Betül Kaçar: Origin of Life, Ancient DNA, Panspermia, and Aliens
嘉宾：Betül Kaçar
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本篇目录17 章节
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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.
Earth.
That's it.
Yeah.
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 is available,
or what is used by life, you need to understand the rules of selection, and that's where evolution and biology comes into play.
The following is a conversation with Batul 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 Batul 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 phylogenetic trees could be one of the most 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 the branches.
It starts from the tip of the branch, actually.
And then, depending on what you collected 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 look like.
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 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 in which way have you approached 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,
or could be even groups of species.
It totally depends on what you want to do with your tree.
If you want to understand 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 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 those ancient organisms back?
So the reason I ask that kind of ridiculous sounding question is
maybe it gives us context of what we can and can't do by looking back in time.
- Yeah, so dinosaurs or all these mammals, at least for us,
is the exciting thing already happened by the time we hit to larger organisms or to eukaryotes.
- Or to you, the fun stuff is before we got to the mammals?
- The fun stuff is what people think is boring, I think.
The phase that's, well, there's two different times in the geologic history.
One is the first life, 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 part?
So you say, the fun stuff to you is after the origin of life,
which we'll talk about, after the origin of life, there's single cell organisms,
the whole thing with the photosynthesis,
the whole thing with the eukaryotes and multicellular organisms,
and what else is the fun stuff?
The whole oxygen thing, which mixes in with the origin of life.
There's a bunch of different inventions,
all they 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 following the emergence of life.
How did the first cells look like?
And then pretty much anything that we think shaped the environments
and 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,
I don't want to even say data because they are 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 I like that you said fog.
It is pretty foggy, what we are, and it gets foggier and foggier
the more you, the further you try to see into the past.
Biology is, you basically study the survivors, broadly speaking.
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,
it's erased its own history in a way, right?
So you work with this 4 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
because it is responding to the environment.
- Yeah, so what we have, that's fascinating.
What we have is the survivors, the successful organisms,
even the primitive ones, even the bacteria we have today.
- So bacteria is not primitive and we--
- Sorry, sorry to offend the bacteria.
- We should be very grateful to bacteria.
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?
But bacteria is in your dinner, bacteria is in your gut,
bacteria is helping you along the way.
- So we do invite them for dinner.
- Well, they get themselves invited in a way.
And so we, and they're definitely older
and definitely very sophisticated,
very resilient than anything else.
As someone working at, 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 hints about what ancient organisms were like?
Is it bacteria, is it viruses?
What do you study in the lab?
- We study a variety of different bacteria
depending on the questions that we ask.
We engineer bacteria.
So ideally, we wanna work with bacteria
that we can engineer.
Seldom we develop 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 fundamental innovations across billions of years,
there are really good candidates like cyanobacteria.
So we use cyanobacteria very frequently in the lab.
We can engineer its genome.
We can perturb 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 terms of model systems 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 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 inject it with foreign DNA?
- We inject pretty much all the bacteria
that we work with, with foreign DNA.
We also work with diazotrophs.
These are azotobacteria.
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
that's pretty abundant in the atmosphere.
But nitrogen itself cannot be directly utilized by cells
given it is triple-bond.
It needs to be converted to ammonia
that is then used for the downstream cellular functions.
- And that's what counts as nitrogen-fixing.
- Yes, so nitrogen needs to be fixed
before our cells can make use of it.
And it's--
- No offense to nitrogen either.
- Well, it's actually a very important element.
It's one of the most abundant elements on our planet
that is used by biology.
It's in ATP, it's in chlorophyll
that's 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, to fix it.
- So far we know 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 singularity across geologic time.
We think it evolved around 2.7, maybe,
roughly three, probably less than three billion years ago.
And that's the only way that nature invented
§02Transcript · 12:07–21:43
to fix the nitrogen in the atmosphere
for the subsequent use.
- Would we still have life as we know it today
if we didn't invent that nitrogen-fixing step?
- I cannot think of it, no.
It's essential to life as we know.
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, oxygen, nitrogen, carbon,
what are, in terms of being able to work
with these 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 schnapps. - 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 happen
on our own planet.
And there are many abiotic ways to fix nitrogen,
like lightning, right?
Lightning can accumulate ammonia.
Humans found a way about 100 years ago,
I think around World War I, the Haber-Bosch process
that we can abiotically convert nitrogen into ammonia.
Actually, 50% of the nitrogen in our bodies
comes from the human conversion of nitrogen to ammonia.
It's helped, it's the fertilizer that we use,
urea comes from that process.
It's in our food.
So we helped, we found a way to fix our own nitrogen
for ourselves.
- Yeah, but that's way after the original invention
of how to fix nitrogen. - Oh, absolutely, absolutely.
- And without that, we wouldn't have all the steps
of evolution along the way.
- Oh, absolutely.
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,
so E. coli does nitrogen fixing in part,
or is that a different one?
- So some biological engineers engineered E. coli
to fix nitrogen, I believe, not us.
We use nature's 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 are we talking about?
- Depends on how we define complication.
- Okay, so I can tell that you appreciate
and respect the full complexity
of even the most seemingly primitive organisms,
'cause none of them are primitive.
Okay, that said, what kind of, what are we talking about?
How, 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 a very unique subsystem of cellular life
in comparison to, I would say, metabolism.
And we used to, you know,
when we are thinking about cellular life,
we think of cell as the basic unit,
or the building block.
But from a key perspective, that's 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 the entire cell is hopelessly addicted
to this main informatic computing,
biological chemical system that is operating
at the heart of the cell.
- Which is the translation?
- It is the translation.
- What's the translation from what to what?
So RNA to enzymes?
- It converts a linear sequence of mRNA
into a folded, later folded protein.
That's when the, that's the core processing center
for information for life.
It has multiple steps.
It initiates, it elongates,
it terminates, and it recycles.
It operates 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, or chemicals.
It's physical.
It tracks the energy to make its job, to do its job.
It's 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, there's variability and inheritance
that come from imperfect replication even
and imperfect computation.
- Oh man, that's so good.
So from the biology comes the,
like when you mess up, the bugs are 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 bits.
It's done computation, physical.
There's a, I guess, almost like a mechanical process
to the whole thing that requires energy.
And actually, it's manipulating actual physical objects
and chemicals 'cause you have to,
ultimately it's all chemistry.
- Yeah, and it tracks this information.
So it is almost a mini computer device inside ourselves.
And that's the oldest computational device of life.
It's likely the key operation system
that had to evolve for life to emerge.
- It's 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 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 yes, it's informatic
and we can discuss this further too.
- 100%, let's please discuss this further.
Which part are we discussing further?
Each one of those are fascinating worlds,
each of the five.
- Yeah, so well, we can start with the more,
I guess the ones that are more established,
which is the chemical aspect of the translation machinery.
It's 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 operates
not only as an information system itself
or information itself, but also as an enzyme.
And origin of life chemists make these molecules easily.
Now we know we can manipulate RNA,
we can make even with single pot chemistries,
we can create compounds.
- What's a single pot chemistry?
- I would say when you add all the recipes
that you know that will lead you to the final product.
- This is what original life chemists do
is they come up with this pot,
they throw a bunch of chemicals in
and they 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 it's very mathematical
once you know the right environment
and the right chemistry that needs to get
into this container or this pot.
You know what the outcome is.
There is no luck there anymore.
It's a pretty rigid, established input-output system
and it's all chemistry.
- So you actually wear a lot of hats
§03Transcript · 21:45–30:59
as one of them original life chemists?
- My PhD is in chemistry,
but I don't do original life chemistry.
- But you're interested in original life?
- Yes, absolutely.
- So some of your best friends are original life chemists.
- Just make sure that you have good chemist friends
if you're interested in original life.
That's 100% requirement.
It should be mandatory.
- Okay, so chemistry.
So what else about this machinery
that we need to know chemically?
- Well, chemically I think that's it.
You have enzymes, you have proteins.
Enzymes are doing their thing.
They know how to chew energy using ATP or GTP.
They know what to do 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 at about 100 different components
that compose this machinery.
- Well, let me ask, 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, I guess there's a lot
of different chemical possibilities on earth.
Is this translation machinery just like picking
and choosing different chemical reactions
that it can use to achieve a purpose?
Or did the chemistry basically,
there's like a momentum, like a constraint to the thing
that can only build a certain kind of machinery?
Basically, is chemistry fundamental or is it just emergent?
Like how important is chemistry to this whole process?
- You cannot have life without chemistry.
You cannot have any cellular 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 a way it shouldn't, there is resilience
within the system that it can maybe not necessarily
repair itself, but it moves on.
However imperfect, mistakes can be handled.
- That's where the biology comes in.
- That's where the biology comes in.
But in terms of chemistry, you absolutely cannot have
a transition machinery without chemistry.
And so as I said, there are four main steps.
These are the core steps that are conserved
in all transition machinery.
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?
- I cannot separate the two.
I think what makes this machinery fascinating
is that those five components that I listed,
they coexist.
So for instance, if we, let's just,
talking about the chemistry part,
we know the certain 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 information
to the transition machinery and you are the initiator
of this computation system, you need to have,
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.
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 the system collapses.
- So it's like a jazz ensemble, the notes of the chemistry,
but you can be a little off- - I love that you said jazz.
It's definitely true.
It's a party and it's like everybody's invited
and they need to operate together, right?
And what's really cool about it, I think,
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,
put this translation 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,
because we are far from evolving a translation,
maybe not so far, evolving a translation in the lab
or a machinery that can process information
as it generates it.
We have not done that yet.
- That's a pretty complicated machinery,
so it's hard for those origin of life chemists
to find a pot that generates.
- Because it's far more than chemistry.
You need biology, obviously.
You need biochemistry.
You need to think as a, I think, network systems folk.
You need to think about computation.
You need to think about information.
And that is not happening yet,
except we are trying to bring this perspective.
But the more you understand how information systems work,
you cannot, once you see it, you cannot unsee it.
It's one of those things.
- So, but you could still rip it out
and the chemistry happens.
- Yes, and chemistry can happen
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 chemists showed from linear,
you can generate information that arrives
to the 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 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 the, there's only one.
And then there's two, if not three, that says stop.
So that's what you work with,
but you can have 64 possible states,
but life only uses 20 amino acids.
So we use six, life uses 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 are 500 different amino acids life can choose, right?
Narrowed it down to 20.
We don't know why a lot of people think
about this genetic code is quite fascinating.
- So far, right? - Right.
I mean, it didn't do it for 4 billion years.
I don't know, we may wait for another 4 billion years, but.
- But you didn't have those amino acids
in the very beginning, right?
Like. - We don't know.
So we wouldn't 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 wasn't the same.
- Or similar. - Yeah.
We don't have a good reason,
but because roughly 20 out of 60 states are used,
you're using one third of your possible states
in your information system.
So this may seem like a waste,
but informatically it's important
because it's abundant and it is redundant, right?
So this code degeneracy, you see this in,
that's implemented by this translation machinery
inside the cell.
So it means you can make errors, right?
You can make errors, but the message will still get through.
You can speak, missing some letters,
the information can miss some parts,
but the message will still get through.
So that's two thirds of the not used states
gives you that robustness and resilience within the system.
- So at the informatic level, there's room for error.
There's probably room for error probably
in all five categories that we're talking about.
There's probably room for error in the computation.
There's probably room for error in the physical.
- Yes, exactly. - Everywhere there's room
for error. - Yeah, because
the informatic capacity is made possible
together with the other components.
And not only that, but also the product yields
a function, no, in this case, enzyme or protein, right?
So that's really amazing to me.
§04Transcript · 31:04–40:27
- It is, I mean, in my head, just so you know,
because I'm a computer science AI person,
the parallels between even like language models
that encode language, or now they're able to encode
basically any kind of thing, including images and actions,
all in this kind of way.
The parallel in terms of informatic and computation
is just incredible.
- Actually, 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 up.
Yeah, it's a very standard table.
So I can explain why this is so amazing.
So you're looking at, this is life's alphabet, right?
And so I also wanna make a very quick link now
to your first question, the tree of life.
When we try to understand ancient languages,
or the cultures that use these extinct languages,
we start with the modern languages, right?
So we look at Indo-European languages
and try to understand certain words.
And make trees to understand,
this is what Slavic word is for snow, something like snig.
- Now we jumped to languages that humans spoke.
- Humans spoke, 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 it was snowy,
that's why they needed that word.
It's the same thing for biology, right?
If we understand some function about that enzyme,
we can understand the environment that they lived in.
It's similar in that sense.
So now you're looking at the alphabet 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 compose 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 start.
There's no other start code.
So you sent the AUG to the cell,
when that information arrives,
the translation knows, all right, I got to start,
function is coming.
Following this is a chain of information
until the stop code arrives,
which are highlights in black squares.
- So for people just listening,
we're looking at a standard RNA color table
organized in a wheel.
There's an outer shell and there's an inner shell,
all using the four letters that we're talking about.
And with that, we can compose all of the amino acids
and there's a start and there's a stop.
And presumably you put together,
with these letters, you walk around the wheel
to put together the words, the sentences
that make-- - Yeah, the words, the sentences.
And 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 messed that up,
you still can rescue yourself.
So you can get, for instance,
I'm looking at the lysine K,
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 and a G,
you still get the lysine.
So there are different combinations.
So even if there's an error,
we don't know if these are selected
because they were erroneous and somehow they got locked down.
We don't know if there's a mechanism behind this too,
or we certainly don't know this definitively.
But this is informatic part of this.
And notice that the colors, and in some tables too,
the colors will be coded in a way
that the type of the nucleotides can be similar chemically.
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 output,
like the same function and which don't?
Which actually results in a dysfunction, which are?
- We understand to some degree how translation
and the rest of the cell work together,
how an error at the translation level,
this is the really core level, can impact entire cell.
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.
Even though it is so essential.
So this is, yeah, you're looking at the language of life,
so to speak, and how it can found ways
rather to tolerate its own mistakes.
- So the entire phylogenetic tree
can be like 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 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,
which may be a little easier way to track the information
when we create the tree.
- So using this language,
we can describe all life that's lived on earth.
- I wish. - One perspective.
- 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 from a molecular perspective,
this would be the way to do it.
And this is what nature narrowed its code down to.
So when we think of nitrogen,
when we think of carbon, when we think of sulfur,
it's all in this,
that all these nucleotides are built based on those elements.
- And this is fundamentally the informatic perspective.
- Exactly, that's the informatic perspective.
And it's important to emphasize
that this is not engineered by humans.
This evolved by itself.
- 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 appears to be a highly optimized chemical
and information code.
It may indicate that a great deal of chemical evolution
and this may indicate that a lot of selection pressure
and Darwinian evolution happened
prior to the rise of last universal common ancestor.
Because this is almost a bridge
that connects the earliest cells
to the last universal common ancestor.
- Okay, can you describe what the heck you just said?
So this mechanism evolved before the,
what common ancestor?
The last universal common ancestor.
- Yes, so when we talk about the tree,
when we think about the root,
if you ideally included all the living information
or all the available information
that comes from living organisms on your tree,
then on the root of your tree
lies the last universal common ancestor, LUCA, right?
- Why last?
Last universal?
Because the earlier universal,
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 don't know
what we cannot track, right?
- There's one organism that started the whole thing.
- It's more like, I would think of it
as more like a population, a group of organisms.
- Okay, hold on a second.
I tweeted this, so I wanna know the accuracy of my tweet.
All right.
Sometimes early in the morning,
I tweet very pothead-like things.
It said that we all evolved from one common ancestor
that was a single cell organism 3.5 billion years ago,
something like this.
How true is that tweet?
Do I need to delete it?
No, there's not actually, correct.
I mean, I think, of course, there's a lot to say,
which is like, we don't know exactly,
but to what degree is the single organism aspect,
is that true, versus multiple organisms?
- Do you want me to be--
- Brutally honest?
Yes, please.
There's still time.
This is how we get like caveats to tweets.
- All right, so first of all, it's not,
3.5 is still a very conservative estimate.
That's what's-- - In which direction?
- I would say it's 3.8 is probably safer
§05Transcript · 40:30–50:05
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, you're 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?
- No, no, no, I'm relating to my--
- Your own development.
- My own development, I started from a single cell.
It's like, it built up a cell, okay.
That, and then, so that's for a single biological organism.
And then from an evolutionary perspective, the Luca,
like I start, like my ancestor is 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
through this brutal search for adaptation
through the 3.5, .8 billion years.
- So you defy the code of Douglas Adams.
You are proud of your ancestors,
and you invite them over to dinner,
and you invite them over to your Twitter.
- Yeah, 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, so you see that translation
is a fundamentally intelligent mechanism.
- In its own way, and again,
if we manage to figure out how to drive life's evolution,
if it can evolve a sophisticated
sort of informatic 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.
They don't need the big picture.
- So that's a great segue
into what makes this biological, right?
The heart of the cellular activities are translation.
You kill translation, you kill the cell.
Not only the translation itself,
you kill the component that initiates it,
you kill the cell.
You remove the component that elongates it,
you kill the cell.
So there are many different ways to disrupt this machinery.
All the parts are important.
Now, it can vary across different organisms.
We see variation between bacteria
versus eukaryotes versus archaea, right?
So it is not the same exact steps,
but it can get more crowded
as we get closer to eukaryotes, for instance.
But you are still computing
about 20 amino acids per second, right?
This is what you're generating every second.
- That single machinery is doing 20 a second?
- 21 for bacteria, I believe eight for 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 actually do nine amino acids.
- Yeah, but it's way slower than a computer
could generate through simulation.
- I think, if you can show me a computer that does this,
we are done 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?
- Yes, you can show me that,
but you cannot show me the one that has all.
- For now.
- For now.
- I'm gonna ask you about probably what, alpha fold, right?
- 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 is 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 back to the biological component,
all of these attributes that we think about life
or that we associate with biology
stems from translation as well as metabolism.
But I see metabolism as a way to keep translation going
and translation keeps metabolism going.
But translation 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 a way to process materials
and it is inherently dynamic and it is flexible,
but it is not focused on repetition as translation does.
So that's the main difference.
Translation is the kind of in a way, just it's repeats.
So you have the metabolism that can synthesize materials,
creates or benefits from available energy.
And again, it's a dynamic system.
And then you have computation
that is inherently repetitive, right?
Needs to carry out repetitive processes.
And it does the tasks and 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 life
if you don't find a way to process the information
around you.
- In a repetitive dynamic way.
- Yeah, and somehow that's what got selected,
maybe not selected, I don't know if it was accidental,
but 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
another weird thing that life just started doing,
wanting to just replicate itself.
- I think when we truly understand the answer
to that question, we may have just made ourselves life.
I don't think we know quite how translation machinery
as a whole fits into equation.
'Cause we try to understand ribosomes, RNA,
how the linear information is processed.
Or the genetic code, why this codon's not others,
why 20 not more, not less.
And we are sort of moving towards translation,
that's what we are working on anyway.
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.
- 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 published in 2013,
I wanna say the first author is Zirnoff.
So they surveyed a computational,
engineered systems level computation energy consumption.
And they tried to understand whether the universe
is using its own, or life is using its full capacity
of energy consumption.
And whether if different planets in the universe
had life, would the capacity would increase or decrease?
Does life operate at its energy maximum?
And they think that it does,
that it actually operates at an efficiency
that is far more above and beyond any computational system.
- How is that possible to determine at all?
- That you tell me, that's why I dropped the citation.
I found the citation, it's quite an interesting paper.
It's a bit, you know, it's a,
obviously we 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 it to computers,
it seems to be incredibly efficient at using energy.
- I think they look at the theoretical optimum
for electronic devices. - Got it.
- And then try to understand where life falls 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 you?
And so given all the resilience to errors
and all that kind of stuff,
it seems that it's close to its maximum.
And 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 personally define life?
Do you have a favorite definition
you try to sneak up on?
Is it possible to 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,
§06Transcript · 50:08–59:09
then it probably needs to have some quantification in it
so that you can use it in whatever the mission
that you're operating to.
- So you mean like it's not binary,
it's like a seven out of 10?
- Life-like?
- Life-like.
- I don't know.
I don't think that defining is that essential.
I think it's a good exercise,
but I'm not sure if we need to agree
a universally defined way of understanding life
because the definition itself
seems to be ever evolving anyway, right?
We have the NASA's definition.
It has its minuses and pluses,
but it seems to be doing its job.
- Well, 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 kind of an important thing
to think 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 the different moons in our solar system,
when we go outside our solar system
to look for life on other planets?
- It's unlikely to be a sort of a smoking gun event, right?
It's not gonna 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, there's life here.
- No, but isn't there a dynamic nature to the thing?
Like 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 grow, but there are plants
that can be also pretty dormant.
And arguably they do everything
that one of my favorite professors once said,
that the plant does everything
that a giraffe does without moving.
So movement is not necessarily.
- But on a certain timescale,
the plant does move, it just moves slower.
- Yes.
- It moves pretty quickly.
- I would say that, it's hard to quantify this
or even measure it, but it is,
life is definitely chemistry finding solutions, right?
So it is chemistry exploring itself
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 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 chemistry or the solutions
that it embarks upon are maintained in a form of memory.
Right, so you don't just need to have
the 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 will be very upset with you.
Okay, so memory could be a fundamental requirement for life.
- I mean, life is obviously chemistry and physics
leading to biology.
So this is not a disciplinary problem of one discipline
trying to bring other disciplines.
But what you need to have is definitely,
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.
- Earth.
- That's it.
- Yeah.
- So definitely something very fundamental happened here
and you cannot take biology out of the equation.
If you wanna understand how that vast chemistry space,
how that general sequence space got narrowed down
to what is available or what is used by life,
you need to understand the rules of selection.
And that's where evolution and biology comes into play.
- 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.
It would be fascinating to find
in terms of the biology's rules.
That's a very interesting
and it's a very fascinating area of study now.
And probably we will hear more about that decades to come.
But if you wanna go from the broad to specific,
you need to understand the rules of selection.
And that is gonna come from understanding biology, yes.
- Well, actually, let me ask you about selection.
You have a paper on evolutionary stalling
where you describe that evolution's not good at multitasking.
Or like in populations that evolve 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,
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--
- Should or should not?
- You shouldn't.
As I said, there are many ways to break it
and all life needs it.
- That's one of your favorite things to do
is to break life to see what happens.
- Yeah, because that's how kids learn, right?
So you have to break something
and see how it will,
then you do it over and over again
to see if it will fix itself in the same ways.
So it's our, I don't know,
it's the most fundamental properties
of ourselves as human beings.
So if we shouldn't break translation,
then we should try to break it
to see how it will repair.
- So which part did you break?
- I broke elongation.
- What's the role of elongation in this process?
- So we have four steps of the translations,
initiate, elongate.
So you elongate the chain,
of the information chain
that you're now creating, the peptide chain,
or let's say broadly polymer chain.
And there's a termination step
and there's the recycling.
So all of these steps are carried out by proteins
that are also named after these steps.
Initiation is the initiation factor,
protein elongation is the elongator protein.
We 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 its own ancestral version.
So we inserted roughly 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 a hybrid organism.
It's not necessarily,
because the rest of the cell,
the rest of the 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 are doing it.
But also we are not necessarily,
I think in Jurassic Park they are taking
an ancient, they find an ancient organism
and then put a 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 organism.
- So 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, which is doing things.
- Yeah, so it's a more complicated organism
than just a car.
- Yeah.
- I got it.
So what does that teach you?
- We wanted to understand multiple things.
One is how does the cell respond to perturbation?
And we didn't just put the ancient DNA,
we inserted, we sampled DNA from currently existing organisms
§07Transcript · 59:14–1:08:48
or the cousins of this microbe,
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 variant 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 to figure out
how evolution figures out what to try to improve?
Did that help?
- Yes, because we were not supposed to
mess with the translation.
That's exactly what we did.
And we altered elongation by changing it
with different versions of elongation
that are either coming from species
that still are around today.
You can imagine them as sitting on the tips of the tree
near branch, far branch, compared to the organism
that we're working with, distant cousins,
as well as the ancestors of the bacteria
that we are now modifying.
- How much different variation is there
in that elongation step?
Like what are the different flavors of elongation?
- That's a very good question.
So mechanistically or mechanically, it's the same.
It's very conserved.
So all life elongates the same way.
It's nothing but a shuttle.
You just carry the chemical with you,
the bit, to the heart of the machine.
- Is it essentially doing like a copy paste operation?
- It has its tail that's attached to the code,
which is then carried biochemically to the linear chain,
to the core of ribosome.
And it sits on there.
It's released and the peptides click.
The codes rather click.
Once that chemistry, that's at the tail end, occurs,
the protein leaves the center.
So you can imagine it's like it hops in there and hops out.
And when it hops in, hops out,
it leaves the information behind.
That's all it does,
is bring the information, get out of there.
And it's all triggered by biophysics, biochemistry,
because of the way the enzyme choose energy,
in this case, GTP, how the phosphor leaves the center,
that kicks, that gives the additional kick
to the enzyme to leave the center.
- So which parts are different then?
Where's the flavors, different flavors of the location?
- Usually the parts that matter don't change over time.
Nature conserves the sites of these proteins
that are important for its job.
If there's a difference, then we wanna know,
especially if there's a difference between two cousins.
And we look at the sites that interact
with the most important parts of this machinery.
If we see any difference, we tend to mutate,
or we revert, we engineer that part, we alter that part,
because it gives us a clue
that there must be something interesting
going on here or not.
- Okay, so that's not the fundamental part of the machinery,
but it's some flavorful characteristic
that you can play with.
- So now you stripped the machinery down to its parts,
and now you're looking at the parts of the parts.
And it depends where you're looking
and how you're looking and what you're looking at.
But usually we see up to 70% level conserved identity
across all modern versions.
When you travel back in time, the identity decreases.
So elongation likely existed.
We have good reason to think that it existed
at the dawn of life.
So you're looking at a 3.8 billion year old mechanism.
And when we look at the ancestors that we resurrect,
we see about 40% identity.
So the identity definitely decreases as you go back in time.
But still 60% shared information over four billion year,
it's pretty good.
- Is that just for elongation
or for the entire translation?
- Depends on what you do.
So for initiation, we've also recently published this.
It's a different story.
But overall you see high level of identity
that is kept intact,
especially if the component is essential for life.
- Okay, so 40% and 60%, 70% you said.
But like from generation to generation,
how does evolution,
and presumably that's what that paper is looking at
is the parts of the parts.
- Yeah.
- How does it able to say, like mess with the parts
and try to come up with a cooler,
improved version of the organism?
- Yeah, so let me describe to you
what we did in that experiment.
We took bacteria,
we perturbed the elongation in all of these
with different variants.
So we had an initial set of a group of bacteria that we had.
We then subjected these bacteria to evolution in the lab.
So first of all, we knew we broke it
because upon engineering,
we measured what's going on with the cell.
It's not growing as well.
They're not healthy.
We can see it with our eyes.
We can measure it.
That if they were generating an offspring every 20 minutes,
now it is 40 minutes, right?
So we really messed them up.
They don't wanna work with this thing.
They don't want each other, but they need each other.
So we created that situation for them,
which is good because we wanted to see
how they will cooperate with each other to fix this problem
because we know that that's not the condition
that they wanna live in,
especially when they know what they can do.
So with that, we subjected these organisms
to evolution in the lab.
We refer to this as experimental evolution.
We subject bacteria to different selection pressure,
project them through bottlenecks.
Every day, we randomly collect a handful of bacteria
from the flask, put them in a new fresh environment
with fresh food, keep them in this environment for 24 hours
until they reach a more dormant state.
And then we subject, introduce them to a new environment.
So we repeated this for about, I will say, 150 days.
So every day, nonstop, we repeated this experiment.
- So kind of how many different kinds
of environments are there?
- We kept the environments to the same
because we had different initial conditions.
We kept the environment constant, same temperature,
same food, same source of carbon,
but we created replicates for each lineage.
So in some ways, we created our own fossil record
in the lab by evolving and generating these flasks.
And every step of the way, we also froze these cells
and took stocks of them in the cryo-freezer.
- How long does it take to go from one generation
to the next of bacteria?
- For E. coli, it's usually 20 minutes.
- Okay, great.
So that's the experiment. - That's the experiment.
- And you're always messing with it in the same way
for the initial condition? - It's the same way.
So we introduced variation at the elongation level
because we perturbed it with different elongations.
We found that if we introduce a different protein
that is very different, the cells don't like that, right?
So if the distance is larger, the consequences also large,
meaning that you hit them harder.
If you introduce a variant that is really foreign to them,
that's really distant.
In our case, it was the ancestor.
They really did not like the ancestor,
but they were okay with their nearest cousin.
- Right, okay, great.
So you did vary in the distance.
- We varied the evolutionary distance
and then we kept the experimental conditions the same
and we propagated these populations every day for 150 days
and we collected bacteria at every step of the way
and looked at the sequence.
We wanted to understand what sort of changes
may have happened in the genome
to respond to the variation that we've introduced.
- So what kind of changes would you be seeing
depending on the evolutionary distance
of the thing you shoved into it?
- Exactly, so we knew where we punched, right?
We punched right at the heart, right?
We punched the translation.
So we expected, is it gonna be, is it translation?
Are we gonna see a change?
Will translation respond to this
by fixing itself right away?
Or will it be another, outside of translation,
something completely different, a different module,
because translation itself is a module?
Or will it be within elongation,
a really sub-protein level thing?
So we had a strategy to identify the mutational pathways
by categorizing what we expected to find or where.
- Okay, so why does it not do multitasking?
Why is it not improving multiple things simultaneously?
- It turned out that what we observed in general
§08Transcript · 1:08:51–1:17:22
is that first of all, the harder we hit the cells,
the more likely they were to respond to our changes, right,
at where we hit it.
- When you say hit it,
you mean like changing something about the elongation?
- I like to think of it as hitting,
because I like to think of this as breaking the cell, right?
I mean, not breaking enough to kill it,
but we still, because they're still alive,
they're not doing their job well.
- So the bigger the evolutionary distance
of the thing you put in there,
the harder the hit is how you think about it?
The bigger the hammer?
- Bigger the hammer, exactly.
- That you hit it with, okay.
- That's what it turned out to be,
'cause that's what the data told us,
that if the variation is higher,
then the consequences will also be higher,
in the sense that the cells will not grow as healthy
compared to a variant that is coming from a near,
or a variant that is coming from a near evolutionary distance.
- Is it wrong to think of this kind of hitting
as akin to a mutation, or no?
What are we supposed to learn from this hitting?
Like how the thing evolves after it's being hit in this way,
what does that teach us?
- Because we see translation machinery as almost,
it is so conserved and so essential,
it is not even clear whether we can remove some of the parts
or whether the entire translation will need
all of the same parts in the same efficiency.
We don't understand the rules of this machinery.
So the first thing we understand is that,
what is the resilience?
What are we really talking about here
when we talk about you cannot mess with this translation?
Is this true?
Because it is so conserved and so similar
and functions in the most conserved ways,
that was the first thing that we wanted to understand.
- Did you learn anything interesting about the resilience
at the chemical, physical, informatic,
computational, biological?
- No, I wouldn't say that,
I think the biological level, yes,
because we found that the different modules
started responding to the changes that we've introduced,
and that we could never recover the translation
as effectively as it used to be.
So that it never reached to it is optimality,
that it was always suboptimal.
It needed say one more mutation perhaps to get there,
it accumulated four mutations that was,
we did a lot of experiments to understand this of course,
it was accumulating mutations,
it was getting better at its task,
maybe it needed a couple other mutations
to get really good at it,
but somehow those mutations never happened.
And before those mutations happened,
we saw another module emerging through mutations
and getting better at its own different tasks
that is not translation.
You can think of cell as a web of networks, right?
And we think of these as multiple almost airports
that are proteins that are more central hubs,
versus their proteins that maybe are not as important hub.
If you introduce a problem in the most populated hub,
you're gonna mess up the traffic system more drastically.
And that's what we were messing with
in the biological terms as well.
- So when we say module,
like translation would be one of the modules.
- Translation would be one.
- So you're basically saying when you mess with translation,
the organism would choose to either try to fix that module
or another module, depending.
- Exactly.
- But it wouldn't do multiple modules.
- It wouldn't do multiple modules.
It focused on one module at a time.
And right before that module maybe reached
to its own maximum, it stalled its optimality
at a certain degree.
So you never get to a degree that is more optimal
than you can achieve,
even though perhaps another mutation could get you there.
- Since you messed with the translation
from a sort of optimal perspective,
wouldn't it make sense for the cell
to try to start fixing the translation?
- That's exactly what we thought.
And it was not the case
for all the broken translation missionaries.
For instance, if the variant was coming from a near ancestor,
that didn't happen.
It was almost cruising around, trying different modules
and sort of living its best life still without,
because there is no real urgency in the system
to fix the most important problem.
- And there's also not a direction.
Maybe to you it's obvious that's the problem,
but to the cell, maybe you're the problem.
I'm living, like you said, my best life.
I mean, I guess that's the thing about evolution
is we don't know what the right direction to-
- Yeah, it's almost like you can imagine
that you have this messy closet and you can-
- Go on.
Happens to be an accurate representation of my life.
- So you take a look at it
and you see all the sweaters or jeans all over the place.
And then you look at a drawer
that has socks coming out of it.
And you'd think that's the most important one.
I'm just gonna fix that one.
And then you fix that one.
And then you think you will get to the other one,
but you don't because you just fix the most important one.
That is the, whatever that was getting into your way.
That's really what evolution is.
It's quite lazy.
It fixes the problem that seems to be the most immediate
and it doesn't go beyond what it really needs to.
It seems like at least for our experimental setup,
that was the case.
- Especially for rapidly evolving systems.
So like, or is the environment they're operating
in pretty constrained?
Like, is there an urgency?
- I would say that we definitely
constrain the environment.
It's definitely removed from their natural setup.
We are not evolving them in a gut.
It's a very homogeneous system,
very controlled temperature,
controlled food, controlled carbon.
- So just looking at that,
let me ask the romantic question.
How did evolution create so much beautiful,
complex variety on earth?
Like from that, you're saying that we're talking
about improving different modules,
but if we step back and look at the entirety of the tree
or the different organisms that created
all throughout history,
the stuff that's fun to you with the first few billion
and the stuff that's fun to me when I watch on YouTube,
which is like the lion versus gorilla fights and so on,
but the whole thing is fun.
So with all that beautiful variety
from the predator and the prey,
from the self-replicating bacteria
and all that kind of stuff, how did it do it?
- How is a very difficult question,
especially when we don't understand the past
with clarity at all.
I can tell you that there seems to be very critical
innovations that happened throughout the history of life
that are each themselves very sophisticated singularities
that emerged once and then they set the tone.
One of which is emergence of translation.
It's seems like it happened once.
It had to happen once.
It seems like that's all it took.
3.8 billion year, maybe older,
clearly subjected to a lot of chemical evolution
even prior to last universal common ancestor.
And then you jump and you see emergence of cyanobacteria
that's undeniably changed the course of those planets
in the subsequent aerobic photosynthesis that's life learned
how to utilize what's available in the environment
in the most profound way.
And then you move forward,
you see the emergence of eukaryotes,
that is endosymbiosis, also another singular event.
And then you move forward and then comes the plants.
So these are, I counted, I think six different things
that seems to have happened just once.
- And the singularity events
in the history of evolution of life on earth.
- So what's really fascinating here
is that there seems to be two different courses,
the time course.
Evolution is operating at the molecular level.
We're talking about seconds.
We're talking about mutations that happen every second.
We're talking about selection
that's also happening under a minute.
So that is a very fast process.
The fact that I can evolve bacteria in a lab
and I say, almost complaining,
"Oh my goodness, it took me 150 days."
I mean, that's pretty rapid for a change to be seen.
But then the big changes and the ones that I'm talking,
the really big innovations that caused an increase
of oxygen on this planet or even its own mere presence
are due to these molecular innovations.
§09Transcript · 1:17:24–1:27:03
Seems to only happen a handful of times
over billions of years of timescale.
- Let me ask you this question
having to do with my half asleep tweet.
So saying that we all originated from one common ancestor,
that's just one of the miraculous things
about life on earth.
Of course, you could say there's multiple common ancestors
in the beginning, multiple organisms and so on.
But the other stuff that you're talking about
is these singular events,
these leaps of invention throughout evolutionary history.
Now there's a bunch of people who were commenting,
a bit surprising to me,
who were basically skeptical of this idea.
- The idea of?
- Well, I would say evolution, honestly.
The process of evolution,
but when you just actually focus in on like,
"Holy crap, eukaryotes were invented.
"Holy crap, photosynthesis was invented."
Like those are incredible inventions.
And also, we can even go to Homo sapiens,
like intelligence, like where did that come from?
It's these mysteries.
I think where that skeptical comments are coming from
were also just the general skepticism of science.
I think from the pandemic,
people, maybe a failure of institutions and so on,
there's been a growing distrust of science.
And it's not so much that it's anti-evolution,
it's more of a stepping back and saying,
"Wait a minute,
"maybe scientists don't have it all figured out."
And I think to steel man that case
is almost a step back into realize
there's so much mystery to each of these leaps.
So it makes you wonder,
is there something that in 100, 200 years
we'll figure out that we totally don't understand yet?
Like some, you know, there's,
I talked to a bunch of people about another mystery,
which is consciousness, right?
And there's people called panpsychists
who believe consciousness
is one of the fundamental laws of the universe.
So there could be, you know,
like we have laws of physics that could be something
that's like a consciousness field or something
that permeates all matter.
And so like there might be,
it's kind of like Newtonian physics
versus general relativity.
Like we have a good understanding of how things happen,
but we need another layer of understanding
to fill in the gaps of the mysteries of it all.
And that sort of is a sobering reality
that maybe there is something
we really deeply don't understand.
Do you have a sense of where the biggest mysteries here are?
Is it at the origin of life itself?
Is it the leaps that we're talking about?
So you see the beauty,
you're fascinated about the translation mechanism.
What are the deep mysteries there to you?
- We are nothing but chemical systems
capable of formulating or answering questions
about our own existence.
- We humans or all of life, you think?
- Humans, humans are,
I mean, the fact that we can,
we even have this conversation about
our place in the universe is,
at least to our knowledge,
is quite specific to our own chemical species.
But-
- Yeah, it's kind of wild.
We're introspecting on our evolutionary history
and we're just a couple of organisms.
- Yes, and we're-
- We're like another organism listening to this
and like they're mind blown.
There's like three organisms,
two of them talking and the third one's like, holy shit.
- I think that understanding the,
what I really find interesting
about understanding origin of life
or even contemplating about our own place in the universe,
if at the end of this would come down to appreciating
or even before appreciating,
really truly comprehending what it is that we got here,
that to me is a huge gain.
'Cause there's no single question in biology,
I think, that will give that,
that will deliver that magnitude
of that message and understanding.
But understanding how life here started at first place,
if we truly comprehend that.
This is not a concept that is well thought in schools.
We ask students to memorize these concepts.
If they are lucky, they learned RNA world,
chicken and egg problem, et cetera.
That's the extent to which that got,
maybe their biology teacher was personally interested
in the subject matter, if they're lucky.
You know the saying that the brains are evenly distributed
across any metric you can imagine, but opportunities are not.
So if people aren't understanding the importance of this
is because that's a lack of opportunity right there.
That's was skipped through the proper education
and training in the delivery of why science matters
or how science actually works.
- Yeah, but how do you even begin to seriously think
about the origin of life?
I mean, every problem of existence, of life has its time.
So I don't know if it's time to understand consciousness yet.
We might be a hundred years away from that.
The origin of life, I don't know if it's time for us
to understand that yet.
Maybe we need to solve so many more problems along the way.
- It's not a competition of problems, right?
So there are all kinds of problems
and it takes a lot of people to make the world.
So you will always have some interesting brain
going after an interesting problem to their own.
The issue here is that we need to first of all
understand that what we have going on on this planet
is pretty good.
Good planets are hard to find.
If we are alone in the universe, that's huge.
We need to take care of what we got here.
And we are incredibly vulnerable to the changes
that our own species also helped create
at the biosphere, at the ecosystem level.
We take it for granted.
We take what we created for granted.
Because of the fact that we think we are some sort of
ultimate end point, the most sophisticated, amazing thing
that nature could generate.
I think understanding, not even understanding,
but asking these questions of where did this even come from?
How did this even begin?
And attempting to understand that using chemistry
and physics and biology, and because we can,
that's the ultimate gift we can give back
to the entire species on this planet.
- Yeah, I mean, it's humbling.
It's humbling to realize the complexity
of this whole mechanism.
It certainly puts humans in their proper perspective.
That we're not, just 'cause we have brains
and brains are intelligent, doesn't mean
we're the most intelligent thing.
Because ultimately the whole mechanism of nature
seems to be orders of magnitude more intelligent.
All of it, like we're a bunch,
we're like a hierarchy of organisms
that have a history of several billion years.
And that all somehow came together to make a human.
And there'll be life after us, just as it was life before us.
And something that comes after will be
perhaps even more fascinating.
- Yeah, I think when you understand the magnitude
of what happened here, there is no room for arrogance.
It should overwhelm you and humiliate.
It's pretty humiliating.
- Yeah.
- You know, it's quite amazing what happened here.
And there is no other discipline that will deliver that.
But exploring our own origins and looking at life
as a more planetary system phenomena
rather than one single species at a time, a collective look.
- You mentioned this question in your TED Talk is,
the two possibilities of the universe being full of life
and the universe being empty
and we're the only life in the universe.
How do you feel about both options?
Just actually you as a single chemical organism
introspecting about its existence in this world.
- It's having a planet flow of life is interesting
because there are, we talked about life being all about
chemistry exploring solutions.
And having solutions in front of you is great.
It's beneficial, right?
- Solutions being different organisms.
Like other humans, you see them as a solution
to a chemistry problem.
- Different, yeah.
- That's an interesting solution.
That's not, next time we're in Austin
so there's a bunch of weirdos.
Every time I see a weirdo, I'll be like,
oh, that's an interesting solution
to this chemistry problem.
- Now you think like an origin of life science.
But it's--
- Funny that that one worked out.
Let's see where else it goes.
- But having this emptiness and unpredictability
of uncovering a novel solution
§10Transcript · 1:27:05–1:36:58
can also have its own benefits.
And we should be open to what other solutions
might be out there and exploring those solutions.
- Or to different chemistry problems.
So that's where you see-- - Different chemistry problems.
- You see the other planets out there
as different chemistry problems.
- To their own local environment, yes.
So how many chemistry problems have solutions
that are lifelike to you out there in the universe?
- It's a wide open palette if you think about it.
I don't quite know.
It's the, we know the chemistry is chemistry.
I don't think the chemistry will be different elsewhere.
But again, what is selected by chemistry
will be determined by the environment most likely.
- See, I think there is life everywhere out there.
So there's a guy named Nick Lane
whose gut, and it's interesting to me,
I wonder what you think about it,
his gut is there's life everywhere out there,
but it stops at the bacteria stage.
So he says the eukaryotes is the biggest invention
and the hardest one.
- I wonder if he thinks that's an accidental outcome,
if he thinks that's inevitable.
I wonder what that means.
But it's a likely possibility
that the bacterial or microbial life
is definitely more attainable.
- So that's a weird world
where our entire galaxy just has bacteria everywhere.
- So you know, if you don't like microbes,
you are on the wrong planet.
- No, I know, yeah.
And viruses, I don't know which one there's more of.
But they're both, and most of them are productive.
- They're fascinating.
They do everything for us.
- I don't like microbes, you're on the wrong planet.
You're full of good lines.
Okay, right, right.
I just can't, there's like an imperative to the whole thing.
To me, the origin is the hard question.
But once it gets going, I just don't see--
- Wait, go ahead.
- It seems like it's constantly creating
more intelligent things,
more fascinating, complex things
that are able to solve complicated problems.
- That's a very interesting,
I definitely agree that the initial steps
may be the ultimate determinants.
That once it's, you cannot stop it once it starts.
It's possible, right?
And--
- I just have never on Earth, maybe, but maybe,
I just, whenever I see life, it seems to flourish.
Everywhere.
The thing is, I don't,
the only thing I haven't seen is the start of it.
- Exactly, but, and how are we gonna understand that
if we don't know the origin of life science?
I mean, that's the, and the question here isn't exactly
our ability to recapitulate everything that happened
in the exact way that it happened, right?
This is about what can happen, rather than,
or maybe how it can happen.
- You think it's possible to study the origin of language
using English?
So, like, there's a very particular chemistry here.
There's a particular set of assumptions,
understanding about what life is,
what everything is, our perception of reality
is very specifically constructed
through the evolutionary process.
I wonder if it's possible to get to some first principles,
deep understanding of how life originates
in such a way that you can actually
construct it on other planets.
Ultimately, it feels like if you're doing it
in a lab on Earth, you're always going to be using
some aspect of the life that's already here.
- So, that's what I sort of talked about in my talk as well.
And-- - Everyone should go
watch the TED Talks, very good.
The annoying thing to me about TED Talks,
I guess it's by design, is they're too short.
It's like, come on.
- And did you know that there's no prompter involved?
- There's no, wait, there is?
- There isn't.
- Yeah, you have to memorize stuff.
Yeah.
- It's a--
- It must be a grueling process.
- Amazing editor who probably is watching this too,
David Bielo, that was very, very helpful.
But I would say that--
- Very professional organization.
I like this podcast, it's a very professional organization.
I respect that medium.
Yeah, anyway, in the TED Talk about, yeah, life,
life creating life.
- So, it's a likely scenario that once we understand
how life as a chemical system is capable
of formulating its own expression and generating a memory
and manages its existence on a planetary body
for billions of years,
once we understand what conditions gave rise to that,
we may be very likely to understand
whether a different planet also be likely
to instigate its own chemical revolution
if it was provided through some missing ingredients.
So you can think of it as a sending fertilizer
to a different planet that is missing
its own chemical composition or lacking
or that it needs more of what it has.
The difference between making that planet Earth-like,
which was, this is not what that's about.
We're not talking about terraforming
or we're not talking about turning that planet
into Earth-like system.
We are talking about first understanding that planet,
studying its chemistry, studying its properties well enough
to understand whether it is close
to its own chemical revolution
and maybe giving it that extra nudge.
So this is obviously a pretty big speculation and suggestion.
And it's a very interesting proposition
because this is a yes or no question, right?
This is the ultimate would you rather.
And I think it says a lot about the perception
of the person who's answering this question.
That if the answer is no, no, no, absolutely not.
That's not something we wanna do.
I wanna know why that is the case.
- So just to be clear, what we're talking about
is looking at the chemical cocktail of a particular planet
and having like tasting it and seeing what's missing.
So having a very systematic, rigorous,
scientific process for understanding what is missing.
Not what is missing in terms of to make it Earth-like,
but what is missing in order to be sufficiently,
have the spark or the capacity of the spark
to launch the evolution revolution,
the evolutionary process.
- Exactly, so--
- And then the question is,
do we want to then complete the cocktail?
- The proposition is to also make us think
that we will likely have this capacity at some point,
especially when we understand origin of life
better and better, right?
So we will be asking ourselves this question.
I guess I wanted to bring this to daylight a little bit
because maybe in 10, 20 years, maybe more.
- So you wanted to ask the ethical question,
should we basically start life elsewhere on another planet?
Or enable the chemical capacity of that planet
that it may one day itself get there?
- Okay, so for me, the answer is yes.
So if you were to try to argue against my yes,
what would you say?
Why not?
What's the worst that can happen
if we seed another planet with life?
What are the things we should think about?
Is your main concern a chemical biological one
or is it an ethical one?
What do you think about?
- Well, the worst thing that can happen
is that it wouldn't work, right?
So that it's not likely that an attempt like this would work.
That's probably, 'cause how do you--
- I think so.
- You gotta be very, you have to have an understanding
that I don't think we have just yet.
- I see 'cause if it doesn't work,
then we could try again, right?
- To me, the worst case, the thing I would be worried about
is we create life, I mean, the same stuff I worry about
like with plants is things that might have
a conscious experience.
And then the dark aspect of life
is life is increasingly a complex life.
Maybe I'm anthropomorphizing,
but it seems to have the capacity to suffer.
And so we're creating something.
It's like when you have children,
you put creatures into this world
that will suffer, can suffer and may suffer
depending on how you view life, may likely suffer.
And so now you carry this responsibility
for doing your best to alleviate any suffering
that might go through.
And that perhaps is a romanticizing this notion
of life, perhaps bacteria are not capable of suffering,
but perhaps it'll create more complex life forms
that would be able to suffer.
§11Transcript · 1:37:00–1:46:45
And that feels like a responsibility as well.
Of course, other people would be concerned.
The more obvious concern is like,
well, you just created a life form.
How do you know it's not gonna be a super deadly virus
that somehow is able to hurt humans?
Yeah, my concern is more,
I feel like that's a solvable problem.
The problem of creating conscious beings
that are able to suffer, that's a tricky one.
- Yeah, I can see why, because it goes back to, again,
would we, first of all, do we have a responsibility
to propagate more of this chemistry
that we have on this planet elsewhere,
given that we know ultimately we will be vanished
by the entire planet?
And if this is in fact a very rare chemical event
that happens because all the right circumstances
came together and we were the lucky one,
do we have a responsibility to sponsor it?
If we were to back up--
- Sponsor, I like it.
(Lex laughing)
That's a good way to put it, yeah.
- If we try to back up remnants of our civilization,
so we wanna potentially create conditions
on the different planets so that humans can survive,
given that we know, or we want to,
just for the sake of growing.
- Yeah, propagating, becoming a multi-planetary species.
- Exactly, but what really is at stake here,
I think is actually, or what is really more interesting
is what we don't see, which is, again,
that chemical behavior that enabled everything
in the first place.
That's different than sending potato crops
or engineering bacteria to live on a different planet.
That's very different.
You are really stripping it down to what is possible
at the chemical level.
So even if you are instigating the chemistry
on different planets, you are letting that very planet
to do its thing.
You're not necessarily contaminating this planet
with different chemistry, because the idea behind this,
at least the way I thought about,
is that you understand that planet,
you understand the conditions,
you understand the chemistry of the planet really well
before choosing the planet as a candidate at first place.
And then it's not about sending a missing ingredient per se,
but again, just sending more of what it already has.
That will be respecting that planet's condition too.
So I'm not suggesting any occupation.
I'm not suggesting any colonization.
I'm not suggesting any, like, let's just strip everything
and make everything Earth-like.
That's not what I'm saying.
It's more about empowering that place.
What you are saying is likely to be
the motivator behind all this.
That's not, because I see suffering, I see pain.
It's very interesting.
I think this is a question that really reveals
a lot about the person who's answering it.
- Well, okay, so the pushback on my pushback.
If I saw deeply troubled by suffering,
then I should be probably paralyzed
about the history of life on Earth.
And, you know, there's--
- Can you elaborate, what do you mean?
- Most of life who's ever lived,
suffered in ways that are almost unimaginable to me.
- You mean, like, our own species?
- Our own species and before, and animals living today.
And we're not even talking about factory farms.
We're just animals living in extreme poverty in the jungle.
You don't, people think like in the natural environment,
animals live in a happy place.
No, it's a brutal place of desperately trying to survive,
of desperately trying to look for food.
And it's just like all of that life, that's just mammals.
And we understand mammals, but like throughout,
like trillions of organisms that led up to those mammals.
And the organisms living everywhere, like even bacteria,
there's death everywhere.
So maybe this idea of death, this idea of suffering,
is actually, this thing that we see as a bug,
is actually a feature.
- I don't think suffering is a linear property
like that with life.
And I may be with Nick Lane on this one,
that the likeliness of anything similar
to what we got here, evolving in another planetary body,
I think is quite low.
- Where would you say is the biggest unlikely thing?
Do you mean humans,
or do you mean even multicellular organisms?
- Probably multicellular, multicellularly.
But I understand both sides of the equation, right?
In one level, I can see that we may not have
any other choice, but to back up this chemistry
somewhere else.
So you would be saving, it's the ultimate saving,
or our own record.
It's not about, yes, let's also save Beatles
and all the amazing songs, but this would be
the ultimate repository of life.
But I can also see your point of view, for sure.
- It's really interesting.
So like, don't seed a plant with a missing ingredient.
Try to understand what the ingredients it has.
Is it possible to construct life?
For me, from a computer person,
it just feels like something
that could be solved computationally.
We can learn from the mistakes that we've done here
and aspire not to repeat them.
It is possible.
We do amazing things as humans.
There's a lot of suffering,
but there's also a lot of beauty.
And we could choose what we want to be,
or what we want to see, right?
So these attempts don't need not to come from,
need not to come from a place of fear,
but it can be ultimately,
can come from a piece of hope and love.
- I think we're just very recently figuring out stuff.
Like we've, even just a century ago,
we're doing atrocities that weren't seen
as atrocities at the time.
I mean, I think we're learning very quickly
of what is right and wrong.
- Yes, and I work with a lot of,
maybe because I'm at the university,
I get to teach young people every day,
even at a time of four year or three, few years,
you see generational difference already
unfolding in front of you.
And maybe that's why I see hope,
because I think what we get to interact with in classrooms,
every year, it's just getting better.
They are aware of issues in a way
that I sure wasn't at their age.
Some levels I was,
but in many levels I didn't think about.
I wasn't concerned of the problems.
Well, they maybe have to be concerned
because it's hitting the reality,
he's hitting them hard,
but younger people are not afraid of these things.
An 18 year old can face these brutal facts
about the planet in ways that I don't think
any other generation before them did.
- Yeah, it's super cool.
And like the, you know,
there's all these cool technologies
that aid in the process of a human being
being able to see the truth at deeper, deeper levels,
like, you know, Wikipedia and just the internet in general
is enabling education at a level
that was unimaginable before the internet.
- Yes, and I think space exploration,
even contemplating about these possibilities,
ultimately, and I will emphasize this again,
should make us think about our own place in the universe.
If we are alone, that is quite fascinating.
And we definitely have a responsibility
to guard what we got better and protect it better
and don't take it for granted.
If we are not the only one,
that's also a lot of responsibility
to understand what else is out there.
So either proposition, as famously being told,
is fascinating, but as a scientist, I think,
and I think that's a general behavior,
maybe not my fellow scientists listening to this
can correct me if they aren't like this,
but you need to have a level of optimism and hope.
That's something, you know,
that things are worth working for,
worth dreaming, worth imagining.
And we cannot just have fear of suffering or fear of pain
stopping us from doing marvelous things.
- I've talked to quite a few people in my life
who've gotten a lot of shit done,
have helped a lot of people.
And I don't know a single one of them
who's not an optimist.
Now, there's a place for critics and cynicism in this world,
but in terms of actually building things
and creating things in this world that help a lot of people,
I think optimism is a requirement, is a precondition,
in almost all cases,
in my limited, humble human experience.
But I tend to, when I look out there,
think that aliens are everywhere.
I think there's,
to me, I have a humility about,
§12Transcript · 1:46:47–1:56:23
I tend to see us humans as being very limited cognitively.
Like, there's so many things we don't understand.
I think eventually we'll understand,
of course, we don't know this, but my gut says,
we'll understand that alien signals
and life has been all around us,
and we're too dumb to see it.
Like, whatever life is, whatever the life force is,
whatever consciousness is, whatever intelligence,
whatever the mechanism that led to the origin of life
on Earth was everywhere, and we're just too dumb to see it.
It's in the physics.
It's somewhere, we'll find it somewhere in the physics.
- I think that's one of the most humbling parts
of also being a scientist,
that we know that we never know for sure.
And for the outsiders, perhaps,
that may be a very strange way of living,
especially when your pursuit is about creating knowledge,
and that you'll know that what you created can also be,
and hopefully will be disproven
so that another level will rise.
And I think we've seen that, this lack of maybe connection
between the approach to science or knowledge
versus folks who are maybe not thinking
about these problems every day,
that we are okay with being wrong.
In fact, we know that that's the only way
to push the limits of knowledge.
- How do you think life originated on Earth?
We've talked about this a bit.
Do you have a gut feeling about,
first of all, actually even to step back,
do you think, 'cause you were flirting with this idea,
did the translation mechanism came before life?
- I think that you cannot separate
from emergence of translation machinery
from emergence of life,
or something like translation machinery,
this whole informatic chemical computing system
that is also capable of dynamism and evolvability
that comes with biology, biological behavior,
from emergence of life itself.
We've definitely took a lot of steps
towards understanding origins.
We are able to create molecules from environments,
lightning, heat, and you make amino acids.
So we are able to create the building blocks,
the Miller-Urey experiment, that's now 60 years ago.
We are able to create the building blocks,
we are able to make them interact with one another.
They can get more complex, some call this messy,
there's all this chemistry that's going on.
We are able to have these chemicals interact with one another,
maybe have even some emergent properties
that we can quantify.
Definitely there is this trend
towards more systems-level approach to origins,
more introduction of systems-level chemistry,
more network-level chemistry,
and complex system integration
in order to understand how,
now that we can make these building blocks,
we can make them interact with one another,
but how do we make them interact with one another
in more intelligent ways
that will have the properties of a biological system,
will be heritable, it will be responding to the environment,
it will mutate, and it will sustain itself.
That is the final bit, I think,
in our origin of life adventure.
And we are extremely close.
I'm very optimistic that our community
will get a handle of this problem in this decade.
This is, in fact, I think,
one of the most exciting times to be doing this work.
- What would be super convincing to you,
like incredibly amazing, would blow your mind
if X was done in a lab?
Like what would, I mean,
I don't know if you would call it origin of life,
but something really truly remarkable
and special done in a lab.
What would that look like to you?
- The properties that I listed,
this was five properties that I listed about
in the machinery that is capable of sensing
and responding to the environment.
If we can, I would imagine,
similar to Miller-Urey experiments
where they only sparked particular environmental forces
and were able to produce a chemical
that is important for life,
or a mix of chemicals important for life,
or building blocks rather,
if I saw that a similar experiment
that a well-defined geochemical parameter
was subjected on a mix of chemistry,
which led that chemistry to form some level of computation,
informatic, biological property,
and by biological, I'm gonna keep it to very minimum,
as I defined early on,
that would be super exciting to me,
a self-organizing chemistry
that we can create experimentally in a flask
by simulating the conditions of early Earth,
be it radiation, be it temperature, or mix of both,
that would be very cool.
- And doing all the five,
the chemical, physical, informatic, computational, biological.
- Yes.
- So like simulation and a computer would not--
- No.
- Would not be good enough.
- It would be great because they help
to understand the parameters,
maybe formulate, maybe quantify, create models,
but ultimately you need to experiment.
- Unless it's quantum mechanical simulation,
but that's going to be extremely difficult.
So simulating from the physics up,
that's going to be very,
'cause you're gonna have to simulate
the physical, the chemical, the informatic.
I mean, honestly, it's very difficult
to start the quantum mechanics
and end up in biology all through simulation.
But the stuff that DeepMind did with alpha fold
and protein folding is really inspiring.
It's inspiring in that you're able to do,
to solve a difficult biology problem.
- Yeah, absolutely.
That's why there's definitely a lot of benefits
to those models, predictions,
'cause they at least help the experimentalist
to come up with the priors
and parameterize things better,
maybe eliminates very obvious dead ends early on,
given that experiments take such a long time
and it's a huge investment.
And no one's a better experimentalist than nature, so.
- Let me ask you perhaps a depressing, sad for you question.
- You really want to make me sad.
You're not gonna win.
- No, I know.
There's a flame of optimism in you
that will never be extinguished.
Okay, the idea of panspermia.
You mentioned would we seed another planet with life?
Is it possible that our planet
was seeded with life from elsewhere?
- So what the proposition I made,
I like to think of it as protospermia
rather than panspermia,
because it's even more,
it's a more proto state than acknowledging.
Because in panspermia, you still have a cell, right?
You still have something that is very,
even a cell to me would be very Earth-like, right?
I'm talking at sub-cellular level
in the proposition of spreading chemistry.
- So spreading chemical ingredients, not spreading life.
- Exactly.
It will be more like the fertilizer
that is well-adopted and compatible
with that planetary body.
In panspermia, you're still imagining
either an entire bacteria or microbe or a cell
or something that is DNA, which is still Terran.
- So in that sense, that doesn't matter to you
'cause it's chemistry, that's the initial conditions.
It doesn't matter how the initial conditions came to be.
They are what they are and let's go from there.
And there's all kinds of fascinatingly different
initial conditions in terms of chemistry
on different planets.
- Yes, but in terms of panspermia,
I mean, obviously there's gonna be always room
for those sort of discussions or there will be,
those discussions will always be present,
I think, in any life in universe debates.
But the problem I have with panspermia
is that it removes the problem
from the planet to somewhere else.
It makes it very difficult to answer scientifically, right?
You just took the problem away from this planet
and formulate it in a way that I cannot go
and try to understand in the lab,
doing experiments or even through models.
- Does it though, so I've heard brilliant biologists
like yourself say that, but I just, to me,
okay, here's how I think of Earth.
So I actually am able to hold all these possibilities
in my head and all of them are inspiring to me.
I kind of think there's a possibility
that Earth is just an experiment by a graduate student,
by an alien graduate student.
- So I know the exact episodes
of "Star Trek" you're talking about.
- But there is some, to me, that's inspiring.
§13Transcript · 1:56:26–2:04:59
If we are--
- But that's not what panspermia is about.
You're talking about my proposition.
That's not what panspermia is.
- What's panspermia?
Oh, life just came from elsewhere.
Still, that's interesting because there's still giant leaps
that happened on Earth, it seems like,
beyond the initial primitive organisms like eukaryotes.
- I don't think panspermia usually articulates
at the level of eukaryotes.
I think they talk about bacteria primarily.
I think so.
- Right.
So that's still interesting 'cause all the different leaps
of evolution still happen here on Earth.
That's still interesting.
- Yeah, but it's, I mean, it's definitely
interesting to listen to, but I wouldn't place it in,
I wouldn't know how to place it
in the studies of origin of life, I guess, or--
- Here's how we place it.
You have the initial conditions for the origin of life,
and you try to create life in that way
that you've described in the five components,
and it keeps failing.
So what panspermia allows you to do
is to also consider the question,
maybe there's missing components.
How do you answer that question?
- Through exploration and through science.
- Yes, yeah, tell me--
- Looking outside of Earth,
looking at the fundamentals of chemistry and physics.
- How do you understand that with fundamentals
of chemistry and physics?
- How do you understand gravity?
- But you're talking about panspermia, right?
Just I don't understand how would you,
it's different than, if you think it's similar
to looking for life in the universe,
is that what you're thinking?
- No, I'm saying there's a missing component
that came from elsewhere.
- But a whole entire organism
is not a missing component right there, right?
I mean, when you're thinking about origin of life.
- No, no, no, that's an assumption.
Your assumption is all the ingredients
for the origin of life are here on Earth.
Now, I tend to believe that most likely that's the case.
I'm just saying it's inspiring
to think that there is some ingredients
you're gonna push back 'cause that's not panspermia.
That's part of it.
But-- (laughs)
- See, okay, so think,
but yeah, I'm like--
- It's also kind of fun to push back on you.
No, I understand, I understand.
I understand if actually a living organism
ended up here from elsewhere,
that means a lot of the exploration we're doing here
with the ingredients that we know
will not give us the clues to the origin of life.
But it just seems like it's still very useful
to try to create life here
and then we'll see, wait a minute,
don't you think we'll be able to prove,
not prove, but show that panspermia is very likely?
Like if we just keep failing,
we understand biology deeply,
we understand chemistry deeply.
- See, that's the thing.
I don't think so.
I mean, there will be,
the failure is not gonna indicate
that this must have been,
I don't think anyone will put the problem
to something else just because our failures,
our experiments failed.
So failure means we don't understand
the chemistry deeply enough.
- Yeah, and given the progress we made
and how many brilliant people are working on this right now,
and it's definitely more,
I would say that we are approaching this problem
in more broader ways, different ways possible.
I'm confident that we will get there.
For us, again, we are interested in early cells
and first cells and what followed origin of life,
but we cannot, given that it's a continuum,
that's between the origin and emergence of first cells,
it's hard to separate these two ends from one another.
- So given that life is a solution to a chemistry problem,
if we re-ran Earth a million times,
how different would the results be?
If we look at that wheel,
how different would be the tree of life, do you think?
Like what's your gut say?
- My mind asks, are you imagining,
if we are repeating the planet one million times,
are we seeing, are the things that happened,
I'm not talking at the chemical level,
but at the environment level,
do they happen at the same time, at the same frequency,
at the same intensity every time you're running this tape
over and over again?
- Yes, you mean like geological stuff?
- Yeah, like so is the same--
- So you're saying those are important.
I mean, the fact that you would ask that question
is also fascinating, so that's important?
The timing, the frequency, the intensity of geological--
- Yeah, so when we run this imaginary
rewind and replay experiments in our minds,
I wanna know whether we are positioning
all the same geologic events
at the same chronological order as well,
or whether we are also giving them more randomness.
So if the volcano erupted, is it happening at the same time?
If you have, are dinosaurs getting wiped off every time
with the same meteorite that's hitting the same--
- But also like temperature changes and all that--
- Temperature changes, everything.
- That's actually, I've heard you say somewhere
that one of the things that's fascinating to you
about this whole process of evolution
is that the process of evolution,
all the mechanisms were invented and developed
despite all the variation geologically
through the hardship that Earth has gone through.
- That the biological innovations persisted despite that?
- Yeah, despite that, which is interesting.
You kind of think of the biological innovations
kind of happening on their own.
- Because we, so we actually have a center
exploring this problem.
We wanna understand whether,
it's almost like judging a book by its cover, right?
Do you just look at an environment
and then see whatever is present
or scarce in that environment,
and then think that, okay, the life form
that will exist in this environment
will obviously have a lot of molybdenum in its system.
Look at all this molybdenum around here.
Or will it be, because if you say that,
you are now putting the environment
in the more prime driver role, right?
That you're saying that environment will determine
what biology will or will not use.
But we've done studies that show
that it's not necessarily this straightforward.
That for instance, we looked at going back to nitrogen.
One thing that's fascinating about the way cells
fix nitrogen, the ones that can do,
is that they also do this through a lot of help
of a lot of metals, a lot of elemental support really.
And which geologists use to understand
where did this metabolism even evolved,
where at first place.
So we look at ancient oceans,
we try to understand the elemental composition
of ancient oceans.
And what we see is that in some cases,
the metabolisms, even though they prefer a certain metal
or an element that is in the environment,
that metal wasn't abundant in the environment,
but still life chose that.
So it's not that straightforward as though whatever,
you are what you eat,
but you don't necessarily eat what is obvious to you.
Just because there's a lot of that food around
it doesn't mean life will ultimately go there.
Maybe most of the time it will,
but it seems like in the case of nitrogen fixation,
it didn't and maybe that made the difference.
- It's so cool that, right, it's not the abundant resource
that's going to be the definition
of what kind of life flourishes.
So it's not a straightforward thing.
- Yes.
- My sense is that the different timing,
the different conditions of the environment
would change the way evolution happens.
- Yeah, for instance, I mean, I think it's in the 80s,
maybe earlier than that,
Stephen Jay Gould's book, "Wonderful Life,"
which changed, I think, a lot of scientists' life,
including mine.
He contemplates on this notion of the tape of life.
Of course, I hope people still know what tape is,
but I think your listeners will know what tape is.
I don't know.
It's the--
- Tape?
Go on, tell me about the tape.
Is it like a TikTok?
Can you swipe on it?
§14Transcript · 2:05:01–2:13:54
I'm sorry, go ahead.
I apologize for my rude interruption.
- I kind of ask for it.
But he speculated or he suggested
this hypothetical experiment,
whether if life was recorded on,
or can be imagined to be recorded on a linear,
is it linear chain of events recorded on a tape?
And if we were to rewind the state,
would we listen to the same song?
Right, so this was,
and in his proposition, I also thought,
yeah, but are we replaying the tape
in the same exact manner?
Or are we, meaning all the geological
and environmental events,
are they happening at the same time?
Because then you removed the randomness
from equation a little bit, right?
You just removed it,
because you're assuming everything will happen
at the same time, at the same intensity.
So that's not too contingent.
That means that the natural selection,
you're thinking is really operating at more,
or evolution is operating at more,
under more random forces,
than that can be dictated by the environment.
So in our way of understanding
or thinking about rewinding, replaying,
I don't think we're thinking about
the role of the environment as clearly,
or don't seem to be integrated as much.
- But I also wonder if it's possible
that the chemistry ultimately defines the destination,
that despite all the environmental changes,
despite all the randomness,
we'll end up in something.
- But we are not talking about
whether life will emerge and sustain itself.
We are talking about whether life will emerge
and sustain itself in the shape and form
that is similar to what we have right now.
So you are chemistry, I'm chemistry,
we're having this conversation,
and your plants are chemistry too.
They're also having their own conversation.
- These plants are fake, but yes.
- I knew that, I didn't wanna say that,
but they're fake.
- But do you look at my place,
of course they would be fake, otherwise they would die.
- What's wrong with this place?
- It's wonderful.
I'm Alice and this is Wonderland, this is great.
This is great, it's just that,
this is a place where robots flourish,
and those plants are fake.
- Are you saying that you and I
are the only living organisms?
Well, obviously there are microbes in this room,
but-- - Yeah, we are
the only living organisms.
Let's take care of getting a dog.
- This is not a clean room, so you have microbes here.
- Yes, many, millions.
- Yes, so you and I and all the microbes in this room,
we are chemical systems that are operating
in a way that we can respond and sense
and our environments and whatnot.
But if you are asking if we are gonna be here,
then you're imagining that another solution
is also possible, which is different
than the fundamentals of life.
Because life will do always, life will do its life thing.
- I guess it goes all the way back
to the things we were talking about, translation,
and the stuff you were messing with,
is figuring out what is the important stuff and what isn't.
Makes me wonder about, just like with the translation
machinery with human beings,
I wonder what's the important stuff.
Is it important to have two limbs?
Is it important to have eyes?
Like it was obvious that the sensory mechanism of eyes,
like sight, were to develop.
How many times if we re-reinter Earth
would the sensory mechanism of sight develop?
And what would it look like?
Would it be one giant eye?
Or would it be two?
What's with the symmetry?
Why are we so damn symmetrical?
- In response to Steve Jay Gould's proposition,
most people who argue that life is convergent
and it will in fact lead to a few determined outcomes,
or it's not that the outcome is determined per se,
but the pathways are restricted
and the mutational trajectories that life can act upon
are already very limited,
so that the final outcomes are a few,
and eyes being one of them.
So the convergence at the eye level was suggested
as an example, was presented as an example
of why life may actually embark on the same solution
over and over again, given that many species
evolved independently from one another.
- Do you think there's any inkling of truth to that?
Like is it just us humans thinking we're special?
- I think those innovations came again so far after the...
(laughing)
I know it's the fun stuff, yes.
Because it's--
- Thank you, I mean, thank you.
We humans tend to talk about the later stuff,
but without the earlier stuff--
- Yeah, so when we think of earlier,
and I ask this to my students too,
I want them to close their eyes
and think about just nothingness but dust.
We don't have trees, we don't have plants.
When we say an empty place, or visually at least,
we are talking about a planet that is really alien.
So understanding our own past is similar
to understanding an alien planet altogether,
given that it is a very different planet
that did not have any oxygen for two billion years.
There's nothing that is familiar to us
that we would even think about when we think about life
that is present in our past, yet here we are.
- So cool, that from that came this,
like houses and people--
- And we are very, very,
we are the super late arrivals to the party, right?
So this is definitely not our planet.
It's the microbial planet that we live in.
- But the potential to create us was always there.
- How do you know that?
- 'Cause we were created.
Oh, I don't know.
What is it, you think it's possible that it's,
even for the early stuff, yeah,
maybe if it's super unlikely, yeah,
that we just got super,
this is the planet that got really lucky,
given the chemistry.
Like maybe to create the bacteria is not so lucky,
but to create complex organisms
all the way up to mammals, that's super lucky.
- Yes, and it may all come down to a few innovations
that happened at the molecular level
that may or may not be inevitable.
So all these molecular tricks may have enabled
the sort of mere existence of whatever you are able
to define as familiar to yourself.
- And you have a hope that science can answer
these questions to reconstruct?
- Science is answering these questions.
I mean, we are limited to going back to the beginning
in our ways, right?
So we rely on biology, it's overwritten.
You're talking about four billion year old records
that is ever changing, that again makes it beautiful,
but also makes it difficult.
It's not tractable.
Geology has to some degree, it has a record,
of a more static, frozen state record
that is embedded on itself, on the surface of this planet,
if we can find them.
And that's the key that most of these recorded remnants
are, if we're lucky, we find them.
They are not naturally selected.
They're found, they need to be found for us to be able
to read them, so we work with a very handful set of samples,
especially when we talk about the deep past,
the planet with no oxygen, when we passed
the Great Oxidation Event threshold,
that is about 2.5 billion years.
So the earliest life is even harder.
You are trying to write the story of life
based on a handful of rocks and what is recorded on them.
Speaking of finding select remnants of our deep past,
you said that you've been thinking about Nick Nealon's
essay on scientific knowledge and scientific abstraction.
So let me ask you, where do you think scientific questions
and answers, or in general, ideas come from?
You're a scientist, you ask very good questions,
and try systematically and rigorously
to answer them through experiment.
Where do you think ideas come from?
- So ideas come all the time, right?
There are all kinds of ideas.
There are good ideas, there are not so good ideas.
There are really exciting ideas, maybe some boring ones.
But if you are really interested
in doing something different, then you need to be willing
to take the risk to be wrong.
And that's incredibly difficult, even though we talked
about the idealist notion behind science
that we ultimately want to be rejected,
§15Transcript · 2:13:56–2:23:46
or our ideas need to be rejected
for the entire infrastructure to move forward.
There is a level of risk-taking, I think,
behind any creative idea.
And I mean that in a true sense.
If you are disappointed that your idea didn't work,
then it wasn't a risk,
'cause you still hoped that it will work.
True risk is that you accept that it may not work,
so that the failure shouldn't also surprise you.
- Yeah.
Is it when you embark on stuff, when you embark on an idea,
do you actually contemplate and accept failure?
Like as a possibility? - Not consciously,
I wouldn't say so.
But I eliminated a lot of the things out of my work line
by simply not feeling like studying them.
I was bored chasing certain questions.
- So you trusted the signal of boredom as a good sign
that it's not a good question?
- It should definitely be,
whatever you're doing should be exciting to you.
If there's only one person that should be ever excited
about what you're doing, that should be you.
And that's enough for that idea to go somewhere.
I think that you need to believe in the idea,
but at the same time,
I think it's important to not fall in love
with your mistakes.
That if something isn't working, you should let it go
instead of trying to fix it.
Even though you feel that this is a mistake
or you know that it's a mistake,
in order to, sorry, instead of trying to fix it,
you should wrap it up and move on to something else,
which is incredibly hard.
- Good advice for science,
but also good advice for relationships.
But okay, so that's actually really hard,
especially, I mean, this is like PhD stuff.
Like if you sink in so much of your time,
not even PhD, the entire scientific career,
it's really tough to let go.
- Yes, and there is not a lot of room for true freedom,
maybe at this certain degree.
So first you need to be trained, right?
It's not that scientists are just brilliant, amazing humans.
I mean, they just know and learn,
they know how to do science
because they're trained in how to do science.
So that is important because as someone
who wants to definitely, I'm hoping,
giving the message that this is for everybody,
that there's this notion of science,
scientists being super smart people,
that's definitely not true, right?
It is a method that you learn to solve a problem.
That's really what science is.
And some are really good at it,
and they get better at it under really good guidance,
maybe good mentorship.
And ultimately everyone finds their own style
of problem solving and what sort of problems they solve.
But I have not met a scientist
that finds their own pursuit boring.
- Well, it can happen,
but they're not going to be effective,
just like you said, I think.
It's kind of interesting because in the age of social media
and attention economies and stuff like that,
I've interacted with a lot of folks,
like YouTubers and so on.
I think a lot of their work is driven
by what others find exciting.
And I think that ultimately leads
to a life that's not fulfilling.
- I can see the reason behind it,
or perhaps there's a fear of failure
that can be a major determinant of that pattern, right?
So you try to do something that is accepted by others
because that's maybe unlikely to give results right away.
But it's a long game, it's a very long game.
And if you are aiming a long-term change
and long-term impact,
you've got to be very, very patient about it.
And you better tame your ego.
- I mean, on YouTube and those kinds of places
on the internet, on social media,
you get feedback right away.
And so it's even harder to be patient.
Because change and ideas develop
over a period of months and years, not decades.
And the response from social media and so on
is on the rate of seconds, minutes, and hours.
- So I recommend actual physical libraries
for people who may wanna appreciate
or remember the sense of time
and how long it takes to build something.
I think it is, you're right,
that's the immediacy and the right response.
And the fact that these places,
the algorithm wants you to respond right away
and interact with itself, right?
So I can see the appeal,
but true innovation, I think, doesn't even scream.
It's not shiny, especially in the beginning.
But it's also important to not fool ourselves
and think that everything that people criticize
has some super important meaning behind it.
So it's a mix of the technique,
the methods, and your gut feeling.
- Yeah, and a weird dance between learning
and accepting the ideas of the current science,
and at times trusting your gut and rejecting those.
'Cause science progresses by sometimes rejecting
the ideas of the past or sometimes building on them
in a way that changes them, transforms them.
- Yes, and I think what is hard
is to really drill down into a concept, right?
So you can create a new thing,
and then it may be appealing and gain a lot of traction,
but to sustain that, to continue that,
you really need to show the true expertise.
And so it's not only about defining a problem,
but then really systematically solve that problem
maybe over the course of decades.
- You mentioned the library.
I've also saw that you've translated scientific documents,
or at least mentioned that you did it
at some point in your life.
So let me ask you, how much do you think
is lost in translation in science and in life?
How many languages do you speak?
- Two. - Two.
How much is lost in translation in science
and in life between those two?
- No, it's actually three, because science
is like another language, right?
- It is.
I speak Russian, a little bit of French,
and it's always fascinating to see how much is lost.
And the Soviet Union has a tradition of science
and mathematics and so on, and it's interesting
that a lot of the wisdom gained
from that part of the world is lost,
basically because it was never translated.
- Well, I'm not sure if it is lost per se.
I mean, maybe it's more like a gain in some sense, right?
Because you understand,
science is ultimately a human pursuit,
so you cannot separate as much as,
maybe it's the best system that humans ever came up with
to seek knowledge, to generate and make sense of the world.
It works most of the time.
It doesn't mean it's perfect.
- Did the kind of translation you do, by the way,
was for scientific work?
- I directly translated for scientific work, yes.
I think that, again,
brains are equally distributed,
but opportunities are not, right?
So if you want to include,
if you want to benefit from all human power,
whatever we can generate as human beings,
you need to include everybody on the table.
And that is by extending the opportunity.
I think most of us that make it
tend to think that we did
because of something special about ourselves.
But it is important to know that,
no, we were given opportunities,
and that's why we are here,
not because there was something inherently special about us,
or that the system truly selects for the ones
that really are--
- Yeah, and language is a part of the opportunity.
- Yeah, language is an opportunity
because it comes with, similar to bacteria, right?
They speak these languages.
Even we call culturing the bacteria,
we call it culturing, right?
When we grow bacteria
that we isolate from the environment in the lab,
meaning that you create an environment
for them to grow and thrive and sustain themselves.
That's what we say,
but culture is for microbiologists.
For language, with language comes a different culture,
a different perspective,
and you bring that to the table.
I mean, it brings the sense of diversity
that can only be achieved by clashing, perhaps,
two different cultures, two different languages,
two different approaches,
maybe in some cases, four different approaches.
- Yeah, I think language is not just
a mechanism of communication.
It's a way to,
it's a dynamic system of exploring ideas,
and it's interesting to see
§16Transcript · 2:23:47–2:33:47
that different languages explore ideas differently.
- Yes, and I think that,
so when I said science is like a language itself,
I said it in two different ways.
One is very literal meaning,
that you can speak English,
but that doesn't mean you will understand
the scientific paper.
It's a different level of English
that you need to learn to understand.
Even, not just for scientific papers,
even from discipline to discipline.
I challenge any chemist to read
an evolutionary biology paper, and vice versa.
It may sound extremely different,
and a different language altogether.
But there's also the language of communicating,
and because words matter, how we talk matter,
how we represent our science matters.
So yes, just learning English as a second language alone
is not gonna make you fluent in science either.
- And it's interesting 'cause in that sense,
you speak many more than three languages
because you're pretty cross-disciplinary.
It seems like you have a foot in a lot of disciplines.
I mean, you're mentioning geology, biology,
evolutionary biology, I mean, there's chemistry.
- Biochemistry, biophysics, even we do a lot of statistics.
So there's a lot of mathematics to what I do as well.
Yes, we like to think of it as this,
now it's astrobiology program, I repeat it because it's fun,
that it is not a fruit salad, but it's a smoothie.
That that's what we are generating.
(laughing)
It's not a fruit salad.
So a smoothie is a successful combination of those fields
and a fruit salad is not.
- I wouldn't say it's success unnecessarily.
If you put the wrong ingredient and you press the blender
and you've made it a smoothie,
you mean it can ruin the entire mix.
- Can it though?
Because I feel like--
- Yes, I can definitely assess that for ginger,
for instance, that ruins every smoothie.
I don't like it. - Ginger?
- I think so, but it's just a personal thing.
And also I don't like cinnamon.
- Ginger has a cinnamony taste?
'Cause I thought ginger was--
- No, I don't think they do, but I also don't like--
- Wasn't that a thing they add in a lot of smoothies?
I was forced a smoothie.
I went to Malibu with a good friend of mine, Dan Reynolds,
and he forced me to consume a smoothie.
And it was probably the first smoothie I've ever had.
'Cause I always said it was very judgmental
of the kind of places and people that drink smoothies,
but it was good, it was good.
- Well, smoothie is very American,
so I-- - Yeah, it is an American thing.
- I wouldn't say success per se,
but it is true that when you dance
at the edge of different disciplines,
that that's when inevitably the innovation will rise,
because you will see things maybe a little differently
when you're on the edge, right?
So, but it will probably take longer,
and it may not be understood right away.
It may not come into final form quickly,
given that it is a new concept rising.
So, therefore, the patience will make more sense.
I'm sorry, patience will be even more important.
So, if you are, in other words,
if you are into immediate appreciation,
that's probably not the way to go.
- You're one chemical organism.
So, let me ask maybe a little bit more of a personal thing.
Where did your life form originate?
And what fond memory do you have
from the early days of childhood
that are representative of your bacteria culture?
- I was born in Istanbul, so I grew up in Turkey.
It's a city that has two continents,
which is quite interesting.
You have a, you see a "Welcome to Europe" sign,
and then "Welcome to Asia" sign, same day,
depending on which part of the bridge you are.
So, that's where I was born,
and I spent about roughly 20 years of my life,
and then I immigrated to United States.
- And it's a very proud culture.
It's a beautiful culture.
It's a very flavorful culture.
What aspects of it is part of who you are?
What are the beautiful aspects
that you carry with you in your heart?
- I think we are very sincerely human as a culture.
I think that we have the saying that don't go to bed full
if your neighbor is hungry.
So, you wouldn't eat any food in front of someone
where I come from without offering to share the bite.
So, I think those things, however small they may sound,
they're really big deal,
especially when you are put in or move to a place
that may not have those attributes.
So, I think that culturally, we had a lot of conscious,
like, just raw, deep human--
- The connection, you value the connection
between human beings.
- I think so, yeah.
I think I definitely carried that with me.
- We talk a lot about biology.
Let me ask you about the romantic question.
What role does love play in the human condition
or in the entirety of life on earth?
- It's not easy to learn how to love if you're not loved.
Okay?
So, this is something, but the good news
is that it is something that you can learn, I think.
That you can practice and teach yourself
how to maybe give yourself the thing
that wasn't given to you
and then ultimately give it to others.
I think it would be quite arrogant to think
that we will be capable of loving.
It could be anything, really.
- So, just like translation,
it's a repeating and a dynamical process.
- That you can learn.
- Yeah, that you can learn.
- Yes, and you should learn.
There's no excuse to not learning.
- To love. - Yeah.
- 'Cause that's a deeply human thing.
- It is a deeply human thing.
It is a very sad thing if any one of us
passes this planet without knowing what love is.
And that could be a love to a pet, a love to a plant.
- To a robot.
Just kidding.
Or a fake plant.
We can't help who we love.
What advice would you give to a young person today?
High school, college?
How to have a career they can be proud of
or how to have a life they can be proud of?
You said an interesting thing about brains
being distributed evenly but opportunities not.
It's really interesting to think about.
I've talked to folks from Africa.
You realize that there's whole areas of this earth
that have so much brilliance.
But unfortunately so little opportunity.
And one of the exciting things about the 21st century
is more and more opportunities are created.
And so the brilliance is unlocked
in all those different places.
And so all these young people now have the opportunity
to do something to change the world.
- I had a chance to visit Bosnia.
So I was invited to give a talk in a very,
very northern most part of the country
that was impacted by the war tremendously.
And it was a public talk.
It was open to everybody in the village.
And I was told even people drew from Sarajevo to attend.
Whenever I think about our role as a scientist
or the beneficiaries of the knowledge
that we create, I always think about that night.
That's how many people were in that room.
It was incredibly crowded.
And lots of young people who were trying
to start everything new and not do or not carry,
replace whatever maybe the feeling that was taken
from them with hope and love, start a new beginning,
be the seed for the next generation.
And it's moved me so much that they all came
to hear about early life space,
something maybe different for them
that maybe they were always interested in
and never thought about.
But what stayed with me was just the look and the feeling,
the look on their faces and the feeling in the room,
the energy just was really moving to me.
- Their willingness to be the seed,
the first of their family and generation
to do that big new thing.
- Yes, and that's exactly why I'm telling this whole story.
Because for most of us, we may have to be that seed
in our families, the first one to do something new,
to break that cycle, whatever it is
that you want to break free from.
I would want the young people to know that you can be that,
that there are just wonderful things
to learn from this life.
And it's just incredible to be living.
And I would want them to know that their voice matters
and they need to use it, especially those who think
that their voice doesn't matter.
§17Transcript · 2:33:49–2:40:11
And ultimately, I think what it comes down to
is to trusting yourself, trusting and respecting your voice.
If you're not loved, learn how to love.
If you are not respected, start by respecting yourself.
Learn how to respect yourself.
You can teach yourself things.
- Yeah, it's really difficult when you're surrounded
by people that don't believe in you.
- Yes, I definitely know the feeling.
And I would just want them to know
that they don't need to be defined.
By or reduced down to what others see in them.
- Believe in yourself, have the respect,
try to develop the respect and the love for yourself.
And then from that, it flourishes.
You'll find others that'll give you love.
- It may not.
I mean, life is not fair, it's true.
- Yeah, yeah.
- Be prepared that it's not very fair, unfortunately.
And so I don't want to depict this Disney story
that, and then yes, and everything will be just fine.
It's mostly isn't, but you learn a way.
Learn, you know, life does it all the time.
- Speaking of which, what do you think
is the meaning of all this?
What's the meaning of life?
Why are we here?
- Why we are here?
- All the beauty you've discussed.
Why is the translational mechanism machinery here?
- Why?
- I don't think there's--
- Why so much beauty?
- Why so much beauty?
It is because we choose to see it that way.
It's beautiful.
But there is no meaning, I don't think, no, yeah.
- But why is it so beautiful?
Why did we choose?
Why, from where is the imperative to see it,
to see so much beauty in a thing
that scientifically speaking,
or from a rational perspective, is void of beauty?
It's just, it just is.
- Not everybody chooses to see the beauty.
- Haters gonna hate.
I mean, we have the capacity to see the beauty.
- We have the capacity, so why not use it to the fullest?
Right, we have the capacity.
- But that capacity, isn't that fascinating?
That we developed that?
It feels like that was always laid in there
in the whole process of life,
this ability to find, to introspect ourselves.
- I mean, it's definitely soothing to think like that,
but I don't think there is a meaning like that way.
It's fascinating that we can understand it.
- But why is it soothing?
There's a desire, there's a longing for it.
- But soothing doesn't mean that there's a meaning.
Why is soothing a meaning?
Let me just put it this way,
because there is just, I think, so much unfairness going on,
I wouldn't even dare myself to think that there's a meaning
out of respect to the ones that are suffering.
- I see.
I think out of suffering emerges flourishing and beauty.
I mean, that's what I see.
- I agree with you.
- When I went to Ukraine,
it's all the people suffering in their eyes
and in their stories is a hope for the future,
is a love for the people who are still living,
is a love for life.
So it's there, and that's the dark thing,
is the suffering and the loss somehow intensifies
your appreciation of the life that is still left.
That's a weird thing too.
- I think that there is something about
still doing your best and believing that there's,
whatever goodness is worth working for,
is beyond, and to do that without a meaning,
there's something more humbling and profound about that.
And we have a,
this will come out very random, okay, so just.
In Turkish bathrooms, there is this sign that says,
"Leave it as you want to find it."
- Yeah.
- And I think that's a pretty good--
- That's your meaning of life found in the Turkish.
There's wisdom to that.
- There's wisdom to that, but it also is because
however you leave defines you, right?
So I think there's some profound meaning to that too,
that just leave it as you would want to find it.
- So that your little scribble in the long story
of life on Earth is one that ultimately
did a pretty good job, at least kept it the same
as you found it.
- Or at least I left it in the way that I wish I found it.
- Yeah, yeah, right.
Oh man.
- Yes, that's the wisdom from Turkish bathrooms.
- That's where I search for wisdom as well.
And as we started with the origin of life
and ended with the wisdom in a Turkish bathroom,
I think that's a perfect conversation.
You're an incredible person.
The humor, the humanity,
but also the brilliance of your work.
I really appreciate that you would talk with me today.
This was really fun.
- Thanks for having me.
- Thanks for listening to this conversation
with Batool Kachar.
To support this podcast,
please check out our sponsors in the description.
And now let me leave you with one of my favorite quotes
from Robert Frost.
"In three words, I can sum up everything
"I've ever learned about life.
"It goes on."
Thank you for listening.
I hope to see you next time.
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