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Language: en
what we put in our bodies impacts our
health our lifespan our mental state we
live in a world where there are so many
choices the vast majority of choices are
not great choices people will often take
the the path of least resistance and
they'll get the fastest most available
uh food for their for their day in many
cases what they're doing is they're
poisoning themselves
to Bob Harari welcome to the show Tom
good to see you and it's um it's a
privilege to be here in your beautiful
beautiful Studio thank you man I'm
excited to have you I want to know what
are three things that people do daily
that shorten their lifespan first and
foremost I think inactivity and a
dependence on technology for for
physical activities is damaging uh you
got a dependence on techno technology
what do you mean even even depending on
uh motorized vehicles to drive to get
three blocks to the store to pick up a
gallon of milk people need to be more
physically active they need to uh to to
build and maintain their muscle mass
that's one of the most actionable things
we can do to maintain our health and
there's fundamental biological reasons
for that we can talk about but that to
me is one of the principal principal
factors that if you just pay attention
can impact your your lifespan all right
so lack of activity right
diet what else so everybody the go-to is
Diet right 100 the go-to's diet if you
say it's not diet those are going to be
fighting words I couldn't agree with you
I'm going to come at you at the end of
this I was saving it for number three
but but let's let's leave it at number
two so there's no doubt what we put in
our bodies impacts our health uh our
lifespan
um our mental state you name it the
problem is we we live in a world where
there are so many choices and the vast
majority of choices are not great
choices people will often take the the
path of least resistance and they'll get
the fastest most available uh food for
their for their day and in many cases
what they're doing is they're poisoning
themselves
um how do you feel about people that say
a calorie is a calorie it doesn't matter
I don't believe that at all
um there's a very big difference between
a a calorie of protein versus a calorie
of fat versus a calorie of carbohydrates
we know that and we know that what you
want to do is you want to provide
yourself not just with energy but you
want to provide yourself with building
blocks the building blocks are essential
to the repair and regenerative process
which is what I'm very focused on you
can't build new cells and new tissues
and new organs unless you have the
components that are necessary and those
components for the most part are found
in proteins fats are very very good
because the byproduct of fat digestion
gives you some of those building blocks
but we also have to take into
consideration that many of the things we
eat
have um have pro-inflammatory elements
to them and at the end of the day
controlling inflammation and
um uh and controlling the exposure your
body has to the toxic nature of things
like raw sugars clearly has a big impact
the reason you and I first became
friends was how thrilled I was what you
were doing at Quest building these
really fantastic products that were
delicious satisfied those Cravings but
provided you with the building blocks
I'm just talking about
um so so clearly nutrition is something
that that people uh unless they pay
attention to it may in fact be doing
themselves harm rather than rather than
benefits do you have a rule of thumb on
diet like you have 30 seconds to explain
to somebody what to either do or not do
if they care about longevity
specifically well you know somebody
who's who's always always been plagued
by a tendency to to become overweight
because of you know it less than than
ideal activity and the wrong diet I've
decided that that I'm gonna I'm gonna
focus on one thing that I know I can
measure and I'm going to use that as my
metric to follow and so for me it's
blood sugar and we all know and I think
it's increasingly recognized that blood
sugar is is linked to metabolic
inefficiency that exposes our entire
sufficiency why inefficiency so what's
happening so I eat a carbohydrate for
those that don't know I eat a
carbohydrate doesn't matter if it's a
carrot or it's a bread whatever some
portion of that is going to break down
into glucose
that's what we're talking about when we
say blood sugar because a lot of people
think as long as it doesn't say sugar on
the pack that it's not going to be a
problem now carrots was probably a
terrible example because so much of
that's blunted by fiber but your eating
carbohydrates are going to end up in
your bloodstream as glucose
but why does that cause metabolic
inefficiency the easier it is for what
you ingest to become that free
circulating glucose the easier that is
the less efficient it is for you for
your for your system what I mean by that
is if your body has to go through a
digestive process to turn the
carbohydrate in a carrot into an
absorbable form of glucose that's better
than if you get raw glucose just as a
sugary coating on a product because if I
have to work to get that glucose out of
the product into my system that's better
is it better because it's slower or is
it better because there's just less of
it well it's better because it's slower
and because you're you're actually
utilizing energy to do that digestive
process you're actually balancing the
the the asymmetry between availability
of glucose
the raw availability and the usability
of glucose what I mean by that is I
would rather you
um uh you have to work a little bit to
get the glucose out of a product than to
just have an infusion of raw glucose
into your bloodstream and why does
glucose cause so much inflammation
you know
um
I think in part because as the food
industry evolved it was about quantity
not quality and the sugar plantations
recognize it's real easy to grow sugar
cane and grow other raw sources of
glucose molasses et cetera et cetera and
to put these into products in as simple
a form as possible so that the process
of making the product was easier and
less expensive
that that means that your exposure to
these sugars is much much higher than
under under by normal biological
circumstances if we were if we were back
you know 2000 years and we were foraging
for food or growing our own food the
effort used to produce that helps burn
some of this raw raw glucose that we're
absorbing the inefficiency in my mind is
all about
you don't you don't want to fill your
system with glucose you didn't pay for
and you didn't pay for
um energetically and and that may not be
the best description but I just think
about it you're if you have to run
before you get to the restaurant and
order your meal that's probably better
for you going in so we've got two things
not enough activity a poor diet a
pro-inflammatory diet those are going to
be problematic pro-inflammatory and the
quick example would be high blood sugar
diets or anything that's spiking your
blood sugar consistently
what's one more thing
so the third thing to me
um uh really relates to something else
we put into our bodies which is the
medicines the supplements and the other
things that we think are benefiting us
but might in fact uh not really be be
all that useful everybody I know takes
some form of supplement
either either in a pill form a capsule
form in a powder form we have to
consider how that product got to be in
the format we're ingesting you avoid
supplements altogether no no I don't but
I avoid for example as much as possible
the the gelatin encapsulated supplements
people don't recognize that gelatin has
to go through a process of being broken
down digested in order to release the
the contents I remember a situation
where a gentleman who was very health
conscious was ingesting a tremendous
number of supplements a day actually
developed an obstruction in his
intestinal system from gelatin what yeah
yeah so so it's a lot of supplements
it's a lot of supplements and by the way
it's not uncommon for people to take 20
30 40 capsules a day dude there's people
that take even more than that which is
crazy I try not to supplement anything
now are you only so you're worried about
quality of supplementation versus
supplementation itself
is it just the gelatin are there other
things that people are ingesting like
what are typical ones that mess with
people I think that if you don't look at
all of the components of what you put in
your body
um some of the other ingredients they
may be binding agents they may be
excipients that improve the solubility
of the product any of those things that
you're putting in your body although
there are minor ingredients of the
supplement they do over time have an
effect and so you have to pay attention
to this you know like like you and I
were just talking about uh
the concept of Whole Food whole real
natural unadulterated forms of food
helps avoid some of those added
ingredients you don't need and you may
get your thousand milligrams of Vitamin
C but if the vitamin C tablet you take
is bound together by an algae based or
gelatin-based component you have to
consider that's going in your body as
well when you think about aging and
people doing things that are decreasing
their life is it are we doing things
that are like I think a lot about
methylation of the DNA right so you've
got people have heard me talk about this
a lot but for people that are hearing
this for the first time so in every cell
you've got the DNA which is the program
that tells your cells what to do but
over time there's little misreads
mistakes in the replication and you've
got these little things which I never
remember what they're called but they
run along and they like Mark like this
part should be read for this cell this
is a liver cell so only this part of the
DNA should be exposed and should be read
and as that begins to get confused and
the bookmarks get put in the wrong place
the cell starts to de-differentiate and
as we de-differentiate we age one did I
capture that idea correctly and then two
as you think about people doing things
that shorten their life
is that effective what they're doing
they're doing things that cause the the
wrapping of the DNA to be wrapped or
marked poorly or is it something else
entirely
so you're hitting on a topic that's near
and dear to my heart and I may I expand
on it a little bit please so educate me
because I know it like just enough to be
dangerous but it won't take me to the
deep water it's almost like I primed
this entire conversation every cell in
our body
can be thought of as a computer a
computer that has in the nucleus all of
the biological software which drives the
processes that provide all the synthetic
products of the cell proteins peptides
Etc
and also drives the the sequence of
events necessary for that cell to
continue to perform its function whether
it's a liver cell or a heart cell or a
brain cell that software can get
corrupted it gets corrupted through
normal processes as well as
abnormal processes that in effect means
the software doesn't get read properly
give me an example of an abnormal
process a mutation induced by a virus
one of the ways that viruses actually
create the symptoms is they begin to
destroy your cells by taking over the
Machinery in the cell
actually damaging damaging that cell's
ability to replicate normally and
fortunately our immune system will come
in and clean that out and fortunately
not all your cells necessarily are
affect affected so viruses can cause
these mutations and abnormalities
exposure to radiation ionizing radiation
can obviously do that and then there's
and then there's evidence that chemicals
we ingest maybe some of the things we've
been talking about some of those
chemicals might in fact
either either stimulate or or prolong
the the what we call the epigenetic
changes to our DNA which affects the
performance of the cell so so just to
get back to what you were sort of
alluding to if our software in order to
run properly has to be uncorrupted
anything that corrupts the software just
like the software on your computer if it
gets corrupted your program doesn't run
properly that same process occurs in
ourselves and and if you think about the
nucleus result is where the software
resides and the cytoplasm of the cell
the body of the cell is where the
processing takes place and if you think
of the surface of the cell as the
keyboard then
that that kind of model of the cell as a
computer means that what's the best way
to protect yourself is to keep your
master boot disk
stored away somewhere so that it can't
be damaged as a way of protecting the
Integrity of that software as early in
life as possible in the event you need
to reboot your system one of the things
that I want to answer today is If stem
cells are as amazing as you would have
me believe why don't I see super
soldiers running around why don't 100
year olds look 25 but before we get to
that I just want to Prime the audience
that that's one of the places we're
going to go but I really want to
understand how the cell operates so I've
got the nucleus all the DNA is jammed in
there I've got the cytoplasm is that we
called it right uh how is it doing the
processing like the more I can Envision
this the more I'll be able to remember
it so I have maybe a slight
understanding of the way that DNA is
read right but I don't understand how
the processing is happening in the
cytoplasm what what's actually going on
not metaphor what's actually happening
so the DNA has a partner in in cellular
processes called RNA that's what's in
the cytoplasm so RNA Transit between the
nucleus and the cytoplasm and they are
little things that move around they're
little nucleic acids they're they're
little pieces of nucleic acid that copy
the corresponding sequence from the DNA
but can they move oh absolutely they
traffic around the cell they actually
move through pores in the nuclear
membrane and are they like if I was
looking at them for people watching you
can see my hand for people listening I'm
like doing a crawling motion like how
how do they actually ambulate is that
the word they don't
traffic by their own motion what they do
is they move
sort of through brownie in motion they
float what the hell is Brownian I don't
want to get it I can't understand it
though so there's are they they're not
just sloshing around they must have like
they're doing something willfully and
now I know I'm getting into metaphorics
obviously they're not they don't have a
nervous system or anything like that but
like if I was looking at them under a
microscope I would see them move right
so traffic you can see rnas yep these
little molecules of ribonucleic you need
my DNA that first the way the RNA is
created is that they but they actually
come up to the DNA itself and they
create a corresponding sequence to that
DNA that's now and they're just grabbing
that [ __ ] out of the out of the floaty
stuff right ctga they're just grabbing
those letters and going uh c c t t g g
right that's right they have they have a
correspondence so that the the sequence
of DNA is written onto the RNA the RNA
then traffics from the nucleus into the
cytoplasm and it attaches to parts of
the cell cytoplasm
called ribosomes and those ribosomes are
the are the place in which the RNA is is
translated into protein okay that's
where the cell is going to split so no
that's so we're talking about two
different things we're talking about
protein synthesis from your that's
that's encoded in your DNA the these so
the DNA says create this protein exactly
exactly so the genes for a specific
protein they end up getting out of the
cytoplasm or does it it does so so the
ribosome allows the MRNA the messenger
RNA so the first step is you transcribe
the message from the DNA to the RNA yeah
then the RNA traffics transits into the
cytoplasm with the copy of that with the
with the recipe
it just says the recipe it doesn't
actually have the protein it doesn't
have the protein yet got it so I now
have the recipe so I wrote down the
recipe that's right then now I go into
the cytoplasm that's right then this
this this little molecule that could
constitutes the ribosome
um allows for that messenger RNA to be
translated
into a sequence of amino acids okay and
if you ever watch the process it's it's
a fascinating process it looks very
mechanical and the translation of the
message from the gene
in the in the DNA says make this
particular protein make make growth
hormone the growth hormone recipe which
is encoded in the DNA and transcribed to
the MRNA and then translated to the
protein in the in the cytoplasm takes
place on a piece of the cell called the
endoplasmic reticulum this is a little
gonna guess that well this is a little
organelle and by the way you know it's a
good name for your next dog and a
reticulum organelle is a good name too
but um but once once you translate into
the sequence of amino acids and you now
have a length of amino acids that
constitute a protein the protein then
gets packaged in part of the cell an
organelle called the Golgi apparatus and
the Golgi apparatus puts layers of cell
membrane around this this uh this new
protein that protein then gets connected
to the cell membrane itself where it can
be expelled into the into the
extracellular space that's how proteins
go from recipe
to design to production to secretion
okay and so now once it's outside of the
cell it's gonna
I assume it's made locally so muscle
cells are going to make the protein that
I need to affix to the muscle in order
to make a bigger repair damage whatever
the case may be How does it go from
you're now free my child to being used
in the way that it's intended so that
that's the beauty of biology okay so
um the system is designed to read and
express genes that are necessary for
certain functions and we don't fully
understand the process by which those
genes are turned on and turned off but
there is a series of signaling events
that calls upon the production so for
example while you're growing the need
for growth hormone actually commands the
expression of those proteins that then
get produced and then secreted and they
now influence the cells around them and
in some cases even remotely by
transiting through the bloodstream to go
and affect cells in the rest of the body
that's called the paracrine effect okay
and then the autocrine effects where
where your single cell may drive
functions in cells all around it as well
as as distant to that okay so this [ __ ]
is insanely complicated very complicated
I've said this probably a dozen times on
the show if you want to believe in God
look inside the cell this stuff is so
crazy and complicated it is unbelievable
but all right cool so that was an
amazing walk through I actually want to
now look at this under a Microsoft to
see what it actually looks like well the
beauty is I'm going to send you some
remarkable videos where where artists
have actually created computerized
graphic representations of this process
and when you actually see it you'll say
how could that possibly have been
designed it is so intricate and it is so
elegant literally some of the molecules
necessary for reading and writing the
DNA walk these molecules walk you you
you have that little ambulate they
literally walk across the DNA the
chromatin what are those called
polymerases DNA polymerases it's it's
it's amazing remarkable stuff and and
believe me I'm a surgeon so this is
probably way above my pay grade but the
um the fact is we recognize that every
cell is a synthetic Factory that
produces products encoded in the DNA and
those products are necessary not just
for the function of that cell but for
the function and and and integrity of
the cells around it and to influence
cells even far away other parts of the
body okay so knowing that your specialty
is stem cells so what is it that stem
cells are doing in that process
so for people that don't know the brief
history of stem cells is that they can
become anything so when we're first
developing in the placenta in fact tell
people because this is a very
fascinating take on the placenta walk
people through the sort of early Insight
that you had that made you think
placentas aren't what people think they
are if you're ready to level up all you
need to do is take the steps with the
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life you know back at back in the early
part of my professional medical career
my entire Focus uh was on the treatment
of head and spinal cord injury I was um
I was I was interesting futile at the
time well it was it was very depressing
when you started that had to be just
like oh sorry you got hit in the head
you're done what made you think you
could be helpful well you know maybe it
was a little bit of optimism combined
with um uh with fearlessness the fact
that the outcomes were so bad after a
traumatic brain injury we could do much
worse um I tried to as an engineer by
training I tried to break it down to the
root cause of why people do badly after
traumatic brain injuries and my partner
at the time was a brilliant neurosurgeon
up here at Stanford now a jam guitar we
we built a laboratory where we studied
these processes and we reckoned living
brains have you poked around on too many
to remember living yeah yeah he's alive
and you're done and and and virtually
all of them ever and virtually all of
them
um were the victims of some traumatic
event uh where where we knew that if we
could control the post-traumatic
inflammatory process so the the immune
system response becomes the bigger
problem there's no doubt ever everything
associated with the health wellness
repairability and recoverability in our
body is driven by the immune system the
immune system is designed to
interrogate to make sure things are
working properly and then respond when
they're not and so in the case of a
traumatic brain injury
the mechanical insult to your brain
disrupts even at the cellular level the
Integrity of those living cells and we
showed this we actually we actually
create you're going to love this Tom we
actually created a model in the
laboratory to to replicate what happens
in a car accident
by creating a water-filled piston that
was percussed by a hammer and the shock
wave was transmitted through this
connection into an experimental brain in
order to compress the brain the way it
does when it when when the head hits a
windshield okay and what we found was
that that that perturbation of the cell
released factors which stimulated and
and and recruited cells from the
inflammation the inflammatory system
from the immune system to come in and
release factors which disrupted the
blood-brain barrier and caused brain
swelling
uh and affected the the the Integrity of
the cerebral vascular system the blood
supply of the brain what people were
dying from after traumatic brain injury
was
was unchecked brain swelling now what
happens if you bang your arm in the car
door when you're leaving tonight it's
going to hurt and it's going to swell up
yeah
fortunately
for most of our body the swelling is is
can occur without encroaching upon any
of the anatomic structures
but not the brain the brain is encased
in a rigid skull which means that as the
pressure builds because of swelling
what what happens either the brain gets
squeezed out of the skull and that
actually happens it's called a
herniation oh god oh yeah where does it
go well you remember you have this hole
at the bottom of your skull called the
foramen magnum that's where your brain
connects to your spinal cord believe it
or not your brain can be squeezed out
through that little tiny hump yeah yeah
that's horrifying not not a good will it
shrink back or is that like once it's
there it is all over if you've
progressed to that point it's pretty
pretty far along but but here's the
interesting thing
the brain as an anatomical structure has
brain tissue it has blood vessels and it
has fluid the fluid is called cerebral
spinal fluid
if you think about you have three things
in a box you need the brain tissue and
you need the blood right if you squeeze
the blood out you get a stroke right
the fluid that's in there the cerebral
spinal fluid if you can get that out you
can make room for the brain to swell a
little bit okay so what we actually were
very focused on early on is control of
intracranial pressure that was a
plumbing Problem by draining that fluid
by just getting a catheter into that
system and draining that fluid you know
with with my partner and our team we
actually looked at at device strategies
to help doctors in the acute environment
control that pressure okay I'm going to
walk through this is so fascinating my
audience will have to forgive if they
don't care but this is really
interesting to me okay so you're in an
ER somebody just got in a car accident
they have battered their head they come
in presumably unconscious and do you cut
their head open like what are you doing
because I if let's say I don't
understand the fluid part I would think
you got to take the top off the head and
just let the brain swell that was
old-fashioned so believe it or not if
you go back historically in the
management of traumatic brain injury and
uncontrollable brain swelling one of the
strategies was to do a a craniotomy
craniectomy removing the skull and
allowing the brain to swell out and in
some cases actually removing part of the
brain oh okay okay that seems really bad
well it's it's a it's a last-ditch
effort to make enough room so that the
rest of the brain can potentially be
salvaged it doesn't always work that way
and you can imagine you know removing a
significant portion of brain tissue has
significant consequences yeah how long
can you leave a brain exposed like that
well you know again it depends upon the
surgical environment the and the
surgical skill set and so on
um in some cases surgeons will remove
this part of the skull and just cover
the scalp back over in order to give
time for the swelling to subside but you
know pardon me an hour it all depends on
the situation it depends upon the uh the
extent of the injury to begin with it it
depends upon the the underlying
inflammatory state of the individual but
suffice it to say that's not the ideal
way to manage that problem that sounds
unideal so you know as I mentioned my
the my partner that I worked with uh Jam
guitar uh we we were very fascinated by
the fact that you have an acute window
of opportunity to address this brain
swelling could you do it by getting a a
proper drainage system into that fluid
compartment of the brain and controlling
pressure by relieving fluid so there's a
specific place that that's happening so
the fluids in your brain circulate
around the outside of the brain and
there's a system within the brain called
the ventricular system and the
ventricular system are cavities they're
open spaces where the cerebral spinal
fluid circulates so if you can get a
catheter in there and you can remove the
fluid you actually can get some control
over the pressure but it's complicated
it right you know the old saying is that
if you if you relieve the pressure too
too rapidly you may actually exacerbate
the problem and cause more brain
swelling than than than existed before
that's surprising but okay so the bottom
bottom line is that that technology to
control brain pressure
control intracranial pressure has
impacted the management of traumatic
brain injury considerably but the
generation that has evolved since then
because this this is work we did in the
80s since then is to mostly look at ways
to control the inflammatory process and
and and and by the way there are some
relatively straightforward approaches
that appear to work hypothermia you know
cooling tissues off actually helps
control things like like swelling and
then also using using certain
um uh methods to reduce the metabolic
demands of the brain will reduce the
need for blood flow do you do that well
you've heard of induced Comas yes okay
so if you if you have a patient who
you're basically just trying to shut the
brain off you're basically lowering the
demand for blood supply and by lowering
demand for blood supply you lower
intracranial blood volume if you're
lower intracranial blood volume along
with intracranial pressure control by
draining that fluid cerebral spinal
fluid you can potentially actually
manage this wave of swelling that occurs
and you want to get to a point where
where swelling starts to decline you can
restore blood flow and you you haven't
damaged the brain so much that it can't
recover that was you know kind of the
the the fundamental strategy behind all
of this
taking it a couple of steps forward we
now we now work in a in a world where
there are tools to use to control
inflammation some of those tools are
pharmacologic tools or biologic tools
there are even methods that are
mechanical that are being developed you
know methods that use certain pressure
differentials and so on all that being
said I'm at the point in my life I'm
more concerned about okay after all
these acute events what can I do to
restore function in these patients and
now I assume we're loop back to stem
cells thank you so here's I'm bitter
about stem cells so I don't know if this
is just it's still early days or what
but I want to see 100 year olds go
backwards to looking like 25 year olds
and I know Tony's story it's amazing
but like do you think that there there
is going to be progress and
understanding of like the the so let me
back up I'm going to make a hypothesis
here's how I look at it stem cells can
become anything but stem cells are not
the only part of what's going on inside
the placenta which we actually didn't
even get to that part I derailed you uh
so we're gonna have to walk through okay
what was your Insight around the stem
cell
and then why my hypothesis is going to
be that that what you're about to
describe there what's happening in the
placenta is so [ __ ] complicated that
injecting someone with stem cells is
like five percent of that milia and that
we would have to get into sequencing
different like chemistry and signals and
all kinds of stuff if we really want to
have radical transformation but give us
that first insight and this time I will
try to stay on task as you explain
uh why it isn't what people originally
thought
you're hitting upon some really
um
important opportunities to distinguish
what we think the history was and what
it really was for for decades now
biologists scientists and and clinical
people have recognized that since we all
start from a single cell
and that single cell has all of the
information all of the ability to
produce every mature specialized cell
type of our body and do it at such scale
that from a single cell in your lifetime
tens of trillions of cells are produced
um what is the the fundamental the
fundamental unit if you will that's
responsible for that level of
differentiation specialization scale and
integrity if you think about it right
every cell in our body Tom originated
from a cell that originated in the
placenta
so you know Peter diamandis and I we I
think you and I Peter probably sat
around talking about that the placenta
is Nature's 3D printer it prints the the
newborn baby in doing so it deposits
cells that will take up residence and
give give off progeny that will populate
that developing human being for the rest
of their lifetime if you think about
that right from one cell to tens of
trillions of cells in our lifetime
how perfect does all of that information
resident in the cell have to be and how
perfect have those systems have to be in
order to support that level of expansion
and differentiation and propagation so I
was fascinated by that because I said
well you know couldn't every disease and
every illness and every injury in our
body be addressed simply by replacing
the damaged or disease cells and if you
can do that what what tool would you
need to do that so when stem cells first
emerged in the scientific literature
um I was fascinated by the possibility
that I could use them to restore the
functions that are lost after a bad
brain injury
the problem is what was the tool that I
would use where would I get it from
could I produce it to a to a form that
the the average clinical Community could
utilize because let's face it it's one
thing to do work in a laboratory and and
to have have discoveries and and develop
some interesting theories that you test
in on at the at the bench it's a whole
other ball game putting it in the hands
of a clinician to use to treat hundreds
or thousands of patients in their
professional career
that's why the industry of
pharmaceuticals has grown to where it is
because what the pharmaceutical industry
does is it puts tools in the hands of
clinicians you know if you go back a
couple hundred years doctors have to
make their own medicines right so so if
you think of cells as a medicine as a
biological medicine
I had to figure out a place to get them
where could you Source these cells and
what would you have to do to turn those
cells into a product that was of the
quality the consistency the reliability
and the scalability and economics to fit
our Health Care system so if you go back
25 30 years when most of the work around
stem cells was being done on stem cells
derived from Human embryos that were
discarded
or hugely controversial very
controversial and by the way aside from
the moral and ethical debate around the
use of embryos consider that at the
stage of an embryos development where
you isolate the cells which is the
blastocyst stage it's very early in
development
although the embryo might look normal
only four out of only one out of four
one out of five embryos that reach the
blast as his stage ever go on to form a
full healthy newborn
most of them spontaneously dissolute
sometime after that blast is his stage
because the body detects a problem
exactly because nature detects that the
underlying
quality of that embryo isn't good enough
to make it all the way through and it
turns out that the most common reason
for those early early pregnancies from
not continuing is that there's a
fundamental defect in the genetic
material of the developing embryo so let
me explain that
as you know we we are produced by an egg
and a sperm which are which have half
the the DNA content of a full cell
because when they recombine they create
the full content of DNA which means that
the cells that that are that are used
the egg and the sperm are produced by a
process called meiosis meiosis is
different than mitosis mitosis is a cell
makes an extra copy of its DNA and then
splits meiosis is when a cell splits its
DNA apart into two half it's two half
portions of pasta okay all right you
know when I go to an Italian restaurant
sometimes I want The Bolognese sometimes
I want the carbonara it's really nice
when you can get half and half that's
sort of what happens in the cell after
meiosis the cells that are that make up
the sperm or the Egg are produced by
tearing apart the the chromosomes when
those chromosomes are torn apart there
are often mechanical defects those
things are called
deletions
translocations trisomies quattrosomes
all of the aberrant copies of your DNA
that may be present in a in a blastocyst
but not capable of going all the way to
a full full complete pregnancy is the
reason why embryos are probably not the
best source of cells because you don't
know how what how good their quality is
early on very interesting so so many of
these things are dysfunctional anyway
going there even if it wasn't a moral
and ethical problem still not a good
idea that's right I made the commitment
to one fundamental principle which was
if you make it through a full-term
pregnancy and there's a healthy product
of that pregnancy healthy newborn that's
gone through Nature's Quality Control
process right and so if that's where I'm
harvesting my cells to develop a
cellular medicine at least at least I
eliminated the potential problems that
may have been carried through by using
the wrong cell source
that's the way that's the way I looked
at it makes sense there's another
Insight that I've heard you talk about
before which goes to your point about
the placenta being the 3D printer but if
people don't understand like if they're
lost at the level of analogy they'll
miss something really cool so you're you
were thinking about the placenta and the
embryo and you're like well they should
grow at the same rate but you looked at
it and they don't the placenta blows up
huge massive resources go to the
placenta and then the embryo develops
that's interesting because then you
start thinking of okay the placenta is
making all these stem cells and it the
stem cells in effect and I know that
this probably is not biologically
accurate but now this helps me picture
why the placenta becomes so important if
it is a stem cell Factory a stem cells
are already coming quote unquote from
the outside so there's this thing the
placenta creating the stem cells and
basically sending them over to the fetus
then the fetus is going to grow that
would give me the okay well then if I
already know that it can get this
injection air quotes from the placenta
then it might work later down the road
but
it obviously has a way bigger impact in
the placenta so again stealing your own
story from you spina bifida the skin
doesn't close for whatever reason it's
gonna have horrible consequences if left
unchecked but you can actually do
surgery on the fetus which is already
insane all you have to do is close the
skin and they will grow up normal and PS
they won't have a scar on their back
which is crazy you had surgery you have
no scar right but if you do that to a
one-year-old presumably they would have
a scar and certainly do a six-year-old I
love it Tom because it means that all
the time we've spent together you're
paying more attention to me than I'm
paying attention which is fabulous but
but so here's here's what really
intrigued me so first and foremost
um uh when my when my oldest daughter
was in utero and I ran down from the
surgical ICU where I was covering to go
and look at the first trimester
ultrasound and I saw that she was a
peanut sized embryo but the placenta was
already this developed organ and getting
bigger it dawned on me that as an
engineer for it to be bigger when I
thought from my early medical school
training that the placenta was a
vascular interface between the
developing fetus and the maternal system
they'd grow at the same rate the
maternal system right right it's a
loving way to say mother I'm trying to
be as politically correct as possible
but I was I was fascinated by the by the
fact that
um this to me indicated that the
placenta was the governor of
embryogenesis and fetogenesis and
actually finishing the production of
that newborn okay now if that was the
case why
um and it just seemed to me obvious
since the the net change in in cellular
mass of a developing embryo de fetus is
enormous where does all that cellular
Mass come from some of it develops de
novo in the developing embryo and Venus
but some has to come in there from this
organ that was my thesis and so I
started to look at the placenta and
found that in this complicated organ
was basically the anatomy of a
bioreactor it was basically a
cultivation and and cellular propagation
environment it was it was it was a
nursery for developing cells and since
those cells had access to a circulatory
system that could gain access to the
developing fetus some of them were
clearly trafficking in and out of the
fetus and so I came up with this concept
that well the placenta is basically
Nature's stem cell Factory
and if it's nature stem cell Factory and
we throw away in the world 150 million
of these a year
is that may be the best place to find
cells for the emerging field of cellular
medicine that was you know that was the
crazy idea you know the crazy Epiphany
that I had looking at my my daughter's
first trimester ultrasound
fast forward we did the work to show
that in fact the placenta is a an
environment for the propagation and
expansion of these stem cells and their
ultimate trafficking into the developing
fetus but after the fetus is separated
at Birth when you cut down umbilical
cord and the and the newborn baby is no
longer connected to the placenta and
that placenta comes out
is there any way of harvesting some of
these Surplus cells from the organ and
that's what we based all of our efforts
in our company on 20 some odd years ago
and and knock wood we were we were
fortunate that Not only was it an ideal
source of these cells
but I could develop systems to procure
these leftovers I could I could create
what I call a procurement Network where
in partnership with obstetric practices
and birthing hospitals and expectant
parents we could we could ethically
morally legally and under high quality
control collect these organs that would
normally just wind up in the waste
basket they'd wind up in the
biohazardous waste material and by the
way hospitals have to pay to get rid of
them
I could recover these bring them to the
laboratory extract the cells we need and
use those to produce the cellular
medicines we were all dreaming of at the
at the Genesis of this of this industry
that's what was really our driving our
driving force so why don't I look 25
then well first of all you look amazing
very generous but uh at 25 I do not look
well I got to tell you something since
the last time I saw you you look more
youthful and uh and clearly clearly like
you're working using this gym very
effectively very kind so here's where we
are
cellular medicine is a therapeutic
platform therapeutic technology which
goes through the same process of review
a demonstration of safety and efficacy
and then ultimately approval by Our Food
and Drug Administration that other
therapeutic products go through
as you can imagine
the modern FDA was designed to evaluate
test and and and approve traditional
Therapeutics those are chemicals
discrete chemicals and biologic products
are you saying that they're just slowing
you down and like in reality if you
could just go crazy like we really would
have that kind of
regeneration like I I have dude I am the
ignorant one at this table but I I have
a feeling that there is sequencing it's
maybe not the right word but something
like that where there's a whole bunch of
things a whole bunch of contextual cues
that the placenta has or sends out that
cause stem cells to have the massive
impact that they have that
maybe not impossible to replicate but is
decades in the future as we like learn
all the like nuances or no you think
this is really a Slowdown just from
testing and approval so
you know the FDA and other regulatory
bodies throughout the world have a very
very tough job on their hands
um considering all of the theoretical
Technologies and then and then reduced
to practice technologies that are
looking to gain approval for broad
clinical use you have to ensure that
your your exposing you're using the
right lens on those Technologies to
ensure safety first and foremost and
then you have to you have to link that
safe product to to to clear expectation
of clinical of clinically meaningful
benefit okay what's often used the term
is efficacy now
discriminating between safety and
efficacy is one is one thing
the other is do you have the right
metrics to use to determine whether
something is clinically meaningful
as a cellular medicine versus a biologic
product versus a chemical because
remember
if I put a chemical in your body and the
chemical is going to block an enzyme
okay there's a there's a there's a what
we call a Stoichiometry there's a
there's a mathematics that's a word it's
a great word too I love that word I use
it all the time
the Stoichiometry of of will that will
that particular product work the
chemical product you can you can
actually figure out you need so much of
this chemical to block so much of this
enzyme that's how you come up with
things like dose and that's how you come
up with things like
um interval or frequency of dosing
that's pharmacokinetics okay that
pharmacokinetic analysis is what guides
the whether or not you give somebody
five grams of aspirin or 80 milligrams
of aspirin okay okay this is all going
to answer the punchline though why I
don't look 25 yes okay I'm working
towards gone I'm working towards it so
with cells
the industry and the regulatory
community
took some time to better understand how
would we even measure how would we even
determine the pharmacokinetics of
cellular products because they're they
you don't just administer them and then
and then they have a discrete function
and nothing else a living cell a living
cellular therapy is going to have many
many different biological activities
based upon the environment it's
introduced into this the health state of
the recipient the chemical State the
milieu Etc and so being able to
discriminate between biologically
meaningful effects and biologically
irrelevant effects had to be worked
through and so it didn't surprise me
that that those who have to ultimately
give the seal of approval had to figure
a lot of this out plus if you go back 20
years we still didn't even know which
cells we were going to use for these
products what we tried to do at our
company's cellularity and ultimately at
um in in the the the next Generations of
these of these uh corporate efforts is
to first and foremost come up with a
reliable platform of cellular Source
material that could meet this need in
the industry show that we can
manufacture products to scale quality
and consistency that was going to fit
the Health Care system
identify the clinically meaningful
effect in a disease
show that it's better than the
Alternatives and then submit the data to
get approvals so that's kind of the
process you've got to take now
why why aren't these products available
to make us look 25 right now it's
because the current the current standard
by which we get these products approved
are first to show that they're useful in
unmet medical needs but do you so
reading through this uh are you saying
that you really have the faith that once
this we're able to get it through the
system it really is going to be that
impactful or do you think we're at the
beginning of a longer Journey where we
have to figure out okay you give them
the stem cell but then you hit him with
this other thing and then this other
thing and those three things together
have the massive effect
I think we're we're approaching a
threshold a watershed event where
approval FDA and other regulatory
approval of cellular medicines in a
discrete clinical area and I think that
the first area is going to be a limited
condition where there aren't a lot of
good alternative because that's where
the the regulatory Community is most
willing to be uh most risk tolerant if
you will
when that happens and we begin to expand
the safety database around those
products you're going to see an
explosion in the number of additional
approvals that will occur and what and
what what what what's really encouraging
to me is I think we're really close to
that happening and so the first approval
of a Cell Therapy product and a really
nasty disease like a cancer or an
autoimmune disease that that destroys
people's lives following those approvals
you will see these products rapidly
taken up and employed in in much more
mainstream illnesses do you have to be
careful how you answer this question
because you're in a public company
because I want to know like if I the guy
that gave himself H pylori and then gave
himself that antibiotic solution like I
want to know the answers of those
questions like if I'm do you know Ben
Greenfield yeah sure that [ __ ]
injected stem cells everywhere in his
face and his dick like right literally
everything right and he was even saying
like he thought it gave him an extra
like quarter inch if I remember I was
like what like people are going to abuse
this Ben Greenfield uh so yes I
understand you have to be very
thoughtful and careful about how you
answer that I'm very eager to uh probe
off camera perhaps okay so this is
fascinating it's going somewhere very
interesting what do we have right now
today like maybe using Tony's story as
an example like if we're really
committed we follow through with the
therapy like what kind of benefits right
now today with what's approved can we
get so you're asking a really
the interesting
challenging and treacherous question
so my favorite kind of question and
you're so good at it Tom the the truth
of the matter is we are going to first
first move approvals for cellular
medicines in the worst diseases where we
don't have really good therapeutic
Alternatives and when we prove the
utility there are you guys going like
for covid so so we we've actually we've
actually
we've actually pursued the treatment of
various cancers we work in the cell like
so so that's where so that's where
cellular medicine has evolved we went
from originally wanting to put stem
cells as the as the primary product into
different conditions like autoimmune
diseases to now saying well if the stem
cell can give rise to an immune cell
that has biological activity like a
natural killer cell that could be used
to fight cancer prevent you from from uh
help treat viral infections so are you
training the stem cell before injecting
it in like you're a killer cell now go
that's a good way of looking at it
instead of using the word training what
I'll say is we're we're specializing
from a stem cell a discrete population
of cells we know the activity of so
natural killer cells which are a how do
you do that yeah what would you give it
an instruction it has those instructions
already pre-programmed all you have to
do is lead it down the path how do you
do that like literally no analogy how do
you do that you do it with a with a
cocktail of factors which under normal
circumstances Drive the specialization
of your stem cells in your body to
become a red blood cell or become a
white blood cell or become a hair cell
we understand what those signals are
that's [ __ ] crazy yeah you may not
understand this but this is really
interesting dude this is bananas I love
this [ __ ] like we are at the we're
beginning to live in the future it feels
like that and Thomas I've spent I've
devoted the last 25 years of my life to
this
um it's it's what I it's what I get up
every day to pursue because I do believe
like you that that we are on we are on
the threshold of cellular medicine
becoming the most logical the most
Deployable the most the most impactful
way of treating disease because it's the
way nature treats disease we know how I
often used to used to say that stem
cells are nature's first aid kit
when you have an injury or disease your
body is signaling the compartments in
your body that house these stem cells to
send them to me
by the way I'll tell you something
fascinating you're going to love do you
know that that
a pregnant woman
um who is injured
for example a pregnant woman in a car
accident where even the fetus might have
some degree of injury do you know that
there's evidence that stem cells from
the placenta actually traffic into the
mother and find their way into her
injuries impact Theory University one
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not miss it
dude that that's how I know that a fetus
is basically a parasite yeah and it's
like no no I can't have you dying on me
because I need to exist so I'm going to
give you a little something something to
get you back in business that's crazy
and I know the punchline about cancer as
well that women can go into remission
when they're pregnant that's insane so
sorry I derailed this again so but I
love it too but use the term parasite
they're actually they're actually a
separate fight they actually a sap it's
another term so a parasite would be if
all the benefit was unidirectional yeah
right yeah Fair they actually benefit
each other fair and and you mentioned
something which was one of the Hallmarks
of our working autoimmune disease we
recognized early early on that that
certain women with autoimmune diseases
multiple sclerosis Crohn's disease and
so on would experience profound
Improvement in their symptoms during
pregnancy and you know what's the reason
some guys said well it's hormonal but
when you use hormones it doesn't work
and some guys don't well you know what
maybe maybe the the same cells which are
making the mother accept the placenta so
so let's may I tease this out a bit yeah
please all right
you know a PL a placenta is produced
with the fetus from the fertilized egg
and sperm it is a unique individual with
its unique Geno genomic and and genotype
right which means the mother that
carries it is not a perfect match for it
and should reject it should reject it
but she doesn't she carries it for nine
months without any immune conflict that
would terminate the pregnancy or damage
her health right moms carrying the
placenta and fetus aren't more subject
to infectious diseases things like that
well consider this in surrogate
pregnancy
the mother's not even related to this
pills it's crazy she's not even that is
more like a true parasite but the fetus
coexists in the maternal system without
that immunologic conflict now we said
well can we use that to our advantage
so since we saw how fast I want to give
people one anchor so one of the things
with Ms you get lesions in your brain
right you've seen lesions
be eradicated that's crazy okay with
that in mind of how dramatic I know
please continue so and the best the best
evidence of that was a a report in the
New England Journal of Medicine probably
10 years ago
the study followed 300 women with
multiple sclerosis who were pregnant and
they found enormously high percentage I
think it was 80 percent of the women
went into profound states of remission
where just like you said the lesions in
their brains improved their symptoms
improved in fact many women came out of
pregnancy and they relapsed and they
said you know what I gotta get pregnant
again yeah dude I literally was singing
the same thing I'd be like I'd stay
pregnant forever yeah so on the basis of
that we theorize is it possible that the
same cells from the placenta that permit
cohabitation in a surrogate mom if we
productize those and use those as a
therapeutic could we induce a state of
remission and in fact we saw that in
fact when we use placental cells these
are just pluripotent stem cells these
are versatile stem cells from the
placenta from any donor from any donor
this is bananas because remember once
the placenta is a one-size-fits-all cell
if you take those cells and put them
into a into a patient with an autoimmune
disease like Crohn's disease we saw
evidence of really significant
improvements in the patient's patient's
disease when stem cells have DNA they do
so they Dow on Earth can they be a
universal donor because it should be
like a male cell is telling you to be
male a female cell is telling you to be
female like if I inject you with stem
cells does your hair color change like
what
I don't understand that so it it it just
turns out that
the cells from the placenta
because of Evolution's brilliance
have the ability
to
um to to turn off any immune response
against them and induce a state of
Tolerance do they stay around though
they do and when they split how are they
not like if I gave my wife stem cells
how does she not start getting my cells
populating in her brain her liver her
kidney like and and if they did you got
to think about the Stoichiometry of this
okay if you're if you're 25 trillion
cells and you get a million cells from
your wife think of the or vice versa
think of the tiny contribution of those
cells to your overall your overall uh
biology and genome right in other words
in other words if it's not like you're
replacing your entire body with these
new cells you're just supplementing your
body with these new cells do you have to
keep topping them up then so I love it
Tom
this is exactly what I believe May in
fact be a a method or a strategy to help
um improve our health and biology during
our lifetimes by simply giving us the
benefit of an added set of instructions
okay so think about this for a second
you know what the term Chimera means yes
okay so
you can actually create chimerism in an
individual by delivering cells from a
from an a a a donor an unrelated donor
and those cells take up residence in you
for a period of time you now carry two
sets of instructions right yeah and by
the way we know from our friends in the
in the microbiome world you carry lots
of instructions not even not even human
instructions but these additional
instructions that you carry in the cells
that maybe make up one millionth of a
percent of your total cell volume they
still respond to the same signals and
factors in your body that you that
you're exposed to so so let's say let's
say you've got um
you've got a susceptibility to develop
let me give you an actual example
HIV
um the the the the
causative agent behind immunodeficiency
of AIDS
occurs because the virus gains access to
the cells by docking to a molecule on
your white blood cells your lymphocytes
called ccr5
now ccr5 is a molecule that in a
percentage of the population just isn't
expressed they are natural what we call
ccr5 Knockouts and interestingly about
four percent of the human population in
the United States is naturally ccr5
negative if you if you inject HIV into
them they do not get AIDS what yes now
by the way roughly 10 percent of the
population in Europe is thought to be
ccr5 negative because
Bubonic plague selected for them that is
Isn't that cool so interesting so listen
to this if I if I can't get infected
with HIV because of my cells not
expressing that molecule but I take some
of my stem cells and put them in a
patient who is HIV positive who actually
has ccr5 and has been infected and has
developed a disease
we actually now know you can actually
convert them to HIV negative holy [ __ ]
you can you can take somebody 100 HIV
negative yeah
and it's now being possible not
eradicated then so so all HIV does is it
damages the integrity and the
functionality of your immune system
right that's why you get opportunistic
infections and so on and so forth if if
I now give you give you cells that
create your immune integrity
but resistant to HIV you now can combat
and battle HIV and in fact some of those
cells will actually go and kill off the
HIV infected cells so so this is now
being done and published on and some of
the pioneering work in fact that my alma
mater Cornell uh they actually showed
the ability to convert an HIV patient
from positive to negative doing this
Jesus I thought I heard a headline like
that but I never that do you think
that'll become standard of care over
some period of time it's my dream so so
in fact
um
many many years ago almost 20 years ago
I had a concept that I wanted to explore
one of the one of the motivations for
creating cellularity was to was to look
at the possibility that I could induce a
state of super Health by simply giving
you more than one copy of DNA different
copy of DNA and allow natural selection
to upregulate those things that give you
a Health Advantage so you know what
hybrid Vigor is hybrid Vigor is Mom and
Dad have two separate genetic makeups
the more distant they are from one
another when they recombine The
Offspring has certain biological
advantages that's hybrid vigor okay it's
it's why it's why every generation
Health improves that's why sexual
reproduction is the things exactly now
a hybrid Vigor occurs between
Generations right
if I gave you oh my God I know where
you're going if I gave you a dose of
stem cells that had a completely new
complement of DNA is this being tested
so finish the sentence yeah my concept
was can I create chimeric vigor
can I create a stable Chimera that gave
you the advantages of all the DNA in the
world that was disease resistant and let
nature let natural selection let's put
Darwin in the driver's seat okay and let
natural selection upregulate those
things that give you the highest quality
of Health
so the theory of chimeric vigor is
simply this
you have 23 24
000 genes in your body that you're born
with what if I gave you access to to
10 different times the number of alleles
at those different genes so that you
could you could have the advantages that
every individual has
but but you can't package in one
individual and so here's here's
something that's really interesting I
believe and it's one of the theories
that that I again based my work on
that chimerism is in fact biologically
sound
chimerism occurs in for example in
animals that create litters like dogs
would have five or six puppies in a
litter each one of those puppies is a
unique genome
but they ex they are exchanging cells
with each other and some of those cells
will take up residence in the animal for
their lifetime so the animals become
chimeras of one another
and as chimeras of one another they have
the advantage of more than one G one one
more than one form of a gene to call
upon in order to advance their health
and by the way natural selection will
always upregulate the trait that gives
you a survival advantage
dude that's bananas is that being tested
now it's one of the things we're very
excited about testing and we and and
again you know it's it's it goes It goes
back to why over 25 years we've built
the one of the largest libraries of
newborn cells that are cryo preserved so
that I can interrogate the Genome of all
of those donors and eventually I'm
working with I'm working with some
absolute rock stars in the field
um uh one of my dear friends and one of
the smartest people I've ever met Jack
hittery has a new company called sandbox
AQ sandbox is a Quantum Computing
artificial intelligence expert expert
company and we've been talking for some
time about using that type of technology
to interrogate the library of donors
interrogate their genetics and then use
machine learning to pull out which
donors give me the best traits to
convert to this patient and and if I can
give those to a patient who might have
an underlying genetic predisposition to
a disease can I counteract that
and so that's where I think the future
of cellular medicine is the future is
coming up with the right mix of donors
that allowed allowed Darwin natural
selection darwinian natural selection to
to select for those traits that maximize
and optimize your health and disease
resistance and and it's one of the
things that turns me on I mean this is
what gets me excited Jesus yeah that's
very interesting so go back to covet for
a second so
so let me give you so I know where
you're going let me preempt you please
we talked before about the fact that
from any stem cell in the placenta I can
produce any mature phenotype any mature
cell type a brain cell a heart cell an
immune cell
now we recognize another observation we
made we talked about the observation of
um uh placentas being one size fits all
universal donor cells and all that the
other observation we made was that
one out of every thousand pregnant women
has some form of cancer during pregnancy
but the transmission of cancer from a
mother to a developing fetus essentially
is non-existent it's so rare that the
few few reports of it haven't even
created a causal relationship
so the theory was the theory was that
something is protecting something was
selected for in nature to protect
protect the developing fetus from a
threat like a like a transfer disease
from the mother like a transferred
cancer from the mother okay now we went
looking what could possibly behind that
and we found that the placenta has a
population of immune cells called
placental natural killer cells that are
part of the innate immune system which
means that they don't have to be
educated they come out they come out
punching they're already primed to
protect the developing fetus and if you
think about it right a human being
devotes nine months of reproductive
energy to one offspring
natural selection is going to do
everything to keep that Offspring viable
to get to full term
so to protect against cancer
transmission threat to protect against
infectious disease threat we theorize
that this natural killer cell played a
role because remember when a baby is
born they're born with their innate
immune system and a limited adaptive
immune system because they haven't been
exposed anything yet in the window after
birth what's protecting that newborn
from an infectious death
so we started to test this hypothesis
and found that the natural killer cell
is pre-programmed to traffic to and
destroy cells that Express certain
markers on their surface called stress
antigens
a stress antigen is a flag it's a flag
that cell waves to say hey something's
not good here
kill me
right so it turns out that stress
antigens expressed on cancer cells
virally infected cells and this is
exciting
senescence cells
the same stress antigens make them the
target for these NK cells so think of
the NK cell as the cleanup cell
it's the Seek and Destroy cell that goes
out kills kills
stress antigen expressing cancer cells
stress energy
expressing infected cells stress antigen
infecting old senescent cells now we
tested this hypothesis and it works and
so we currently are TR are using
placental natural killer cells to treat
cancer
we've used them to treat viral viral
infections like covid
and we're using them to treat
age-related degenerative cells senescent
cells as well so we believe that the
placenta is the best source of immune
cells that clean up bad stuff
help create an environment that promotes
survival of the healthy cells
and is renewable can be redosed
reutilized as you live your life because
the threats you are exposed to in your
life differ it's coveted today what's
it's going to be 10 years from now so
that same mechanism that protects you
today we believe will be therapeutically
useful to protect you in the future
whoa okay so we are
we're able to train the stem cell nope
you didn't want me to use the word train
we are able to create the milia so that
it becomes the cell that we want it to
become can we turn one into one of these
killer cells absolutely or or do those
have to come from the placenta or we now
know what the chemical signals are to
get it to become what you call it an HK
and NK NK so I can I can
convince I'll use the word convince I
can convince a stem cell from the
placenta to mature and specialize into
virtually any phenotype mature cell we
know of in order to get them to become
natural killer cells we get to a state
where we have the hematopoietic
progenitor stem cell that's the stem
cell that matures from the original stem
cell but specializes to become red blood
cells white blood cells and platelets
and when I get it to the point of making
a white blood cell I simply nudge it to
become a natural killer cell
now I can Mass produce those natural
killer cells and I can administer them
to you as a therapeutic as a
one-size-fits-all therapeutic product
so if you think about it
for a Cell Therapy product to be
meaningful you got to make it you got to
make it with such quality that it meets
a high standard like a pharmaceutical
you gotta you gotta make sure that you
can administer it safely and you got to
be able to do this without breaking the
bank
so there's no better place to find cells
to do all this than the placenta there's
no better place there's a hot this this
is a this is a raw material this is the
in my opinion the most valuable
biological raw material we know of and
and we've been we've been working on
this for 25 years we built all the
systems we've procured cells and
biomaterials from approaching a hundred
thousand newborn donors in our in our
history and that's just the tip of the
iceberg so here you've got a natural
resource I call it Nature's crude oil
and all we had to do was develop a
Refinery system and by the way aside
from the cells we get from the placenta
we also harvest the structural
biomaterials in the placenta and we turn
those into products what does that do so
um I think you may have seen I may have
shown you
from the placenta we take the membranes
which create the amniotic sac and those
membranes can be can be processed to
remove the cells but leave behind the
three-dimensional architecture I can
then dehydrate it and sterilize it and
put it on the shelf and if a surgeon
needs to replace a tissue and create a
tissue repair template they can use that
product right off the shelf
I can take the Structural Materials and
break them down into the component
structural structural elements that are
a couple of couple of microns in size
and I can administer those to boost or
augment your your your structure in
order to allow the repair process to
occur so let's look at a thing like a
like a wound or a non-healing fracture
in the defect of the wound or the
non-healing fracture I have cells that
are dividing but they need to stick to
something
if I can give them something to stick to
what we call a template a repair
template we actually can can support the
functional restoration of that tissue
and I could show you examples in burn
patients I could show you examples in
patients with non-healing diabetic
ulcers I can show you examples in
patients with uh with defects from
traumatic injuries where just the
introduction of the structural material
supports repair now think about if I use
that plus the cells how how much you are
basically mimicking Nature's attempt to
and you're augmenting Nature's process
of repair and that's what what
cellularity in our technology is focused
on providing these very very
biologically logical tools to augment
repair regeneration and restoration of
function what's the state of the art
with Burns I heard about the skin gun
yeah yeah like six years ago is that
real absolutely so so Steve battleack at
Pittsburgh one of my one of my heroes a
brilliant brilliant it by the way I
think he's an MD DVM PhD he's got all
he's got lots of credentials lots of
initials it's got the longest business
card in biotech
um you know Steve showed that that that
you can spray some of these structural
elements onto a defect
and they will again set up a repair
template encourage the the arrival and
that attachment of cells and then the
cells will start the process of
rebuilding that tissue
makes a lot of sense you know again as
an engineer every every structure in our
body every every piece of our anatomy is
a combination of structure and cells
it's like if you build a house what do
you put up first the frame right the
frame then supports the attachment of of
the of the Matrix components the cells
that ultimately create the living tissue
the functional tissue so if if your
problem after a burn or after an injury
is you're making cells but you're not
making Matrix then where do the cells
stick to and so I I often I often
described it this way
at the heart of a wound a non-healing
wound you have a tremendous stimulus for
cell division at the margins right at
the margins of the open wound the cells
say hey wait a second
we're not this isn't a closed tissue I
need to make more cells to close the gap
when they make more cells but there's no
temp there's no Matrix there the cells
just get dumped into the into the void
and they become what's called exudate an
exudate is that liquidy kind of material
that [ __ ] sort of material that is is
basically washes away over time and the
defect doesn't close but if I put a
template in there if I put this
structural material in there and the
cells can attach to that structure
they're happy
they start to divide and when they get
close enough you know what the cells do
they form what are called tight
junctional complexes the cells at
connection points anchor to one another
and when they anchor to one another they
can actually contract and pull the wound
closed
that's how wounds heal so all we're
doing by taking these materials out of
the leftover placenta is we're providing
a an alternative to Nature's attempt to
close these defects by supporting it
with a supplement and the supplement is
in the form of a structural material and
or the cells are we at the point now
where we could if somebody had a scar we
could go in sort of create the wound
again and lay this structural material
down and eliminate the SCAR or are we
still a ways away from that so we're
absolutely at this point
in fact scar revision surgery when
someone has a has a an injury or a wound
and it doesn't heal and they get these
nasty
um hypertrophic scars that look terrible
what surgeons do is they cut that scar
out as cleanly as possible
doing as little damage the underlying
tissue is possible and they hope that
they can restore continuity and minimize
the the secondary the next scar well the
best way to do this is to introduce
components that the body would have to
synthesize on its own in order to
shorten the time for that process to
occur and so so we already know that
these biomaterial products can help and
we are certain that the cellular
products
even the byproducts of these cells can
help support and encourage and augment
and and accelerate that repair process
that's crazy so you kind of melted my
brain a little bit with the uh Chimera
idea and being able to
make somebody's
I don't know if it's only the immune
system or if it's anything but to make
them more robust by introducing the new
cell types and then
um also I want to go back to
you've got the stress flag that the
cells are waving how advanced is that
process because theoretically if you can
swap out all of your senescent cells
that really would be where you're aging
literally backwards
and so is there a tolerance like is
there a point at which it's too many
cells like going back to lease and I so
if you take my some stem cells and
you're putting them in her you were
saying well if she's 20 trillion cells
or whatever and you inject one million
it's not a big deal but what if it's 10
trillion like is there a point at which
like it becomes an issue or no we can
just the more the merrier
you know we're still working on the
calculus of cell therapy right we know
for example in in immunotherapy for
cancer where we're introducing an immune
cell that there's clearly there's
clearly a calculus you need so many
immune cells to defeat so many cancer
cells right there's no doubt about that
in regenerative applications
regenerative medicine we're going to
figure that out too but remember if the
cells I deliver to you in a million cell
dose
take up residence in your body and they
themselves propagate and expand maybe
that million cells over the course of
six months to a year turns out to be a
billion cells so the contribution to
your overall biology will actually be be
enhanced
now consider this for a second the
process of Aging okay which you know
there's lots of theories behind it and
so on and we don't yet have great tools
to figure out what's your real biologic
age is
I've been convinced what do you think
about the Horvath clock I think that
these clocks are really important in
fact I was with Morgan Levine from all
those Laboratories uh maybe a week or
two ago talking about this there's no
doubt in my mind
that epigenetic changes
that are accumulated in your lifetime
can be thought of as a metric for the
age of your of your the biological age
of that cell
now we we still don't fully understand
how much DNA methylation is too much
but here's the bottom line
the closer you get to a newborn source
of cells the lower the amount of
methylation that exists on the DNA so if
I introduce that cell into an individual
by definition I've put a younger cell
into an older system now now hear me
after a minute
if you say that we are we are the
summation we are the sigma of all of the
all of the ages of the cells in our body
by the time we reach 40 50 60 years of
age the vast majority of our cells are
going to have
Advanced age biological age
and if I want to if I want to change
that I either have to pull out the
really old cells
or I have to introduce younger cells
that change the sigma right if if the
average is a function of the age of 5
billion cells out of 5 trillion cells do
the math you can figure out how much you
can affect your your overall biological
age by looking at that that calculus
but consider also that we're at a point
now where
you have to look not just at the DNA
methylation as a marker of of the age of
the cell but you've got to look at
things like telomere length and you know
telomeres often at one time thought of
as being a potential biological clock
telomeres which protect the ends of our
chromatin and are are exhausted after
repeated cell divisions because you
literally degrade the telomere as you as
you divide
the other thing to keep in mind is that
your your your mitochondria
age as well so any cell coming from an
older donor older source that has short
telomeres older mitochondria and lots of
DNA methylation by definition ain't
going to make you younger
but a cell from a newborn with long
telomeres with with very very little if
if any DNA methylation and really young
mitochondria
that's what I want to put into my into
my uh into my tank so stem cells if if I
were to take my own skin cell or
whatever spin it into a stem cell and
re-inject it those are going to be aged
cells yes okay so they're still going to
carry some of the methylation the short
telomeres that's right so so that's
always wondered about that so that's a
that's a really good point because
the world has made great advances in
induced pluripotent stem cells what that
means is and yamanaka who won the Nobel
Prize showed that you can take you can
take a mature cell
and you can you can
coax it into becoming more stem-like
with a with a series of factors a
cocktail we call it the the
reason for inducing pluripotency is
because most adults don't have their own
cells stored away from birth
right
the problem is that everything that's
done to induce pluripotency in a mature
cell
is already resident in a Cell found in a
newborn
and so although I might be able to coax
this cell into behaving like a stem cell
it doesn't necessarily have the
biological quality of a newborn stem
cell so if you think about this
how do we get to that mature cell that
mature specialized cell
we get there by a series of
cell divisions and cell differentiations
when a cell goes from a stem cell to a
mature cholinergic Neuron a specialized
brain cell
every time it divides and specializes
those specializations are a series of
gene silencing events so if you think
about it you have all this chromatin
okay when in a in a in a stem cell but
if I want to if I want to become a
cholinergic neuron I don't need 40 50 of
the genes to be expressed and so what
nature does in order to create a more
efficient terminal phenotype is it
silences those genes it literally takes
the chromatin and kind of crumbles it up
and keeps it out of access to these
transcription factors
by doing that you've created a cell
that's very efficient at being a neuron
but not versatile
so yamanaka's work show that you can
take that cell and you can coax it back
in to behaving like a stem cell but you
don't necessarily make it a younger cell
so there's two different things right
there's stemness and then there's and
then there's young versus old so if you
take placental stem cells you can make
them replicate oh yeah and they will
stay young forever
age two but if I have a supply of the
young ones if I have a supply of these
ones which are young and uncorrupted and
I just keep introducing them into the
system
what what effect will that have so you
and I talked about this I think when we
were like sitting around it turns out
that maybe 15 years ago
the theory that we age because we use up
our stem cells drove me to a set of
experiments where I collected the stem
cells from the placenta of newborn rats
and I processed them and just the same
way we did with our human cells and I
cry or preserved them I put them in a
state of suspended animation which means
that they they're going to be the same
10 years later than they are today when
I saw them
when I took those cells and gave them
back to the animals as they were aging
their own cells their own cells when I
gave them back as they were aging
the cells that got the animals that got
their cells back lived 40 percent longer
whoa
40 longer than their litter mates
whoa yeah and and they were bigger and
stronger and meaner you know that to me
said hey one of the most
obvious places to look here is can we
create a biological state with enhanced
youthfulness by simply averaging down
the age by introducing these young cells
into an aging aging something a more
potent effect if they were your stem
cells right now I don't think so because
again the placental cells are the
universal donor I think there are
advantages to giving someone else's
placental cells because you get that
chimeric benefit yeah that
okay so huge impact in rats are we
running any long tail studies on Aging
life extension and stem cells so here's
the Dilemma we have
um
to the regulatory community and to and
to a good part of the clinical community
aging isn't a disease right aging is a
process and and so it's very difficult
to convince that community
in all cases that an attempt to address
aging as the indication it ain't the way
to go
because first of all how long would the
study have to be in humans yeah you know
decades
now how are you going to show that you
can slow aging are you going to start
treating at 20 and look at them when
they're 80. it's kind of tough yes right
it's long it's long and they're sure and
that's what we care about but no one's
going to invest in that fair okay but
very fair we our approach is to say well
well let's look at conditions that are a
Hallmark of Aging one of those
conditions you and I know about very
well sarcopenia
age-related loss of muscle mass
sarcopenia is in fact a a Hallmark of
age-related degenerative processes
if you say that
can and and
you remember from our from our days
developing strategies to block things
like myostatin that if you can if you
can
um
in in essence
um
have a have a a known rate of decline in
an organ or tissue and in muscle we
estimate that after the age of about 25
average people lose one to two percent
of their lean muscle mass every year
whoa right and by the way
you you've helped provide tools to
address one of the reasons why we lose
muscle which is a protein defect right
if you now say okay
I'm going to administer something which
is going to block or reverse the loss of
lean muscle mass and maintain the
Integrity quantity and quality of muscle
tissue into our Advanced years is that a
tool we use to address aging and I argue
that yeah it would be and so where we're
deeply committed to exploring how
placental newborn derived stem cells
administered to support the integrity
and the health of our muscle tissue
might be one of the most actionable ways
to address aging and let me give you one
one clinical reason why I believe that
the karolinsky Institute which is like
the Mayo Clinic of Europe
they did a study where they followed 9
000 men for 25 years like a Framingham
type stuff
and they were looking to see whether
they could correlate body mass index BMI
to risk of risk of death and risk of
risk of death from cancer risk of all
death risk of just death from
cardiovascular disease and the everyone
assumed that of course
BMI is going to definitely have a
relationship what they found was that
BMI wasn't correlated
what was correlated to resistance to
death and death from cancer and heart
disease was was muscle mass that's why
BMI is dumb BM is very dumb doesn't
differentiate between fat and muscle the
average bodybuilder extreme athlete you
find at the gym is morbidly obese by
those scales right right the truth of
the matter is that that BMI ain't
related to your your risk profile for
certain things but if you maintain your
muscle mass and strength into your
Advanced years 70s and 80s
the report showed you had a lower risk
of dying from cancer by 30 to 40 percent
impacts cancer yeah I'm not really
scandalized by that you but let me tell
you why please let me tell you why your
muscle mass makes up in the average
individual 50 of your wet body mass yeah
which means it's the largest venous
capacitance organ in your body you have
more volume of venous blood in your
muscle tissue than anywhere else right
it's just a it's a lot of tissue and a
lot of blood vessels
in your low pressure venous system is
where the blood the blood cells the
immune cells and the stem cells that are
traversing your system they stick to the
walls
they stick to the walls of those little
low pressure blood vessels why do they
do that because they're sitting there
waiting for signals to traffic into the
system what's one of the best things you
can do in response to injury or illness
exercise
exercise helps mobilize those immune and
Stems I have the flu I should work out
absolutely what absolutely and by the
way a hundred years of bed rest after Mi
and after surgery why do you think we
get patients up walking hours after
their surgery
we have a billy family rule if you're
sick you need to take the time off from
the gym because you're going to wear
yourself out you're going to decline
your immune system you're going to stay
sick longer I I could pass a lie
detector that that is 100 guaranteed
true fact and you're telling me that
it's delusion on my part in your
household
that that may be one of the tenants but
I will say you need to test the opposite
which is that if you actually exercise
and if you actually
um are you just running yourself down no
because look if this works the next time
I'm sick I'm [ __ ] hitting you you
have him you have to you have to weird
is this going to shorten the amount of
time that I'm sick absolutely because
I'll do anything to shorten the amount
of time remember the immune cells that
are going to protect you from that
infectious illness if if some of them
are sitting laying in weight in your in
your muscle tissue isn't there such a
thing as fatigue but like you're just
wearing yourself wow the reason you feel
fatigued is that your immune system is
is needs needs reinforcements to combat
the the illness you know like with covid
for example some of the problems with
covet is that you have you have residual
effects of of a highly stimulated immune
system localized that needs support and
and it's very very clear that even
things like massage help mobilize immune
cells and stem cells that take up
residence in your muscle tissue so next
time you're sick give me a call okay
yeah but I'm going to insist you go to
the gym and work out
work at work out work into a big sweat
and and I guarantee you I guarantee you
you will feel differently than you
expect it to feel man that is one thing
like Lisa and I talked a lot about that
because she is a workout demon right and
she no matter what sick whatever she
wants to be in the gym and I'm always
like you are gonna make yourself sick
for longer you're wearing yourself out
you're you know taking your immune
system down that's crazy well don't take
it just for me I want you to talk to any
cardiac surgeon you know any any surgeon
that you know and you ask them when you
guys started 20 30 40 years ago didn't
you keep patients in bed after surgery
how come now you get them up walking
immediately how come you you increase
immediately are we talking oh cardiac
surgeries patients will be walking the
night of their surgery whoa oh yeah oh
yeah
oh yeah wow so there's by the way and
they do it for lots of reasons they do
it in order to prevent stagnation of of
of your circulating blood they want to
make sure that you're that you're not
developing clots in your small blood
vessels and so on but there's another
big component of it which is that active
muscle active muscle actually helps your
immune function and helps initiate the
process of repair and Recovery
all right if I'm injecting stem cells
in the way that you're talking about to
fight the loss of muscle mass
am I going to just not lose the muscle
mass or does this have uh an androgenic
effect like if I am taking stem cells
obviously I still have to work out but
if I'm taking stem cells would I add
more muscle mass than I otherwise would
we have we have data from some of our
clinical studies not in muscle loss in
other diseases where the injection of
these stem cells into muscle tissue
encourage both improved circulation in
the muscle actually actually allowed us
we saw
that collateral circulation was
improving and we saw improvements in
muscle mass and function now we are
studying now we have a current IND an
investigational new drug application on
file to look at forms of muscle loss
associated with inherited diseases and
ultimately acquired diseases I am
extremely con that we will show
that you can in fact augment
um uh and and increase the quality and I
believe the quantity of muscle tissue
with the introduction of these stem
cells into your muscle uh as a
therapeutic
all right that definitely starts to get
interesting especially with the
correlation I'd never heard that it's
muscle mass is correlated to inversely
correlated to incidence of cancer
that is really intriguing talk to me
about genomics like what is the role of
our genes play in this is this gonna be
able to combat that kind of thing or
they're just totally unrelated no
there's listen everything everything
draws back to
your underlying biological software and
what that encodes for everything from
the health and integrity of your stem
cell population to how those stem cells
function there's no doubt about that
however
we already know that that you you may be
born with a certain genome
that genome May in fact be affected by
we talked about before epigenetic
changes and so on
but consider that if you can actually
boost or augment your genomic
capabilities with chimeric therapy or
the introdu introduction of a
therapeutic product that even exists
transiently in your body like a Cell
Therapy that the more the more genetic
alleles you have access to select from
the more likely you are to accommodate
for any disease or illness and that's
again that's that's that's the process
of natural selection
biology biology is driven towards
whatever allows survival right
it's one of the reasons why um uh even
even viruses which are not living need a
host and if the host isn't viable the
virus goes away so viruses that kill too
fast don't stay in this don't stay in
the environment too long right
um so
you know it's a complicated it's a
complicated
um dance between the programming in your
genes
the quality of the stem cells in your
body
and the and the the diseases and the
threats they have to address and if you
and if that balance is always shifted
towards giving you the greatest
optionality genetic optionality cellular
optionality you have the greatest
probability of being able to survive
what do you think about fat in all of
that so obviously keeping muscle mass
High critically important but fat is an
organ as a
as an organ that secretes hormones like
what what is that role I do worry about
that in terms of you can have all the
muscle in the world but if you also have
a ton of fat you're going to be creating
problems for yourself
you know the reality is that the the
experts in metabolism
um will tell you that that
um you need a certain degree of fat for
normal
biologic and anatomic functions you know
fat plays a lot more of a role than just
storing uh storing energy fat also plays
a role in in cushioning your organs and
your tissues in other words believe it
or not you have fat around your organs
and tissues that are there to provide
shocks shock suppression okay
um and and there's different types of
fat that when stored
harder to mobilize them in order to
create energy and in some cases that fat
can actually wind up having negative
impacts on your anatomy and so on
however when you are operating at a
maximum optimal lean muscle mass
I guarantee you you'll have the best
balance to the to your fat stores
because that muscle mass helps control
the level of fat that you develop right
I mean you know the the um you've heard
about the uh uh the the what do they
call it they call it the the skinny fat
right people who appear to be thin and
in shape who actually if you actually
look at them if you actually dissect
them you realize that they have very
little muscle mass and it's been
replaced by by fatty tissue that's
actually age-related sarcopenia
there is a there is a balance there that
that can be optimized if you optim if
you focus on optimizing one system which
is the lean muscle mass very interesting
so you have less concern I'm putting
words in your mouth so correct me if I'm
wrong but you have less concern about
somebody carrying too much fat if
they've got the muscle to back it up and
in fact there is such a thing as too
little fat absolutely I mean we know
that from the population of cachptic and
anorexic patients right you also put the
muscle back on the anorexic patient or a
bodybuilder for that matter they're
getting down to you know two three
percent fat like are they I doubt this
has been studied but are there if you've
got a gaggle of muscle mass but very
little fat are you does your
survivability start to go down
so
I don't want to I don't want to make any
statements about how how long can you be
in the true bodybuilder phenotype in
your lifetime and still be healthy yeah
I don't I I can't answer that but I
don't believe personally that the the
true competitive bodybuilder phenotype
is a form that you can sustain your
entire lifetime okay look at you
remember Jack LaLanne of course Jack
LaLanne was an incredibly fit guy
he wasn't two percent body fat right he
was more like the norm
I think that that the the quest to
reduce body fat for the aesthetic
purposes okay
in temporary or transient use
supports the the objectives of that
particular individual but over a long
sustained period of time I think it's
dangerous
all right obviously you co-authored the
amazing book life force where else can
people find you so a couple of things so
I'm really excited you know one of my
important Partners
um in in this whole Quest is uh is is
DLP a company that that uh not only has
deep interest in their business but also
in in advancing the state of health
around the world so you know we're very
excited about about the success of the
book but we're also very excited about
working with with one of our partners
DLP Capital uh which is not only
supportive of their of their business
but also using their business to help
Advance progress in our field
um I'm very very excited to be one of
the speakers at their event in Puerto
Rico in San Juan the 9th to the 12th of
November and for those folks who want to
actually come and hear me meet me speak
with me uh or talk to other of my
colleagues we'd love them to go to
dlpcapital.com under events they can
actually register for this program and
they can join us and I can tell you
having been in several of these it's
it's it's one remarkable assembly of of
of of investors health conscious people
uh scientists Physicians and I'm excited
about being able to talk about what you
and I have been talking about as well as
some additional things we're doing at
cellularity and and at um uh Fountain
life which as you know is our Clinic
operations I love it yeah guys if you
haven't already be sure to subscribe and
until next time my friends be legendary
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