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

Summary

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

Date: August 3, 2026
Host: Andrew Huberman, Ph.D.
Guest: Dr. Max Krummel, Professor of Immunology & Cancer Biology, UCSF

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Episode Overview

In this episode, Dr. Andrew Huberman sits down with Dr. Max Krummel to explore the immune system in both scientific depth and with practical, actionable recommendations. The conversation covers the basics of immune function, the role of the immune system throughout life and aging, connections between the brain and immunity, developments in vaccines and immunotherapies, and broader themes of scientific discovery, public trust, and actionable health protocols.

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Key Discussion Points & Insights

1. What is the Immune System & Its Changing Role (03:17–09:32)

• Past and Present Views: Immunology was once seen as a niche or even dubious field, but discoveries around cancer immunotherapy and the immune system's regulatory functions have made it central to understanding health.
  • "Cancer immunotherapy changed that a lot... A tumor is kind of not exactly self, but it’s also not foreign—so I think tumor immunology really changed our perspective." – Krummel (04:02)
• Self vs. Non-Self: The immune system’s primary challenge is distinguishing the body’s cells ("self") from pathogens or abnormal cells ("non-self"), and this can shift as we age or due to factors like cancer.

2. Immune System Development & Aging (09:32–22:11)

• Children: Initially immunosuppressed for the first six months of life (to prevent self-attack during rapid development), children then face frequent infections as their adaptive immune system is "trained" by exposures.
• Elderly: Aging leads to both a decrease in immune cell production and increased cellular mutations. The immune system, faced with a "mosaic" of body cells, may lose the ability to clearly distinguish self from potential threats, which has implications for cancer and autoimmunity.
  • "Every cell in your body is no longer identical to the one next to it... You are becoming like a mosaic." – Krummel (15:55)

3. Analogies and Concepts for Understanding Immunity (22:11–36:52)

• Submarine Analogy: The immune system is like wartime submarines using "sound books" to sort allies from enemies—the "self" and "non-self" libraries.
  • "The immune system has to do the same sort of self versus non-self discrimination problem..." – Krummel (22:32)
• Background Noise of Aging: With age and accumulated mutations, the distinction between self and non-self blurs—making both cancer surveillance and infection defense harder.
• Selective Pruning: The immune system is constantly pruning and removing precancerous cells, which may explain visible changes like skin spots in older adults.

4. The Thymus, T Cells, and Immune Memory (36:52–49:42)

• Critical Early-Life Role: The thymus educates T cells to distinguish self from non-self. It shrinks with age, explaining a decline in new T cell output and possibly increased late-life vulnerability.
  • "Thymus is both the place that makes all your T-cells and educates them..." – Krummel (37:39)
• Potential Future Therapies: Interest in banking thymus cells or peptides, but practical hurdles and unknowns remain.

5. Sleep and Immunity Mechanisms (49:42–55:16)

• Sleep is essential for immune system reset and repair: immune cells clear back to the bone marrow, reparative processes kick in, and certain immune migrations only occur during sleep.
  • "A lot of your immune cells clear back to the bone marrow... there’s a lot of things that are reparative about sleep." – Krummel (49:42)
• Sleep deprivation immediately makes us more vulnerable to infections, likely due to a failure of these restorative processes.
  • "Everybody has bags under their eyes and looks like shit when they are sleep deprived. Sleep for a night or two, it goes away." – Huberman (51:57)

6. Stem Cells, Self-Experimentation, and Longevity (55:16–63:55)

• Umbilical Cord Banking: Useful for potential future bone marrow replacement, but true rescue stories are rare.
• Overemphasis on Interventions: Banking thymic tissue or personalized organoids is exciting, but much of stem cell therapy for longevity or disease remains speculative and underdeveloped.
• Scientific Progress: Fundamental leaps (CRISPR, cancer immunotherapy, GLP-1 drugs) often come unexpectedly after years of slow, frustrating progress and failed experiments.
  • "In science, with all the failures and all the things and then to finally complete something... there’s nothing better than these long term investments." – Huberman (73:14)

7. The Brain-Immune Connection & “Spatial Biology” (74:10–85:56)

• Spatial Biology: Immune cells both migrate and form resident populations in tissues (e.g., the gut or lymph nodes). Transplantation depends on both cell compatibility and the local immune environment.
• Brain States Influence Immunity: Activation of certain brain circuits (the insular cortex) can replicate or "replay" immune states previously associated with specific experiences.
  • "You could train yourself to bring up an immune state in a particular tissue just by firing those neurons." – Krummel (80:03)
  • "That may be what meditation is doing... allowing your brain to communicate and reset less inflammatory states across your body because of this axis." – Krummel quoting Dan Lippman (84:07)

8. The Individualized, Adaptive Immune System (85:56–94:57)

• Psychology Meets Immunology: Mindset and subjective experience (e.g., "I never get sick") may reflect—and influence—immune regulation via brain-immune signaling. Language does not directly affect immune cells, but associated feeling states do.
• Autoimmunity, Peptides, and Biohacking: Context and timing are key—what works as an intervention may depend on the tissue state and broader environment, but personal experiments rarely rise to the level of scientific data.

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Notable Quotes & Memorable Moments

• On Scientific Discovery:
  "You have to start there. Otherwise you’ll just plow this direction and you’ll hit those walls because you don’t have workarounds that come with some orthogonal piece of information." – Krummel (70:33)

• On Communication and Public Trust:
  “If we want to have impact… science as a field needs to make sure that it doesn’t ostracize itself from people. If you relate, if we relate as humans, then you can have impact.” – Krummel (141:23)

• On the Complexity of Biological Systems:
  "If you want this tumor to get cured, you need to first let it not look like it’s a wound that’s healing... It may not just be about a push here. You may have to push some cells that way, create some new environment, and then push, push the biological systems to reach this new state." – Krummel (124:15)

• On Vaccine Protocols and Public Debate:
  "What you’re describing – could we make it less disruptive? Let’s do a study and make that very public... At what point can the government tell you what to do? There’s efficacy in protocol but also room for better studies." – Krummel (102:09–103:06)

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Deep Dives into Key Segments with Timestamps

Historical Overview & Immune Self/Non-Self Dilemma

03:17–09:32

• How immunology evolved and why tuning immunity (not just turning it on or off) matters.
• Tumors as a special “almost self” problem for the immune system.

Immune Development in Kids and Aging

09:32–18:04

• Why kids get sick (and recover fast): unique immune developmental phases, learning immunity.
• Aging: cellular mutations accumulate, immune system struggles to keep up.

The Thymus and T Cells

36:52–43:09

• Thymus' role ("T" cell origin), early-life immune training, implications of thymus shrinkage.

Sleep’s Direct Influence on Immunity

49:42–53:23

• Immune system "resetting" at night; sleep deprivation impairs immune migration and repair.

Spatial Biology & Transplantation

74:10–80:03

• How immune cells “on the move” and “in place” protect us.
• Why transplanting tissues (e.g., pancreas or thymus) requires immune acceptance and microenvironmental support.

Brain-Immune Synergy: Place, Memory & Mindset

80:03–85:56

• Insular cortex can trigger immune states by memory recall.
• Meditation and mindset as potential immune modulators.

Vaccines: Science, Protocols, Public Trust

94:57–112:28

• Vaccine hesitancy, safety, timing, combinations; the need for more nuanced, transparent research and communication.
• Science not as dogma but as a collection of evolving, sometimes fallible, practices and findings.

Autoimmunity

129:01–138:02

• Diverse origins (genetic and environmental), multiple "archetypes" of disease, personalized treatment challenges.
• Adaptive value of genetic diversity (e.g., sickle cell gene and malaria resistance).

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Takeaway Actions & Science-Backed Advice

1. Support Your Immune System:

• Prioritize quality sleep—immune restoration and function depend on nightly reset ([49:42]).
• Embrace a diverse microbiome with diet and healthy environmental exposures ([10:25]).
• Maintain social connection and psychological resilience; brain states (positive or negative) can modulate immunity ([80:03]).

2. Critical Evaluation of Health Interventions:

• Approach stem cell, thymus banking, and peptide trends with measured skepticism; await robust data ([55:16]).
• For parents, understand vaccine protocols and feel empowered to ask about timing and safety; look for more nuanced, science-backed policies ([94:57–104:31]).

3. Science Is a Work in Progress:

• “Breakthroughs” (like immunotherapies, CRISPR) arrive unpredictably after years of frustration; appreciate the need for patience and experimentation ([66:52]).

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Resources

• Dr. Max Krummel’s Substack: The Immune Beyond
• For Comprehensive Lab Testing: Function Health
• Huberman Lab Neural Network Newsletter: hubermanlab.com/newsletter

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Final Reflection

This episode marries hard science with lived experience and public dialogue—a rare, disarmingly candid look into how science thinks, learns, adapts, and sometimes stumbles. Dr. Krummel's accessible analogies, grounded humility, and willingness to address nuance in contentious topics (like vaccines or biohacking) make this discussion invaluable for anyone seeking both foundational knowledge and a deeper appreciation of the evolving nature of immunology and medical science.

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Summary prepared for listeners seeking a comprehensive, actionable, and richly contextual understanding of the immune system and the science that surrounds it.

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Transcript

[A]

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 Motors engine, they wouldn't fire. So that's the sort of like self. I know what self is. And then they had another book that was the engine sounds of the known diesel engines of whatever engines of the German submarines. And if they heard that, then they absolutely would fire. And that's a self versus non self discrimination problem, just like the immune system has to do. But what I bring you with it, aging is this concept that as you get weirder and different and your body is getting like more complex, then those books start to have possibly every possible permutation of every biomolecule could be made by your body at that point. And then a virus doesn't necessarily have anything unique about it.

[B]

Welcome to the Huberman Lab podcast, where we discuss science and science based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Max Krummel, a professor and leading expert in immunology and cancer biology at the University of California, San Francisco. Today we discuss your immune system, how it works, what it needs to function at its best, and how things like aging, vaccines, sleep, and even your thoughts and emotions shape immune function. For instance, most everybody knows that being sleep deprived makes you more prone to getting sick. But why? Meaning, mechanistically, why? Well, it turns out there's a specific set of cells that need to migrate in a particular way during sleep. And we talk about how you can reinforce that process in ways other than sleep. We also discuss incredible findings that certain brain states and memories can be associated with an immune system status you had when those memories formed. And evidence that just recalling those memories, that 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. Crummell 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 access 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. Crummell has an incredible zero cost substack. It's called the Immune Beyond. You can access it by going to the immunebeyond all one word.substack.com and there he teaches about science and more again. It's awesome. It's free, so definitely check it out. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however part of my desire 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 Crummell. Dr. Max Crummell, welcome.

[A]

Thanks.

[B]

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 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.

[A]

When I started in immunology sort of 30 years ago, I was rotating in labs at Berkeley. I think you were at Berkeley as well. And one of the transcription factor biologists mentor said, why do you want to work in immunology? It's not really a field. And so at the time it was kind of true. Everything was about DNA cloning. It's obviously still a lot about molecular biology, what we do, but 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 and otherwise it generally had to be quiescent and kind of leave you alone. I think cancer immunotherapy changed that a lot. That gave us the idea that you could tune its reactivity so that you could get to the point where if you gave an immunotherapy, what it was actually doing was raising the threshold of when a T cell would activate and allowing T cells that might be just letting the tumor get by, they'd be able to go after that tumor and kill it. I think that changed the spectrum a certain degree where we suddenly thought, okay, this isn't just a foreign versus self thing, because a tumor is kind of not exactly self, but 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 to the point where we now think of it as a tunable system. But then I think a lot has happened in the last 20 years. There's been a lot of excitement about cancer immunotherapy because. Or curing people with cancer, which really wasn't done before. You're now in the space where 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, et cetera. But it's in your gut. It's allowing microbes to live in you, but it's titrating them. It's keeping them there in kind of like the right quantity. So it's kind of guarding yourself. It's, you know, sits in your liver, regulating how much you metabolize. There's a collection of cells there. It's in your heart. It's regulating cardiomyocyte function. Those are the muscle cells of your heart. 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 heart. So it has all these additional functions that kind of. Before were lost in just the foreign battle against the foreign. And now we have this kind of perspective of this system that measures us all the time, everything about us. And it exists in some ways, I think, is to. To help us be who we are, you know, and that's hopefully that's you as a healthy person, you know, and chronic disease, unfortunately, can be part of the problem where it becomes part of the things that's letting the chronic thing, whether that's a tumor or kidney disease or what have you, it can. It can actually help perpetuate it because, well, it's, you know, some ways it's trying its best, but it's applying the wrong program to the wrong situation. So, yeah, it's changed a Ton. And I'll give you another little funny story, which is that when I first came into immunology, again, we had the story like mentor who says, this isn't really a field. The year was. I came to the field in 1989, and that's right at the peak of AIDS. And AIDS was, like, as a biologist was really interesting because 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 cel cells. And you have a subset of T cells that are called CD4T cells. They're kind of a flavor of T cells, and the virus gets rid of those. So HIV virus will infect the CD4T cells, and then you end up with not having them. And the manifestations of AIDS for those that weren't around during it was. It was just a ton of different opportunistic infections. So, like, soil bacteria that you and I fight off without even thinking about it would. Would kill people, but so too would you. See, you saw people with carbosarcoma. You saw like a opportunistic, like, where, you know, cancers emerging, and you just saw all these kind of manifestations of where the immune system was important. Dementias in people with HIV as well. You know, it was early accent at the time on how many different things the immune system might be important for. So regardless of whether, you know, it was a 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. Some of those, I think it's worth pointing out, were just these curiosity questions, like, what are these cells? They were hard to study in the beginning. They don't live, sometimes hard to keep cells out of a human body alive. So there's issues about how do you keep these things alive in the very first place, and then what kinds of things trigger them to do stuff? And you got to make reagents to test those 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 cel and the behaviors that they can engage in. And it just gets more complex and more rich as we understand that 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 set of biomolecules proteins in the form of peptides. They can measure that, and each one then can say that's out of range or that's in range. So it's like you have like 10 to the 11th little sensors going around you, curating you, you know, making sure you're the right thing. And if they see something that's out of range, they can do something about it. You know, like, the whole thing is magnificent.

[B]

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.

[A]

Yeah.

[B]

Maybe you could describe what's going on there.

[A]

Yeah.

[B]

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? Or is there something more broadly happening at level of just kind of energetics, mitochondrial function? Very curious about this.

[A]

If I can take a step even further back, I will ask you a question of, like, who are you? And I don't mean that like, in a personal sense, but I talk about that too, if you want. But the more the question is, like, at some point, where does your body end and where does the world outside start? And one of the things that, you know, you start to realize if you look in a microscope is that we're covered with microbes all over our surface. We're covered with microbes all the way in our gut. In fact, we can't. You know, you can't digest. You've probably heard this before, but you can't digest animal fats. If it weren't for the bugs, the bacteria in your gut, they make some of the key components of 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 cell that starts to divide and gives rise to every other cell in our body. You might say that your body is just that collection of cells, but in fact, it's absorbed a lot of viruses and bacteria from our environment. And 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. Like you said. Like I was saying, the bacteria in 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 seaweed, you know, nutrients from seaweed. So taking this into your question, you know, when you're first born, you've never really seen anything. And so two things are, I think, worth pointing out the early phase of life. One of them is for the first six months or so, your immune system is pretty poor at being trained on things. And it's presumably we presume that for those six, six months, that's because your body's developing so fast that if you were to have a super active immune system, you might actually find yourself attacking yourself. You might think that you're foreign because some genes turn on during development. And then all of a sudden your immune system's like, oh, I see something different and now I need to react. So that's well known. And that's one of the reasons why some childhood vaccinations, they're really important to protect kids over life. Why they aren't given until you're six months or older. But I think to your point, one of the things that's happening with kids is that then, then as they go into their, like until they're 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 because they've never seen the body's, never that body, kid's body has never seen flu before. So every single virus and pathogen that hits it is going to elicit some, you know, some amount of illness. But then they have a very strong immune system. It reacts and gets rid of that. With the exception of the ones that, those certain viruses and bacterias, mumps, measles, rubella that are lethal. And that's why we immunize, as we say. And 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. That's the front end. The front end has this initial 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 reach a detente with some of them. We have to get to the point where the immune system can kind of fire back when they show up if they're bad 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 can see that both in the form of kids getting sick a lot, but you'll also see that their guts develop way diverse microbiome. They allow a whole bunch of things that come in from the outside and are acceptable and are quite good for you. That's the front end. In the back end of life, it's a little bit more complicated. But I'll tell you two things that I think are important. On the one hand is the idea that is the fact that a lot of your cells in general become less functional, including immune cells, and you get less cells produced. And that might just be because we were never selected as organisms to live as long as we do right now. That's one idea of aging, right?

[B]

Did you know that, that we just were supposed to be dead by 70?

[A]

Well, no, but we do know that we can reproduce and pass on our genes successfully already when we're 16. So 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 on the crop. But at some point, maybe there's no selection. So we don't know that. But 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.

[B]

The psychologists would tell us that the wisdom of people, you know, 60, 70, 80 and beyond, is useful for groups of humans that live in, you know, villages of 100 or so people, because they can give information to younger people that is on the periodicity of like every five to 10 years, maybe every 30 years. But that's a just so story, right? I mean, it's a nice just so story.

[A]

I like it too. And I think the geneticists will refer to that 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 the elderly that do, you know, they're going to have effects on the fitness of their grandchildren, which is their genes. And so I think there's something to be said for that. In conceptual space. I don't know if I can prove

[B]

it to you that that's a tough experiment to do.

[A]

It's a really tough experience to have two villages where the, you know, the grandparents are elimina or like kept, you know, both non ethical and also nonetheless.

[B]

Right.

[A]

But we were 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? And I was saying, okay, well, in aging you have this issue that the immune system is tapering in its efficacy. It's many of the cells that you, you know, you've been holding your whole life start to literally, they die off. But there's another thing which is, I think a lot of people don't realize when you say, when the basic biology would say the sperm, you know, like fertilizes the egg. So you've got your mom's genes and your dad's genes. You've got 23 chrom for your mom, 23 chromosomes for your dad. And at least when you're first born, every cell is a clone. It has exactly the same information. But DNA replication and DNA sort of like fidelity isn't perfect. 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 basic sun exposure. And that's higher than some of the other organs. But the basic idea is that your DNA is susceptible to UV radiation. That's one of the reasons we put on sunscreen. But what it practically means, no matter what number you put in there, whether it's 10,000 mutations per day or remember, the genomes are huge. 10,000 mutations out of terabytes of information still is only a certain number. But do that over years. 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. And I say mosaic because like the tile you see in Morocco, very intricate designs. Because if you actually start to look into tissue, 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 new cell has to form, they might be the fittest to fill that void. And one of the other clones over here that got a different mutation may not be fit to fill that clone. And so 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? Okay, you want another analogy?

[B]

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

[A]

Same cells, but they're same cells.

[B]

But so you're saying mutations are constantly accruing in the neurons, in the DNA.

[A]

So it is fascinating, by the way, that neurons live that long. And hair cells, they say that the proteins in our hair cells every year are the same exact molecules, atoms, as we had when we were born. So 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. We tend to think that 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 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 aeration. They hang out and stem cells are, you know, the bone actually serves not only a structural purpose in our body, but it's a cavity in which things can live.

[B]

Keep it away from solar radiation.

[A]

Solar radiation.

[B]

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

[A]

Sequester your stem cells and don't burn them.

[B]

Yeah, that kind of thing.

[A]

Yeah, yeah.

[B]

Likewise, the neurons in the. In the inside of the skull.

[A]

Yeah.

[B]

And the spinal cord are protected. They're protected.

[A]

Yeah.

[B]

And that's interesting.

[A]

Yeah, yeah.

[B]

I would like to take a quick break and acknowledge one of our sponsors, Joovv. Joovv, makes medical grade red light therapy devices. Now, if there's one thing that I have consistently emphasized on this podcast, is the incredible impact that light can have on our biology and our health. Health. Now, in addition to sunlight, which I've talked about a lot on this podcast, red light, near infrared, and infrared light have been specifically shown to have positive effects on improving numerous aspects of cellular and organ health. These include faster muscle recovery, improved skin health, wound healing, improvements in acne, reduced pain and inflammation, improved mitochondrial function, and even improvements in vision. Nowadays, there are a lot of red light devices out there. But what sets Joov lights apart and why they're my preferred red light therapy device is that clinically proven wavelengths, meaning they use the specific wavelengths of red light, near infrared and infrared light in combination to trigger the optimal cellular adaptations. Personally, I use the Joovv whole body panel about three to four times a week, usually for about 10 to 20 minutes per session, and I use the Joovv handheld light both at home and when I travel. If you would like to try Joovv, they're offering up to $400 off select products for listeners of this podcast. To learn more, visit Joovv spelled J-O-O-V-V.com Huberville Again, that's J-O-O-V dash V dot com Huberman Today's episode is also brought to us by Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating and sleep tracking capacity One of the best ways to ensure you get a great night's sleep is to make sure that the temperature of your sleeping environment is correct. And that's because in order to fall asleep and stay deeply asleep, your body temperature actually has to drop by about 1 to 3 degrees. And in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about 1 to 3 degrees. 8 Sleep automatically regulates the temperature of your bed throughout the night according to your unique needs. I've been sleeping on an eight Sleep mattress cover for nearly five years now, and it has completely transformed and improved the quality of my sleep. The latest eight sleep model is the Pod 5. This is what I'm now sleeping on and I absolutely love it. It has so many incredible features. For instance, the Pod 5 has a feature called autopilot, which is an AI engine that learns your sleep patterns and then adjusts the temperature of your sleeping environment across different sleep stages. It'll even elevate your head if you're snoring makes other shifts to optimize your sleep. If you'd like to try Eight Sleep, go to eightsleep.com huberman to get up to $350 off the new Pod 5. Eight Sleep ships to many countries worldwide, including Mexico and the UAE. Again, that's eightsleep.com huberMAN to save up to $350.

[A]

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

[B]

a lot of half the audience.

[A]

No, I'm just kidding.

[B]

I'm totally joking. We're a bipartisan audience.

[A]

Take it how you want, but by analogy, I'm joking. It's the argument for why certain influx of, in this case, organisms onto us create a more robust person than we were before. But I want to give you this story that a famous immunologist in the 1970s drew this parallel in wartime and said in, you know, World War II, submarines would be underneath the ocean and they'd be traveling around, and they would, if they could, if they heard another submarine, they would scuttle the missiles, the torpedoes, because that could be the enemy, and the enemy could fire at them. And so they had two sets of books that they used. One of them was a book that gave them the sound profile of all. Let's say it's a US of all the US submarines. And so they could listen to the whir of the engines. And if they heard a whir of the engine that had the certain cycle of a General Motors engine, they wouldn't fire. So that's the sort of like self. I know what self is. And then they had another book that was the engine sounds of the known diesel engines of whatever engines of the German submarines. And if they heard that, then they absolutely would fire. And that's a self versus non self discrimination problem. Just like the immune system has to with do too. But what I bring you with it, aging, is this concept that as you get weirder and different, your body is getting more complex. Then those books start to have possibly every possible permutation of every biomolecule 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, oh, a new thing has come in and that's out of range. And now I need to mount that T cell response against this. I need to bring in the troo. But with aging, we have this kind of us diverging problem. So that this system that's supposed to sense us has a lot of cosmic background, has a lot of noise in it. And so I think that's one of the reasons why we also have issue when we're aging. And I think it's also one of the reasons why cancer is more prevalent in later life. There's two parts of that. One is, of course, you've accumulated mutations in your cells that could be cancerous, but also the immune System has been seeing those and all the various different accumulations of them and ones like them, you know, over these years to the point where the weird doesn't look that weird anymore. You know, something like a cancer that is different than you. It's not that much different than like another cell over here that's gone. You know, like, and it's just happily making skin and isn't cancerous. But you know, it's got some differences.

[B]

What about the argument that there's so much cellular turnover that the cells that accumulate these mutations are being eliminated? You're saying because they're clonal, they're producing different, they become different, they produce cells that are also different, then they die. Is that the way it works?

[A]

Yeah. And I think you are bringing something up that's also true, which is that all the time I think the immune system is defending us against mutations. So one example that everybody sees when they get to be about 40 or 50 is little these white spots on your skin. And 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 so a lot of the origin of cancers in skin is melanin producing cells. Like melanoma is what we call skin cancer. Those melanocytes, that white area, they've been wiped of a whole collection of melanocytes. And that's why it's white instead of as dark as the rest of your skin. So to that extent, the ide immune system is pruning you all the time is, you know, there's, it looks like there's pretty good evidence for that. And the question is, when does somebody become dangerous? That's fundamentally the question with cancer and these sorts of things. If you said I want to actually have the fittest cells in my skin to 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.

[B]

Right. Because they have an abundance of these

[A]

cells that I think, I think they're wound healing. I mean there's a group out of Stanford that studies this. But essentially, you know, wound he in, in young is quite, quite a bit faster and more efficient. And, and there's many levels, there's many levels of that. Yeah, yeah. But yeah, remarkably faster. And if you're a parent, you've seen this. You know, you cut yourself on the same day as a kid, your kid cut yourself and they're, they're three days later, they can't even find it on them. And, you know, like, four weeks later, you're still like, you know, scab or something. But I was just coming to the point that if you do that and you want this, do you want. You maybe 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 heal quickly. Well, if a mutation has happened that fills that cell in 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 in some sense. All these events in your life where 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. They may be a little bit better at growing. Then again, the cool question is, how much better do you want that? You want it to help you, but at some point, you don't want it to basically form a lesion and 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 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. 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, low for itself. 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 in general. 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 where I was saying, you know, it can. It can like, quarantine bacteria. It's not going to kill them. It's in that zone. Bacteria, as long as they're in the right zone, there's not too many of them, there's not too few of them. Immune system can actually help them be there. It can produce things that either tighters them out of circulation or keeps them there. And all these other settings, like I say in the heart can go to almost any organ, and the 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 multi mutations that you might have accrued and all the bacteria and the viruses. We have a lot of viruses in our bodies that we tend to think that at the end of a illness that we've gone back to our pure state. This may came from religion. We were born pure. And if God made us correctly, then we would be pure at the end of things and that would be pure immunity, which would purify us of 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 the goal for the immune system to kind of quarantine that, to say 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. For example, herpes virus infection infects the nerves and when people have emergence, 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 it's immunopathology. The immune system is causing as much of the damage and problem as the viruses, and it's the failure of that detente. And when certain viruses are sitting in us, we're perfectly fine. We have new viruses sitting around. As long as they're laying dormant, our immune system can say, okay, I'm just hang out here and if anything bad happens, I'm going to squelch that. But it's not like we've been purified. That's a reality that's a little bit too bad. But it's also one where you say again, if the goal of us is to make it to 30, let's say you get an early liver infection of HCV or HPV. 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 mounted 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 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 it has all these specialized roles, tools that are not always about getting rid of things. At all cost.

[B]

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

[A]

You're going to be one by the end of today.

[B]

I like the sound of that. As will the audience. One potentially useful strategy the immune system could have perhaps would be rather than to decide to launch an attack on a particular cell because it's. That's mutated and different 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 in the biological sense, let's just keep it there for sake of today's discussion. And you know, by time we are 32 years old, we are a mosaic of mutations, as 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, the number 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 gonna fight.

[A]

Yep.

[B]

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 enough of an, of an attack, they'll fight back.

[A]

Yeah.

[B]

It seems like there should be some way to that the immune system could quantify either body wide or, or local organ or over some period of time they could integrate over time. I have to imagine that, that such a mechanism exists.

[A]

You're coming from neurobiologies. I know. And so there is that in neurobiology of accommodation. Right. If I always tell the story of, I went to a little village in, in France called Epoise, if you know the name. Epoise 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, you don't notice it. And that's neuronal accommodation where you're nervous. There's the same kind of thing you're talking about where the sensors in your nose can become, they're like, okay, I've seen it, I've seen it now it's not anymore. And so I'm going to tune that out because then your nose has the potential to smell other dangers or other stuff, right? So that's the nervous system. I think you're exactly right where you're going with this. And we think this is true, that the immune system is for danger. It's looking for something that you would call. It's how it's seen the signal over time. So a virus may. Let's say you're a T cell that recognizes 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 mount an immune response and you learn it. And so the next time around, it'll be faster to respond to it and keep you from getting 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 insulin, which we think in general, it has a little bit of signal up and down as you have a trigger. But there's a range for that. And so your body gets used to that range. And the T cells that see insulin, they are very low. They're going to only be very low, reactive to that. And 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 virus. And so like a mutant cell. And maybe it's just a tiny, tiny bit above normal for months, and then it makes two copies of your cells and now it's a little bit higher than normal. And the immune system is, you know, has. I think one of the deficits with cancer is exactly that, that things that you do. And this is sort of like, I try to live my life a little bit this way, but it's not. Not validated by any experimental stuff is the idea that whatever you are is what the immune system is going to help you be. If it's a slow direction this way, it's going to be okay with that. What it doesn't like is big spikes. And that's maybe the signal that you're asking about. Could you actually get to the point where you'd be reactive. The problem with cancer is that it is slow and nefarious. It grows over time. And I think we're, we're made to absorb slow change 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. That's commensal, so long as it doesn't accompany again. Viruses have two features in common. One is this spike of appearance, but they also cause damage in that window. And so you have 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 additional proteins that come in and then they exchange information. Just like your brain. You know, you can talk about the fact that the brain has this wired set of cells that are wired in space. They're across your body from your brain all the way to a muscle. Let's say immune system has this collection of cells that are, they're literally crawling around us right now. We still do a lot of imaging. If you look in a piece of scan, you can see the cell, cells, the immune system are really, really surveying us. They're crawling around, but they get together like neurons and they can form synapses. And one can say to another one, this is what I saw. Oh, you saw that? Well, I'm just seeing this. And they can 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 gotta do something about that. But I think the slow burn doesn't do that. The slow burn is one of the ones where the cells are like, yeah,

[B]

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, 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 because 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. For therapeutic. I mean, maybe we, in a few years we'll all be banking our thymic 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?

[A]

Yeah, well, I can back up one step, and I've used the word T cell before, and T cell originally was thymus. So cell. So for those that maybe don't, you know, have gone to and had blood taken, you know, if you have blood taken in the 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. Me. Well, they come in multiple flavors, but for the moment, we'll talk about two. One are called B cells and one are called T cells. And T cells were named because of the thymus. So the thymus is this funny organ and it has a funny history. In fact, I'm writing these substacks these days, and I'm writing one that's supposed to be released tomorrow by the thymus because it really should have gotten the Nobel Prize. There's a guy who's alive, he's like 97 years old in, in Australia who did this, saw, did this remarkable kind of experiment. There was this time when kids that had heart issues would come in for surgeries and they would discover this enormous white, whiteish organ as growth near the heart. As they were taking the body, you know, they're cutting open and. And all the autopsies up to that point had been done mostly with adults. And in adults, there's only this small little thing there. And so they're like, oh my God. Part of the heart thing is this overgrown thing. They didn't really know what it did, and so they would remove it and the kids then go home. And it was usually exploratory heart surgery. But then kids would go home and far from dying of heart disease, many of them would die from opportunistic infections. They'd get all these infections, they'd get flu and et cetera. And so there was this hint that maybe this removal had taken out a critical part of your immune system, had made it so you were super susceptible to bacteria. And so this guy named Jacques Miller, who's this nice seven year old codger in Australia, at the time, he was in England, and he basically took a bunch of mice and when they were newborn, he removed their thymus, the same little whitish organ. And sure enough, those mice, they basically grew up. Okay. But then they all would succumb to bacterial infection. 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 comes from a kind of a convoluted path. But 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 their bone and they travel through your bones, through your blood, to the thymus and become T cells. And 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. The T cells that come in there, the T cells are developing and they each have a possible 10 to the 11th different kinds of receptors to smell different things. And you don't want any 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 kill your pancreas or kill your big toe or anything. You want to maintain tolerance. So you want to make sure that you don't make the immune system that's too harsh. This thymus has the role of producing T cells cells, but also of educating them in some ways of only letting the ones that come out that have sensors that are correctly tuned to let you be you in that way. Now, to the point about the story, and you were asking about aging, is that in kids those are really big because at that point we were talking about the developing immune system. It has to go from 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. So your thymus has this huge output so as like between really from three to six months old and into your four or five years age, tapering your body makes tons of T cells. And it's because probably what you're talking about, you're getting exposed to all kinds of different bacteria and viruses. And so you need to make that collection of immune cells that both some of them 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, not needing that later and maybe we don't even want that. The thymus involutes, it gets super, super small so that in Aged people, it's like, tiny, and 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 revitalize the thymus is that, like in cancer, for example, wouldn't you like to have a whole bunch of new T cells that could come into you, flood in there with exactly the specificity for the tumor. The tumor has managed to teach all your normal cells, your 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 mentioned you talked to Alex Marson not too long ago, and I'm sure he would have talked about engineering cells that you can engineer on the outside and give them specificity. But the sort of, like, if you will, the more natural route to that might be to let the thymus make use of more T cells 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, the T cells in that case. But it does have this, like, aging, you know, this sort of aging effect that seems to make us a little bit more susceptible to things later in life. And, you know, again, we could argue about what whether there was a big evolutionary design behind doing that or whether it just wasn't needed. Because if you had to 30 and you died of an arrow wound, but you'd give them your genes, you're a winner in the evolutionary sense.

[B]

I love this stance on, well, if you've already reproduced, I'll just give a brief vignette. We were introduced by our mutual friend David Feldheim, who's a phenomenal developmental biologist from UC Santa Cruz, and his wife, Sophie Salama, was also phenomenal biologist, a mutual friend. And years ago, I was in Dave's lab because we were longtime collaborators and published a bunch of papers together, and he was doing some injections. I'm going to get you in trouble, Dave. He doesn't do this any longer.

[A]

Yeah, I'm going to. I'm going to join him to get you in trouble because we was doing

[B]

some injections and he might have been using. Might have been using carbocyanide dyes. This was kind of conventional tool back. You put a little crystal in a piece of tissue that's fixed tissue, so it's not a Live animal or anything. And then you put it in the fridge. And then the, the fluorescent dye would label a set of neurons in a pathway. And I walked over and I saw Dave doing this and he wasn't wearing any gloves. And I thought, these are carbocyanide dyes with cyanide being. Cyanide being the key. And I said, dave, don't you want to put on gloves? And he literally looked up from the microscope and me, I'll never forget, and he said, I've already successfully reproduced. And he went back to doing it. And it's his lab and everyone else was following safety protocol. Don't go after him. He doesn't do this any longer, folks. But there's an interesting mindset among you because he comes from cell biology.

[A]

Yeah, yeah.

[B]

Randy Shekman's lab. You both trained in Nobel prize winning laboratories as graduate students. So I, I find it remarkable that this, this stance of, well, if you've already successfully reproduced, really aren't needed. But 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.

[A]

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 pur would have been the source of what we are today. What would have been the selective pressures on them. And it would have been a little bit like David saying, you got to, you know, the selective pressure is to get your, you know, for, for, for my genes to be passed on, my offspring have to be 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 they, you know, drop out and within an hour they're running. So that period of raising children, I think creates more pressure in humans to successfully be healthy longer. But I guess just maybe a negative viewpoint, but that concept that maybe there isn't as much pressure for you to be healthy. 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, we get. I think this issue that I brought up of our mosaics is a real confounder to everything because that creates something that is quite hard to defend against. I think that aging backdrop and some of the immune system that is really going to be important to just be super reactive early on may have some compensatory problems when faced with that new reality of a 50 year old, old or 70 year old or whatever that looks quite, you know, looks quite more complex. But you would have, you would have definitely wanted in gene space, you know, 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, 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 distinct, some questions that are. Almost 90% of them are going to be dead ends. You cannot hypothesize. It's one thing. Well, you got to do the experiment to 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 I made or other people have made, there is hundreds and hundreds of disappointments. And you'll recognize this where you just go home from the lab at the end of the day and you've done everything right. But the answer isn't the right one.

[B]

One control experiment can't. Can nuke your whole project.

[A]

Well, there's that one good control. There's obviously that you have to do the experiment well and have it controlled. 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. This is the better experiments, the kind of what we call them killer experiments, right? The ones that got to kill them. Kill the idea if they're wrong, if the idea is wrong but it's killer because it, if it turns out the way you hope it will. You know, again, when we get to some of these aging things, there's a lot of intuition that we all can put into this, whether we're like professional scientists or at home scientists. But it's really hard to say that intuition, like your idea about how the way the world should work is in fact the way the world does work. You know, that I wish that because of the age, certain things would happen. That's lovely. But it could be super. The word was baroque, you know, like the whole system could be configured in a completely weird way that doesn't really initially make intuitive sense to us. And that's also why some of those discoveries are so big to us. We're like, oh my God, I didn't realize that this system that seems like it might be quite as simple is so complicated. The world is so strange.

[B]

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

[A]

Yes.

[B]

There weren't supposed to be immune cells there. And thanks to the beautiful work of Carla Schatz with the major histocompatibility complex work and Ben Barris and I'm failing to ment, and all their scientific offspring, Beth, Steven, Chala, Araglu, and on and on. It would take the rest of the episode to name all of Ben's scientific offspring and Carlos too, and being you. Right. I didn't work on those issues, but I was in those labs when it was happening. We now know that the immune system is active and alive in the central nervous system throughout the whole lifespan, serving critical roles. There are two things that, well, three really 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 infections? Do we know what's happening? Is it like you've got so much adenosine, which is the sleepy molecule, and 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 don't sleep well or enough for a couple of nights, we're much more susceptible to getting sick. Is there a mechanistic understanding of why that's so?

[A]

I think there are bits and pieces of it. I think some, some really nice work shows that at night a few wacky things when you sleep, 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. Body. And, and so there's a lot of things that I think are reparative about sleep. I've thought about this a lot in my own life, as probably you have with sleep is too. One of the questions, of course, is why do we bother to have sleep? And, and I guess I can only imagine this 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, consumptive and they make all these byproducts during the day, that. That at some point you just need a cleanup phase. And that's. That's one interpretation of sleep. It just needs a reset. So the immune system is definitely resetting. And as I said, there's evidence that a lot of the cells go kind of quiescent into the tissues, and they may leave you alone for those reparative processes and actually allow those. In terms of the data on there, there's a lot of studies that are being done, and I can't say that I've come to a conclusion about that. This comes in the question of is it known or do I not know it, or does nobody know it? And I'd say this might be one of these areas where about 10 factions of people know it, but they don't agree. You know, so there's variations on things. But I think the data, for example, that immune cells dive into the bone marrow at night is pretty solid.

[B]

That makes sense what they're doing and

[A]

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, things that happen overnight, you're definitely. Your cognition improves. Is that immune or is that neuronal or both? I think it's both.

[B]

Something in the lymph plumbing immune system. One thing that's just striking like that is undeniable is probably the best way to put. Is everybody has bags under their eyes and looks like shit. When they are sleep deprived, they sleep for a night or two, and it goes away. That's clearly accumulation of lymph. 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 shit.

[A]

Yeah.

[B]

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. But that, to me, can't explain the immune thing entirely because, like, the lymphatic system is like, among other things, you know, immune surveillance. But, I mean, one night 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 might wash my hands or just kind of avoid them. And you're good.

[A]

Yeah.

[B]

So it's. It's. I mean, it's an incredible effect.

[A]

Yeah.

[B]

One way or the other.

[A]

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, places where it's doing little cleanup that you can imagine that if the. The thing it's trying to get rid of is granularity, that. That you need to have sleep where you just aren't making more granularity so that it can, you know, sort of like when you wash your car windshield, you do it completely at that point, and you. But you can't be driving with fly city and everyone. Right. Yeah, you'll never.

[B]

That's a great analogy.

[A]

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

[B]

I'd like to take a quick break and acknowledge our sponsor, AG1. I'm excited to share that AG1 has just launched their newest formulation, AG1 Pro. Pro. AG1 Pro takes the clinically backed AG1 formula, which is a blend of vitamins, minerals, probiotics, and adaptogens, and adds three important new ingredients. Creatine monohydrate, calcium HMB, and zinc carnosine. Each serving has 5 grams of creatine monohydrate to support muscle strength and performance as well as brain health, calcium HMB to support muscle recovery and reduce muscle breakdown, and zinc carnosine to support and improve the lining of your gut. All three of these ingredients have compelling science to support them, and therefore, I love seeing them added to the existing AG1 formula. As most of you know, I've been taking AG1 every day for nearly 14 years now. I started taking it long before I even knew what a podcast was. It's a great product and it's now made even better with the new AG1 Pro formula. If you would like to try AG1 Pro, you can go to drink ag1.comhuberman to get a special offer. AG1 is giving away a free bottle of Omega 3 Coenzyme Q2 Q10 with your first subscription. Again, go to drinkag1.comhuberman to get A free bottle of Omega 3 Coenchurch Q10 with your first AG1 subscription. This thymus thing is really intriguing, and I know a lot of people who opted to bank their child's umbilical cord in the hopes that the stem cells from the umbilical cord will someday be useful.

[A]

Yeah.

[B]

How invasive is it? And. Or should we be banking thymic cells? 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 had a little. Little chunk of my thymus.

[A]

Yeah.

[B]

In a minus 80 freezer someplace so that when I'm 85 years old.

[A]

You might be able to exploit.

[B]

I might be able to exploit that.

[A]

Yeah. Well, I'll say that the umbilical cord one is pretty straightforward. The umbilical cord is being essentially discarded anyway. And it contains a lot of, as you know, bone marrow stem cells that. The utility of those is a little different than the thymus. The utility of banking that material. And banking just means you put it into a vial. Small, little, you know, small little vial with the right 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, 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.

[B]

Has that ever been done successfully?

[A]

Yeah, yeah. You can do autologous.

[B]

Autologous kids or adults that are alive today because they banked their umbilical cords,

[A]

but certainly companies sell access to that.

[B]

Well, somebody has to pay to keep the freezers on backup generators and things like that. So people invest time and money into this idea.

[A]

Yeah.

[B]

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.

[A]

It's a really good question.

[B]

I don't know.

[A]

The Answer to that question.

[B]

I guess the parents paid.

[A]

I can tell you. And this will be just like. This is, this is the depths of. To which you're. You're describing default. I'm injecting a, you know, like 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. I'm sure you can do it in humans too. I have zero doubt that it also works. I don't know whether those companies have done that. That's, that's just actually something where I.

[B]

Because this is offered in mass now.

[A]

Yeah.

[B]

Do you want to, do you want to keep the umbilical cord?

[A]

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 I, you know, it depends on your, your how much money you have to spend because that's something.

[B]

It's within the noise.

[A]

Yeah, yeah, it's one of those. So it's one of those ones where you, particularly 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 I think this would. If they happen to have a childhood leukemia, this would, this would cure it.

[B]

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 by virtue of a new technology. You said it would cure it. I mean, that's a big statement. You can tell I'm ratcheting up from 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, however, are 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, my, whatever organs in the so called organoids or whatever they're referred to. 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. It actually could have some mutations that seems important to compare against a sort of a standard cell. I don't want to grow organoids from, from an IPS environment that Carries mutations. That, that seems like a bad idea. 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, you know, a liver disease or a heart disease. But if those are mutant cells, that's a lousy experiment.

[A]

Yeah, I wouldn't, I wouldn't say they're like to be mutant cells for that reason. I think the biggest question would be whether you, your induction of them to become the organ that you want was successful, was replicating the actual organ itself. So you're referencing these things called organoids, which are collections of cells from a body of a human, for example, that are induced with various different factors to grow to resemble maybe an organ, a particular organ. I think all of us have little doubt, and this is the source of the California Institute for Regenerative Medicine, that making stem cells that can become particular organs. Will it someday happen? We will figure all these things out. And I believe in science, I believe in our ability to sort of like test, learn, test, learn, test, learn. How soon 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, because it's not yet ready. The technology and the understanding isn't yet ready, get ready. But the other problem about those is you probably will dive something else. You get hit by a car, it won't help you that you've got those things banked. So I think in some of these cases overemphasizing. This might be your point about the storage of umbilical cords is like at what point is that a high odds situation where your kid needs it and you have it stored away versus all the other things, fates that can befall us as humans that have nothing to do with stem cells from the bone marrow. And to me that's a point where you could spend your life worrying about how you're going to die. And maybe that's not a good way to live.

[B]

Well, certainly not how I live right now. There's a lot of kind of excitement, 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 are healthy exactly Vital, healthy, you know, being able to move, sense and, and think seems like, and remember, you know, those seem like

[A]

the critical ones, you know. You know, a moment ago you mentioned the concept of like removing a bit of thymus. And I think that the issues with, for me, with that 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, I mean, in fact, you can make thymic. So the thymus is, is both the cells that come into it from the bone marrow. So as an organ, it has contents, but its structure are some thymic epithelial cells, a kind of cell that make a matrix that all those cells live in. And they get educated in. And there's definitely 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 hold onto the thymic cells and we would be in a position to do something important for longevity, 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 and do the next thing. Two things that, so you're like, you know, the California Institute for Regenerative Medicine, 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 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, and then one hour and you understand everything because, you know, so all of a sudden all those failures make, make, 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'll have them in time for like, you or me, I, I don't know. I just don't know. And I, I think that's true of a lot of these things that say, oh, you know, we seem to be right on the cusp right now. For example, in. In cancer therapy, we've been 10 or 15 years of these things called Car Ts. Alex will have told you about these, where you engineer your T cells and you give them special receptors that can get them to go into. To eliminate tumors. But for whatever reason, they haven't worked in patients. They haven't worked. They haven't worked. They haven't worked. And T cell, the immune system gets turned off. These cells don't make it. They don't fail. They fail to eliminate the tumor. We will figure that out. But we've been thinking we've figured out for five or 10 years, and that gets frustrating. And I think it gets frustrating for people that are, like, waiting for it, too, 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.

[B]

This is an important discussion that we haven't spent enough time on in this podcast that I think is very important for people to hear. And I have some thoughts about it, but I'd love for any disagreements. I'm not looking for 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. So I'm very immersed in, like, what's happening right at the cutting edge and 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 Ellie Tanaka's work has just shown that you're like, wow, this would be incredible for amputees and brain regeneration and. 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 calcium phosphate. Like, great research tools. Tons of things happen that's like, we're going to modify genes. Zinc finger, nucleus, 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 gene alterations with crisper sickle cell anemia treatments as well. This is more benevolent example. But then the person who went rogue and just kind of did this in humans in China, but crisper just kind of broke through it all. 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. Like, run up against the dam.

[A]

Yeah.

[B]

But I feel like in 10 years, some or all of that information will be extremely relevant when, boom. One thing will just, like, leap out of bacteria or like grasshoppers, no pun intended, with the grasshoppers. But the. The last example would be, you know, for years it was like, the country's getting fatter. The c. 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.

[A]

Yeah, yeah.

[B]

Tells people what they already knew because the GLPs 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, dare I say, cure for obesity. It's got problems. There's muscle wasting. You know, there could be other issues, apathy, et cetera. 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 something comes out of nowhere, and it almost seems prerequisite to have all those years of frustration and failure.

[A]

Yeah.

[B]

And then. And you say, well, couldn't we have just gotten CRISPR first? Or the GLPs first? Like, why did we go through all these, you know, billions of dollars of expenditures? Time, energy.

[A]

Yeah.

[B]

I don't know. I feel like there's some natural order to this. And. And I just would like your thoughts on.

[A]

I feel like.

[B]

Like it's necessary but not sufficient to have lots and lots and lots of failures.

[A]

Yeah. And I think it's necessary and necessary, absolutely necessary to study things that are just at some point, curiosities. And that sounds like science is about trivia, but you gave example clip 1. Somebody was just curious as to why Gila monsters. The feature was that gila monsters can go into dormancy for, like, 10 months, not eat and then come out. And, like, how do they manage that? And so that was just like, what is that? What is it? What 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 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, that which we now use for all this human engineering. 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 the lifespan of this. This field we call cancer immunotherapy. I did the first immunotherapy experiment. I injected a mouse with an antibody that I had made. It was against molecules on T cells. And I'd 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. Of other mouse experiments of all kinds of diseases, and it kept jamming up the T cells. And then, Jim, my path, I said, we got some tumors in the fridge. And so we set up that experiment and injected this antibody, and the tumors melted. Well, that was the start of cancer immunotherapy. We're like, that's the origin.

[B]

This is the experiment for which, let's just be direct here, that your advisor won the Nobel Prize, Correct?

[A]

Correct.

[B]

Did you at least get to attend the ceremony?

[A]

Yeah. So it was a little thing.

[B]

This is how science works, folks. Doesn't matter who did the experiment. It matters what lab you're in.

[A]

Get go to go. The after parties were good, but I guess I'll take you back. We weren't trying to cure cancer when we started this, the thesis project. When I went into Jim, my mentor, at that point, the discussion was like, well, there's some molecules on T cells. And I said, you know, we knew from AIDS and a few other things that T cells were important. So that was the attraction. Even though had people say, why would you do immunology? Well, they seem to be interested. And there was a molecule. And I 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 set an immune system. You can dial up. You can say, well, if I could dial up, what will happen to vaccination? Well, it got better. What will happen to multiple sclerosis? The disease got worse. What will happen to cancer? Ooh, we can start to have an Effects on it and the X ray. The people were studying physics, and then it turns out to be that they were like, oh, I can measure bone. And that's how we use X rays now 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 work around that comes with some orthogonal piece of information. Orthogonal, meaning at right angles. Right. So, you know, again, the 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 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 the first dregs of doing, doing it. This would become an industry, you know, this would become a whole thing.

[B]

And.

[A]

And maybe that's important because you need to foster that. 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 the piste. You can't ski on the slope. You got to be, like, in the trees, and maybe you'll bonk your head a bunch of times. I think that's the reality. And it's like, you got a lot of people out there that have decided to do that for a life, because it's a chance to solve a puzzle. There's puzzles about how the world works. And if you've ever done a jigsaw puzzle with your hand, there's always like, oh, you get in. And especially in the end, you're like, what pieces come together to do it. I think that's what makes this whole science thing really fun. That's the reward is that you get the puzzle piece and oh, it makes sense that now I know what I've been building. I've been building this puzzle. And then you go back and you do it again because that's really satisfying at the end of it. Even though again with the family puzzle, the first parts are so hard. Thousand pieces and maybe you find the edge, but the intervening where there's all clouds super hard. And I think that is what science is a lot about is doing that and then realizing what the picture is, what is that picture of? And then all the brakes are off. I often tell people that if an experiment you'll do in Lab has a 10% chance of yielding anything interesting, you got to do at least 10 to even meet the fundamental stats. You actually have to do quite a few more. So that's where it's not a cost effective thing. It's really difficult to be a scientist because there's no quid pro quo. There's nothing to say if you put in five hours that you'll get five units of goodness of knowledge out of it. A lot of times you get zero, but then sometimes you put five and you get 500.

[B]

Right.

[A]

And those are the jackpot moments where it's like life. It's like life. It really is.

[B]

It is. 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 or finishing graduate school, should they go the research route, they want to do a postdoc. And I'm like, yes, yes and yes. Rather than answer publicly, I decided, decided to just have a call with this individual because it's a rather niche question. But I mean also just in training, your reward system to work for five years on something is so valuable, especially in this day and age because everything else feels like it comes at like warp speed.

[A]

Yeah. So it clicks.

[B]

Yeah. Like, and 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 quite the opposite.

[A]

Yeah.

[B]

It's like anyone that's like done a triathlon or well, you know, raised, raised a kid or done anything, you're like, oh my goodness, like. And that never ends.

[A]

Right. Yeah.

[B]

There's nothing better than these long term investments.

[A]

Yeah.

[B]

Nothing.

[A]

Yeah. When they break through that. Your analogy, when you break through that dam or when you realize sometimes that you've broken through the dam, that's one of the funny things. About, I think, science. And maybe it's true in triathlons and tough too, where you've realized that you've all of a sudden got somewhere.

[B]

I haven't done a triathlon, so I have, to be fair. Rob, our producer, sitting to our left, he has done many Ironmans and he has that mindset of just steady pressure. I mean, his relationship to work and effort is remarkable because he burns so little energy worrying about things that we refer to as in the left column, like the stuff you can't impact and just focusing on what you can impact. Yeah. 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 to force yourself not to do or think about.

[A]

Yeah.

[B]

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.

[A]

Okay.

[B]

And I'm going to pose a question that may or may not fit with 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. 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. Was truly barbaric. It was like surgeries done on warriors and without anesthesia. And we've known for a long time that if 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 it back on. Turns out that's true.

[A]

Is that true? Yeah.

[B]

There's a bunch of juicy stuff in the. In the gut that maybe it's the warmth, maybe it's the immune system.

[A]

Okay.

[B]

Maybe it's the lack of infection from being inside as opposed to outside the body. Who knows?

[A]

Gut? You mean the intestine or you mean the stomach? Within the stomach? The stomach itself.

[B]

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 limb or tissue preservation and restoration. Like for instance, I've talked many times on this podcast about the fact that about above our. The roof of our mouth, we have this small cluster of neurons. The superchiasmatic nucleus organizes the circadian rhythms of every cell in our body, from the genetic to the transmitter level peptides et Cetera keeps us sleep, wake cycles, does all the organization that we need 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, 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 animal. 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. At least in the brain they can do what they need to do, which is super cool.

[A]

Yeah.

[B]

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. Not ideal, but you get some function back. So I'm fascinated by this because we like to think that the organization of our organs is so critical.

[A]

Yeah.

[B]

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 marrow, but you also talked about the massive migration of these cells that are working in this network. 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.

[A]

Well, the answer is yes and yes, you know, it' both. So although I described the immune system in the earlier part of this discussion as super migratory and 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 who don't know, lymphatics are like drainage. It's how you drain the fluid back out of your tissue. So although there's these mass migration of cells, there's also in like even just in T cells, there's T cells that lodge in particular sets settings and they act to protect that tissue. And they're resident cells of those tissues. They never leave. And so both are true, you have parts of your immune system that are protective or nurturing of particular areas. And then there's ones that are circulating and can hit any spot. 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 space. Like, does it have the growth factors and the blood flow and the lymphatic outflow and maybe even some neuronal activity that, you know, makes that tissue work. So, so that's where like, if you take the pancreas, you can 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. 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 diabetes. For those, type 1 diabetes is caused by the immune system. It gets too active against the pancreas. It's autoimmunity. It's where it's now saying the pancreas is not self, it's something foreign, and it wipes it out. And that's the source of what I said earlier. Your immune system can be quite dangerous. So when you talk about this concept of spatial, there's a few things to bring in. One is, 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, like, if 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. They can hitch some signals on neurons. And that's a really interesting thing. We could talk about the capacity for your 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 the vagus, can, can essentially program

[B]

by levels of, of calm or stress or by thoughts themselves.

[A]

Well, 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, it's the source of some of our moral decision making. It's also the thought to be the part of our brain where if you cut your hand and I see it bleeding, I can feel it in my hand. Oh, wow. I can sense. And you can sense each other's pain. It's a set that this very nice Israeli group did this Royce lab did this very nice study where they induced into the guts of mice inflammatory bowel disease. They fed them a really kind of weird sugar that causes the bowel to puncture. And then they get a really bad stomachache. Stomachache, inflammatory bowel disease, diarrhea. And in that period they used, you know what dreads are, so they marked for the crowd. They used a way to mark all the neurons that were firing during that period in the cortex. And then later they could fire them like after the mouse had recovered. Recovered. And they saw evidence that the immune system was resetting up itself in the gut as if it had just been punctured. And the cues for that in that case were a drug. But we know that we can cue the insular cortex, like me watching you do things. So it's made me wonder whether some of the things we smell cut grass and 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, you know, train yourself to, to, you know, to bring up an immune state in a particular tissue.

[B]

And just so I'm. We make sure everyone's on board what you just described because there's a lot there. If I understand correctly, we know that the nervous system can do contextual learning. Like if it, like if an animal or human, human, let's just keep it to humans. Gets shocked, scared or traumatized in a given region or even. I've had friends visit San Francisco and get their cars broken into and their computer stolen. You can develop a context, context dependent or end 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 you have a great experience someplace and you actually really love San Francisco because you met your future spouse there. 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 merely by recalling the positive or negative, but in this case positive memory, we can also rec. 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.

[A]

That's what these studies are starting to emerge.

[B]

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, with all due respect to my colleagues who've focused on the ill effects of chronically elevated cortisol, the immune enhancing effects of acute cortisol and stress are really important, and I think they've been overlooked. But I love this because one of the problems, luxuries that I have is I sit sort of at the interface between real science and biology and like what most people perceive as complete nonsense wackiness. But more and more we're finding that within the complete nonsense wackiness, 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. And that's seeming less and less wacky, even outside California. Yeah, because of studies like the one you described.

[A]

One of my friends who's a faculty, Dan Lippman at nyu, we were talking about the same study, and he was like, that may be what meditation is doing because it may be allowing your brain to, you know, communicate and reset, you know, less inflammatory states 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. 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, you know, you, it's one of the ways that you can control your autonomous nervous system is through, is through your breath. That happens with meditation. I think that to me there's something intuitive about that. But you know, I think I, I just an hour ago warned you about the problem of science being intuitive, that some things that make that they sort of make a great story in our minds that don't turn out to be true. But the, the data on this insert cortex thing is starting to look like it's a real thing. Like there's a real connection between some of the peripheral states and, and like regions of the brain and however those are triggered. Now maybe, you know, again, I've, I've often, 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 kind of crazy thoughts. But again there's an element of that that's intuitive too where we say, oh, that seems to be the case. My mom makes me a comfort meal. Is it really the meal settling in or is it just that the sensations that make me feel like less stressed in one sense, but maybe also to this point and literally resetting your tissue.

[B]

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[A]

Yeah.

[B]

But there does seem to be this quote unquote positive, or let's just call it a reinforced mindset as opposed like an immune reinforcement associated with mindset. Because some people will say, like, I, I just always get sick, and I believe them. They always seem sick. But it could be that you get sick in a given environment once and then you, you just decide that you're sickly. So then, you know, it could be that the immune system is listening to these thoughts, but not in the form of words. I think this is where, like, it gets hokey for people. Like real biologists and people and physicians are like, yeah, you gotta be kidding me. Like, but because immune cells don't listen to thoughts, they listen to brain states.

[A]

Triggers of some sort.

[B]

Triggers of some sort. Right. 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 biological level makes total sense.

[A]

Yeah.

[B]

So we were talking about spatial biology and the fact that you can tuck some pancreas in the kidney. And unless someone has type 1 diabetes, a lot of the functions of the pancreas can, can still function or transplantation of these clock neurons. And clearly there are limits to this, but in the context of the immune system, I'm wondering, can we take a little bit of thymic Tissue bank it and then just later, like, put it in a slow release capsule under our skin of our hand, you know, like. And that might sound crazy, but I have friends, one of whom might be at Neuralink now, who actually embedded a little radio receiver under his hand to be able to open his 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. But if I knew that I could be much healthier by taking a few thymic cells and in a, you know, sterile capsule and sliding it under the skin, you know, people get their ears pierced with, you know.

[A]

Right, right, right.

[B]

Less, less invasive procedures. Why not?

[A]

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. Idea. But, you know, is there. It's more than likely one of the nine out of ten, I would guess.

[B]

Sure. But 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.

[A]

Yeah, yeah.

[B]

And give animals drugs or give animals stuff.

[A]

Very common.

[B]

Yeah, yeah. Tumors are happy to thrive in novel environments. So why wouldn't healthy cells.

[A]

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, replacing an organ with one that might be better, is that at some point if you come in. So one of the challenges of tissue engineering is if you want to bring in new genes, the vector, the material, the surrounding, whether you bring in using a virus to. And, 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 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 just like you just put an infected cell in you. 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. So that represents an issue. I think when we talk about any kind of engineering, the moment is if you engineer a system to be maybe better, the immune system isn't necessarily going to want better. And so you have to overcome this issue of tolerance maybe at the same time. 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 is

[B]

going to let it fly, I'm not considering doing this. I just. I think we are at. I don't know how old you are, but I can guess based on some mutual friends we have. But I'm getting 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 so forth to overcome a lot of the issues that our parents and grandparents were not able to overcome.

[A]

You know, with regards to, like the peptide side of things and even the cells. And this is maybe where you're going with this space, is that context does matter for the immune system and it matters for all biological systems. I'll just give you an example. We did a study of wound healing some years ago. And if you have a wound in a mouse, it's maybe just 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. There's zone bones within there where certain biology is really important to be happening. And then so imagine 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 actually sensed all like a gradient, almost like in the neurons. And so these cells need to do different things than these cells. So if you wanted to administer some, 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 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 development happens that way. You know about gradients, and we were talking about this earlier, that there's gradients. 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 would say that more so than ever in our lives, you know, we're seeing, you know, people kind of like experimenting with things on themselves. And one of the sad parts about this, we don't capture a lot of data, therefore, you know, because it's not seen as a study. And we can't say everybody that took this gets this result. And then you have this rise of things on the Internet of anecdotes that become seen as data. Like, I took this thing and this happened, and that's, you know, I could drink this drink and have something great happen to me or something bad happened to me, but it might have nothing to do with the drink. Right. You know, that, that issue is one that I think is really, is really critical in this window of time right now. And honestly, I don't know what to think about the idea that people, you know, do experiments on themselves. I think we all want to improve ourselves. We all do some kind of experiments on ourselves. You read a book, you're trying to improve yourself. Right. The physical one gets a bit tricky when, and, you know, you're not sure whether something's going to be dangerous or not. But.

[B]

Oh, yeah, and I'm not promoting that people do this. I think that of course you would want to see pre, clinical, clinical and other trials for this.

[A]

I think I would. Personally. I mean, just.

[B]

Yeah, I mean, I'm. I. There are a few areas, well, where I am a bit more adventurous, but for the most part, I'm like, you know, based on my training and background, I have to orient toward, you know, I'd like a bunch of. Let me put it this way, I'd like a bunch of other people to do it first. Yeah, like, who wouldn't? 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.

[A]

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

[B]

No, but you can feel open.

[A]

Well, I'll just point out 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. Because there's really good data that you can promote more immune cells against the tumor by making a vaccine that consists of some of the proteins and peptides that are unique to the tumor and not different from you. And you introduce those as if you had introduced a virus or anything in a childhood vaccine. You know, similar concept, just different peptides. They're peptides from the tumor. And in those situations it's context. Right. So if you and I had cancer and we don't have. 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 cancers. And so that's the only thing we got. But if you have access to something that's relatively new and particularly vaccines, despite what some people worry about, they're pretty safe. And so. And so the certain die versus try out a vaccine drives a lot of people to be interested in vaccines. And I would say, yeah, in that case it's a really, you know, you can see where people's. Their question about whether they're going to try something or not is very context dependent.

[B]

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

[A]

Sure.

[B]

Which is, I think there are a very large number of people for whom they are neither anti vaccine nor super pro, but they are. They're asking about timing and combinations.

[A]

Agreed.

[B]

They're saying, okay, listen. And we had Jay Bhattachary on here and I've had several others who said maybe there should be an investigation of the spacing of these things, how many, how critical it is to do at a given age, you know, know, and on and on. We could pick any vaccine for that reason. And as an 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 delivery of those vaccines. I'm not saying don't give them all. I'm saying over what time window does one give them? I think a lot of people, many more people are asking that question. Question. It's just a quieter murmur than our saying, listen, we don't want to take any of these things. Yeah, we don't want our Kids to take any of these.

[A]

Well, I've heard that too. And I think there's some fair aspect to which most of these vaccines were not studied in the context when they were studied, of what it does in combination and these sorts of timings. The fact is that the evidence that there's bad things happening doesn't look to me, you know, tremendously strong. It's almost like anecdotal sort of information.

[B]

So unless it's your kid.

[A]

Unless it's your kid, in which case you're going to look for an explanation. So I don't know.

[B]

Just being fair. As long as we're admitting psychology as a factor.

[A]

Yeah, yeah, yeah. So 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. As a parent, I actually had something very similar where I delayed my first daughter's one of her vaccines, partly because I know that there's a certain element to which when we design a protocol, the protocol for immunotherapy of cancer for patients 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 and protocol is protocol. And that's how it's done in medicine. And that's. That's because you have a fairly good sense of the safety of it because of 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 and also safest or safest or even one that is less disruptive to the lives of the children and the parents. We delayed one of our kids vaccines by just a month or something because she had not been feeling well, just straight up. And it is true. And I'd say that a couple of the vaccines have come out that I've had recently. The shingles one is a good example I had the other day just knock me completely out. And it, you know, it's very, very heavily adjuvanted. So it's clear that it's, you know, it's having to. Does. 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 of which, you know, I don't know that we're all 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. Some of them were chosen by competing pharma. Pharma companies that each make their own, you know, materials and you know, again, I think there's a, there's a lot in this question. I don't know how much of it also represents. The one problem of science that I could talk about is this issue that a lot of science treat science as a kind of a papacy. Like we know the language, we know the facts, and we probably don't have time to tell you why we think this and where the holes are.

[B]

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

[A]

I know.

[B]

I mean, I know all these incredibly smart, incredibly well meaning people who have lives of their own, health lives of their own, health challenges of their own, kids of their own, and on and on and no one was hearing from them. Yeah, 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 also offering perhaps the opportunity for better understanding and certainly delivery of the information. Yeah, I mean, it's a huge problem.

[A]

Yeah. Well, I guess it's one of those ones that I can only speak about what I did 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, the percentages of these things. I absolutely, in fact vaccinated kids. And that was, it seemed like, it seems even now like a reasonable no brainer. But I just told you too that I, I asked to go off protocol because at some point I know these protocols have a little bit of like, again, they were designed on a one study. It doesn't mean that it doesn't work if you wait another month. In fact, if you do, if you've done enough mouse experiments as I have, you know that when you vaccinate on a slightly different schedule, you can still end up with the same outcome. You know, that is protection, you know, with slightly different schedule, it's not that convenient for doctors and hospitals and even sometimes for patients to get off on weird schedule and then you forget a dose and then it isn't as effective.

[B]

Right.

[A]

So there's efficacy that comes with 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 like brushing your teeth in the morning. You do it in the morning, the evening when you do it and so you'll do it twice a day. So there's a lot in this. I mean there's a lot of politics I think involved in vaccine too that relates to the question of like at what point can the government do. Tell you what to do? Which is, you know, it's a surrogate question to the vaccine. One where a vaccine is, you know, if there's a harm, who gets to choose with the harm benefit and then how resources are given out for like schools and you know, we know all these, we know all these sort of nuances. From the science standpoint, I don't think you want to wipe out the baby with the bathwater. I don't think you personally like, I wouldn't not immunize my kids. Kids. Could there be additional studies about the combination of these into like fewer shots? I think so. I don't see why not. Here's where you get the financial rise. What's the benefit to any pharma company of doing that?

[B]

Well, I think this is again, I have to be careful that I don't place myself into an advocacy group that I'm not. I look at everything on a case by case basis. I really try to do that. But the, you know, and I've tried to be, 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 SSRI saved their life. So then you go, okay, well you know, so we can say all we want about pharma. Are you talking about people getting, taking insulin or you know, until recently the GLPs were mostly available through, through pharma. Now they're sort of, it's kind of the wild west. People are microdosing them from all sorts of compounding pharmacies as their own issues and so on. 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 your Persona non grata. That kind of like people not people being shunned in both directions in either direction rather that's, you know, that's really the source of the problem. There really hasn't ever been a conversation. Conversation quite like this.

[A]

Yeah.

[B]

At least not when I've seen publicly. Yeah. There are not 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.

[A]

Yeah. Fair.

[B]

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 three days later started exhibiting symptoms that then set them off on a course that was, was really, really tragic.

[A]

Yeah.

[B]

And those groups are the ones that have accumulated the most oomph out there. And if you think about the. Those parents, it's totally understandable.

[A]

Yeah.

[B]

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 another way and you can't do anything about it. That's got to be mad. I mean, beyond maddening.

[A]

And, and, and the question is, what could you have done differently? I think is in those situations, having been in them, not that exact situation where you said, oh, now it's done and now it can't go backward and

[B]

you did that to them. This is the thing that. Well, 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 guilt slash anger. I mean there's a whole psychology to it that's completely understand. Understandable.

[A]

Yeah.

[B]

It didn't wander into the clinic.

[A]

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 medical space. And 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 late. Well, not even off label. They're just getting them from, from wherever. The Internet. And you know, I was thinking, well, you know, there's a funny thing there because the legitimacy of pharma companies is sort of of fallen into even worse straits than before. Because I think 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 side effects are worse than the, than the symptoms that we were leaving and that sort of, you know, again, 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 the idea that we can do Experiments on ourselves, on our own bodies again. And it's quite different to say, read a book. Although you can be infected by, we believe, like by, you know, stricture, scripture and things and your behavior. But somehow in here, this idea that, that, 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, well, why, why can't I choose my best interest, you know, who, who are these experts that I can't always trust?

[B]

What's more American than that, after all?

[A]

Well, 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 it 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 something you're trying to work out and maybe even surfacing these ideas that are hard to talk about. Like, should we trust farm company companies? I know a lot of people that work for pharma and they really, they are doing good. They're like you and me, they really think and they are treating disease, they're making really good drugs and they do really good things. But that's not always true. Not just because a bunch of people. And it's not always true that the subtle best interest of a corporation is the same as the best interest of an individual. So we have to surface 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, of perverse incentives exist. I wonder why, you know, like pharma companies haven't gotten better tests for who's going to respond to these checkpoint drugs that we made. 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 coming with melanoma, even though there's only a 50% chance you're going to be cured, which is great. It 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, they are. And so everybody takes it. So the companies that sell those have no incentive to develop a test. Although get. If they develop a test that shows who is and who isn't going to respond. They'll cut their market into 50 in half. So I don't think any pharma executives out there are going, but 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 brought, brought forward, some of which are better and worse than others. We get told that this is going to be good for us and we should take it. And again, you're getting to the American kind of mentality, which is to say, well, at some point, if you fool me twice or I'm not going to believe it and I might not believe it against an entire spectrum of things called science. And the problem is that there's people like you and me that are trying to actually do. Most of us, I'd say 99.9% of us are working our asses off to, like you, figure things out and discover stuff that's important for mankind. And then you have these sort of issues that arise and you're like, well, then should you distrust as a species, should you distrust the entire class of science? Probably not. You just need to maybe make it so that knowledge is freer and knowledge is better communicated and you do watch out for those situations where there should be. And maybe vaccines are one. We just need to do something sensible, like what you're describing, and just do a study and say, let's do that study and make that very public that we do it and say we're going to do that. And obviously people can sign up for. You can have this regimen or the old regimen or the new regiment. Again, I may be speaking, I don't do vaccines. It's not what my lab studies. But there could be some sense to saying, well, maybe science is a whole. Could take this on and say what would be Maybe the answer isn't to say no vaccines. And we think they do. There's good evidence that they're protective. But to the extent that you're coming out, could we make it less. 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 describing an experiment. What would be the experiment?

[B]

Yeah, well, the discussions haven't happened. And I should say a couple of things. First of all, thank you. Thank you for being willing to venture into this area. I seriously doubt that any of your colleagues are going to be Upset that you're having this conversation. I will make sure that anything we put out is in context. If anyone cuts a clip, I will be the first to dive in there and say, this is taken out of context. But 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, et cetera. I will say this. The idea that you need to push back with a. With just a fire hose of do this or else 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 vac 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 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 in the meantime, you're not preventing anyone from getting vaccines. There's now a hunger for more nuanced conversation around these things. I think it's the right time to have it when we're not in the throes of a pandemic yet. I mean, there's some things that are on the rise. It is scary. I'll be quite blunt. The rise in measles is scary. People say, well, measles. They used to have measles parties. Talk to somebody who had massive inflammation and brain inflammation from measles. Not a pretty picture. Not a pretty picture.

[A]

Yeah.

[B]

So I think it's great that these conversations are starting and it won't be taken out of context.

[A]

Yeah, well, I mean, on the vaccination front, I mean, I just wrote a little subcycle, so about, you know, the origins of smallpox vaccination. And I think what's lost in those stories. Stories is if you look on the Internet, the. The absolute, That's a terrible disease. I mean, you know, the reality of what we're protecting against, we haven't. It was just really hard to. To, like, also have the conversation without doing a little bit of reading into Your history, you know, 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.

[B]

Smallpox was dreadful.

[A]

So, so there's an element of that, though, that I think, you know, that we have to make sure, sure that the conversation focuses on, on what are we, what are we trying to 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 knobs and, and, and, and you know, as we know, like measles is not a, a theoretical again, you know, it's certain that that concept 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, 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 that's also an important. Again, that's what, that's me as a parent, and 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? Propose experiment. That's, that's, you know, I think there's a, you know, the cutting off, you know, the concept of human curiosity and science at the legs is probably not the way to figure 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. 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. Of bad stuff happening versus the odds of an adverse effect. They were all that high. But again, if you're one of the people that even if it is. That even if it is caused by a vaccine, which I don't, by the way, can I tell you a little story, please? Maybe you know this already, but if you want to 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 channel challenge can affect the neurons of a developing pup. So it's not outside the realm to say that in some situations, in an adjuvant situation, again, I May regret saying this because it's going to open up a conversation to have this, but it's not outside the bounds to say that a immune insult will have influence on neural development, period. Is it the source of autistic children or was it in fact that the mom had infection during pregnancy? That'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 cells of the brain.

[B]

Yeah.

[A]

In fact, one of the best experiments that I look along these lines, it's not about autism at all, but it's about when you get a flu, you tend to feel like you want to socially isolate yourself. At least I do. And most people do. I think they kind of want to crawl in a hole, a colon, oil field. There's an experiment that was done that involved injecting gamma nerf uron, which is one of the things your immune system makes when it's fighting off an infection into the bloodstream of a mouse. And then just watching it and they become, you know, socially isolating from just the molecule that's made by the immune response during infection.

[B]

Not even from being sick.

[A]

Not even being sick. They're not sick. They just are given 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 also showed that the brain has receptors for these immune molecules. The simple conclusion of that paper, there's still always work to be done, but simple conclusion was that the brain could sense infection and it would affect behavior. Even in mature. And also it's mature again, these ideas that there's something that, that, I mean, scientists use that infection of a mom to lead to neuronal changes that lead us to be able to study autism in later mice. So there's definitely potential there. I don't know that the vaccines and all of them, or whether there's a circumstance or whether it's again, the mom actually had a fever before and the vaccine now just triggered or didn't or just circumstance because you give vaccines at two years of age, which is when autism appears, there's all kinds of options and those sort of anecdotes of that. And I just think that fact that the way that we study autism is by giving a pregnant female mouse an infection is sort of like, okay, that's important to know 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, we need data.

[B]

We definitely need data.

[A]

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 you about this project of trying to work on the publishing problem. But it's not just the publishing problem. It's how we synthesize knowledge that under data sparse circumstances to make decisions. I think we're not very good at that societally. When we have tons of data and it says, absolutely, if you have cancer and 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 take that drug every time. But if it's sort of a case where you're like, oh, there's some things that are happening 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 labels 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. Could we get it from blood? And, and that kind of went on for a while.

[B]

Right?

[A]

And this was the source of like a lot of confusion that came from the medical. It was seen as, seen as confusion. That natural effect 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 data that we had was 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?

[B]

Well, I think that's the major argument when they're, you know, there are people that will critique peak people saying, okay, your experience is anecdota, it's correlative. But then the, the with regard to vaccines and autism and other issues, but then the pushback is, well, this vaccine, et cetera, was directionally guided by sparse information to begin with. Under times of pressure, there's financial incentives. So it's just this ping pong that goes back and forth. But many thousands of parents write to me and say, should I wait on certain vaccines? And I'm like, listen, I am not the person to answer that question. But you have every right to ask your doctor. Right? But they're not asking because they're extremists they're not anti vaxxers. 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 reality, the data cannot be as polarized as it's been presented.

[A]

Yeah, certainly in media some of these things get presented it quite, quite, you know, inflammatory. And again, if newspapers want to sell a newspaper, they show a plane crash so it's not happening every day.

[B]

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

[A]

Well, there's that too. I think one of the interesting things that we could get into is that in a lot of these studies, scientists are. There's a motivation 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, you know, X rays, you look for that orthogonal use for it.

[B]

Right.

[A]

And you. Or that, that orthogonal meaning. Sometimes we call it 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 I can drop all kinds of things. I can make gravity work for me. You know, it becomes a tool. And, and I think one of the things that's, that, that that is lost sometimes is that some things are not extensible. So you know, you can imagine that like if I, if I had something that move, makes a sense 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 degrees to 110 degrees. We cannot eat for a long time. 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 would lead. And I think a lot of science sometimes doesn't, you know, from the outside or even as an insider you can read a paper and they point to why it might be important, but they're really doing that to garner interest for their story and then say this might be important for this, but I haven't shown it's important for. They don't say that it's important, it might be important. And they're trying to look for 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, 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 take a pill and it cures everything forever. It's sort of found of youth ish. And we found a few of those. I'd say checkpoint blockade is one of those that you can take it and 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 resistant, resilient. A virus can exploit that button. That can cause collapse. And so most things are wired in these 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. You remember we 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. Your cells develop through states and you push, push the biological systems to reach this new state in a way that doesn't look like the linear between low immune reactivity and high reactivity. You might have to push it in a serious way. Because resiliency the systems even in chronic disease, but even in health, we're pretty resilient. You can stand up to a lot of stuff.

[B]

Can humans do that even in the context of abundant funding for basic research? Can what you just described, 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. Because 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 that theoretical physicists and therefore engineers, you know, develop all sorts of incredible theorems and real experiments and then technologies based on all of that. Because the math works, not because we can conceptualize it. And I wonder, given the complexity of biological Systems, perhaps in 20, 20, 26, 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 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 better or at least helpful in doing these experiments?

[A]

I take the standpoint that AI is, and I think, you know, this is back to talking to AI experts. It's really quite good 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, 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 answer the question you're trying to raise, if I get a tumor from a patient and I take apart all the cell 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 what would be the possible consequence of clipping this molecule's ability touch that cell? That's now doable, but it relies on an area of math that's 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 the relationship between this feature of the cell and this other feature of the cell? So it's learning about it and then 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 do. Some experiments are just 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 studying this question or am I going to study a little bit more and try to understand some things in a greater detail than maybe the machine learning gave me. But it's not clear to me that anywhere right now we can say the corpus of knowledge doesn't have a bunch of examples of cures across from treatment and say, oh, all I need to do is mash those up. Which is kind of what AI does when it comes to large language model. You query it, it looks statistically and says, what are the relationships between what you queried and what I give you back as an answer in a discovery space, we don't have examples of the other end. Sure, I can tell you all the things you could do, but knowing which one is going to be the orthogonal big hit, isn't there? But what I'm talking about a little bit is to take a problem apart and say, if I have something, like I want to change something and anything, this could be how if I want to change the world, it's unlikely that any one act will do it. Also, the world is pretty early. Political systems, despite what we think are somehow semi stable. But a series 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 to want us banging on it. It'll bang back. What in fact we need to do is if we want this tumor to get heat and 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 might not be able to do that until we kind of dissemble some of its defenses. And that's a way of. Again, in this kind of deep computational space, we end up with a lot of feature of the. Of tissue cells and how they're organized and what genes are 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. 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 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 and that that's when you really want to like, hammer to get the system to go to that, but then it might be like, 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 looked for. Single, you know, single hits one, one and done. But it may be a collection of. And you know, this is probably. This is how I live my life for health too. There's a collection of behaviors and food you eat and sleep you get and all these things create. And partners, you know, you know, your loves of your life, the friends you have, they're all part of, I think this, this and that's getting a little away from immunology, obviously, but.

[B]

No, but now when you think about the insula, you know, not so much. A good friend of mine who's a physician in the Bay Area says, you know, better living through chemistry still requires better living, which I love because it says you should never abandon as much as one can, the foundational stuff of sleep, exercise, nutrition, circadian rhythm, light, social connection, stress mitigation, and on and on. Could I ask you a couple of additional questions about the immune system?

[A]

Yeah, please.

[B]

Before we wrap, because I know many people are curious about autoimmune issues. More and more I hear about, you know, I don't know if 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. They're tired. I believe them. I know someone who had a myalgia recently. Psoriasis is something that I maybe have known to be. Now, autoimmune asthma, these are interesting conditions, not all of them life threatening.

[A]

Yeah.

[B]

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, fewer treatments that might be available or are currently available for those and other things? It's a big question, but.

[A]

Yeah, it's a big question. Well, fundamentally, again, this is, I think, where the 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. And 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. And I think if you look at autoimmunities, there's a view of them that they represent a misplaced immune system that either 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 lupus. There's a familial mutation in a receptor that's on a B cell that normally helps turn off the immune system, and it's defective. And so 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 prune to jazz up for Covid vaccines. Those can be overactive, and they can be genetically overactive. And one wonders why we'd ever have such genes and why they'd be propagated, except that maybe in some circumstances you need it when there's a big pandemic or something, those people might have a particularly good, good response. So there's definitely genetic origins of some of these things. I think what's, you know, what's interesting to some extent is something that you alluded to with asthma, where asthma was one of these things that historically would be called an allergy, and it still is an allergy 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 is coming in part and parcel with, you know, the immune system recognizing, you know, is, is a, is a 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? 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 in a microscope and say, oh, yeah, I can really see that the. There's thickening of the airways and that's why they couldn't breathe. 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 seven or eight. And they have. And that's why some people can take the inhalers and it works and other people can't. Some people, they're very chlorine sensitive. They go to a pool and it initiates their cold sensitive. So 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. Fail, you know, difficulty breathing. But it has many different sort of configurations. And. And I guess 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 variations in lupus, for sure, and inflammatory bowel disease. And you know this in the clinic because inflammatory dialysis. 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, it blocks a cytokine. And some people with ibd, this is like really bad diarrhea. It manifests and very painful. Um, you know, some people, they. 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. Inflammatory bowel diseases and autoimmunity is pretty tricky too, because people will respond to a drug for a while and then they'll stop. And then 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 they. Where it doesn't work.

[B]

Sounds like psychiatry.

[A]

It does, yeah. There's a lot. It sounds like a.

[B]

No disrespect to the psychiatrist.

[A]

No, but you're trying.

[B]

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.

[A]

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. With cancer, starting to understand the fact that it comes in these. These different immune flavors. And so the drugs that you try to use, it's clearly the 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 just got a different football team out there playing or they've got running a different play.

[B]

If somebody has a mild autoimmune condition, like let's say mild psoriasis does that I've read but that doesn't necessarily mean anything. 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 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 this or. Yeah, but anti interleukin 17. But, but you, you that individual is maybe 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, sort of an individual. Interesting case point for why autoimmunity could actually be useful. Yeah, it's not always the case. It's like there to give us asthma or flaky scalp.

[A]

You know, we 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 hem, you know, 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 seems to be the case. So having that, I think this 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 maybe viral infection at the cost of having things like psoriasis pop up or various other autoimmunities is the only way that a billion strong strong population has to move forward. And I always give this example because I think it's a really straightforward one. If you take a flask of bacteria and you put them in glucose, which is like sugar you put in your coffee, maybe sucrose, either one, you put them in a simple sugar and you watch the colony grow, you'll get these cells that grow really, really fast. The bacteria becomes billions trillions of individual cells. But there's almost always some just losers that are dividing slowly. And it's for whatever reason the system always springs us off. And you're like, why would you do that? Why would the system, 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 crowd fitness that comes from diverse diversity of genes. And so some of these things that make some of us susceptible to disease are also, as you're pointing out in other situations going to be quite good for you. 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, right? So I think there's a lot to be said 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. I mean, I don't know how much you know about this literature, but. But the differences in your and mind 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 numbers are averages. Some people may need five times that amount of, you know, vitamin X, other people may need a fifth.

[B]

I think this is super critical. The supplement world is kind of like scattershot. Well, I appreciate the rational grounding and all of it, I think thread throughout today's conversation, I think that I picked up on 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 communicated the right ways as the same way with vaccines and all the rest. You have an amazing sub stack. I know that because I've spent time there.

[A]

No thanks.

[B]

Part of the reason we invited you here today is to learn about the immune system and we barely talked about cancer. I realized we're going to have to get you back 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 the ways that you have. And as somebody who thinks in analogy and likes to teach in analogy, I really appreciate that.

[A]

Thanks.

[B]

That stance, what inspired you to get into public education about science and, 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 show notes. It's so thoughtful, so nuanced, so relevant to all the issues that we're talking about, if not directly, then in the general contour and in some cases directly. And I imagine you're going to continue doing this. So what inspired you to do it and how can we make sure that you continue to do it?

[A]

Yeah, well, thank you for the call out. It is something I've been trying to work on for about 10 years and it, it really started when a group of us, you know, were, were 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 is, is the capacity for everybody, everyone else to think as a scientist. Like what? You can ask yourself, 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. Two things are important about it. I think one of them is if you present the information in a format that isn't familiar, you're not going to be able to teach anybody anything about what's important. But the other thing is that we spent some time talking about this and we, we consulted some other folks that are in science comms and we realized the other thing is 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, there's hesitancy among African American, for example, to take drugs because of things of history of Tuskegee, which is like 80 years ago or however long ago, 60 years ago. Why it's, it's not in their lifetime in many of these people. And so part of the realization was like, maybe part of what we really should be doing as scientists, 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 and obviously the media and things to help this happen because it makes it interesting to have a, you know, kind of a nerdy scientist. And we can all be, you can be a nerdy scientist. I heard you. And you know, but also you're human. You're a human being. You have, you know, foibles to, you know, loves and hates and, and certainly foibles.

[B]

I have plenty of those.

[A]

We can get in that off the podcast. But, but you know, this concept of if we want to relate, 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, let's use the word 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 straight strikes me is really, really important to the impact that you can have with your science and that science can have in terms of teaching people what we could 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 designs, then you've lost the potential for it to do good is gone. So the substack can't about it because I was like, well, I need to write as a person a little bit more and tell about some of the, you know, time that you spend on this and why it matters and what it's like to, to do this work and, and in some respects also what it's like to, to lose in this which happens way more often than the, you know, 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 not winning. Well put. So I feel like that's kind of an important part of this. That again, it's not the glory story. Always some of the best selling books about science are the winds. But it might be more relatable at some point to get all of it. So that's kind of what I was trying to put together 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.

[B]

Well, I hope you continue to. And 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 for your advocacy for science and public education, it's huge. We need more people like you, but you've 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 just really cool. And with all the meaningless dribble out there, it's nice to go to a place like your 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. So I'm saying this intentionally, mark my words, at some point somebody's going to contact you that they decided to study the immune system or they learned something or they explored a novel treatment with their physician in a given, unfortunate or maybe even fortunate situation that bettered their lives. It's incredible what substacks and conversations like the one you've been willing to have today and going forward, 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.

[A]

Yeah, well, same here. Thanks so much.

[B]

Thank you for joining me for Today's discussion with Dr. Max Crummell to learn more about his work and to find a link to his superb substack, please see the links in the show Notes. Caption if you're learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero cost way to support us. In addition, please follow the podcast by clicking the follow button on both Spotify and Apple and on both Spotify and Apple. You can leave us up to a five star review and you can now leave us comments at both Spotify and Apple. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcast, podcasts or guests or topics that you'd like me to consider for the Huberman Lab podcast, please put those in the comments section on YouTube. I do read all the comments. For those of you that haven't heard, I have a new book coming out. It's my very first book. It's entitled Protocols An Operating Manual for the Human Body. This is a book that I've been working on for more than five years and that's based on more than 30 years of research and experience and it covers protocols for everything from sleep to exercise exercise to stress control, protocols related to focus and motivation and of course I provide the scientific substantiation for the protocols that are included. The book is now available by pre [e-mail] there you can find links to various vendors. You can pick the one that you like best. Again, the book is called Protocols An Operating Manual for the Human Body. And if you're not already following me on social media, I am Huberman Lab on all social media platforms platforms. So that's Instagram X threads, Facebook and LinkedIn. And on all those platforms I discuss science and science related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the information on the Huberman Lab podcast. Again, it's Huberman Lab on all social media platforms. And if you haven't already subscribed to our Neural Network newsletter, the Neural Network Newsletter is a zero cost monthly newsletter that includes podcast summaries as well well as what we call protocols in the form of one to three page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure. We have a foundational fitness protocol that covers cardiovascular training and resistance training. All of that is available completely zero cost. You Simply go to hubermanlab.com, go to the menu tab in the top right corner, scroll down to newsletter and enter your email. And I should emphasize that we do not share your email with anybody. Thank you once again for joining me for today's discussion discussion with Dr. Max Crummell. And last but certainly not least, thank you for your interest in science.