Betül Kaçar: Origin of Life, Ancient DNA, Panspermia, and Aliens

00:00:00.000 | You can study chemistry, you can study physics, you can study geology, anywhere in the universe,

00:00:04.320 | but this is the only place you can study biology.

00:00:07.120 | This is the only place to be a biologist.

00:00:10.620 | So, definitely something very fundamental happened here, and you cannot take biology out of the equation.

00:00:16.000 | If you want to understand how that vast chemistry space, how that general sequence space got narrowed down to what is available,

00:00:26.520 | or what is used by life, you need to understand the rules of selection, and that's where evolution and biology comes into play.

00:00:34.200 | The following is a conversation with Batul Kachar, an astrobiologist at University of Wisconsin,

00:00:42.320 | studying the essential biological attributes of life.

00:00:46.800 | This is the Lex Friedman Podcast.

00:00:48.720 | To support it, please check out our sponsors in the description.

00:00:51.680 | And now, dear friends, here's Batul Kachar.

00:00:56.640 | What is the phylogenetic tree, or the evolutionary tree of life,

00:01:00.280 | and what can we learn by running it back and studying ancient gene sequences as you have?

00:01:04.840 | I think phylogenetic trees could be one of the most romantic and beautiful notions that can come out of biology.

00:01:14.720 | It shows us a way to depict the connectedness of life and all living beings with one another.

00:01:22.400 | It itself is an ever-evolving notion.

00:01:26.240 | Biologists like visualizations, they like these graphics, these diagrams, and tree of life is one of them.

00:01:33.080 | So the tree starts at a common ancestor?

00:01:36.520 | It's actually the other way around. It starts from the branches.

00:01:42.240 | It starts from the tip of the branch, actually.

00:01:44.880 | And then, depending on what you collected to build the tree.

00:01:51.560 | So depending on the branches, depending on what's on the tip of the branch,

00:01:54.960 | and I will explain what I mean,

00:01:56.760 | the root will be determined by what is really sitting on the tip of the branch of the tree.

00:02:01.080 | So we could study the leaves of the tree by looking at what we have today,

00:02:04.120 | and then start to reverse engineer, start to move back in time to try to understand

00:02:08.920 | what the rest of the tree, what the roots of the tree look like.

00:02:11.000 | Exactly. So the tree itself, by just taking a few steps back and looking at the entire tree itself,

00:02:16.840 | can give you an idea about the connectedness, the relatedness of the organisms,

00:02:22.080 | or whatever, again, you use to create your tree.

00:02:24.640 | There are different ways, but in this case, I'm imagining entire diversity of life today

00:02:32.560 | is sitting on the tips of the branches of this tree.

00:02:35.360 | And we look at biologists, look at the tree itself,

00:02:42.520 | we like to think of it as the topology of the tree,

00:02:45.000 | to understand when certain organisms or their ancestry may have merged over time.

00:02:53.400 | Depending on the tools you use, you might use this tree to then reconstruct the ancestors as well.

00:03:01.920 | And so what are the different ways to do the reconstruction?

00:03:04.800 | So you can do that at the gene level, or you could do it at the higher complex biology level, right?

00:03:12.640 | So in which way have you approached this fascinating problem?

00:03:17.520 | We approached it in every way we can.

00:03:19.560 | So it's the gene, could be protein, the product of the gene, or species,

00:03:25.560 | or could be even groups of species.

00:03:28.480 | It totally depends on what you want to do with your tree.

00:03:31.760 | If you want to understand certain past events,

00:03:35.240 | whether an organism exchanged a certain DNA with another one along the course of evolution,

00:03:41.600 | you can build your tree accordingly.

00:03:43.880 | If you rather use the tree to reconstruct or resurrect ancient DNA, which is what we do,

00:03:50.960 | then in our case, for instance, we do both gene, protein, and species,

00:03:55.680 | because we want to compare the tree that we create using these different information.

00:04:02.400 | - Okay, well, let me ask you the ridiculous question then.

00:04:04.760 | So how realistic is Jurassic Park?

00:04:08.240 | Can we study the genes of ancient organisms, and can we bring those ancient organisms back?

00:04:14.360 | So the reason I ask that kind of ridiculous sounding question is

00:04:18.640 | maybe it gives us context of what we can and can't do by looking back in time.

00:04:23.280 | - Yeah, so dinosaurs or all these mammals, at least for us,

00:04:28.600 | is the exciting thing already happened by the time we hit to larger organisms or to eukaryotes.

00:04:36.320 | - Or to you, the fun stuff is before we got to the mammals?

00:04:39.000 | - The fun stuff is what people think is boring, I think.

00:04:41.640 | The phase that's, well, there's two different times in the geologic history.

00:04:46.560 | One is the first life, past origin of life, how did first life look like?

00:04:53.600 | And the second is why do we think that over certain periods of geologic time,

00:05:00.280 | no significant innovation happened to the degree of leaving no record behind?

00:05:05.640 | So what do we not have a record of?

00:05:08.000 | Which part?

00:05:08.920 | So you say, the fun stuff to you is after the origin of life,

00:05:13.040 | which we'll talk about, after the origin of life, there's single cell organisms,

00:05:17.000 | the whole thing with the photosynthesis,

00:05:18.920 | the whole thing with the eukaryotes and multicellular organisms,

00:05:22.600 | and what else is the fun stuff?

00:05:25.160 | The whole oxygen thing, which mixes in with the origin of life.

00:05:30.320 | There's a bunch of different inventions,

00:05:31.720 | all they have to do with this primitive kind of looking organisms.

00:05:35.200 | That we don't have a good record of.

00:05:38.200 | So I will tell you the more interesting things for us.

00:05:41.680 | One is the origin of life or what happened following the emergence of life.

00:05:47.800 | How did the first cells look like?

00:05:50.360 | And then pretty much anything that we think shaped the environments

00:05:56.200 | and was shaped by the environments in a way that impacted the entire planet

00:06:01.600 | that enabled you and I to have this conversation.

00:06:04.400 | We have very little understanding of the biological innovations

00:06:08.320 | that took place in the past of this planet.

00:06:11.560 | We work with a very limited set of,

00:06:16.200 | I don't want to even say data because they are fossil records.

00:06:19.440 | So let's say imprints, either that comes from the rock and the rock record itself,

00:06:25.800 | or what I just described, these trees that we create

00:06:30.120 | and whatever we can infer about the past.

00:06:32.720 | So we have two distinct ways that comes from geology and biology

00:06:37.920 | and they each have their limitations.

00:06:40.560 | - Okay, so, right, so there's an interplay.

00:06:43.600 | The geology gives you that little bit of data

00:06:46.240 | and then the biology gives you that little bit of kind of constraints

00:06:52.960 | in the materials you get to work with to infer

00:06:55.480 | how does this result in the kind of data that we're seeing.

00:06:58.480 | And now we can have this through the fog.

00:07:01.360 | We can see, we can look back hundreds of millions of years,

00:07:05.080 | a couple of billion years and try to infer.

00:07:07.680 | - Even further, and I like that you said fog.

00:07:10.160 | It is pretty foggy, what we are, and it gets foggier and foggier

00:07:14.520 | the more you, the further you try to see into the past.

00:07:17.560 | Biology is, you basically study the survivors, broadly speaking.

00:07:23.440 | And you're trying to pitch the, sort of put together their history

00:07:28.360 | based on whatever you can recover today.

00:07:30.360 | What makes biology fascinating also let it,

00:07:34.040 | it's erased its own history in a way, right?

00:07:38.200 | So you work with this 4 billion year product,

00:07:40.720 | that's genome, that's the DNA.

00:07:43.200 | It's great, it's a very dynamic, ever evolving chemical thing.

00:07:48.200 | And so you will get some information,

00:07:50.760 | but you're not gonna get much unless you know where to look

00:07:55.200 | because it is responding to the environment.

00:08:00.600 | - Yeah, so what we have, that's fascinating.

00:08:03.520 | What we have is the survivors, the successful organisms,

00:08:08.520 | even the primitive ones, even the bacteria we have today.

00:08:12.320 | - So bacteria is not primitive and we--

00:08:15.240 | - Sorry, sorry to offend the bacteria.

00:08:17.720 | - We should be very grateful to bacteria.

00:08:19.720 | First of all, they are our great, great ancestors.

00:08:23.800 | I like this quote by Douglas Adams,

00:08:25.440 | "Humans don't like their ancestors.

00:08:28.000 | They rarely invite them over for dinner."

00:08:30.200 | - Yeah. - Right?

00:08:31.520 | But bacteria is in your dinner, bacteria is in your gut,

00:08:34.160 | bacteria is helping you along the way.

00:08:35.000 | - So we do invite them for dinner.

00:08:37.080 | - Well, they get themselves invited in a way.

00:08:39.520 | And so we, and they're definitely older

00:08:42.960 | and definitely very sophisticated,

00:08:46.880 | very resilient than anything else.

00:08:50.360 | As someone working at, as a bacteriologist,

00:08:53.520 | I feel like I need to defend them in this case

00:08:56.800 | because they don't get much shout out

00:08:58.640 | when we think about life.

00:08:59.480 | - So you do study bacteria.

00:09:00.840 | So which organisms gives you hints that are alive today

00:09:03.800 | that give you hints about what ancient organisms were like?

00:09:08.800 | Is it bacteria, is it viruses?

00:09:11.040 | What do you study in the lab?

00:09:12.480 | - We study a variety of different bacteria

00:09:14.560 | depending on the questions that we ask.

00:09:16.720 | We engineer bacteria.

00:09:19.040 | So ideally, we wanna work with bacteria

00:09:21.120 | that we can engineer.

00:09:23.320 | Seldom we develop the tools to engineer them.

00:09:26.600 | And it depends on the question that we are interested in.

00:09:31.080 | If we are interested in connecting the biology and geology

00:09:34.840 | to understand the early life

00:09:36.560 | and fundamental innovations across billions of years,

00:09:40.560 | there are really good candidates like cyanobacteria.

00:09:43.480 | So we use cyanobacteria very frequently in the lab.

00:09:48.480 | We can engineer its genome.

00:09:50.160 | We can perturb its function by poking its own DNA

00:09:54.560 | with the foreign DNA that we engineer in the lab.

00:09:58.720 | We work with E. coli.

00:10:00.840 | It's the most simple in terms of model systems goes.

00:10:05.480 | Organism that one can study well-established,

00:10:09.320 | sort of a pet, lab pet that we use it a lot for cloning

00:10:14.120 | and for understanding basic functions of the cell

00:10:18.520 | given that it's really well studied.

00:10:20.520 | - So, and what you do with that E. coli,

00:10:23.280 | you said that you inject it with foreign DNA?

00:10:25.560 | - We inject pretty much all the bacteria

00:10:27.480 | that we work with, with foreign DNA.

00:10:29.440 | We also work with diazotrophs.

00:10:31.200 | These are azotobacteria.

00:10:33.360 | They're one of the prime nitrogen fixers,

00:10:36.640 | nitrogen-fixing bacteria.

00:10:39.120 | - Can you explain what that is, nitrogen-fixing?

00:10:41.240 | Is that, is the source of its energy?

00:10:43.640 | - So nitrogen is a triple-bond gas

00:10:46.720 | that's pretty abundant in the atmosphere.

00:10:49.240 | But nitrogen itself cannot be directly utilized by cells

00:10:52.800 | given it is triple-bond.

00:10:54.320 | It needs to be converted to ammonia

00:10:57.560 | that is then used for the downstream cellular functions.

00:11:02.560 | - And that's what counts as nitrogen-fixing.

00:11:07.200 | - Yes, so nitrogen needs to be fixed

00:11:09.280 | before our cells can make use of it.

00:11:11.800 | And it's--

00:11:13.120 | - No offense to nitrogen either.

00:11:14.400 | - Well, it's actually a very important element.

00:11:17.520 | It's one of the most abundant elements on our planet

00:11:21.320 | that is used by biology.

00:11:22.760 | It's in ATP, it's in chlorophyll

00:11:26.080 | that's uses, that relies on nitrogen.

00:11:30.040 | So it's a very important enzyme

00:11:31.680 | for a lot of cell functions.

00:11:34.040 | - And there's just one mechanism

00:11:35.800 | that evolution invented to convert it, to fix it.

00:11:39.920 | - So far we know there's only one nitrogen-fixation pathway,

00:11:43.680 | as opposed to, say, carbon.

00:11:45.280 | You can find up to seven or eight different carbon-based

00:11:49.160 | microbes invented to fix carbon.

00:11:51.360 | That's not the case for nitrogen.

00:11:53.040 | It's a singularity across geologic time.

00:11:56.280 | We think it evolved around 2.7, maybe,

00:11:59.840 | roughly three, probably less than three billion years ago.

00:12:04.600 | And that's the only way that nature invented

00:12:07.920 | to fix the nitrogen in the atmosphere

00:12:10.760 | for the subsequent use.

00:12:12.480 | - Would we still have life as we know it today

00:12:14.760 | if we didn't invent that nitrogen-fixing step?

00:12:17.720 | - I cannot think of it, no.

00:12:20.160 | It's essential to life as we know.

00:12:22.320 | You and I are having this conversation

00:12:24.160 | because life found a way to fix nitrogen.

00:12:27.760 | - Is that one of the tougher ones?

00:12:29.480 | If you put it, sort of, oxygen, nitrogen, carbon,

00:12:34.480 | what are, in terms of being able to work

00:12:38.160 | with these elements, what is the hardest thing?

00:12:43.160 | What is the most essential for life?

00:12:45.240 | Just to give context.

00:12:46.240 | - Well, we think of this as the cocktail.

00:12:48.520 | You may hear schnapps. - What's in the cocktail?

00:12:50.480 | - It's the schnapps, right?

00:12:51.640 | Carbon, hydrogen, oxygen, nitrogen, sulfur.

00:12:54.920 | So there are five elements that life relies on.

00:12:59.000 | We don't quite know whether that's the only,

00:13:02.680 | out of many options, that life necessarily

00:13:06.160 | needs to operate on, but that's just how it happen

00:13:09.280 | on our own planet.

00:13:10.720 | And there are many abiotic ways to fix nitrogen,

00:13:14.600 | like lightning, right?

00:13:16.920 | Lightning can accumulate ammonia.

00:13:19.560 | Humans found a way about 100 years ago,

00:13:23.680 | I think around World War I, the Haber-Bosch process

00:13:28.680 | that we can abiotically convert nitrogen into ammonia.

00:13:34.000 | Actually, 50% of the nitrogen in our bodies

00:13:37.640 | comes from the human conversion of nitrogen to ammonia.

00:13:42.640 | It's helped, it's the fertilizer that we use,

00:13:45.800 | urea comes from that process.

00:13:48.360 | It's in our food.

00:13:49.600 | So we helped, we found a way to fix our own nitrogen

00:13:54.000 | for ourselves.

00:13:55.200 | - Yeah, but that's way after the original invention

00:13:59.760 | of how to fix nitrogen. - Oh, absolutely, absolutely.

00:14:01.480 | - And without that, we wouldn't have all the steps

00:14:05.400 | of evolution along the way.

00:14:06.680 | - Oh, absolutely.

00:14:07.760 | We tried to replicate in the most simplest way

00:14:11.800 | what nature has come up with, right?

00:14:15.200 | We do this by taking nitrogen, using a lot of pressure,

00:14:18.520 | and then generating ammonia.

00:14:20.320 | Life does this in a more sophisticated way,

00:14:22.960 | relying on one single enzyme called nitrogenase.

00:14:26.200 | It's the nitrogen that is used together

00:14:29.400 | with eight electron donor and ATP,

00:14:33.120 | together with a lot of hydrogen.

00:14:35.880 | Life pushes this metabolism down to create fixed nitrogen.

00:14:40.880 | It's quite remarkable.

00:14:42.640 | - So the lab pet E. coli, inject them with DNA,

00:14:45.400 | so E. coli does nitrogen fixing in part,

00:14:48.680 | or is that a different one?

00:14:50.200 | - So some biological engineers engineered E. coli

00:14:54.000 | to fix nitrogen, I believe, not us.

00:14:57.760 | We use nature's nitrogen fixing bug

00:15:02.600 | and engineer it with the nitrogen fixing metabolism

00:15:07.400 | that we resurrected using our computational

00:15:10.240 | and phylogenetic tools.

00:15:11.880 | - How complicated are these little organisms?

00:15:13.920 | What are we talking about?

00:15:15.280 | - Depends on how we define complication.

00:15:18.040 | - Okay, so I can tell that you appreciate

00:15:23.040 | and respect the full complexity

00:15:25.080 | of even the most seemingly primitive organisms,

00:15:29.760 | 'cause none of them are primitive.

00:15:31.480 | Okay, that said, what kind of, what are we talking about?

00:15:36.120 | How, what kind of machineries do they have

00:15:40.760 | that you're working with when you're injecting them with DNA?

00:15:43.280 | - So I will start with one of the most fascinating

00:15:46.960 | machineries that we target,

00:15:48.280 | which is the translation machinery.

00:15:50.880 | It is a very unique subsystem of cellular life

00:15:55.880 | in comparison to, I would say, metabolism.

00:16:01.200 | And we used to, you know,

00:16:05.040 | when we are thinking about cellular life,

00:16:07.440 | we think of cell as the basic unit,

00:16:10.280 | or the building block.

00:16:13.040 | But from a key perspective, that's not the case.

00:16:17.840 | That one may argue that everything that happens

00:16:20.320 | inside the cell serves the translation

00:16:23.920 | and the translation machinery.

00:16:26.680 | There is a nice paper that called this,

00:16:28.640 | that the entire cell is hopelessly addicted

00:16:32.400 | to this main informatic computing,

00:16:36.920 | biological chemical system that is operating

00:16:40.960 | at the heart of the cell.

00:16:42.320 | - Which is the translation?

00:16:43.720 | - It is the translation.

00:16:44.560 | - What's the translation from what to what?

00:16:47.200 | So RNA to enzymes?

00:16:49.240 | - It converts a linear sequence of mRNA

00:16:53.160 | into a folded, later folded protein.

00:16:56.500 | That's when the, that's the core processing center

00:17:01.800 | for information for life.

00:17:04.360 | It has multiple steps.

00:17:06.520 | It initiates, it elongates,

00:17:09.040 | it terminates, and it recycles.

00:17:12.980 | It operates discrete bits of information.

00:17:17.980 | It's itself is like a chemical decoding device.

00:17:22.760 | And that is incredibly unique for translation

00:17:26.860 | that I don't think you will find anywhere else

00:17:29.920 | in the cell that does this.

00:17:31.840 | - So even though it's called translation,

00:17:34.620 | it's really like a factory that reads the schematic

00:17:39.520 | and builds a three-dimensional object.

00:17:43.320 | It's like a printer.

00:17:44.680 | - I would divide it into actually even four more

00:17:48.080 | additional steps or disciplines

00:17:50.220 | than what would it take to study it

00:17:52.800 | by the way you described it.

00:17:54.520 | It's a chemical system.

00:17:56.760 | It's the compounds that make it up, or chemicals.

00:17:59.800 | It's physical.

00:18:00.760 | It tracks the energy to make its job, to do its job.

00:18:05.760 | It's informatic.

00:18:08.180 | What is processed are the bits.

00:18:10.380 | It's computational.

00:18:12.420 | The discrete states that the system is placed

00:18:16.140 | when the information is being processed,

00:18:17.700 | that's itself is computational.

00:18:20.100 | And it's biological.

00:18:21.260 | It's, there's variability and inheritance

00:18:24.460 | that come from imperfect replication even

00:18:27.800 | and imperfect computation.

00:18:30.340 | - Oh man, that's so good.

00:18:31.860 | So from the biology comes the,

00:18:35.140 | like when you mess up, the bugs are the features.

00:18:38.340 | That's the biology.

00:18:39.900 | Informatics is obvious in the RNA.

00:18:41.660 | That's a set of information there.

00:18:44.300 | The different steps along the way

00:18:46.500 | is actually kind of what the computer does with bits.

00:18:49.600 | It's done computation, physical.

00:18:51.740 | There's a, I guess, almost like a mechanical process

00:18:56.740 | to the whole thing that requires energy.

00:18:59.140 | And actually, it's manipulating actual physical objects

00:19:02.980 | and chemicals 'cause you have to,

00:19:06.540 | ultimately it's all chemistry.

00:19:08.020 | - Yeah, and it tracks this information.

00:19:09.860 | So it is almost a mini computer device inside ourselves.

00:19:13.860 | And that's the oldest computational device of life.

00:19:18.300 | It's likely the key operation system

00:19:23.300 | that had to evolve for life to emerge.

00:19:28.620 | - It's more interesting or it's more complicated

00:19:33.620 | in interesting ways than the computers we have today.

00:19:36.780 | I mean, everything you said, which is really, really nice.

00:19:39.380 | I mean, I guess our computers have the informatic

00:19:42.100 | and they have the computational,

00:19:43.940 | but they don't have the chemical,

00:19:45.540 | the physical or the biology.

00:19:46.620 | - Exactly, and the computers don't have,

00:19:49.620 | don't link information to function, right?

00:19:52.900 | They are not tightly coupled,

00:19:54.340 | nowhere close to what translation

00:19:57.780 | or the way translation does it.

00:19:59.740 | So that's the number one, I think, difference

00:20:02.020 | between the two.

00:20:03.580 | And yes, it's informatic

00:20:05.900 | and we can discuss this further too.

00:20:09.980 | - 100%, let's please discuss this further.

00:20:13.900 | Which part are we discussing further?

00:20:15.220 | Each one of those are fascinating worlds,

00:20:17.100 | each of the five.

00:20:18.500 | - Yeah, so well, we can start with the more,

00:20:20.980 | I guess the ones that are more established,

00:20:23.660 | which is the chemical aspect of the translation machinery.

00:20:28.260 | It's the specific compounds make up the assembly of RNA.

00:20:33.140 | Chemists showed this in many different ways.

00:20:36.740 | We can rip apart the entire machinery.

00:20:39.060 | We know that at the core of it,

00:20:40.900 | there's an RNA that operates

00:20:45.780 | not only as an information system itself

00:20:48.540 | or information itself, but also as an enzyme.

00:20:51.180 | And origin of life chemists make these molecules easily.

00:20:54.900 | Now we know we can manipulate RNA,

00:20:56.740 | we can make even with single pot chemistries,

00:20:59.900 | we can create compounds.

00:21:01.380 | - What's a single pot chemistry?

00:21:02.980 | - I would say when you add all the recipes

00:21:07.100 | that you know that will lead you to the final product.

00:21:09.980 | - This is what original life chemists do

00:21:12.020 | is they come up with this pot,

00:21:13.820 | they throw a bunch of chemicals in

00:21:15.340 | and they try to, they're basically chefs of a certain kind.

00:21:20.020 | - I'm not sure if that's what they call it,

00:21:21.500 | but that's how I think of it

00:21:22.660 | because it is all combined in a test tube

00:21:24.740 | and you know the outcome.

00:21:26.180 | And it's very mathematical

00:21:28.860 | once you know the right environment

00:21:30.860 | and the right chemistry that needs to get

00:21:32.420 | into this container or this pot.

00:21:35.020 | You know what the outcome is.

00:21:36.020 | There is no luck there anymore.

00:21:37.820 | It's a pretty rigid, established input-output system

00:21:42.420 | and it's all chemistry.

00:21:43.820 | - So you actually wear a lot of hats

00:21:45.620 | as one of them original life chemists?

00:21:48.460 | - My PhD is in chemistry,

00:21:49.860 | but I don't do original life chemistry.

00:21:52.580 | - But you're interested in original life?

00:21:54.260 | - Yes, absolutely.

00:21:55.380 | - So some of your best friends are original life chemists.

00:21:58.940 | - Just make sure that you have good chemist friends

00:22:01.380 | if you're interested in original life.

00:22:03.380 | That's 100% requirement.

00:22:05.900 | It should be mandatory.

00:22:07.060 | - Okay, so chemistry.

00:22:09.900 | So what else about this machinery

00:22:11.340 | that we need to know chemically?

00:22:12.700 | - Well, chemically I think that's it.

00:22:15.700 | You have enzymes, you have proteins.

00:22:17.740 | Enzymes are doing their thing.

00:22:19.260 | They know how to chew energy using ATP or GTP.

00:22:23.380 | They know what to do in their own way.

00:22:26.740 | They do their enzymatic thing.

00:22:28.980 | So it's not just the ribosome

00:22:31.420 | that is at the heart of the transition,

00:22:33.420 | but there are a lot of different proteins.

00:22:35.580 | You're looking at about 100 different components

00:22:38.300 | that compose this machinery.

00:22:40.580 | - Well, let me ask, maybe it's a ridiculous question,

00:22:43.300 | but did the chemistry make this machine

00:22:47.940 | or did the machine use chemistry to achieve a purpose?

00:22:52.940 | So like, I guess there's a lot

00:22:58.900 | of different chemical possibilities on earth.

00:23:01.460 | Is this translation machinery just like picking

00:23:07.340 | and choosing different chemical reactions

00:23:10.980 | that it can use to achieve a purpose?

00:23:14.700 | Or did the chemistry basically,

00:23:16.860 | there's like a momentum, like a constraint to the thing

00:23:20.980 | that can only build a certain kind of machinery?

00:23:24.460 | Basically, is chemistry fundamental or is it just emergent?

00:23:29.460 | Like how important is chemistry to this whole process?

00:23:33.260 | - You cannot have life without chemistry.

00:23:35.820 | You cannot have any cellular process without chemistry.

00:23:40.540 | What makes life interesting is that

00:23:42.060 | even if the chemistry isn't perfect,

00:23:44.100 | even if there are accidents along the way,

00:23:46.340 | if something binds to another chemical

00:23:50.860 | in a way it shouldn't, there is resilience

00:23:54.500 | within the system that it can maybe not necessarily

00:23:57.340 | repair itself, but it moves on.

00:23:59.300 | However imperfect, mistakes can be handled.

00:24:02.700 | - That's where the biology comes in.

00:24:03.740 | - That's where the biology comes in.

00:24:04.780 | But in terms of chemistry, you absolutely cannot have

00:24:07.100 | a transition machinery without chemistry.

00:24:09.300 | And so as I said, there are four main steps.

00:24:12.620 | These are the core steps that are conserved

00:24:15.700 | in all transition machinery.

00:24:17.020 | And I should say all life has this machine, right?

00:24:20.900 | Every cell, everything. - On Earth.

00:24:23.460 | - On Earth. - Yeah.

00:24:24.580 | - Yes.

00:24:26.340 | - When you think of this machine,

00:24:28.140 | do you think very specifically about the kind of machinery

00:24:30.620 | that we're talking about?

00:24:31.860 | Or do you think more philosophically,

00:24:34.140 | a machine that converts information into function?

00:24:37.940 | - I cannot separate the two.

00:24:39.980 | I think what makes this machinery fascinating

00:24:42.700 | is that those five components that I listed,

00:24:45.460 | they coexist.

00:24:47.180 | So for instance, if we, let's just,

00:24:49.820 | talking about the chemistry part,

00:24:53.860 | we know the certain rate constant,

00:25:00.460 | all these proteins that operate in this machinery

00:25:02.820 | needs to harbor in order to get the mechanism going, right?

00:25:09.620 | If you are bringing the information

00:25:12.700 | to the transition machinery and you are the initiator

00:25:15.700 | of this computation system, you need to have,

00:25:20.020 | you can only afford a certain range of mistakes.

00:25:23.500 | If you're too fast,

00:25:24.900 | then the next message cannot be delivered fast.

00:25:27.500 | If you're too slow, then you may stall the process.

00:25:30.580 | So there is definitely a chemistry constant going on

00:25:34.180 | within the machinery.

00:25:36.180 | Again, it's not perfect, far from it,

00:25:39.540 | but they all have their own margin of error

00:25:44.140 | that they can tolerate versus they cannot,

00:25:45.860 | otherwise the system collapses.

00:25:47.660 | - So it's like a jazz ensemble, the notes of the chemistry,

00:25:51.900 | but you can be a little off- - I love that you said jazz.

00:25:53.620 | It's definitely true.

00:25:54.500 | It's a party and it's like everybody's invited

00:25:56.780 | and they need to operate together, right?

00:26:00.540 | And what's really cool about it, I think,

00:26:03.820 | there are many things that are very interesting

00:26:06.140 | about this thing, but if you take,

00:26:07.380 | if you remove it from the cell

00:26:09.700 | and put it in a cell-free environment,

00:26:11.700 | it works just fine, right?

00:26:14.060 | So you can get cell-free translation systems,

00:26:17.700 | put this translation in a test tube

00:26:21.660 | and it is doing its thing.

00:26:24.020 | It doesn't need the rest of the cell

00:26:25.980 | to translate information.

00:26:27.940 | Of course, you need to feed the information,

00:26:29.900 | at least so far,

00:26:31.180 | because we are far from evolving a translation,

00:26:36.180 | maybe not so far, evolving a translation in the lab

00:26:40.620 | or a machinery that can process information

00:26:43.780 | as it generates it.

00:26:44.900 | We have not done that yet.

00:26:46.620 | - That's a pretty complicated machinery,

00:26:47.980 | so it's hard for those origin of life chemists

00:26:51.860 | to find a pot that generates.

00:26:53.580 | - Because it's far more than chemistry.

00:26:55.620 | You need biology, obviously.

00:26:58.980 | You need biochemistry.

00:27:00.660 | You need to think as a, I think, network systems folk.

00:27:04.940 | You need to think about computation.

00:27:06.340 | You need to think about information.

00:27:07.820 | And that is not happening yet,

00:27:10.180 | except we are trying to bring this perspective.

00:27:14.220 | But the more you understand how information systems work,

00:27:18.540 | you cannot, once you see it, you cannot unsee it.

00:27:20.780 | It's one of those things.

00:27:22.020 | - So, but you could still rip it out

00:27:23.580 | and the chemistry happens.

00:27:25.100 | - Yes, and chemistry can happen

00:27:27.100 | even if you strip some of the parts out.

00:27:31.620 | It can, you can get very minimal level

00:27:35.260 | of information processing that does not look anything

00:27:38.780 | like the translation that cells relies on,

00:27:41.420 | but chemists showed from linear,

00:27:44.740 | you can generate information that arrives

00:27:48.060 | to the processing center in the form of a linear polymer.

00:27:52.620 | The informatic part of this system

00:27:55.740 | that I think sets it apart from computation

00:27:59.300 | and from metabolism comes in,

00:28:01.820 | if you think about the information itself, right?

00:28:05.300 | So we have four nucleotide letters that compose DNA

00:28:09.940 | and they are processed in the translation in triplets.

00:28:14.380 | So you have in triplet codon fragments.

00:28:18.220 | So you have four times four times four.

00:28:21.060 | So you have 64 possible states that can be encoded

00:28:25.340 | by four letters in three positions.

00:28:29.660 | All right, so.

00:28:30.500 | - It's so amazing.

00:28:31.780 | - Yeah. - It's so amazing.

00:28:32.900 | - There is only one code that says start.

00:28:36.020 | That's the, there's only one.

00:28:38.180 | And then there's two, if not three, that says stop.

00:28:41.820 | So that's what you work with,

00:28:45.100 | but you can have 64 possible states,

00:28:48.460 | but life only uses 20 amino acids.

00:28:52.460 | So we use six, life uses 64 possible states

00:28:55.540 | minus four of the starts and stops.

00:28:58.340 | To code for 20 amino acids in different combinations.

00:29:01.900 | That is really amazing.

00:29:05.100 | If you think about,

00:29:06.380 | there are 500 different amino acids life can choose, right?

00:29:09.420 | Narrowed it down to 20.

00:29:12.180 | We don't know why a lot of people think

00:29:14.340 | about this genetic code is quite fascinating.

00:29:16.820 | - So far, right? - Right.

00:29:18.220 | I mean, it didn't do it for 4 billion years.

00:29:19.980 | I don't know, we may wait for another 4 billion years, but.

00:29:22.340 | - But you didn't have those amino acids

00:29:23.820 | in the very beginning, right?

00:29:24.860 | Like. - We don't know.

00:29:26.100 | So we wouldn't be fooling ourselves

00:29:28.100 | if we said we know exactly how many amino acids existed

00:29:32.420 | early on, but there's no reason to think

00:29:34.060 | that it wasn't the same.

00:29:37.300 | - Or similar. - Yeah.

00:29:39.060 | We don't have a good reason,

00:29:40.860 | but because roughly 20 out of 60 states are used,

00:29:45.860 | you're using one third of your possible states

00:29:50.180 | in your information system.

00:29:52.300 | So this may seem like a waste,

00:29:55.580 | but informatically it's important

00:29:58.060 | because it's abundant and it is redundant, right?

00:30:02.380 | So this code degeneracy, you see this in,

00:30:07.060 | that's implemented by this translation machinery

00:30:09.220 | inside the cell.

00:30:10.100 | So it means you can make errors, right?

00:30:13.220 | You can make errors, but the message will still get through.

00:30:16.460 | You can speak, missing some letters,

00:30:19.060 | the information can miss some parts,

00:30:20.940 | but the message will still get through.

00:30:22.700 | So that's two thirds of the not used states

00:30:26.180 | gives you that robustness and resilience within the system.

00:30:28.980 | - So at the informatic level, there's room for error.

00:30:32.260 | There's probably room for error probably

00:30:34.140 | in all five categories that we're talking about.

00:30:38.420 | There's probably room for error in the computation.

00:30:40.100 | There's probably room for error in the physical.

00:30:41.780 | - Yes, exactly. - Everywhere there's room

00:30:43.460 | for error. - Yeah, because

00:30:44.420 | the informatic capacity is made possible

00:30:47.260 | together with the other components.

00:30:49.980 | And not only that, but also the product yields

00:30:53.980 | a function, no, in this case, enzyme or protein, right?

00:30:59.900 | So that's really amazing to me.

00:31:04.500 | - It is, I mean, in my head, just so you know,

00:31:06.780 | because I'm a computer science AI person,

00:31:10.060 | the parallels between even like language models

00:31:13.900 | that encode language, or now they're able to encode

00:31:17.740 | basically any kind of thing, including images and actions,

00:31:22.740 | all in this kind of way.

00:31:24.500 | The parallel in terms of informatic and computation

00:31:30.700 | is just incredible.

00:31:32.380 | - Actually, I have a image, maybe I can send you.

00:31:36.260 | - Can we pull it up now?

00:31:37.340 | - If you just do genetic codon charts, we can pull that up.

00:31:40.780 | Yeah, it's a very standard table.

00:31:42.980 | So I can explain why this is so amazing.

00:31:47.340 | So you're looking at, this is life's alphabet, right?

00:31:50.340 | And so I also wanna make a very quick link now

00:31:52.860 | to your first question, the tree of life.

00:31:55.140 | When we try to understand ancient languages,

00:32:01.380 | or the cultures that use these extinct languages,

00:32:06.380 | we start with the modern languages, right?

00:32:10.220 | So we look at Indo-European languages

00:32:14.420 | and try to understand certain words.

00:32:17.300 | And make trees to understand,

00:32:20.580 | this is what Slavic word is for snow, something like snig.

00:32:25.580 | - Now we jumped to languages that humans spoke.

00:32:27.780 | - Humans spoke, exactly.

00:32:29.100 | So we make trees to understand

00:32:31.260 | what is the original ancestor,

00:32:33.620 | what did they use to say snow?

00:32:35.980 | And if you have a lot of cultures who use the word snow,

00:32:38.740 | you can imagine that it was snowy,

00:32:41.740 | that's why they needed that word.

00:32:43.460 | It's the same thing for biology, right?

00:32:46.220 | If we understand some function about that enzyme,

00:32:50.580 | we can understand the environment that they lived in.

00:32:53.580 | It's similar in that sense.

00:32:56.260 | So now you're looking at the alphabet of life.

00:32:59.380 | In this case, it's not 20 or 25 letters,

00:33:01.940 | it's you have four letters.

00:33:04.820 | So what is really interesting that stands out to me

00:33:08.740 | when I look at this, on the outer shell,

00:33:11.020 | you're looking at the 20 amino acids

00:33:12.940 | that compose life, right?

00:33:14.780 | The one, the methionine that you see, that's the start.

00:33:18.980 | So the start is always the same.

00:33:21.020 | To me, that is fascinating

00:33:22.660 | that all life starts with the same start.

00:33:24.940 | There's no other start code.

00:33:26.820 | So you sent the AUG to the cell,

00:33:31.820 | when that information arrives,

00:33:33.540 | the translation knows, all right, I got to start,

00:33:36.460 | function is coming.

00:33:37.420 | Following this is a chain of information

00:33:41.020 | until the stop code arrives,

00:33:43.500 | which are highlights in black squares.

00:33:46.340 | - So for people just listening,

00:33:47.540 | we're looking at a standard RNA color table

00:33:50.300 | organized in a wheel.

00:33:51.780 | There's an outer shell and there's an inner shell,

00:33:54.060 | all using the four letters that we're talking about.

00:33:56.100 | And with that, we can compose all of the amino acids

00:33:59.220 | and there's a start and there's a stop.

00:34:01.940 | And presumably you put together,

00:34:03.980 | with these letters, you walk around the wheel

00:34:07.860 | to put together the words, the sentences

00:34:10.620 | that make-- - Yeah, the words, the sentences.

00:34:12.060 | And again, you get one start,

00:34:15.500 | you get three, there are three different ways to stop this,

00:34:18.180 | one way to start it.

00:34:19.780 | And for each letter, you have multiple options.

00:34:24.060 | So you say you have a code A,

00:34:26.300 | the second code can be another A.

00:34:28.820 | And even if you messed that up,

00:34:30.540 | you still can rescue yourself.

00:34:32.100 | So you can get, for instance,

00:34:33.620 | I'm looking at the lysine K,

00:34:35.860 | you get an A and you get an A

00:34:37.540 | and then you get an A that gives you the lysine.

00:34:40.100 | Right, but if you get an A and if you get an A and a G,

00:34:43.060 | you still get the lysine.

00:34:44.100 | So there are different combinations.

00:34:46.980 | So even if there's an error,

00:34:48.340 | we don't know if these are selected

00:34:49.700 | because they were erroneous and somehow they got locked down.

00:34:53.020 | We don't know if there's a mechanism behind this too,

00:34:56.660 | or we certainly don't know this definitively.

00:35:00.380 | But this is informatic part of this.

00:35:03.220 | And notice that the colors, and in some tables too,

00:35:06.220 | the colors will be coded in a way

00:35:08.340 | that the type of the nucleotides can be similar chemically.

00:35:13.340 | But the point is that you will still end up

00:35:16.180 | with the same amino acids or something similar to it,

00:35:19.260 | even if you mess up the code.

00:35:20.740 | - Do we understand the mechanism,

00:35:22.140 | how natural selection interplays

00:35:24.580 | with this resilience to error?

00:35:27.420 | So which errors result in the same output,

00:35:32.460 | like the same function and which don't?

00:35:37.860 | Which actually results in a dysfunction, which are?

00:35:40.580 | - We understand to some degree how translation

00:35:44.540 | and the rest of the cell work together,

00:35:47.100 | how an error at the translation level,

00:35:50.100 | this is the really core level, can impact entire cell.

00:35:54.060 | But we understand very little

00:35:55.820 | about the evolutionary mechanisms

00:35:58.660 | behind the selection of the system.

00:36:01.500 | It's thought to be as one of the hardest problems in biology,

00:36:05.220 | and it is still the dark side of biology.

00:36:07.620 | Even though it is so essential.

00:36:11.060 | So this is, yeah, you're looking at the language of life,

00:36:16.060 | so to speak, and how it can found ways

00:36:20.020 | rather to tolerate its own mistakes.

00:36:23.980 | - So the entire phylogenetic tree

00:36:26.020 | can be like deconstructed with this wheel of language.

00:36:31.940 | - Because all the final letters,

00:36:35.300 | those are, that's the 20 amino acids,

00:36:37.100 | that's our alphabet.

00:36:38.340 | They are all brought together

00:36:40.580 | with these bits of information, right?

00:36:43.340 | So when you look at the genes,

00:36:44.820 | you're looking at those four letters.

00:36:46.180 | When you look at the proteins,

00:36:47.460 | you're looking at the 20 amino acids,

00:36:50.020 | which may be a little easier way to track the information

00:36:53.340 | when we create the tree.

00:36:55.980 | - So using this language,

00:36:58.060 | we can describe all life that's lived on earth.

00:37:01.080 | - I wish. - One perspective.

00:37:04.500 | - We are not that good at it yet, right?

00:37:06.980 | - So in theory, this is one way to look at life on earth.

00:37:11.460 | - If you're a biologist and you want to understand

00:37:14.740 | how life evolved from a molecular perspective,

00:37:18.940 | this would be the way to do it.

00:37:21.220 | And this is what nature narrowed its code down to.

00:37:25.180 | So when we think of nitrogen,

00:37:26.860 | when we think of carbon, when we think of sulfur,

00:37:29.820 | it's all in this,

00:37:31.300 | that all these nucleotides are built based on those elements.

00:37:36.620 | - And this is fundamentally the informatic perspective.

00:37:39.060 | - Exactly, that's the informatic perspective.

00:37:41.820 | And it's important to emphasize

00:37:43.860 | that this is not engineered by humans.

00:37:47.340 | This evolved by itself.

00:37:49.680 | - Right, humans didn't invent this

00:37:52.940 | just because we were just describing,

00:37:55.020 | we're trying to find,

00:37:56.340 | trying to describe the language of life.

00:37:58.620 | - It appears to be a highly optimized chemical

00:38:03.140 | and information code.

00:38:05.700 | It may indicate that a great deal of chemical evolution

00:38:10.700 | and this may indicate that a lot of selection pressure

00:38:15.820 | and Darwinian evolution happened

00:38:18.060 | prior to the rise of last universal common ancestor.

00:38:20.860 | Because this is almost a bridge

00:38:23.260 | that connects the earliest cells

00:38:24.860 | to the last universal common ancestor.

00:38:26.500 | - Okay, can you describe what the heck you just said?

00:38:29.500 | So this mechanism evolved before the,

00:38:34.900 | what common ancestor?

00:38:36.260 | The last universal common ancestor.

00:38:38.260 | - Yes, so when we talk about the tree,

00:38:39.540 | when we think about the root,

00:38:41.020 | if you ideally included all the living information

00:38:46.020 | or all the available information

00:38:49.620 | that comes from living organisms on your tree,

00:38:52.740 | then on the root of your tree

00:38:54.340 | lies the last universal common ancestor, LUCA, right?

00:38:57.580 | - Why last?

00:38:58.720 | Last universal?

00:39:00.580 | Because the earlier universal,

00:39:02.460 | it also had trees, but they all died off.

00:39:04.860 | We call it the last because it is sort of the first one

00:39:08.820 | that we can track because we don't know

00:39:13.580 | what we cannot track, right?

00:39:15.300 | - There's one organism that started the whole thing.

00:39:19.580 | - It's more like, I would think of it

00:39:21.540 | as more like a population, a group of organisms.

00:39:23.780 | - Okay, hold on a second.

00:39:24.620 | I tweeted this, so I wanna know the accuracy of my tweet.

00:39:27.340 | All right.

00:39:28.180 | Sometimes early in the morning,

00:39:31.300 | I tweet very pothead-like things.

00:39:33.860 | It said that we all evolved from one common ancestor

00:39:38.860 | that was a single cell organism 3.5 billion years ago,

00:39:46.820 | something like this.

00:39:49.260 | How true is that tweet?

00:39:51.420 | Do I need to delete it?

00:39:52.420 | No, there's not actually, correct.

00:39:54.900 | I mean, I think, of course, there's a lot to say,

00:39:58.900 | which is like, we don't know exactly,

00:40:01.540 | but to what degree is the single organism aspect,

00:40:05.100 | is that true, versus multiple organisms?

00:40:09.180 | - Do you want me to be--

00:40:10.780 | - Brutally honest?

00:40:11.620 | Yes, please.

00:40:12.460 | There's still time.

00:40:16.300 | This is how we get like caveats to tweets.

00:40:19.860 | - All right, so first of all, it's not,

00:40:22.540 | 3.5 is still a very conservative estimate.

00:40:25.460 | That's what's-- - In which direction?

00:40:27.340 | - I would say it's 3.8 is probably safer

00:40:30.700 | to say at this point.

00:40:31.980 | - A bunch of people said it probably way before.

00:40:34.580 | - If you put an approximately, I'll take that.

00:40:36.820 | - I didn't.

00:40:37.660 | I just love the idea that I was once,

00:40:42.100 | first of all, as a single organism, I was once a cell.

00:40:46.220 | - Well, you're still is.

00:40:47.700 | You're a group of cells.

00:40:49.100 | - No, but I started from a single cell, me, Lex.

00:40:53.060 | - You mean like you versus Luca?

00:40:55.340 | Are you relating to Luca right now?

00:40:57.180 | - No, no, no, I'm relating to my--

00:40:58.700 | - Your own development.

00:40:59.860 | - My own development, I started from a single cell.

00:41:02.620 | It's like, it built up a cell, okay.

00:41:05.500 | That, and then, so that's for a single biological organism.

00:41:09.820 | And then from an evolutionary perspective, the Luca,

00:41:13.020 | like I start, like my ancestor is a single cell,

00:41:16.540 | and then here I am sitting half asleep tweeting.

00:41:20.180 | Like I started from a single cell,

00:41:23.780 | evolved a ton of murder along the way

00:41:28.100 | through this brutal search for adaptation

00:41:33.100 | through the 3.5, .8 billion years.

00:41:37.460 | - So you defy the code of Douglas Adams.

00:41:40.020 | You are proud of your ancestors,

00:41:41.340 | and you invite them over to dinner,

00:41:42.900 | and you invite them over to your Twitter.

00:41:44.580 | - Yeah, and it's amazing that this intelligence,

00:41:47.860 | to the degree you can call it intelligence,

00:41:49.620 | emerged to be able to tweet whatever the heck I want.

00:41:52.780 | - Yes, it's almost intelligence at the chemical level,

00:41:55.740 | and this is also probably one of the first

00:41:59.580 | chemically intelligent system

00:42:01.780 | that evolved by itself in nature.

00:42:04.140 | - Yeah, so you see that translation

00:42:06.060 | is a fundamentally intelligent mechanism.

00:42:10.140 | - In its own way, and again,

00:42:12.940 | if we manage to figure out how to drive life's evolution,

00:42:21.700 | if it can evolve a sophisticated

00:42:25.220 | sort of informatic processing system like this,

00:42:30.220 | you may ask yourself what might chemical systems

00:42:34.780 | be capable of independently doing

00:42:37.860 | under different circumstances?

00:42:40.900 | - Yeah, so like locally, they're intelligent locally.

00:42:43.860 | They don't need the rest of the shebang.

00:42:45.660 | They don't need the big picture.

00:42:47.820 | - So that's a great segue

00:42:50.820 | into what makes this biological, right?

00:42:53.580 | The heart of the cellular activities are translation.

00:42:57.500 | You kill translation, you kill the cell.

00:42:59.860 | Not only the translation itself,

00:43:01.460 | you kill the component that initiates it,

00:43:05.740 | you kill the cell.

00:43:06.580 | You remove the component that elongates it,

00:43:09.180 | you kill the cell.

00:43:10.460 | So there are many different ways to disrupt this machinery.

00:43:13.340 | All the parts are important.

00:43:16.180 | Now, it can vary across different organisms.

00:43:19.500 | We see variation between bacteria

00:43:21.820 | versus eukaryotes versus archaea, right?

00:43:24.020 | So it is not the same exact steps,

00:43:26.740 | but it can get more crowded

00:43:29.900 | as we get closer to eukaryotes, for instance.

00:43:32.740 | But you are still computing

00:43:34.140 | about 20 amino acids per second, right?

00:43:37.820 | This is what you're generating every second.

00:43:40.740 | - That single machinery is doing 20 a second?

00:43:43.060 | - 21 for bacteria, I believe eight for eukaryotes, or nine.

00:43:47.740 | - 21 a second.

00:43:49.140 | I mean, that's super inefficient or super efficient,

00:43:51.660 | depending on how you think about it.

00:43:53.700 | - I think it's great.

00:43:54.940 | I mean, I can actually do nine amino acids.

00:43:55.780 | - Yeah, but it's way slower than a computer

00:43:58.260 | could generate through simulation.

00:44:00.180 | - I think, if you can show me a computer that does this,

00:44:03.740 | we are done here.

00:44:04.580 | - Well, this is the big, this includes the five things,

00:44:08.420 | not just, but I could show you a computer

00:44:10.220 | that's doing the informatic, right?

00:44:13.060 | - Yes, you can show me that,

00:44:14.540 | but you cannot show me the one that has all.

00:44:16.580 | - For now.

00:44:17.820 | - For now.

00:44:18.660 | - I'm gonna ask you about probably what, alpha fold, right?

00:44:22.100 | - I think the more we learn about,

00:44:24.460 | and this is why early life and origin

00:44:27.380 | is also very fascinating and applicable

00:44:29.900 | to many different disciplines.

00:44:32.380 | There is no way you see this the way we just described it,

00:44:35.580 | unless you think about early life and early geochemistry

00:44:39.580 | and earliest emergent systems.

00:44:42.900 | But going back to the biological component,

00:44:48.700 | all of these attributes that we think about life

00:44:53.620 | or that we associate with biology

00:44:55.740 | stems from translation as well as metabolism.

00:45:00.300 | But I see metabolism as a way to keep translation going

00:45:04.420 | and translation keeps metabolism going.

00:45:07.100 | But translation is arguably a bit more sophisticated process

00:45:11.060 | for the reasons that I just described.

00:45:14.100 | - So metabolism is a source of energy

00:45:15.960 | for this translation process.

00:45:17.620 | - It's a way to process materials

00:45:21.260 | and it is inherently dynamic and it is flexible,

00:45:25.460 | but it is not focused on repetition as translation does.

00:45:29.900 | So that's the main difference.

00:45:30.940 | Translation is the kind of in a way, just it's repeats.

00:45:34.180 | So you have the metabolism that can synthesize materials,

00:45:38.460 | creates or benefits from available energy.

00:45:41.660 | And again, it's a dynamic system.

00:45:44.380 | And then you have computation

00:45:45.940 | that is inherently repetitive, right?

00:45:49.260 | Needs to carry out repetitive processes.

00:45:51.260 | And it does the tasks and it implements an algorithm,

00:45:56.000 | but it is not dynamic.

00:45:57.540 | So you see both of those attributes in translation combined.

00:46:01.420 | It is repetitive and it is dynamic

00:46:04.840 | and it also processes this information.

00:46:07.720 | So they are fundamentally different.

00:46:10.260 | I don't know if you can get life

00:46:14.180 | if you don't find a way to process the information

00:46:17.340 | around you.

00:46:18.200 | - In a repetitive dynamic way.

00:46:20.940 | - Yeah, and somehow that's what got selected,

00:46:25.460 | maybe not selected, I don't know if it was accidental,

00:46:28.820 | but that's what it seems to be conserved

00:46:31.900 | for four billion years, that that's what life established.

00:46:35.700 | - What's the connection between translation

00:46:37.580 | and the self-replication, which seems to be

00:46:40.180 | another weird thing that life just started doing,

00:46:44.140 | wanting to just replicate itself.

00:46:45.540 | - I think when we truly understand the answer

00:46:47.620 | to that question, we may have just made ourselves life.

00:46:50.460 | I don't think we know quite how translation machinery

00:46:54.460 | as a whole fits into equation.

00:46:57.180 | 'Cause we try to understand ribosomes, RNA,

00:47:02.180 | how the linear information is processed.

00:47:06.040 | Or the genetic code, why this codon's not others,

00:47:11.040 | why 20 not more, not less.

00:47:14.200 | And we are sort of moving towards translation,

00:47:17.120 | that's what we are working on anyway.

00:47:19.720 | To finally look at the patterns

00:47:21.720 | in which this system operates itself.

00:47:25.080 | And if you understand that, you're really unlocking

00:47:28.000 | a very emergent behavior.

00:47:30.060 | - One of the things you didn't mention is physical.

00:47:34.560 | Is there something to mention about that component

00:47:36.440 | that's interesting?

00:47:37.320 | - There's actually a paper published in 2013,

00:47:41.320 | I wanna say the first author is Zirnoff.

00:47:44.600 | So they surveyed a computational,

00:47:49.600 | engineered systems level computation energy consumption.

00:47:56.720 | And they tried to understand whether the universe

00:48:01.360 | is using its own, or life is using its full capacity

00:48:05.760 | of energy consumption.

00:48:07.320 | And whether if different planets in the universe

00:48:10.760 | had life, would the capacity would increase or decrease?

00:48:14.080 | Does life operate at its energy maximum?

00:48:17.360 | And they think that it does,

00:48:20.960 | that it actually operates at an efficiency

00:48:23.520 | that is far more above and beyond any computational system.

00:48:27.440 | - How is that possible to determine at all?

00:48:29.440 | - That you tell me, that's why I dropped the citation.

00:48:32.200 | I found the citation, it's quite an interesting paper.

00:48:35.000 | It's a bit, you know, it's a,

00:48:36.500 | obviously we can only calculate and infer these things.

00:48:42.520 | But-- - That's a good question to ask.

00:48:44.720 | Is the life that we see here on earth

00:48:47.800 | and life elsewhere in the universe,

00:48:49.680 | is it using the energy most efficiently?

00:48:54.000 | - Yeah, yeah.

00:48:55.280 | - It seems to be very efficient.

00:48:57.120 | Again, if we compare it to computers,

00:48:58.600 | it seems to be incredibly efficient at using energy.

00:49:01.360 | - I think they look at the theoretical optimum

00:49:04.240 | for electronic devices. - Got it.

00:49:05.960 | - And then try to understand where life falls on this.

00:49:09.520 | And life is certainly more efficient.

00:49:12.040 | - And that's ultimately the physical side.

00:49:13.520 | How well are you using for this entire mechanism,

00:49:16.080 | the energy available to you?

00:49:18.480 | And so given all the resilience to errors

00:49:22.560 | and all that kind of stuff,

00:49:23.400 | it seems that it's close to its maximum.

00:49:26.080 | And this paper aside, it does seem that life,

00:49:30.320 | obviously that's the constraint we have on earth, right,

00:49:33.440 | is the amount of energy.

00:49:35.480 | - Yeah.

00:49:36.320 | - So that's one way to define life.

00:49:38.320 | Well, the input is energy and the output is what?

00:49:44.280 | I don't know.

00:49:45.800 | Self-replicating.

00:49:47.340 | Wait, how, okay, let's go there.

00:49:50.280 | How do you personally define life?

00:49:52.480 | Do you have a favorite definition

00:49:55.320 | you try to sneak up on?

00:49:57.120 | Is it possible to define life on earth?

00:50:02.680 | - I don't know.

00:50:03.520 | It depends on what you are defining it for.

00:50:05.600 | If you're defining it for finding different life forms,

00:50:08.840 | then it probably needs to have some quantification in it

00:50:12.760 | so that you can use it in whatever the mission

00:50:17.760 | that you're operating to.

00:50:19.040 | - So you mean like it's not binary,

00:50:20.480 | it's like a seven out of 10?

00:50:23.560 | - Life-like?

00:50:26.720 | - Life-like.

00:50:27.920 | - I don't know.

00:50:28.760 | I don't think that defining is that essential.

00:50:32.400 | I think it's a good exercise,

00:50:34.520 | but I'm not sure if we need to agree

00:50:39.520 | a universally defined way of understanding life

00:50:42.640 | because the definition itself

00:50:44.960 | seems to be ever evolving anyway, right?

00:50:46.880 | We have the NASA's definition.

00:50:48.480 | It has its minuses and pluses,

00:50:53.240 | but it seems to be doing its job.

00:50:55.120 | - Well, what are the different,

00:50:56.400 | if there is a line and it's impossible

00:50:59.680 | or unproductive to define that line,

00:51:01.720 | nevertheless, we know it when we see it

00:51:03.840 | is one definition that the Supreme Court likes.

00:51:09.400 | And that's kind of an important thing

00:51:12.200 | to think about when we look at life on other planets.

00:51:18.440 | So how do we try to identify if a thing is living

00:51:23.440 | when we go to Mars,

00:51:24.560 | when we go to the different moons in our solar system,

00:51:29.480 | when we go outside our solar system

00:51:31.000 | to look for life on other planets?

00:51:33.280 | - It's unlikely to be a sort of a smoking gun event, right?

00:51:37.520 | It's not gonna be, hey, I found this.

00:51:39.640 | - You don't think so?

00:51:40.480 | - I don't think so, unless you find an elephant

00:51:42.640 | on some exoplanet, then I can say,

00:51:44.880 | yeah, there's life here.

00:51:46.320 | - No, but isn't there a dynamic nature to the thing?

00:51:49.920 | Like it moves, it has a membrane

00:51:54.600 | that looks like there's stuff inside.

00:51:57.520 | - It doesn't need to move, right?

00:51:58.880 | I mean, like look at plants.

00:52:00.480 | I mean, they grow, but there are plants

00:52:02.600 | that can be also pretty dormant.

00:52:04.640 | And arguably they do everything

00:52:08.400 | that one of my favorite professors once said,

00:52:12.480 | that the plant does everything

00:52:13.560 | that a giraffe does without moving.

00:52:15.760 | So movement is not necessarily.

00:52:19.240 | - But on a certain timescale,

00:52:21.480 | the plant does move, it just moves slower.

00:52:24.120 | - Yes.

00:52:24.960 | - It moves pretty quickly.

00:52:25.800 | - I would say that, it's hard to quantify this

00:52:28.840 | or even measure it, but it is,

00:52:30.340 | life is definitely chemistry finding solutions, right?

00:52:36.560 | So it is chemistry exploring itself

00:52:39.960 | and maintaining this exploration for billions of years.

00:52:45.000 | - So, okay, so a planet is a bunch of chemistry

00:52:49.480 | and then you run it and say, all right,

00:52:52.360 | figure out what cool stuff you can come up with.

00:52:56.080 | That's essentially what life is.

00:52:58.080 | Given a chemistry, what is the cool stuff I can come up with?

00:53:01.120 | - If that chemistry or the solutions

00:53:03.720 | that it embarks upon are maintained in a form of memory.

00:53:08.720 | Right, so you don't just need to have

00:53:12.520 | the exploring chemical space,

00:53:16.720 | but you need to also maintain a memory

00:53:18.760 | of some of those solutions for over long periods of time.

00:53:23.760 | So that's the memory component makes it more living to me.

00:53:28.880 | Because chemistry can always sample, right?

00:53:32.000 | So chemistry is chemistry,

00:53:34.020 | but are you just constantly sampling

00:53:36.420 | or are you building on your former solutions

00:53:39.560 | and then maintaining a memory of those solutions

00:53:42.040 | over billions of years?

00:53:43.120 | Or at least that's what happened here.

00:53:45.680 | - Chemistry can't build life

00:53:47.400 | if it's always living in the moment.

00:53:49.520 | The physicists will be very upset with you.

00:53:51.960 | Okay, so memory could be a fundamental requirement for life.

00:53:56.960 | - I mean, life is obviously chemistry and physics

00:54:02.840 | leading to biology.

00:54:04.960 | So this is not a disciplinary problem of one discipline

00:54:09.760 | trying to bring other disciplines.

00:54:11.600 | But what you need to have is definitely,

00:54:14.560 | chemistry is everywhere, right?

00:54:15.640 | I tend to think you can be a chemist,

00:54:19.240 | you can study chemistry, you can study physics,

00:54:21.040 | you can study geology anywhere in the universe,

00:54:23.500 | but this is the only place you can study biology.

00:54:26.340 | This is the only place to be a biologist.

00:54:27.960 | - Earth.

00:54:28.800 | - That's it.

00:54:29.640 | - Yeah.

00:54:30.460 | - So definitely something very fundamental happened here

00:54:32.880 | and you cannot take biology out of the equation.

00:54:35.200 | If you wanna understand how that vast chemistry space,

00:54:38.440 | how that general sequence space got narrowed down

00:54:43.160 | to what is available or what is used by life,

00:54:47.800 | you need to understand the rules of selection.

00:54:50.520 | And that's where evolution and biology comes into play.

00:54:53.000 | - So the rules of natural selection operate to you

00:54:56.280 | on the level of biology?

00:54:57.640 | - Rules?

00:54:59.800 | I don't know if there are any rules like that.

00:55:02.080 | It would be fascinating to find

00:55:04.160 | in terms of the biology's rules.

00:55:06.560 | That's a very interesting

00:55:08.200 | and it's a very fascinating area of study now.

00:55:12.440 | And probably we will hear more about that decades to come.

00:55:15.680 | But if you wanna go from the broad to specific,

00:55:19.900 | you need to understand the rules of selection.

00:55:22.160 | And that is gonna come from understanding biology, yes.

00:55:26.000 | - Well, actually, let me ask you about selection.

00:55:29.000 | You have a paper on evolutionary stalling

00:55:33.040 | where you describe that evolution's not good at multitasking.

00:55:36.480 | Or like in populations that evolve quickly.

00:55:41.160 | I mean, it's a very specific thing,

00:55:42.560 | but there could be a generalizable fundamental thing to this

00:55:46.320 | that evolution is not able to improve

00:55:48.520 | multiple modules simultaneously.

00:55:51.680 | I guess the question is,

00:55:53.500 | what part of the organism does evolution

00:55:56.080 | quote unquote focus on to improve?

00:55:58.760 | - Yeah, that was the driving question.

00:56:00.900 | We meddled with the part

00:56:04.040 | where you shouldn't be messing up with translation.

00:56:06.560 | This is the--

00:56:07.600 | - Should or should not?

00:56:08.920 | - You shouldn't.

00:56:09.760 | As I said, there are many ways to break it

00:56:11.560 | and all life needs it.

00:56:13.120 | - That's one of your favorite things to do

00:56:16.000 | is to break life to see what happens.

00:56:18.420 | - Yeah, because that's how kids learn, right?

00:56:22.520 | So you have to break something

00:56:23.680 | and see how it will,

00:56:25.520 | then you do it over and over again

00:56:26.660 | to see if it will fix itself in the same ways.

00:56:29.480 | So it's our, I don't know,

00:56:31.560 | it's the most fundamental properties

00:56:33.160 | of ourselves as human beings.

00:56:35.520 | So if we shouldn't break translation,

00:56:37.040 | then we should try to break it

00:56:38.600 | to see how it will repair.

00:56:39.880 | - So which part did you break?

00:56:41.200 | - I broke elongation.

00:56:42.820 | - What's the role of elongation in this process?

00:56:46.560 | - So we have four steps of the translations,

00:56:50.720 | initiate, elongate.

00:56:51.960 | So you elongate the chain,

00:56:53.400 | of the information chain

00:56:55.020 | that you're now creating, the peptide chain,

00:56:57.740 | or let's say broadly polymer chain.

00:57:01.940 | And there's a termination step

00:57:03.820 | and there's the recycling.

00:57:05.380 | So all of these steps are carried out by proteins

00:57:09.340 | that are also named after these steps.

00:57:11.660 | Initiation is the initiation factor,

00:57:14.420 | protein elongation is the elongator protein.

00:57:17.520 | We broke elongation.

00:57:23.380 | So the cell, the starting codon could still arrive

00:57:27.140 | to where it's supposed to go,

00:57:29.260 | but the following information couldn't get carried out

00:57:34.120 | because we replaced elongation

00:57:36.820 | with its own ancestral version.

00:57:39.540 | So we inserted roughly 700 million year old

00:57:44.540 | elongation factor protein

00:57:47.100 | after removing the modern gene.

00:57:53.240 | So we made this ancient modern hybrid organism.

00:57:57.660 | - And that essentially creates in some way

00:57:59.940 | the ancient version of that organism.

00:58:01.860 | - I wouldn't say so.

00:58:04.100 | It's a hybrid organism.

00:58:06.420 | It's not necessarily,

00:58:07.240 | because the rest of the cell,

00:58:09.500 | the rest of the genome is still modern.

00:58:14.500 | And that goes back to the difference between Jurassic Park.

00:58:17.380 | There are many differences, obviously,

00:58:19.340 | given that this is not fiction, we are doing it.

00:58:21.460 | But also we are not necessarily,

00:58:24.820 | I think in Jurassic Park they are taking

00:58:27.060 | an ancient, they find an ancient organism

00:58:29.940 | and then put a modern gene inside the ancient organism.

00:58:32.740 | In our case, we are still working with what we got,

00:58:35.420 | but putting an ancestral DNA inside the modern organism.

00:58:38.500 | - So you're like taking a new car

00:58:40.100 | and putting an old engine into it.

00:58:42.620 | - In a way, yeah, yes.

00:58:43.980 | - Seeing what happens.

00:58:45.260 | - Yes, but in our case, it's more like a transformer

00:58:47.660 | than just a regular car, which is doing things.

00:58:51.060 | - Yeah, so it's a more complicated organism

00:58:54.220 | than just a car.

00:58:55.060 | - Yeah.

00:58:56.540 | - I got it.

00:58:57.380 | So what does that teach you?

00:59:00.000 | - We wanted to understand multiple things.

00:59:02.900 | One is how does the cell respond to perturbation?

00:59:07.100 | And we didn't just put the ancient DNA,

00:59:09.460 | we inserted, we sampled DNA from currently existing organisms

00:59:14.460 | or the cousins of this microbe,

00:59:16.700 | and collected DNA sequences from the cousins as well.

00:59:21.020 | So both ancestor and the current cousin DNA, so to speak.

00:59:25.700 | And engineered all of these things to the modern bacteria

00:59:28.900 | and generated a collection of microbes

00:59:32.460 | that either have the ancient component

00:59:35.140 | or the variant elongator component that still alive today,

00:59:40.140 | but coming from a different part of the tree.

00:59:43.980 | - So you broke elongation.

00:59:45.960 | Was that something you did as part of the paper

00:59:49.740 | on evolutionary stalling to try to figure out

00:59:52.820 | how evolution figures out what to try to improve?

00:59:55.860 | Did that help?

00:59:56.920 | - Yes, because we were not supposed to

00:59:59.700 | mess with the translation.

01:00:01.060 | That's exactly what we did.

01:00:02.900 | And we altered elongation by changing it

01:00:07.460 | with different versions of elongation

01:00:09.900 | that are either coming from species

01:00:13.100 | that still are around today.

01:00:16.140 | You can imagine them as sitting on the tips of the tree

01:00:19.240 | near branch, far branch, compared to the organism

01:00:23.640 | that we're working with, distant cousins,

01:00:26.820 | as well as the ancestors of the bacteria

01:00:31.140 | that we are now modifying.

01:00:33.260 | - How much different variation is there

01:00:35.640 | in that elongation step?

01:00:36.880 | Like what are the different flavors of elongation?

01:00:39.120 | - That's a very good question.

01:00:40.060 | So mechanistically or mechanically, it's the same.

01:00:43.880 | It's very conserved.

01:00:45.360 | So all life elongates the same way.

01:00:48.240 | It's nothing but a shuttle.

01:00:49.760 | You just carry the chemical with you,

01:00:54.280 | the bit, to the heart of the machine.

01:00:58.240 | - Is it essentially doing like a copy paste operation?

01:01:01.000 | - It has its tail that's attached to the code,

01:01:06.000 | which is then carried biochemically to the linear chain,

01:01:11.420 | to the core of ribosome.

01:01:13.240 | And it sits on there.

01:01:15.560 | It's released and the peptides click.

01:01:18.120 | The codes rather click.

01:01:20.600 | Once that chemistry, that's at the tail end, occurs,

01:01:23.960 | the protein leaves the center.

01:01:28.680 | So you can imagine it's like it hops in there and hops out.

01:01:31.700 | And when it hops in, hops out,

01:01:33.040 | it leaves the information behind.

01:01:34.980 | That's all it does,

01:01:35.820 | is bring the information, get out of there.

01:01:37.720 | And it's all triggered by biophysics, biochemistry,

01:01:42.040 | because of the way the enzyme choose energy,

01:01:44.560 | in this case, GTP, how the phosphor leaves the center,

01:01:48.640 | that kicks, that gives the additional kick

01:01:51.480 | to the enzyme to leave the center.

01:01:55.240 | - So which parts are different then?

01:01:57.080 | Where's the flavors, different flavors of the location?

01:01:59.840 | - Usually the parts that matter don't change over time.

01:02:03.480 | Nature conserves the sites of these proteins

01:02:07.120 | that are important for its job.

01:02:09.840 | If there's a difference, then we wanna know,

01:02:12.920 | especially if there's a difference between two cousins.

01:02:16.960 | And we look at the sites that interact

01:02:20.480 | with the most important parts of this machinery.

01:02:24.640 | If we see any difference, we tend to mutate,

01:02:26.800 | or we revert, we engineer that part, we alter that part,

01:02:29.960 | because it gives us a clue

01:02:30.880 | that there must be something interesting

01:02:32.520 | going on here or not.

01:02:33.920 | - Okay, so that's not the fundamental part of the machinery,

01:02:37.280 | but it's some flavorful characteristic

01:02:39.960 | that you can play with.

01:02:40.800 | - So now you stripped the machinery down to its parts,

01:02:43.400 | and now you're looking at the parts of the parts.

01:02:46.160 | And it depends where you're looking

01:02:49.880 | and how you're looking and what you're looking at.

01:02:52.160 | But usually we see up to 70% level conserved identity

01:02:57.160 | across all modern versions.

01:03:02.320 | When you travel back in time, the identity decreases.

01:03:05.360 | So elongation likely existed.

01:03:08.240 | We have good reason to think that it existed

01:03:10.400 | at the dawn of life.

01:03:11.280 | So you're looking at a 3.8 billion year old mechanism.

01:03:14.920 | And when we look at the ancestors that we resurrect,

01:03:19.000 | we see about 40% identity.

01:03:21.640 | So the identity definitely decreases as you go back in time.

01:03:25.040 | But still 60% shared information over four billion year,

01:03:29.560 | it's pretty good.

01:03:30.640 | - Is that just for elongation

01:03:31.920 | or for the entire translation?

01:03:33.040 | - Depends on what you do.

01:03:34.280 | So for initiation, we've also recently published this.

01:03:37.760 | It's a different story.

01:03:40.200 | But overall you see high level of identity

01:03:44.600 | that is kept intact,

01:03:46.440 | especially if the component is essential for life.

01:03:49.360 | - Okay, so 40% and 60%, 70% you said.

01:03:53.520 | But like from generation to generation,

01:03:55.800 | how does evolution,

01:03:57.520 | and presumably that's what that paper is looking at

01:03:59.800 | is the parts of the parts.

01:04:01.200 | - Yeah.

01:04:02.040 | - How does it able to say, like mess with the parts

01:04:07.920 | and try to come up with a cooler,

01:04:09.480 | improved version of the organism?

01:04:12.000 | - Yeah, so let me describe to you

01:04:13.080 | what we did in that experiment.

01:04:14.320 | We took bacteria,

01:04:17.160 | we perturbed the elongation in all of these

01:04:20.200 | with different variants.

01:04:21.360 | So we had an initial set of a group of bacteria that we had.

01:04:26.360 | We then subjected these bacteria to evolution in the lab.

01:04:30.960 | So first of all, we knew we broke it

01:04:33.640 | because upon engineering,

01:04:35.000 | we measured what's going on with the cell.

01:04:37.320 | It's not growing as well.

01:04:38.520 | They're not healthy.

01:04:39.360 | We can see it with our eyes.

01:04:40.720 | We can measure it.

01:04:42.040 | That if they were generating an offspring every 20 minutes,

01:04:45.040 | now it is 40 minutes, right?

01:04:46.560 | So we really messed them up.

01:04:47.800 | They don't wanna work with this thing.

01:04:50.040 | They don't want each other, but they need each other.

01:04:52.560 | So we created that situation for them,

01:04:55.360 | which is good because we wanted to see

01:04:58.360 | how they will cooperate with each other to fix this problem

01:05:05.880 | because we know that that's not the condition

01:05:07.880 | that they wanna live in,

01:05:09.520 | especially when they know what they can do.

01:05:11.760 | So with that, we subjected these organisms

01:05:15.240 | to evolution in the lab.

01:05:17.240 | We refer to this as experimental evolution.

01:05:21.680 | We subject bacteria to different selection pressure,

01:05:26.680 | project them through bottlenecks.

01:05:30.600 | Every day, we randomly collect a handful of bacteria

01:05:35.440 | from the flask, put them in a new fresh environment

01:05:38.800 | with fresh food, keep them in this environment for 24 hours

01:05:42.520 | until they reach a more dormant state.

01:05:45.160 | And then we subject, introduce them to a new environment.

01:05:48.600 | So we repeated this for about, I will say, 150 days.

01:05:53.600 | So every day, nonstop, we repeated this experiment.

01:05:58.280 | - So kind of how many different kinds

01:06:02.240 | of environments are there?

01:06:03.640 | - We kept the environments to the same

01:06:06.200 | because we had different initial conditions.

01:06:08.040 | We kept the environment constant, same temperature,

01:06:10.920 | same food, same source of carbon,

01:06:14.160 | but we created replicates for each lineage.

01:06:19.160 | So in some ways, we created our own fossil record

01:06:22.720 | in the lab by evolving and generating these flasks.

01:06:25.840 | And every step of the way, we also froze these cells

01:06:30.680 | and took stocks of them in the cryo-freezer.

01:06:33.760 | - How long does it take to go from one generation

01:06:35.760 | to the next of bacteria?

01:06:37.080 | - For E. coli, it's usually 20 minutes.

01:06:41.300 | - Okay, great.

01:06:43.480 | So that's the experiment. - That's the experiment.

01:06:46.600 | - And you're always messing with it in the same way

01:06:50.480 | for the initial condition? - It's the same way.

01:06:52.600 | So we introduced variation at the elongation level

01:06:55.720 | because we perturbed it with different elongations.

01:06:59.880 | We found that if we introduce a different protein

01:07:03.320 | that is very different, the cells don't like that, right?

01:07:06.600 | So if the distance is larger, the consequences also large,

01:07:11.600 | meaning that you hit them harder.

01:07:13.680 | If you introduce a variant that is really foreign to them,

01:07:16.280 | that's really distant.

01:07:17.560 | In our case, it was the ancestor.

01:07:19.520 | They really did not like the ancestor,

01:07:21.340 | but they were okay with their nearest cousin.

01:07:23.640 | - Right, okay, great.

01:07:26.000 | So you did vary in the distance.

01:07:27.840 | - We varied the evolutionary distance

01:07:29.680 | and then we kept the experimental conditions the same

01:07:33.440 | and we propagated these populations every day for 150 days

01:07:38.280 | and we collected bacteria at every step of the way

01:07:42.880 | and looked at the sequence.

01:07:44.920 | We wanted to understand what sort of changes

01:07:47.240 | may have happened in the genome

01:07:49.020 | to respond to the variation that we've introduced.

01:07:53.940 | - So what kind of changes would you be seeing

01:07:56.180 | depending on the evolutionary distance

01:07:57.680 | of the thing you shoved into it?

01:07:59.100 | - Exactly, so we knew where we punched, right?

01:08:01.080 | We punched right at the heart, right?

01:08:02.560 | We punched the translation.

01:08:03.960 | So we expected, is it gonna be, is it translation?

01:08:08.800 | Are we gonna see a change?

01:08:10.760 | Will translation respond to this

01:08:12.120 | by fixing itself right away?

01:08:13.840 | Or will it be another, outside of translation,

01:08:18.360 | something completely different, a different module,

01:08:20.320 | because translation itself is a module?

01:08:23.000 | Or will it be within elongation,

01:08:25.480 | a really sub-protein level thing?

01:08:28.080 | So we had a strategy to identify the mutational pathways

01:08:33.080 | by categorizing what we expected to find or where.

01:08:37.640 | - Okay, so why does it not do multitasking?

01:08:43.280 | Why is it not improving multiple things simultaneously?

01:08:48.740 | - It turned out that what we observed in general

01:08:51.980 | is that first of all, the harder we hit the cells,

01:08:54.980 | the more likely they were to respond to our changes, right,

01:08:57.500 | at where we hit it.

01:08:59.820 | - When you say hit it,

01:09:00.700 | you mean like changing something about the elongation?

01:09:02.380 | - I like to think of it as hitting,

01:09:03.380 | because I like to think of this as breaking the cell, right?

01:09:06.260 | I mean, not breaking enough to kill it,

01:09:08.300 | but we still, because they're still alive,

01:09:10.520 | they're not doing their job well.

01:09:12.340 | - So the bigger the evolutionary distance

01:09:16.040 | of the thing you put in there,

01:09:17.900 | the harder the hit is how you think about it?

01:09:20.980 | The bigger the hammer?

01:09:21.980 | - Bigger the hammer, exactly.

01:09:22.820 | - That you hit it with, okay.

01:09:24.340 | - That's what it turned out to be,

01:09:25.420 | 'cause that's what the data told us,

01:09:26.820 | that if the variation is higher,

01:09:30.160 | then the consequences will also be higher,

01:09:34.140 | in the sense that the cells will not grow as healthy

01:09:36.580 | compared to a variant that is coming from a near,

01:09:40.620 | or a variant that is coming from a near evolutionary distance.

01:09:43.900 | - Is it wrong to think of this kind of hitting

01:09:45.860 | as akin to a mutation, or no?

01:09:49.980 | What are we supposed to learn from this hitting?

01:09:51.580 | Like how the thing evolves after it's being hit in this way,

01:09:55.800 | what does that teach us?

01:09:56.820 | - Because we see translation machinery as almost,

01:10:00.460 | it is so conserved and so essential,

01:10:03.780 | it is not even clear whether we can remove some of the parts

01:10:06.500 | or whether the entire translation will need

01:10:08.740 | all of the same parts in the same efficiency.

01:10:11.100 | We don't understand the rules of this machinery.

01:10:14.540 | So the first thing we understand is that,

01:10:16.980 | what is the resilience?

01:10:17.820 | What are we really talking about here

01:10:19.300 | when we talk about you cannot mess with this translation?

01:10:22.100 | Is this true?

01:10:23.460 | Because it is so conserved and so similar

01:10:26.160 | and functions in the most conserved ways,

01:10:29.320 | that was the first thing that we wanted to understand.

01:10:31.160 | - Did you learn anything interesting about the resilience

01:10:33.240 | at the chemical, physical, informatic,

01:10:35.160 | computational, biological?

01:10:36.000 | - No, I wouldn't say that,

01:10:37.320 | I think the biological level, yes,

01:10:39.480 | because we found that the different modules

01:10:42.800 | started responding to the changes that we've introduced,

01:10:46.520 | and that we could never recover the translation

01:10:50.320 | as effectively as it used to be.

01:10:52.000 | So that it never reached to it is optimality,

01:10:57.000 | that it was always suboptimal.

01:10:58.900 | It needed say one more mutation perhaps to get there,

01:11:01.460 | it accumulated four mutations that was,

01:11:04.660 | we did a lot of experiments to understand this of course,

01:11:07.700 | it was accumulating mutations,

01:11:09.460 | it was getting better at its task,

01:11:11.680 | maybe it needed a couple other mutations

01:11:13.780 | to get really good at it,

01:11:14.940 | but somehow those mutations never happened.

01:11:16.860 | And before those mutations happened,

01:11:18.820 | we saw another module emerging through mutations

01:11:23.320 | and getting better at its own different tasks

01:11:25.680 | that is not translation.

01:11:27.340 | You can think of cell as a web of networks, right?

01:11:30.460 | And we think of these as multiple almost airports

01:11:34.180 | that are proteins that are more central hubs,

01:11:36.880 | versus their proteins that maybe are not as important hub.

01:11:39.280 | If you introduce a problem in the most populated hub,

01:11:43.280 | you're gonna mess up the traffic system more drastically.

01:11:46.340 | And that's what we were messing with

01:11:49.000 | in the biological terms as well.

01:11:51.720 | - So when we say module,

01:11:53.000 | like translation would be one of the modules.

01:11:54.600 | - Translation would be one.

01:11:55.520 | - So you're basically saying when you mess with translation,

01:11:59.120 | the organism would choose to either try to fix that module

01:12:04.120 | or another module, depending.

01:12:06.860 | - Exactly.

01:12:07.700 | - But it wouldn't do multiple modules.

01:12:09.040 | - It wouldn't do multiple modules.

01:12:10.220 | It focused on one module at a time.

01:12:12.240 | And right before that module maybe reached

01:12:14.160 | to its own maximum, it stalled its optimality

01:12:18.160 | at a certain degree.

01:12:19.080 | So you never get to a degree that is more optimal

01:12:23.200 | than you can achieve,

01:12:24.320 | even though perhaps another mutation could get you there.

01:12:26.960 | - Since you messed with the translation

01:12:29.720 | from a sort of optimal perspective,

01:12:31.400 | wouldn't it make sense for the cell

01:12:33.240 | to try to start fixing the translation?

01:12:35.960 | - That's exactly what we thought.

01:12:37.520 | And it was not the case

01:12:38.980 | for all the broken translation missionaries.

01:12:41.240 | For instance, if the variant was coming from a near ancestor,

01:12:44.640 | that didn't happen.

01:12:45.880 | It was almost cruising around, trying different modules

01:12:49.000 | and sort of living its best life still without,

01:12:51.960 | because there is no real urgency in the system

01:12:53.720 | to fix the most important problem.

01:12:56.040 | - And there's also not a direction.

01:12:58.640 | Maybe to you it's obvious that's the problem,

01:13:02.520 | but to the cell, maybe you're the problem.

01:13:05.320 | I'm living, like you said, my best life.

01:13:08.320 | I mean, I guess that's the thing about evolution

01:13:10.240 | is we don't know what the right direction to-

01:13:14.040 | - Yeah, it's almost like you can imagine

01:13:15.800 | that you have this messy closet and you can-

01:13:19.000 | - Go on.

01:13:19.840 | Happens to be an accurate representation of my life.

01:13:25.040 | - So you take a look at it

01:13:26.880 | and you see all the sweaters or jeans all over the place.

01:13:30.680 | And then you look at a drawer

01:13:32.280 | that has socks coming out of it.

01:13:34.480 | And you'd think that's the most important one.

01:13:35.880 | I'm just gonna fix that one.

01:13:37.600 | And then you fix that one.

01:13:38.760 | And then you think you will get to the other one,

01:13:40.160 | but you don't because you just fix the most important one.

01:13:42.960 | That is the, whatever that was getting into your way.

01:13:46.000 | That's really what evolution is.

01:13:47.240 | It's quite lazy.

01:13:48.120 | It fixes the problem that seems to be the most immediate

01:13:50.520 | and it doesn't go beyond what it really needs to.

01:13:53.280 | It seems like at least for our experimental setup,

01:13:55.080 | that was the case.

01:13:56.800 | - Especially for rapidly evolving systems.

01:13:59.640 | So like, or is the environment they're operating

01:14:02.000 | in pretty constrained?

01:14:03.800 | Like, is there an urgency?

01:14:06.200 | - I would say that we definitely

01:14:07.520 | constrain the environment.

01:14:08.560 | It's definitely removed from their natural setup.

01:14:13.560 | We are not evolving them in a gut.

01:14:16.120 | It's a very homogeneous system,

01:14:18.600 | very controlled temperature,

01:14:20.360 | controlled food, controlled carbon.

01:14:22.880 | - So just looking at that,

01:14:24.200 | let me ask the romantic question.

01:14:26.200 | How did evolution create so much beautiful,

01:14:28.160 | complex variety on earth?

01:14:30.440 | Like from that, you're saying that we're talking

01:14:34.080 | about improving different modules,

01:14:35.520 | but if we step back and look at the entirety of the tree

01:14:37.800 | or the different organisms that created

01:14:39.720 | all throughout history,

01:14:41.760 | the stuff that's fun to you with the first few billion

01:14:45.960 | and the stuff that's fun to me when I watch on YouTube,

01:14:49.480 | which is like the lion versus gorilla fights and so on,

01:14:53.280 | but the whole thing is fun.

01:14:55.200 | So with all that beautiful variety

01:14:56.880 | from the predator and the prey,

01:14:58.440 | from the self-replicating bacteria

01:15:01.640 | and all that kind of stuff, how did it do it?

01:15:04.560 | - How is a very difficult question,

01:15:07.240 | especially when we don't understand the past

01:15:11.360 | with clarity at all.

01:15:13.120 | I can tell you that there seems to be very critical

01:15:17.480 | innovations that happened throughout the history of life

01:15:21.320 | that are each themselves very sophisticated singularities

01:15:26.320 | that emerged once and then they set the tone.

01:15:30.360 | One of which is emergence of translation.

01:15:34.160 | It's seems like it happened once.

01:15:36.240 | It had to happen once.

01:15:37.640 | It seems like that's all it took.

01:15:39.880 | 3.8 billion year, maybe older,

01:15:43.000 | clearly subjected to a lot of chemical evolution

01:15:46.720 | even prior to last universal common ancestor.

01:15:50.120 | And then you jump and you see emergence of cyanobacteria

01:15:55.120 | that's undeniably changed the course of those planets

01:16:02.680 | in the subsequent aerobic photosynthesis that's life learned

01:16:07.680 | how to utilize what's available in the environment

01:16:12.480 | in the most profound way.

01:16:14.440 | And then you move forward,

01:16:15.640 | you see the emergence of eukaryotes,

01:16:18.720 | that is endosymbiosis, also another singular event.

01:16:23.040 | And then you move forward and then comes the plants.

01:16:25.960 | So these are, I counted, I think six different things

01:16:29.880 | that seems to have happened just once.

01:16:32.920 | - And the singularity events

01:16:34.640 | in the history of evolution of life on earth.

01:16:37.320 | - So what's really fascinating here

01:16:39.400 | is that there seems to be two different courses,

01:16:42.000 | the time course.

01:16:43.440 | Evolution is operating at the molecular level.

01:16:46.520 | We're talking about seconds.

01:16:49.040 | We're talking about mutations that happen every second.

01:16:51.360 | We're talking about selection

01:16:52.680 | that's also happening under a minute.

01:16:55.240 | So that is a very fast process.

01:16:57.540 | The fact that I can evolve bacteria in a lab

01:17:00.800 | and I say, almost complaining,

01:17:03.120 | "Oh my goodness, it took me 150 days."

01:17:06.160 | I mean, that's pretty rapid for a change to be seen.

01:17:10.100 | But then the big changes and the ones that I'm talking,

01:17:14.400 | the really big innovations that caused an increase

01:17:18.560 | of oxygen on this planet or even its own mere presence

01:17:22.160 | are due to these molecular innovations.

01:17:24.640 | Seems to only happen a handful of times

01:17:27.280 | over billions of years of timescale.

01:17:29.400 | - Let me ask you this question

01:17:30.800 | having to do with my half asleep tweet.

01:17:33.260 | So saying that we all originated from one common ancestor,

01:17:37.880 | that's just one of the miraculous things

01:17:43.480 | about life on earth.

01:17:45.640 | Of course, you could say there's multiple common ancestors

01:17:47.960 | in the beginning, multiple organisms and so on.

01:17:50.480 | But the other stuff that you're talking about

01:17:52.440 | is these singular events,

01:17:54.540 | these leaps of invention throughout evolutionary history.

01:17:58.840 | Now there's a bunch of people who were commenting,

01:18:01.820 | a bit surprising to me,

01:18:03.580 | who were basically skeptical of this idea.

01:18:06.860 | - The idea of?

01:18:07.860 | - Well, I would say evolution, honestly.

01:18:10.780 | The process of evolution,

01:18:12.020 | but when you just actually focus in on like,

01:18:15.460 | "Holy crap, eukaryotes were invented.

01:18:20.460 | "Holy crap, photosynthesis was invented."

01:18:23.180 | Like those are incredible inventions.

01:18:25.380 | And also, we can even go to Homo sapiens,

01:18:27.980 | like intelligence, like where did that come from?

01:18:30.780 | It's these mysteries.

01:18:33.580 | I think where that skeptical comments are coming from

01:18:37.180 | were also just the general skepticism of science.

01:18:40.760 | I think from the pandemic,

01:18:43.940 | people, maybe a failure of institutions and so on,

01:18:46.680 | there's been a growing distrust of science.

01:18:51.900 | And it's not so much that it's anti-evolution,

01:18:55.180 | it's more of a stepping back and saying,

01:18:57.980 | "Wait a minute,

01:18:59.080 | "maybe scientists don't have it all figured out."

01:19:01.780 | And I think to steel man that case

01:19:06.780 | is almost a step back into realize

01:19:09.780 | there's so much mystery to each of these leaps.

01:19:13.400 | So it makes you wonder,

01:19:14.900 | is there something that in 100, 200 years

01:19:16.980 | we'll figure out that we totally don't understand yet?

01:19:20.940 | Like some, you know, there's,

01:19:22.580 | I talked to a bunch of people about another mystery,

01:19:25.740 | which is consciousness, right?

01:19:27.420 | And there's people called panpsychists

01:19:29.420 | who believe consciousness

01:19:31.500 | is one of the fundamental laws of the universe.

01:19:34.020 | So there could be, you know,

01:19:36.260 | like we have laws of physics that could be something

01:19:39.300 | that's like a consciousness field or something

01:19:43.300 | that permeates all matter.

01:19:45.220 | And so like there might be,

01:19:47.480 | it's kind of like Newtonian physics

01:19:49.140 | versus general relativity.

01:19:50.940 | Like we have a good understanding of how things happen,

01:19:54.580 | but we need another layer of understanding

01:19:57.420 | to fill in the gaps of the mysteries of it all.

01:20:00.420 | And that sort of is a sobering reality

01:20:03.940 | that maybe there is something

01:20:05.620 | we really deeply don't understand.

01:20:07.460 | Do you have a sense of where the biggest mysteries here are?

01:20:11.900 | Is it at the origin of life itself?

01:20:14.540 | Is it the leaps that we're talking about?

01:20:18.360 | So you see the beauty,

01:20:20.660 | you're fascinated about the translation mechanism.

01:20:23.160 | What are the deep mysteries there to you?

01:20:27.780 | - We are nothing but chemical systems

01:20:33.240 | capable of formulating or answering questions

01:20:36.940 | about our own existence.

01:20:38.900 | - We humans or all of life, you think?

01:20:42.980 | - Humans, humans are,

01:20:44.820 | I mean, the fact that we can,

01:20:45.900 | we even have this conversation about

01:20:48.200 | our place in the universe is,

01:20:52.360 | at least to our knowledge,

01:20:54.320 | is quite specific to our own chemical species.

01:20:58.120 | But-

01:21:00.300 | - Yeah, it's kind of wild.

01:21:02.280 | We're introspecting on our evolutionary history

01:21:05.700 | and we're just a couple of organisms.

01:21:08.240 | - Yes, and we're-

01:21:09.080 | - We're like another organism listening to this

01:21:11.560 | and like they're mind blown.

01:21:13.960 | There's like three organisms,

01:21:16.020 | two of them talking and the third one's like, holy shit.

01:21:18.820 | - I think that understanding the,

01:21:22.940 | what I really find interesting

01:21:24.380 | about understanding origin of life

01:21:26.100 | or even contemplating about our own place in the universe,

01:21:29.700 | if at the end of this would come down to appreciating

01:21:33.740 | or even before appreciating,

01:21:36.040 | really truly comprehending what it is that we got here,

01:21:39.700 | that to me is a huge gain.

01:21:43.500 | 'Cause there's no single question in biology,

01:21:47.600 | I think, that will give that,

01:21:49.860 | that will deliver that magnitude

01:21:51.540 | of that message and understanding.

01:21:53.540 | But understanding how life here started at first place,

01:21:57.340 | if we truly comprehend that.

01:22:00.220 | This is not a concept that is well thought in schools.

01:22:03.740 | We ask students to memorize these concepts.

01:22:07.180 | If they are lucky, they learned RNA world,

01:22:09.640 | chicken and egg problem, et cetera.

01:22:13.220 | That's the extent to which that got,

01:22:14.900 | maybe their biology teacher was personally interested

01:22:17.540 | in the subject matter, if they're lucky.

01:22:20.180 | You know the saying that the brains are evenly distributed

01:22:25.180 | across any metric you can imagine, but opportunities are not.

01:22:31.860 | So if people aren't understanding the importance of this

01:22:38.340 | is because that's a lack of opportunity right there.

01:22:40.860 | That's was skipped through the proper education

01:22:45.260 | and training in the delivery of why science matters

01:22:49.940 | or how science actually works.

01:22:51.140 | - Yeah, but how do you even begin to seriously think

01:22:56.140 | about the origin of life?

01:22:57.880 | I mean, every problem of existence, of life has its time.

01:23:08.580 | So I don't know if it's time to understand consciousness yet.

01:23:11.980 | We might be a hundred years away from that.

01:23:14.940 | The origin of life, I don't know if it's time for us

01:23:17.900 | to understand that yet.

01:23:18.860 | Maybe we need to solve so many more problems along the way.

01:23:22.420 | - It's not a competition of problems, right?

01:23:24.980 | So there are all kinds of problems

01:23:26.980 | and it takes a lot of people to make the world.

01:23:28.900 | So you will always have some interesting brain

01:23:31.940 | going after an interesting problem to their own.

01:23:35.220 | The issue here is that we need to first of all

01:23:38.220 | understand that what we have going on on this planet

01:23:42.380 | is pretty good.

01:23:43.860 | Good planets are hard to find.

01:23:46.380 | If we are alone in the universe, that's huge.

01:23:49.760 | We need to take care of what we got here.

01:23:53.500 | And we are incredibly vulnerable to the changes

01:23:57.980 | that our own species also helped create

01:24:00.860 | at the biosphere, at the ecosystem level.

01:24:04.260 | We take it for granted.

01:24:05.980 | We take what we created for granted.

01:24:08.040 | Because of the fact that we think we are some sort of

01:24:10.860 | ultimate end point, the most sophisticated, amazing thing

01:24:14.400 | that nature could generate.

01:24:16.080 | I think understanding, not even understanding,

01:24:21.340 | but asking these questions of where did this even come from?

01:24:25.880 | How did this even begin?

01:24:28.060 | And attempting to understand that using chemistry

01:24:32.940 | and physics and biology, and because we can,

01:24:37.460 | that's the ultimate gift we can give back

01:24:39.440 | to the entire species on this planet.

01:24:41.580 | - Yeah, I mean, it's humbling.

01:24:44.600 | It's humbling to realize the complexity

01:24:46.960 | of this whole mechanism.

01:24:48.040 | It certainly puts humans in their proper perspective.

01:24:51.240 | That we're not, just 'cause we have brains

01:24:54.640 | and brains are intelligent, doesn't mean

01:24:57.080 | we're the most intelligent thing.

01:24:59.580 | Because ultimately the whole mechanism of nature

01:25:02.080 | seems to be orders of magnitude more intelligent.

01:25:04.560 | All of it, like we're a bunch,

01:25:06.580 | we're like a hierarchy of organisms

01:25:09.220 | that have a history of several billion years.

01:25:12.100 | And that all somehow came together to make a human.

01:25:14.820 | And there'll be life after us, just as it was life before us.

01:25:18.860 | And something that comes after will be

01:25:21.100 | perhaps even more fascinating.

01:25:23.180 | - Yeah, I think when you understand the magnitude

01:25:25.620 | of what happened here, there is no room for arrogance.

01:25:29.060 | It should overwhelm you and humiliate.

01:25:31.220 | It's pretty humiliating.

01:25:32.540 | - Yeah.

01:25:33.380 | - You know, it's quite amazing what happened here.

01:25:38.140 | And there is no other discipline that will deliver that.

01:25:42.420 | But exploring our own origins and looking at life

01:25:46.980 | as a more planetary system phenomena

01:25:49.340 | rather than one single species at a time, a collective look.

01:25:54.140 | - You mentioned this question in your TED Talk is,

01:26:00.000 | the two possibilities of the universe being full of life

01:26:05.000 | and the universe being empty

01:26:07.040 | and we're the only life in the universe.

01:26:09.140 | How do you feel about both options?

01:26:12.760 | Just actually you as a single chemical organism

01:26:16.960 | introspecting about its existence in this world.

01:26:21.000 | - It's having a planet flow of life is interesting

01:26:23.780 | because there are, we talked about life being all about

01:26:28.400 | chemistry exploring solutions.

01:26:30.440 | And having solutions in front of you is great.

01:26:33.360 | It's beneficial, right?

01:26:35.440 | - Solutions being different organisms.

01:26:37.120 | Like other humans, you see them as a solution

01:26:38.960 | to a chemistry problem.

01:26:39.800 | - Different, yeah.

01:26:41.120 | - That's an interesting solution.

01:26:42.600 | That's not, next time we're in Austin

01:26:44.400 | so there's a bunch of weirdos.

01:26:45.560 | Every time I see a weirdo, I'll be like,

01:26:47.040 | oh, that's an interesting solution

01:26:48.760 | to this chemistry problem.

01:26:50.160 | - Now you think like an origin of life science.

01:26:54.480 | But it's--

01:26:55.320 | - Funny that that one worked out.

01:26:57.480 | Let's see where else it goes.

01:26:58.840 | - But having this emptiness and unpredictability

01:27:03.080 | of uncovering a novel solution

01:27:05.920 | can also have its own benefits.

01:27:08.000 | And we should be open to what other solutions

01:27:13.000 | might be out there and exploring those solutions.

01:27:16.120 | - Or to different chemistry problems.

01:27:17.560 | So that's where you see-- - Different chemistry problems.

01:27:18.720 | - You see the other planets out there

01:27:20.440 | as different chemistry problems.

01:27:21.520 | - To their own local environment, yes.

01:27:23.360 | So how many chemistry problems have solutions

01:27:28.360 | that are lifelike to you out there in the universe?

01:27:33.200 | - It's a wide open palette if you think about it.

01:27:35.560 | I don't quite know.

01:27:36.520 | It's the, we know the chemistry is chemistry.

01:27:39.560 | I don't think the chemistry will be different elsewhere.

01:27:41.720 | But again, what is selected by chemistry

01:27:43.840 | will be determined by the environment most likely.

01:27:46.560 | - See, I think there is life everywhere out there.

01:27:52.720 | So there's a guy named Nick Lane

01:27:54.360 | whose gut, and it's interesting to me,

01:27:59.440 | I wonder what you think about it,

01:28:01.360 | his gut is there's life everywhere out there,

01:28:04.240 | but it stops at the bacteria stage.

01:28:06.880 | So he says the eukaryotes is the biggest invention

01:28:11.880 | and the hardest one.

01:28:13.440 | - I wonder if he thinks that's an accidental outcome,

01:28:16.480 | if he thinks that's inevitable.

01:28:18.000 | I wonder what that means.

01:28:19.520 | But it's a likely possibility

01:28:22.200 | that the bacterial or microbial life

01:28:25.480 | is definitely more attainable.

01:28:27.240 | - So that's a weird world

01:28:31.160 | where our entire galaxy just has bacteria everywhere.

01:28:34.840 | - So you know, if you don't like microbes,

01:28:37.280 | you are on the wrong planet.

01:28:39.200 | - No, I know, yeah.

01:28:41.200 | And viruses, I don't know which one there's more of.

01:28:44.360 | But they're both, and most of them are productive.

01:28:48.000 | - They're fascinating.

01:28:48.840 | They do everything for us.

01:28:50.760 | - I don't like microbes, you're on the wrong planet.

01:28:53.720 | You're full of good lines.

01:28:54.760 | Okay, right, right.

01:28:56.480 | I just can't, there's like an imperative to the whole thing.

01:29:00.440 | To me, the origin is the hard question.

01:29:05.440 | But once it gets going, I just don't see--

01:29:09.920 | - Wait, go ahead.

01:29:11.080 | - It seems like it's constantly creating

01:29:13.160 | more intelligent things,

01:29:15.040 | more fascinating, complex things

01:29:19.440 | that are able to solve complicated problems.

01:29:21.080 | - That's a very interesting,

01:29:23.120 | I definitely agree that the initial steps

01:29:26.680 | may be the ultimate determinants.

01:29:28.080 | That once it's, you cannot stop it once it starts.

01:29:31.320 | It's possible, right?

01:29:33.400 | And--

01:29:34.280 | - I just have never on Earth, maybe, but maybe,

01:29:37.880 | I just, whenever I see life, it seems to flourish.

01:29:42.880 | Everywhere.

01:29:46.320 | The thing is, I don't,

01:29:49.000 | the only thing I haven't seen is the start of it.

01:29:51.760 | - Exactly, but, and how are we gonna understand that

01:29:56.400 | if we don't know the origin of life science?

01:29:58.600 | I mean, that's the, and the question here isn't exactly

01:30:03.000 | our ability to recapitulate everything that happened

01:30:05.560 | in the exact way that it happened, right?

01:30:08.280 | This is about what can happen, rather than,

01:30:11.440 | or maybe how it can happen.

01:30:12.920 | - You think it's possible to study the origin of language

01:30:17.320 | using English?

01:30:19.160 | So, like, there's a very particular chemistry here.

01:30:22.720 | There's a particular set of assumptions,

01:30:25.160 | understanding about what life is,

01:30:26.880 | what everything is, our perception of reality

01:30:29.720 | is very specifically constructed

01:30:32.960 | through the evolutionary process.

01:30:34.680 | I wonder if it's possible to get to some first principles,

01:30:38.640 | deep understanding of how life originates

01:30:42.080 | in such a way that you can actually

01:30:44.160 | construct it on other planets.

01:30:46.760 | Ultimately, it feels like if you're doing it

01:30:49.160 | in a lab on Earth, you're always going to be using

01:30:53.360 | some aspect of the life that's already here.

01:30:56.840 | - So, that's what I sort of talked about in my talk as well.

01:31:01.840 | And-- - Everyone should go

01:31:05.440 | watch the TED Talks, very good.

01:31:08.800 | The annoying thing to me about TED Talks,

01:31:10.960 | I guess it's by design, is they're too short.

01:31:13.320 | It's like, come on.

01:31:14.880 | - And did you know that there's no prompter involved?

01:31:19.720 | - There's no, wait, there is?

01:31:21.280 | - There isn't.

01:31:22.440 | - Yeah, you have to memorize stuff.

01:31:24.320 | Yeah.

01:31:25.160 | - It's a--

01:31:26.040 | - It must be a grueling process.

01:31:27.720 | - Amazing editor who probably is watching this too,

01:31:30.520 | David Bielo, that was very, very helpful.

01:31:33.200 | But I would say that--

01:31:34.720 | - Very professional organization.

01:31:35.560 | I like this podcast, it's a very professional organization.

01:31:38.920 | I respect that medium.

01:31:40.760 | Yeah, anyway, in the TED Talk about, yeah, life,

01:31:45.640 | life creating life.

01:31:46.880 | - So, it's a likely scenario that once we understand

01:31:51.880 | how life as a chemical system is capable

01:31:57.120 | of formulating its own expression and generating a memory

01:32:05.080 | and manages its existence on a planetary body

01:32:08.800 | for billions of years,

01:32:11.000 | once we understand what conditions gave rise to that,

01:32:16.000 | we may be very likely to understand

01:32:21.120 | whether a different planet also be likely

01:32:26.040 | to instigate its own chemical revolution

01:32:29.480 | if it was provided through some missing ingredients.

01:32:35.480 | So you can think of it as a sending fertilizer

01:32:37.480 | to a different planet that is missing

01:32:39.240 | its own chemical composition or lacking

01:32:41.840 | or that it needs more of what it has.

01:32:46.280 | The difference between making that planet Earth-like,

01:32:50.040 | which was, this is not what that's about.

01:32:52.040 | We're not talking about terraforming

01:32:53.880 | or we're not talking about turning that planet

01:32:56.040 | into Earth-like system.

01:32:58.400 | We are talking about first understanding that planet,

01:33:01.960 | studying its chemistry, studying its properties well enough

01:33:06.320 | to understand whether it is close

01:33:08.960 | to its own chemical revolution

01:33:11.080 | and maybe giving it that extra nudge.

01:33:14.240 | So this is obviously a pretty big speculation and suggestion.

01:33:19.160 | And it's a very interesting proposition

01:33:22.080 | because this is a yes or no question, right?

01:33:24.920 | This is the ultimate would you rather.

01:33:26.840 | And I think it says a lot about the perception

01:33:31.560 | of the person who's answering this question.

01:33:34.080 | That if the answer is no, no, no, absolutely not.

01:33:37.160 | That's not something we wanna do.

01:33:39.000 | I wanna know why that is the case.

01:33:41.000 | - So just to be clear, what we're talking about

01:33:42.600 | is looking at the chemical cocktail of a particular planet

01:33:45.560 | and having like tasting it and seeing what's missing.

01:33:51.640 | So having a very systematic, rigorous,

01:33:55.040 | scientific process for understanding what is missing.

01:33:58.320 | Not what is missing in terms of to make it Earth-like,

01:34:00.720 | but what is missing in order to be sufficiently,

01:34:05.320 | have the spark or the capacity of the spark

01:34:09.000 | to launch the evolution revolution,

01:34:13.320 | the evolutionary process.

01:34:14.960 | - Exactly, so--

01:34:15.800 | - And then the question is,

01:34:16.720 | do we want to then complete the cocktail?

01:34:21.480 | - The proposition is to also make us think

01:34:24.640 | that we will likely have this capacity at some point,

01:34:28.200 | especially when we understand origin of life

01:34:32.400 | better and better, right?

01:34:34.320 | So we will be asking ourselves this question.

01:34:37.440 | I guess I wanted to bring this to daylight a little bit

01:34:40.400 | because maybe in 10, 20 years, maybe more.

01:34:44.920 | - So you wanted to ask the ethical question,

01:34:46.800 | should we basically start life elsewhere on another planet?

01:34:54.920 | Or enable the chemical capacity of that planet

01:34:59.920 | that it may one day itself get there?

01:35:03.840 | - Okay, so for me, the answer is yes.

01:35:07.360 | So if you were to try to argue against my yes,

01:35:10.900 | what would you say?

01:35:11.740 | Why not?

01:35:12.720 | What's the worst that can happen

01:35:14.880 | if we seed another planet with life?

01:35:17.880 | What are the things we should think about?

01:35:19.720 | Is your main concern a chemical biological one

01:35:23.280 | or is it an ethical one?

01:35:25.360 | What do you think about?

01:35:26.200 | - Well, the worst thing that can happen

01:35:27.440 | is that it wouldn't work, right?

01:35:29.240 | So that it's not likely that an attempt like this would work.

01:35:34.240 | That's probably, 'cause how do you--

01:35:38.880 | - I think so.

01:35:39.720 | - You gotta be very, you have to have an understanding

01:35:43.580 | that I don't think we have just yet.

01:35:45.760 | - I see 'cause if it doesn't work,

01:35:47.820 | then we could try again, right?

01:35:51.480 | - To me, the worst case, the thing I would be worried about

01:35:56.360 | is we create life, I mean, the same stuff I worry about

01:36:00.600 | like with plants is things that might have

01:36:04.800 | a conscious experience.

01:36:06.800 | And then the dark aspect of life

01:36:11.240 | is life is increasingly a complex life.

01:36:15.560 | Maybe I'm anthropomorphizing,

01:36:17.160 | but it seems to have the capacity to suffer.

01:36:21.120 | And so we're creating something.

01:36:24.800 | It's like when you have children,

01:36:26.600 | you put creatures into this world

01:36:29.720 | that will suffer, can suffer and may suffer

01:36:36.100 | depending on how you view life, may likely suffer.

01:36:40.000 | And so now you carry this responsibility

01:36:42.540 | for doing your best to alleviate any suffering

01:36:45.520 | that might go through.

01:36:46.680 | And that perhaps is a romanticizing this notion

01:36:51.000 | of life, perhaps bacteria are not capable of suffering,

01:36:55.240 | but perhaps it'll create more complex life forms

01:36:58.000 | that would be able to suffer.

01:37:00.620 | And that feels like a responsibility as well.

01:37:05.360 | Of course, other people would be concerned.

01:37:07.680 | The more obvious concern is like,

01:37:10.360 | well, you just created a life form.

01:37:12.040 | How do you know it's not gonna be a super deadly virus

01:37:14.920 | that somehow is able to hurt humans?

01:37:17.740 | Yeah, my concern is more,

01:37:19.200 | I feel like that's a solvable problem.

01:37:21.240 | The problem of creating conscious beings

01:37:24.760 | that are able to suffer, that's a tricky one.

01:37:27.280 | - Yeah, I can see why, because it goes back to, again,

01:37:31.600 | would we, first of all, do we have a responsibility

01:37:36.600 | to propagate more of this chemistry

01:37:41.940 | that we have on this planet elsewhere,

01:37:45.000 | given that we know ultimately we will be vanished

01:37:48.880 | by the entire planet?

01:37:52.000 | And if this is in fact a very rare chemical event

01:37:58.360 | that happens because all the right circumstances

01:38:02.200 | came together and we were the lucky one,

01:38:05.520 | do we have a responsibility to sponsor it?

01:38:09.960 | If we were to back up--

01:38:12.880 | - Sponsor, I like it.

01:38:14.040 | (Lex laughing)

01:38:14.960 | That's a good way to put it, yeah.

01:38:16.360 | - If we try to back up remnants of our civilization,

01:38:21.000 | so we wanna potentially create conditions

01:38:26.000 | on the different planets so that humans can survive,

01:38:29.560 | given that we know, or we want to,

01:38:32.360 | just for the sake of growing.

01:38:35.480 | - Yeah, propagating, becoming a multi-planetary species.

01:38:39.240 | - Exactly, but what really is at stake here,

01:38:42.320 | I think is actually, or what is really more interesting

01:38:44.840 | is what we don't see, which is, again,

01:38:48.640 | that chemical behavior that enabled everything

01:38:51.400 | in the first place.

01:38:52.440 | That's different than sending potato crops

01:38:56.360 | or engineering bacteria to live on a different planet.

01:38:59.000 | That's very different.

01:39:00.560 | You are really stripping it down to what is possible

01:39:05.560 | at the chemical level.

01:39:08.000 | So even if you are instigating the chemistry

01:39:12.000 | on different planets, you are letting that very planet

01:39:15.040 | to do its thing.

01:39:16.720 | You're not necessarily contaminating this planet

01:39:19.320 | with different chemistry, because the idea behind this,

01:39:22.880 | at least the way I thought about,

01:39:26.080 | is that you understand that planet,

01:39:28.320 | you understand the conditions,

01:39:29.560 | you understand the chemistry of the planet really well

01:39:32.440 | before choosing the planet as a candidate at first place.

01:39:38.320 | And then it's not about sending a missing ingredient per se,

01:39:42.480 | but again, just sending more of what it already has.

01:39:45.760 | That will be respecting that planet's condition too.

01:39:50.280 | So I'm not suggesting any occupation.

01:39:52.440 | I'm not suggesting any colonization.

01:39:54.600 | I'm not suggesting any, like, let's just strip everything

01:39:57.400 | and make everything Earth-like.

01:39:59.480 | That's not what I'm saying.

01:40:00.800 | It's more about empowering that place.

01:40:03.360 | What you are saying is likely to be

01:40:08.280 | the motivator behind all this.

01:40:10.000 | That's not, because I see suffering, I see pain.

01:40:13.240 | It's very interesting.

01:40:14.680 | I think this is a question that really reveals

01:40:17.000 | a lot about the person who's answering it.

01:40:20.040 | - Well, okay, so the pushback on my pushback.

01:40:24.120 | If I saw deeply troubled by suffering,

01:40:28.840 | then I should be probably paralyzed

01:40:30.800 | about the history of life on Earth.

01:40:32.520 | And, you know, there's--

01:40:36.560 | - Can you elaborate, what do you mean?

01:40:38.560 | - Most of life who's ever lived,

01:40:41.640 | suffered in ways that are almost unimaginable to me.

01:40:45.400 | - You mean, like, our own species?

01:40:48.360 | - Our own species and before, and animals living today.

01:40:51.920 | And we're not even talking about factory farms.

01:40:54.400 | We're just animals living in extreme poverty in the jungle.

01:41:01.120 | You don't, people think like in the natural environment,

01:41:04.240 | animals live in a happy place.

01:41:06.120 | No, it's a brutal place of desperately trying to survive,

01:41:10.240 | of desperately trying to look for food.

01:41:12.400 | And it's just like all of that life, that's just mammals.

01:41:15.520 | And we understand mammals, but like throughout,

01:41:18.640 | like trillions of organisms that led up to those mammals.

01:41:22.520 | And the organisms living everywhere, like even bacteria,

01:41:25.640 | there's death everywhere.

01:41:27.320 | So maybe this idea of death, this idea of suffering,

01:41:31.600 | is actually, this thing that we see as a bug,

01:41:35.160 | is actually a feature.

01:41:37.280 | - I don't think suffering is a linear property

01:41:39.960 | like that with life.

01:41:42.040 | And I may be with Nick Lane on this one,

01:41:44.160 | that the likeliness of anything similar

01:41:46.600 | to what we got here, evolving in another planetary body,

01:41:49.920 | I think is quite low.

01:41:51.800 | - Where would you say is the biggest unlikely thing?

01:41:55.920 | Do you mean humans,

01:41:57.000 | or do you mean even multicellular organisms?

01:41:59.160 | - Probably multicellular, multicellularly.

01:42:02.480 | But I understand both sides of the equation, right?

01:42:07.480 | In one level, I can see that we may not have

01:42:12.440 | any other choice, but to back up this chemistry

01:42:17.440 | somewhere else.

01:42:18.640 | So you would be saving, it's the ultimate saving,

01:42:22.600 | or our own record.

01:42:24.920 | It's not about, yes, let's also save Beatles

01:42:29.640 | and all the amazing songs, but this would be

01:42:32.120 | the ultimate repository of life.

01:42:35.720 | But I can also see your point of view, for sure.

01:42:39.600 | - It's really interesting.

01:42:40.760 | So like, don't seed a plant with a missing ingredient.

01:42:44.480 | Try to understand what the ingredients it has.

01:42:47.640 | Is it possible to construct life?

01:42:49.640 | For me, from a computer person,

01:42:53.720 | it just feels like something

01:42:54.760 | that could be solved computationally.

01:42:56.800 | We can learn from the mistakes that we've done here

01:43:00.280 | and aspire not to repeat them.

01:43:03.760 | It is possible.

01:43:05.280 | We do amazing things as humans.

01:43:07.040 | There's a lot of suffering,

01:43:08.080 | but there's also a lot of beauty.

01:43:09.560 | And we could choose what we want to be,

01:43:14.560 | or what we want to see, right?

01:43:20.520 | So these attempts don't need not to come from,

01:43:23.360 | need not to come from a place of fear,

01:43:25.800 | but it can be ultimately,

01:43:27.040 | can come from a piece of hope and love.

01:43:29.120 | - I think we're just very recently figuring out stuff.

01:43:32.000 | Like we've, even just a century ago,

01:43:33.800 | we're doing atrocities that weren't seen

01:43:36.600 | as atrocities at the time.

01:43:38.400 | I mean, I think we're learning very quickly

01:43:42.040 | of what is right and wrong.

01:43:43.280 | - Yes, and I work with a lot of,

01:43:45.400 | maybe because I'm at the university,

01:43:47.200 | I get to teach young people every day,

01:43:51.880 | even at a time of four year or three, few years,

01:43:56.600 | you see generational difference already

01:44:01.480 | unfolding in front of you.

01:44:03.360 | And maybe that's why I see hope,

01:44:05.920 | because I think what we get to interact with in classrooms,

01:44:10.920 | every year, it's just getting better.

01:44:14.000 | They are aware of issues in a way

01:44:16.520 | that I sure wasn't at their age.

01:44:19.760 | Some levels I was,

01:44:20.800 | but in many levels I didn't think about.

01:44:23.600 | I wasn't concerned of the problems.

01:44:25.960 | Well, they maybe have to be concerned

01:44:28.360 | because it's hitting the reality,

01:44:30.360 | he's hitting them hard,

01:44:31.360 | but younger people are not afraid of these things.

01:44:34.800 | An 18 year old can face these brutal facts

01:44:37.520 | about the planet in ways that I don't think

01:44:39.840 | any other generation before them did.

01:44:41.920 | - Yeah, it's super cool.

01:44:42.800 | And like the, you know,

01:44:45.560 | there's all these cool technologies

01:44:47.520 | that aid in the process of a human being

01:44:51.880 | being able to see the truth at deeper, deeper levels,

01:44:55.320 | like, you know, Wikipedia and just the internet in general

01:44:58.400 | is enabling education at a level

01:45:00.400 | that was unimaginable before the internet.

01:45:02.160 | - Yes, and I think space exploration,

01:45:05.040 | even contemplating about these possibilities,

01:45:07.400 | ultimately, and I will emphasize this again,

01:45:10.560 | should make us think about our own place in the universe.

01:45:14.440 | If we are alone, that is quite fascinating.

01:45:17.320 | And we definitely have a responsibility

01:45:19.280 | to guard what we got better and protect it better

01:45:22.200 | and don't take it for granted.

01:45:24.040 | If we are not the only one,

01:45:25.680 | that's also a lot of responsibility

01:45:27.320 | to understand what else is out there.

01:45:30.240 | So either proposition, as famously being told,

01:45:33.840 | is fascinating, but as a scientist, I think,

01:45:38.560 | and I think that's a general behavior,

01:45:41.760 | maybe not my fellow scientists listening to this

01:45:44.320 | can correct me if they aren't like this,

01:45:45.720 | but you need to have a level of optimism and hope.

01:45:49.920 | That's something, you know,

01:45:51.800 | that things are worth working for,

01:45:54.640 | worth dreaming, worth imagining.

01:45:57.120 | And we cannot just have fear of suffering or fear of pain

01:46:01.320 | stopping us from doing marvelous things.

01:46:05.840 | - I've talked to quite a few people in my life

01:46:08.040 | who've gotten a lot of shit done,

01:46:10.840 | have helped a lot of people.

01:46:13.040 | And I don't know a single one of them

01:46:15.600 | who's not an optimist.

01:46:17.560 | Now, there's a place for critics and cynicism in this world,

01:46:20.920 | but in terms of actually building things

01:46:24.360 | and creating things in this world that help a lot of people,

01:46:27.660 | I think optimism is a requirement, is a precondition,

01:46:32.520 | in almost all cases,

01:46:33.840 | in my limited, humble human experience.

01:46:38.160 | But I tend to, when I look out there,

01:46:40.280 | think that aliens are everywhere.

01:46:42.240 | I think there's,

01:46:45.040 | to me, I have a humility about,

01:46:47.280 | I tend to see us humans as being very limited cognitively.

01:46:51.300 | Like, there's so many things we don't understand.

01:46:55.800 | I think eventually we'll understand,

01:46:58.280 | of course, we don't know this, but my gut says,

01:47:01.200 | we'll understand that alien signals

01:47:04.520 | and life has been all around us,

01:47:08.080 | and we're too dumb to see it.

01:47:09.660 | Like, whatever life is, whatever the life force is,

01:47:14.080 | whatever consciousness is, whatever intelligence,

01:47:16.240 | whatever the mechanism that led to the origin of life

01:47:21.240 | on Earth was everywhere, and we're just too dumb to see it.

01:47:25.560 | It's in the physics.

01:47:26.600 | It's somewhere, we'll find it somewhere in the physics.

01:47:29.380 | - I think that's one of the most humbling parts

01:47:34.880 | of also being a scientist,

01:47:37.200 | that we know that we never know for sure.

01:47:41.080 | And for the outsiders, perhaps,

01:47:45.200 | that may be a very strange way of living,

01:47:50.200 | especially when your pursuit is about creating knowledge,

01:47:55.400 | and that you'll know that what you created can also be,

01:47:59.320 | and hopefully will be disproven

01:48:02.760 | so that another level will rise.

01:48:06.240 | And I think we've seen that, this lack of maybe connection

01:48:11.240 | between the approach to science or knowledge

01:48:14.640 | versus folks who are maybe not thinking

01:48:17.520 | about these problems every day,

01:48:19.200 | that we are okay with being wrong.

01:48:21.600 | In fact, we know that that's the only way

01:48:23.880 | to push the limits of knowledge.

01:48:26.160 | - How do you think life originated on Earth?

01:48:29.480 | We've talked about this a bit.

01:48:31.480 | Do you have a gut feeling about,

01:48:34.640 | first of all, actually even to step back,

01:48:36.440 | do you think, 'cause you were flirting with this idea,

01:48:39.720 | did the translation mechanism came before life?

01:48:42.760 | - I think that you cannot separate

01:48:44.640 | from emergence of translation machinery

01:48:47.560 | from emergence of life,

01:48:48.800 | or something like translation machinery,

01:48:51.200 | this whole informatic chemical computing system

01:48:55.720 | that is also capable of dynamism and evolvability

01:49:00.560 | that comes with biology, biological behavior,

01:49:04.080 | from emergence of life itself.

01:49:06.240 | We've definitely took a lot of steps

01:49:08.720 | towards understanding origins.

01:49:10.040 | We are able to create molecules from environments,

01:49:15.040 | lightning, heat, and you make amino acids.

01:49:20.640 | So we are able to create the building blocks,

01:49:23.200 | the Miller-Urey experiment, that's now 60 years ago.

01:49:27.860 | We are able to create the building blocks,

01:49:32.400 | we are able to make them interact with one another.

01:49:34.760 | They can get more complex, some call this messy,

01:49:37.680 | there's all this chemistry that's going on.

01:49:39.200 | We are able to have these chemicals interact with one another,

01:49:43.480 | maybe have even some emergent properties

01:49:48.480 | that we can quantify.

01:49:49.880 | Definitely there is this trend

01:49:53.240 | towards more systems-level approach to origins,

01:49:57.360 | more introduction of systems-level chemistry,

01:50:00.560 | more network-level chemistry,

01:50:02.720 | and complex system integration

01:50:05.040 | in order to understand how,

01:50:07.240 | now that we can make these building blocks,

01:50:08.760 | we can make them interact with one another,

01:50:10.160 | but how do we make them interact with one another

01:50:11.760 | in more intelligent ways

01:50:12.880 | that will have the properties of a biological system,

01:50:16.840 | will be heritable, it will be responding to the environment,

01:50:20.120 | it will mutate, and it will sustain itself.

01:50:22.960 | That is the final bit, I think,

01:50:25.080 | in our origin of life adventure.

01:50:29.480 | And we are extremely close.

01:50:31.600 | I'm very optimistic that our community

01:50:33.560 | will get a handle of this problem in this decade.

01:50:37.200 | This is, in fact, I think,

01:50:38.040 | one of the most exciting times to be doing this work.

01:50:41.040 | - What would be super convincing to you,

01:50:43.320 | like incredibly amazing, would blow your mind

01:50:48.320 | if X was done in a lab?

01:50:52.400 | Like what would, I mean,

01:50:55.560 | I don't know if you would call it origin of life,

01:50:58.000 | but something really truly remarkable

01:51:00.480 | and special done in a lab.

01:51:01.840 | What would that look like to you?

01:51:03.400 | - The properties that I listed,

01:51:05.480 | this was five properties that I listed about

01:51:08.200 | in the machinery that is capable of sensing

01:51:11.480 | and responding to the environment.

01:51:13.200 | If we can, I would imagine,

01:51:17.960 | similar to Miller-Urey experiments

01:51:19.800 | where they only sparked particular environmental forces

01:51:26.120 | and were able to produce a chemical

01:51:29.400 | that is important for life,

01:51:30.600 | or a mix of chemicals important for life,

01:51:33.760 | or building blocks rather,

01:51:35.120 | if I saw that a similar experiment

01:51:39.480 | that a well-defined geochemical parameter

01:51:43.000 | was subjected on a mix of chemistry,

01:51:46.840 | which led that chemistry to form some level of computation,

01:51:51.840 | informatic, biological property,

01:51:55.560 | and by biological, I'm gonna keep it to very minimum,

01:51:58.200 | as I defined early on,

01:52:01.400 | that would be super exciting to me,

01:52:04.600 | a self-organizing chemistry

01:52:07.400 | that we can create experimentally in a flask

01:52:10.160 | by simulating the conditions of early Earth,

01:52:13.600 | be it radiation, be it temperature, or mix of both,

01:52:17.440 | that would be very cool.

01:52:20.280 | - And doing all the five,

01:52:21.520 | the chemical, physical, informatic, computational, biological.

01:52:24.880 | - Yes.

01:52:26.280 | - So like simulation and a computer would not--

01:52:29.880 | - No.

01:52:30.720 | - Would not be good enough.

01:52:31.560 | - It would be great because they help

01:52:33.520 | to understand the parameters,

01:52:36.520 | maybe formulate, maybe quantify, create models,

01:52:39.680 | but ultimately you need to experiment.

01:52:41.720 | - Unless it's quantum mechanical simulation,

01:52:43.680 | but that's going to be extremely difficult.

01:52:45.520 | So simulating from the physics up,

01:52:47.680 | that's going to be very,

01:52:49.920 | 'cause you're gonna have to simulate

01:52:52.080 | the physical, the chemical, the informatic.

01:52:54.920 | I mean, honestly, it's very difficult

01:52:59.040 | to start the quantum mechanics

01:53:01.080 | and end up in biology all through simulation.

01:53:04.360 | But the stuff that DeepMind did with alpha fold

01:53:06.800 | and protein folding is really inspiring.

01:53:08.800 | It's inspiring in that you're able to do,

01:53:13.360 | to solve a difficult biology problem.

01:53:14.800 | - Yeah, absolutely.

01:53:15.800 | That's why there's definitely a lot of benefits

01:53:19.160 | to those models, predictions,

01:53:21.240 | 'cause they at least help the experimentalist

01:53:25.440 | to come up with the priors

01:53:27.640 | and parameterize things better,

01:53:29.240 | maybe eliminates very obvious dead ends early on,

01:53:33.160 | given that experiments take such a long time

01:53:35.480 | and it's a huge investment.

01:53:36.880 | And no one's a better experimentalist than nature, so.

01:53:42.160 | - Let me ask you perhaps a depressing, sad for you question.

01:53:46.800 | - You really want to make me sad.

01:53:47.640 | You're not gonna win.

01:53:48.800 | - No, I know.

01:53:50.240 | There's a flame of optimism in you

01:53:52.120 | that will never be extinguished.

01:53:53.360 | Okay, the idea of panspermia.

01:53:57.120 | You mentioned would we seed another planet with life?

01:54:02.540 | Is it possible that our planet

01:54:04.880 | was seeded with life from elsewhere?

01:54:06.920 | - So what the proposition I made,

01:54:10.120 | I like to think of it as protospermia

01:54:12.640 | rather than panspermia,

01:54:13.760 | because it's even more,

01:54:15.480 | it's a more proto state than acknowledging.

01:54:19.320 | Because in panspermia, you still have a cell, right?

01:54:23.440 | You still have something that is very,

01:54:25.520 | even a cell to me would be very Earth-like, right?

01:54:28.600 | I'm talking at sub-cellular level

01:54:31.680 | in the proposition of spreading chemistry.

01:54:36.680 | - So spreading chemical ingredients, not spreading life.

01:54:40.400 | - Exactly.

01:54:41.400 | It will be more like the fertilizer

01:54:43.160 | that is well-adopted and compatible

01:54:45.880 | with that planetary body.

01:54:46.880 | In panspermia, you're still imagining

01:54:49.240 | either an entire bacteria or microbe or a cell

01:54:52.680 | or something that is DNA, which is still Terran.

01:54:55.920 | - So in that sense, that doesn't matter to you

01:54:59.840 | 'cause it's chemistry, that's the initial conditions.

01:55:02.760 | It doesn't matter how the initial conditions came to be.

01:55:05.160 | They are what they are and let's go from there.

01:55:07.600 | And there's all kinds of fascinatingly different

01:55:11.400 | initial conditions in terms of chemistry

01:55:13.120 | on different planets.

01:55:13.960 | - Yes, but in terms of panspermia,

01:55:16.080 | I mean, obviously there's gonna be always room

01:55:19.360 | for those sort of discussions or there will be,

01:55:22.840 | those discussions will always be present,

01:55:26.080 | I think, in any life in universe debates.

01:55:30.160 | But the problem I have with panspermia

01:55:33.120 | is that it removes the problem

01:55:34.720 | from the planet to somewhere else.

01:55:38.040 | It makes it very difficult to answer scientifically, right?

01:55:43.760 | You just took the problem away from this planet

01:55:47.160 | and formulate it in a way that I cannot go

01:55:51.360 | and try to understand in the lab,

01:55:54.120 | doing experiments or even through models.

01:55:56.200 | - Does it though, so I've heard brilliant biologists

01:55:58.960 | like yourself say that, but I just, to me,

01:56:02.920 | okay, here's how I think of Earth.

01:56:05.160 | So I actually am able to hold all these possibilities

01:56:08.080 | in my head and all of them are inspiring to me.

01:56:11.120 | I kind of think there's a possibility

01:56:12.880 | that Earth is just an experiment by a graduate student,

01:56:17.080 | by an alien graduate student.

01:56:18.920 | - So I know the exact episodes

01:56:21.160 | of "Star Trek" you're talking about.

01:56:23.600 | - But there is some, to me, that's inspiring.

01:56:26.800 | If we are--

01:56:28.120 | - But that's not what panspermia is about.

01:56:31.760 | You're talking about my proposition.

01:56:33.600 | That's not what panspermia is.

01:56:35.320 | - What's panspermia?

01:56:36.880 | Oh, life just came from elsewhere.

01:56:39.360 | Still, that's interesting because there's still giant leaps

01:56:42.800 | that happened on Earth, it seems like,

01:56:45.720 | beyond the initial primitive organisms like eukaryotes.

01:56:49.200 | - I don't think panspermia usually articulates

01:56:52.200 | at the level of eukaryotes.

01:56:56.080 | I think they talk about bacteria primarily.

01:57:00.320 | I think so.

01:57:01.160 | - Right.

01:57:02.040 | So that's still interesting 'cause all the different leaps

01:57:04.400 | of evolution still happen here on Earth.

01:57:06.040 | That's still interesting.

01:57:06.880 | - Yeah, but it's, I mean, it's definitely

01:57:12.160 | interesting to listen to, but I wouldn't place it in,

01:57:16.320 | I wouldn't know how to place it

01:57:17.880 | in the studies of origin of life, I guess, or--

01:57:20.400 | - Here's how we place it.

01:57:21.640 | You have the initial conditions for the origin of life,

01:57:24.800 | and you try to create life in that way

01:57:27.840 | that you've described in the five components,

01:57:30.160 | and it keeps failing.

01:57:32.000 | So what panspermia allows you to do

01:57:35.280 | is to also consider the question,

01:57:37.620 | maybe there's missing components.

01:57:40.920 | How do you answer that question?

01:57:43.160 | - Through exploration and through science.

01:57:45.160 | - Yes, yeah, tell me--

01:57:46.000 | - Looking outside of Earth,

01:57:48.400 | looking at the fundamentals of chemistry and physics.

01:57:51.000 | - How do you understand that with fundamentals

01:57:53.160 | of chemistry and physics?

01:57:55.280 | - How do you understand gravity?

01:57:58.120 | - But you're talking about panspermia, right?

01:58:00.280 | Just I don't understand how would you,

01:58:02.600 | it's different than, if you think it's similar

01:58:05.160 | to looking for life in the universe,

01:58:07.280 | is that what you're thinking?

01:58:08.760 | - No, I'm saying there's a missing component

01:58:10.680 | that came from elsewhere.

01:58:12.160 | - But a whole entire organism

01:58:13.680 | is not a missing component right there, right?

01:58:15.480 | I mean, when you're thinking about origin of life.

01:58:17.320 | - No, no, no, that's an assumption.

01:58:19.480 | Your assumption is all the ingredients

01:58:22.680 | for the origin of life are here on Earth.

01:58:24.840 | Now, I tend to believe that most likely that's the case.

01:58:28.000 | I'm just saying it's inspiring

01:58:30.320 | to think that there is some ingredients

01:58:33.400 | you're gonna push back 'cause that's not panspermia.

01:58:35.360 | That's part of it.

01:58:36.320 | But-- (laughs)

01:58:37.960 | - See, okay, so think,

01:58:40.440 | but yeah, I'm like--

01:58:41.280 | - It's also kind of fun to push back on you.

01:58:43.840 | No, I understand, I understand.

01:58:46.360 | I understand if actually a living organism

01:58:49.800 | ended up here from elsewhere,

01:58:51.960 | that means a lot of the exploration we're doing here

01:58:54.560 | with the ingredients that we know

01:58:56.520 | will not give us the clues to the origin of life.

01:59:01.520 | But it just seems like it's still very useful

01:59:07.080 | to try to create life here

01:59:10.400 | and then we'll see, wait a minute,

01:59:12.360 | don't you think we'll be able to prove,

01:59:15.280 | not prove, but show that panspermia is very likely?

01:59:18.680 | Like if we just keep failing,

01:59:20.480 | we understand biology deeply,

01:59:22.120 | we understand chemistry deeply.

01:59:22.960 | - See, that's the thing.

01:59:23.800 | I don't think so.

01:59:24.640 | I mean, there will be,

01:59:26.680 | the failure is not gonna indicate

01:59:29.560 | that this must have been,

01:59:31.480 | I don't think anyone will put the problem

01:59:34.320 | to something else just because our failures,

01:59:37.920 | our experiments failed.

01:59:39.680 | So failure means we don't understand

01:59:41.240 | the chemistry deeply enough.

01:59:42.320 | - Yeah, and given the progress we made

01:59:45.560 | and how many brilliant people are working on this right now,

01:59:49.040 | and it's definitely more,

01:59:51.720 | I would say that we are approaching this problem

01:59:53.920 | in more broader ways, different ways possible.

01:59:57.480 | I'm confident that we will get there.

01:59:59.040 | For us, again, we are interested in early cells

02:00:04.040 | and first cells and what followed origin of life,

02:00:06.160 | but we cannot, given that it's a continuum,

02:00:08.960 | that's between the origin and emergence of first cells,

02:00:13.680 | it's hard to separate these two ends from one another.

02:00:17.520 | - So given that life is a solution to a chemistry problem,

02:00:21.400 | if we re-ran Earth a million times,

02:00:25.120 | how different would the results be?

02:00:29.160 | If we look at that wheel,

02:00:31.760 | how different would be the tree of life, do you think?

02:00:34.440 | Like what's your gut say?

02:00:37.520 | - My mind asks, are you imagining,

02:00:42.000 | if we are repeating the planet one million times,

02:00:45.160 | are we seeing, are the things that happened,

02:00:50.160 | I'm not talking at the chemical level,

02:00:52.240 | but at the environment level,

02:00:54.000 | do they happen at the same time, at the same frequency,

02:00:57.120 | at the same intensity every time you're running this tape

02:01:00.720 | over and over again?

02:01:02.000 | - Yes, you mean like geological stuff?

02:01:04.200 | - Yeah, like so is the same--

02:01:05.040 | - So you're saying those are important.

02:01:06.560 | I mean, the fact that you would ask that question

02:01:09.600 | is also fascinating, so that's important?

02:01:11.880 | The timing, the frequency, the intensity of geological--

02:01:14.920 | - Yeah, so when we run this imaginary

02:01:16.960 | rewind and replay experiments in our minds,

02:01:19.400 | I wanna know whether we are positioning

02:01:22.120 | all the same geologic events

02:01:23.640 | at the same chronological order as well,

02:01:25.880 | or whether we are also giving them more randomness.

02:01:28.880 | So if the volcano erupted, is it happening at the same time?

02:01:31.720 | If you have, are dinosaurs getting wiped off every time

02:01:35.200 | with the same meteorite that's hitting the same--

02:01:38.000 | - But also like temperature changes and all that--

02:01:39.680 | - Temperature changes, everything.

02:01:41.520 | - That's actually, I've heard you say somewhere

02:01:43.480 | that one of the things that's fascinating to you

02:01:45.960 | about this whole process of evolution

02:01:48.240 | is that the process of evolution,

02:01:53.240 | all the mechanisms were invented and developed

02:01:56.280 | despite all the variation geologically

02:02:00.600 | through the hardship that Earth has gone through.

02:02:03.040 | - That the biological innovations persisted despite that?

02:02:06.560 | - Yeah, despite that, which is interesting.

02:02:09.720 | You kind of think of the biological innovations

02:02:12.480 | kind of happening on their own.

02:02:13.880 | - Because we, so we actually have a center

02:02:17.240 | exploring this problem.

02:02:18.520 | We wanna understand whether,

02:02:21.760 | it's almost like judging a book by its cover, right?

02:02:24.060 | Do you just look at an environment

02:02:25.840 | and then see whatever is present

02:02:28.320 | or scarce in that environment,

02:02:30.000 | and then think that, okay, the life form

02:02:32.360 | that will exist in this environment

02:02:34.080 | will obviously have a lot of molybdenum in its system.

02:02:38.240 | Look at all this molybdenum around here.

02:02:40.520 | Or will it be, because if you say that,

02:02:43.760 | you are now putting the environment

02:02:45.520 | in the more prime driver role, right?

02:02:49.760 | That you're saying that environment will determine

02:02:52.000 | what biology will or will not use.

02:02:55.800 | But we've done studies that show

02:02:59.600 | that it's not necessarily this straightforward.

02:03:02.640 | That for instance, we looked at going back to nitrogen.

02:03:06.240 | One thing that's fascinating about the way cells

02:03:09.440 | fix nitrogen, the ones that can do,

02:03:13.520 | is that they also do this through a lot of help

02:03:16.560 | of a lot of metals, a lot of elemental support really.

02:03:19.640 | And which geologists use to understand

02:03:26.280 | where did this metabolism even evolved,

02:03:29.160 | where at first place.

02:03:30.840 | So we look at ancient oceans,

02:03:32.280 | we try to understand the elemental composition

02:03:34.280 | of ancient oceans.

02:03:35.900 | And what we see is that in some cases,

02:03:39.520 | the metabolisms, even though they prefer a certain metal

02:03:42.560 | or an element that is in the environment,

02:03:44.560 | that metal wasn't abundant in the environment,

02:03:48.640 | but still life chose that.

02:03:51.040 | So it's not that straightforward as though whatever,

02:03:53.920 | you are what you eat,

02:03:56.760 | but you don't necessarily eat what is obvious to you.

02:03:59.880 | Just because there's a lot of that food around

02:04:01.560 | it doesn't mean life will ultimately go there.

02:04:03.320 | Maybe most of the time it will,

02:04:05.200 | but it seems like in the case of nitrogen fixation,

02:04:07.560 | it didn't and maybe that made the difference.

02:04:09.480 | - It's so cool that, right, it's not the abundant resource

02:04:12.520 | that's going to be the definition

02:04:13.760 | of what kind of life flourishes.

02:04:15.740 | So it's not a straightforward thing.

02:04:21.000 | - Yes.

02:04:21.840 | - My sense is that the different timing,

02:04:24.920 | the different conditions of the environment

02:04:26.720 | would change the way evolution happens.

02:04:29.880 | - Yeah, for instance, I mean, I think it's in the 80s,

02:04:33.080 | maybe earlier than that,

02:04:35.040 | Stephen Jay Gould's book, "Wonderful Life,"

02:04:37.800 | which changed, I think, a lot of scientists' life,

02:04:41.720 | including mine.

02:04:42.740 | He contemplates on this notion of the tape of life.

02:04:48.500 | Of course, I hope people still know what tape is,

02:04:51.360 | but I think your listeners will know what tape is.

02:04:53.480 | I don't know.

02:04:54.400 | It's the--

02:04:55.520 | - Tape?

02:04:56.340 | Go on, tell me about the tape.

02:04:58.120 | Is it like a TikTok?

02:04:59.840 | Can you swipe on it?

02:05:01.080 | I'm sorry, go ahead.

02:05:04.040 | I apologize for my rude interruption.

02:05:06.720 | - I kind of ask for it.

02:05:07.840 | But he speculated or he suggested

02:05:11.000 | this hypothetical experiment,

02:05:12.560 | whether if life was recorded on,

02:05:16.240 | or can be imagined to be recorded on a linear,

02:05:19.840 | is it linear chain of events recorded on a tape?

02:05:22.840 | And if we were to rewind the state,

02:05:24.440 | would we listen to the same song?

02:05:26.040 | Right, so this was,

02:05:27.120 | and in his proposition, I also thought,

02:05:29.060 | yeah, but are we replaying the tape

02:05:32.720 | in the same exact manner?

02:05:33.880 | Or are we, meaning all the geological

02:05:36.800 | and environmental events,

02:05:38.000 | are they happening at the same time?

02:05:39.620 | Because then you removed the randomness

02:05:41.920 | from equation a little bit, right?

02:05:43.620 | You just removed it,

02:05:45.880 | because you're assuming everything will happen

02:05:47.680 | at the same time, at the same intensity.

02:05:49.040 | So that's not too contingent.

02:05:50.600 | That means that the natural selection,

02:05:53.280 | you're thinking is really operating at more,

02:05:55.160 | or evolution is operating at more,

02:05:57.520 | under more random forces,

02:06:00.220 | than that can be dictated by the environment.

02:06:02.280 | So in our way of understanding

02:06:04.880 | or thinking about rewinding, replaying,

02:06:06.440 | I don't think we're thinking about

02:06:08.000 | the role of the environment as clearly,

02:06:09.800 | or don't seem to be integrated as much.

02:06:13.180 | - But I also wonder if it's possible

02:06:15.720 | that the chemistry ultimately defines the destination,

02:06:19.600 | that despite all the environmental changes,

02:06:23.500 | despite all the randomness,

02:06:26.240 | we'll end up in something.

02:06:28.200 | - But we are not talking about

02:06:29.400 | whether life will emerge and sustain itself.

02:06:31.960 | We are talking about whether life will emerge

02:06:33.680 | and sustain itself in the shape and form

02:06:36.040 | that is similar to what we have right now.

02:06:38.220 | So you are chemistry, I'm chemistry,

02:06:40.720 | we're having this conversation,

02:06:41.960 | and your plants are chemistry too.

02:06:43.800 | They're also having their own conversation.

02:06:45.720 | - These plants are fake, but yes.

02:06:47.560 | - I knew that, I didn't wanna say that,

02:06:49.000 | but they're fake.

02:06:50.160 | - But do you look at my place,

02:06:52.080 | of course they would be fake, otherwise they would die.

02:06:54.480 | - What's wrong with this place?

02:06:56.400 | - It's wonderful.

02:06:57.400 | I'm Alice and this is Wonderland, this is great.

02:07:02.280 | This is great, it's just that,

02:07:04.280 | this is a place where robots flourish,

02:07:06.120 | and those plants are fake.

02:07:09.360 | - Are you saying that you and I

02:07:10.320 | are the only living organisms?

02:07:11.400 | Well, obviously there are microbes in this room,

02:07:13.160 | but-- - Yeah, we are

02:07:15.000 | the only living organisms.

02:07:16.680 | Let's take care of getting a dog.

02:07:18.840 | - This is not a clean room, so you have microbes here.

02:07:20.960 | - Yes, many, millions.

02:07:22.160 | - Yes, so you and I and all the microbes in this room,

02:07:25.240 | we are chemical systems that are operating

02:07:27.600 | in a way that we can respond and sense

02:07:29.260 | and our environments and whatnot.

02:07:31.660 | But if you are asking if we are gonna be here,

02:07:34.400 | then you're imagining that another solution

02:07:36.960 | is also possible, which is different

02:07:39.720 | than the fundamentals of life.

02:07:41.940 | Because life will do always, life will do its life thing.

02:07:44.800 | - I guess it goes all the way back

02:07:48.800 | to the things we were talking about, translation,

02:07:51.360 | and the stuff you were messing with,

02:07:53.060 | is figuring out what is the important stuff and what isn't.

02:07:56.000 | Makes me wonder about, just like with the translation

02:08:02.280 | machinery with human beings,

02:08:04.960 | I wonder what's the important stuff.

02:08:06.160 | Is it important to have two limbs?

02:08:07.860 | Is it important to have eyes?

02:08:10.500 | Like it was obvious that the sensory mechanism of eyes,

02:08:13.840 | like sight, were to develop.

02:08:16.480 | How many times if we re-reinter Earth

02:08:18.400 | would the sensory mechanism of sight develop?

02:08:21.880 | And what would it look like?

02:08:22.960 | Would it be one giant eye?

02:08:25.000 | Or would it be two?

02:08:26.200 | What's with the symmetry?

02:08:27.160 | Why are we so damn symmetrical?

02:08:29.360 | - In response to Steve Jay Gould's proposition,

02:08:32.340 | most people who argue that life is convergent

02:08:38.680 | and it will in fact lead to a few determined outcomes,

02:08:43.480 | or it's not that the outcome is determined per se,

02:08:47.160 | but the pathways are restricted

02:08:50.160 | and the mutational trajectories that life can act upon

02:08:54.920 | are already very limited,

02:08:56.880 | so that the final outcomes are a few,

02:08:59.600 | and eyes being one of them.

02:09:01.940 | So the convergence at the eye level was suggested

02:09:07.700 | as an example, was presented as an example

02:09:11.020 | of why life may actually embark on the same solution

02:09:14.460 | over and over again, given that many species

02:09:17.140 | evolved independently from one another.

02:09:19.300 | - Do you think there's any inkling of truth to that?

02:09:21.900 | Like is it just us humans thinking we're special?

02:09:25.540 | - I think those innovations came again so far after the...

02:09:30.100 | (laughing)

02:09:31.660 | I know it's the fun stuff, yes.

02:09:34.620 | Because it's--

02:09:36.500 | - Thank you, I mean, thank you.

02:09:38.540 | We humans tend to talk about the later stuff,

02:09:41.340 | but without the earlier stuff--

02:09:42.540 | - Yeah, so when we think of earlier,

02:09:44.340 | and I ask this to my students too,

02:09:47.500 | I want them to close their eyes

02:09:49.300 | and think about just nothingness but dust.

02:09:52.260 | We don't have trees, we don't have plants.

02:09:54.140 | When we say an empty place, or visually at least,

02:09:57.700 | we are talking about a planet that is really alien.

02:10:00.600 | So understanding our own past is similar

02:10:03.100 | to understanding an alien planet altogether,

02:10:05.680 | given that it is a very different planet

02:10:07.860 | that did not have any oxygen for two billion years.

02:10:10.820 | There's nothing that is familiar to us

02:10:13.700 | that we would even think about when we think about life

02:10:17.900 | that is present in our past, yet here we are.

02:10:20.820 | - So cool, that from that came this,

02:10:23.900 | like houses and people--

02:10:24.900 | - And we are very, very,

02:10:26.700 | we are the super late arrivals to the party, right?

02:10:30.100 | So this is definitely not our planet.

02:10:33.060 | It's the microbial planet that we live in.

02:10:35.020 | - But the potential to create us was always there.

02:10:37.580 | - How do you know that?

02:10:40.700 | - 'Cause we were created.

02:10:42.040 | Oh, I don't know.

02:10:45.920 | What is it, you think it's possible that it's,

02:10:48.680 | even for the early stuff, yeah,

02:10:51.060 | maybe if it's super unlikely, yeah,

02:10:53.180 | that we just got super,

02:10:54.620 | this is the planet that got really lucky,

02:10:56.740 | given the chemistry.

02:10:57.860 | Like maybe to create the bacteria is not so lucky,

02:11:02.980 | but to create complex organisms

02:11:05.180 | all the way up to mammals, that's super lucky.

02:11:07.740 | - Yes, and it may all come down to a few innovations

02:11:10.840 | that happened at the molecular level

02:11:12.660 | that may or may not be inevitable.

02:11:15.740 | So all these molecular tricks may have enabled

02:11:22.220 | the sort of mere existence of whatever you are able

02:11:26.500 | to define as familiar to yourself.

02:11:28.660 | - And you have a hope that science can answer

02:11:31.020 | these questions to reconstruct?

02:11:33.780 | - Science is answering these questions.

02:11:35.340 | I mean, we are limited to going back to the beginning

02:11:40.340 | in our ways, right?

02:11:41.840 | So we rely on biology, it's overwritten.

02:11:45.380 | You're talking about four billion year old records

02:11:47.860 | that is ever changing, that again makes it beautiful,

02:11:50.380 | but also makes it difficult.

02:11:52.080 | It's not tractable.

02:11:53.900 | Geology has to some degree, it has a record,

02:11:58.900 | of a more static, frozen state record

02:12:03.900 | that is embedded on itself, on the surface of this planet,

02:12:09.100 | if we can find them.

02:12:11.060 | And that's the key that most of these recorded remnants

02:12:16.060 | are, if we're lucky, we find them.

02:12:21.380 | They are not naturally selected.

02:12:23.200 | They're found, they need to be found for us to be able

02:12:27.500 | to read them, so we work with a very handful set of samples,

02:12:32.500 | especially when we talk about the deep past,

02:12:36.860 | the planet with no oxygen, when we passed

02:12:40.580 | the Great Oxidation Event threshold,

02:12:42.300 | that is about 2.5 billion years.

02:12:44.460 | So the earliest life is even harder.

02:12:46.780 | You are trying to write the story of life

02:12:49.860 | based on a handful of rocks and what is recorded on them.

02:12:53.420 | Speaking of finding select remnants of our deep past,

02:12:58.420 | you said that you've been thinking about Nick Nealon's

02:13:02.980 | essay on scientific knowledge and scientific abstraction.

02:13:05.940 | So let me ask you, where do you think scientific questions

02:13:09.100 | and answers, or in general, ideas come from?

02:13:11.860 | You're a scientist, you ask very good questions,

02:13:17.500 | and try systematically and rigorously

02:13:19.940 | to answer them through experiment.

02:13:22.260 | Where do you think ideas come from?

02:13:24.380 | - So ideas come all the time, right?

02:13:26.500 | There are all kinds of ideas.

02:13:27.340 | There are good ideas, there are not so good ideas.

02:13:29.980 | There are really exciting ideas, maybe some boring ones.

02:13:34.980 | But if you are really interested

02:13:39.980 | in doing something different, then you need to be willing

02:13:43.300 | to take the risk to be wrong.

02:13:45.100 | And that's incredibly difficult, even though we talked

02:13:50.260 | about the idealist notion behind science

02:13:54.340 | that we ultimately want to be rejected,

02:13:56.500 | or our ideas need to be rejected

02:13:58.100 | for the entire infrastructure to move forward.

02:14:01.820 | There is a level of risk-taking, I think,

02:14:06.620 | behind any creative idea.

02:14:11.620 | And I mean that in a true sense.

02:14:14.220 | If you are disappointed that your idea didn't work,

02:14:18.100 | then it wasn't a risk,

02:14:20.260 | 'cause you still hoped that it will work.

02:14:22.300 | True risk is that you accept that it may not work,

02:14:25.860 | so that the failure shouldn't also surprise you.

02:14:28.260 | - Yeah.

02:14:30.780 | Is it when you embark on stuff, when you embark on an idea,

02:14:35.060 | do you actually contemplate and accept failure?

02:14:40.060 | Like as a possibility? - Not consciously,

02:14:42.660 | I wouldn't say so.

02:14:43.620 | But I eliminated a lot of the things out of my work line

02:14:48.620 | by simply not feeling like studying them.

02:14:55.980 | I was bored chasing certain questions.

02:14:59.260 | - So you trusted the signal of boredom as a good sign

02:15:04.300 | that it's not a good question?

02:15:06.260 | - It should definitely be,

02:15:09.340 | whatever you're doing should be exciting to you.

02:15:11.980 | If there's only one person that should be ever excited

02:15:14.100 | about what you're doing, that should be you.

02:15:16.860 | And that's enough for that idea to go somewhere.

02:15:19.740 | I think that you need to believe in the idea,

02:15:22.140 | but at the same time,

02:15:23.700 | I think it's important to not fall in love

02:15:26.700 | with your mistakes.

02:15:28.020 | That if something isn't working, you should let it go

02:15:34.500 | instead of trying to fix it.

02:15:37.420 | Even though you feel that this is a mistake

02:15:39.260 | or you know that it's a mistake,

02:15:41.380 | in order to, sorry, instead of trying to fix it,

02:15:46.380 | you should wrap it up and move on to something else,

02:15:51.620 | which is incredibly hard.

02:15:52.940 | - Good advice for science,

02:15:54.260 | but also good advice for relationships.

02:15:56.260 | But okay, so that's actually really hard,

02:16:00.900 | especially, I mean, this is like PhD stuff.

02:16:02.900 | Like if you sink in so much of your time,

02:16:06.100 | not even PhD, the entire scientific career,

02:16:09.340 | it's really tough to let go.

02:16:11.300 | - Yes, and there is not a lot of room for true freedom,

02:16:15.460 | maybe at this certain degree.

02:16:19.620 | So first you need to be trained, right?

02:16:22.020 | It's not that scientists are just brilliant, amazing humans.

02:16:25.900 | I mean, they just know and learn,

02:16:28.260 | they know how to do science

02:16:29.780 | because they're trained in how to do science.

02:16:32.460 | So that is important because as someone

02:16:35.980 | who wants to definitely, I'm hoping,

02:16:41.060 | giving the message that this is for everybody,

02:16:43.500 | that there's this notion of science,

02:16:45.900 | scientists being super smart people,

02:16:47.260 | that's definitely not true, right?

02:16:50.740 | It is a method that you learn to solve a problem.

02:16:53.980 | That's really what science is.

02:16:55.780 | And some are really good at it,

02:16:57.820 | and they get better at it under really good guidance,

02:17:01.540 | maybe good mentorship.

02:17:02.700 | And ultimately everyone finds their own style

02:17:06.740 | of problem solving and what sort of problems they solve.

02:17:09.460 | But I have not met a scientist

02:17:10.900 | that finds their own pursuit boring.

02:17:13.500 | - Well, it can happen,

02:17:17.300 | but they're not going to be effective,

02:17:18.420 | just like you said, I think.

02:17:20.620 | It's kind of interesting because in the age of social media

02:17:24.260 | and attention economies and stuff like that,

02:17:26.860 | I've interacted with a lot of folks,

02:17:29.780 | like YouTubers and so on.

02:17:31.380 | I think a lot of their work is driven

02:17:34.300 | by what others find exciting.

02:17:37.380 | And I think that ultimately leads

02:17:39.540 | to a life that's not fulfilling.

02:17:41.900 | - I can see the reason behind it,

02:17:44.540 | or perhaps there's a fear of failure

02:17:48.900 | that can be a major determinant of that pattern, right?

02:17:53.860 | So you try to do something that is accepted by others

02:17:57.940 | because that's maybe unlikely to give results right away.

02:18:02.940 | But it's a long game, it's a very long game.

02:18:06.100 | And if you are aiming a long-term change

02:18:08.900 | and long-term impact,

02:18:10.660 | you've got to be very, very patient about it.

02:18:13.020 | And you better tame your ego.

02:18:17.020 | - I mean, on YouTube and those kinds of places

02:18:20.900 | on the internet, on social media,

02:18:23.160 | you get feedback right away.

02:18:26.580 | And so it's even harder to be patient.

02:18:29.180 | Because change and ideas develop

02:18:34.060 | over a period of months and years, not decades.

02:18:37.540 | And the response from social media and so on

02:18:40.300 | is on the rate of seconds, minutes, and hours.

02:18:43.220 | - So I recommend actual physical libraries

02:18:46.420 | for people who may wanna appreciate

02:18:49.540 | or remember the sense of time

02:18:52.180 | and how long it takes to build something.

02:18:55.580 | I think it is, you're right,

02:18:57.980 | that's the immediacy and the right response.

02:19:01.460 | And the fact that these places,

02:19:05.900 | the algorithm wants you to respond right away

02:19:07.940 | and interact with itself, right?

02:19:09.740 | So I can see the appeal,

02:19:13.100 | but true innovation, I think, doesn't even scream.

02:19:16.740 | It's not shiny, especially in the beginning.

02:19:20.400 | But it's also important to not fool ourselves

02:19:23.420 | and think that everything that people criticize

02:19:25.620 | has some super important meaning behind it.

02:19:29.220 | So it's a mix of the technique,

02:19:31.340 | the methods, and your gut feeling.

02:19:33.600 | - Yeah, and a weird dance between learning

02:19:38.380 | and accepting the ideas of the current science,

02:19:43.380 | and at times trusting your gut and rejecting those.

02:19:48.460 | 'Cause science progresses by sometimes rejecting

02:19:52.580 | the ideas of the past or sometimes building on them

02:19:55.180 | in a way that changes them, transforms them.

02:19:57.180 | - Yes, and I think what is hard

02:19:59.420 | is to really drill down into a concept, right?

02:20:04.420 | So you can create a new thing,

02:20:07.740 | and then it may be appealing and gain a lot of traction,

02:20:12.620 | but to sustain that, to continue that,

02:20:15.460 | you really need to show the true expertise.

02:20:17.900 | And so it's not only about defining a problem,

02:20:20.320 | but then really systematically solve that problem

02:20:23.420 | maybe over the course of decades.

02:20:27.820 | - You mentioned the library.

02:20:30.380 | I've also saw that you've translated scientific documents,

02:20:33.260 | or at least mentioned that you did it

02:20:35.460 | at some point in your life.

02:20:37.120 | So let me ask you, how much do you think

02:20:40.980 | is lost in translation in science and in life?

02:20:44.660 | How many languages do you speak?

02:20:48.100 | - Two. - Two.

02:20:49.660 | How much is lost in translation in science

02:20:54.220 | and in life between those two?

02:20:55.500 | - No, it's actually three, because science

02:20:56.980 | is like another language, right?

02:20:58.860 | - It is.

02:20:59.740 | I speak Russian, a little bit of French,

02:21:02.340 | and it's always fascinating to see how much is lost.

02:21:04.500 | And the Soviet Union has a tradition of science

02:21:07.580 | and mathematics and so on, and it's interesting

02:21:10.120 | that a lot of the wisdom gained

02:21:12.580 | from that part of the world is lost,

02:21:16.500 | basically because it was never translated.

02:21:19.220 | - Well, I'm not sure if it is lost per se.

02:21:24.700 | I mean, maybe it's more like a gain in some sense, right?

02:21:28.820 | Because you understand,

02:21:30.380 | science is ultimately a human pursuit,

02:21:35.300 | so you cannot separate as much as,

02:21:39.300 | maybe it's the best system that humans ever came up with

02:21:43.800 | to seek knowledge, to generate and make sense of the world.

02:21:47.440 | It works most of the time.

02:21:50.340 | It doesn't mean it's perfect.

02:21:52.580 | - Did the kind of translation you do, by the way,

02:21:54.220 | was for scientific work?

02:21:55.940 | - I directly translated for scientific work, yes.

02:21:59.260 | I think that, again,

02:22:03.180 | brains are equally distributed,

02:22:06.340 | but opportunities are not, right?

02:22:08.540 | So if you want to include,

02:22:13.500 | if you want to benefit from all human power,

02:22:16.180 | whatever we can generate as human beings,

02:22:18.060 | you need to include everybody on the table.

02:22:20.700 | And that is by extending the opportunity.

02:22:23.900 | I think most of us that make it

02:22:26.940 | tend to think that we did

02:22:28.100 | because of something special about ourselves.

02:22:30.820 | But it is important to know that,

02:22:33.140 | no, we were given opportunities,

02:22:35.420 | and that's why we are here,

02:22:36.540 | not because there was something inherently special about us,

02:22:41.020 | or that the system truly selects for the ones

02:22:45.420 | that really are--

02:22:46.940 | - Yeah, and language is a part of the opportunity.

02:22:49.420 | - Yeah, language is an opportunity

02:22:50.700 | because it comes with, similar to bacteria, right?

02:22:53.700 | They speak these languages.

02:22:55.420 | Even we call culturing the bacteria,

02:22:59.620 | we call it culturing, right?

02:23:01.100 | When we grow bacteria

02:23:02.500 | that we isolate from the environment in the lab,

02:23:05.220 | meaning that you create an environment

02:23:06.860 | for them to grow and thrive and sustain themselves.

02:23:10.300 | That's what we say,

02:23:11.380 | but culture is for microbiologists.

02:23:14.700 | For language, with language comes a different culture,

02:23:18.060 | a different perspective,

02:23:19.420 | and you bring that to the table.

02:23:23.420 | I mean, it brings the sense of diversity

02:23:26.460 | that can only be achieved by clashing, perhaps,

02:23:30.060 | two different cultures, two different languages,

02:23:32.540 | two different approaches,

02:23:33.740 | maybe in some cases, four different approaches.

02:23:36.860 | - Yeah, I think language is not just

02:23:39.420 | a mechanism of communication.

02:23:41.140 | It's a way to,

02:23:42.180 | it's a dynamic system of exploring ideas,

02:23:46.700 | and it's interesting to see

02:23:47.980 | that different languages explore ideas differently.

02:23:50.740 | - Yes, and I think that,

02:23:52.140 | so when I said science is like a language itself,

02:23:55.180 | I said it in two different ways.

02:23:56.500 | One is very literal meaning,

02:23:59.780 | that you can speak English,

02:24:01.180 | but that doesn't mean you will understand

02:24:02.820 | the scientific paper.

02:24:04.620 | It's a different level of English

02:24:06.180 | that you need to learn to understand.

02:24:08.140 | Even, not just for scientific papers,

02:24:10.420 | even from discipline to discipline.

02:24:12.580 | I challenge any chemist to read

02:24:15.660 | an evolutionary biology paper, and vice versa.

02:24:18.820 | It may sound extremely different,

02:24:21.220 | and a different language altogether.

02:24:23.140 | But there's also the language of communicating,

02:24:25.860 | and because words matter, how we talk matter,

02:24:28.900 | how we represent our science matters.

02:24:30.820 | So yes, just learning English as a second language alone

02:24:34.340 | is not gonna make you fluent in science either.

02:24:37.700 | - And it's interesting 'cause in that sense,

02:24:40.220 | you speak many more than three languages

02:24:42.180 | because you're pretty cross-disciplinary.

02:24:45.220 | It seems like you have a foot in a lot of disciplines.

02:24:49.660 | I mean, you're mentioning geology, biology,

02:24:52.660 | evolutionary biology, I mean, there's chemistry.

02:24:57.460 | - Biochemistry, biophysics, even we do a lot of statistics.

02:25:02.380 | So there's a lot of mathematics to what I do as well.

02:25:04.420 | Yes, we like to think of it as this,

02:25:06.660 | now it's astrobiology program, I repeat it because it's fun,

02:25:12.180 | that it is not a fruit salad, but it's a smoothie.

02:25:17.180 | That that's what we are generating.

02:25:20.380 | (laughing)

02:25:21.500 | It's not a fruit salad.

02:25:23.140 | So a smoothie is a successful combination of those fields

02:25:28.140 | and a fruit salad is not.

02:25:30.380 | - I wouldn't say it's success unnecessarily.

02:25:32.580 | If you put the wrong ingredient and you press the blender

02:25:37.580 | and you've made it a smoothie,

02:25:38.740 | you mean it can ruin the entire mix.

02:25:41.500 | - Can it though?

02:25:42.340 | Because I feel like--

02:25:43.420 | - Yes, I can definitely assess that for ginger,

02:25:45.380 | for instance, that ruins every smoothie.

02:25:47.020 | I don't like it. - Ginger?

02:25:47.940 | - I think so, but it's just a personal thing.

02:25:50.020 | And also I don't like cinnamon.

02:25:51.540 | - Ginger has a cinnamony taste?

02:25:54.740 | 'Cause I thought ginger was--

02:25:55.580 | - No, I don't think they do, but I also don't like--

02:25:57.540 | - Wasn't that a thing they add in a lot of smoothies?

02:25:59.900 | I was forced a smoothie.

02:26:01.660 | I went to Malibu with a good friend of mine, Dan Reynolds,

02:26:04.500 | and he forced me to consume a smoothie.

02:26:07.020 | And it was probably the first smoothie I've ever had.

02:26:10.460 | 'Cause I always said it was very judgmental

02:26:12.180 | of the kind of places and people that drink smoothies,

02:26:14.580 | but it was good, it was good.

02:26:16.100 | - Well, smoothie is very American,

02:26:17.380 | so I-- - Yeah, it is an American thing.

02:26:19.140 | - I wouldn't say success per se,

02:26:20.700 | but it is true that when you dance

02:26:23.500 | at the edge of different disciplines,

02:26:25.060 | that that's when inevitably the innovation will rise,

02:26:29.300 | because you will see things maybe a little differently

02:26:33.500 | when you're on the edge, right?

02:26:34.500 | So, but it will probably take longer,

02:26:38.860 | and it may not be understood right away.

02:26:41.540 | It may not come into final form quickly,

02:26:45.300 | given that it is a new concept rising.

02:26:48.300 | So, therefore, the patience will make more sense.

02:26:55.300 | I'm sorry, patience will be even more important.

02:26:57.300 | So, if you are, in other words,

02:26:59.900 | if you are into immediate appreciation,

02:27:04.380 | that's probably not the way to go.

02:27:07.260 | - You're one chemical organism.

02:27:11.220 | So, let me ask maybe a little bit more of a personal thing.

02:27:14.780 | Where did your life form originate?

02:27:18.020 | And what fond memory do you have

02:27:21.140 | from the early days of childhood

02:27:23.020 | that are representative of your bacteria culture?

02:27:28.300 | - I was born in Istanbul, so I grew up in Turkey.

02:27:34.640 | It's a city that has two continents,

02:27:39.220 | which is quite interesting.

02:27:41.260 | You have a, you see a "Welcome to Europe" sign,

02:27:45.180 | and then "Welcome to Asia" sign, same day,

02:27:48.540 | depending on which part of the bridge you are.

02:27:50.840 | So, that's where I was born,

02:27:53.740 | and I spent about roughly 20 years of my life,

02:27:57.300 | and then I immigrated to United States.

02:28:00.380 | - And it's a very proud culture.

02:28:01.780 | It's a beautiful culture.

02:28:03.260 | It's a very flavorful culture.

02:28:04.980 | What aspects of it is part of who you are?

02:28:09.900 | What are the beautiful aspects

02:28:11.620 | that you carry with you in your heart?

02:28:13.520 | - I think we are very sincerely human as a culture.

02:28:20.540 | I think that we have the saying that don't go to bed full

02:28:26.100 | if your neighbor is hungry.

02:28:29.820 | So, you wouldn't eat any food in front of someone

02:28:34.700 | where I come from without offering to share the bite.

02:28:38.580 | So, I think those things, however small they may sound,

02:28:41.320 | they're really big deal,

02:28:44.300 | especially when you are put in or move to a place

02:28:48.340 | that may not have those attributes.

02:28:51.020 | So, I think that culturally, we had a lot of conscious,

02:28:55.900 | like, just raw, deep human--

02:29:00.900 | - The connection, you value the connection

02:29:03.140 | between human beings.

02:29:04.100 | - I think so, yeah.

02:29:05.060 | I think I definitely carried that with me.

02:29:07.020 | - We talk a lot about biology.

02:29:08.900 | Let me ask you about the romantic question.

02:29:11.220 | What role does love play in the human condition

02:29:15.020 | or in the entirety of life on earth?

02:29:18.760 | - It's not easy to learn how to love if you're not loved.

02:29:25.340 | Okay?

02:29:28.700 | So, this is something, but the good news

02:29:31.060 | is that it is something that you can learn, I think.

02:29:35.540 | That you can practice and teach yourself

02:29:40.480 | how to maybe give yourself the thing

02:29:42.740 | that wasn't given to you

02:29:43.900 | and then ultimately give it to others.

02:29:46.340 | I think it would be quite arrogant to think

02:29:49.660 | that we will be capable of loving.

02:29:52.820 | It could be anything, really.

02:29:54.620 | - So, just like translation,

02:29:56.740 | it's a repeating and a dynamical process.

02:29:59.500 | - That you can learn.

02:30:00.500 | - Yeah, that you can learn.

02:30:01.580 | - Yes, and you should learn.

02:30:04.260 | There's no excuse to not learning.

02:30:06.940 | - To love. - Yeah.

02:30:07.900 | - 'Cause that's a deeply human thing.

02:30:09.340 | - It is a deeply human thing.

02:30:10.380 | It is a very sad thing if any one of us

02:30:13.580 | passes this planet without knowing what love is.

02:30:18.260 | And that could be a love to a pet, a love to a plant.

02:30:21.740 | - To a robot.

02:30:22.580 | Just kidding.

02:30:24.580 | Or a fake plant.

02:30:27.580 | We can't help who we love.

02:30:31.180 | What advice would you give to a young person today?

02:30:33.860 | High school, college?

02:30:35.300 | How to have a career they can be proud of

02:30:42.060 | or how to have a life they can be proud of?

02:30:44.420 | You said an interesting thing about brains

02:30:46.540 | being distributed evenly but opportunities not.

02:30:49.180 | It's really interesting to think about.

02:30:52.620 | I've talked to folks from Africa.

02:30:55.020 | You realize that there's whole areas of this earth

02:30:58.380 | that have so much brilliance.

02:31:00.860 | But unfortunately so little opportunity.

02:31:03.020 | And one of the exciting things about the 21st century

02:31:06.780 | is more and more opportunities are created.

02:31:09.140 | And so the brilliance is unlocked

02:31:10.580 | in all those different places.

02:31:12.100 | And so all these young people now have the opportunity

02:31:15.940 | to do something to change the world.

02:31:19.620 | - I had a chance to visit Bosnia.

02:31:24.620 | So I was invited to give a talk in a very,

02:31:30.660 | very northern most part of the country

02:31:35.020 | that was impacted by the war tremendously.

02:31:38.500 | And it was a public talk.

02:31:42.660 | It was open to everybody in the village.

02:31:45.180 | And I was told even people drew from Sarajevo to attend.

02:31:48.780 | Whenever I think about our role as a scientist

02:31:54.820 | or the beneficiaries of the knowledge

02:31:59.580 | that we create, I always think about that night.

02:32:03.180 | That's how many people were in that room.

02:32:05.780 | It was incredibly crowded.

02:32:09.260 | And lots of young people who were trying

02:32:14.260 | to start everything new and not do or not carry,

02:32:19.300 | replace whatever maybe the feeling that was taken

02:32:26.580 | from them with hope and love, start a new beginning,

02:32:31.020 | be the seed for the next generation.

02:32:33.740 | And it's moved me so much that they all came

02:32:36.540 | to hear about early life space,

02:32:40.260 | something maybe different for them

02:32:41.780 | that maybe they were always interested in

02:32:43.660 | and never thought about.

02:32:44.860 | But what stayed with me was just the look and the feeling,

02:32:50.180 | the look on their faces and the feeling in the room,

02:32:52.820 | the energy just was really moving to me.

02:32:55.340 | - Their willingness to be the seed,

02:32:58.180 | the first of their family and generation

02:33:01.220 | to do that big new thing.

02:33:02.540 | - Yes, and that's exactly why I'm telling this whole story.

02:33:07.540 | Because for most of us, we may have to be that seed

02:33:13.340 | in our families, the first one to do something new,

02:33:16.700 | to break that cycle, whatever it is

02:33:20.700 | that you want to break free from.

02:33:24.260 | I would want the young people to know that you can be that,

02:33:27.500 | that there are just wonderful things

02:33:32.500 | to learn from this life.

02:33:35.700 | And it's just incredible to be living.

02:33:39.060 | And I would want them to know that their voice matters

02:33:42.300 | and they need to use it, especially those who think

02:33:47.300 | that their voice doesn't matter.

02:33:49.500 | And ultimately, I think what it comes down to

02:33:54.140 | is to trusting yourself, trusting and respecting your voice.

02:33:59.100 | If you're not loved, learn how to love.

02:34:01.540 | If you are not respected, start by respecting yourself.

02:34:04.540 | Learn how to respect yourself.

02:34:05.780 | You can teach yourself things.

02:34:07.280 | - Yeah, it's really difficult when you're surrounded

02:34:11.300 | by people that don't believe in you.

02:34:14.180 | - Yes, I definitely know the feeling.

02:34:17.900 | And I would just want them to know

02:34:20.500 | that they don't need to be defined.

02:34:24.540 | By or reduced down to what others see in them.

02:34:29.020 | - Believe in yourself, have the respect,

02:34:32.300 | try to develop the respect and the love for yourself.

02:34:35.700 | And then from that, it flourishes.

02:34:38.260 | You'll find others that'll give you love.

02:34:40.020 | - It may not.

02:34:41.300 | I mean, life is not fair, it's true.

02:34:43.260 | - Yeah, yeah.

02:34:44.460 | - Be prepared that it's not very fair, unfortunately.

02:34:49.460 | And so I don't want to depict this Disney story

02:34:52.940 | that, and then yes, and everything will be just fine.

02:34:56.220 | It's mostly isn't, but you learn a way.

02:34:58.460 | Learn, you know, life does it all the time.

02:35:00.780 | - Speaking of which, what do you think

02:35:05.660 | is the meaning of all this?

02:35:07.820 | What's the meaning of life?

02:35:09.260 | Why are we here?

02:35:12.060 | - Why we are here?

02:35:13.020 | - All the beauty you've discussed.

02:35:16.580 | Why is the translational mechanism machinery here?

02:35:22.300 | - Why?

02:35:23.140 | - I don't think there's--

02:35:23.980 | - Why so much beauty?

02:35:26.180 | - Why so much beauty?

02:35:27.300 | It is because we choose to see it that way.

02:35:30.860 | It's beautiful.

02:35:32.380 | But there is no meaning, I don't think, no, yeah.

02:35:35.580 | - But why is it so beautiful?

02:35:38.100 | Why did we choose?

02:35:39.620 | Why, from where is the imperative to see it,

02:35:44.060 | to see so much beauty in a thing

02:35:48.020 | that scientifically speaking,

02:35:50.980 | or from a rational perspective, is void of beauty?

02:35:55.700 | It's just, it just is.

02:35:57.440 | - Not everybody chooses to see the beauty.

02:36:01.540 | - Haters gonna hate.

02:36:04.940 | I mean, we have the capacity to see the beauty.

02:36:09.100 | - We have the capacity, so why not use it to the fullest?

02:36:12.340 | Right, we have the capacity.

02:36:14.100 | - But that capacity, isn't that fascinating?

02:36:16.700 | That we developed that?

02:36:18.020 | It feels like that was always laid in there

02:36:20.860 | in the whole process of life,

02:36:22.580 | this ability to find, to introspect ourselves.

02:36:28.420 | - I mean, it's definitely soothing to think like that,

02:36:31.980 | but I don't think there is a meaning like that way.

02:36:35.020 | It's fascinating that we can understand it.

02:36:38.520 | - But why is it soothing?

02:36:41.460 | There's a desire, there's a longing for it.

02:36:44.940 | - But soothing doesn't mean that there's a meaning.

02:36:48.980 | Why is soothing a meaning?

02:36:51.460 | Let me just put it this way,

02:36:52.820 | because there is just, I think, so much unfairness going on,

02:36:56.320 | I wouldn't even dare myself to think that there's a meaning

02:37:00.780 | out of respect to the ones that are suffering.

02:37:03.520 | - I see.

02:37:05.740 | I think out of suffering emerges flourishing and beauty.

02:37:12.540 | I mean, that's what I see.

02:37:13.980 | - I agree with you.

02:37:15.100 | - When I went to Ukraine,

02:37:16.980 | it's all the people suffering in their eyes

02:37:20.620 | and in their stories is a hope for the future,

02:37:23.940 | is a love for the people who are still living,

02:37:28.380 | is a love for life.

02:37:29.500 | So it's there, and that's the dark thing,

02:37:32.060 | is the suffering and the loss somehow intensifies

02:37:35.620 | your appreciation of the life that is still left.

02:37:39.420 | That's a weird thing too.

02:37:40.260 | - I think that there is something about

02:37:44.340 | still doing your best and believing that there's,

02:37:49.800 | whatever goodness is worth working for,

02:37:56.480 | is beyond, and to do that without a meaning,

02:38:03.160 | there's something more humbling and profound about that.

02:38:09.140 | And we have a,

02:38:13.780 | this will come out very random, okay, so just.

02:38:19.800 | In Turkish bathrooms, there is this sign that says,

02:38:27.060 | "Leave it as you want to find it."

02:38:32.340 | - Yeah.

02:38:35.220 | - And I think that's a pretty good--

02:38:38.620 | - That's your meaning of life found in the Turkish.

02:38:41.220 | There's wisdom to that.

02:38:42.460 | - There's wisdom to that, but it also is because

02:38:45.180 | however you leave defines you, right?

02:38:49.260 | So I think there's some profound meaning to that too,

02:38:52.460 | that just leave it as you would want to find it.

02:38:57.180 | - So that your little scribble in the long story

02:39:03.620 | of life on Earth is one that ultimately

02:39:06.740 | did a pretty good job, at least kept it the same

02:39:10.780 | as you found it.

02:39:11.620 | - Or at least I left it in the way that I wish I found it.

02:39:15.780 | - Yeah, yeah, right.

02:39:17.020 | Oh man.

02:39:20.420 | - Yes, that's the wisdom from Turkish bathrooms.

02:39:22.620 | - That's where I search for wisdom as well.

02:39:25.260 | And as we started with the origin of life

02:39:29.860 | and ended with the wisdom in a Turkish bathroom,

02:39:33.140 | I think that's a perfect conversation.

02:39:34.740 | You're an incredible person.

02:39:36.860 | The humor, the humanity,

02:39:38.780 | but also the brilliance of your work.

02:39:40.700 | I really appreciate that you would talk with me today.

02:39:43.300 | This was really fun.

02:39:44.780 | - Thanks for having me.

02:39:46.780 | - Thanks for listening to this conversation

02:39:48.380 | with Batool Kachar.

02:39:49.900 | To support this podcast,

02:39:51.060 | please check out our sponsors in the description.

02:39:53.660 | And now let me leave you with one of my favorite quotes

02:39:56.820 | from Robert Frost.

02:39:57.980 | "In three words, I can sum up everything

02:40:00.780 | "I've ever learned about life.

02:40:02.900 | "It goes on."

02:40:05.940 | Thank you for listening.

02:40:07.260 | I hope to see you next time.

02:40:09.020 | (upbeat music)

02:40:11.620 | (upbeat music)

02:40:14.220 | [BLANK_AUDIO]

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

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