a famous um marinologist 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 were of the engines and if they

heard a were of the engine that had the

certain cycle of a general mo you know

motors engine they wouldn't fire. So

that's the sort of like self I know what

self is. And then they had another book

that was the engine sounds of the known

diesel engines of whatever engines of

the German submarines. And if they heard

that then they absolutely would fire.

And that's a self versus

non-self-discrimination problem just

like the immune system has to do. But

what I bring you with it aging is this

concept that as you get weirder and

different your body is getting like more

complex then that those books you know

start to have every possible possibly

every possible permutation of every

biomolelecule could could could be made

by your body at that point and then a

virus doesn't necessarily have anything

unique about it.

>> Welcome to the Huberman Lab podcast

where we discuss science [music]

and science-based tools for everyday

life.

>> [music]

>> I'm Andrew Huberman and I'm a professor

of neurobiology and opthalmology at

Stanford School of Medicine. My guest

today is Dr. Max Kuml, 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 sleepd

deprived makes you more prone to getting

sick. But why? Meaning mechanistically

why? Well, it turns out there's a

specific set of cells that need to

migrate in a particular way during

sleep. And we talk about how you can

reinforce that process in ways other

than sleep. We also discuss incredible

findings that certain brain states and

memories can be associated with an

immune system status you had when those

memories formed and evidence that just

recalling those memories, thinking about

where you were, what you were feeling at

those times when the memories formed can

activate your immune system in the same

way, which is remarkable. We also have a

very candid discussion about vaccines

and medications more broadly. You'll

notice that Dr. Dr. Croml is incredibly

balanced throughout today's conversation

and yet he's also willing to state his

views very clearly. So it provides a

very rich discussion about vaccines and

all the rest. Indeed, thanks to Max's

incredible breadth of understanding of

immunology and much more and his ability

to break down complex topics and make

them accessible, plus his genuine care

for public education and science.

Today's is a truly special and important

episode to educate and inform you in

actionable ways. I should also mention

that Dr. Dr. Crumbl has an incredible

zerocost substack. It's called the

immune beyond. You can access it by

going to the immune beyond all

oneword.substack.com.

And there he teaches about science and

more. Again, it's awesome. It's free. So

definitely check it out. Before we

begin, I'd like to emphasize that this

podcast is separate from my teaching and

research roles at Stanford. It is,

however, part of my desire and effort to

bring zerocost 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. Maxruml. Dr. Max Kuml, welcome.

>> Thanks.

>> Most everybody, including me, has heard

of this thing we call the immune system.

And most people just think, okay, this

is the thing that when I'm rested, keeps

me from getting sick. And when I'm not

as well rested, I tend to get more sick.

And there are these airborne things and

we can get sick. And there's like

funguses and viruses and and I think

that's probably what most people

understand and they probably also

understand that there are like cells and

T- cells and B cells. But if we want to

think about a little bit of the history

of our understanding of the immune

system and what we understand now, maybe

you could orient us because in reading

your work prior to this discussion, I'm

realizing that this is a very recent

field and also there's still a lot that

we do not understand. When I started

immunology sort of 30 years ago, I was

rotating in labs at Berkeley. I think

you were at Berkeley as well. And uh one

of the transcription factor biologists,

you know, mentor said, uh, you know, why

do you want to work in imunology? It's

not really a field. And so at the time

it was kind of true, you know,

everything was about um DNA cloning. We

still, you know, it's obviously still a

lot about molecular biology, what we do,

but uh, you know, at the time it was

pretty simple. We thought of the immune

system as something that on the one hand

it had to come into play when you saw a

virus or something foreign.

Um and otherwise it generally had to be

quiet and kind of leave you alone. I

think cancer imunotherapy changed that a

lot. that that gave us the idea that you

could tune its reactivity so that you

could get to the point where if you gave

an amnotherapy, what it was actually

doing was raising the threshold of when

a T- cell would activate and allowing

tea cells that might be just letting the

tumor get by get they'd be able to go

and go after that tumor and and and kill

it. I think that changed the spectrum a

certain degree where we suddenly saw

okay this isn't just a just a you know

foreign versus self thing because it's a

tumor is kind of not exactly self but

it's exactly it's also not foreign it's

was once you it's a cell that's kind of

evolved so I think tumor immunology

really changed our perspective on that

you know to the point where we now think

of it as a as a tunable system

but then I think you know a lot has

happened in the last 20 years there's

been a lot of excitement about cancer

imunotherapy because we're curing people

with cancer

which really wasn't done before. And

you're now in this space where um the

immune system is showing all these other

roles. I mean, you know it in the in the

nervous system, the brain, there's

microglea that do various functions,

cleaning up, etc. But it's in your gut.

It's allowing microbes to live in you,

but it's titrating them. It's keeping

them there in kind of like the right

quantity. So, it's kind of guarding

yourself. It's uh, you know, it sits in

your liver regulating how how much you

metabolize. there's a collection of

cells there. Um, it's in your heart.

It's, you know, regulating cardiomyio

function. Those are the the muscle cells

of your heart. Uh, they have to be

cleaned up from time to time. So,

there's a set of immune cells that will

help get rid of their byproducts in in

the in the heart. So, it has all these

additional functions that kind of before

were were lost in the in the just, you

know, the foreign battle against the

foreign and now we have this kind of

perspective of this system that measures

us all the time. It measures everything

about us and it exists in some ways. I

think it's to to help us be who we are,

you know, 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 um well it's you know some ways

it's trying its best

>> but it's applying the wrong program to

the wrong situation. Um so yeah it's

it's changed a ton and I'll give you

another little funny story which is that

that um you know when I first came into

immunology again we had the story like

you know the mentor who says you know

this isn't really a field the year was

like came to the field in 1989 and

that's right at the peak of AIDS and um

AIDS was like as as a biologist was

really interesting because you know the

HIV virus infects tea cells so your body

is filled with 10 the 11th or so T-

cells like a ton of different kinds of

T- cells and um you had a you have a

subset of TE- cells that are called CD4

T cells they're kind of a flavor of TE-

cells and the virus gets rid of those so

HIV virus will infect the CD4 T cells

and then then you end up with not having

them and the the manifestations of AIDS

for those that weren't around dur was it

was just a ton of different

opportunistic infections so like soil

bacteria that you and I you know fight

off without even thinking about it would

would would kill people but so too would

you see you saw people with carbosio

saroma you saw like a opportunistic vi

like where you know a cancer is emerging

um and you just saw all these kind of

manifestations of where the immune

system was important dementias in in

people with HIV as well you know it was

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 ies

that have led to where we are right now.

And some of those I, you know, I think

it's worth pointing out were just these

curiosity questions like what are these

cells? Like they were hard to study at

in the beginning. You know, they're they

don't live, you know, it's sometimes

hard to keep cells out of out of a out

of a human body alive. So, you know,

there's there's issues about how do you

keep these things alive in the very

first place and then and then what kinds

of things, you know, trigger them to do

stuff and you got to make reagents to

test those, you know, ideas you might

have about what they might do. It was a

long haul, I think, to get ourselves

together where we now have a pretty good

understanding of all the molecules and

the cell types and the and the behaviors

that they can engage in. And it just

gets more comp, you know, more more

complex and more like rich as we

understand that they're basically every

single T- cell in your body is like a

free agent and they're part of a sensory

system. Each one can measure the

concentration of a of a of a set of

biomolelecules, proteins, and they form

a 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

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. It is magnificent. Do you

mind if we take a developmental um

perspective on this for a second and

then I have a basic health question.

Yeah. The developmental perspective is I

think most of us either remember or have

observed that when humans are young they

get sick a lot more. Presumably that's

because their immune system isn't as

well developed. But kids tend to get

sick and then get over being sick pretty

quickly.

>> Yeah.

>> Maybe you could describe what's going on

there.

>> Yeah. And it also is the case that you

know as we get older much older in fact

uh last quarter of life let's say people

tend to get sick more uh what's going on

um in terms of immune system function um

or is there something more broadly

happening at level of just kind of

energetics mitochondrial function very

curious about this

>> if I can take a step even further back

I'll ask you a question of like who are

you and I don't mean that like in the

personal sense, but I can talk about

that too if you want. Uh, but the more

the question is like at at some point

where does your body end and where does

the world outside start

and one of the things that, you know,

you start to realize if you look in a

microscope is that we're covered with

microbes all over our surface. We're

covered with microbes all the way in our

gut. In fact, we can't, you know, you

can't digest, you've probably heard this

before, but you can't digest animal fats

if it weren't for the bugs, the bacteria

in your gut. They make some of the key

components of of bile acids that allow

you to digest animal fats. So, you need

this system that's around you. So, you

aren't just the cell like if you learn

biology, you've got the again, we're

going to go way back. There's the egg

and the sperm and they fertilize and now

you got this this this cell that starts

to divide and gives rise to every other

cell in our body. So you might say that

your body is just that collection of

cells, [snorts]

but in fact it's it's it's it's absorbed

a lot of viruses and and bacteria from

our environment. And you know, to go

into that really briefly, that's really

important because we only have 20,000

genes in our genome. So there's only so

much in a given life that we can do with

those genes. And so by absorbing all

kinds of other species onto us, we get

their genomes. So like you said, like I

was saying, the the bacteria in your gut

can now help you absorb nutrients that

you wouldn't otherwise. If you eat

sushi, you know, you've heard this

probably, right? You get you get

bacteria in your gut that can help you

absorb the the the seaweed, you know,

nutrients from seaweed. So, so taking

this into your question, you know, when

you're first born, you've never really

seen anything. And so, two things are

are I think worth pointing out at the

early phase of life. One of them is for

the first six months or so, your immune

system is pretty poor at being trained

on things. And it's presumably we

presume that for those six six months

that's because your body is developing

so fast that if you were to have a super

active immune system you might actually

find yourself attacking yourself. You

might think that you're foreign because

some genes turn on during development

and then all of a sudden you're you know

your immune system's like oh I see

something different and now I need to

react. So that's well known and that's

that's one of the reasons why some

childhood vaccinations they're really

important to protect kids in long over

life. Why they aren't given until you're

6 months or or older. But I think to

your point, one of the things that's

happening with kids is that they then

then as they go into their like until

they're 10 and you're talking about they

get sick a lot, they just haven't seen a

lot of these bugs before. So they don't

have an immune system that knows what

flu is cuz they've never seen the body's

never that body and kids 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 you

know gets rid of that with the exception

of the ones that you know are those

those certain viruses and bacteras

mumps, measles, rebella that are they're

lethal and that's why we immunize as we

say and that's those are things that

your immune system if they get too much

of those kids will die and so it's

better to protect them with a vaccine.

All right. So that's the front end,

right? The front end has this initial,

you know, imunosuppression, then just

exposure to all these things that are in

our environment and you and I take on as

part of our genomes. But we have to get

a we have to reach a day tant with some

of them. You know, we have to get to the

point where the immune system can kind

of like fire back when they show up if

they're bad and and and allow them to

live in us if they're good with us. And

so I think that's what's happening a lot

in those first years of life. And you

know, you can see that both in the form

of, you know, kids getting sick a lot,

but you'll also see that their guts

develop way diverse microbiome. You

know, 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 I'll tell

you two things that I think are

important. On the one hand is the idea

that is is the fact that a lot of your

cells in general become less functional,

including immune cells, and you get less

cells produced. And and that might just

be because, you know, we were never

selected as organisms to live as long as

we do right now. That's one idea of

aging, right?

>> We know that that we just were supposed

to be dead by 70.

>> Well, no, but we do know that that we

can reproduce and and you pass on our

genes successfully already when we're

16. So, you know, 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.

um you know at some point maybe there's

no selection. So we don't know that but

it's it's a reasonable hypothesis to say

there wasn't any real selective pressure

for passing on genes that do anything

past when you're actually having kids.

The psychologists would tell us that uh

the wisdom of people, you know, 60, 70,

80 and beyond is useful for um groups of

humans that live in, you know, you know,

villages of 100 or so people because

they can give information to younger

people that is on the periodicity of

like every 5 to 10 years, maybe every 30

years.

>> But that's a just so story, right? I

mean, it's a nice just so story.

>> I like it too. And the I think the

genome 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 in for for for the elderly

that do you know they're going to have

effects on the fitness of their

grandchildren which is their genes.

>> And so this yeah I think there's

something to be said for that in in

conceptual space. I don't know if I can

prove it to you that that's

>> it's a tough experiment to do. It's a

really tough experience to have two

villages where the you know the

grandparents are eliminated or like kept

you know both non-ethical and also non

>> 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 you like

who are you um and I was saying okay

well in aging you have this issue that

the immune system is is tapering in its

efficacy it's many of the cells that you

you know you've been holding your whole

life start to to literally they die off

but there's another thing which is I

think a lot of people don't realize when

you say when basic biology ology say

that sperm, you know, like uh fertilizes

the egg. So, you've got your mom's genes

and your dad's genes. You got 23

chromosomes for your mom, 23 chromosomes

for your dad. And and and at least in

when you're first born, every cell is a

clone. It has exactly the same

information.

But DNA replication and and DNA sort of

like fidelity isn't perfect. Like they

say that on your skin, the cells of your

skin may have somewhere between 10 and

30,000 mutations per cell per day just

from like by basic sun exposure. And

it's that that's higher than some of the

other organs. But the basic idea is that

your DNA, you know, it's susceptible to

UV radiation. That's one of the reasons

we put on sunscreen. [gasps]

But what it what it practically means,

no matter what number you put in there,

whether it's 10,000 mutations per day or

remember the the genomes are huge,

right? So 10,000 mutations out of

terabytes of of of information, still is

only a certain number. But do that over

every over years. And the main thing is

that that means is that every cell in

your body is no longer identical to the

one next to it because this one got

different mutations on day one. This one

got some mutations on day two. And

slowly but surely, you are becoming like

a mosaic. And I say mosaic, you know,

because like the tile that you see in

Morocco, you know, very intricate

designs because if you actually, you

know, start to look into tissue, you

know, you'll find that certain clones,

certain mutations do make certain cells

more fit. And they're the ones that if

you scratch yourself and a cell has to

like some some new has to has to form,

they might be the fittest to fill that

void. [laughter]

>> And one of the other clones over here

that got a different mutation may not be

fit to fill that clone. And so you you

end up with this pastiche of who you

are. So now again I ask you like who are

you now? So if I want to defend against

something that looks different, what if

everything looks different? What if

every cell is different from every other

cell? It's it's it okay. You want you

want another analogy? I would like

another analogy. The only um exception

that I can think of to this and I could

be wrong is that our neurons, our

central nervous system neurons, our

brain and spinal cord, most all of them

are the same ones that we were born

with.

>> Same cells, but

>> same cells, but so you're saying

mutations are constantly occurring in

the neurons in the DNA. So there it is

fascinating by the way that neurons live

that long. and you know hair cells that

they say that the the proteins in in our

hair hair cells of our ear are the same

exact molecules atoms as we had when we

were born. So there's there's some cells

that are along the but in their nuclei

the DNA that's encoding who they are who

those cells are is subject to mutation

ongoing and it depends on how deep they

are like the we tend to think that one

of the reasons that immune stem cells

live in our bone marrows you know our

long bones are hollow and in there is

the source of the immune systems you

know revitalization it's the stem cells

that make more white blood cells we like

to think that they live in there because

it protects them from a reagent they

they they they hang out stem cells are

You know that the bone actually serves

not only a structural purpose in our

body, but they it's a cavity in which

things can live and

>> keep it away from from solar radiation.

>> Keep it away from chemical cues in the

environment that can mutate.

>> Sequester your stem cells

>> and um

>> don't burn them.

>> Yeah.

>> That kind of thing.

>> Yeah. Likewise, the neurons in the in

the uh inside of the skull.

>> Yeah.

>> And the spinal cord

>> are protected.

>> They're protected.

>> Yeah.

>> And that's interesting.

>> Yeah.

>> Yeah. I would like to take a quick break

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>> 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's if you want to

take a political statement from it's

pro- immigration because all these

bacteria that live on us are actually

bringing us goods and they they do a

lot.

>> We just lost half the audience. No, I'm

just kidding. I'm I'm totally joking. We

we're a bipartisan audience. I'm joking.

Take it how you want. But by analogy,

it's the argument for, you know, why why

certain um you know, influx of of of u

in this case organisms onto us, you

know, create a more robust, you know,

person than we were before. But I want

to give you this story that one of a

famous um marinologist 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.

[snorts] And so they had two sets of

books that they used. Uh, one of them

was a book that gave them the sound

profile of all, let's say it's a US, of

all the US submarines. And so they could

listen to the were of the engines and if

they heard a were of the engine that had

the certain cycle of a general mo, you

know, motors engine, they wouldn't fire.

So that's the sort of like self I know

what self is. And then they had another

book that was the engine sounds of the

known diesel engines of whatever engines

of the German uh, you know, submarines.

And if they heard that then they

absolutely would fire. And that's a self

versus non-self-discrimination problem

just like the immune system has to do.

But what I bring you with the aging is

this concept that as you get weirder and

different your body is getting like more

complex then that those books you know

start to have every possible possibly

every possible permutation of every

biomolelecule could could could be made

by your body at that point. And then a

virus doesn't necessarily have anything

unique about it. A virus is also going

to make proteins and that's your immune

system can see the viral proteins and

say oh a new thing has come in and

that's you know that's out of range and

now I need to mount that a T- cell

response against this I need to make the

you know bring in the troops but with

aging we have this this kind of you know

us diverging problem so that this you

know this system that's supposed to

sense us

>> is just you know has a lot of cosmic

background has a lot of noise in it and

so I think it I think that's one of the

reasons why we also have issue when

we're aging and it's I I think it's also

one of the issu reasons why cancer is

more prevalent in later life for I mean

there's two parts 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 you know, is it's got

some differences.

>> What about the argument that there's so

much cellular turnover that um 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 this is that the way

it works?

>> Yeah. And I think I think you you are

bringing something up that's also true,

which is that all the time I think the

immune system is defending us against,

you know, mutations. So, one example

that everybody sees when they get to be

about 40 or 50 is is little these white

spots on your skin. And we we think that

those are places where the immune system

has sensed a collection of cells that

were precancerous, maybe they were even

beginning of cancer, and has wiped them

out. And and so the you know, a lot of

the origin of cancers in skin is is

melanin producing cells like melan, you

know, melanoma is what we call skin

cancer. um those melanocytes that that

white area they've been wiped of a whole

collection of melanocytes and that's why

it's you know it's white instead

[snorts] of as dark as your as the rest

of your skin. So you know to that extent

the idea that the immune system is is

pruning you all the time is you know

there it looks like there's pretty good

evidence for that.

>> Um and the question is when does

something become dangerous

that's that's that's you know that's

fundamentally question with cancer and

these sorts of things. If you said, "I

want to actually have the fittest cells

in my skin to uh fill in a gap if I

scratch myself. I would like to have

cells that quickly replicate just like

maybe in kids. Kids heal so ridiculously

quickly, right? Because they have an

abundance of these cells that

>> I think I think they're they're their

wound healing. I mean, there's a group

out of Stanford that studies this, but

essentially, you know, wound healing in

in in young is quite quite a bit faster

and more efficient and and there's many

that there's many levels of that. Yeah.

>> But um yeah, remarkably faster. 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 3 days later, they can't

even find it on them and you know, like

four weeks later, you're still like got,

you know, scap or something. But I was

just coming to the point that if you do

that and you you want this, do you want

you maybe want that to fill back in

because you certainly out in the wild

having an open wound is a bad thing. So,

you like to heal quickly. Well, if a

mutation has happened that fills that

cell in quick, more quickly, that is

almost by definition a mutation that's

let that cell divide faster.

Well, what is cancer? It's cells that

divide faster. So, in some sense, all

these 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. And then again, the question

is like, well, how much better do you

want that? You want it to like help you,

but at some point you don't want it to

basically form a lesion and grow grow

grow and go other places and grow, which

is called metastasis in cancer, which is

how most people die. To me, that 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, you know. And

then at the same time, the idea of what

you can do with that information is also

I call this kind of a new immunity.

Immunity used to be like a fuel gauge.

You'd say it was low for itself and it

was really high against viruses and it

was like a fuel gauge. You don't know.

Now it's really hot. And what we

originally thought we were doing with

cancer imotherapy was making it just

hotter generally. But now you realize

that in between like the immune system

not caring about something at all and

and going and you know like releasing

all its fury on something are all these

other things it can do with the

information it gathers in there. And

that's where I was saying you know it

can it can like quarantine bacteria.

It's not going to kill them. It's it's

in that zone. The bacteria as long as

they're in the right zone, there's not

too many of them, there's not too few of

them, immune system can actually help

them be there. It can produce things

that like either tighters them out of

circulation or keeps them there. You

know, in all these other settings, like

I say, in the heart and the can go to

almost any organ and uh and the immune

system is consistently present and it's

consistently measuring you. And the U

again is this complex you. It's not just

what came from the egg, it's the you

that's you right now, including all the

mutations that you might have acred and

all the bacteria and and and the

viruses. You know, we have a lot of

viruses in our bodies that we tend to

think that at the end of a of a illness

that we've gone back to our pure state.

This may came from religion. You know,

that we were born pure and if God made

us correctly, then we would be pure at

the end of things and you know that

would be pure immunity would 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 a then

there's the goal for the immune system

to kind of quarantine that to say this,

you know, maybe we don't want to kill

every one of our cells to get rid of

every virus that's infected one of our

cells. We need to leave some of those

alive. We don't like for example herpes

virus infection infects the nerves and

when people have uh you know emergence

they they get nerve pain and worse. A

lot of that is caused by the immune

system reacting to the virus trying to

get out and then killing off neurons. So

the the the it's imopathology. The

immune system is c causing as much of

the damage and problem as the virus is.

And it's the failure of that day tant.

And when certain viruses are just

sitting in us, we're perfectly fine. You

know, we have new viruses sitting

around. As long as they're laying

dormant, our immune system can say,

"Okay, I'm going to hang out here and if

anything bad happens, I'm going to

squatchch that." But it's not like we've

been purified.

>> You know, that's a reality that's a

little bit too bad. But, you know, it's

also one where you say, again, if if the

goal of us is to make it to 30, let's

say you get a a an early liver infection

of a 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's can 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 that are not always

about getting rid of things at all cost.

This raises a question for me and

obviously I'm not an immunologist but it

seems like one

>> you're going to be one by the end of I

like the sound of that. Um 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 mutated and different

>> um enough to assess how many cells

throughout the body or even just get a

local average of how many cells have

similar mutations or just are different.

Right? So that if we are indeed born

pure um in the biological sense um

[laughter]

let's just keep it there for sake of

today's discussion and you know by the

time we are um you know 32 years old we

are a mosaic of mutations

>> as it it appears we are if the immune

system could surveil multiple regions in

the body

>> maybe compare organs or maybe keep it

within organ system and say you know the

number of of mutated cells or not pure

me cells would be one way to do it more

simply perhaps has exceeded a certain

threshold measured I don't know like

enough receptors have something in them

that the cell goes okay you know what

I'm going to fight y

>> right in the same way that you know

soldiers you know they might hear a shot

whis 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 uh fight back

>> it seems like there should be some way

to that the immune system could quantify

either bodywide or or local organ or or

over some period of time they could

integrate over time. I have to imagine

that such a mechanism exists. you're

coming from neurobiology as I know and

so there is that in neurobiology of

accommodation right if I always tell the

story of I went to this little village

in in France called aas if you know the

names 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 striking it really hits you

but after being in the town for like an

hour

>> Mhm. you don't notice it. Yeah.

>> And that's neuronal accommodation where

your nervous the same kind of thing

you're talking about where the you know

the sensors in your nose can become

they're like okay I've seen it. I'm

seeing it now it's not anymore and and

so I'm going to tune that out because

then your nose has the potential to

smell other dangers or other stuff.

Right. So that's the nervous system. I I

think you're exactly right where you're

going with this is and we think this is

true that the immune system is it you

know for danger it's looking for

something you would call like a it's how

it's seeing the signal over time. So, a

virus may, you know, let's let's say

you're a T- cell that recognize a virus.

Well, you're looking for something that

you've had nothing of before and then

all of a sudden the virus comes in, it

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 [clears throat] response

and you learn it and so the next time

around you'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 a maybe it's insulin, you

know, which we think in general, you

know, it has a little bit of signal up

and down as you have a sugar, but

there's a range for that. And so your

body gets used to that range. And the

tea cells that see insulin, they are

very low. They're going to only be very

very low reactive to that. And there's

there's a whole story behind that, but

basically they're going to see that

level. But you can also have things that

the immune system is going to want to

treat like self that maybe do a slow

rise. they don't have this peak that you

have with virus and so like a 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

validated by any you know any

experimental stuff is the idea that

whatever you are is what the immune

system is going to help you be if it if

it's if If it's a slow direction this

way, it's going to it's going to be okay

with that. What it doesn't like is like

big spikes and and and and that's maybe

the signal that you're asking about,

like could you actually get to the point

where you be reactive? The problem with

cancer is that it is, you know, slow and

nefarious. It grows over time and it and

and I think 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, you know, this commensal is

so long as it doesn't accompany. Again,

viruses have two features in common. One

one is this spike of of, you know,

appearance. But they also cause damage

in that window. And so you have like

these cues that I think the immune

system, and I say the immune system

because it's some cells are going to see

the damage and some cells are going to

see the the additional proteins that

come in and then they exchange

information just like your brain, you

know, uh you can talk about the fact

that the brain has this wired, you know,

set of cells that are wired in space.

They're, you know, across your body from

your brain all the way to a muscle.

Let's say immune system has this

collection of cells that are they're

literally crawling around us right now.

And we used to do we still do a lot of

imaging. If you look in a piece of skin,

you can see the cells the immune system

are really really surveying us. They're

crawling around. But they get together

like neurons and they can form synapses

and one can say to another one, "This is

what I saw." And oh, you saw that? Oh, I

you know, I'm just being this. and they

can, you know, form a cluster of cells

that basically get together like a

neural little mini brain in our tissue

and they can say this is bad. We got to

do something about that. But I think the

slow burn doesn't do that. The slow burn

is one of the ones where the cells are

like, "Yeah, it's not that bad." I

realize this perhaps is not your

immediate area of uh research, but

recently I've been seeing a lot more

interest um in the thymus,

>> 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.

um because [snorts] we've never covered

the thymus on this podcast in any amount

of detail. If you could just uh educate

us a bit uh what it is, what it does,

and why it might be interesting as a as

a um therapeutic. I mean, maybe we in a

few years we'll all be banking our

thymic cells. Um maybe we will be

>> I know some people are already injecting

non-FDA approved peptides that uh come

from the thymus. I'm not recommending

anyone do that, but people are already

doing it um because that's the the

internet in 2026. But what's the thymus?

What does it do? Wh why this interest?

>> Yeah. Well, I can back up one step and

I've I've used the word T- cell before

>> and T- cell originally was thymus cell.

So, for those that maybe don't, you

know, have gone to had blood taken, you

know, if you have blood taken in

hospital, whatever, you 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 we for the moment

we'll talk about two. One are called B

cells and one are called T- cells. And

TE- 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 and I'm writing one that's

supposed to be released tomorrow about

the thymus because it uh 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 whitish organ as

growth near the heart as they were

taking the body, you know, this cutting

open. And all the autopsies up to that

point had been done mostly with adults.

And in adults, there's only this small

little thing there. And so they were

like, "Oh my god, part of the heart

thing is this overgrown thing." they

they didn't really know what it did

[snorts] and so they would remove it and

uh the kids then would go home and it

was usually exploratory heart surgery

but then kids would go home and uh far

from you know dying of heart disease

many of them would die from like

opportunistic infections they get all

these infections they get flu and etc

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 Jo Miller

who's this this 97-year-old codger in in

Australia at the time he was in in

England and he basically took a bunch of

mice and then when they were newborn he

removed their thymus the same same

little whitish organ. And sure enough,

those mice were they basically grew up,

okay? But then they all would succumb to

bacterial infections. And in fact, a few

of them even got tumors, which was kind

of noted at the time, but forgot. And

the reason why that is is because the

thymus is the place that makes all your

tea cells. And it and it comes from a

kind of a convoluted path, but you

remember how we talking about how the

stem cells of your immune system lives

in your bone? Well, there's stem cells

that live in your bone and they travel

through your bone through your blood to

the thymus and become te- cells. And

[snorts] the the reason they need to do

that is that the thymus is this kind of

super special place that is able to

present to them to show them all of the

genes in your genome in various

different ways. And so the tea cells

that come in there, the tea 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

you don't want to produce tea cells that

are going to go off and kill your

pancreas or, you know, kill your big toe

or anything, right? you want to you want

to maintain like tolerance. So you want

to make sure that you don't make the

immune system that's too harsh. So the

the thymus has the the role of producing

tea 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 to let you be you in

that way. Now to [snorts] the point

about the the story and you were asking

about aging is that is that in kids

those are really big because at that

point we were talking about the

developing immune system. It has to go

from like, you know, living under the

veil of your mother's immunity and then

it needs to let some development happen

and then it needs to burst out and start

to be able to react against whatever

bacteria and viruses you're going to see

over life. So your thymus has this huge

output. So as like between [snorts]

really from you know three to six months

old and you know into your into your

four or five years age but tapering your

body makes tons of tea cells and it's

because probably what you're talking

about you're getting exposed to all

kinds of different back bacteria and

viruses and so you need to make that

make that collection of immune cells

that both some of them you know see self

at low levels but then they also can

maybe react against different things in

the environment including the ones you

need to defend against. Then what

happens is because again I think we're

not needing that later and maybe we

don't even want that the thymus

involutes it gets super super small so

that in aged people it's like tiny

[snorts] and um and so it's not putting

out new tea cells and so the reason why

there's interest in like these peptides

but all these other approaches to like

revitalize the thymus is that like in

cancer for example wouldn't you like to

have a whole bunch of new tea cells that

could come into into you flood in there

with exactly the specificity for the for

the tumor the tumor has managed to teach

all your normal cell your other diesel

cell in your body that it's normal maybe

you need a source of new material to

come in and do that and there's really

two ways I think you you mentioned you

talked to Alex Marson not 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 [snorts] the sort of like if you

will the more natural route to that

might be to to let the thymus make use

more tea cells and and make sure that as

they come out you make sure that they

can react against this tumor or whatever

it is you need to defend against. It's

always been a fascinating organ from the

sense that it's the origin of all the

cell types that we care about, the T-

cells in that case. But it does have

this like aging hit, you know, sort of

aging effect that seems to make us a

little bit more susceptible to things

later in life.

You know, again, we could argue about

what whether there was a big

evolutionary design behind doing that or

whether there just wasn't needed because

if you got you got to 30 and you died of

an arrow wound, you know, you know, and

but you given your genes, you're you're

a winner in the evolutionary sense. You

know, I love this uh uh this stance on

well, if you've already reproduced, I'll

just give a brief uh vignette. Uh we

were introduced by our uh mutual friend

uh David Felheim who's a a phenomenal

developmental biologist from UC Santa

Cruz and his wife Sophie Salama's also

phenomenal biologist a mutual friend and

years ago I was in Dave's lab because we

are longtime collaborators and published

a bunch of papers together and uh he was

doing some injections. I'm going to get

you in trouble Dave. He doesn't do this

any longer.

>> Yeah. I'm going to I'm going to join him

to get you in trouble cuz we

>> he was doing some injections and he

might have been using might have been

using carocyanide 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

fluorescent dye would label a set of

neurons in a pathway. And um and I

walked over and I I saw Dave doing this

and he wasn't wearing any gloves.

>> And I thought, these are carboyanide

dyes

>> with cyanide.

>> Cyanide being the And I said, um

>> Dave, uh don't you want to put on

gloves? And he literally looked up from

the microscope at me. I'll never forget.

And he said, I've already successfully

reproduced. And he went back to doing

it. And it's his lab. So, and everyone

else was following a safety protocol.

Don't go after him. doesn't do this any

longer, folks. But, um, there's an

interesting mindset among you because he

comes from cell biology, Randy

Sheckchman's lab. You both trained in

Nobel Prize winning laboratories as

graduate students. So, I I find it

remarkable that this this stance of uh,

well, if you've already successfully

reproduced, we really aren't needed.

But, um, his kids are now graduated or

in college. So, there is this thing

about raising the young, too, and not

just creating them and then dying.

>> Agreed. I think there's a fitness

associated with being older than that.

And again when I say that this it is

maybe just taking this from a purely

like what would have been the source of

what we are today. You know what would

have been the selective pressures on

them and it would have been a little bit

like David saying you got to you know

the selective pressure is to get your uh

you know 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. Um [clears throat] so that that

that period of of raising children I

think creates more pressure in in humans

to to to you know to successfully be

healthy longer. But I guess just you

know that there may be a negative

viewpoint there may but that concept

that maybe there isn't as much pressure

for you to be healthy and and going with

this is the idea that some of the things

that we want to be super efficient early

on might actually be bad for us as we

get like I'm like like I think this

issue that I that I brought up of our

mosaics is is a is a real confounder to

everything because that creates

something that is

>> quite hard to defend against. I think

that that that that aging backdrop um

and uh you know some of the immune

system that is really going to be

important to just be super reactive

early on may have some you know

compensatory problems when in faced with

that new reality of a 50-year-old or

70-year-old or whatever it looks quite

you know looks quite more complex but

you would have 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 that say who 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 some questions that are almost 90%

of them are going to be dead ends. You

know you can hypothesize it's one thing.

Well, you got to do the experiment to

like eliminate that. Mhm.

>> And this is one of the things that

people I don't think always understand

about science is that for all the

discoveries that you know I made or

other people have made, there is

hundreds [snorts] and hundreds of like

disappointments. You know, and you'll

recognize this where you you just go

home from the lab at the end of the day

and you've you know you've you've done

everything right, but the answer isn't

the one isn't the right one.

>> Yeah. One control experiment can

>> nuke your whole project.

>> Well, there's that.

There's obviously that you have to do

the experiment well and have 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 more importantly try to prove that

it's not true. So the better

experiments, the kind of we call them

killer experiments, right? The ones that

kill them kill the idea if they're

wrong. if the idea is wrong, but it's

killer because it if it's turns out the

way you hope it will, you know, again,

when we get to some of these aging

things, there's a lot of in there's a

lot of intuition that we all can put

into this, whether we're like

professional scientists or at home

scientists, but it's really hard to say

that intuition like your idea about how

the way the world should work is in fact

the way the world does work. You know,

that that I I wish that because of age

certain things would happen. That's

that's a that's lovely. But it could be

super the word was baroque, you know,

like [clears throat] it should the whole

system could be, you know, configured in

a completely weird way that doesn't

really initially make intuitive sense to

us. And that's also why some of those

discoveries are so big to us. We're

like, "Oh my god, I didn't realize that

this system that seems like it might be

quite as simple is so complicated. The

world is so strange."

>> Well, when I started in neurobiology,

the brain, the actually the entire

central nervous system was considered an

immuneprivileged organ. Yes. There

weren't supposed to be immune cells

there. And thanks to the beautiful work

of Carla Shatz with the major histo

compatibility complex work and um Ben

Baris and I'm failing to mention all

their scientific offspring but Beth

Steven, Shala Ergloo like and on and on.

Um it would take the rest of the episode

to name all all of Ben's scientific

offspring and Carlos too being you one

of

>> right I didn't work on those issues but

um but I was in those labs when it was

happening. We now know that the immune

system is active and alive in the

central nervous system throughout the

whole lifespan serving critical roles.

>> There are two things that well three

really that that are somewhat practical

questions. I'll start with the most

basic one. Why is it at a mechanistic

level that if you miss a night or two of

sleep that your immune system seems so

less effective in fighting off off

infections? Do we know what's happening?

Is it like you've got so much adenosine

which is the sleeping molecule and and

[clears throat] uh like that that

adenosine inhibits T- cell function or

something? Do we actually know? Because

I think all of us are familiar with the

fact that if we we don't sleep well or

enough for a couple of nights, we're

much more susceptible to getting sick.

Yeah.

>> Is there a mechanistic understanding of

why that's so?

>> I think there are bits and pieces of it.

I think um some some really nice work

shows that at night a few wacky thing

when you're 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

um and and your tissues become populated

with a bunch of neutrfils that come out

of the bone marrow and and seem to be

you know depositing collagen around your

body and and so there's a lot of things

that I think are reparative about sleep.

But I've thought about this a lot in my

own life as probably you have with sleep

is to 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 um 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. You just need

to reset. So the immune system is

definitely resetting and and you know

there's as I said there's evidence that

a lot of the cells go kind of quesuscent

into the tissues and they they may leave

you alone for those reparative processes

and actually allow those

>> you know in terms of the data on there

there's there's a lot of studies that

are being done and and I can't say that

I've come to a a conclusion about that.

This is this comes in the question of

like is it known or do I do I not know

it or is it does nobody know it and I'd

say this is might be one of these areas

where about 10 factions of people know

it but they don't agree

>> you know so there's variations on things

but I I think the data for example that

immune cells dive into the bone marrow

at night is is pretty solid

>> that makes sense

>> what they're doing and why that's

important in the long sense of like what

you're talking about everything from

well but I think it's you know things

that happen overnight you you're

definitely your cognition improves is

that immune immune or is that neuronal

or both? I think it's both.

>> Something in the lymph plumbing immune

system. One thing that's just striking

like that is undeniable is probably the

best way to put it is um everybody has

bags under their eyes and looks like

when they are sleepd deprived. They

sleep for a night or two

>> and it goes away.

>> That's clearly accumulation of lymph. We

we actually know that. That's just lymph

fluid that's not being cleared. And it

might not even be the brain's uh

glimpmphatic clearance system. It's just

there's a bunch of lymph pooling under

your eyes. That's why you look like

>> Yeah.

>> And then you sleep for two nights.

>> Well, and you look better again. And the

eyes get glassy. We know that the eyes

get glassy when we're sleepd deprived.

>> That's also a 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 but that to me can't explain the

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 n

like okay, I might wash my hands or just

kind of avoid them and you're good.

>> Yeah. So it's it's I mean it's an

incredible effect one way or the other.

>> Again, I don't know the degree to which

we can nail down, you know, which which

part of things that are happening is

which. I always like the story that that

the um there's macrofasages, 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 they can you know sort of

like when you wash your car windshield

you do it completely at that point and

but you can't be driving with flying and

right [laughter]

you'll never clean.

>> That's a great analogy

>> you So, I think there's certain elements

of some of these cleanup processes that

happen best when you're not getting

things, you know, you know, dirty or

again, I think a lot of what we're

talking about is byproducts of our

energetics that leave, you know, some

damage behind it. I I think we just use

a lot of ATP and we do a lot of stuff as

our bodies in in the sleep time where

you can not be, you know, producing more

of that and get ahead of the curve on

cleaning things up a bit.

>> Um, like pulling into a gas station,

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subscription. This thymus thing is

really intriguing. And uh I know a lot

of people who um opted to bank their

child's umbilical cord in the hopes that

the stem cells from the umbilical cord

will someday be useful.

>> Yeah.

>> How invasive is it? Andor should we be

uh banking thyic cells?

>> Uh because these seem like incredibly

valuable cells for their ability to

immune surveil and create kind of the

perfect situation using our own

indogenous tea cells to battle

infections. I mean, I kind of wish I had

a little little chunk of my thymus.

Yeah.

>> Um, in a minus 80 freezer someplace so

that when I'm 85 years old,

>> you might

>> I might be able to exploit that.

>> Yeah.

>> Well, I'll I'll say that the umbilical

cord one is is pretty straightforward.

It's, you know, the umbilical cord is

being essentially discarded anyway and

it contains a lot of, as you know, bone

marrow stem cells that um the utility of

those is a little different than the

thymus. the utility of of banking that

material and banking just means you put

it into a vial small little you know

small little vial with 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

>> has that ever been done successfully

>> yeah you can do Are there kids even kids

or adults that are alive today because

they banked their umbilical courses?

>> But certainly companies sell access to

that

>> somebody has to pay to keep the freezers

on backup generators and things like

that. So people invest time and money

into this idea. 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?

>> It's a really good question. I don't

know the answer to that question. I

guess the parents pay the

>> I can tell you and this will be just

like this is this is the depth of to

which you're you're describing uh Dave

Felheim injecting a you know 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

>> this is offered in mass now.

>> Yeah. Yeah.

Do you want to do you want to keep the

umbilical cord?

>> Honestly, honestly, I would do it

because it's one of those situations

where if it's not too Well, I don't know

if it you know, it depends on your your

how much money you have to spend because

the

>> it's within within the noise. 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 then I think this would if if they

happen to have a a childhood leukemia

this would this would cure it

>> which is an incredible statement if you

think about it even if it hasn't been

done successfully yet you didn't say it

might be able to lead to a cure 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 like

sleep to banking thymus and umbilical

cord. Now I'm going to go to the sort of

next level which is um not just in the

Bay Area. A lot of people uh however are

starting to think about oh maybe I make

some induced pur potent stem cells from

a fiberblast from one of my skin cells

put the so-called Yamanaka factors on

revert to stemness and then I might be

able to grow a new pancreas or study my

uh you know whatever organs in these

so-called organoids or what however

they're referred to. Yep.

>> But I learned today from you that if I

take that fibroblast now, that

fibroblast might not be completely

Andrew Huberman as I know him to be

[clears throat] genetically. It's

actually could have some uh mutations.

That seems important to compare against

a sort of um a standard cell.

>> I don't want to grow organ organoids

from a from an IPS environment that um

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 uh, you know, a

liver [snorts] disease or a heart

disease. But if those are mutant cells,

that's a lousy experiment.

>> Yeah, I wouldn't I wouldn't say they're

likely mutant cells for that reason. I

think the biggest question would be

whether your induction of them to become

the organ that you, you know, want was

successful, was replicating the actual

organ itself. So you're you're

referencing these things called

organoids which are collections of cells

from a body of a human for example that

are are induced with various different

factors to grow to resemble maybe an

organ a particular organ.

You know I think all of us have little

doubt and this this is the source of the

California Institute for Regenerative

Medicine that making stem cells that can

become particular organs will at some

happen. We will figure all these things

out. And I I believe in science. I

believe in our ability to sort of like

test learn test learn test learn how

soon you know that becomes useful is a

bigger question. If you take out your

fiberblast 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. But the other problem about

those is you probably will die of

something else. You get hit by a car,

you know, [laughter]

it won't help you that you've got those

things bang. I think in some of these

cases like overemphasizing this might be

your point about the storage of of

umbilical cords is like at what point is

that a high odds situation where you

your kid needs it and you have it stored

away versus all the other things fates

that can be flawless as humans that have

nothing to do with you know stem cells

from the bone marrow and and to me

that's that's a point where you could

spend your life worrying about how

you're going to die and and maybe that's

not a good way to live. Well, that's

certainly not how I live right now.

There's a lot of

>> kind of excitement, attention around

so-called longevity. And um at at the

extremes of never dying or living to be

120, which seems to be the

>> perhaps the genetic limit uh currently.

Um it's not my fascination. I'm more

interested in living in the years I've

got as it seems you are too. Exactly.

Vital, healthy, you know, being able to

move,

>> sense, and and think [clears throat]

seems like and remember, you know, those

seem like the critical ones. You know,

you know, a moment ago you mentioned the

concept of like removing a bit of thymus

and I I think that the issues with for

me with that are or 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 thyic that so the thymus is

both the cells that come into it from

the bone marrow. So it 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 um

there's definitely you know pretty

strong work that says that you can

create sort of a thymic epithelium that

will do some of this work but whether

you know a guy at home [laughter] could

hold on to the thymic cells and we would

be in a position to do something

important for longevity in our lifetime

I don't No, I I I 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

were 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, they we thought

that we would have some stem cell

therapies, you know, within the seven or

eight year window of that bond, first

bond, and then there's a second bond. We

didn't really get very many out of that.

We learn a lot and that is the risk

>> about stem cell biology

>> about stem cell about biology and that

is the risk we take when we do research.

You know we're talking a moment ago

about how many times you might be in a

lab spending hundreds of hours and not

getting anything that you understand and

then and then one hour and you

understand everything because you know

so all of a sudden all those failures

make us make make sense. I think when we

get into some of this 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 [clears throat] 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 on the cusp for 10 or 15 years of

these things called cartis. Alex will

have told you about these where you

engineer your tea 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