. One one is the spike of of, you know, appearance. But they also cause damage in that window. And so you have like these cues that I think the immune system, and I say the immune system because it's some cells are going to see the damage and some cells are going to see the the additional proteins that come in.

And and then they exchange information just like your brain, you know, we know, we know, we 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. say. say. The immune system has this collection of cells that are they're literally crawling around us right now. And we used to do we still do a lot of imaging. If you look in a a of skin, you can see the cells of the immune system are really really surveying us.

They're crawling around. crawling around. 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." And then the other says, "Oh, you saw that? Well, I you know, I'm just seeing this." And they can, you know, form a cluster of cells that basically get together like a neural little mini brain in our tissue and they can say, "This is bad. We got to 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, yeah, it's not that bad." I realize this perhaps is not your immediate area of research, but recently I've been seeing a lot more interest in the thymus. Mhm. Mhm. Mhm. This organ that we have when we're young and it disappears as we get older and there's a lot of interest in the thymus. Maybe Maybe Maybe because [snorts] we've never covered the thymus on this podcast in any amount of detail. If you could just educate us a bit what it is, what it does, and why it might be interesting as a as a therapeutic.

I mean, maybe we in a few years we'll all be banking our thymic cells. cells. cells. Maybe we will be I know some people are already injecting non-FDA approved peptides that come from the thymus. I'm not recommending anyone do that, but people are already doing it because that's the the internet in 2026. What's the thymus? What does it do? Why this interest? this interest? this interest? Yeah. Well, I can back up one step and I've I've used the word T cell before. And T cell originally was thymus cell.

So So So for those that maybe don't, you know, have gone to had blood taken, you know, you 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 organ 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's a There's a who's alive, he's like 97 years old in in Australia who did this saw that did this remarkable kind of experiment. There was this time when kids that had heart issues heart issues 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, they're they're cutting open.

open. 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. thing there. thing there. And so they're like, "Oh my god, part of the heart thing is this overgrown thing." They didn't really know what it did. did. did. [snorts] [snorts] [snorts] And so they would remove it. And uh the kids then go home and they it was usually exploratory heart surgery, but kids would go home and uh far from you know, dying of heart disease, many of them would die from like opportunistic infections.

They'd get all these infections, they'd get flu and and 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 who's who's this this nice 70-year-old codger in in Australia. Australia. Australia. At the time he was in in England and he basically took a bunch of mice and and when they're newborn he removed their thymus, the same same little whitish organ.

organ. organ. And sure enough, those mice were they they basically grew up okay, but then they all would succumb to bacterial infections. And in fact, a few of them even got tumors, which was kind of 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 convoluted pathway. You remember how we were talking about how the stem cells of your immune system lives in your bone?

Well, there's stem cells that live in your bone and they travel through your bone through your blood to the thymus and become T cells. And [snorts] the the reason they need to do that is that the thymus is this kind of super special place that is able to present to them to show them all of the genes in your genome in various different ways. different ways. different ways. And so the T cells that come in there, they're T cells are developing and they each have a possible 10 to the 11th different kinds of receptors to smell different things.

different things. different things. And you don't want any of them to come out that are too reactive to you. So, you don't want to produce T cells that are going to go off and and and kill your pancreas or, you know, kill your big toe or anything, right? You want to you want to maintain like tolerance. So, you want to make sure that you don't make the immune system that's too harsh. So, the the 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 correctly tuned correctly tuned to to let you be you in that way.

Now, [snorts] to the point about the the story and you were asking about aging is that is that in kids those are really big because at that point we're talking about the developing immune system. It has to has to 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 going to see over life.

So, your thymus has this huge output. So, as a like between like between like between [snorts] [snorts] [snorts] really from, you know, three to six months old and, you know, into your into your four or five years age and but tapering, your body makes tons of T cells and it's because of probably what you're talking about. You're getting exposed to all kinds of different back 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. tiny. tiny. [snorts] [snorts] [snorts] And um And um 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, example, 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 of your normal cells and other T cells in your body that it's normal. Maybe 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 so long ago, and he I'm sure he would have talked about engineering cells that you can engineer on the outside and give them specificity. But [snorts] the sort of like if you will the more natural route to that might be to to let the thymus make you some 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, and 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 there just wasn't needed. Because if you've got you get to 30 and you died of an arrow wound, you know, you know, and but you've given your genes, you're you're a winner in the evolutionary sense.

sense. sense. You know. You know. You know. I love this uh uh this stance on well, if you've already reproduced, I'll just I'll 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 UC Santa Cruz, and his wife Sophie Salama is also phenomenal biologist, a mutual friend. And years ago I was in Dave's lab because we're long-time collaborators and published a bunch of papers together, and uh he was doing some injections. I'm going to get you in trouble, Dave.

He doesn't do this any longer. Yeah, I'm going to join him Yeah, I'm going to join him to get you in trouble cuz we doing some injections, and he might have been using been using might have been using carbocyanide dyes. carbocyanide dyes. carbocyanide dyes. This was kind of conventional tool bag. 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 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 carbocyanide dyes. dyes. dyes. With cyanide being the being the being the And I said um Dave, Dave, Dave, uh uh uh don't you want to put on gloves? And he literally looked up from the microscope and he I'll never forget and he said I've already successfully reproduced. 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. But um there's an interesting mindset among you because he comes from cell biology. Yeah, yeah. Yeah, yeah. Yeah, yeah. Randy Schekman's lab. Nobel Prize in Nobel Prize joining laboratories as graduate student. So I I find it remarkable that this this stance of 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. And not just creating them and then dying.

Agreed. I think there's a fitness associated with being older than that. And And again, when I say that this it is maybe just taking this from a purely like what would have been the source of what we are today? You know, what would have been the selective pressures on them? And it would have been a little bit like Dave is saying, you got to you know, the selective pressure is to get your your your uh you know, for it for for my genes to be passed on, my offspring have to be born.

born. born. And then have to get to some age because most humans are born pretty incapable for a period. It's not like giraffes where they drop off and then you know, drop out and within an hour they're running. running. running. Um Um Um [clears throat] [clears throat] [clears throat] so that that that period of of raising children, I think creates more pressure in in humans to to to you know, to successfully be healthy longer. But I guess just you know, that maybe a negative viewpoint and then maybe but that concept that maybe there isn't as much pressure for you to be healthy.

And And going with this is the idea that some of the things that we want to be super efficient early on might actually be bad for us as we get Like I'm like I like I think this issue that I that I brought up of our mosaics is is a is a real confounder of everything because that creates something that is quite hard to defend against, I think, that that that that aging backdrop. Um, and uh, you know, some of the immune system that is really going to be important to just be super reactive early on may have some, you know, compensatory problems when in faced with that new reality of a 50-year-old or 70-year-old or whatever.

It looks quite, you know, looks quite more complex, but you would have definitely you would have definitely wanted in gene space, you know, in that gene space gene space gene space what genes you have to select for, you know, an immune system, let's say, or even just your body system that makes sure that you get to 30, let's say, are you. And and it's again, you know, there's That isn't to say that we can't overcome some of those deficiencies if we understand them. But here's my plug for basic research is that to understand them we have to ask some to some questions that are almost 90% of them are going to be dead ends.

You know, you can hypothesize it's one thing, but you got to do the experiment to like eliminate that. And this is one of the things that people I don't think always understand about science is that for all the discoveries that, you know, I've made or other people have made there were hundreds [snorts] and hundreds of like disappointments. You know, and you'll recognize this where you you just go home from the lab at the end of the day and you've, you know, you've you've done everything right right right but the answer isn't the one you isn't the right one.

Yeah, one control experiment can nuke your whole project. Well, there's that. There's obviously that you have to do the experiment well and have a control, but but the answer just could be not the one you thought. And and you know, we can only imagine stuff and then try and see if it's true and or or or more importantly try to prove that it's not true. That's what the better experiments that kind of we we call them killer experiments, right? The ones that going to 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, you know, there's a lot of intuition that lot of there's a lot of intuition that we all can put into this whether we're like like like professional scientists or at-home scientists. scientists. 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 maybe the word is baroque, you know, like like like [clears throat] [clears throat] [clears throat] 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 seemed like it might be kind of simple is so complicated.

The world is so strange." Well, when I started in neurobiology, the brain the actually the entire central nervous system was considered an immune privileged organ. Yes. Yes. Yes. There weren't supposed to be immune cells there. And thanks to the beautiful work of Carla Shatz with the major histocompatibility complex work and Ben Barres Ben Barres and I'm failing to mention all their scientific offspring Steven Chala Erdoglu like and on and on. It take the rest of the episode to name all all of Ben's scientific offspring and Carla's too.

too. too. And you and being you. Right, I didn't work on those issues, but but but but I was in those labs when it was happening. We now know that the immune system is actively alive in the central nervous system throughout the whole lifespan serving critical roles. Yeah. Yeah. Yeah. 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 and and [clears throat] like that that adenosine inhibits T-cell function or something? Do we actually know? Because I think all of us are familiar with the fact that if we we don't sleep well or enough for a couple of nights, we're much more susceptible to getting sick. Yeah. Yeah. Yeah. Is there a mechanistic understanding of why that's so? I think there are bits and pieces of it. I think I think I think some some really nice work shows that at night a few wacky things when you're asleep a few what you might have thought would be wacky things happen and and one of them is that a lot of your immune cells clear back to the bone marrow.

And and your tissues become populated with a bunch of neutrophils that come out of the bone marrow and and seem to be you know depositing collagen around your body and and so there's a lot of things that I think are reparative about sleep. I thought about this a lot in my own life as probably you have with sleep as to one one of the questions of course is why do we bother to have sleep? And and I guess I can only imagine it's because our you know we've created these these bodies of ours are so capable and they're so energetically and you know you know um consumptive and they make all these byproducts during the day that that that some point you just need a clean up phase and that's that's one interpretation of sleep is just need to reset.

reset. reset. So the immune system is definitely resetting and and you know there's as I say there's evidence that a lot of the cells go kind of quiescent into the tissues and they they leave you alone for those reparative processes and actually allow those You know in terms of the data on there there's a there's a lot of studies that are being done and and I can't say that I've come to a a conclusion about that. This is this comes in the question of like is it known or do I do I not know it or is it does nobody know it?

And I'd say this is might be one of these areas where about 10 factions of people know it but they don't agree. don't agree. don't agree. Mhm. Mhm. Mhm. You know so there's variations on things but I I think the data for example that immune cells dive into the bone marrow at night is pretty solid. That makes sense. What they're doing and why that's important in the long sense of like what you're talking about everything from well but I think it's You know the things that happen overnight you're you're definitely your cognition improves.

Is that immune or is that neuronal or both? I think it's both. both. both. Something in the lymph plumbing immune system. One thing that's just striking like that is undeniable is probably the best way to put it is everybody has bags under their eyes and looks like when they are sleep deprived. They sleep for a night or two and it and it and it goes away. That's clearly accumulation of lymph. We we actually know that. That's just lymph fluid that's not being cleared, and it might not even be the brain's glymphatic clearance system.

It's just There's a bunch of lymph pooling under your eyes. That's why you look like look like look like Yeah. Yeah. Yeah. And then you sleep for two nights well, and then you look better again. And the eyes get glassy. We know that the eyes get glassy when we're sleep deprived. That's also a lymphatic clearance issue. This is well established. Like so there's some things that are just like plumbing works better when we sleep and get up again. There's something literally about lying down and getting up.

getting up. getting up. But that to me can't explain the the immune immune immune thing entirely because like the lymphatic system is like among other things, you know, immune surveillance, but surveillance, but surveillance, but I mean, one night's lou- lousy sleep and the person coughing across the room gets you sick often. But when you're well rested, you actually feel this robustness like, man, like, okay, I'm going to might wash my hands or just kind of avoid them, and you're good. you're good. you're good. Yeah. Yeah.

Yeah. So it's it's I mean, it's an an incredible effect one way or the other. Again, I don't know the degree to which we can nail down, you know, which which part of things that are happening is which. I always like the story that that the There's macrophages, immune cells, in your eye that are basically clearing the clearing the lens. You know, so there's there's all these like like like places where it's doing little clean up 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, it's 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 flies hitting you. That would would right? Or you you'll never clear You know, so I think there's certain elements of some of these clean up 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 think we just use a lot of ATP and we do a lot of stuff as our body's in the in the sleep is this time where you cannot be you know you know producing more of that and get ahead of the curve on cleaning things up a bit.

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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 I know a lot of people who um opted to bank their child's umbilical cord in the hopes that the stem cells from the umbilical cord will someday be useful. useful. useful. Yeah. Yeah. Yeah. How invasive is it and or should we be uh uh uh banking thymic cells? Mhm. Mhm. Mhm. Uh because these seem like incredibly valuable cells for their ability to immune surveil and create kind of the perfect situation using our own endogenous T cells to battle infections.

I mean I kind of wish I I a little like chunk of my thymus Yeah. Yeah. Yeah. um in a minus 80 freezer someplace so that when I'm 85 years old You might be able to exploit um I might be able to exploit that. Yeah. Yeah. Yeah. Well, I'll 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 a lot of 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 system 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 get this vial here, you've got a little replacement. little replacement. little replacement. Has that ever been done successfully? Yeah, yeah, you can do So are there are there are there kids or adults that are alive today because they banked their umbilical cord? umbilical cord? umbilical cord? But certainly companies sell access to that. that. that. has to pay to keep the freezers on backup generators and things like that. So people invest time and money into this idea. this idea. this idea. Yeah. Yeah. Yeah.

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? cord? cord? It's a really good question. I don't know the answer to that question. I guess the parents paid. 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 Feldtman injecting a you know, a mouse 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 blood cancer and you can do that.

that. 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. It's that's just actually something where I Cuz this this is offered in mass now. Yeah. Yeah, when when it is When a baby is born they say, "Do you want to Do you want to keep the umbilical cord?" umbilical cord?" umbilical cord?" Honestly, honestly, I would do it because it's one of those situations where if it's not too exp- well, I don't know if it you know, depends on your your how much money you have to spend because the the cost is within within the noise, yeah.

So, it's one of those ones where you particularly if you when you have kids, there's this whole aspect of like I would like to protect them from anything that could come their way and and and I think this would if if they happen to have a a childhood leukemia, this would this would cure it. Which is an incredible statement if you think about it, even if it hasn't been done successfully yet. You didn't say it might be able to lead to a cure No, it would.

by virtue of a new technology. You said it would cure it. Yeah. Yeah. Yeah. I mean, that's a big statement. Yeah. Yeah. Yeah. You can tell I'm ratcheting up from like sleep to banking thymus and umbilical cord. Now, I'm going to go to the sort of next level, which is not just in the Bay Area. A lot of people people people however starting to think about oh, maybe I make some induced pluripotent stem cells from a fibroblast from one of my skin cells, put the so-called Yamanaka factors on, revert that to stemness and then I might be able to grow a new pancreas or study my you know, whatever organs in the so-called organoids, whatever they're referred to.

referred to. referred to. Yep. Yep. Yep. But I learned today from you that if I take that fibroblast now, that fibroblast might not be completely Andrew Huberman as I know him to be genetically. [clears throat] It's actually could have some mutations. mutations. mutations. That seems important to compare against a sort of a standard cell. I don't want to grow organ- organoids from a from an IPS environment that environment that environment that carries mutations. That that seems like a bad idea. Yeah. Yeah. Yeah. Because then anything I would I'm not talking about transplanting in those organoids.

I'm talking about studying them, thinking I'm getting information about them. People are doing this and thinking oh, I'm seeing what drugs are effective in treating treating treating you know, a liver disease [snorts] or a heart disease, but if those are mutant cells, that's a lousy experiment. Yeah, I wouldn't I wouldn't say they're likely to be mutant cells for that reason. I think the biggest question would be whether your induction of them to become the organ that you you know want was successful was replicating the actual organ itself.

So, you're you're referencing these things called organoids, which are collections of cells from a body of a human, for example, that are are induced with various different factors to grow to resemble maybe an organ a particular organ. You know, I think all of us have little doubt in this this is the source of the California Institute for Regenerative Medicine that making stem cells that can become particular organs will at someday happen. happen. happen. We will figure all these things out. I I I believe in science.

I believe in our ability to sort of like test, learn, test, learn, test, learn. How soon, you know, that becomes useful is a bigger question. If you take out your fibroblast today, that might only cure you someday in the future. And meanwhile, you may die of that thing that you wish you had the stem cells in it because it's not yet ready. The technology and the understanding isn't yet ready. But the other problem with those is you probably will die from something else. You get hit by a car, you know.

It won't help you that you've got those things back. So, I think in some of these cases like overemphasizing, this might be your point about the storage of of umbilical cords, is like at what point is that a high odds situation where you your kid needs it and you have it stored away versus all the other things fates that can befall us as humans humans humans that have nothing to do with it, you know, you know, stem cells from the bone marrow. marrow. marrow. And and to me that's that's a point where you could spend your life worrying about how you're going to die.

And and maybe that's not a good way to live. live. live. Well, certainly not how I live. Right now, there's a lot of kind of excitement and attention around so-called longevity and at the extremes of never dying or living to be 120, which seems to be the perhaps the genetic limit currently. It's not my fascination. I'm more interested in living in the years I've got as it seems you all do. Vital, healthy, you know, being able to move, sense, and and think. [clears throat] Seems like and remember, you know, those seem like the critical ones.

ones. ones. You know, you know, a month ago you mentioned the concept of like removing a bit of thymus and I I think that the issues with for me with that are are, you know, it's an invasive surgery and like if you were to take out thymus, it would It's not clear to me that it's the thymus that you need. You might be able to I mean, the fact you can make thymic the the So, the the thymus is both the cells that come into it from the bone marrow.

So, it as an organ it has contents. contents. contents. But, its structure are some thymic epithelial cells that a kind of cell that make a matrix that all those cells live in and they get educated in. And um there's definitely, you know, pretty strong work that says that you can create sort of a thymic epithelium that will do some of this work. But, whether, you know, a guy at home could could hold on to the thymic cells and we would be in a position to do something important for longevity in our lifetime, I don't know.

I honestly don't know. Some things in my career, I've seen things happen really fast. So fast that almost like you didn't realize that you're doing it. You're like, "Oh my god, we've got a cure for cancer. That's great. Okay, let's go on and do the next thing." Two things that So, you're like you know, you know, the California Institute for Regenerative Medicine, they we thought that we would have some stem cell therapies, you know, within the seven or eight year window of that bond, first bond, and then there's a second bond.

We didn't really get very many out of that. We learned a lot and that is the risk about stem cell biology. About stem cell about biology and that is the risk we take when we do research. You know, we're talking a moment ago about how many times you might be in a lab spending hundreds of hours and not getting anything that you understand and then in one hour and you understand everything because, you know, so all of a sudden all those failures make us make sense.

I think when we get into some of the stem cell biology, it's it's intuitive and it's almost certainly true that we will have some of these things. Whether we will have them in time for like you or me, I I don't know. I just don't know [clears throat] and I I think that's true of a lot of these things. things. things. Say, "Oh, you know, we 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." and Alex will told you about these where you engineer your T cells and you get 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. And T cell the immune system gets turned off. These cells don't make it. They don't fail they fail to eliminate the tumor. We will figure that out. But we've been thinking we've figured it out, you know, for the first 5 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 of discovery. If we knew what we needed to do, we would engineer it and it would work. work. work. Yeah. I um This is an important discussion that we haven't spent enough time on in this podcast that I think is a very important for people to hear. And I have some thoughts about it, but I I'd love for any disagreements. I'm not looking for looking for looking for um just agreements, but yeah. 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. So, that's the podcast. [clears throat] 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 water on rock pressure. Like, "Okay, we're going to understand like salamanders regenerate. Wouldn't it be great if we could do that, too? Cut off a limb, it could grow back." Okay, amazing. I think it's like Elly Tanaka's work has just shown that.

You're like, "Wow, this would be incredible for amputees and brain regeneration and Right. Right. Right. But then it never really transfers. Or like, "Oh, we're going to figure out ways to get genes into cells. We're going to electroporate liposomes. We're going to use a calcium phosphate like great research tools. Tons of things happen. Then it's like, "We're going to modify genes. Zinc finger nuclease." All this Okay, CRISPR, boom. And one thing just breaks through and goes so much further. And even though, you know, the ethics are questionable, there are babies that have deliberately induced uh gene alterations for with CRISPR, a sickle cell anemia treatments as well.

It's a more benevolent example, but then the person who went rogue and just kind of did this in humans in China. But CRISPR just kind of broke through it all. all. all. This 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 kind of like run up against the dam. Yeah. Yeah. Yeah. But I feel like in 10 years some or all of that information will be extremely relevant when 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 the country's getting obese. What are we going to do? Do calories matter? Of course calories matter. This kind of thing energy, you know, laws of thermodynamics still apply. And then all of a sudden this freaking Gila monster biologist Yeah, yeah. Yeah, yeah. Yeah, yeah. tells people what they already knew because the GLP-1s were already being used as a drug, just not at significantly high levels. And all of a sudden we have a imperfect, but very important more or less less less dare I say cure Yeah.

Yeah. Yeah. for obesity. It's got problems, there's muscle wasting, you know, there could be other issues, apathy, etc. I'm not I'm not trying to discount any of that. But I feel like that's the way science works. It's like steady pressure, steady pressure, steady pressure, frustration, and then something comes out of nowhere. And it almost seems prerequisite to have all those years of frustration and failure. failure. failure. Yeah. Yeah. Yeah. And then and you say, "Well, couldn't we have just gotten CRISPR first or the GLP-1s first?

Like why did we go through all these, you know, billions of dollars of expenditures, time, energy?" Yeah. Yeah. Yeah. I don't know. I feel like there's some natural order to this and and I just just would like your thoughts on it. I feel like it's necessary, but not sufficient to have lots and lots and lots of failures. Yeah. And I think it's necessary and and necessary, absolutely necessary, to study things that are just at some point curiosities. And that sounds like science is about trivia. But you know, you you gave the example clip one, somebody was just curious as to why Gila monsters it was the feature was that Gila monsters can go into you know, dormancy for like 10 months, not eat, and then come out.

And like how do they manage that? And so that's that was just like what is that? What is it what causes that? causes that? causes that? CRISPR, you know, that was people were studying like how do bacteria defend against other bacteria? Well, they use this it turns out there's this enzyme and it and it and it remembers the sequence of this one bacteria that has come and invaded you before and then can like modify the genome and get rid of it and like kill it. Well, that same you know, that same enzyme then be which we now use for all this human engineering came out of a basic like how do bacteria defend themselves?

It's not anything about like you know, modifying sickle cell anemia. It was about how does the world work? My career is exactly as long as is the as the lifespan of of this this field we call cancer immunotherapy. I did the first immunotherapy experiment. I injected a mouse with an antibody that I'd made. It was against a molecules on T cells. T cells. T cells. And I shown already in the lab that that molecule caused the T cells to get more activated when you blocked it.

And and we did a series of like other mouse experiments of like all kinds of diseases and it you know, kept humming up the T cells and then and you know, Jim I I got that I said we got some tumors in the fridge and so we set up that experiment. And you know, you injected this antibody and the tumors melted. Well, that was the start of cancer immunotherapy really that's that's this that's the origin of experiment for which let's just be direct here that your your advisor won the Nobel Prize.

Correct. Correct. Correct. Did you at least get to attend the ceremony? ceremony? ceremony? Yeah. Yeah. Yeah. Oh, well, that was that was a little thing. thing. thing. This is how science works. Doesn't matter who did the experiment. Yeah. Yeah. Yeah. Matters what lab you're in. Yeah, you guys didn't you didn't get to go learn. The the after parties were good. Uh, but I guess I'm not not take you back like we weren't trying to cure cancer when we started this. I did the thesis project when I went into Jim this is my my mentor at that point.

The discussion was like, well, there's some molecules on T cells and and I said you know, we we knew from AIDS and a few other things that T cells were important. So, So was the attraction and though you had people say, "Why would you do immunology?" Well, they seem to be interested. And there was a molecule and it was like, "Well, yeah, let's just see what it does." And once you saw you could turn things off, then everything became possible, right? Now you study immune system you could dial up.

You could say, "Well, if I could dial up, well, what will happen to vaccination?" Well, it got better. What will happen to, you know, multiple sclerosis? The disease got worse. You know, what will happen to cancer? Ooh, we can start to have an effect on it. And and and you know, know, know, the X-ray, you know, the people were studying physics and then it turns out to be that that they were like, "Oh, I can measure I can I can measure bone." And that's how we use X-rays now, like to to you know, so there's all these examples that everything you know, like the big things often come from these orthogonal directions and then we realize what it might mean.

And I think you have to start there, otherwise you'll just plow this direction and you'll hit those walls because you don't have to work around it comes with some orthogonal piece of information. Orthogonal meaning at right angles, right? So, you know, again, CRISPR came from bacteria, but it's really useful in us as an engineering tool. But we wouldn't have known that if somebody hadn't been out there sort of saying, "Okay, well, how do how do bacteria do it? You know, how do they defend themselves?" Oh, they use this enzyme.

And I think that's a really important message that that dispels this idea that everything is sort of like basically just easy for us to engineer. Yes, once you have the CRISPR tool it becomes actually kind of easy to do some really cool things with it and still creative. But the fundamental leap that you're describing, I don't think in many of those cases that people were kind of conceiving when they were in in the first dregs of doing it that this would become an industry. You know, this would become a whole thing.

And and maybe that's important because you need to foster that. If if everybody always thought they were doing it to build a company and, you know, sell a product or something, then then I don't think we would do the things that get us new. You know, that's that's all that's all kind of what we already know. That's human knowledge. We want to build human knowledge. And to build human knowledge we got to go off piste. You can't ski on the slope. You got to be like in the trees and maybe and bump your head a bunch of times.

I I think that's the reality and it's like you got a lot of people out there that are that are that have decided to do that for a life because it's a it's a it's a chance to like solve a puzzle. It's like there's there's puzzles about how the world works. And if you've ever done a jigsaw puzzle you find there's always like the oh, you get in and especially in the end you're like how do you know what pieces come together to do it? I think that's what makes this whole science thing really fun.

It's that's the that's the reward. Is that you get the puzzle piece in and you're like oh, I you know, it makes sense that now I know what I've been building I've been building this puzzle. And and then you go back and you do it again because that's really satisfying at the end of it even though, you know, you know, again with the family puzzle the first parts are so hard. Thousand pieces and you can you maybe find the edge. edge. edge. But the intervening where there's like all clouds super hard.

And and I think that's that's that is what science is a lot about. Is is doing that and then realizing what the picture is. You know, what is that picture of it? And then and then all the you know, the brakes are are off. I often tell people that if if an if an experiment you'll do in experiment if an experiment you'll do in lab has a 10% chance of yielding anything interesting, you got to do at least 10, you know, to even meet fundamental stats.

You actually have to do quite quite a few more. So, that's where it's not a cost-effective thing if you it's it's really difficult to be a scientist because there's no quid pro quo. There's no there's nothing to say if you put in 5 hours that you'll get five units of goodness of of knowledge out of it. A lot of times you get zero. And and but then sometimes you put five in you get 500. Right. Right. Right. And and those are the jackpot moments. It's like life.

It really is. It's like yeah. like yeah. like yeah. that anyone who's considering a PhD, we had a call in from audience recently and someone said they're finishing undergraduate. They want to go the finishing graduate school. Should they go the research route? They want to do a post doc. And I'm like yes, yes, and yes. I rather than answer publicly I decided to just have a call with this individual because it's a rather niche question, but I mean also just in training your training your training your reward system to work for 5 years on something is so valuable, especially in this day and age, cuz everything else feels like it comes at like warp speed.

Yeah. Yeah. Yeah. It's like clicks. Yeah, like and um to just put steady pressure on something with all the failures and all the things and then to finally complete something, it's a lot of people think it'll be underwhelming. I think I think quite the opposite. opposite. opposite. Yeah. Yeah. Yeah. It's like anyone that's like done a triathlon or triathlon or triathlon or Well, you know raise raise a kid or done a You're like, oh my goodness. Yeah. Yeah. Yeah. And that never ends, right? There's nothing better than these long-term investments.

investments. investments. Yeah. Yeah. Yeah. Nothing. Nothing. Nothing. Yeah. When they break through that way you're like your analogy, when you break through that dam or when you realize sometimes that you broken through the dam. And 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 realize that you've all of a sudden got somewhere. I haven't done a triathlon, so I have to be fair. Rob, our producer sitting to our left as he has done many Iron Mans.

And he has that mindset. Yeah. Yeah. Yeah. 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 and just focusing on what you can impact. And so, a lot of it is about learning energetic control. Like doing science that is or anything is about what not to think about, what not what to force yourself not to do or think about.

think about. think about. 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. biology. biology. Okay. Okay. Okay. And I'm going to pose a question that may or may not fit with Um Um Um this framework, but either way I'd like to like you to educate us on it. I'm fascinated by these old kind of barbaric experiments in medicine. Um wonderful book, by the way, folks is the Prince of Medicine about Galen, if you ever want to learn about how we learned about medicine back when it was truly barbaric.

It was like surgeries done on warriors and without anesthesia and we've known for a long time that if uh somebody god forbid has a finger lopped off or a hand lopped off that might actually be a worthwhile investment to make an incision in the gut and stuff that thing in the gut to keep it warm and keep the tissue viable for regeneration once you try and put put it back on. Turns out that's true. Is that true? Yeah, there's a bunch of juicy stuff in the in the gut that maybe it's the warmth, maybe it's the immune system.

Okay. Okay. Okay. Maybe it's the lack of infection from being inside as opposed to outside the body. Who knows? Gut you mean the intestine or you mean the stomach? the stomach? the stomach? Within the stomach, yeah. The stomach itself. Yeah, I'm not suggesting anyone do this experiment. As I started reading into this, I discovered that there are a lot of really cool experiments not just in re- re- re- limb or tissue preservation and and restoration. Like for instance, I've talked many times on this podcast about the fact that above our the roof of our mouth, we have this small cluster of neurons the suprachiasmatic nucleus organizes the circadian rhythms of every cell in our body from the genetic to the transmitter level peptides, etc.

Keeps us sleep-wake cycles, does all the organization that we need Yeah. Yeah. Yeah. for circadian rhythms. So much so that you can take just one subpopulation of these neurons, the calbindin expressing suprachiasmatic nucleus neurons. It's like 5% of the total neurons in this already tiny cluster of neurons and you can transplant them pretty much anywhere and certainly in the brain and you'll restore the circadian rhythm of an arrhythmic arrhythmic arrhythmic animal. animal. animal. Okay. Okay. Okay. So that tells you a lot of cool things. It says, "Okay, there's probably something that's secreted or but like these cells are that important and it doesn't really matter where they are are are Mhm.

Mhm. Mhm. at least in the brain, they can do what they need to do, which is super cool. Yeah. Yeah. Yeah. And then I started reading about, "Oh, like you could actually take perhaps like a little bit of pancreatic tissue and like stuff it in the you know, under the skin." the skin." the skin." You mean the kidney capsule? It's not ideal, but you get some function back. function back. function back. Mhm. Mhm. Mhm. So I'm fascinated by this because we like to think that the organization of our organs is so critical.

Yeah. Yeah. Yeah. But maybe they just need to be there. Now, no one should test this hypothesis unless they have to. But when we think about the immune system, you describe the function of the thymus beautifully. You talked about the bone marrow. But you also talked about the massive migration of these cells that are working in this network. Mhm. Mhm. Mhm. How important is spatial compartmentalization of these cells? Or is the rule eliminate spatial compartmentalization in order to make the immune system function at its best?

And there's a very specific practical question which I'm asking this, but I'm just going to tuck that away to pique people's interest and I'll get to it. But this is relevant to how we to decision important decisions that we make, I believe. The answer is yes and yes. You know, it's it's both. So, although I described the immune system in the earlier part of this discussion as super migratory and you know, hitches a ride in the blood, gets into tissues, it travels through your lymphatics. There are these things called lymph nodes down the lymphatic tubing which for those of you who don't know, lymphatics are like drainage.

It's how you drain the the fluid back out of your tissue. your tissue. your tissue. [snorts] [snorts] [snorts] So, [clears throat] although there's you know, these mass migration of cells, there's also in like even just in T cells, there's T cells that lodge in particular settings and they you know, act to protect that tissue and they and they're resident cells of those tissues. They never leave. And um so, both are true. You have you know, parts of your immune system that are you know, protective or or like nurturing of particular areas and then there's ones that are circulating and can hit any any spot.

You know, going back to your idea of organs and such being moved, I think there's two components to that that you might be thinking about. One of them is the question of whether the organ can survive in the new space. Like does it have the growth factors and the blood flow and the and lymphatic outflow and maybe even some neuronal activity that you know, makes that tissue work. tissue work. tissue work. So, so that's where like if you take the pancreas, you you famously put it underneath the kidney capsule.

Kidney has kind of like a skin around it. You can tuck some some some pancreatic cells in there. And they're super happy. They love that. They get all the blood flow they need and it seems to be just right for them. for them. for them. But, if you've got somebody with diabetes, for example, and you try to put new pancreatic cells in anywhere in their body, the immune system will attack it just as it did the first that it did. it did. it did. Diabetes, for those who don't know, type 1 diabetes or is caused by the immune system that gets too active against the pancreas.

It's autoimmunity. It's where it's now saying the pancreas is is not self. It's something foreign and it wipes it out and that's the source of what I said earlier, like your immune system can be quite dangerous. quite dangerous. quite dangerous. So, like when you talk about this concept of like spatial, um there's a few things to bring in. One is this the organ. Can the organ get what it needs? And then does the immune system accept it in some ways in that environment? And that's where like some some of your immune system that lives spatially in certain areas is going to be very like defensive against whatever it's, you know, specific against in that area, but may not care what's happening elsewhere because those cells just aren't It's not like the brain where you like if I I do something here, it's sensed in my brain.

Immune system that if it does if the cells don't migrate, they don't have really a lot of ways to communicate. Like they can they can just hitch some signals on neurons. And that's a really interesting we could talk about the the capacity for your brain and brain and brain and you know, the insular cortex. There's a great set of stories emerging about how your insular cortex can program your immune state into organs and can via via the vagus can can can essentially program immune system. of of calm or stress or by thoughts themselves?

themselves? themselves? Well, the the one the latter one is the one that gets me super excited about the possibility that you could have triggers for thoughts that So, the insular cortex, as I understand it, you know, it's a source of some of our moral decision-making. It's also the the thought to be the part of our brain where if you cut your hand and and I see it bleeding, I can feel it in my hand. I oh wow, you know, I can sense and you can sense each other's pain.

It's a set set that there's very nice uh Israeli group that did this Royce lab that did very nice study where they induced into the guts of of mice inflammatory bowel disease. They fed them a really kind of weird sugar that causes them the bowel to puncture and then they get they get a really bad, you know, stomach ache. Um, a stomach ache and inflammatory bowel disease, diarrhea. And um, and in that period they used, you know, you know what dreads are. So they they marked uh, for the for the crowd it's they used they used a way to to mark all the neurons that were firing during that period in the insular cortex.

And then later they could fire them like after the mouse had recovered and the they saw evidence that the immune system was resetting up itself in the gut as if it had just been punctured, you know, like with a and the cues for that in that case were a drug. a drug. a drug. But we know that we can, you know, cue the insular cortex like me watching you do things. do things. do things. So it's always it's made me wonder whether, you know, like some of the things we we smell cut grass and we can we're, you know, instantly take us back to a whole bunch of thoughts about how we were when we were kids and maybe even make you feel a little like that.

Whether there's aspects to this to which are, you know, our ability of our thoughts to control that region are are going to be revealed to, you know, to have potential that you could train uh, you know, train yourself to to, you know, to bring up an immune state in a particular tissue. particular tissue. particular tissue. Um, just so I'm we make sure everyone's on on board what you just described cuz there's a lot there. If I understand correctly, correctly, correctly, we know that the nervous system can do contextual learning.

Like if it like if if an animal or or human, let's just keep it a human, gets um, shocked, scared, or traumatized in a given region yeah, or even I've had friends visit San Francisco and get their cars broken into and their computers stolen, you can develop a context context-dependent or and or place-dependent memory where you kind of don't like San Francisco as much even though the rest of the trip was awesome. That's a pretty broad interpretation. Or um, you have a great experience someplace and you actually really love San Francisco because you met your future spouse there or you just had a particularly awesome experience there.

Even if it was just in one part, you might feel better about your computer getting stolen anyway. Okay. Insula seems like a you know, let's take the positive example. Let's keep it positive for a moment. I think what you're describing is that if we remember the positive thing, if there was a positive immune status associated with that. The immune system is also part of that contextual memory. And so [snorts] merely by recalling the positive or negative, but in this case positive memory, we can also we recall not just the memory, but also the body state and the body state includes the immune status that accompanied the positive or negative event.

That's what these studies are starting to emerge and That's cool. That's really cool because we've heard for so long that like we know that chronic stress impedes immunity. We also know that acute stress boosts it. And that's something that, you know, with all due respect to my colleagues who've focused on the ill effects of chronically elevated cortisol, like the the the immune-enhancing effects of acute cortisol and stress are are really important and and I think they've been overlooked. But I love this because one of the problems {slash} luxuries that I I have is I sit sort of at the interface between like real science and biology and like what most people perceive as complete nonsense whackiness.

But more and more we're finding that's within the complete nonsense whackiness there are kernels of truth like that you can actually meditate your way into a better state which helps serve your immune system and so on and so on. And that's seeming less and less wacky even outside California because of studies like the one you described. One of my friends who's a faculty down at NYU, we were talking about the same study and he was like, "That may be what meditation is doing." Cuz it may be allowing your brain to, you know, communicate and reset um you know, less inflammatory states Mhm.

across your body because of this axis. And the study was really I think it was you know there's still work to be done in it but the you know the the fundamentals of it was in the actual event there were certain cells that would accumulate in there and then in the induced event when you made the the brain fire again of this mouse you would see you know not as profound but you saw this this evidence of these same sorts of cells accumulating there as if they you know they're ready for that inflammation.

And I think what we're talking about is the idea that you could have that go both directions and that again you know the concept of I mean I'm sure you've talked about this before of of meditation where the idea is that you um you know you you it's one of the ways that you can control your autonomous nervous system is through is through your breath Mhm. Mhm. Mhm. 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 that some things that make they sort of make a great story in our minds that 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 there's there's a real connection between some of the peripheral states and and like a regions of the brain. And however those are triggered now maybe maybe maybe you know again I've I've often thought well maybe when you're healthy you should smell like mint and then when you want to be healthy again like you know there's it's it's it's kind of crazy thoughts but but again there's an element of that that's intuitive too where you 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 but I was stressed in one sense Mhm. Mhm. Mhm. but maybe also on to this point and literally 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.

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Mhm. Mhm. And they don't get sick, and it's super frustrating. 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 like pay more attention to the sleep piece. piece. piece. Mhm. Mhm. Mhm. Um then I certainly than I did when I was a graduate student, post-doc, or junior professor. Yeah. But there does seem to be this {quote} {unquote} positive, or let's just call it a reinforced mindset, as opposed like [clears throat] an immune reinforcement associated with 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 in a given environment once and then you you just decide that you're sickly. So then then then you know you know you know 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 biologists and and physicians like yeah, you got to be kidding me. Like but cuz immune cells don't listen to thoughts.

They listen to brain states. Triggers of some sort. Triggers of some sort, right? 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 but it's the feeling state associated with that that Probably Probably Probably level makes total sense. Yeah. Yeah. Yeah. So it's we were talking about spatial biology and the fact that you can tuck some pancreas in the kidney and unless say someone has type 1 diabetes Mhm.

Mhm. Mhm. a lot of the functions of the pancreas can can can can still function. or or or transplantation of these clock neurons and clearly there are limits to this but in the context of the immune system I'm wondering I'm wondering I'm wondering can we take a little bit of thymic tissue tissue 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 have friends one of whom might be at Neuralink [clears throat] now who actually embedded a little radio receiver under his hand to be able to open his open his open his um it locks at his home 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.

biohacking. biohacking. Yeah. Yeah. Yeah. But But But if I knew that I could be much healthier like taking a few thymic cells and 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? not? not? Well, I mean the question is why would that you know is that likely to work? 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 you know, is there, it's it's more than likely that one of the nine out of 10, I would guess. guess. guess. Sure. Is there a correlate from any studies on animals? We know that 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 and study them and give animals drugs or give animals stuff. And tumors are happy to thrive in novel environments. So why wouldn't healthy cells?

cells? cells? 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, um, 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 want to bring in new genes, the vector, the material that the the the the the surrounding, whether you're bringing it using a virus to you know, to bring it into those cells that you're going to now put into the person, whether it's a virus or a a small piece of DNA called plasmid, 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. 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 cell with a huge number of new things being expressed, and some of them viral, literally. literally. 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 you know, the moment is is if you engineer a system to be maybe better, the immune system isn't necessarily going to 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 going to let it fly. I'm not considering doing this. I just I I think we are I don't know how old you are, but I I can guess based on some of 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.

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 matter 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 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. healing happen. 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 the neurons.

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 even just a cell type, you have to be a little bit conscious of like where it's going to 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. So like development happens that way. You know about gradients and we talked 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 for a process and when is it only good when it's given in the right dose at the right time? And I think that's one of the tricks about some of these things. And again, that's where, you know, both in the lab and you know, like I I would say that more so ever in in in our lives, you know, we're seeing, you know, people kind of like experimenting with things on themselves.

on themselves. on themselves. And one of the sad parts about this, we don't capture a lot of data therefore, you know, cuz it's not seen as a study and we can't say everybody that took this gets this result and and then you have this rise of things on the internet of of anecdotes that become seen as data. Like I took this thing and this happened. And that's, you know, I I can drink this drink and it doesn't mean great happen to me or something bad happen to me.

It might have nothing to do with the drink, right? You know, that that issue is one that I think it's really um is really critical in in this in this window of time right now. And I don't know what you think about the idea that people, you know, do experiments on themselves. I I think we all want to improve ourselves. We all do all I would do some kind of experiments ourselves. Like you read a book, you're trying to improve yourself, right? Um the physical one gets a bit tricky when you know, you're not sure whether something's going to be dangerous or not.

But not. But not. But I'm not and I'm not promoting that people do this. I think that of course you wouldn't would want to see preclinical, clinical and and other um trials for this. I think I would personally. I mean, just personally. personally. personally. I'm I there are a few areas well where I am um a bit more adventurous, but for the most part I'm I like, you know, based on my training and background, [clears throat] I have to orient toward, you know, I I'd like a bunch of Let me put it this way.

I'd like to a bunch of other people to do it first. Yeah. Yeah. Yeah. Like who It's fun to be first unless you're doing something really stupid and that can get you killed, in which case like let other people go first. Yeah. Well, I think a good example that right now is and this is you know, sort of nationwide or even international, is vaccine hesitancy. I know this is a touchy topic, so we can No, but you can feel free open. Well, I'll just point out that that the 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, if those people have cancer, they're very interested in vaccines cuz it's a 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 did not different from you.

And you introduce those as if you would introduce the virus or anything in a in a childhood vaccine, similar concept. Um just different different 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 going to work on us. We know there we know statistics really well. Chemo is not very good for a lot of chemo and cancers and but it'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 they're 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 is their their question about whether they're going to try something or not is very context dependent. dependent. dependent. Very. I think uh I don't want to go too deep into the vaccine debate and I don't want to be a spokesperson for either side because that's not my role today, but but but Yeah.

Yeah. Yeah. I think that the um um 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. Sure. Sure. Sure. Um which is I think there are a very large number of people for whom they are neither anti-vaccine neither anti-vaccine neither anti-vaccine nor super pro, but they are um they're asking about timing and combinations. Agreed. Agreed. Agreed. They're saying, "Okay, listen." And we had Jay Bhattacharya on here and I've had had had several others who said, "Maybe there should be an investigation of the spacing of these things.

How many? Um how critical it is to do at a given age, you know, um and on and on." We could pick any vaccine for that reason. And as an immunologist, immunologist, immunologist, do any of those questions make sense to ask? I mean, I could see how, you know, bombarding the immune the young immune system with a lot of vaccines is a very different thing than spacing out the uh delivery of those vaccines. Yeah. I'm not saying don't give them all. I'm saying saying saying over what time window does one give them?

them? them? Yeah. Yeah. Yeah. I think a lot of people many more people are asking that question. Yeah. Yeah. Yeah. It's just a quieter murmur than our um saying, "Listen, we don't want to take any of these things." Yeah. Yeah. Yeah. Or we don't want our kids to take any of these. these. these. I agree with that, too. And I I think there's some fair aspect to which most of these vaccines were not studied in the context when they were studied of of what it does, you know, in in in com- in in combination and in in these sorts of timings.

timings. timings. The fact is that, you know, the the evidence that there's any that there's bad things happening doesn't look to me, you know, tremendously strong. It's almost like anecdotal sort of information. information. information. So, unless it's your kid. Unless it's your kid, in which case you're going to look for an explanation. So, I I don't know. Just being fair as long as we're admitting psychology as a factor. Yeah. Yeah. Yeah. Yeah. So, Yeah. So, Yeah. So, there there's fairness on both sides of that discussion.

And I think I think that almost certainly where we are now, there's probably ways to put together vaccines and certainly more convenient ways. It's I I I as as a parent I I actually had something very similar where I delayed, you know, my first daughter's one of her vaccines. Partly because I know that that as a, you know, like there's a certain element to which when we design a protocol, like the the protocol for immunotherapy of cancer for patients was was actually based a little bit on the mouse work a lot on the mouse work that I did.

You can imagine that mice and humans are quite different. But, that is the protocol. Protocol is protocol, and that's how it's done in medicine. And that's because you have a fairly good sense of the safety of it because of statistics. statistics. statistics. But, that isn't to say that it's the only protocol that would work. And I think you're getting at this concept of like could there be at least a more convenient one? convenient one? convenient one? Or one that's the safest. Or safest, or even one that is less disruptive to the lives of the children and the parents.

I We we delayed one of our kids' vaccines, you know, by just a month or something because uh she had not been feeling well. Just straight up. And And it is true, you know. And I'd say that a couple of vaccines have come out there I've had recently, shingles one is a good example. I had a other day is knocked me completely out. And then you know, it's very very heavily advented, so it's clearly 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 aspect to which 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. were chosen. were chosen. Mhm. Mhm. Mhm. Um some of them are chosen by competing pharma pharma companies that each make their own you know, materials and you know, I 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 of 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 where the holes are. Excuse me for interrupting, but you know, a huge basis of this podcast is to counter exactly that. exactly that. exactly that. I mean I know all these incredibly smart, incredibly well-meaning people who have lives of their own, health health lives of their own, health challenges of their own, kids of their own own own and on and on and no one was hearing from them.

from them. from them. Yeah. Yeah. Yeah. 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, but you're you're offering um perhaps the opportunity for or better understanding and certainly of the information. information. information. Yeah. Yeah. Yeah. Yeah. I mean it's it's a huge problem. 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 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 off protocol 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 experiences 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. protection. 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 going to do it. It's um it's like it's like brushing your teeth in the morning. You do it in the morning and evening is when you do it. And so, you'll do it twice a day. So, there's a lot in this. I mean, you know, there's a lot of politics I think involved in in vaccine too that relates to the question of like 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 vaccine is, you know, if there's a harm, who gets to choose with the harm and benefit and then how resources are given out for like schools and you know, we know all these sort of nuances. From the science standpoint, I don't think you want to 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 fewer shots? I think so. See why not. Here's where you get the financial rise.

What's the benefit to any pharma company of doing that? Well, I think this is again, I I have [clears throat] to be careful that I don't place myself into an advocacy group that I'm not. I'm I look at everything on a case-by-case basis. case-by-case basis. case-by-case basis. 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. 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.

Mhm. Mhm. Mhm. So, 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 kind of wild west. People are microdosing them from all sorts of compounding pharmacies as their own issues and so on. Yeah. Yeah. Yeah. But, my sense is that the frustration around the kind of dictatorial, like, you're going to do this at this point because this or else, like, you're persona non grata.

Mhm. Mhm. Mhm. 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. like this. like this. Yeah, I agree. At least not when I've seen publicly. Yeah, there are a lot of labs that are going to devote themselves to this. People will wage the argument that and I don't know if this is actually true, but that the pharma companies are protected against lawsuits about vaccine injuries.

Yeah, yeah. Yeah, yeah. Yeah, yeah. I mean, I think that probably is frustrating to very frustrating, excuse me, to a parent whose kid seemed essentially fine, got a vaccine and 3 days later started exhibiting symptoms that then set them off on a course that was uh really really tragic. Yeah. Yeah. Yeah. Um and those groups are the ones that have have have accumulated the most oomph out there. Yeah. Yeah. Yeah. And if you think about the those parents, totally understandable Yeah. Yeah. Yeah. why they would feel that way.

Whether or not the basis of their feelings is exactly right, I can't speak to, but you can understand if your kid is one way, walk out of the doctor's office is is another way. another way. another way. And you can't do anything about it. That's got to be super frustrating. I mean, beyond maddening. And and and and the question is, what could you have done differently? I think is uh in those situations, having been in them, not that exact situation where you said, "Oh, now it's done and now I can't go backwards." And you did that to them.

This is the thing that This is the thing I think that is not often discussed is that the the parents made that choice on the basis of what they thought was the best. So that there's a certain um guilt slash anger. I mean, there's a whole psychology to it that's completely understandable. understandable. understandable. Yeah. Yeah. Yeah. The kid didn't wander into the clinic. Yeah. Well, I mean, you know, on the way over here, I was thinking about some of the things that you know, are happening in in uh medical space and then you know, you guys have obviously from time to time talk about peptides and these sorts of things that people are using, you know, off-label Well, not even off-label, they're just from uh wherever, the internet.

And you know, that I was thinking, well, you know, there's a funny thing there because the legitimacy of pharma companies has sort of fallen into even worse straits than before because I think it I was thinking about this, a lot of it does relate to the fact that we are advertised to take a lot of things that often aren't, you know, the the side effects are worse than the than the symptoms that we're we're leaving and and that sort of uh you know, again, I I may find myself like having a bunch of colleagues hate me for talking about this with you, but I do think it's kind of important at some point to surface where all this comes from, you know, and and and the idea that we can do experiments on ourselves, on our own bodies, again, bodies, again, bodies, again, it's quite different to say read a book.

Although you can be infected by we believe like by, you know, scripture and scripture and things and and then your behavior. behavior. behavior. But somehow [snorts] in here this idea that that that that um you know, we can be told to do things by people that aren't quite in our best interests. I think it opens up the idea that well, why why can't I choose my best interest? You know, who who are these experts that I can't always trust? What's more American than that after all?

all? all? it is it is it is part of the pioneering spirit. Like if the if the government's not going to protect my 40 acres, I got to have a gun and protect myself. And that's that's been a part of our culture for a very long time. And I think this idea of individuality plays into this, but it could be exacerbated at the moment by the by the fact that there you know, haven't always been good communication with somebody you're trying to work out and and and maybe even surfacing of these ideas that are hard to talk about.

Like should we trust farm companies? I know a lot of people that work for pharma and they really they are doing good. They They, you know, they're they're like you and me. They They really think and they are treating disease. They're making really good drugs and they do really good things. But this is not always true. Not just because of, you know, a bunch of people doing it, it's not always true that the subtle best interest of a corporation is the same as the best interest of an individual.

So, you know, we have to surface that those things exist. It's not like we have to say that it's right or wrong or whatever, but at some point those kind of perverse incentives exist. I I wonder why, you know, like pharma companies haven't um gotten better tests for who's going to respond to these checkpoint drugs that we made. We've had We've had a few papers that show who are the responders and who are not, but it's still the case that if you get to come in with melanoma, even though there's only a 50% chance you're going to be cured, which is great.

You You used to be zero with these drugs. You still take 100% of the market takes that drug. Well, because the 50% that aren't going to respond, they don't know who they are. are. are. And so everybody takes it. So, the companies that sell those have no incentive incentive incentive to develop a test. Although again, if they develop a test that shows who is and who isn't going to respond, they'll cut their market into 50 in in half. half. half. So, I don't think any pharma executives out there going But if there's no there's no positive incentive to do that study, to study those things.

And I think it's kind of true in some of these other drugs that we've been, you know, brought brought forward, some of which are better and worse than others. We could told that this is going to be good for us and and we should take it and and there's a again, you're you're getting into the American kind of like mentality, which is a say, well, some point if you fool me twice or, you know, I'm not going to believe it and and I might not believe it against the entire spectrum of things called science.

And the problem is that there's people like you and me that are trying to actually do and and most of us, I'd say, 99.9% of us are working our asses off to like, you know, figure things out and discover stuff that's important for mankind. mankind. mankind. And then you have these sort of issues that arise and you're like, well, then should you distrust as a as a as a species, should you distrust the entire class of science? Probably not. You You just need to maybe make it so that 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, uh and maybe vaccines are one we You know, we just need to do something sensible like what you're describing and just just do a study and say let's do that study.

And and make that very public that we do it and say we're going to do that and and and you obviously people can sign up for, you know, the the you can have this regimen or you the old regimen or the new regimen and we You know, again, I I I may be speaking out I don't do vaccines. 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 they 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 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 actually actually describing an experiment. What would be the experiment? Yeah, well, the discussions haven't happened and I should say a couple of things. Um first of all, thank you for 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. If anyone cuts a clip, I will be the first to dive in there and say this is taken out of context. But But But I to any people, colleagues or otherwise, that would say, "Hey, actually this is the wrong stance. You don't want to be talking about nuance in a time when there's so much threat to traditional medicine and vaccines, etc." I will say this. The idea that you need to push back with a with just a fire hose of do this or else did not work.

The pandemic proved that. In fact, I think one of the biggest mistakes was to have one individual as opposed to a panel of people with more nuanced communicating public health information at that time. 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 and the path forward is really this kind of conversation.

It's conversation. It's conversation. It's highly educated people like yourself in the educated in the immune system who understand this, who have children, who made certain choices saying yes and I can understand why you would be considering the following questions and we should do a study 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 and I think it's the right time to have it when we're not in the throws of a pandemic. Yeah.

Yeah. Yeah. Yet. Yet. I mean there's some things that are on the rise. It is scary. I'll I'll be quite blunt. You know, the the rise in measles is scary. People say, "Well, measles, I used to have measles parties." Talk to somebody who had massive inflammation and brain inflammation from measles, not a pretty picture. No. No. No. Not a pretty picture. Yeah. Yeah. Yeah. So, I think it's great that these conversations are starting and it won't be taken out of context. Yeah, well, I mean on the vaccination front, I mean I just wrote a little little little sub-cycle so about you know, the origins of smallpox and the vaccination and I think what's lost in those stories is if you look on the internet to internet to internet to the yeah, so that that's a terrible disease.

I mean that you know, the reality of what we're protecting against we haven't there's just really hard to to like also have that conversation without doing a little bit of reading into your history. You know, and and I I don't think the history books are pulling the wool over our eyes by saying some of these things were really horrendous. horrendous. horrendous. Well, smallpox was dreadful. So, so there's an element of that though that I think you know, that we have to make sure that the conversation focuses on on what are we trying to on on what are we trying to achieve here?

achieve here? achieve here? And and and sometimes that that question is can get lost, but I think man, if my kid got smallpox or got measles or got mumps and and and and you know, as we know like measles is not a a theoretical again, you know, it's it's certain that that concept uh is enough to say well, there is a risk of that and that's one where you it's like you and you're not teaching your kid how to cross the street properly if you didn't do that and then the kid got hit by a car, you'd just be decimated.

So, decimated. So, decimated. So, you know, just because we haven't seen these things for a while doesn't mean that they're not still real and I think [clears throat] that's also an important I think that's what that's me as a parent saying like yeah, I did look at the history and of these things and they really are bad. And so we are you know, we are defending against something, but you know, is there a better way to do it? Uh it? Uh it? Uh you know, propose experiment.

That's that's you know, I think there's a you know, like cutting off you know, the concept of human curiosity and science at the legs is probably not probably not probably not the way to figure out something out from my experience. You you you you dive in, you think of the experiment that would answer the question and you say well, that is that the killer experiment for this thing? this thing? this thing? Again, I think you look at the numbers and the numbers from my this is me as a parent looking at the numbers of of you know, like the the danger of of of bad stuff happening versus the the odds of an adverse effect.

They weren't all that high, but you know, again, if you're one of the people that even if it is caused even if it is that even if it is caused by vaccine, which I don't by the way Can I tell you a little story? I believe maybe you know this already, but if you wanted induce autism in mice, people do it by injecting a bacterial infection into the mom when she's pregnant. Which tells you that an immune challenge can affect the neurons of the of a developing pup.

developing pup. developing pup. So, it's not outside the realm to say that in some situations and adjuvant situation again, again, I may regret saying this because it's you know, Uh, it's to open up a conversation to have this, but it's it's not outside the bounds to say that a immune insult will have influence on neurodevelopment, period. period. period. Is it the source of autistic children? Or was it in fact that the mom had infection during pregnancy? It's not absolutely wacko to think, and you should think this is a neurobiologist, I think you'll probably agree, to think that inflammation, some of the molecules of inflammation, will affect the the the cells of the brain.

Yeah. Yeah. Yeah. In fact, one of the best In fact, one of the best experience that I love along these lines, it's not about about autism at all, but it's about when you get a flu, you tend to go you you tend to feel like you want to social isolate yourself. At least I do, and most people do, I think. They kind of want to crawl in a hole. Is that crawl in a hole feel? There's an experiment that was done that involved injecting gamma interferon, which is one of the things your immune system makes when it's fighting off an infection, into the blood bloodstream of a mouse, a mouse, a mouse, and then just watching it.

And [snorts] they become, uh, you know, socially isolating from just the molecule that's made by the immune response during Not even from sick. Not even being sick. They're not sick. Well, they just are given this this cue that's part of the systemic immune response, and then they show the signs of social isolation. And the lab that did this, um, also showed that the brain has receptors for these immune molecules. immune molecules. immune molecules. And you know, the simple conclusion of that paper is, you know, there's still always work to be done, but simple conclusion was that the brain could sense infection and and it would affect behavior.

behavior. behavior. [snorts] [snorts] [snorts] Um, even in mature you know, in us as mature. So, you know, again, there's these these ideas that there is there's something that I mean, scientists used that infection of a mom, you know, to lead to neuronal changes that lead us to be able to under to study autism in later mice. So, there there's definitely potential there. I don't know that the vaccines and all of them in or whether it's a circumstance or whether it's, you know, getting the mom actually had a fever before and the vaccine now just triggered or didn't or just circumstance because you give vaccines at 2 years of age, which is when autism appears.

There's all kinds of options, you know, and the and and those sort of anecdotes of of that and and um I just think that that that fact that, you know, the way that we study autism is by giving a pregnant female mouse an infection. It's sort sort of like, okay, that's that's important to know. Mhm. Mhm. Mhm. That work is still ongoing by laboratories to understand autism. They want to understand the origins of it. And maybe it will not turn out to be vaccines at all.

Again, Again, Again, we we need data. And and we're in a data We definitely need data. We're we're almost in a COVID situation. I describe the COVID situation now in retrospect as one that is data sparse. And this is why I've been trying to work on I was telling telling you about this project I'm trying to work on the publishing problem. But it's not it's not just the publishing problem. It's how we how we synthesize knowledge. That under data sparse circumstances to make decisions, I think we're not very good at that societally.

Um and when we have tons of data and it says, "Absolutely, if you have cancer or you take immunotherapy, then there's a 50% chance you're going to revive." Great. Those stats are solid, they're very good, and I would I would take that drug every time. But if it's sort of a case where you're like, "Yeah, there's some things that are happening and and and there's some other things that happen we don't know." You remember the beginning of COVID, we talked about it amongst ourselves in the lab walls, and we were coming in to analyze blood, and it was kind of unsafe because we didn't know what was safe.

We didn't know how it was transmitted, we didn't know anything about it. It was it could it could we get it from blood? Um and and that kind of went on for a while, right? And this was the source of like a lot of confusion that came from the medical It was seemed seen as confusion that not your face is like, do you mask, do you not mask, do you touch, do you not touch? I think that's a that's a data sparse situation. You know, the the data that we had was sparse.

sparse. sparse. It wasn't a lot of information, and so, you know, how do you make a decision when you don't have a lot of data? Well, I think that's the major argument when there when there when there you know, there are people that will critique critique critique people saying, "Okay, your experience is anecdote, it's correlative, but then the the the what with regard to vaccines and autism and other issues, but then the pushback is, well, this vaccine, etc., was directionally guided by sparse information to begin with under times of [clears throat] 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." Yeah. Yeah. Yeah. Um but you have every right to ask your doctor. Right? But they're not asking because they're extremists. They're not anti-vaxers. They're asking because they love their kids 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. Yeah, certainly certainly in media some of these things get presented quite quite um, you know, inflammatory. And again, if if if newspapers want to sell a newspaper, they show a plane crash. Right. So, it's not happening every day, but they'll show you an airline ad in the same issue. Well, there's that, too. Yeah, you know. So. I think one of the interesting things that that we could get into is it it is that in you 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 we sometimes we call extensibility. Like I see that if I if I drop coffee cup on the thing that gravity pulls it down. Well, then I can learn that it I can drop all kinds of thing. I can make gravity work for me. You know, it becomes a tool. And and [snorts] I think one of the things that's that that it 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 moved 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 20° to, you know, 110°. We can not eat for a long time. You know, all 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 and from the outside or 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 garner interest for their story, you know, and then say this might be important for this, but I haven't shown this important for they they don't say that's important as it might be important. And they're trying to look for 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 take a pill and it cures everything, you know, forever. That's sort of found of youthish. youthish. youthish. And 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. button. button. You know, that that that can cause you know, collapse. And so, most things are wired like in in really complicated ways. And I think what a few of us are thinking, this is for cancer in particular where you want to get the immune state from like you know, where I had a little concept of a fuel gauge. You want to 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 biological systems to reach this new state in a way that doesn't look like the linear between like low immune reactivity and high reactivity. You might have to push it in a serious way because resiliency the the systems like even in chronic disease, but even in health, we're pretty resilient.

And I think you can stand up to a lot of stuff. Can humans do that even in the context of abundant funding for basic research? Can what you just described actually be tested to the point where we can develop things? 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. You need the math to prove it.

And this is when whenever somebody he also warned whenever somebody says they understand quantum stuff you have to ask them to demonstrate it for you because these people talk quantum because and and we make all these assumptions about quantum they talk about quantum fields so we think they're smart but but the theoretical physicists theoretical physicists theoretical physicists and for engineers get you know develop all sorts of incredible theorems and real experiments and then technologies based on based on based on all of that because of the math works not because we can conceptualize it and I wonder given the complexity of biological systems perhaps in 2026 we're running up against this barrier where by virtue of the sociology of science that papers need to have one maybe two take home messages by virtue of the fact that that that there's a limited amount of funding people need to sleep at night and on and on that doing the kinds of experiments like you described like pushing the cells this way nudging them that way and then drugging the the outcome in a way that is beneficial but not detrimental is this a place where machines are going to be to be to be better or at least helpful in doing these experiments?

these experiments? these experiments? I take the standpoint that AI's and I think you know this is back to talking about AI experts it's really quite good at at producing stuff that is in the corpus. The corpus is the knowledge that we already have. Almost by definition when you're coming at that with or something discovery you're discovering something it doesn't exist in the corpus. You might have hints of it there but you still have to do experiments at some point. So, if I'm going to get an answer, you know, the question you're trying to raise, if I get a tumor from a patient and I take apart all the cells and I look at all the genes that are expressed in all the different cell types, I can build in silico a network where I can look at how all those cells are wired together now.

And I can ask, you know, what would be the possible consequence of clipping this molecule's ability to touch that cell. cell. cell. [snorts] [snorts] [snorts] That that's that's now in doable, but it relies on a area of math that is not really AI. It's called machine learning, and sometimes these things are conflated. But machine learning is basically looking to say, what are some of the relationships that I can discover about, about, about, you know, the relationship between this feature of the cell and this other feature of the cell.

So, it's it's learning about it, and then it's it allows you to propose a bunch of experiments, but you still kind of have to choose and select which ones you're going to do. Some experiments are just really expensive. really expensive. really expensive. And that's where you have to have, I think, still human judgment that comes into that and say, am I going to spend a year year year studying this question and we're already doing Am I going to study a little bit more and try to understand some some things in a greater detail than maybe the machine learning gave me.

But it's not clear to me that any anywhere right now we can say the the corpus of knowledge doesn't have a bunch of examples of cures from, you know, across from treatments and say, oh, all I need to do is match those up, which is kind of what AI does when it comes to large language models. You query it, it looks and statistically it says, what are the relationships between what you queried and what I give you back as an answer. And in discovery space, we don't have examples of the, you know, the other end.

We have, you know, sure, I can tell you all the things that you could do, but, you know, knowing which one is going to be orthogonal big big hit isn't there. But what I'm talking about a little bit is is to just is to take a problem apart and say, if I have something like I want to change something change something change something in anything. This could be how if I want to change the world. It's unlikely that any one act will do it. The also the world is pretty durable.

The political systems, despite what we think, are somehow semi-stable. But a series of of of these nudges can create the condition where the last one takes you across the border. And I think that's what we're going to have to do in disease, where we say, "Look, nature doesn't necessarily want us banging on it. It'll bang back." What in fact in fact in fact we need to do is if we want this tumor to get eaten cured, we need to first let it not look like it's a wound that's healing.

So, don't give it the power of the immune system, the positive power. And then get to the point where we can say, "Well, now we want it to teach the immune system to kill it." But we may not be able to do that until we kind of dissemble some of its defenses. And that's that's a way of of, you know, again in this in this kind of deep computational space, we end up with a lot of feature that tissue of the of tissue cells and how they're organized and what genes they're expressing expressing expressing that start to look like Magellan's map of the of the of the world that, you know, in its early phase it only had parts.

And then, you know, it starts as you explore and you add things to it. You know, I think when we start to think about how tissues are configured, we're starting to be able to see these really complicated states where the immune system is doing this and fibroblasts, certain cells are doing this and epithelial cells are doing this. And that's a that's a we call them archetypes. They're archetypes. They're archetypes. They're [snorts] [snorts] [snorts] they're like they're like a way that biology organizes itself. And to get from one to the next, we need to understand how it does it developmentally.

That would be a really nice thing to follow. And then we need to give those cues in order. And that's where I was coming back, you know, when you were talking about peptides earlier. I was saying, "Well, they may some some of these drugs may well work, but I might imagine that they might work best if given in the right sequence and the time and the place." place." place." And that that's when you really want to like hammer to get the system go that, but then it might be a connected to another one.

And we all want to 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 looking for a single, you know, single hits one and 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. So, there's like collection of behaviors and what you eat and sleep you get and all these things create and partners, you know, and yeah, you're loves of your life, the the friends you have, they're all part of I think this this this this and that's getting a little away from immunology obviously, but it It's an analogy.

Could I ask you a couple of additional questions about the immune system? Yeah, please. Yeah, please. Yeah, please. Before we wrap because I know um many people are curious about autoimmune issues. More and more I hear about, you know, I don't know if it's chronic fatigue considered an autoimmune issue by most. A lot of people seem to have chronic fatigue. There was a debate, does it really exist? For someone who believes they have it, they it absolutely exists and they're tired. I believe them. I know someone who had a myalgia uh recently um psoriasis is something that I maybe have known to be now autoimmune, autoimmune, autoimmune, asthma.

These are interesting conditions, not all of them life-threatening, but some of them cause a lot of discomfort. What is known about the formation of autoimmune conditions, either inheritance, lifestyle factors, and then what excites you about some of the newer treatments that might be available or currently available for those and other things. It's a big question, but Yeah, it's a big question. Well, fundamentally, again, this is I think where um immune system and you know, our bodies have I think they have playbooks like a football team or something that they can run and they can put players in particular configurations.

Again, we call those archetypes. The immune system is trying to do a certain kind of thing. It's genetically and through history it's wired to work with with cells in certain ways. certain ways. certain ways. And I think if you look at auto immunities, there's a there's a view of them that they represent a misplaced immune system that's you know, thinks that it's under attack or it thinks that it's meant to be doing something that it really isn't. And so the origins of some of those are genetic, for sure.

There's um, you know, lupus, there's a familial mutation in a a receptor that's on a B cell that normally helps turn off the immune system. immune system. immune system. And it's defective, and so those those people are susceptible to getting what are called autoantibodies. That's where the B cells, we talked a lot about T cells, but B cells are the ones that make antibodies, and they're the ones that you try to prove you know, to jazz up for COVID vaccines. You know, those can be overactive, and they can be genetically overactive, and you know, one wonders why we'd ever have such genes and why they'd be propagated except that maybe in some sort of circumstances you need it when there's a big pandemic or something, those people might have a particularly good response.

So there's definitely genetic origins of some of these things. I think what's you know, what's interesting that to some extent is is something that you alluded to with asthma asthma asthma where asthma was one of these things that historically would be called an allergy, and it still is an allergy and where you have, you know, inciting things that are grass, pollen, you know, these sorts of things. But in a lot of these settings, the concept that that is is coming in part and parcel with, you know, the immune system system system recognizing self, you know, is is a is a thing.

And thing. And thing. And to the degree that we don't understand some of the diseases as well as we should given the tools we have today, there's a lot there's actually work to be done in a lot of these areas where you say, "What is the immune system up to?" to?" to?" Like like 10 years ago we might have just said, "Well, you know, what is if I I might have taken a a lung of a asthmatic patient who died and like cut it and look at it on a microscope and say, 'Oh, yeah, I can really see that there's thickening of the airways, and that's why that's why they couldn't breathe.'" breathe.'" breathe.'" But like I'm saying, now we can go into those and we can look at every single cell and ask how those are wired together.

Is there only one form of asthma? That's no, there's actually definitely there's seven or eight. And they have And that's why some people are, you know, like can take the inhalers and it works and other people can't. Some people they're very like chlorine sensitive. They go to a pool and it and and it's just like cold sensitive. So, there's there's variations on what sets up that inflammatory focus. And I would call it like an archetype. Some of them have lots of cells called eosinophils. Other ones have lots of cells called neutrophils.

So, it's Asthma isn't just one disease. It's one symptom failure, you know, difficulty breathing, but it has many different sort of configurations. configurations. configurations. And and I guess I'm I would just say that in a lot of this domain, I mean, we have a study right now that's looking at across a bunch of autoimmunities to figure out whether they have things in common with each other. And psoriasis is one where you start to see, you know, variations and lupus for sure and inflammatory bowel disease and and and you know this in the clinic because inflammatory bowel disease, you asked about drugs, is a good case where there's a couple different drugs that for some patients work really well.

TNF therapy, for example, saying that it blocks a cytokine. And some people with IBD, this is like really bad diarrhea and it's and manifests in very very painful um painful um painful um you know, some people they there's a So, there starts to be classes of patients that have responses to these things. Those drugs are exciting because they say you can modulate this. But a little bit like the checkpoint drugs, we don't really understand why one works in one patient and one doesn't. And inflammatory bowel disease is an autoimmunity is pretty tricky too because people will respond to a drug for a while and then they'll stop.

And then the the doctors just have to do this like whack-a-mole thing where they try one and it doesn't work, they try the next and it doesn't work. Sounds like psychiatry. It does Yeah, there's a lot of It sounds like a No disrespect to the psychiatrists, but No, but you're trying to They have a hard job, right? I mean Drugs will work for a while, then they don't work. Side effects crop up that never existed before. It's it's a tough one. one. one. Yeah, agreed. Agreed.

So, yeah, autoimmunity is a real thing. It's it has you know, I think it's similar to cancer where we're just dealing starting to understand the fact that it comes in these different immune flavors. And so the drugs that you try to use is clearly immune system can do a lot of good work for us. But what you need to do to it in these different sort of archetypal immune systems is going to be different. You know, you see it's just going to be a different football team out there playing or they're going to running a different play.

different play. different play. If somebody has a mild autoimmune condition, like let's say mild psoriasis, psoriasis, psoriasis, Mhm. Mhm. Mhm. does that I've read, but that doesn't necessarily mean anything. Um I've read that that might confer, because it's autoimmune, that might confer them with a bit better viral and bacterial infection resistance. So, you know, there's a trade-off there. Like, okay, so scalps the cells are like sloughing off and like I think it's like interleukin 17 or something now. Like the treatment, they have some good shampoos for that.

So, but but but And and anti-interleukin 17. And anti-interleukin 17, but but you that individual is um be better at fighting out other infections. So, you know, given there's a anti-interleukin 17 treatment that works, cool. Like, no flaky itchy scalp and and yet you're more resistant to infection. So, you could see how it's adaptive in the modern context. And now severe psoriasis can be very disruptive for people. And people might wonder like are we really talking about psoriasis, but I think it's sort of a individual interesting case point for why autoimmunity could actually be useful.

Yeah. Yeah. Yeah. Um it's not always the case that it's like there to give us asthma or or flaky scalp. scalp. scalp. You know, what you could talk about there's a lot of disease states, you know, the argument for why we would ever have a sickle cell gene. This is the one that causes people to have hemophilia, and it's a lot of sub-Saharan African gene people from that origin have this is that it's actually defensive against malaria. It's you know, it seems to be the case that so so having that, I think that's is true a lot of these situations where the diversity of the human population over time, by having some of these things that make some people hypersensitive to you know to maybe bacteria viral infection at the cost of cost of cost of having things like psoriasis pop up or you know various various other auto immunities immunities immunities is the only way that you know like a a billion strong population has to to to to move forward and I always give this example to cuz I think it's a really straightforward one.

straightforward one. straightforward one. If you take a a flask of bacteria and and you put them in glucose which is like sugar like you put in your coffee. Um maybe sucrose either one. You put them in a in a in a simple sugar uh and you watch the colony grow. You'll get these cells that grow really really fast. The bacteria you know becomes billions trillions of of individual cells but there's almost always some just losers that are dividing slowly. And it's for whatever reason the system always brings us off you know like why would you do that?

Why would the system why why wouldn't just the winners win? But if you take a little bit of that culture and you put it into galactose which is a milk sugar often the ones that were winners don't win anymore and it's from the loser pool that the new ones emerge. And this is a case of like you know like a crowd crowd crowd uh fitness that comes from diversity of of genes and so some of these things that make some of us susceptible disease are also as you're pointing out in other situations going to be quite good for you and and and that seems unfair at the time that you have these kind of bad genes but like a different day you would have been happy or So I think there's a lot to be said and and that's also why a lot of the things that we look at you know anecdotally somebody takes a supplement and it works for them.

for them. for them. I mean I don't know how much you know about this literature but the the differences in your and my vitamin requirements is going to be quite profound because the metabolic enzymes we have for the vitamins that we might take in are going to be different between us and so these FDA limits these these numbers are averages. Some people may need five times that amount of you know vitamin X other do may need a fifth. fifth. fifth. No I think this super critical.

The supplement world is kind of like scattershot. While I appreciate the rational grounding in all of it, I I think uh think uh think uh throughout today's conversation, I think that that that I picked up on you know, I the fact that we covered things like peptides and things like that. And I'm not certain about the peptide question across the board. It's clear some are beneficial, it's clear some are still experimental. I'm just a big fan of more data. And more data collected the right ways and communicate the right ways as the same way with the vaccines and all the rest.

You have an amazing Substack. I know that because I've spent time there. Oh, thanks. Oh, thanks. Oh, thanks. Part of the reason we invited you here today is to learn about the immune system and we barely talked about cancer, I realize. We're going to have to get you back to talk about that. But you've done an amazing job of educating us on the immune system. I really want to thank you and speak on behalf of many, many people for that. Never before has somebody presented in in the ways that you have.

And as somebody who thinks in analogy I and likes to teach in analogy, I really appreciate that. Thanks. Thanks. Thanks. The uh that uh that stance. What inspired you to get into Mhm. Mhm. Mhm. public education about science and health before coming on this podcast? And by the way, everyone should check out Max's Substack. We'll put a link to it in the in the show notes. It's it's so thoughtful, so thoughtful, so thoughtful, so nuanced, so relevant to all the issues that we're talking about if not directly then in the in the general contour and in some cases directly.

And I I imagine you're going to continue doing this. So what inspired you to do it and um how can we make sure that you continue to do it? Yeah. Well, thank you for the call out. Um Um Um it is a something I've been trying to work on for about 10 years and it it really started when um a group of us, you know, we're we're hanging around after a conference and we were talking about some of the issues with science and society. And there were many.

You know, there's many. There's there's we've surfaced a few of them today. But I think something that you guys are working on it is is the capacity for everyone else to think as a scientist. Like what you can ask yourself you know, oh, why don't people agree with this data that you show and take the action that seems logical? But then you present it in such a way that they can't, you know, that they did two things two things are important about it. I think one of them is you if you present the information in a format that isn't, you know, familiar, you're not going to be able to teach anything anybody anything about what's important.

But the other thing is that, you know, we were talking we we spent some time talking about this and we consulted some other folks that are in science comms and we realized, you know, the other thing is that that that if you say you're a scientist, it's not a neutral statement. Science has a history and history is stronger than science actually. So the history like, you know, so there's there's there's hesitancy among African Americans, for example, to take drugs because of things of history of Tuskegee, which is like 80 years ago.

All right, you know, however long ago, 60 years ago. Well, it's it's it's it's it's not in their lifetime and in many of these people. And so part of the realization was like maybe part of what we really should be doing as scientists is one of part of our job should be to figure out how we relate to other humans. And it's you know, there's a painting of this in the obviously the media and and things help this happen because it makes it interesting to have us, you know, kind of a nerdy scientist and and we got all the you can be a nerdy scientist.

I heard you and you know, but also you're a human, you're a human being. You have you know, every everything foibles too, you know, loves and hates and and um Certainly foibles. I have plenty of those. those. those. We can get in that after the podcast, but but you know, the this concept of if we want to relate, um you know, if we want to have impact of the work you do, if you want it to be relevant, at some point you have to the science science as a field needs to make sure that it doesn't ostracize itself from people.

And I think one of the issues there I'll just use the word ostracize. You know, is separate is is this concept that we speak in our our vocabulary that is gets very precise and we forget that, you know, if you hear a foreign language and you hear one word that you don't recognize it, it throws you off for a few sentences. And next thing you know, you don't know what people are talking about. And I I think that concept that that, you know, and again, this is where I think bringing it down a level and saying, let's give it analogy, let's give it That strikes [clears throat] me as really, really important to the impact that you can have with with your science.

And and that and and that science can have in in terms of teaching people what we could do better, do better, do better, which I think we all want to do. But if you end up thinking that science is a distrusted, weird collection of people that have different motivations and um designs, then then you've lost. The The The that that the potential for it to do good is is gone. So, the Substack came about it because I was like, well, I need to write as a person a little bit more and and tell about some of the you know, the the time that you spend on this and why it matters and what it's like to to do this work and and and some respects also what it's like to to lose in this, which happens way more often than the, you know, it's it's like a casino, right?

In science In science you hear the bells and some cool device comes out and it's But but there's a bunch of people pulling the arm, you know, and they're they're they're not winning. And so, And so, And so, Well put. Well put. Well put. So, I feel like that's kind of an important part of this that that Again, it's not the glory story always. Um you know, the best some of the best selling books about science are the wins. wins. wins. But um you know, that might be more relatable at some point to get all of it.

So, that's kind of what what I was trying to put together and and at the same time, I think the immune system is also just so relevant and so important and it's got all these different facets and these archetypes and these sorts of things that it's doing that we kind of scratch the surface today. So, anyway, thanks for calling it out. I've been working on it for a bit. Well, I hope you continue to and um thank you so much for the work you've been doing in your laboratory and all the people in your laboratory doing that work because now you're the one calling the shots while other people do experiments, but um for your advocacy for science and public education is huge.

We need more people like you, but you certainly put your own unique signature on it and the Substack reflects that. It's an incredibly interesting set of reads and people will really learn. So that's essential especially in this day and age, but even not in this day and age science is is just really cool and with all the meaningless drivel out there, it's nice to go to a place like your Substack and Substack and Substack and I'm speaking to the audience now. You will learn if you read Max's Substack.

You will be inspired by certain things and I promise you and so I'm saying this intentionally mark my words at some point some somebody's going to contact you that they decided to study the immune system or they learn something or they explored a a novel treatment with their physician in a in a given unfortunate or maybe even fortunate situation that bettered their lives. It's it's incredible what um Substacks and conversations like the one you've been willing to have today and going forward can can really do.

So thank you so much. Definitely come back again and tell us about cancer and other other things because I I took us off course quite a lot, but I I had a great time talking about all of this and I'm going to be thinking about a lot of it and really appreciate you. Yeah, well same here. Thanks so much. Thank you for joining me for today's discussion with Dr. Max Crummel. To learn more about his work and to find a link to his superb Substack, please see the links in the show note caption.

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