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,
cleaning off your windshield. I'd like
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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
tumor. We will figure that out. But
we've been thinking, we've figured out,
you know, sort of for five or 10 years.
And it's it's, you know, that gets
frustrating. And I think it gets
frustrating for people that are like
waiting for it to um on the outside like
why can't you solve this? And you're
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.
>> 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 I'd love for
any disagreements. I'm not looking for
um just agreements, but
>> yeah.
>> So my observation from a couple decades
or more doing science and then mainly
shifting to podcasting, but this is what
I do. I talk with great scientists.
>> So that's the podcast. [clears throat]
So I'm very immersed in like what's
happening right at the cutting edge. And
um because of great guests like you, you
know, my my sense is that in every field
there's been like this kind of steady
pressure like 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. Uh we're going
to use calcium phosphate. Like great
research tools. Tons of things happen.
It's like we're going to modify genes.
Zinc finger nucleus. All this. Okay.
Crisper. Boom. And one thing just breaks
through and goes so much further. And
even though you know the ethics are
questionable, there are babies that have
deliberately induced uh gene alterations
with crisper cickle cell anemia
treatments as well. More benevolent
example.
than the person who went rogue and just
kind of did this in humans in China. But
Crisper just kind of broke through it
all.
>> This the excitement about stem cells led
to like Yeah. I mean even initiatives at
the legislative level and like all these
labs working on things and then as you
said it's kind of like
>> run up against the dam.
>> Yeah.
>> 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 is getting fatter. The
c the country is getting obese. What are
we going to do? Do calories matter? Of
course calories matter. This kind of
thing, you know, laws of thermodynamics
still apply. And then all of a sudden,
this freaking helila monster biologist.
>> Yeah. Yeah.
>> Tells people what they already knew
because the GLPs were already being used
as a drug, just not at significantly
high levels. Yeah.
>> 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, etc. I'm not I'm
not trying to discount any of that. But
I feel like that's the way science
works. It's like steady pressure, steady
pressure, steady pressure, frustration,
and something comes out of nowhere
>> and it almost seems prerequisite to have
all those years of frustration and
failure.
>> Yeah. And then and you say, "Well,
couldn't we have just gotten Crisper
first or the GLP's first? Like, why did
we go through all these, you know,
billions of dollars of expenditures,
time, energy?"
>> Yeah.
>> I don't know. I feel like there's some
natural order to this. And and I ju just
would like your thoughts on I feel like
it's necessary, but not sufficient to
have lots and lots and lots of failures.
>> Yeah. And I think it's necessary and
necessary, absolutely necessary to study
things that are just at some point
curiosities. And that sounds like
science is about trivia, but you know,
you you gave the example clip one.
Somebody was just curious as to why Hila
monsters. It was the feature was that
Hila monsters can go into, you know,
dormcancy for like 10 months, not eat,
and then uh and then come out and like
how do they manage that? And so that's
that was just like what is that? What is
it? What causes that? Crisper, 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 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 that and like kill
it. Well, that same you know that same
enzyme then which we now use for all
this human engineering came out of a
basic like how do bacteria defend
themselves. It's not anything about like
you know modifying single cell anemia.
It was about how does the world work? My
career is exactly as long as as the as
the lifespan of of this this field we
call cancer imotherapy. I did the first
imotherapy experiment. I injected a
mouse with an antibbody that I had made.
It was against molecules on te- cells
and I'd shown already in the lab that
that molecule caused the tea cells to
get more activated when you blocked it
and uh and we did a series of like other
mouse experiments of like all kinds of
diseases and it you know kept jamming up
the tea cells and then then you know Jim
I said we got some tumors in the fridge
and so we set up that experiment and uh
you know he injected this antibbody and
the tumors melted. Well that was the
start of cancer imunotherapy. We're like
that's that's this that's the origin.
This is the experiment for which let's
just be direct here that your your
adviser won the Nobel Prize.
>> Correct. Correct.
>> Did you at least get to attend the
ceremony?
>> Yeah. Yeah.
>> It was a little thing.
>> This is how science works folks. Doesn't
matter who did the experiment. Doesn't
matter what lab you're in.
>> Yeah. You got, you know, got to go to
the the afterparties were good. Uh but I
guess I take you back like we weren't
trying to cure cancer when we started
this. I the thesis project when I went
into Jim my my mentor at that point. The
discussion was like, well, there's some
molecules on TE- cells and 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 you had people say, why
would you do immunology? Well, we they
seem to be interested. And there was a
molecule. 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 could dial
up. You can say, well, if I could dial
up, what will happen to vaccination?
Well, it got better. What will happen
to, you know, multiple scerosis? The
disease got worse. You know, what will
happen to cancer? Oh, we can start to
have an effect on and and and you know
the X-ray you know the people were
studying physics and then it turns out
to be that that they were like oh I can
measure I can I can measure bone and
that's how we use X-rays now like to to
you know so there's all these examples
that everything you know like the big
things often come from these orthogonal
directions and then we realize what it
might mean and I think you have to start
there otherwise you'll just plow this
direction and you'll hit those walls
because you don't have the workaround
that comes with some orthogonal piece of
The orthogonal meaning at right angles,
right? So, you know, again, the crisper
came from bacteria, but it's really
useful in us as an engineering tool. But
we wouldn't have known that if somebody
hadn't been out there sort of saying,
okay, well, how do how do bacteria do
it? You know, how do they defend
themselves? Oh, they use this enzyme.
And I think that's a really important
message that that dispels this idea that
everything is sort of like basically
just easy for us to engineer. Yes, once
you have the crisper tool, it becomes
actually kind of easy to do some really
cool things with it and still creative.
But the fundamental leap that you're
describing, I don't think in many of
those cases that people were kind of
conceiving when they were in in the
first drags of doing it,
this would become an industry.
>> You know, this would become a whole
thing. And and maybe that's important
because you need to foster that. If if
everybody always thought they were doing
it to build a company and, you know,
sell a product or something, then then I
don't think we would do the things that
get us new. You know, that's that's all
that's all kind of what we already know.
That's human knowledge. We want to build
human knowledge. And to build human
knowledge, we got to go off the piece.
You can't ski on the slope. You got to
be like in the trees. And maybe you'll
bunk your head a bunch of times. I I
think that's the reality. And it's like
you got a lot of people out there that
are that have decided to do that for a
life because it's a it's a it's a chance
to like solve a puzzle. It's like
there's there's puzzles about how the
world works. And if you've ever done a
jigsaw puzzle where you there's always
like the oh you get in and especially in
the end you're like how you what pieces
come together to do it. I think that's
what makes this whole science thing
really fun. It's that's the that's the
reward is that you get the puzzle piece
in and you're like oh you know it makes
sense that now I know what I've been
building. and I've been building this
puzzle and and then you go back and you
do it again because that's really
satisfying at the end of it even though
you know you again with a family puzzle
the first parts are so hard thousand
pieces and you you maybe find the edge
but the intervening where there's like
all clouds super hard and and I think
that's that's that is what science is a
lot about is uh is doing that and then
realizing what the picture is you know
what is that picture of and then then
all the you know the brakes are are off
I often tell people that if if an if an
experiment if experiment you'll do in
lab has a 10% chance of yielding
anything interesting you got to do at
least 10 you know to even meet the
fundamental stats you actually have to
do quite a few more. So that's where
it's not a um it's not a cost-effective
thing if you it's it's really difficult
to be a scientist because there's no
quid proquo. There's nothing there's
nothing to say if you put in five hours
that you'll get five units of goodness
of of knowledge out of it. A lot of
times you get zero and and but then
sometimes you put five and you get 500,
>> right?
>> And and those are the jackpot moments
where you're like
>> it's like life.
>> It's like life. It really is. I have to
say anyone who's considering a PhD. We
had a call in from audience recently and
someone said they're finishing
undergraduate, they want to go the or
finishing graduate school, should they
go the research route? They want to do a
posttock. And I'm like yes, yes, and
yes. I rather than answer publicly, I
decided to just have a call with this
individual because it's a rather niche
qu question. But I mean also just in
training your reward system to work for
5 years on something
>> is so valuable especially in this day
and age because everything else feels
like it comes at like warp speed.
>> Yeah, you know it clicks.
>> Yeah. Like and um to just put steady
pressure on something with all the
failures and all the things and then to
finally complete something it's a lot of
people think it'll be underwhelming. I
think I think quite the opposite.
>> Yeah. It's like anyone that's like done
a triathlon or, you know, raised raised
a kid or done anything, you're like, "Oh
my goodness." Like, and that never ends,
right? There's nothing better than these
long-term investments.
>> Yeah.
>> Nothing.
>> Yeah. When they break through that
you're like your analogy, when you break
through that dam or when you realize
sometimes that you broken through the
dam. That's that's one of the funny
things about I think science and maybe
it's true in triathlons and stuff too
where you've realized that you've all of
a sudden got somewhere.
>> I haven't done a triathlon so I have to
be fair. Rob, our producer sitting to
our left is he has done many Iron Mans.
Um, 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.
>> And so, a lot of it is about learning
energetic control, like doing science
that is, or anything is about what not
to think about, what not what to force
yourself not to do or think about.
>> Yeah. 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.
>> Okay?
>> And I'm going to pose a question that
may or may not fit with um this
framework, but either way, I'd like like
you to educate us on it.
>> I'm fascinated by these old kind of
barbaric experiments in medicine. Um
wonderful book, by the way, folks, is uh
The Prince of Medicine about Galen. If
you ever want to learn about how we
learned about medicine back when, it was
truly barbaric. It was like surgeries
done on warriors and without anesthesia.
And we've known for a long time that if
uh somebody, god forbid, has a finger
lpped off or a hand lpped 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.
>> Is that true?
>> Yeah. There's a bunch of juicy stuff in
the in the gut that maybe it's the
warmth. Maybe it's the immune system.
Okay.
>> Maybe it's the lack of infection from
being inside as opposed to outside the
body. Who knows?
>> Gut. You mean the intestine or you mean
the sto within the stomach? The stomach
itself.
>> Yeah. I'm not suggesting anyone do this
experiment. As I started reading into
this, I discovered that there are a lot
of really cool experiments not just in
limb or tissue preservation and and
restoration. Like for instance, I've
talked many times on this podcast about
the fact that above our the roof of our
mouth, we have this small cluster of
neurons, the super kaismatic nucleus
organizes the circadian rhythms of every
cell in our body from the genetic to the
transmitter level, peptides, etc. Keeps
us
>> sleepwake cycles, does all the
organization that we need for circadian
rhythms. So much so that you can take
just one subpopul of these neurons, the
calbindon expressing super chaismatic
nucleus neurons. It's like 5% of the
total neurons in this already tiny
cluster of neurons and you can
transplant them pretty much anywhere
and certainly in the brain and you'll
restore the circadian rhythm of an
arythmic 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."
>> Yeah.
>> And then I started reading about, oh,
like you could actually take perhaps
like a little bit of pancreatic tissue
and like stuff it in the, you know,
under the skin. 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.
>> Yeah. But maybe they just need to be
there. Now, no one should test this
hypothesis unless they have to. But when
we think about the immune system,
>> you described the function of the thymus
beautifully. You talked about the bone
marrow, but you also talked about the
massive migration of these cells that
are working in this network.
>> 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 for which I'm asking this, but
I'm just going to tuck that away uh to
peique 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.
>> Well, the the answer is yes and yes, you
know, it's it's both. So although I
described the immune system in the
earlier part of this discussion as super
migratory, it you know hitches a ride in
the blood gets into tissues. It travels
through your lymphatics. There are these
things called lymph nodes down the
lymphatic tubing which for those that
don't know lymphatics are like drainage.
It's how you drain the the fluid back
out of your tissue. [snorts]
So [clears throat] although there's you
know these mass migration of cells
there's also in like even in just in T-
cells there's tea cells that lodge in
particular settings and they you know
act to protect that tissue and they um
and they're resident cells of those
tissues. they never leave. And um so
both are true that you have, you know,
parts of your immune system that are,
you know, protective or or like
nurturing of particular areas and then
there's ones that are circulating and
can hit any any spot. You know, going
back to your idea of organs and and such
being moved. I think there's two
components of that that you might be
thinking about. One of them is the
question of whether the organ can
survive in the new space like does it
have the growth factors and the blood
flow and the and lymphatic outflow and
maybe even some neuronal activity that
you know makes that tissue work. So so
that's where like if you take the
pancreas you can famously put it
underneath a 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, you know, type 1
diabetes or 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 is not
self. It's something foreign and it
wipes it out. And that's the source of
what I said earlier, like your immune
system can be quite dangerous.
So like when you talk about this concept
of like spatial um there's a few things
to bring in. One is does the organ can
the organ get what it needs and then
does the immune system accept it in some
ways in that environment. And that's
where like some some of your immune
system that lives spatially in certain
areas is going to be very like defensive
against whatever it's you know specific
against in that area but may not care
what's happening elsewhere because those
cells just aren't it's not like the
brain where like if I I do something
here it's sensed in my brain immune
system that if it does if the cells
don't migrate they don't have really a
lot of ways to communicate that they can
they can hitch some signals on neurons
and that's a really interesting we could
talk about the the capacity for your
brain and you know the insular cortex
there's great set of stories emerging
about how your insular cortex can
program your immune state into organs
and can via via the Vegas can can
essentially program
>> by levels of of calm or stress or by
thoughts themselves.
>> Well, the the one the latter one is the
one that gets me super excited about the
possibility that you could have triggers
for thoughts that so the insular cortex
as I understand it it's a source of some
of our moral decision- making. And it's
also the the thought to be the part of
our brain where if you cut your hand and
and I see a bleeding, I can feel it in
my hand, I oh ow. You know, I can sense
and you can sense each other's pain.
It's a set set that this very nice uh
Israeli group did this Royce lab did
this very nice study where they induced
into the guts of of mice inflammatory
bowel disease. They fed them a really
kind of weird sugar that causes the the
bowel to puncture and then they get they
get a really bad, you know, stomach
ache. um uh stomach ache, inflammatory
bowel disease, diarrhea and um and in
that period they used you know you know
what dreads are. So they they marked um
for the for the crowd it's they used
they they used they used a way to to
mark all the neurons that were firing
during that period in the instrumental
cortex and then later they could fire
them like after the mouse had recovered
and the they saw evidence that the
immune system was resetting up itself in
the gut as if it had just been punctured
you know like with and the cues for that
in that case were a drug but we know
that we can you know cue the insular
cortex like me watching you do things
>> so it's always it's maybe wonder whether
you know like some of the things we we
smell all cut grass and we can it'll
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 our you know
our ability of our thoughts to control
that region are are going to be revealed
to you know to have potential that you
could train
>> uh you know train yourself to to you
know to bring up an immune state in a
particular tissue.
>> 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 like if an animal or or human, let's
just keep it at humans, gets um shocked,
scared, or traumatized in a given
region. Yeah.
>> Or even I've had friends visit San
Francisco and get their cars broken into
and their computers stolen.
>> You can develop a context context
dependent or and or place dependent
memory where you kind of don't like San
Francisco as much even though the rest
of the trip was awesome. That's a pretty
broad interpretation. or um you have a
great experience someplace and you
actually really love
>> San Francisco because you met your
future spouse there or you just had a
particularly awesome experience there
even if it was just in one part you
might feel better about your computer
getting stolen anyway okay insula seems
like a you know let's take the positive
example let's keep it positive for a
moment I think what you're describing is
that if we remember the positive thing
if there was a positive immune status
>> associated
The immune system is also part of that
contextual memory. And [snorts] 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.
>> That's what these studies are starting
to emerge. And
>> that's cool. That's really cool because
um we've heard for so long that like we
know that chronic stress impedes
>> immunity. We also know that acute stress
>> boosts it. And that's something that you
know with all due respect to my
colleagues who've focused on the ill
effects of chronically elevated cortisol
like that the the immune enhancing
effects of acute cortisol and stress are
are really important and and I think
they've been overlooked. But I love this
because one of the problems slash um
luxuries that I I have is I sit sort of
at the interface between like real
science and biology and like what most
people perceive as complete nonsense
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. One of my friends who's a
faculty, Dan Lim 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 um 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 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 that
the concept of I mean I'm sure you've
talked about this before of of
meditation where the idea is that you um
you know you it's one of the ways that
you can control your autonomous nervous
system is through is through your breath
>> um that happens with meditation I think
that
>> to me there's something intuitive about
that. But you know, 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 and 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 a regions
of the brain and however those are
triggered. Now, maybe, you know, again,
I've I've lost that. 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
there kind of crazy thoughts, but but
again, there's an element of that that's
intuitive, too, where we say, "Oh, that
seems to be the case. My mom makes me a
comfort meal." Is it really the meal
settling in, or is it just the that the
sensations that make me feel like, you
know, less, you know, stressed in one
sense,
>> but maybe also to this point and
literally resetting your tissue. I'd
like to take a quick break and
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I'm always struck by um extreme of
personality but in both directions. So
there are these [clears throat] people
who just say like I don't get sick
>> and they don't get sick and it's super
frustrating because I'm not one of these
people that's very sickly but I
occasionally get like a sniffle or a
cold or something you less and less with
each year because I do feel I pay more
attention to the sleep piece
>> um than I certainly than I did when I
was a graduate student postto or junior
professor but there does seem to be this
quote unquote
>> positive or let's just call it a
reinforced mindset as opposed like
[clears throat] an immune rein
reinforcement associated with mindset
because um some people will say like I I
just always get sick and I believe them.
They always seem sick. But it could be
that um you get sick in in a given
environment once and then you you just
decide that you're sickly. So then you
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 and
physicians are like yeah you got to be
kidding me like but because immune cells
don't listen to thoughts they listen to
brain states
>> triggers of some sort
>> triggers of some sort right um and then
there's like as humans we have this
obsession with language that makes it
seem like you can you know write
affirmations and then it's the word
content but it's the feeling state
associated with that that
>> a biological level makes total sense. So
we were talking about spatial biology
and the fact that you can tuck some
pancreas in the kidney and unless they
someone has type 1 diabetes
>> a lot of the functions of the pancreas
can um can persist 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 thyic tissue
bank it just later like put it in a
slowrelease 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 Neurolink
[clears throat]
now, who actually embedded a little
radio receiver under his hand to be able
to open his
>> um 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 thyic cells and in a you
know a sterile capsule and sliding it
under the skin, you know, people get
their ears pierced with, you know, right
>> less less invasive uh procedures. Why
not?
>> Well, I mean the question is why would
that you know is that likely to work?
You're basically remember how we were
just talking about if I do 10
experiments, one might work. yours isn't
a bad idea, but you know, is there it's
it's more than likely at one of the nine
out of 10, I would guess.
>> Sure. But is there a correlate from any
studies on animals? Um I mean, we know
that in a lot of studies of cancer and
tumors, I used to see these mice down in
the vivarium,
>> they would slide tumors under the skin
and study them
>> and give animals drugs or give animals
stuff.
>> Very common. Yeah.
>> Yeah. Uh tumors are happy to thrive in
novel environments. So why wouldn't
healthy cells
>> No, I think you can. I think one of the
things that comes into play a little bit
about that that's more about you know um
replacing an organ with one that might
be better is that at some point if you
come in so one of the the challenges of
tissue engineering is if you want to
bring in new genes the vector the
material the the 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 a plasmid you you effectively
are giving that a new bit of identity
and when that when you go to transplant
that organ back in it's seen as foreign
>> and it's it's just like you just put an
infected cell in you you know as far as
the immune system knows all of a sudden
there's a cell with huge number of new
things being expressed and some of them
viral literally so you know that's a
that represents an issue I think when we
talk about any kind of you know sort of
engineering at the you know the moment
is is if you engineer a system to be
maybe better the immune system isn't
necessarily going want better and and so
you have to overcome this issue of
tolerance maybe at the same time and and
and again that's why that particular
experiment depending on what you're
putting under the kidney capsule or
whatever it matters what the immune
state is and what that thing is as to
whether your immune system is going to
let it fly.
>> I'm not considering doing this. I just I
think we are I don't know how old you
are, but I can guess based on some
mutual friends we have, but I'm guessing
>> that a lot of people
who are able to understand speech,
they're old enough to understand speech,
are thinking that in our lifetime, we
are going to be able to use our own
cells or peptides or synthetic versions
of peptides from our own cells and and
so forth to to overcome a lot of the
issues that our parents and grandparents
were not able to overcome. you know,
with regards to like the peptide side of
things and even the cells and this is
maybe where you're going with space is
that context does matter for the immune
system. So,
and and it matters for all biological
systems. I'll just give you an example.
We did a study of of wound healing uh
some years ago and if you have a wound
in a mouse that's maybe just a like you
know if you ever have a melanoma removed
they do a punch biopsy. It's a little
circle. So you can do that in the back
of a mouse and then you can watch the
wound healing happen. The there's zones
within there where certain biology is
really important to be happening and
then so so imagine the the wound is like
this and it's open. The cells like one
layer back are doing certain things but
the other ones behind that are also
induced to do so. The wound isn't just
this area. It's 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 you know
like like a peptide or even just a cell
type you have to be a little bit
conscious of like where it's going to do
the work you want it to do and the
natural system does that naturally like
the cells on the inside actually
instruct the cells one layer back
>> but you don't necessarily want everybody
getting the same signal
>> so like development happens that way you
know about gradients and we were talking
about this earlier that there's
gradients so so I think one of the
tricks that we don't really understand
about this is when is something good uh
for a process and when is it only good
when it's given in the right dose at the
right time.
>> And I think that's one of the tricks
about some of these things. And again,
that's where, you know, both in the lab
and, you know, like I I would say that
more so than ever in in 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 and then you have this rise
of things on the internet of of
anecdotes that become seen as data like
I took this thing and this happened. And
that's you know I I I could drink this
drink and have something great happen to
me or something bad happen to me but
might have nothing to do with the drink,
right?
>> You know that that issue is one that I
think is really um is really critical in
in this in this window of time right
now. And honestly I don't know what to
think about the idea that people you
know do experiments on themselves. I I
think we all want to improve ourselves.
We all do all all do some kind of
experiments on ourselves. you read a
book, you're trying to improve yourself,
right? Um the physical one gets a bit
tricky when uh you know, you're not sure
whether something's going to be
dangerous or not, but
>> 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 and other um trials for
this. I
>> think I would personally. I mean, just
>> Yeah. I mean, I'm I there are a few
areas well where I am um a bit more
adventurous, but for the most part, I'm
like, you know, based on my training and
[clears throat] background, I have to
orient toward, you know, I'd like a
bunch of Let me put this way. I'd like
to 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.
>> 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 open. Well,
I'll just point out that that the one
group that's completely no matter
whether they're hesitant against
childhood vaccines and the number of
them we get and the the fact that the
government makes you take them and these
sort of things, if those people have
cancer, they're very interested in
vaccines because it's a there there's
really good data that you can promote
more immune cells against the um tumor
by making a vaccine that consists of
some of the proteins and peptides that
are unique to the tumor and not
different from you. and you introduce
those as if you would introduce a virus
or anything in in a childhood vaccine on
similar concept um just different
peptides. their peptides from the tumor
and and in those situations it's
context, right? So if if you and I had
cancer and we don't have the the
conventional cures are not going to work
on us. We know there we know statistics
really well. Chemo is not very good for
a lot of you know cancers and that's the
only thing we got. But if you have
access to something that's relatively
new and particularly vaccines despite
what you know some people worry about
they're pretty safe. Um, and so the the
certain die versus try out a vaccine
drives a lot of people to be interested
in vaccines. And I would say yeah in
that case it's a really you know you can
see where people's their their question
about whether they're going to try
something or not is very context
dependent
>> very I think uh I don't want to go too
deep into the vaccine debate and I don't
want to be a spokesperson for either
side because that's not my role today
but
>> I think that the um the what you refer
to as vaccine hesitancy actually comes
back to an earlier issue that maybe
you'd be willing to comment on.
>> Sure. um which is I think there are a
very large number of people for whom
they are neither antivaccine
nor super pro but they are um they're
asking about timing and combinations.
>> Agreed.
>> They're saying okay listen and we had
Jay Bachari on here and I've had several
others who said maybe there should be an
investigation of the spacing of these
things how many um how critical it is to
do at a given age you know um and on and
on. We could pick any vaccine for that
reason. And as an immunologist,
do any of those questions make sense to
ask? I mean, I could see how, you know,
bombarding the immune the young immune
system with a lot of vaccines is a very
different thing than spacing out the uh
delivery of those vaccines. I'm not
saying don't give them all. I'm saying
>> over what time window does one give
them? Yeah.
>> I think a lot of people, many more
people are asking that question. Yeah.
It's just a quieter murmur
>> than our um saying, "Listen, we don't
want to take any of these things."
>> Yeah.
>> We don't want our kids to take any of
these.
>> Well, I've heard that, too. And I I
think there's some fair aspect to which
most of these vaccines were not studied
in the context when they were studied of
of what it does, you know, in in in
combination and and these sorts of
timings. The fact is that, you know, the
the evidence that there's that there's
bad things happening doesn't look to me,
you know, tremendously strong. It's
almost like anecdotal sort of
information. So,
>> unless it's your kid.
>> Unless it's your kid, in which case
you're going to look for an explanation.
So, I I don't know.
>> Just being fair, as long as we're
admitting psychology as a factor.
>> Yeah.
>> Yeah.
>> Yeah. So, there there's fairness on both
sides of that discussion. And I think I
think that almost certainly where we are
now, there's probably ways to put
together vaccines and certainly more
convenient ways. It's I I I as a parent
I I actually had something very similar
where we delayed you know my first
daughter's one of her vaccines partly
because I know that that as a you know
like there's a certain element to which
when we designed a protocol like the the
protocol for imotherapy of cancer for
patients was was actually based a little
bit on the mouse work a lot on the mouse
work that I did you can imagine that
mice and humans are quite different but
that is the protocol the protocol is
protocol and that's how it's done in
medicine and that's because you have a
fairly good sense of the safety of it
because of statistics
But that isn't to say that it's the only
protocol that would work. And I think
you're getting at this concept like
could there be at least a more
convenient one
>> and also or safest or even one that is
less disruptive to the lives of the
children and the parents. We we delayed
one of our kids vaccines, you know, by
just a month or something because uh she
had not been feeling well just straight
up. And it is true, you know, and I'd
say that a couple of the vaccines that
have come out that I've had recently,
the shingles one is a good example. I
had the other has knocked me completely
out and it, you know, it's very very
heavily advented. So, it's clear that
it's, you know, it's having to um does
it does it need to be, you know, I
actually don't know. I don't know what
studies were done. And and there's kind
of an aspect to which you I don't know
that we're all um being shielded from
the information, but I don't know that
we all know how to read the information
about how these regimens were chosen.
>> Um some of them are chosen by competing
far 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. And I
don't know how much of it also
represents the one problem of science
that I could talk about is this um this
issue that's a lot of science treat
science as a kind of a papacy like we
know the language we know the facts and
and we probably don't have time to tell
you why we think this and where where
the holes are.
>> Excuse me for interrupting but you know
a huge basis of this podcast is to
counter exactly that. I know.
>> 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 it was and as things get more
politicized, there's less incentive to
give nuance. I actually really
appreciate you providing some nuance on
the I mean it's clear where you stand on
vaccines generally based on what you've
said but you're you're offering perhaps
the opportunity for for better
understanding and certainly delivery of
the information.
>> Yeah.
>> Yeah. I mean it's it's a huge problem.
>> Yeah. Well, I guess it's it's one of
those ones that I can only speak about
what I did, right, as a as a as a human
when I had kids and I looked at the data
and I have probably better capacity than
some anyways to read it and look at risk
versus harm, you know, the percentages
of these things. I absolutely, you know,
vaccinated kids and that was it seemed
like it seems even now like a a
reasonable no-brainer. But I just told
you too that I I asked to go off
protocol because at some point I know
that these protocols have a little bit
of like again they were designed on a
one study but it doesn't mean that it
doesn't work if you wait another month.
In fact if you do if you've done enough
mouse experiments as I have you know
that when you vaccinate on a slightly
different schedule you can still end up
with the same outcome you know that is
protection you know with slightly
different schedules. It's not that
convenient for doctors and hospitals and
and even sometimes for patients to get
off on, you know, like weird schedule
and then you forget a dose and then it
isn't as effective, right? So there's
there's efficacy that comes with, you
know, trying to follow the protocol and
because the protocol has some
convenience built into it that means
you're going to do it. It's um it's like
it's like brushing your teeth in the
morning, you do it in the morning, the
evening, it's when you do it and so
you'll do it twice a day. So there's a
lot in this. I mean, you know, there's a
lot of politics, I think, involved in in
vaccine 2 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 it's a surrogate question
to the vaccine one where vaccine is, you
know, if there's a harm, who gets to
choose with the harm 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
bath water. I don't think you personally
like I wouldn't not immunize my kids.
Could there be additional studies about
the combination of these into like fewer
shots? I think so. I don't see why not.
Here's where you get the financial re.
What's the benefit to any pharma company
of doing that?
>> Well, I think this is again I I
[clears throat] have to be careful that
I don't place myself into an advocacy
group that I'm not. I I'm I look at
everything on a case- by case basis. I
try to do that.
>> I really try to do that. But the you
know and I've tried to be in recent
years more open to the to at least
understanding what the anti- big pharma
stance is really about.
>> You know it comes up a lot around SSRIs.
But you talk to somebody with clinical
grade OCD and they will tell you that
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 in
taking insulin or you know and till
recently the GLPs were mostly available
through pharma. Now they're sort of it's
kind of the wild west. People are micro
doing them from all sorts of
compoundingies 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 that's
really the source of the problem there.
There really hasn't ever been a
conversation quite like this.
>> Yeah, I agree.
>> At least not one I've seen publicly.
Yeah, there 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.
>> Yeah. Yeah. I mean, I think that
probably is frustrating to very
frustrating, excuse me, to a parent
whose kid seemed essentially fine, got a
vaccine, and 3 days later started
exhibiting symptoms that then set them
off on a course that was um really,
really tragic.
>> Yeah.
>> Um 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.
>> Yeah. why they would feel that way.
Whether or not the basis of their
feelings is exactly right, I can't speak
to. But you can understand if your kid
is one way, walked out of the doctor's
office is is another way. And you can't
do anything about it. That's got to be
>> I mean beyond maddening
>> 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 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 um
>> guilt/ anger. I mean there's a whole
psychology to it that's completely
understandable.
>> Yeah.
>> Didn't wander into the clinic.
>> Yeah. Well, I mean, you know, on the way
over here, I was thinking about some of
the things that, you know, are happening
in in uh medical space and, you know,
you guys obviously from time to time
talk about peptides and these sorts of
things that people are using, you know,
off lab, well, not even off label,
they're just getting them from from uh
who wherever the internet. And you know
that I was thinking, well, you know,
there's a funny thing there because the
legitimacy of pharma companies has sort
of fallen into even worse straits than
before because I think it I was thinking
about this a lot of it does relate to
the fact that we are advertised to take
a lot of things that often aren't you
know the side effects are worse than the
than the symptoms that we're leaving and
and that sort of uh you know again I I
may find myself like having a bunch of
colleagues hate me for talking about
this with you but I do think it's kind
of important at some point to surface
where all this comes from you know and
and the idea that we can do experiments
on ourselves on our own bodies. Again,
it's quite different to say read a book
although you can be infected by we
believe like by you know strict
scripture and things and than your
behavior but somehow [snorts] in here
this idea that that um you know we can
be told to do things by people that
aren't quite in our best interests. I
think it opens up the idea well why why
can't I choose my best interest? You
know who who are these experts that I
can't always trust?
>> What's more American than that after
all? 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 and and maybe
even surface any of these ideas that are
hard to talk about like should we trust
farm companies? I know a lot of people
that work for pharma and they really
they are doing good. They they you know
they're like you and me. They they
really think and they are treating
disease. They're making really good
drugs and they do really good things.
But that's not always true. Not just
just because you know 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 you know 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 these kind of perverse incentives
exist. I I wonder why, you know, like
pharma companies haven't um gotten
better tests for who's going to respond
to these checkpoint drugs that we made.
We've had we've had a few papers that
show who are the responders and who are
not. But it's still the case that if you
get come in with melanoma, even though
there's only a 50% chance you're going
to be cured, which is great. You used to
be zero with these drugs, you still take
100% of the market takes that drug.
Well, because the 50% that aren't going
to respond, they don't know who they
are. 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
out there going but there's no there's
no positive incentive to do that study
to study those things and I think it's
kind of true in some of these other
drugs that we've been you know brought
brought forward some of which are better
and worse than others we could told that
this is going to be good for us and and
we should take it and and there's a
again you're you're getting to the
American kind of like mentality which is
to say well some point if you fool me
twice or you know I'm not going to
believe it and and I might not believe
it against the entire spectrum of things
called science. And the problem is that
there's people like you and me that are
trying to actually do and and most of
us, I'd say 99.9% of us are working our
asses off to like you 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 as a as a
species, should you distrust the entire
class of science? Probably not. You just
need to maybe make it so that knowledge
is is freer and knowledge is better
communicated and that
>> and that um and you do watch out for
those situations where there should be
you know uh you know and maybe vaccines
are one we you know we just need to do
something sensible like what you're
describing and just to do a study and
say let's do that study and and make
that very public that we do it and say
we're going to do that and and and
obviously people can sign up for you
know be you can have this regimen or you
the old regimen or the new regimen and
you know again I I may speaking. I don't
do vaccines. It's not what my lab
studies, but there could be some sense
to saying, well, maybe science as a
whole could take this on and say what
would be maybe the answer isn't just say
no vaccines and we we think they do.
There's good evidence that they're
protective. But to the extent that
you're coming 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?
>> Yeah. Well, the discussions haven't
happened and I should say a couple of
things. Um, first of all, thank you for
being willing to venture into this area.
I seriously doubt that any of your
colleagues are going to be upset that
you're having this conversation. I will
make sure that anything we put out is in
context. If anyone cuts a clip, I will
be the first to dive in there and say
this is taken out of context. It um 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 uh traditional
medicine and vaccines etc. I will say
this
the idea that you need to push back with
a with just a fire hose of do this or
else
>> did not work.
>> The pandemic proved that the in fact I
think one of the biggest mistakes was to
have one individual as opposed to a
panel of people
>> with more nuance communicating public
health information at that time. any
person, scientist, doctor, or otherwise,
who thinks that the way to convince
people to change their behavior around
vaccines or anything else is to just ram
it down the public's throat and say, "Or
else, you're whatever. You're political
this or you're a fascist or whatever."
Okay, that is proven to be wrong.
>> And the path forward is really this kind
of conversation. It's highly educated
people like yourself in the educated in
the immune system who understand this
who have children who've made certain
choices saying yes and I can understand
why you would be considering the
following um questions and we should do
a study and and in the meantime you're
not preventing anyone from getting
vaccines. There's now a hunger for more
nuanced conversation around these
things. I think it's the right time to
have it when we're not in the throws of
a pandemic.
>> Yeah.
>> Yet yet. I mean, there's some things
that are on the rise. It is scary. I'll
I'll be quite blunt. Um, you know, the
the rise in measles is scary. People
say, "Well, measles, they used to have
measles parties." Talk to somebody who
had massive inflammation
>> and brain inflammation from measles. Not
a pretty picture.
>> Not a pretty picture. Yeah.
>> So, I think it's great that these
conversations are starting
>> and it won't be taken out of context.
>> Yeah. Well, I mean on the vaccination
front, I mean, I just wrote a little a
little subsequ um you know, the origins
of small vaccination and I think what's
lost in those stories is if you look on
the internet that the the absolute that
that's a terrible disease. I mean that
you know the reality of what we're
protecting against we haven't it's
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
>> small box was dreadful
>> so so there's an element of that though
that I think you know that we have to
make sure that the conversation focuses
on on what are we 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 smallox or got
measles or got mouse and and and and you
know, as we know like measles is not a a
theoretical again, you know, that that
concept uh is enough to say, well, there
is a risk of that. And that's one where
you
>> it's like you you know, 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 [clears throat] think that's
also an important again that's what
that's me as a parent saying and I did
look at the history of these things and
they really are bad and so we are you
know we are defending against something
but you know is there a better way to do
it uh you propose experiment that's
let's you know I think there's a you
know like cutting off you know the
concept of human curiosity and science
at the legs is probably not the way to
figure something out from my experience
you you you dive in you think of the
experiment they 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 u
you know like the the danger of of of of
bad stuff happening versus the the odds
of an adverse effect they were all that
high but you know 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.
>> Mhm.
>> Which tells you that an immune challenge
can affect the neurons of the of a
developing pup. So, it's not outside the
realm to say that in some situations and
in an aduant situation. Again, I I may
regret saying this because it's, you
know, it's going to open up a
conversation to have this, but to say
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 the the
cells of the brain.
>> In fact, one of the one of the best
experiments that I love along these
lines, it's not about about autism at
all, but it's about um when you get a
flu,
>> you tend to go you 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 in a hole. There's an experiment
that was done that involved injecting
gamurfon 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
[snorts] they become uh you know
socially isolating from just the
molecule that's made by the immune
response during infection
>> not even from being sick
>> not even being sick they're not sick
they just are given this this cue that's
part of the systemic immune response and
then they they show the signs of social
isolation and
>> the lab that did this um also showed
that the brain has receptors for these
immune molecules. And you know the
simple conclusion of that paper and you
know there's still always work to be
done but simple conclusion was that the
brain could sense infection and and it
would affect behavior [snorts] um even
in mature in us as mature. So, you know,
again, there's these these ideas that
there is there's something that I mean,
scientists use that infection of a mom,
you know, to lead to neuronal changes
that lead us to be able to under study
autism in later mice. So, there there's
definitely potential there. I don't know
that the vaccines and all of them and or
whether there's a circumstance or
whether it's, you know, again, the mom
actually had a fever before and that
vaccine now disgued or didn't or just
circumstance because you give vaccines
at 2 years of age, which is when autism
appears. there's all kinds of options,
you know, and that and and the sort of
anecdotes of of that. And and um I just
think that that that fact that, you
know, the way that we study autism is by
giving a pregnant female mouse an
infection is sort of like, okay, that's
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 we need data
and and we're in we definitely need
data.
>> We're almost in a co situation. I
describe the co 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 it's not just the
publishing problem. It's how we how we
synthesize knowledge that under data
sparse circumstances to make decisions.
I think we're not very good at that
society. Um you when we have tons of
data and it says absolutely if you have
cancer and you take imotherapy then
there's a 50% chance you're going to
revive great those stats are solid
they're very good and I would I would
take that drug every time but if it's
sort of a case where you're like no
there's some things that are happening
and there's some other things that
happen we don't know you remember at the
beginning of co 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 was it could we get it from
blood um and and that kind of went on
for a while, right? And this was the
source of like a lot of confusion that
came from the medical it was seem seen
as confusion that matter of fact it's
like do you mask 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 well I think
that's the major argument when there you
know there are people that will critique
people saying okay your experience is
anecdata it's correlative but then the
the the w with regard to vaccines and
autism and other issues, but then the
push back is well this vaccine, etc. was
directionally guided by sparse
information to begin with under times
[clears throat] of pressure. There's
financial incentives. So, it's just this
pingpong 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."
>> Um, but you have every right to ask your
doctor,
>> right? But they're not asking because
they're extremists. They're not
antivaxers. They're asking because they
love their kids and they've seen enough
things to call into question the
incentives and they just know that the
conversation cannot be as polarized as
it's presented to them in re in reality.
The data cannot be as polarized as it's
been presented.
>> Yeah. Certainly certainly in media some
of these things get presented quite
quite um you know inflammatory and again
if if newspapers want to sell a
newspaper they show a plane crash you
know so it's not happening every day
>> but they'll show you an airline ad in
the same issue. Well, there's that, too.
Yeah. So,
>> I think one of the interesting things
that we could get into is that in you in
a lot of these studies, scientists are
there's a motivation to to make the most
of your result. And we've talked about
why that's important is that if you find
something orthogonal, crisper,
checkpoint blockade, uh, you know,
x-rays, you look for that orthogonal use
for it, right? And you or that that
orthogonal meaning that would sometimes
be called 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
[snorts] I think one of the things
that's that that is lost sometimes is
that some things are not extensible. So,
you know, you can imagine that like if I
if I had something that move makes a
cell move that that might screw up the
whole system forever. But humans and our
bodies turn out to be remarkably
resilient. I mean, we can go from
minus20 degrees to, you know, 110
degrees. We can not eat for a long time.
you know, all you know, all these things
don't cause us to fall apart. So, if we
didn't have resilience, I think our
species wouldn't exist because there's
all these pressures and all these
varieties of life under which we lead.
And I think a lot of science sometimes
doesn't, you know, and and from the
outsider, even as an insider, you can
read a paper and they they they point to
why it might be important, but they're
really doing that to to to get garner
interest for their story, you know, and
then say, "This might be important for
this, but I haven't shown it's important
for they don't say it's important as it
might be important." And they're trying
to look for that orthor that orthogonal
or that extensibility of it. And I think
that's kind of important also just to go
a little bit off this topic for a moment
in how we think about drugging diseases
as we go forward. And that is to say
we've looked for these oneanddone drugs
that you you take a pill and it cures
everything you know forever. That's sort
of found of youthish. And um you know we
found a few of those. I'd say check one
blockade is one of those that you can
take it and you know in 50% of melanomas
everything the tumor goes away and
everything's great.
But most biological systems, if you have
one button to push, they're super
non-resilient. A virus can exploit that
button. Uh, you know, that that can
cause, you know, collapse. And so, most
things are wired like in these really
complicated ways. And I think what a few
of us are thinking, this is for cancer
in particular, where you want to get the
immune state from like, you remember I
had a little concept of a fuel gauge.
You want to get it from one position to
another position. It may not just be
about a push here. You may have to push
some cells that way, create some new
environment that looks like development.
You know, your cells develop through
states and and you push the the
biological systems to reach this new
state in a way that doesn't look like
the linear between like low immune
reactivity and high reactivity. You
might have to push it in a serious way
because resiliency the res the systems
like even in chronic disease but even in
health we're pretty resilient and like
we you can stand up to a lot of stuff.
Can humans do that even in the context
of abundant funding for basic research?
Can what you just described actually be
tested to the point where we can develop
things? And the analogy here is I had my
dad on the podcast. He's a theoretical
physicist and he explained to me that
one of the most important things you
learn in physics is that you can't
really understand quantum mechanics
using your logical brain. You need the
math to prove it. M
>> 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 2026, we're running up
against this barrier where by virtue of
the sociology of science that papers
need to have one maybe two take-home
messages by virtue of the fact that
>> there's 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?
>> I take the standpoint that AI is and I
think you know this is back to talking
to experts. It's really quite good at at
at producing stuff that is in the
corpus. The corpus is the knowledge that
we already have.
almost by definition when you're coming
at that with orthopedic discovery you're
discovering something it doesn't exist
in the corpus you might have hints of it
there but you still have to do
experiments at some point so if I mean
going answer you know 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 silicico a network
where I can look at how all those cells
are wired together now and I can ask you
know what would be the possible
consequence of clipping this molecule's
ability to touch that cell. [snorts]
That that's that's now doable, but it
relies on an area of math is not really
AI. It's called machine learning. And
sometimes these things are conflated,
but machine learning is basically
looking to say what are some of the
relationships that I can discover about,
you know, um the relationship between
this feature of the cell and this other
feature of the cell. So it's it's
learning about it and then it's it
allows you to propose a bunch of
experiments but you still kind of have
to choose and select which ones you're
going to do. Some experiments are just
really expensive 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 some
things in a greater detail than maybe
the machine learning gave me but it's
not clear to me that any anywhere right
now we can say the the corpus of
knowledge doesn't have a bunch of
examples of cures you know across from
treatments and say oh all I need to do
is match those up which is kind of what
AI does when it comes to large language
Well, you query it. It looks in
statistically and says what are the what
are the relationships between what you
query and what I give you back as an
answer. In a discovery space, we don't
have examples of the you know the other
end. we have you know sure I can tell
you all the things you could do but you
know knowing which one is going to be
orthogonal big big hit isn't there but
what I'm talking about a little bit is
is to 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 sure
political systems despite what we think
are somehow semi-stable but a series of
of of these nudges can create the
condition where the last one takes you
across the border. And I think that's
what we're going to have to do in
disease where we say, look, nature
doesn't necessarily want us banging on
it, it'll bang back. What in in fact we
need to do is if we want this tumor to
get 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 that's a way of
you know again in this in this kind of
deep computational space we end up with
a lot of feature the tissue of the of
tissue cells and how they're organized
and what genes are expressing that start
to look like Mellin's map of the of the
of the world that you know in its early
phase it only had parts and then you
know starts as you explore and you add
things to it 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
fibroblast certain cells are doing this
and epithelial cells are doing this and
that's That's a we call them archetypes.
They're [snorts] they're like they're
like a way that biology organizes
itself. And to get from one to the next,
we need to understand how it does it
developmentally. That would be a really
nice thing to follow. And then we need
to give those cues in order. And that's
where I was coming back. You know, when
you were talking about peptides earlier
and 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 it to get the
system to go to that but then it might
be 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 looked for a
single you know single hits 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 collection of
behaviors and foods you eat and sleep
you get and all these things create and
partners you know your
>> loves of your life, the the friends you
have, they're all part of I think this
this and that's getting a little away
from imology obviously, but
>> no, but an thing about the insula, you
know, not so much a good friend of mine
who's a physician in the Bay Area says
uh you know, better living through
chemistry still requires better living,
>> 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, you know, stress
mitigation and on and on. Could I ask
you a couple of additional questions
about the immune system?
>> Yeah, please.
>> Before we wrap because I know um
>> many people are curious about autoimmune
>> issues. More and more I hear about, you
know, I don't know is 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, uh they it absolutely
exists. Um they're tired. I believe
them. I know someone who had a myalgia
>> uh recently. Um psoriasis is something
that I maybe have known to be now
>> autoimmune. Um asthma
>> these are interesting conditions not all
of them life-threatening. Yeah.
>> But some of them cause a lot of
discomfort. um what is known about the
formation of autoimmune conditions
either inheritance lifestyle factors and
then what excites you about some of the
newer treatments that might be available
or currently available for those and
other things. It's a big question but
>> yeah it's a big question. Well,
fundamentally, again, this is I think
where um 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. 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 there's a view
of them that they represent a misplaced
immune system that's 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
um you know lupus there's a familial
mutation in a a receptor that's on a B
cell that normally helps turn off the
immune system and it's defective. And so
those those people are susceptible to
getting what are called auto antibodies.
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 pro, you know,
to jazz up for COVID vaccines, you know,
those can be overactive and they can be
genetically overactive and you know, one
wonders why we'd ever have such genes
and why they would be propagated except
that maybe in some s circumstances you
need it when there's a big pandemic or
something people might have a
particularly good response. So there's
definitely genetic origins of some of
these things. I think what's uh you know
what's interesting to some extent is is
something that you'd alluded to with
asthma where asthma was one of these
things that historically would be called
an allergy and it still is an allergy
you know where you have you know
inciting things that are grass pollen
you know these sorts of things but in a
lot of these settings the concept that
that is is coming in part and parcel
with you know the immune system
recognizing self 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 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 it in a microscope and say oh yeah
I can really see that there's thickening
of the airways and that why that's why
they couldn't breathe but like I'm
saying now we can go into those and we
can look at every single cell and ask
how those are wired together. Is there
only one form of asthma? That's no.
There's actually definitely like seven
or eight and they have and that's why
some people are, you know, like can take
the inhalers and it works and other
people can't. Some people they're very
like chlorine sensitive. They go to a
pool and it and initiates are cold
sensitive. So there's there's variations
on what sets up that inflammatory focus
and I would call it like an archetype.
Some of them have lots of cells called
eosinaphils. Other ones have lots of
cells called neutrfils. 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'm I
would just say that in a lot of this
domain, I mean, we have a study right
now that's looking at across a bunch of
autoimmunities to figure out whether
they have things in common with each
other and psoriasis is one where you
start to see, you know, variations and
lupus for sure and inflammatory bowel
disease and and and you know this in the
clinic because inflammatory bowel
disease, you ask about drugs, is a good
case where there's a couple different
drugs is that for some patients work
really well. TNF therapy for example it
blocks a cytoine and some people with
IBDs is like really bad diarrhea and
manifests and very 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
disease 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 thing then where it doesn't
work.
>> Sounds like psychiatry.
>> It does. Yeah, there's [laughter] a lot.
It sounds like a
>> no disrespect to the psychiatrist.
>> But 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.
>> 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 different immune flavors.
And so the drugs that you try to use,
it's clearly immune system can do a lot
of good work for us, but what you need
to do to it in these different sort of
archetypal immune systems is going to be
different. You know, you you just got a
different football team out there
playing or they running a different
play. If somebody has a kind of mild
autoimmune condition like let's say mild
psoriasis
>> does that I've read but that doesn't
necessarily mean anything. Um I've read
that that might confer because it's
autoimmune that might confer them with a
bit better uh viral and bacterial
infection resistance. So, you know,
there's a trade-off there like, okay, so
scalp cells are like sloing off and like
I think it's like interlucan 17 or
something now like the treatment they
have some good shampoos for this or but
>> anti-influc
but but you that individual is um maybe
better at fighting out other infections.
So, you know, given there's a
anti-influcch
um and uh and yet you're more resistant
to infection. So, you could see how it's
adaptive in the modern context. And now,
severe psoriasis can be very disruptive
for people. And people might wonder
like, are we really talking about
psoriasis? But I think it's sort of a
individ
point for why autoimmunity could
actually be useful. Yeah.
>> Um it's not always the case. It's like
there to give us asthma or flaky scalp.
>> You know, we could talk about there's a
lot of disease states, you know, the
argument for why we would ever have a
cickle cell gene. This is the one that
causes people to have hemoph you know
hemophilia and it's a lot of subsaharan
African gene people from that origin
have this is that it's actually
defensive against malaria is you know it
seems to be the case that so so having
that I think this is true a lot of these
situations where the diversity of the
human population over time you by having
some of these things that make some
people hyper sensitive to you know uh to
maybe bacter viral infection at the cost
of having things like psoriasis pop up
or you know various various other
autoimmunities is the only way that you
know like a a billion strong population
has to to to to move forward and I I
always give this example that because I
think it's a really straightforward one
if you take a a flask of bacteria
and um and you put them in glucose which
is like sugar like you put in your
coffee um maybe sucrossse either one you
put them in a in a in a simple sugar uh
and you watch the colony grow you'll get
these cells that grow really really fast
the bacteria you know becomes billions,
trillions of of individual cells, but
there's almost always some just losers
that are dividing slowly. And it's for
whatever reason, the system always
springs us off. You're like, why would
you do that? Why would the system why
why wouldn't just the winners win? But
if you take a little bit of that culture
and you put it into galactose, which is
a milk sugar, often the ones that were
winners don't win anymore. And it's from
the loser pool that the new ones emerge.
And this is a case of like, you know,
like uh crowd uh fitness that comes from
diversity of 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 and
and that seems unfair at the time that
you have these kind of bad genes, but
like a different day you would have been
happy, right? you know, so I think
there's a lot to be said and and that's
also why a lot of the things that we
look at, you know, anecdotally somebody
takes a supplement and it works for
them.
>> I mean, I don't know how much you know
about this literature, but the the
differences in urine mine vitamin
requirements is going to be quite
profound because the metabolic enzymes
we have for the vitamins that we might
take in are going to be different
between us. And so these FDA limits,
these these numbers are averages. Some
people may need five times that amount
of, you know, vitamin X and other people
may need a fifth. And I think this is
super critical. The supplement world is
kind of like scattershot. Well, I
appreciate the rational grounding in all
of it. I I think uh thread throughout
today's conversation. I think that um I
picked up on, you know, I the fact that
we covered things like peptides and
things like that. And I'm not certain
about the peptide question across the
board. It's clear some are beneficial.
It's clear some are still experimental.
I'm just a big fan of more data and more
data collected the right ways and
communicated the right ways as the same
way with vaccines and all the rest. You
have an amazing substack. I know that
because I've spent time there.
>> No, thanks.
>> Part of the reason we invited you here
today is to learn about the immune
system and we barely talked about
cancer. I realize we're going to have to
get you back to talk about that, but
you've done an amazing job of educating
us on the immune system. I really want
to thank you and speak on behalf of
many, many people for that. Never before
has somebody presented in in the ways
that you have and uh as somebody who
thinks in analogy I and likes to teach
in analogy. I really appreciate that
that uh that stance. What inspired you
to get into
>> public education about science and
health before coming on this podcast?
And by the way, everyone should check
out Max's uh Substack. We'll put a link
to it in the in the show notes. It's
it's so thoughtful, so nuanced, so
relevant to all the issues that we're
talking about, if not directly, then in
in the general contour, and in some
cases directly, and I I imagine you're
going to continue doing this. So, what
inspired you to do it, and um how can we
make sure that you continue to do it?
>> Yeah. Well, thank you for the call out.
Um it is it's something I've been trying
to work on for about 10 years and it it
really started when um a group of us you
know were were hanging around after a
conference and we were talking about
some of the issues with science in
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 everyone else to
think as a scientist like why you can
ask yourself you know oh why don't
people agree agree with this data that
you show and take the action that seems
logical but then you present it in such
a way that they can't you know that two
things two things are important about it
I think one of them is you if you
present the information in a format that
isn't you know familiar you're not going
to be able to teach anything anybody
anything about what's important but the
other thing is that you know we were
talking we we spent some time talking
about this and we consulted some other
folks that are in science comms and we
realized you know the other thing is
that that that if you say you're a
scientist
it's not a neutral statement. Science
has a history and history is stronger
than science actually. So the history
like you know there's 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. Wow.
It's it's 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 is one of part of our job
should be to figure out how we relate to
other humans. And it's you know that
there's a painting of this and you
obviously the media and and things help
this happen because it makes it
interesting to have a you know kind of a
nerdy scientist and and we all you can
be a nerdy scientist. I heard you and
you know but also you're a human. You're
a human being. You have you know there's
foibless to you know loves and hates and
and um
>> certainly foibless. I have plenty of
those. [laughter]
>> We can get in that off the podcast. But
you know that this concept of if we want
to relate um you know if we want to have
impact of the work you do if you want it
to be relevant at some point you have to
the science science as a field needs to
make sure that it doesn't ostracize
itself from people and I think one of
the issues there I just use the word o
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
recog 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 [clears throat]
strikes me as really really important to
the impact that you can have with with
your science and and that science can
have in 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 u designs, then then
you've lost that that that the potential
for it to do good is is gone. So the
Substack came about it because I was
like, well, I need to write as a person
a little bit more and and tell about
some of the, you know, the 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. Science you
hear the bells and some cool device
comes out and it's but but there's a
bunch of people pulling the arm, you
know, and they're they're not winning.
And so, [laughter]
you know, so I feel like that's kind of
an important part of this that that
again, it's not the glory story always.
>> Um, you know, the best some of the
bestselling books about science or are
the winds, but um, you know, it's might
be more relatable at some point to get
all of it. So, that's kind of what what
I was trying to put together. And and at
the same time, I think the immune system
is also just so relevant and so
important and it's got all these
different facets and these archetypes
and these sorts of things that it's
doing that we kind of scratch the
surface today. So, anyway, thanks for
calling it out. been
>> working on for a bit.
>> Well, I hope you continue to and um
>> thank you so much for the work you've
been doing in your laboratory and all
the people in your laboratory doing that
work because now you're the one calling
the shots while other people do
experiments. But
>> um for your advocacy for science and
public education, it's huge. Uh 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 um and people will really
learn. So that's essential especially in
this day and age. But even not in this
day and age, science is is just really
cool. And with all the meaningless dril
out there, it's nice to go to a place
like your Substack and I'm speaking to
the audience now. You 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 some somebody's going to contact
you that they decided to study the
immune system or they learned something
or they explored a a novel treatment
with their physician in a in a given
unfortunate or maybe even fortunate
situation that bettered their lives.
It's it's incredible what um Substacks
and conversations like the one you've
been willing to have today and going
forward can can really do. So, thank you
so much. should definitely come back
again and tell us about cancer and other
other things because I I took us off
course quite a lot but I I had a great
time talking about all of this and I'm
going to be thinking about a lot of it
and really appreciate you.
>> Yeah. Well, same here. Thanks so much.
>> Thank you for joining me for today's
discussion with Dr. Max Crumbl. To learn
more about his work and to find a link
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