Kind: captions
Language: en
the following is a conversation with
Paulo Lara Lara she's a professor of
stem cell and regenerative biology at
Harvard University and is interested in
understanding the molecular laws that
govern the birth differentiation and
assembly of the human brains cerebral
cortex she explores the complexity of
the brain by studying and engineering
elements of how the brain develops this
was a fascinating conversation to me
it's part of the artificial intelligence
podcast if you enjoy it subscribe on
YouTube give it five stars and iTunes
supported on patreon
I simply connect with me on Twitter at
Lex Friedman spelled Fri D ma a.m. and
I'd like to give a special thank you to
Amy Jeffress for support of the podcast
on patreon she's an artist you should
definitely check out her Instagram and
love truth good three beautiful words
your support means a lot and inspires me
to keep the series going and now here's
my conversation with Paola our Lada
you studied the development of the human
brain for many years so let me ask you
and out-of-the-box question first how
likely is it that there's intelligent
life out there in the universe outside
of Earth with something like the human
brain so I could put it another way how
unlikely is the human brain how
difficult is it to build a thing through
the evolutionary process well it has
happened here I on this planet once yes
once so that simply tells you that it
could of course happen again other
places is only a matter of probability
what the probability that you would get
a brain like the ones that we have like
like the human brain so how difficult is
it to make the human brain it's pretty
difficult but most importantly I guess
we know very little about how this
process really happens and there is a
reason for that actually multiple
reasons for that most of what we know
about how the mammalian brain so the
brain of mammals developed comes from
studying in labs other brains not our
own brain the brain of mice for example
but if I showed you a picture of a mouse
brain and then you put it next to a
picture of a human brain they don't look
at all like each other so they're very
different and and therefore there is a
limit to what you can learn about how
the human brain is made by studying the
mouse brain the region there is a huge
value and studying the mouse brain there
are many things that we have learned but
it's not the same thing
so in having studied the human brain or
through the mouse and through other
methodologies that we'll talk about do
you have a sense I mean you're one of
the experts in the world how much do you
feel you know about the brain and how
much how often do you find yourself in
awe of this mysterious thing yeah you
pretty much find yourself you know all
the time it's an amazing process it's a
process
which by means that we don't fully
understand
at the very beginning of embryogenesis
the structure called the neural tube
literally self-assembles and it happens
in an embryo and it can happen also from
stem cells in a dish okay and then from
there these stem cells that are present
within the neural tube give rise to all
of the thousands and thousands of
different cell types per present in the
brain through time right with the
interesting very intriguing interesting
observation is that the time that it
takes for the human brain to be made
it's human time meaning that for me and
you it took almost nine months of
gestation to build the brain and then
another twenty years of learning
postnatally to get the brain we have
today that allows us to this
conversation a mouse takes twenty days
or so too small for an embryo to be born
and so and and so the brain is built in
a much shorter period of time and the
beauty of it is that if you take mouse
stem cells and you put them in and
culture - the brain the orbit the brain
organoid that you get from a mouse is
formed faster that if you took human
stem cells and put them in the dish and
let them make a human brain organoid so
the very developmental process is
controlled by the speed of the species
which means it's by its own purpose it's
not accidental or there is something in
that temporal it's very exactly that is
very important for us to get the brain
we have and we can speculate for why
that is you know it takes us a long time
as as human beings after we're born to
learn all the things that we have to
learn to have the adult brain it's
actually 20 years think about it from
when a baby is born or - when a teenager
goes through puberty to adults it's a
long time do you think you can maybe
talk through
the first few months and then on to the
first 20 years and then for the rest of
their lives
what is the development of the human
brain look like what are the different
stages at the beginning you have to
build a brain right and the brain is
made of cells what's the very beginning
which beginning I were talking in the
embryo as the embryo is developing in
the womb in addition to making all of
the other tissues of the embryo the
muscle the heart the blood the embryo is
also building the brain and it builds
from a very simple structure called the
neural tube which is basically nothing
but a cube of cells that spans sort of
the length of the embryo from the head
all the way to the tail let's say of the
embryo and then over in human means over
many months of gestation from that
neural tube which contains stem
cell-like cells of the brain you will
make many many other building blocks of
the brain so all of the other cell types
there are many many different types of
cells in the brain that will form
specific structures of the brain so you
can think about embryonic development of
the brain is just the time in which you
are making the building blocks the cells
at the stem cells relatively homogeneous
like uniform or they all different ok
good question it's exactly how it works
you start with a more homogeneous
perhaps more multipotent type of stem
cell that most importantly means that it
can it has the potential to make many
many different types of other cells and
then with time these progenitors become
more heterogeneous which means more
diverse there are going to be many
different types of the stem cells and
also they will give rise to progeny to
other cells that are not themselves that
are specific cells of the brain that are
very different from the mothers
themselves and now you think about this
process of making cells from the stem
cells over many many months of
development for humans and
and what you're doing you're building
the cells they physically make the brain
and then you arrange them in specific
structures that are present in the final
brain so you can think about the
embryonic development of the brain as
the time where you're building the
bricks you're putting a bricks together
to form buildings structures regions of
the brain and where you make the
connections between these many different
type of cells especially nerve cells
neurons right that transmit action
potentials and electricity I've heard
you also says somewhere I think correct
me if I'm wrong that the order of the
way this builds matters oh yes if you
are an engineer and you think about
development you can think of it as well
I could also take all the cells and
bring them all together into a brain in
the end but development is much more
than that so the cells are made in a
very specific order that subserve the
final product that you need to get and
so for example all of the nerve cells
the neurons are made first and all of
the supportive cells of the neurons like
the glia is made later and there is a
reason for that because they have to
assemble together in specific ways but
you also may say well why don't we just
put them all together in the end it's
because as they develop next to each
other they influence their own
development so it's a different thing
for a glia to be made alone in a dish
then a glia be made in a glial cell be
made in a developing embryo with all
these other cells surrounded they
produce all these other signals first of
all that's mind-blowing that this
development process from my perspective
in artificial intelligence you often
think of how incredible the final
product is the final product the brain
but you just you're making me realize
that the final product is just is the
the beautiful thing is the actual
development and development process do
we know the code that drives that
development
do we have any sense first of all thank
you for saying that
it's really the formation of the brain
it's really its development this
incredibly choreograph dance that
happens the same way every time each one
of us builds the brain right and that
builds an organ that allows us to do
what we're doing today right yeah that
is mind blowing and this is why
developmental neurobiologists never get
tired in that now you're asking about
the code what drives this how is this
done well it's you know millions of
years of evolution of really fine-tuning
gene expression programs that allow
certain cells to be made at a certain
time and to be in to become a certain
you know cell type but also mechanical
forces of pressure bending this embryo
is not just it will not stay a tube this
this brain for very long at some point
is tube in the front of the of the
embryo will expand to make the
primordium of the brain right now they
the forces that control that these cells
feel and this is another beautiful thing
at the very force that they feel which
is different from a week before a week
ago will tell the cell oh you're being
squished in a certain way begin to
produce these new genes because now you
are at the corner or you are you know in
a stretch of cells or whatever it is and
there so that mechanical physical force
shapes the fate of the cell as well so
nala chemical is also mechana mechanical
so from my perspective biology is this
incredibly complex mess gooey mess so
you're seeing mechanical forces how
different is a like a computer or any
kind of mechanical machine that we
humans build and the biological systems
have you been because you've worked a
lot with biological systems are they as
much of a mess as it seems from a
perspective of an engineer mechanical
engineer yeah
they are much more prone to taking
alternative routes right so if you we go
back to printing a brain versus
developing a brain of course if you
print a brain given that you start with
the same building blocks the same cells
you could potentially print it the same
way every time but that final brain may
not work the same way as a brain built
during development does because the
build very build very same building
blocks that you're using developed in a
completely different environment right
there was not the environment of the
brain therefore they're going to be
different just by definition so if you
instead use development to be able to
say a brain organoid which maybe we'll
be talking about in a future those
things are fascinating yes so if you if
you use processes of development then
you when you watch it you can see that
sometime things can go wrong in some
organ weights and by wrong I mean
different one organ way from the next
well if you think about that embryo it
always goes right so it's this
development it's for as complexity as it
is every time a baby is born has you
know with very few exceptions so the
brain is like the next baby but it's not
the same if you develop it in a dish and
first of all is we don't even develop a
brain you develop something much simpler
in the dish but there are more options
for building things differently which
really tells you the evolution as has
played a really tight game here for how
in the end the brain is built in vivo so
just a quick may be dumb question but it
seems like this is not the building
process is not a dictatorship it seems
like there's not a centralized like
high-level mechanism that says ok this
cell built itself the wrong way I'm
going to kill it it seems like it's
there's a really strong distributed
mechanism
is that is that in your sense for there
are a lot of there are a lot of
possibilities right and if you think
about for example different species
building their brain each brain is a
little bit different so the brain of a
lizard is very different from that of a
chicken from that of a you know one of
us and so on and so forth and still is a
brain but it was built differently if
starting from stem cells that pretty
much had the same potential
but in the end evolution builds
different brains in different species
because that serves in a way the purpose
of the species and the well-being of
that organism and so there are many
possibilities but then there is a way
and you were talking about a code nobody
knows what the entire code of
development is of course we don't we
know bitten bits and pieces of very
specific aspects of development of the
brain what genes are involved to make a
certain cell types out those two cells
interact to make the next level
structure that we might know but the
entirety of it oh it's so well control
it's really mind-blowing so in the first
two months in the embryo or whatever the
first few months
so yeah the the building blocks are
constructed the actual the different
regions of the brain I guess in the
nervous system
well this continuous way longer than
just the first few months so over the
the very first in a few months you build
a lot of the cells but then there is a
continuous building of new cell types
all the way through birth and then even
post Natalie you know I don't know if
you ever heard of myelin myelin is this
shrub insulation that is build around a
cable some of the neurons so that the
electricity can go really fast the front
axons I guess the axons are called axons
exactly and and so as human beings we my
alienate ourselves post Natalie a kid
you know a six-year-old kid has barely
started
so making the mature oligodendrocytes
which are the cells then eventually will
wrap with the axons in to myelin and
this will continue believe it or not
until we are about you know 2530 years
old so there is a continuous process of
maturation and tweaking and additions
and and also in response to what we do I
remember taking ap biology in high
school and in the textbook it said that
I'm going by memory here that scientists
disagree on the purpose of myelin in in
the brain is that is that's totally
wrong so like it I guess it speeds up
the book okay might be wrong here but I
guess it speeds up the electricity
traveling down the axon or something
that's the most sort of canonical and
definitely that's the case so you have
to imagine an axon and you can think
about it as a cable or some type with
electricity going through and what
myelin does by insulating the outside I
should say there are tracks of myelin
and pieces of axons that are naked
without my Elaine and so by having the
insulation the electricity instead of
going straight through the cable it
would jump over a piece of myelin right
to the next naked little piece and jump
again and therefore you you know that's
the idea that you go faster and it was
always thought that in order to build a
big brain a big nervous system in order
to have a nervous system it can do very
complex the type of things then you need
a lot of myelin because you want to go
fast with this information from point A
to point B well a few years ago maybe
five years ago or so we discovered that
some of the most evolved which means the
newest type of neurons that we have as
non-human primates as as human beings in
the top of our cerebral cortex which
should be the neurons do some of the
most complex things that we do well
those F axons that have very little
myelin and they have very interesting
way
in which they put the smiling on their
axles you know a little piece here then
a long track with no mining another
chunk there and some don't have mining
at all so now you have to explain where
we're going with evolution and if you
think about it perhaps as an electrical
engineer when I looked at it I initially
thought and I'm a developmental
neurobiology I thought maybe this is
what we see now but if we give evolution
another few million years we see a lot
of myelin on these neurons - but I
actually think now that that's instead
the future brain less myelin am i allow
for more flexibility on what you do with
your actions and therefore more
complicated and unpredictable type of
functions which is also a bit
mind-blowing so it seems like it's
controlling the timing of the signal so
they're in the timing
you can encode a lot of yes information
yeah and so the brain I mean the
chemistry of that little piece of axon
perhaps is a dynamic process where the
myelin can move now you see how many
layers of variability you can add and
that's actually really good
if you're trying to to come up with a
new function or a new capability or
something unpredictable in a way so
we're gonna jump around a little bit but
the old question of how much is nature
and how much is nurture in terms of this
incredible thing after the development
is over we seem to be kind of somewhat
smart intelligent cognition
consciousness all these things are just
incredible ability reasons so on emerge
in your sense how much is in the
hardware in the nature and how much is
in the nurture has learned through with
our parents to interact in the
environment so on it's really both right
if you think about it so we are born
with the brain as babies there has most
of his South and most of structures and
we'll take a few years to you know to
grow to add more to be better but really
then we have this 20 years of
interacting with the environment around
us and so what that brain that was so
you know perfectly built or imperfectly
built due to our genetic cues will then
be used to incorporate the environment
in its further maturation and
development and so your experiences do
shape your your brain I mean we know
that like if you know you and I may have
had a different childhood or a different
we have been going to different schools
we have been learning different things
and our brain is a little bit different
because of that we behave differently
because of that and and so especially
postnatally experience is extremely
important we are born with a plastic
brain what that means it's a brain it is
able to change in response to stimuli
they can be sensory so perhaps some of
the most illuminating studies that were
done were studies in which the sensory
organs were now working right if you are
born with eyes that don't work then your
very brain that no piece of the brain
that normally would process vision the
visual cortex develops postnatally
differently and it might be used to do
something different right so the most
extreme the plasticity of the brain I
guess is the magic hardware that it and
then it's it's flexibility in all forms
is what enables the learning yes Natalie
can you talk about organoids
what are they yes and how can you use
them to help us understand the brain and
the development of the brain this is
very very important so the first thing
I'd like to say please keep this in the
video the first thing I'd like to say is
that an organ or a brain organoid is not
the same as a brain okay it's a
fundamental distinction it's
a system a cellular system that one can
develop in the culture dish
starting from stem cells that will mimic
some aspects of the development of the
of the brain but not all of it they are
very small maximum they become about you
know four to five millimeters in
diameter they are much simpler than than
our brain of course by yet they are the
only system where we can literally watch
a process of human brain development
unfold and by watch I mean study it
remember when I told you that we can't
understand everything about development
our own brain by studying a mouse well
we can study the actual process of
development of the human brain because
it all happens in utero so we will never
have access to that process ever and
therefore this is our next best thing
like a a bunch of stem cells that can be
coaxed into starting a process of neural
tube formation remember that cube that
is made by the embryo early on and from
there a lot of the cell types that are
present within within the brain and you
can simply watch it and study but you
can also think about diseases where
development of the brain does not
proceed normally right properly think
about neurodevelopmental diseases there
are many many different types think
about all these own spectrum disorders
there are also many different types of
autism so there you could take a stem
cell which really means either a sample
of blood or a sample of skin from the
patient make a stem cell and then with
that stem cell watch a process of
formation of a brain organ with of their
person the person with that genetics
with that genetic code in it and you can
ask what is this genetic code doing to
some aspects of development of the brain
for the first time you may come to
solutions like what cells are involved
in autism so right so many questions
around this so if you take
this human stem cell for that particular
person with that genetic code how and
you try to build an organized yeah how
often will it look similar
what's the produce ability yes or how
much variability its website of that
yeah so there is much more variability
in building organoids
than there than there is in building
brain it's really true that the majority
of us when we are born as babies our
brains look a lot like each other this
is the magic that the embryo does where
it builds a brain in the context of a
body and and there is very little
variability there there is disease of
course but in general little variability
when you build an organizer you know we
don't have the full code for how this is
done and so in part the organoid
somewhat built itself because there are
some structures of the brain that the
cells know how to make and another part
comes from the investigator the
scientist add in to the media factors
that we know in the mouse for example
would foster a certain step of
development but it's very limited and so
as a result the kind of product you get
in the end is much more reduction is
this much more simple than what you get
in vivo it mimics early events of
development as of today and it doesn't
build very complex type of anatomy and
structure does not as of today which
happens is that in in vivo and also the
variability that you see one organ or to
the next
tends to be higher than we'll compare an
embryo to the next so okay then the next
question is how hard and maybe another
flip side of that expensive is it to go
from one stem cell to an organized yeah
how many can you build and like this
sounds very complicated
it's work definitely and it's money
definitely but you can really grow a
very high number of this organoids you
know can go
I told you the maximum they become about
five millimeters in diameter so this is
about the size of a of a tiny tiny you
know raising or perhaps the seed of an
apple and so you can grow 50 to 100 of
those inside one big bioreactors which
are these flasks where the media
provides nutrients for the organoids
so the problem is not to grow more or
less of them it it's really to figure
out how to grow them in a way that they
are more and more reproducible for
example orgonite organize so they can be
used to study a biological process
because if you have too much variability
then you never know if what you see is
just an exception or really the rule so
what is an organize look like are there
different neurons already emerging is
there you know well first can you tell
me what kind of neurons are there yes
are they sort of all the same are they
not all the same as to how much do we
understand and how much of that variance
if any can exist in organoids yes so you
could grow I told you that the brain has
different parts so the cerebral cortex
is on top at the top part of the brain
but there is another region called the
striatum that is below the cortex and so
on and so forth all of these regions
have different types of cells in the
actual brain ok and so scientists have
been able to grow organoids that may
mimic some aspects of development of
these different regions of the brain and
so we are very interested in the
cerebral cortex that's the coolest part
you're talking if we didn't have a
cerebral cortex it's also I like to
think the part of the brain that really
truly makes us human the most evolved in
recent evolution and so in the attempt
to make the cerebral cortex and by
figuring out a way to have this
organoids continue to grow and develop
for extended periods of times much like
it happens in the real embryo months and
months in culture there
you can see that there many different
types of neurons of the cortex appear
and at some point also the astrocytes to
the glia cells of the cerebral cortex
also appear what are these the
astrocytes are not neuron so they're not
nerve cells but they they play very
important roles one important role is to
support the neuron but of course they
have much more active type of roles are
very important for example to make the
synapses which are the point of contacts
and communication between two neurons
they all that chemistry fun happens
between the synapses happens because of
these cells are they the medium in which
it happens because of the interactions
happens because you are making the cells
and they have certain properties
including the ability to make you know
neurotransmitters which are the
chemicals that are secreted to the
synapses including the ability of making
this axons grow with their growth cones
and so on and so forth and then you have
other cells around there that release
chemicals or touch the neurons or
interact with them in different ways to
really foster this perfect process in
this case of synaptogenesis and this
does happen within within organized so
the mechanical and the chemists and
chemical stuff happens yes the
connectivity between neurons this video
why is not surprising because scientists
have been culturing neurons forever and
when you take a new don't even a very
young one and you culture it eventually
finds another cell or another neuron to
talk to it will form a synapse are we
talking about Meisner on my human neuron
it doesn't matter both so you can
culture and you out like a single neuron
and give it a little friend
and it starts interacting yes so neurons
are able to it sounds it's more simple
than what it may sound to you neurons
have molecular properties and structural
properties allow them to really
communicate with other cells and so if
you put not one neuron but if you put
several neurons together chances are
that they will form synapse
is with each other okay great so an
organized not a brain but but uh there's
some it's able to especially what you're
talking about mimic some properties of
the cerebral cortex for example so what
what can you understand about the brain
by studying an organize of a cerebral
cortex
I can literally study how all this
incredible diversity of cell type all
these many many different classes of
cells how are they made how do they look
like what do they need to be made
properly and what goes wrong if now the
genetics of that stem cell that I used
to make the organ we came from a patient
with a neurodevelopmental disease can I
actually watch for the very first time
what may have gone wrong years before in
this kid when its own brain was being
made think about that loop in a way it's
a little tiny rudimentary window into
the past into the time when that brain
in a kid they had this you know
developmental disease was being made and
I think that's unbelievably powerful
because today we have no idea of what
cell types we barely know what brain
regions are affected in these diseases
now we have an experimental system that
we can study in the lab and we can ask
what are the cells affected when during
development things went wrong what are
the molecules among the many many
different molecules that that control
brain development which ones are the
ones they're really messed up here and
we want perhaps to fix and what is
really the final product is it a less
strong kind of circuit and brain is it a
brain that lacks a cell type is it what
is it because then we can think about
treatment and and care for these
patients that is informed rather than
just based on current diagnostics so how
hard is it to detect through the
development of process the
super-exciting mech tool
just to see how different conditions
develop how hard is it to detect it wait
a minute this is abnormal development
yeah that's how hard is how much signal
is there how much of it is is it a mess
because things can go wrong multiple
levels right you could have a cell that
is born and built but then doesn't work
properly or a self is not even born or a
cell does interact with other cell
differently and so on and so forth so
today we have technology that we did not
have even five years ago that allows us
to look for example at the molecular
picture of a cell of a single cell in a
sea of cells with high precision and so
that molecular information where you
compare many many single cells for the
genes they produce between a control
individual and an individual with and
your developmental disease that may tell
you what is different molecular Li or
you could see that some cells are not
even made for example or that the
process of maturation of the cells may
be wrong there are many different levels
here and and we can study these cells at
the molecular level but also we can use
the organ is to ask questions about the
properties of the neurons the functional
properties how they communicate with
each other out they respond to a
stimulus and so on and so forth and we
may get at abnormalities their detectors
so how early is this work in a maybe in
the history of science so I mean like so
if you were to if you and I time travel
a thousand years into the future
organize seem to be maybe I'm
romanticizing the notion but you're
building not a brain but something that
has properties of a brain so you it
feels like you might be getting close to
in the building process thought to build
us to understand
so how how far are we in this
understanding process of development
thousand years from now it's a long time
from now so if this planet is still
gonna be here and a thousand years from
now you know like they write a book
obviously you there'll be a chapter
about you that science fiction book
today today but I mean I guess where we
really understood very little about the
brain a century ago was big fan in high
school reading Freud and so on and still
AM of Psychiatry I would say we still
understand very little about the
functional aspect of just yeah but how
in the history of understanding the
biology of the brain the development how
far are we alone it's a very good
question and so this is just of course
my opinion I think that we did not have
technology even ten years ago or 20
certainly not 20 years ago to even think
about experimentally investigating the
development of the human brain so we've
done a lot of work in science to study
the brain or many other organisms now we
have some technologies which I'll spell
out that allow us to actually look at
the real thing and look at the brain at
the human brain so what are these
technologies there is been huge progress
in stem cell biology the moment someone
figured out how to turn a skin cell into
an embryonic stem cell basically and
that out that embryonic stem cell could
begin a process of development again to
correct for example make a brain there
was a huge and you know advance and in
fact there was a Nobel Prize for that
that started the field really of using
stem cells to build organs now we can
build on all the knowledge of
development that we build over the many
many many years to say how do we make
the stem cells now make more and more
complex aspects of development of the
human brain so this field is younger the
field of brain organics but is moving
faster and it's moving fast in a very
serious way that is rooted in labs with
the right ethical framework
and and really building on you know
solid science for reality is and what is
not and but it will go faster and it
will be more and more powerful we also
have technology that allows us to
basically study the properties of single
cells across many many millions of
single cells which we didn't have
perhaps five years ago so now with that
even an organ or that has millions of
cells can be profiled in a way looked at
very very high resolution the single
cell level to really understand what is
going on and you could do it in multiple
stages of development and you can build
your hypothesis and so on and so forth
so it's not going to be a thousand years
it's gonna be a shorter amount of time
and I see this as sort of a an
exponential growth of this field enabled
by these technologies that we didn't
have before
and so we're gonna see something
transformative that we didn't see at all
in the prior thousand years so I
apologize for the crazy sci-fi questions
but the developmental process is
fascinating to watch and study but how
far are we away from and maybe how
difficult is it to build not just an
organ or but a human brain okay from us
themself yeah first of all that's not
the goal for the majority of the serious
scientists that work on this because you
don't have to build the whole human
brain to make this model useful for
understanding of the brain develops or
understanding disease you don't have to
build the whole thing
so let me is let me just comment on that
it's fascinating it shows to me the
difference between you and I is you're
actually trying to understand the beauty
of the human brain and to use it to
really help thousands or millions of
people disease and so on right from an
artificial intelligence but we're trying
to build systems that we can put in
robots and try to create systems that
have echoes of the intelligence
about reasoning about the world
navigating the world its
its different objectives I think we
operate in size fix a little bit but so
so on that point of building a brain
even though that is not the focus or
interest perhaps of the community how
difficult is it is it truly science
fiction at this point I think the field
will progress like I said and that the
system will be more and more complex in
a way right but there are properties
that emerge from the human brain they
have to do with the mind they may have
to do with conscious name I have to do
with intelligence or whatever that we
don't really don't don't understand even
now they can emerge from an actual real
brain and therefore we cannot measure or
study in an organized so so I think that
this field many many years from now may
lead to the building of better neural
circuits of you know that really are
built out of understanding about this
process really works and it's hard to
predict how complex this really will be
I really don't think we're so far from
it makes me laugh really it's really
that far from building the human the
human brain but you're gonna be building
something that is you know always a bad
version of it but that may have really
powerful properties and might be able to
you know respond to stimuli or or be
used in in certain context and this is
why I really think that there is no
other way to do this science but within
the right ethical framework because
where you're going with this is also you
know we can talk about science fiction
and write that book and we could today
but this work happens in a specific
ethical framework that we don't decide
just a scientist but also as a society
so the ethical framework here is a
fascinating one is the complicated one
do you have a sense a grasp of how we
think about ethically of building
organoids
from human stem cells to understand the
brain it seems like a tool for helping
potentially millions of people cure
diseases are at least start the cure by
understanding it but is there more is
there gray areas that are at the that we
have to think about ethically absolutely
we must think about that every
discussion about the ethics of this
needs to be based on actual data from
the models that we have today and from
the ones that we will have tomorrow so
it's a continuous conversation it's not
something that you decide now today
there is no issue really very simple
models they that clearly can help you in
many ways without much much think about
but tomorrow we need to have another
conversation and so on and so forth and
so the way we do this is to actually
really bring together constantly a group
of people that are not only scientists
but also bioethicists the lawyers
philosophers psychiatrist and so on as a
psychologist and so on and so forth to
decide as a society really what we
should and what we should not do so
that's the way to think about the ethics
now I also think though that as a
scientist I have a moral responsibility
so if you if you think about how
transformative it could be for
understanding and curing a
neuropsychiatrist
to be able to actually watch and study
and treat with drugs the very brain of
the patient that you are trying to study
how transformative at this moment in
time this could be we couldn't do it
five years ago we could do it now right
if taking of a particular patient
patient and make an organ or for a
simple and you know different from the
from the human brain he still is his
process of brain development with his
with his or her genetics and we could
understand perhaps what is going wrong
perhaps we could use as a platform as a
cellular platform to screen for drugs to
fix a process
and so on and so forth right so we could
do it now we couldn't do it five years
ago should we not do it what is the
downside of doing it I don't see a
downside if you would but if we invited
a lot of people yes if I'm sure there
would be somebody who would would argue
against it what would be the devil's
advocate argument yeah
so it's exactly perhaps what you eluded
it with your question that you are
making as enabling you know some some
process of formation of the brain that
could be misused at some point or there
could be showing properties that
ethically we don't want to see in a
tissue so today today this is not an
issue and so you you just gain
dramatically from the science without
because the system is so simple and and
so different in a way from from the
actual brain but but because it is the
brain we have an obligation to really
consider all of this right and again
it's it's a balanced conversation where
we should put disease and betterment of
humanity also on that plate what do you
think at least historically there were
some politicization of embryonic stem
cells a stem cell research do you still
see that out there is there is that
still a force that we have to think
about especially in this larger
discourse that we're having about the
role of science in at least American
society yeah this is a very good
question it's very very important I see
a very central role for scientist to
inform decisions about what we should or
should not do in society and this is
because the scientists have the
first-hand look and understanding of
really the work that they are doing and
again this varies depending on what
we're talking about here
so now we're talking about Brian
organoids I think the scientists need to
be part of that conversation about what
is will be allowed in the future or not
allowed in the future to do with the
system and I think it's that is very
very important because they bring
reality of data to the conversation and
and and so they should have a voice so
data should have a voice
it needs to have a voice because a not
only data we should also be good at
communicating with non scientists the
data so there has been often time there
is a lot of discussion and you know
excitement and fights about certain
topics just because of the way they are
described I'll give you an example if I
call that the same cellular system we
just talked about a brain organoid or if
i called it a human mini brain your
reaction is going to be very different
yes to this and so the way the systems
are described I mean we and journalists
alike need to be a bit careful that this
debate is a real debate and inform
burial data that's all I'm asking and
yeah the language matters here so I work
on autonomous vehicles and their the use
of language could it could it could
drastically change the interpretation
and the way people feel about what is
the right way to proceed forward
you are as I've seen from a presentation
you're a parent as I show a couple
pictures of your son is it just the one
to sign a daughter so what have you
learned from the human bracing two of
them what have I learned I've learned
that children really have this amazing
plastic minds right that we have a
responsibility to you know foster their
growth in good healthy ways that keep
them curious that keeps
adventures that doesn't raise them in
fear of things but also respecting who
they are which is in part you know
coming from their genetics we talked
about my children are very different
from each other despite the fact that
they're the product of the same two
parents I also learned that what you do
for them comes back to you like you know
if you're a good parent you're gonna
most of the time have you know perhaps a
decent kids at the end what do you think
just a quick comment what what do you
think is the source of that difference
it's often the surprising thing for
parents is it can't believe that our
kids oh they're so different yet they
came from the same parents well they are
genetically different even they came
from the same two parents because the
mixing of gametes I mean you know we
know these genetics creates every time a
genetically different individual which
will have a specific mix of genes that
is a different mix every time from the
two parents and so so they're not twins
so they are genetically different is
that a little bit of variation as you
said really from a biological
perspective the brains look pretty
similar well so let me clarify that so
the genetics you have the genes that you
have at that play that beautiful
orchestrated symphony of development
different genes will play it slightly
differently it's like playing the same
piece of music but with the different
orchestra and a different director right
the music will not come out it will be
still a piece by the same you know
author but it will come out differently
if it's played by the high school
orchestra instead of and so you are born
superficially with the same brain it has
the same cell types similar patterns of
connectivity but the properties of the
cells and how the cells we then react to
the environment as you experience your
word will be also shaped by pujan
ethically you are speaking just as a
parent
this is not something that comes from my
work I think you can tell a birth
differently that they have a different
personality in a in a way right so both
is needed the genetics as well as the
nurturing afterwards so you are one
human with a brain instead of living
through the whole mess of it the human
condition full of love maybe fear
ultimately mortal how has studying the
brain changed the way you see yourself
and you look in the mirror when you
think about your life the fear is the
love when you see your own life your own
mortality yeah that's a very good
question it's almost impossible to
dissociate sometime for me some of the
things we do or some of the things that
other people do from oh that's because
that part of the brain is working in a
certain way or thinking about a teenager
you know going through teenage years and
being at I'm funny in the way they think
and impossible for me not to think it's
because they're going through this
period of time called critical periods
of plasticity where their synapses are
being eliminated here and there and
they're just confused and so from that
comes perhaps a different take on the
behavior or maybe I can justify
scientifically in some sort of way I
also look at humanity in general and I
am amazed by what we can do and the kind
of ideas that we can come up where then
I cannot stop thinking about how the
brain is continuing to evolve I don't
know if you do this but I think about
the next brain sometimes what are we
going with it's like what are the
features of this brain that you know
evolution is really plain wait to get us
you know in the future the new brain
it's not over right it's it's a work in
progress
so let me just a quick comment on
do you see do you think there's a
there's a lot of fascination and hope
for artificial intelligence of creating
artificial brains you said the next
brain when you imagine over a period of
a thousand years the evolution of the
human brain do you sometimes envisioning
that future see an artificial one
artificial intelligence as it is hoped
by many not hoped thought by many people
would be actually the next evolutionary
step in the development yeah yeah I
think in a way that will happen right
it's almost like a part of the way we
evolved we evolved in the world that we
created that we interact with the shape
has as we grow up and so on and so forth
sometimes I think about something that
may sound silly but think about the use
of of cell phones part of me thinks that
somehow in their brain there will be a
region of the cortex that is this much
attuned to that tool and and this comes
from a lot of studies in in in model
organisms where really the cortex
especially adapts to the kind of things
you have to do so if we need to move our
fingers in a very specific way we have a
part of our cortex that allows us to do
this kind of very precise movement in an
owl that has to see very very far away
with big eyes the visual cortex very big
it's the brain attuned to your
environment so the brain will attune to
the to the technologies that we will
have and will be shaped by it
so the cortex very well maybe we shaped
by it in the artificial intelligence it
may merge with it they may get a envelop
it and adjust if it's not you know
emerge of the kind of oh let's have a
synthetic element together with a
biological one the very space around us
the fact for example think about we put
on some goggles of virtual reality and
we physically are surfing the ocean
right like I've done it and you have all
these emotions that come to you you
brain placed you in that reality and it
was able to do it like that just by
putting the goggles on it didn't take
thousands of years of adapting to this
the brain is plastic so adapts to new
technology so you could do it from the
outside by simply hijacking some sensory
capacities that we have so clearly over
you know recent evolution the cerebral
cortex has been a part of the brain that
has known the most evolution so we have
put a lot of chips on evolving this
specific part of the brain and the
evolution of cortex is plasticity it's
this ability to change in response to
things so yes they will integrate that
we want it or not well there is no
better way to end it Paula thank you so
much for talking about
you