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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 ce