Betül Kaçar is an astrobiologist at University of Wisconsin. Please support this podcast by checking out our sponsors:
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Betül's Twitter: https://twitter.com/betulland
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OUTLINE:
0:00 - Introduction
0:56 - History of life on Earth
9:00 - Origin of life
31:47 - Genetic language of life
44:43 - Life and energy
55:26 - Ancient DNA
1:14:24 - Evolution
1:25:55 - Alien life
1:53:55 - Panspermia
2:00:17 - Restarting life on Earth
2:12:58 - Where ideas come from
2:20:30 - Science and language
2:29:07 - Love
2:30:30 - Advice to young people
2:35:04 - Meaning of life

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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.

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 when 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.

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 phytogenetic trees could be 1 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 1 another.

Biologists like visualizations, they like these graphics, these diagrams, and Tree of Life is 1 of them.

It starts from the tip of the branch, actually.

And then further, 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

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?

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 1 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.

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 gives us context of what we can and can't do by looking back in time.

Yeah, so dinosaurs or all these mammals, in at least for us, is the exciting thing already happened by the time we hit to the larger organisms or to eukaryotes.

Oh, to you, the fun stuff is before we got to the mammals?

The fun stuff is what people think is boring, I think.

The phase that's, well, there's 2 different times in the geologic history.

1 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 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 multi-cell 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 that have to do with this primitive kind of looking organisms that we don't have a good record of.

So I will tell you the more interesting things for us.

1 is the origin of life or what happened following the emergence of life.

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 2 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.

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, right?

But bacteria is in your dinner, bacteria is in your gut, bacteria is helping you along

Well, they get themselves invited in a way.

And they're definitely older and definitely very sophisticated, very resilient than anything else.

As someone working 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 which organisms gives you hints that are alive today that give you hints about what ancient organisms were like?

We study a variety of different bacteria, depending on the questions that we ask.

So ideally, we want to 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.

Coli, It's the most simple in terms of model systems goes.

Organism that 1 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.

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 1 of the prime nitrogen fixers, nitrogen fixing bacteria.

Can you explain what that is, nitrogen fixing?

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.

fixed before our cells can make use of it.

Well, It's actually a very important element.

It's 1 of the most abundant elements on our planet that is used by biology.

It's in ATP, it's in chlorophyll that relies on nitrogen.

So it's a very important enzyme for a lot of cell functions.

And there's just 1 mechanism that evolution invented to convert

So far we know there's only 1 nitrogen fixation pathway, as opposed to, say, carbon.

You can find up to 7 or 8 different carbon based microbes invented to fix carbon.

We think it evolved around 2.7 maybe, roughly 3, probably less than 3000000000 years ago.

And that's the only way that nature invented to fix the nitrogen in the atmosphere for the subsequent use.

Would we still have life as we know it today if we didn't invent that nitrogen fixing step?

You and I are having this conversation because life found a way to fix nitrogen.

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?

Carbon, hydrogen, oxygen, nitrogen, sulfur.

So there are 5 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 happened on our own planet.

And there are many abiotic ways to fix nitrogen, like lightning, right?

Humans found a way about a hundred 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.

So we helped, we found a way to fix our own nitrogen for ourselves.

Yeah, but that, you know, that's way after the original invention of

And without that, we wouldn't have all the steps of evolution along the way.

We tried to replicate in the most simplest way what nature has come up with.

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 1 single enzyme called nitrogenase.

It's the nitrogen that is used together with 8 electron donor and ATP, together with a lot of hydrogen.

Life pushes this metabolism down to create fixed nitrogen.

Coli does nitrogen fixing in part, or is that a different 1?

So some biological engineers engineered E.

We use the 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?

Okay, so I can tell that you appreciate and respect the full complexity of even the most seemingly primitive organisms, because none of them are primitive.

Okay, that said, what kind of, what are we talking about?

What kind of machineries do they have that you're working with when you're injecting them with DNA?

So I will start with 1 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, 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.

1 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.

What's the translation from what to what?

It converts a linear sequence of mRNA into a later folded protein.

That's the core processing center for information for life.

It initiates, it elongates, it terminates, and it recycles.

It operates discrete bits of information.

It 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.

I would divide it into actually even 4 more additional steps or disciplines than what would it take to study it by the way you described it.

It's the compounds that make it up, or chemicals.

It's 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 an imperfect computation.

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 this 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, you know, it's manipulating actual physical objects and chemicals because you have to, ultimately it's all chemistry.

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 1, I think, difference between the 2.

And yes, it's informatic, and we can discuss this further too.

Each 1 of those are fascinating worlds, each of the 5.

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.

The specific compounds make up the assembly of RNA.

Chemists showed this in many different ways.

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.

That's, 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.

It's a pretty rigid, established input-output system and it's all chemistry.

My PhD is in chemistry, but I don't do origin of life chemistry.

So some of your best friends are origin of life chemists.

Just make sure that you have good chemist friends if you're interested in the origin of life.

That's 100% requirement, should be mandatory.

Okay, so chemistry, so what else about this machinery that we need to know chemically?

They know how to chew energy using ATP or GTP.

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 any cellular process without chemistry.

What makes life interesting is that even if the chemistry is imperfect, 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.

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Betül Kaçar: Origin of Life, Ancient DNA, Panspermia, and Aliens | Lex Fridman Podcast #350