Kind: captions
Language: en
you can study chemistry you can study
Physics you can study geology anywhere
in the universe but this is the only
place you can study biology this is the
only place to be a biologist that's it
yeah so so definitely something very
fundamental happened here and you cannot
take biology out of the equation if you
want to understand how that vast
chemistry space of that General
sequence space got narrowed down to what
was what is available or what is used by
life you need to understand the rules of
selection and that's when Evolution and
biology comes into play
the following is a conversation with
Batu kachar an astrobiologist at
University of Wisconsin studying the
essential biological attributes of life
this is the Lex Friedman podcast to
support it please check out our sponsors
in the description and now dear friends
here's Batu kachar
what is the phylogenetic tree or The
evolutionary tree of life and what can
we learn by running it back and studying
ancient Gene sequences as you have I
think phytogenetic trees
could be one of the most uh romantic and
beautiful Notions that can come out of
biology it shows us a way to depict the
connectedness of life and all living
beings with one another
it itself is an Ever evolving notion
biologists like visualizations they like
these Graphics these diagrams and tree
of life is one of them so the tree
starts at a common ancestor
it's actually the other way around it
starts from at the end it starts from
the from the branches it starts from the
tip of the branch actually and then if
the further depending on how what you
collected uh to build the tree so
depending on the branches depending on
what's on the tip of the branch and I
will explain what I mean the root will
be determined by what is really sitting
on the tip of the branch of the tree so
we could study the leaves of the tree by
looking at what we have today and then
start to reverse engineer start to move
back in time to try to understand what
the rest of the tree what the roots of
the tree looks exactly so the tree
Itself by just taking a few steps back
and looking at the entire tree itself
can give you an idea about the
connectedness the relatedness of the
organisms or whatever again you use to
create your tree there are different
ways but in this case I'm imagining
entire diversity of Life Today is
sitting on the tips of the branches of
this tree and we
look at biologists look at the the tree
itself we like to think of it as the
topology of the tree to understand when
certain
organisms or their ancestry may have
merged over time
depending on the tools you use you might
use this tree to then reconstruct the
ancestors as well
and so what are the different ways to do
the Reconstruction so you can do that at
the gene level
or you could do it at the higher complex
biology level right so what what in
which way have you approached this this
fascinating problem we approached it in
every way we can so it's the gene could
be protein the product of the gene or
species
uh or could be even groups of species it
will depend it totally depends on what
you want to do with your tree if you
want to understand a certain past events
whether an organism exchanged a certain
DNA with another one along the course of
evolution you can build your tree
accordingly if you
um rather use the tree to reconstruct or
resurrect ancient DNA which is what we
do then in our case for instance we do
both Gene protein and species because we
want to compare the tree
that we create using these different
information
okay well let me ask you the ridiculous
question then so how realistic is
Jurassic Park
can we study the genes of ancient
organisms and can we bring the those
ancient organisms back so the reason I
asked that kind of ridiculous sounding
question is uh maybe gives us context of
what we can and can't do Yeah by looking
back in time yeah so uh dinosaurs or all
these mammals in in at least for us is
the exciting thing already happened by
the time we hit to the larger organisms
or to eukaryotes oh to you the fun stuff
is before we got to the memo the fun
stuff is what what thing is boring I
think that the the phase that's well at
least two different times in the
geologic history one is the first life
uh past origin of Life how did first
life look like
and the second is why do we think that
over certain periods of geologic time no
significant Innovation happened to the
degree of leaving no record behind
so what do we not have a record of which
which part is it you the fun stuff to
you is after the origin of Life which
we'll talk about after the original life
there's single cell organisms the the
whole thing with the photosynthesis the
whole thing with the eukaryotes and uh
multi-cell organisms and uh what else is
the fun stuff the whole oxygen thing
which mixes in with the origin of Life
uh there's a bunch of different
inventions all that have to do with this
primitive kind of looking organisms that
we don't have a good record of so I will
tell you the more interesting things for
us one is the origin of life or what
happened uh right following the
emergence of Life how did the first
cells look like
and then pretty much anything that we
think shaped the environments and were
was shaped by the environments in a way
that impacted the entire planet that
enabled you and I to have this
conversation
we have very little understanding of the
biological innovations that took place
in the past of this planet
we work with a very limited set of
um I don't want to even say data because
they're fossil records so let's say
imprints either that comes from the Rock
and The Rock record itself
or what I just described these trees
that we create and whatever we can infer
about the past so we have two distinct
ways that comes from geology and biology
and they each have their limitations
okay so right so there's an interplay
the geology gives you that little bit of
data
and then the biology gives you that
little bit of kind of constraints in the
materials you get to work with to infer
how does this result in the kind of data
that we're seeing and now we can have
this through the fog we can see we can
look back hundreds of millions of years
a couple of billion years and try to
infer even further and and I like that
you said fuck it is pretty foggy but
weird and it gets foggier and foggier
the more you the further you try to see
into the past
um biology is you you basically study
with study the survivors
broadly speaking yeah and you're trying
to pitch the sort of put together their
history based on whatever you can
recover today what makes biology
fascinating also let it
erased its own history in a way right so
you work with this four billion year
product that's genome that's the DNA
it's great it's a very Dynamic ever
evolving chemical thing and so you will
get some information but you're not
gonna get
much unless you know where to look
um because it is responding to the
environment
yeah so what we have it's fascinating
what we have is the survivors the
successful
the successful organisms even the
Primitive ones even though the bacteria
you have today so bacteria is not
uh sorry sorry to offend the bacteria
it's we should be very grateful to
bacteria and first of all they are our
great great ancestors I like this quote
by Douglas Adams humans don't like their
ancestors they rarely invite them over
for dinner yeah right that bacteria is
in your dinner bacteria is in your gut
but today is helping you for dinner we
might well they get themselves invited
in a way yes and so we and they're
definitely older
um and and definitely very sophisticated
very resilient than anything
um else is someone working at the as a
bacteriologist I feel like I need to
defend them in this case because they
don't get much shout out when we think
about life so you do study bacteria so
which organisms gives you hints that are
alive today that give you
um hints about what ancient organisms
were like is it bacterias and viruses
what do you study in the lab we study a
variety of different bacteria depending
on the questions that we are
engineer bacteria so ideally we want to
work with bacteria that we can engineer
seldom we developed the tools to
engineer them and it depends on the
question that we are interested in if we
are interested in connecting the biology
and geology to understand the early life
and and fundamental Innovations across
billions of years there are really good
candidates like cyanobacteria so we we
use cyanobacteria very frequently in the
lab we can engineer its genome we can
perdurp its function by poking its own
DNA with the foreign DNA that we
engineer in the lab we work with E coli
it's the most simple in in terms of
models systems go goes organism that one
can study well-established sort of a pet
lab pet that we use it a lot for cloning
and for understanding uh or basic
functions of the cell given that it's
really well studied so and what you do
with that E coli you said that you
injectable foreign DNA we inject as much
all the bacteria that we work with with
foreign DNA we also work with
diazotrophs these are azodobacteria
they're one of the Prime nitrogen fixers
nitrogen fixing bacteria can you explain
what that is nitrogen fixing is that is
the source of its energy so nitrogen is
a triple bond gas
gets pretty abundant in the atmosphere
but nitrogen itself cannot be directly
utilized by cells given it as triple
bond
it needs to be converted to ammonia that
is then used for the Downstream
cellular functions and that's what
causes nitrogen fixing yes needs to be
fixed before our cells can make use of
it and and it's no offense to nitrogen
either well uh it's actually a very
important element it's one of the most
abundant elements on on our planets that
is used by biology it's in ATP it's in
chlorophyll um that's uh uses that
relies on nitrogen so it's a very
important enzyme for a lot of cell
functions and there's just one mechanism
that Evolution invented to convert it is
so far we know there's there's only one
nitrogen fixation pathway as opposed to
say carbon you can find up to seven or
eight different carbon based microbes
invented to fix carbon that's not the
case for nitrogen it's a it's a
singularity across geologic time we
think it evolved around 2.7 maybe
um roughly three probably less than
three billion billion years ago and
that's the only way that nature invented
to fix the nitrogen in the atmosphere
for the subsequent use would we still
have Life as we know today if we didn't
invent that nitrogen fixing step I
cannot think of it no it's it's it's
essential to Life as we know you you and
I are having this conversation because
life found a way to fix nitrogen is that
one of the tougher ones if you put it
sort of uh oxygen
nitrogen carbon what are in terms of
being able to work with these uh
elements
what is the hardest thing what is the
most essential for life just to give
context well we think of this as the
cocktail you may hear what's in the
cocktail it's the schnapps right carbon
hydrogen oxygen nitrogen sulfur so there
are five elements that life relies on
we don't quite know whether that's the
only out of many options that life
necessarily needs to operate on but
that's just how it have it happen on our
own planet and um there are many abiotic
ways to fix nitrogen uh and like
lightning right lightning can accumulate
ammonia
humans found a way about a hundred years
ago I think around World War One the
Haber bash process that we can
abiotically convert nitrogen into
ammonia actually 50 percent of the
nitrogen in our bodies comes from the
human
conversion of nitrogen ceremonia it's
helped it's the fertilizer that we use
urea comes from that process it's it's
not food so we helped we found a way to
fix our own nitrogen for ourselves yeah
but that you know that's way after the
original invention oh absolutely
absolutely and without that we wouldn't
have
we wouldn't have all the steps of
evolution along the way oh absolutely
it's very we tried to replicate in the
most simplest way what Nature has come
up with
right we do this by taking nitrogen
using a lot of pressure and then
generating ammonia life does this in a
more sophisticated way relying on one
single enzyme called nitrogenase it's
the nitrogen that is used together with
eight electron donor and ATP together
with a lot of hydrogen life pushes this
metabolism down to create fixed nitrogen
it's quite remarkable so the lab pet E
coli inject them with DNA those are the
so you call it as nitrogen fixing in
part or is that what's that a different
one so some biological Engineers
Engineers E coli to fix nitrogen I
believe not not us we use the Nature's
nitrogen nitrogen fixing bug and
engineer it with the nitrogen fixing
metabolism that we resurrected using our
computational and phylogenetic tools how
complicated are these little organisms
what talking about it depends on how you
Define complication
okay so I I could tell that you uh
appreciate and respect the full
complexity of even the most seemingly uh
primitive organisms because none of them
are primitive okay that said what what
kind of what what are we talking about
how how
um
what kind of machineries do they have
that you're working with when you're
injecting them with DNA so I will start
with one of the most fascinating
machineries that we target which is the
translation machinery
it is on a very unique
subsystem of cellular life in comparison
to I would say metabolism
and we used to
um you know when we are thinking about
cellular life we think of cell as the
basic units or the building block but
from a key perspective that's uh not the
case that one may argue that everything
that happens inside the cell serves the
translation and the translation
Machinery there is a nice paper that
called this that entire cell is
hopelessly addicted to this main
informatic
Computing biological chemical system
that it is operating at the heart of the
cell which is the translation it is the
translation translation from what to
what so RNA to enzymes it converts a
linear sequence of mRNA into a folded
later folded protein that's that's when
the uh that's the core processing center
for information for life
it's uh has multiple steps it initiates
it elongates its
um terminates and it recycles
it operates uh
discrete bits of information it's itself
is like a chemical decoding device and
that is incredibly unique for
translation that I don't think you will
find anywhere else in the cell that does
this so even though it's called
translation it's really like a factory
that reads the schematic
and builds a three-dimensional object
it's like a printer I would divide it
into actually even four more additional
steps or disciplines than what would it
take to study it by the way you
described it it's a chemical system it's
the compounds that make it up are
chemicals it's physical it's uh tracks
the energy to make its job to do its job
its own informatic what is processed are
the bits it's computational the discrete
states that the system is placed when
the information is being processed
that's itself is computational and it's
biological it's a there's variability
and inheritance that come from imperfect
replication even and infer imperfect
computation so you're and that's so good
so from the biology comes the like when
you mess up
the bugs of the features that's the
biology informatics is obvious in the
RNA that's a set of information there
the different steps along the way is
actually kind of what the computer does
with with bits its own computation
physical there's a uh I guess the the
like almost like a mechanical process to
the whole thing that requires energy and
actually you know it's manipulating
actual physical objects
and uh chemicals because you're
have to ultimately it's all chemistry
yeah and track system for me information
so it is almost a mini computer device
inside ourselves yeah and that's the
oldest uh computational device of life
it's it's uh likely the key uh operation
system that had to evolve for life to
emerge it's uh more interesting
or it's more complicated in interesting
ways than the computers we have today I
mean everything you said which is really
really nice I mean I guess our computers
have the informatic and they have the
computational but they don't have the
chemical the physical or the biology
exactly and and the computers don't have
don't link information to function
right they are not tightly coupled
nowhere close to what translation
or the way translation does it so that's
the number one I think difference
between the two
and um yes it's it's informatic and we
can um uh discuss this further too 100
let's please discuss this further which
part are we discussing for each one of
those are fascinating worlds each each
of the five yeah so about we can start
with the more I guess the the ones that
are more established which is the the
chemical aspect of the translation
Machinery it's uh the specific compounds
make up the Assembly of RNA chemists
showed this in many different ways we
can rip apart the entire Machinery we
know that at the core of it there's an
RNA that's
um
that operates not only as an information
information system itself or information
itself but also as an enzyme and and
origin of Life chemists make these
molecules easily now we know we can
manipulate RNA we can make even with
single part chemistries we can create
compounds what's a single part chemistry
um that's I would say when you add all
the recipes that you know that will lead
you to the final products do is they
they come up with this pod they throw a
bunch of chemicals in and they try to
try to they're basically Chefs of a
certain kind I'm not sure if that's what
they call it but that's how I think of
it because it is all combined in a test
tube and you know the outcome and and
it's it's mathematical once you know the
right environment and the right
chemistry that needs to get into this
container or the spot you know what the
outcome is there's no luck there anymore
it's a pretty rigid established uh input
output system and it's all chemistry so
you actually wear a lot of hats as one
of them original life chemist my PhD is
in chemistry but I don't do original
live chemistry but you're interested in
origin of Life yes absolutely so some of
your some of your best friends the
original life chemists just make sure
that you have good chemist friends if
you're interested in origin of Life yeah
that's a hundred percent requirement
should be mandatory okay so chemistry uh
so what else about this Machinery that
we need to know chemically well uh
chemically I think that that's it you
have enzymes you have proteins the
enzymes are doing their thing they know
how to chew energy using ATP or GTP they
they know what to do on their in their
own way they do their enzymatic thing so
it's not just the ribosome that is at
the heart of the transition but there
are a lot of different proteins you're
looking about a hundred different
components that compose this Machinery
uh well let me ask kind of maybe it's a
ridiculous question but did the
chemistry
make this machine or did the machine
use chemistry to achieve a purpose
so like
um
I guess there's a lot of different
chemical possibilities on Earth
is is this much translation Machinery
just like
uh choosing picking and choosing
different
chemical reactions that it can use to
achieve a purpose
uh or did the chemistry basically
like uh there's like a momentum like a
constraint to the thing that can only
build a certain kind of Machinery that's
basically is is chemistry fundamental or
is is it just emergent like how
important is chemistry to this whole
process you cannot have
chemistry
process without
chemistry what makes life interesting is
that even if the chemistry isn't perfect
even if there are accidents along the
way if something binds to another
chemical in in a way it shouldn't
um there is resilience within the system
that it can maybe not necessarily repair
itself but it moves on however in
perfect
mistakes can be handled that's where the
biology that's where the biology comes
in but in terms of chemistry you
absolutely cannot have a transition
missionary without chemistry and so
you're as I said there are four main
steps these are the core steps that are
conserved in all translation missionary
and I should say all life has this
machine right
every cell everything on Earth on Earth
yeah yes when you think of this machine
do you think very specifically about the
kind of Machinery that we're talking
about or do you think more
philosophically a machine that converts
information into function it's I I
cannot separate
Machinery fascinating
those five components that I listed are
they coexist
so for instance if we uh let's just
talking about the chemistry part
um
we we know the certain
um rate constant all these proteins that
operate in this Machinery needs to
Harbor in order to get the mechanism
going
right if you are bringing the the
information to the translation
missionary and you're the initiator of
this computation system you need to have
uh you can only afford a certain range
of mistakes if you're too fast then the
next message cannot be delivered fast if
you're too slow then you may stall the
process so there is definitely a
chemistry constant going on within the
Machinery
um again it's not perfect far from it
but they all have their own margin of
error that they can tolerate versus they
cannot otherwise they call that the
system collapses so it's like a Jazz
Ensemble the notes of the chemistry but
you can be I love that you said Jazz
it's definitely through it's a party and
it's like everybody's invited and and
and they need to operate together all
right and and they um and what's really
cool about it I think or there are many
things that are very interesting about
this thing but if you take if you remove
it from the cell and put it in a Cell
free environment it works just fine
right so you can get cell free
translation systems uh put this
transition in a test tube and it is
doing its thing it doesn't need the rest
of the cell to translate information of
course you need to feed the information
at least so far
um but because we are far from evolving
a transition maybe not so far uh
evolving a translation in the lab or the
Machinery that can process information
as it generates it we have not done that
yet it's a pretty complicated Machinery
it's hard for it to for those uh origin
of Life chemists to find a part that
generates because it's far more than
chemistry you need you need uh biology
obviously you need biochemistry you need
to think as a I think a network systems
folk you need to think about computation
you need to think about information and
and that is not happening yet except we
are trying to bring this perspective but
the more you understand how the
information systems work you cannot once
you see it you cannot unsee it it's one
of those things so but you can still bit
out and the chemistry happens yes and
chemistry can happen even with even if
you strip some of the parts out it can
you can get very minimal level of
information processing that does not
look anything like the translation that
cells relies on but that what chemists
showed from linear you can generate
information that arrives to a processing
center in the form of a linear polymer
the informatic part of this system that
I think sets it apart from computation
and from metabolism comes in if you
think about the information itself right
so we have four nucleotide letters that
compose DNA and they are processed in
the translation in triplets
so you have an in triplet codon
fragments so you have four times four
times four so you have 64 possible
states that can be encoded
by four letters in three positions
all right so it's so amazing yeah it's
so amazing there is only one code that
says start that's that there's only one
and then there's two if not three that
says stop
so that's that's that's what you work
with but you can have 64 possible States
but life only uses 20. amino acids so we
used six live users 64 possible States
minus four of the starts and stops to
code for 20 amino acids in different
combinations
that is really amazing if you think
about there there are 500 different
amino acids life can choose right it's
narrowed it down to training we don't
know why a lot of people think about
this genetic code is quite fascinating
right I mean it didn't do it for four
billion years I don't know we may wait
for another four billion years but but
you didn't have those amino acids in the
very beginning right like you don't know
so it we would be fooling ourselves if
we said we know exactly how many amino
acids existed early on but there's no
reason to think that it it wasn't the
same or similar yeah we don't we don't
have a good reason but
but because roughly 20 out of 60 states
are used you're using one-third of your
possible states in the in your
information system so it this may seem
like a waste but informatically it's
important because it's abundant and it
is uh redundant right so so this code
degeneracy you see this in that's
implemented by this translation
missionary inside the cell
so it means we can make errors right you
can make errors but the message will
still get through you you can speak
missing some letters to the information
can miss some parts but the message will
still get through so that's two-thirds
of the not used States give gives you
that robustness and resilience within
this system so at the informatic level
there's room for error there's probably
room for probably in all five
uh categories we're talking about
there's probably room for air in the
computation there's probably room from
area there's yes exactly everywhere yeah
because because the the informatic
capacity is made possible together with
the other
um components and not only that but also
the the product yields
a function no
in this case enzyme are pretty right so
so
that's really amazing for me it is I
mean I mean in my head just so you know
because I'm a computer science AI person
the the parallels between even like
language models that encode language
or now they're able to encode basically
any kind of thing including
um images and actions all in this kind
of way
the the parallel in in terms of
informatic and uh computation
is just incredible actually
um I have a image maybe I can send you
can we pull it up now if you just do
genetic codon charts we can pull that
off yeah it's a very standard table
so I can I can explain what why this is
so amazing so you're looking at um like
this is life's alphabet right and so I
also want to make a very quick link now
to your first question the Tree of Life
um when when we link when we try to
understand ancient languages right or
the cultures of the or the cultures uh
that use these extinct languages we
start with the modern languages right so
we look at
um Indo-European
languages and and try to understand
certain words and make trees
um to understand you know this is what
uh Slavic word is for snow something
like snig now we jump to languages that
humans spoken humans talk history
exactly so we make trees to understand
what is the original ancestor what did
they use to say snow and if you have a
lot of cultures who use the word snow
you can imagine that uh it was snowy
that's why they needed that word it's
the same thing for biology right if if
they have some if we understand some
function about that enzyme we can
understand the environment that they
lived in it's it's the similar it's
similar in that sense so now you're
looking at the alphabet for of life in
this case it's not 20 or 25 letters it's
you have four letters so what is really
interesting that stands out to me when I
look at this on the outer shell you're
looking at the 20 amino acids that's
composed life right the one the
methionine that you see that's the start
so the start is always the same to me
that is fascinating that all Life starts
with the same starts there's no other
start code so you sent the uh AG you
know Aug to the cell that when that
information arrives the transition knows
all right I gotta start function is
coming the following this is a chain of
information until the stop code arrives
which are highlighted in black squares
so for people just listening we're
looking at a standard RNA color table
organizing a wheel there's an outer
shell and there's an inner shell all
used in the four letters that we're
talking about with that we can compose
all of the amino acids then there's a
start and there's a stop and presumably
you put together the the with these
letters you walk around the wheel to put
together the words the sentences that
yeah reverse the sentences and you to
again you get one start you get three
there are three different ways to stop
this one way to start it and for each
letter you have multiple options so you
say you have a code a the second code
can be another a and even if you mess
that up you still can rescue yourself so
you can get it for instance I'm looking
at the lysine Decay you get an A and you
get an A and then you get an A that
gives you the lysine right but if you
get an A and if you get an A then get a
g you still get the license so there are
different combinations so even if
there's an error we don't know if these
are selected because they were Earnest
and somehow they got locked down we
don't know if there is a mechanism
behind this to or we we certainly don't
know this definitively
but this is informatic uh part of this
and notice that the colors in some
tables too the colors will be coded in a
way that um the the type of the
nucleotide can be similar chemically uh
but the point is that you will still end
up with the same amino acids or
something similar to it even if you mess
up the code do we understand the
mechanism how natural selection
interplays with this resilience to error
so which errors
result in the same
uh the output like the same function and
which don't
uh which actually results in a
dysfunction which are we understand to
some degree the how translation and the
rest of the cell work together
have an error at the translation level
this is a really core level can impact
entire cells but we understand very
little about the evolutionary mechanisms
behind the selection of the system it's
thought to be as one of the hardest
problems in biology and it is still the
Dark Side of biology we even though it
is so essential
so this is uh yeah you're looking at the
language of life so to speak and how it
can found ways rather to it to tolerate
its own mistakes so the entire
phylogenetic tree
can be like uh deconstructed with this
wheel of language because all the final
letters those are that's the 20 amino
acids that's our alphabet they are all
brought together with these bits of
information right so you when you look
at the genes you're looking at those
four letters when you look at the
proteins you're looking at the 20 amino
acids uh which may be a little easier
way to track the information when we
create
um the tree so using this language we
can describe all life that's lived on
earth
[Music]
we are not that good at it yet right so
in theory this is one way to look at
life on Earth if you're a biologist and
you want to understand how life evolved
uh from a molecular perspective this
would be the way to do it and and this
is what nature narrowed its code down to
so maybe think of nitrogen than we think
of carbon when we think of sulfur it's
all in this that the all these
nucleotides are built based on those
elements and this is fundamentally the
informatic perspective exactly that's
that's the informatic perspective and
it's important to emphasize that this is
not engineered by humans this is this
evolved by itself like right humans
didn't invent this just because we were
just describing we're trying to find
trying to describe the language of life
it's it appears to be a highly optimized
chemical and information code
um it it may indicate that a great deal
of chemical Evolution and uh and and
this may indicate that a lot of
selection pressure and darwinian
evolution happened with prior to the
rise of last Universal common ancestor
because this is uh almost a bridge that
connects the early cells to the last
Universal common ancestor okay can you
describe what the heck you just said uh
so this
mechanism evolved before the what
combination so there's the last
Universal government so when we talk
about the tree when we think about the
root if you I ideally uh included all
the living information or all the
available information that comes from
living organisms on your tree then it on
the root of your tree lies the last
Universal common ancestor Luca right why
last last Universal because the earlier
Universe it also had trees but they all
died off we call it the last because it
is sort of the first one that we can
track
because we cannot we don't know what we
cannot track right so it's one there's
one organism
that started the whole thing it's more
like a I would think of it as more like
a population a group of organisms I
tweeted this I want to know the accuracy
of my tweet all right
um sometimes early in the morning I I
tweet very pothead like things I said uh
that we all evolved from one
common ancestor that was a single cell
organism 3.5 billion years ago uh
something like this
how how true is that tweet do I need to
delete it no there's actually correct
but I mean uh I I think of course
there's a lot to say which is like we we
don't know exactly uh but what to what
degree is that the the single organism
aspect is that true
um versus multiple organisms no
totally honest yes please
this is how we did like caveats the
tweets right so first of all it's not
um 3.5 is still a very conservative
estimate that's the first Direction uh I
would say it's 3.8 is probably safer to
say at this point a bunch of people said
it probably way before if you put an
approximately I'll take that I didn't I
just love the idea
that I was once first of all as a single
organism I was once a cell well your
still is you're a group of cells no but
I started from a single cell
me Lex you mean like you versus Luca are
you relating to Luca right now
like your own development my own
development I started from a single cell
it's like it like built up with stuff
okay that and then so that's a first
single biological and then from an
evolutionary perspective the Luca like I
start like my ancestors a single cell
and then here I am sitting half asleep
tweeting
like I started from a single cell
evolved a ton of murder along the way
into the the this like brutal uh search
for adaptation through the
3.5.8 billion so you you defy the code
of Douglas Adams you are proud of your
ancestors and you you get them over to
dinner and you invite them over to your
Twitter yeah so and it's amazing that
this intelligence to the degree you can
call it intelligence emerged to be able
to tweet whatever the heck I want yes
it's almost intelligence at the chemical
level and this is also probably one of
the first chemically intelligent system
that evolved by itself in nature yeah
you see you see that translation is in a
fundamentally like uh intelligent
mechanism in its own way and and again
the if if we manage to figure out how to
drive life's evolution
in it can if it can evolve uh a
sophisticated sort of informatic
um processing system like this you may
ask yourself what might chemical systems
be capable of independently doing under
different circumstances
yeah so like locally they're intelligent
locally they don't need the rest of the
shebang like they don't need the big
they need so that that's that's a great
segue into what makes this biological
right the the hearts of the cellular
activities are translation you kill
translation you kill the cell yes you
not only the translation itself you kill
the component that initiates that you
kill the cell you kill you remove the
component that elongates it you kill the
cell so there are many different ways to
disrupt this Machinery they all depart
all the parts are important now it it
can vary across different organisms we
see variation between bacteria versus
eukaryotes versus archaea right so it is
not the same same exact steps but it can
get more crowded as we get closer to
eukaryotes for instance but you are
still Computing about
um 20 amino acids per second right this
is this is what you're generating every
second the single Machinery is doing 20
a second 20s 21 for bacteria I believe
eight four eukaryotes or nine 21 a
second I mean that's super inefficient
or super efficient depending on how you
think about it
I think it's great I mean I can yeah but
it's way slower than a computer
could generate it through simulation I I
think if you can show me a computer that
does this we are down here well this is
the big this includes the five things
not just but I could show you a computer
that's doing the informatic right like
yes you can show me that but you cannot
show me the one that has all for now for
now I will ask you about probably what
uh Alpha fold right uh I think the more
we learn about and this is why early
life and origin is also very fascinating
and applicable to many different
disciplines there's no way you see this
the way we just described it unless you
think about early life and early
geochemistry and earliest emergent
systems but going going back to
the biological components
all of these attributes that we think
about life or that we associate with
Biology stems from translation and as
well as metabolism but
I see metabolism as a way to keep
translation going and translation keeps
metabolism going but transition is
arguably a bit more sophisticated
process for the reasons that I just
described so metabolism is a source of
energy for this translation process it's
so it's a it's a way to process
materials and it is inherently Dynamic
and it is flexible but it is not focused
on rapid reputation as translation does
so that's the main difference
translation is the kind of in a way just
it repeats right so you have the
metabolism that can synthesize materials
it creates or benefits from available
energy and again it's a dynamic system
um and then you have computation that it
that is inherently repetitive right
needs to carry out repetitive processes
uh it and it does the tasks and it's it
implements an algorithm but it is not
Dynamic so you see both of those
attributes in Translation combined it is
repetitive and it is dynamic and it also
processes this information so they are
fundamentally different I don't know if
you can get
um the life if you don't find a way to
process the information around you
in a repetitive Dynamic way yeah and
somehow that that's what got
um selected maybe not selected I don't
know if it was
um accidental but that that's what it
seems to be conserved for four billion
years that that's what life established
what's the connection between
translation and the self-replication
which seems to be a another weird thing
that life just started doing wanting to
just replicate it I think when we truly
understand the answer to that question
we may have just made ourselves live
right we I don't think we know quite how
translation Machinery as a whole fits
into equation because so we try to
understand
um ribosomes RNA how the linear
information is processed
um
or the genetic code wise this codons not
others why 20 not more not less and we
are sort of moving towards transition
that's that's what we're working on
anyway uh to finally look at the
patterns in which this system operates
itself and if you understand that you're
really unlocking a very emergent
Behavior
uh one of the things you didn't mention
is physical is there something to
mention about that component that's
interesting there's actually a paper uh
published in 2013 I want to say the
first author zirnoff so they surveyed
computational
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um engineered systems level computation
energy consumption okay and they try to
understand whether the universe is using
its own or life is using its full
capacity of energy consumption and
whether
um if different planets in the universe
had life would the capacity would
increase or decrease it does life
operate at its energy maximum
and uh and they think that it does that
it actually operates at an efficiency
that is far more above and beyond a
computational system how's that possible
to determine at all that you tell me
that's why I dropped the citation I I
found the citation it's quite an
interesting paper it's a bit you know
it's a um
it's a obviously you can only calculate
and infer these things but that's a good
question to ask is the life that we see
here on Earth and life elsewhere in the
universe is it using the energy most
efficiently yeah yeah it seems to be
very efficient again if we compare to
computers it seems to be incredibly
efficient at using it I think they look
at the like the theoretical Optimum for
electronic devices and then try to
understand where life falls on on this
and life is certainly more efficient and
that's ultimately the physical side how
well are you using for this entire
mechanism the energy available to to you
and so given given all the resilience to
errors and all that kind of stuff it
seems that it's close to its maximum yep
and this this paper aside it does seem
that life obviously that's the
constraint we have on earth right is the
amount of energy
yeah so that's one way to Define life
well
the input is energy and the output is
what I don't know
self-replicating
wait how okay let's go there how do you
how do you personally Define life do you
have a do you have a favorite definition
you try to sneak up on
um
is it possible I Define life
on Earth I don't know it depends on what
you are defining it for if you're
defining it for finding different life
forms then it probably needs to have
some quantification in it so that you
can
um
use it in in whatever the mission that
you're operating to me like it's not
binary it's uh this is like a seven out
of ten
I don't know I I don't I don't think
that defining is that essential I think
it's a good exercise but I'm not sure if
the if we need to agree
um a universally defined way of
understanding life uh because the
definition itself seems to be ever
evolving anyway right we have the NASA's
definition it's it says
it has its uh minuses and pluses but it
seems to be doing its job well what what
are the different if there is a line and
it's impossible or unproductive to
Define that line nevertheless we know it
when we see it
is one definition that the Supreme Court
likes
and that's a
kind of an important thing to um
to think about when we look about when
we look at life on other planets
so
how do we try to identify if a thing is
living when we go to Mars when we go to
uh the different moons in our solar
system we would go outside our solar
system to look for Life yeah on other
planets it's unlikely to be a sort of a
Smoking Gun event right it's not going
to be hey I found this you don't think
so I don't think so unless you find an
elephant on some exoplanet then I can
say yeah that's there's life here no but
is there a dynamic nature to the thing
like uh it moves
it has a membrane that looks like
there's stuff inside it doesn't need to
move right I mean like look at plants I
mean they they grow but there are plants
that or can be also pretty dormant and
arguably they are the most they do
everything that is one of my
favorite professors once said that the
plant does everything that the giraffe
does without moving so the movement is
not a Zen statement necessarily but at a
certain time scale the the plant does
move it just moves slower yes it moves
pretty I would I would say that and it's
hard to quantify this or even measure it
but it is a life is definitely the
chemistry finding Solutions right so it
is chemistry exploring itself
but and and maintaining this exploration
for billions of years so okay so a
planet
is a bunch of chemistry
and then you run it and say all right
figure out what uh what cool stuff you
can come up with that's essentially what
life is given a chemistry what is the
cool stuff I can come up with if that's
that chemistry or the solutions that
it's
embarks upon are maintained in a form of
memory
right so it's this you you don't just
need to have the
uh explore exploring chemical space but
you need to also maintain a memory of
some of those solutions for over long
periods of time so that's the memory
component
makes it more living to me because
chemistry can always sample right so
chemistry is chemistry but are you just
constantly sampling or are you building
on your former Solutions and then
maintaining a memory of those Solutions
over billions of years or at least
that's what happened here chemistry
can't build life if it's always living
in the moment the physicists would be
very upset with you okay
so memory could be
a fundamental I mean life is not just I
mean life is obviously the chemistry and
physics uh leading to biology so this is
not a disciplinary
problem of one discipline trying playing
other discipline it's that but what what
you need to have is definitely a big
chemistry is everywhere right I
tend to think you can be a chemist you
can study chemistry you can study
Physics you can study geology anywhere
in the universe but this is the only
place you can study biology this is the
only place to be a biologist that's it
yeah so so definitely something very
fundamental happened here and you cannot
take biology out of the equation if you
want to understand how that vast
chemistry space how that General
sequence space got narrowed down to what
was what is available or what is used by
life you need to understand the rules of
selection and that's when Evolution and
biology comes into so the rules of
natural selection operate to you on the
level of biology
rules I don't know if there are any
rules like that would be fascinating to
find in terms of the biology's rules
that's a very interesting and
um it's a very fascinating area of study
now and probably we will hear more about
that the decades to come but if you want
to go from the the broad to specific you
need to understand the rules of
selection and that is going to come from
understanding biology yes
well actually let me ask you about
selection you have a paper uh on
evolutionary stalling
where you describe that evolution is not
good at multitasking
or like uh in uh populations that have
evolved quickly I mean it's a very
specific thing but there could be a
generalizable fundamental thing to this
that evolution is not able to improve
multiple modules simultaneously I guess
the question is
um what part of the organism does
evolution quote unquote focus on to
improve yeah that was the driving
question we meddled with the part where
you shouldn't be messing up with
translation this is the shooter should
not you shouldn't as I said there are
many ways to break it and all life needs
it so one of the things your favorite
things to do is to break life to see
what happens
it's yeah because that's how kids learn
right so you have to break something and
you see how it will then you do over and
over again to see if it will fix itself
in the same ways yeah so that's it's our
I don't know it's the most fundamental
properties of our ourselves as human
beings so if we shouldn't break
translation then we should try to break
it yes to see how it will repair so
which part you break I broke elongation
so what's the role of elongation in this
process so the we we have uh four steps
of the translations initiate elongate so
to elongate the chain of the the
information chain that you're now
creating the peptide chain uh or let's
say broadly polymer chain
um and there's a termination step and
there's the recycling so all of these
com steps are carried out by proteins
that are also named after these steps
initiation is the initiation Factor
protein elongation is the elongated
protein
um we
um
broke elongation
so the cell the starting codon could
still arrive to where it's supposed to
go but the following information
couldn't get carried out because we
replaced elongation with uh its own
ancestral version so we inserted roughly
a 700 million year old elongation Factor
protein
after removing the modern Gene so we
made this ancient modern hybrid
organism and that essentially creates in
some way the ancient version of that
organism
I wouldn't say so it's the it's a it's
a it's organism it's not necessary
because you the rest of this cell the
rest of the
uh genome is still modern and that goes
back to the difference between Jurassic
Park there are many differences
obviously given that this is not fiction
we're doing it but also
um we are not necessarily I think in
Jurassic Park they are taking and
ancients or they find an ancient
organism and then put in modern Gene
inside the ancient organism in our case
we are still working with what we got
but putting an ancestral DNA inside the
modern organisms you're like taking a
new car and putting an old engine into
it in a way yeah yes seeing what happens
yes but in our case it's more like a
Transformer than just a regular car it
is doing things it's yeah so it's a more
complicated organism than just the car
yeah
uh I got it so what is that what does
that teach you
we
sell respond to
perturbation
didn't just put the ancient DNA we
inserted
um we sampled DNA from currently
existing organisms so the cousins of
this microbe and and collected DNA
sequences from the cousins as well so
both ancestor and the current cousin DNA
so to speak and engineered all of these
things to the modern bacteria and
generated a collection of microbes that
either have the ancient component or the
variants
elongator component that still alive
today but coming from a different part
of the tree so you broke elongation
was that something you did as part of
the paper on evolutionary stalling to
try