Kind: captions
Language: en
the following is a conversation with
manolis kellis
his second time on the podcast he's a
professor at mit
and head of the mit computational
biology group
he's one of the most brilliant
productive and kind people
i've had the fortune of talking to a lot
of my colleagues at mit and
former mit faculty and students wrote to
me
after our first conversation with some
version of
minos is awesome isn't he i'm glad you
guys are not friends
i am too and i'm happy that he makes
time
in his insanely busy schedule to sit
down and have a chat with me
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one of the things that i think made his
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he just had fun and made choices that
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and now here's my conversation with
manolas
kalas what is beautiful about the human
epigenome
don't get me started so first of all as
an engineering feat
the human epigenome manages the most
compact
the most incredible compaction you could
imagine
so every single one of your cells
contains two meters worth of dna and
this is compacted
in a radius which is one thousandth of a
millimeter that's
six orders of magnitude to give you a
sense of scale
it's as if a string as tall as the burj
al khalifa
which is about a kilometer tall was
compacted into a tiny little ball
the size of a millimeter
and if you put it all together if you
stretch the trillions of cells that we
have we have about
30 trillion cells in your body if you
stretch the dna the 2 meters worth of
dna in every one of your trillion cells
you would basically reach all the way to
jupiter
a hundred times yeah it's all curled up
in there
it's 30 trillion cells 30 trillion
human body every one of them two meters
worth of dna so
all of that is compacted through the
epigenome
the epigenome basically has the ability
to compact
this massive amount of dna from here to
jupiter 10 times into one human body
into just the nuclei of one human body
and the vast majority of human bodies
not even
these nuclei and that's sort of the
structural part
so that's the boring part that's the
structural part the functional part
is way more interesting so functionally
what the human epigenome allows you to
do
is basically control the
activity patterns of thousands of genes
so 20 000 genes in your human body every
one of your cells only needs
a few thousand of those but a different
few thousand of those and the way that
your cells remember
what their identity is is basically
driven
by the epigenome so the epidural is both
structural
in sort of making this dramatic
compaction and it's also functional
in being able to actually control the
activity patterns
of all your cells now can we draw
a definition distinction between the
genome and the epigenome
again being greek epi means on top of
so the genome is the dna
and the epigenome is anything on top of
the dna
and there's you know three types of
things on top of the dna
the first is chemical modifications on
the dna itself
so we like to think of four bases of the
dna acgt
c has a methyl form which is sometimes
referred to as the fifth base
so methylc takes a different meaning
so in the same way that you have
annotations
in a orchestra score that basically say
whether you should play something softly
or loudly or space it out or you know
interpret basically the score the human
epigenome allows you to modify
that primary score so a modified c
basically says play this one softly it's
basically a sign of repression
in a gene regulatory region i love how
you're talking about the function that
emerges
from the epigenome as a musical score
it is in many ways and uh every single
cell plays a different part of that
score
it's like having all of human knowledge
in 23 volumes like 23 giant books which
are your chromosomes
and every single cell has a different
profession
a different role some cells play the
piano
and they're looking at chapter seven
from chromosome 23 and chapter four from
chromosome two and so forth
and each of those uh
pieces are all encoding in the same dna
but what the epigenome allows you to do
is effectively conduct the orchestra
and sort of coordinate the pieces so
that every instrument plays only the
things that it needs to play
one thing that kind of blows my mind
maybe you can
tell me your thoughts about it is the
the way evolution works with natural
selection
is uh based on the final sort of
the entirety of the orchestra
musical performance right and then but
there's these
incredibly rich structural things
like each one of them doing their own
little job that somehow work together
like
the evolution selects based on the final
result
and yet all the individual pieces are
doing like infinitely
minuscule specific things how the heck
does that work
right it's a very good insight and you
can even go beyond that
and basically say evolution doesn't
select at the level of
an organism it actually selects at the
level of whole environments whole
ecosystems
so let me break this down so you
basically have
at the very bottom every single
nucleotide
being selected but then that nucleotides
function is selected
at the level of you know each gene
and every not even its gene each
gene regulatory control element and then
those control elements are basically
converging
onto the function of the gene and many
genes are converging onto the function
of one cell
and many cells are converging into the
function of one tissue or organ
and all of these organs are converging
onto the level
of an organism but now that organism is
not in isolation
so if you basically think about why is
altruism for example
a thing why are people being nice to
each other
it was probably selected and it was
probably selected
because those species that were just
nasty to each other
didn't survive as a species and now if
you think about
um symbiosis
of you know there's plants for example
that love co2
and there's humans that love o2 and
we're sort of you know
trading different types of
gases to each other if you look at
ecosystems where one organism which is
really nasty
that organism actually died because
everyone they were being nasty to was
killed off
and then that kind of you know
universe of life is gone so basically
what emerges
is selection at so many different layers
of benefit including
you know all of these nucleotides within
a body
interacting for the emergent functions
at the body level yeah i wonder i wonder
if it's possible to break it down into
levels that's
selection even beyond humans like you
said environment but there's
environments at all different levels too
right
at the minuscule at the organ level the
tissue level like you said
maybe at the microscopic level it would
be fascinating if like
there's a kind of selection going on at
like
both the quantum level and like the
the galaxy level yeah yeah right yeah so
so all the different forms
yeah let's again sort of break down
these different layers so basically if
you think about the environment
in which a gene operates that gene of
course the
first definition of environment that we
think of is pollution
or sunlight or heat or cold
and so forth that's the external
environment but every gene also operates
at the level of the internal cellular
environment that it's in
if i take a gene from say an african
individual and i put it in a european
context
will it perform the same way probably
not because there's a cellular context
of thousands of other genes that that
gene has co-evolved with
you know in the out of africa event and
you know
all of this sort of human history of
evolution
so basically if you look at neandertal
genes for example
which again happened long after that uh
out of africa event
there's incompatibilities between
neanderthal genes
and modern human genes that can lead to
diseases
so in the context of the neonatal genome
that gene version that allele was fine
but in the context of the modern human
genome that neanderthal gene version is
actually detrimental
so it's it's you know that cellular
environment
constitutes the genetics of that gene
but also of course all of the
epigenomics of that gene it's
fascinating that the
the gene has a history i mean we talked
about this a little bit last time but
just and and then some of your research
goes into that but
the genes as they are today have have a
story
from the beginning of time and then some
sometimes their story was like their
path was useful
for survival for the particular
organisms and sometimes not
that's fascinating let me ask as a
tangent
we kind of started talking offline about
neanderthals uh
do you have something interesting
genetically biologically
in terms of difference between uh
neanderthal
and like the different branches of human
evolution that
you find fascinating neanderthals are
only one of about five branches
that we are pretty confident about one
branches of
of out of africa events so basically
there's neanderthals
there's denisovans what is the evidence
for denisovans
one tiny little fragment of one pinky
from one cave in siberia
recent relatively recently discovered
right less than 10 years ago yeah
and those are like little folks right no
no no no no that's yet another one
though homo florences
it had the little folks in sort of
indonesia but then
uh denisovans are basically another
branch that we only know
about genetically from that one bone and
eventually
we realize that it's one of the three
major branches along with neanderthal
modern human
and denisovan and then that one branch
has now resurfaced in many different
areas and we kind of know about the gene
flow that happened in between them
so when i was reading my greek mythology
it was talking about the age of the
heroes
these eras of human like
you know precursors that were wiped out
by zeus or by all kinds
of wars and so forth like the titans and
the you know
it's it's ridiculous to sort of
read these stories as a kid because
you're like oh yeah whatever and then
you're growing up and you're like whoa
layers and layers of human-like
ancestors
and who knows if those stories were
inspired by bones that they found that
kind of looked human-like
but were not quite human-like who knows
if stories of dragons were inspired by
bones of dinosaurs
basically this archaeological evidence
has been there
and has probably entered the folk
imagination
migrated into those stories but it's not
that far you know removed from what
actually happened
of massive wars of wiping out
neanderthals
as humans are modern humans are
populating um
you know europe do you think do you
think what killed the neanderthals
and all those other branches is human
conflict or is it genetic conflict so
is it uh us humans being
the opposite of altruistic towards each
other or
is it uh some other
uh competition at some other level like
as we're discussing
yeah so if you look at a lot of human
traits today
they're probably not that far removed
from the human traits that got us where
we are now
so you know this whole tribalism
you know your my sports team or
your my you know political party or
you're my
you know tiny little village and
therefore
you know if you're from that other
village i hate you but as soon as we're
both
in the major city i can't believe we're
from the same region my friend come
and like two neighboring countries
fighting and as soon as they're off in
another country they're like oh i can't
believe that right so
it's it's kind of funny like this
tribalism is nonsensical in many ways
it's like
cognitive incongruent that basically we
like
kin and selection for for
sort of liking kin is hugely
advantageous genetically
probably across all kinds of organs all
across all kinds of life
yeah so so basically if you now
transport that
to the sort of humans arriving
in europe and neanderthals are
everywhere
what are you going to do you're going to
kill them off you know there's this
battle for territory
and these battle for they're not like us
we have to get rid of them
so basically there's a you know very
interesting mix there but and yet
and yet when you look at the genetics
there's tons of gene flow between them
so basically you know love romance
between you know
tribes but love uh uh spans
uh the gap between the different tribes
it's wrong julia it's across species
boundaries
sneaks away from the village
even before the out of africa there's
you know within africa's election
which was probably massive battles of
larger and larger tribes
selecting for our social networking
and savviness and uh you know probably
all our conspiracy theory
genes or you know dating back from then
and you know it's
so there's a lot of this mischievousness
in the history of human evolution that
unfortunately still present in you know
many ugly forms today
but probably contributed to our success
as a species
in wiping out other species it just
sucks that uh
we don't have neighboring species that
are
you know intelligent like us
that but yet very different than us
so we have like you know dogs or wolves
i guess
uh co-evolved they they figured out
how to uh neighbor up with humans in a
friendly way and collaborate and
it develop into describing this as if
the wolves made a choice
it's possible that the wolves never had
to say that basically humans were just
so
overpowering that they had captive
wolves
and then at every generation killed off
eight of the nine pups
and only kept the one that was milder ah
humans it only takes a few generations
to then sort of have pups that are
really mild
and so the neanderthals weren't useful
in the same way i don't know if it's a
question of useful they were probably
super useful
my thinking is that they were
scary that basically something that
almost resembles you
yeah is something that you try to
eliminate first
it's too close yeah and uh speaking of
um you know species that are intelligent
and sort of
what's left of evolution it is a shame
exactly like you say that
so many different amazing life forms
were extinct
and the kind of boring ones remained
so if you look at dinosaurs i mean the
diversity
that they had if you look at sub you
know like
there's just so many different lineages
of
life that were just abruptly killed
and yet out of that death emerged
you know many new kinds of really
awesome lineages do you think there was
in the history of
life on earth species that may be still
alive today
that are more intelligent than humans
and we just don't know
it's also made for dolphins like if you
look at their brains if you look at the
way that they play if you look at the
way that they learn
uh you know i mean they don't have
possible thumbs and we do
so you know that probably made a big
difference it's terrifying to think that
like
not terrifying i don't know how to feel
about it that they're more intelligent
than us
it's like a hitchhiker's guide i know
but how do you define intelligence
basically like i was saying last time
you know stupid is a stupid does and
smart is a smart does so
yeah if the dolphins are basically super
smart
figure out the meaning of life and just
go around playing with water all day
which is probably the meaning of life
then we wouldn't know because all
they're doing is kicking water just like
sharks are and sharks are probably
pretty stupid
so so basically it's very difficult to
sort of
judge a species intelligence unless you
they kind of go out of their way to
demonstrate it
yeah and that's instructive for our
understanding of any kind of life form
uh you know i recently talked to sarah
seeger looking for
life out there on other planets it'd be
fascinating to think
if we discover a habitable planet that's
you know outside of earth in one day
maybe many centuries away or be able to
travel
with like a robot there how would we
actually know
that this species would probably be able
to detect that it's a living
being but how would we know if it's an
intelligent being
i mean uh it's both exciting and
terrifying
to sort of come face to face with a
life form that's of another world
like something that clearly is moving in
a um
how would you say like a deliberate way
and to then like ask well how do i ask
that thing
with it whether it's intelligent no but
the the question that you're asking is
um applicable to every species on on the
earth on earth now
yeah so basically you know dolphins are
a great example we know that they're
you know clearly capable hardware wise
and behavior-wise
of intelligence you know how do we
communicate
so basically if your question is about
crossing species boundaries of
communication
the way that i want to put it is that
humans have achieved
a level of sophistication in our
behaviors in our communication in our
language
in our ways of expressing ourselves
that i have no doubt that if we
encounter the human-like form of
intelligence we'd figure out their
language
in a few weeks like it'd be just fine as
long as you know of course
they're both trusting each other not
annihilating each other and not sort of
fearing each other and attacking each
other what about
the message just out of curiosity into
science fiction land a little bit
if so uh clearly you're one of the top
scientists in the world
so if we were to discover an alien life
form
uh you would be brought in to study his
genetics
do you think the epigenome that we
talked about the genome
the code the digital code that underlies
that alien life form would be similar to
ours
like the in um in fundamental ways maybe
not exactly but
in fundamental ways of how it's
structured yeah so so
you're getting to the very definition of
life you're getting to the very
definition
of what what makes life life and how do
we
decode that life and it's so easy to
think that every life form would
basically have to
you know like oxygen has to have to like
heat from the sun and rely on sort of
being in the habitable zone
of you know its solar system and so
forth
but i think we have to sort of go beyond
this
sort of oh life on another planet must
be exactly like life is on earth
because of course life on earth happens
to rely on the proximity to the sun
and benefit from that amount of energy
but we're talking at
time scales of human life
where we kind of live i don't know
between and i'm going to be super wide
here
we're going we're going to live between
six earth months and
you know 200 a month earth months or 200
earth years
so basically if you look at the time
scale
that we inhabit on earth it is very much
dictated by the amount of energy that we
receive from the sun
if you look at i don't know europa you
know the smallest the fourth smallest
moon of jupiter the smallest of the
galilean moons and also the smallest
in its distance from jupiter
it has an iron core it has a rock
exterior it has ice all around it
and it has probably massive liquid
oceans underneath
and the gravitational pull the
gravitational pull of jupiter
is probably creating all kinds of
movement under that ice
how did life evolve on earth yes sure
life now most of life that we
above the surface look at has to do with
exploiting the solar energy
for you know our daily behavior but
that's not the case everywhere on the
planet
if you look at the bottom of the ocean
there are hydrothermal vents
there's both black smokers and white
smokers and they are
near these volcanic uh
you know ducts that basically emanate
a massive amount of energy from the core
of our planet
what does life need it needs energy does
it need
energy from the sun it couldn't care
less does it need energy from
you know the earth itself yeah possibly
it could use
that and if you look at how did life
evolve
on you know on earth there are many
theories
i mean a kind of silly theory is that it
came from outer space
that basically there's a meteorite out
there that sort of landed on earth and
it brought with it
dna material i think it's a little silly
because it kind of pushes the buck down
the road
basically the next question is how did
it evolve over there yeah
whereas our planet has basically all of
the right ingredients why wouldn't
evolve here so basically
let's kind of ignore that one and now
that the two other competing hypotheses
are from the
outside in or from the inside out
from the outside in means from the
surface to the bottom of the ocean
ah from the inside out means from the
bottom of the ocean to the surface
so life on the surface is pretty brutal
life obviously evolved in the water
and then there was an out of water event
but basically before it exited
it was clearly in the water which is a
much nicer and shielded environment
so just to be clear on the surface
are you referring to the the surface of
the sea or the bottom of the sea
versus the bottom of the sea and you're
saying
life on the surface is uh it's harsh
like inside the life outside the water
is horrible
it takes huge amounts of evolutionary
innovations to sustain
living outside the water well that's so
interesting why
why is that so it's easier to life is
easier
in the water maybe see i'm telling you
don't
water yeah dolphins went back into the
water really
because dolphins are mammals of course
yeah interesting
well again they might be smarter they
went back
so so if you if you basically think
about
the fact that we are 70 water we're
basically transporting the sea with us
outside the sea you know if we if we
don't have
water for about a year 24 hours we're
dry
yeah and if you look at life under the
sea i mean i don't know if you're a
diver
but when you go diving your brain
explodes
again when i say the light the boring
life forms is what we see all the time
like tetrapods i mean what a stupid
boring
body plan seriously like just go diving
and you'll see that a tiny little
minority
of the stuff under the sea under the
surface of the sea is actually tetrapods
it's like you know snails with all kinds
of crazy appendages and colors and
you know round things and five-way
symmetric things and you know
eight-way symmetric things all kinds of
crazy body plans
and only the tetrapod fish managed to
get out
and then they gave rise to all the
boring plants we kind of see today
of basically you know uh humans with
four limbs
birds with four limbs lizards with four
limbs and you know
right it's kind of boring if you look at
by comparison
life underwater is teeming with
diversity
so now let's roll back the clock and
basically say
where did life in the ocean come from
from the surface
or from the bottom exactly those two
options exactly so basically life on the
surface
is one option and then the idea there is
that
there's tides with the moon and the sun
sort of causing all this movement
and this movement is basically causing
nutrients to sort of
you know coalesce and you know bounce
around et cetera that's one option
the second option massive amount of
energy under
you know from from from our the core of
our planet
basically uh exploited
leading to these basic ingredients of
life forms
and what are these basic ingredients
metabolism
being able to take energy from the
environment and put it as part of
yourself
metabolism it basically means
transformation again in the greek
it basically means taking stuff from you
know
like nutrients or energy source or
anything and then making it your own
the second one is compartmentalization
if there's no notion of
self there can't be evolution you have
to know where your own boundaries end
and where the non-self boundaries begin
and that's basically
the lipid bilayer nowadays which is
extremely simple to to form
it's basically just a bunch of lipids
and then they eventually just
self-organize into a membrane
so that's a very natural way of forming
a self
and then the third component is
replication
replication doesn't need to be
self-replication it could be a
helps make more of b b helps make more
of c
and c helps make more of a any kind of
self-reinforcement
is what you need to ignite the process
of evolution
after you've ignited that process you
know i don't want to say all hell breaks
loose but all paradise breaks loose
so basically you then boom you know have
life going
and the moment you have abc some kind of
thing
looping back onto a you can make
modifications
and you can improve and then you let
natural selection work
is there some element of that that's
like co like uh
like some state representation that
stores information like
maybe i should say information
absolutely is that talking about the
part
we like to think of life as
the information propagation which is dna
the messenger which is rna and then the
action
which is protein so basically dna
we think is an essential part of life
that's where the storage is and
therefore that early life forms must
have had some kind of storage
medium dna if you look at how life
actually evolved dna was invented much
later
proteins were invented later
and rna was find by itself thank you
very much
in an rna world so the early
version of life as we know it today was
in fact
rna molecules performing all of the
functions
the rna molecule itself was the
protein actuator by creating
three-dimensional folds
through self-hybridization itself what
self-hybridization so basically the same
way that dna molecules
can hybridize with themselves and
basically form this double helix
the single-stranded rna molecule can
form
partial double helixes in various places
creating structure
as if you had a long string with
complementary parts and you could then
sort of design
kind of like origami-like structures
that will fall down to themselves
and then you can make any shape from
that
that early rna world eventually got
to replication where
enzymes encoded in rna would replicate
rna itself and then
that process basically kicked off
evolution
and that process of evolution then led
to major innovations
the first innovation was translation
so you start with an rna molecule and
you translate it into another kind of
form and that's the first kind of
encoding you're like well
do you need some kind of code yeah but
the code
was in fact one thing it was conflated
with the actuators the actuators were
separated from the code only later on
so you first had the self-replicating
code which was also the actuator
and then you kind of have a
functionalization
partitioning of the functionalization a
sub-functionalization
of the proteins that are now going to be
the workhorse of life
but they're not self-replicating the
code remains the rna
so the most beautiful and most complex
rna machine
known to man is the ribosome the
ribosome
is this massive factory that is able to
translate
rna into protein the ribosome
if you if you want i don't know divine
intervention in the history of life
the ribosome is it that's one of the
great invention in the history of life
it's it's yeah but again you can't think
of great inventions as
one one-time steps they're basically you
know the
culmination of probably many competing
software infrastructures for life
preservation
that won out and then when the ribosome
was so efficient at making proteins
all the other ones basically died out
and then
the life forms that were using the
modern ribosome
were basically the more successful ones
because it could make proteins
and now those proteins are much more
versatile
because rna only has four bases proteins
eventually have 20 amino acids not
initially but eventually
and then they can form in much more
complex shapes and they can create all
kinds of additional machines
one of which is reverse transcriptase
so you basically now have rna again we
like to think of transcription as the
normal reverse transcription as the
oddball
well rna preceded dna so reverse
transcription actually was the first
invention before transcription itself so
basically
rna invents proteins rna and proteins
together
invent dna so you now have a more stable
medium
a more stable backbone
with two helices instead of one
two strands instead of one the double
helix and rna basically says
listen i'm tired i'm gonna delegate all
information stories to dna
and i'm going to delegate most actuation
to proteins proteins but that's to you
is not like a
that's just an efficiency thing it's not
a fundamental
new correlation that's why when you're
asking is a separate information storage
medium
a definition of life like no any kind of
self
preservation self reinforcement and it
didn't need to be
rna rna-based initially it didn't need
to be self-replication
initially you just need to have enough
rna molecules
randomly arising that reinforce each
other
that ultimately lead to the
you know the closing of that loop and
the ignition of the evolutionary process
can we just rewind a little bit like if
you were to bet all your money on the
two options
in terms of where life started probably
the bottom
at the bottom though i don't know if
this is answerable but
how hard is the first step
or if there's something interesting you
can say about that first leap
yeah yeah yeah about from not from not
life to life
yeah i think it's inevitable
on earth or just in the universe i think
it's inevitable
if you look at europa you know going
back to
the the moon of jupiter it's also a
really nice song by santana
basically has all the ingredients it has
you know the core that can emit energy
it has the shielding through the ice
sheet
protecting it just like an atmosphere
would it even has a layer of oxygen
probably sufficiently dense to sustain
life so
my guess is that there's probably
uh independently a reason
life form already teeming in europa
because as soon as it
today is that exciting or terrifying to
you
it's i mean as a scientist i can't wait
to see
non-dna based life forms i can't wait
because
we are so born uh
in in you know sort of uh borne
as i would say in french but basically
we're sort of you know
we we we are so narrow-minded in our
thinking
of what life should look like that i
can't wait for all that to just be blown
away
by the discovery of life elsewhere let
me bring you into another science
fiction
uh it's a scenario so on that point
if we discover life on europa
and you were brought in
you seem very excited but
how would you start looking at that life
in a way that's useful to you as a
scientist
but also not going to kill all of us
so like to me it's a little bit scary
because not not because it's a
malevolent life like it's a
it's a dictator petting like a cat it's
evil
but just the way life is it seems to be
very good
at conquering other life so there's a
lot of science fiction movies based on
that principle
yeah and that's sort of what causes the
public to be so scared but if you think
about sort of
would europa life be scared of humans
coming over and taking over
chances are no not even like earth
bacteria because earth bacteria would be
wiped out
in an instant in this foreign world
because they don't know how to
metabolize
energy that doesn't come from the types
of energy sources that are here
the levels of acidity may just kill us
all off
and at the same way in this in in the
converse way
if you bring life from europa on earth
it'll die instantly because it's too hot
or because it doesn't need to know how
to cope with
i don't know the sun's radiation so
close to this completely inhabitable
zone
by their standards so so what we call
the habitable zone
might actually be the inhabitants for
them so the difference
if the environments are sufficiently
different you think we'll just
not be able to even attack each other
and a basic
uh it'll take massive amounts of
engineering to create
machines that will go there and sample
the you know oceans basically drill
through
the layers of ice to basically sample
and see
what life is like there and detecting it
will probably be trivial it definitely
won't be dna based it's not like we're
going to send a sequencer
but it'll be you know some other kind of
combination of chemicals that will look
non-random
so if you had to bet if i took that life
form we find on
europa and like put it on a sandwich
that you're eating and like eat that
sandwich
it'll taste just fine and you'll be well
i
don't know about that i don't know
anyone well it tastes fine that's
interesting so
the other question is do we have taste
receptors for this
adaptations to chemical molecules that
we are used to seeing
so you think we don't have case bugs for
things we don't even know about wow so
we won't yeah we want to be able to know
that this chemical tastes funny
but you think it won't be it's likely
not to be dangerous
like it won't know how to even interrupt
do you think our immune system will
will even detect that something weird is
probably
and it'll be very easy to detect because
it'll be very different from very weird
but it won't be able to sort of
attack i mean the scene from i don't
know independence day
where like they're communicating with
the other computer and they're like ooh
i'm in
i mean it's hilarious because like macs
and pcs have trouble communicating
i mean let alone an alien technology or
even alien dna
so okay uh now i was talking about you
being a scientist on earth but
say you were a scientist uh they were
shipped over to europa
to investigate if there's life what
would you look for
in terms of signs of life
life is unmistakable i would say
the way that life transforms a planet
surrounding it
is not the kind of thing that you would
expect from the physical
laws alone so it's
i would say that as soon as life
arises it creates this
compartmentalization
it starts pushing things away it starts
sort of keeping things inside that
herself
and there's a whole signature
that you can see from that so when i was
organizing my meaning of life symposium
my my my friend was an astrophysicist um
basically uh we were deciding on what
would be the themes
for the for the symposium and then uh i
said well we're going to have biology
we're going to have physics and she's
like
come on biology is just a small part of
physics
[Laughter]
everything is a small part of physics
and uh i mean
in in many ways it is but my immediate
answer was no no wait
life challenges physics it supersedes
physics
it sort of fights against physics
and that's what i would look for in
europa i would basically look for this
fight against physics for anything that
sort of
signatures of not just entropy at work
not just things diffusing away
not just gravitational pulls but
clear signatures of you remember when i
was talking earlier about this whole
selection for environment selection for
biospheres for ecosystems
for this multi-organism form
of life and i think that's sort of the
the first thing that you can look for
you know chemical signatures that are
not simply predicted
from the reactions you would get
randomly such a beautiful
way to look at life so you're basically
leveraging some energy source
to enable you to resist the physics of
the universe
fighting against physics but that's
that's the first transformation if you
look at humans
we're way past that what do you mean by
transformation so so
basically there's there's layers i sort
of see
life you know when we talk about the
meaning of life
life can be construed at many levels we
talked about
life in the simplest form of sort of the
ignition
of evolution and that's sort of the
basic definition that you can check off
yes
it's alive but when alexander the great
was asked to whom do you owe
your life to your teachers
or to your parents and alexander the
great
uh answered i owe to my parents
the zine the life itself and i owe to my
teachers the
f zine like euphony f means good
the opposite of cacophony which means
you know bad
so f zine in his
uh words was basically living
a human life a proper life so basically
we can go from the zine to the f-zine
and that transformation has taken
several additional leaps so basically
you know life on europa i'm pretty sure
has gotten to the stage of
a makes b makes c makes a again
but getting to the f zine is a whole
other
level and that level requires
cooperation that level requires
altruism that level requires
specialization
remember how we're talking about the rna
specializing into dna for storage
proteins and then compartmentalizations
and if you look at prokaryotic life
there's no nucleus
it's all one soup of things
intermingling if you look at
eukaryotic life again you for true
good you know so a eukaryote
basically has a nucleus and that's where
you compartmentalize further
the organization of the information
storage
from all of the daily activities if you
look at a you know human body plan or
any animal
you have a comparablization of the
germline you basically have
one lineage that will basically be saved
for the future generations
and everything outside that lineage is
almost superfluous
if you think about it the rest of your
body all it does
is ensure that that lineage will make it
to the next generation
that these germ lines will make to the
next generation the rest is packaging
i'm sorry to be so blunt yeah and if you
look at nutrition
you know where deterostomes what does
the stone mean
dertero means second where
this is the second mouth the first mouth
is actually down here is the esophagus
so dirt or stones have evolved a second
layer of eating kind of like alien with
the two mouths
yeah so you can think of us as alien
where the first mouth is up here
and then the second mouth is down there
is of course is the first mouth just the
the the physical manipulation of the
food to make it more correct
correct and basically again you know if
you look at if you look at a worm
it's an extremely simple life form it
basically has a mouth it has an anus
and it has you know just some organs in
between that consume the food and just
spit spit out poo
humans are basically a fancy form of
that
so you basically have the mouth you have
the digestive tract
and then you have limbs to get better at
getting food you have
eyesight hearing etc to get better
getting food
yeah and then you have of course the
germline and all of this food part
it's just auxiliary to their germline so
you basically have layers of
addition of comparablization of
specialization
on top of this zine to get all the way
to the earth scene
yeah so like the warm is like windows 95
very few features
very basic and then us humans are like
windows vista or windows 10 whatever it
is
well a few innovations beyond that but
yeah and then all right
where i don't know where windows 3000 at
least is such a fascinating way to look
at life as a set of transformations
exactly so like is there some
interesting transformations to our
history here on earth that like appeal
to you of course so
and what are the most brilliant
innovations and transformations yeah
yeah yeah i mean this is such a
fascinating question of course
like you know we're talking about basic
basic life forms and we'll talk about
eukaryotic life forms
and then the next big transformation is
multicellular life forms
where the specialization separates the
germ line
from everything else that accompanies it
and sort of carries it
and then that specialization then sort
of has this
massive new innovation like above the
second mouth
which is this massive brain and this
massive brain
is basically something that arises
much much later on basically you know
notochords like having the first spinal
cord
this whole concept that along with the
this very simple
layers you basically now have a
coordinating agent
and this coordinating agent is starting
to make decisions
and remember when we're talking about uh
free will
i mean you know as a worm is hunting for
food
oh it has plenty of free will it can
choose to you know
follow chemotaxis to the left for
chemotaxis to the right and maybe that's
free will because it's unpredictable
beyond a certain level so you basically
now have
more and more decision making and
coordination of all of these different
body parts and organs
by a central operating system a central
machine that basically will control
the rest of the body and the other thing
that i
love talking about is the different time
scales at which things happen
you know we're talking about the human
epi genome before the human epigenome is
basically able to find
what genes should be expressed in
response to environmental stimuli
in the order of minutes and basically
receive a stimulus
transfer all that data through this
humongously long string
of searching and then sort of find what
genes to turn on
and then create all that all of that is
happening in the time scale of
minutes basically you know three minutes
to a to half an hour
that's the expression response but our
daily life doesn't happen on the order
of three minutes to
half an hour it happens on the order of
milliseconds like i throw a ball at you
you catch it right away
no gene expression changes there you
just don't have time to do that
so you basically have a layer of control
built on a hardware that supports it
but that hardware itself lives in a
different time scale
than the controlling machine on top of
that is that an accident by the way is
that like a feature is it
was it possible for life to have evolved
where
the our the daily life of the organism
as it interacts with its environment
was on time scale similar to uh
the the way our internals work if you
look at
trees they look kind of boring and
stupid you're like looking at a tree
like stupid if you speed up the movie of
a tree
from spring until october you'll be like
oh my god it's intelligent
and the reason for that is that at that
time scale
the tree is basically saying oh i'm
looking for a you know a
thing to catch on to oh i just caught on
to that i'm going to grow more here i'm
going to spawn there etc
like i can see the trees in my garden
just growing and sort of you know
looping around and
um it's all a matter of time scale
and if you look at the human time scale
remember we were talking about neoteny
the last time around
the whole fact that our young are pretty
useless
until you know maybe you know a few
months of age if not a few years of age
if not i don't know getting out of
college
and then we we basically hold them
enabling their brain to continue being
malleable
and infusing it with knowledge and you
know thoughts
as you know that period of neotimi
increases and expands
if you fast forward i don't know another
million years
so humans have only been around you know
different from apes for about that long
jump another unit of that another human
gym divergence
what could happen from an evolutionary
time scale a lot one of the things
that's happening already
is expansion of human lifespan we have
longer and longer periods before we
mature
and we have longer and longer periods
because before we have babies
so intergenerational distance is you
know grown from i don't know 16 years to
40 years you're saying that's in the
genetics like
no no not necessarily but but it's it's
sort of an environmental tendency that's
happening
but as we medically expand
human lifespan the
generations might actually be pushed
instead of 40 years
to 60 years to 100 years if we look at
the long arc
of the evolutionary history exactly so
as we start thinking about intergalactic
travel now
i'm sorry that's that's a heck of a
transition
uh yeah so let's talk about it no no no
no no as as we
as a species start thinking about i mean
i'm talking about these transitions that
are happening right now and that's
that's so
awesome continuing along these
transitions what does the future hold in
the next million years
so the concept of us going to another
planet
and that taking three human lifetimes
might be a joke
if the human lifetime starts being 400
years or
800 years so imagine
this time scale it's all time scale just
different time skills yeah
you asked me offline whether i would
like to live forever i mean
my answer is absolutely
and there's many different types of
forevers one forever
is do i want to live today
forever kind of like groundhog day and
the answer is
absolutely the stuff that i want to
learn today will probably take a
lifetime
just to learn you know basically to
clear my to-do list for the day
you mean like relive the day of the day
and then and then pick up different
things from the richness of the
experiences
there's just so much happening in the
world every single day so much knowledge
that has happened already
that just to catch up on that will
probably take me around forever
and that on that point i just i would
just love to see you in the groundhog
movie
just because you're so
naturally as a scientist but just the
way your mind works beautifully
just all the richness of the experiences
that you would pick up from that
uh that's a beautiful visual but you
just try to live each day as if it was
groundhog
i'm basically every single day waking up
and saying all right how would bill
murray
get out of that one well you know what
on uh
on a funny tangent like i got a chance
to uh
go to a neural link demonstration event
i'm not usually familiar with neurolink
and uh i talked to elon for a while uh
and one of the funny things he said on
this groundhog
day thing is you know it's a beautiful
dream to
eventually be able to replay our
memories so we're
kind of these recording machines our
brain is kind of
uh maybe a noisy recording machine of
memories
and it would be beautiful if we can
someday in the future maybe far