Pod Insights From First Principles JWST’s “Little Red Dots,” TimeVaults, and the Dawn of Math (EP. 23) About this episode Hosted by Lester Nare and Krishna Choudhary, this episode runs from JWST’s “Little Red Dots” (and what they imply about early supermassive black holes), to a TimeVault method for recording gene expression over time, to 8,000-year-old Halaf pottery that may encode geometric sequences — plus a quick Cloud9 follow-up on the “starless dark-matter halo” debate.
Summary
JWST’s Little Red Dots — why these compact red sources don’t behave like normal galaxies or quasars, and how an ionized-gas “cocoon” model could reconcile the data.
TimeVaults — a genetically encoded “vault” that protects RNA long enough to capture time-series biology, not just snapshots.
Math before numbers — Halafian motifs that appear to follow geometric sequences (4–8–16–32–64) and what that suggests about early cognition.
Cloud9 update — what new data would actually settle RELHIC vs. “dark galaxy.”
Show Notes
JWST “Little Red Dots” (Nature)
TimeVaults (Science)
Halaf pottery + prehistoric mathematical thinking (Journal of World Prehistory)
Cloud9 / RELHIC follow-up (arXiv)
Transcript 17,878 words · 2 speakers
Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.
0:00 Lester Nare? Hello, Internet. This is your captain speaking, Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary. We have three great stories lined up for you today, along with the rundown. We're gonna hit astrophysics, genomics, ancient mathematics, couple of housekeeping items at the top of the show. Our new collaboration episode with the guys over at Curiosity Theory is now available on their channel. The episode is focused on the future of intelligence. It's part one of two. It's a great conversation, definitely worth a watch. And at the end of this story, we're gonna do a follow-up
0:39 Lester Nare? from episode 22, as it relates to the Cloud Nine story that we covered, the gas cloud. Because we got some interesting insight about the naming conventions and some of the background from the scientists who put the paper out.
0:53 Krishna Choudhary? Yeah, that was really cool. We sent out the video to the scientists, the authors of that study, and they were gracious enough to give us some of the backstory. So it's really interesting.
1:05 Lester Nare? As always, you're gonna learn something today, because this is from First Principles.
1:25 Lester Nare? For our first story, we're gonna dive into the James Webb Space Telescope in an astrophysics story that was a research paper published in Nature about the little red dots as young supermassive black holes in dense ionized cocoons. This is a paper out of the University of Manchester, University of Copenhagen, and the Cosmic Dawn Center. And it's a Nature study that reveals that these young, supermassive black holes are hiding in dense cosmic cocoons that we were able to sort of get more insight from because of this high-fidelity, high-quality JWST spectra. So what's this story all about?
2:09 Krishna Choudhary? Yeah, so I don't know if you remember, but back in July 2022, JWST came online. I was traveling in Europe and it was a whole frenzy. And within two weeks of when the data was released, we had headlines like this from the Scientific American that said, "The first glimpses of early galaxies could break cosmology." You know, JWST was seeing universe breakers. And it was like, all of astrophysics was, you know, "Oh my God, what's gonna happen? What's gonna happen?" And what it was all about was there were these spots of red light everywhere at really high red shifts. And if they're really far away, that means that they're really old, but that also means that they're very young for the universe, right?
2:53 Krishna Choudhary? Because the universe was only less than a billion years old and we were seeing galaxies. And in order to make galaxies, you need a lot of time, right? And so even there was like creationists that were like going gangbusters, saying that, "Oh, this is proof of God created the universe and all of that stuff." So the focus of our study is something called little red dots. And that is the technical term.
3:19 Lester Nare? Is it really?
3:20 Krishna Choudhary? It is literally the technical term. These are little red dots in the JWST deep field surveys. And they're at a really high red shift, which means they're very young in terms of when the universe was born. So this is, you know, about a billion years, less than a billion years after the Big Bang. And the problem is they're really compact. And the debate is, if these are star-filled galaxies, the galaxies shouldn't have had enough time to become galaxies, okay? Because it takes time to form stars and then from those stars to amass and become a clustered, gravitationally attracted object like a galaxy.
4:01 Lester Nare? And this idea is based off of our current like cosmological models of how the early universe, the mechanics and the dynamics of the early universe.
4:10 Krishna Choudhary? Yes, yes. Based on how much we know dark matter is there, how much we know dark energy is there. In the beginning, there was not a lot of dark energy because the universe was small and dark energy scales with how big the universe is. So. In the beginning, there was really just a lot of dark energy. Sorry, there was a lot of dark matter and a lot of normal matter. But more dark matter than normal matter. And those models of our universe tend to not have galaxies so young.
4:40 Lester Nare? Right.
4:41 Krishna Choudhary? Okay, so these became these universe breakers. And then the debate was, okay, maybe they're not star-filled galaxies, but maybe they're just weird massive black holes.
4:48 Lester Nare? Okay.
4:49 Krishna Choudhary? And you would think, okay, like, maybe that's gonna solve this universe breaking thing. No, it still doesn't because those black holes are, again, too big for how young the universe was.
4:59 Lester Nare? Right.
5:00 Krishna Choudhary? So it was a real conundrum for a while, and this paper might have the answer.
5:03 Lester Nare? Okay.
5:04 Krishna Choudhary? That's the idea.
5:05 Lester Nare? Beautiful.
5:05 Krishna Choudhary? And so it's quite a big deal if it, you know, holds up to scientific scrutiny.
5:10 Lester Nare? Because it's both, it's going to solve this new problem that has arisen as we've gotten higher quality data that's giving us experimentally in the real world, information that doesn't quite map onto our existing models of the early universe.
5:23 Krishna Choudhary? Exactly, and that's why, I mean, people were so excited when the James Webb Space Telescope went online.
5:30 Lester Nare? This is exactly.
5:30 Krishna Choudhary? Because we knew there was gonna be all sorts of random stuff that we were gonna see that we'd never seen before. And, you know, we're at the forefront of technology. It was launched in 2021, late 2021. It came online in July 2022, and these deep space fields were crucial. This is a photo of the James Webb. It was folded up. Incredible engineering feat, by the way, to even get such a scientific instrument to be folded up.
5:59 Lester Nare? Yes.
5:59 Krishna Choudhary? Inside a rocket and then have it go to a Lagrange point. So not even in Earth orbit, really far away from Earth orbit. Get it parked there, have it unfold like origami, no issues. And Biden made an announcement being like, we got this amazing data. And two weeks after that amazing data was published, everyone was like, what's going on? Right? So one of the crucial things about the James Webb Space Telescope is it is an infrared telescope. Unlike the Hubble, which is optical, the James Webb is an infrared telescope. And the reason why it is sensitive in infrared is because infrared is wavelengths of light that are longer than optical. And we want it to be that way because.
6:44 Krishna Choudhary? We want to look at the very depths of the universe, okay? Really, really far back. And because the universe is expanding, you have something called a gravitational red redshift. Actually, no, it's called a cosmological redshift. What ends up happening is light that is coming from really far away. As the universe stretches, you can imagine a little sine wave and then I stretch that sine wave like a spring.
7:10 Lester Nare? Yeah.
7:10 Krishna Choudhary? So the wavelength is going to stretch out.
7:12 Lester Nare? Yes.
7:12 Krishna Choudhary? So if I'm in infrared, I can catch these highly red shifted light.
7:18 Lester Nare? Yes.
7:19 Krishna Choudhary? And that's exactly what we see in this photo. And we see as we get farther and farther into the universe, closer and closer to the Big Bang, the spectra, these unique fingerprints where oxygen should be emitting light or where hydrogen should be emitting light. That stuff gets stretched more and more into the infrared. The James Webb being an infrared telescope means that we are sensitive to that infrared.
7:44 Lester Nare? Got it.
7:44 Krishna Choudhary? Okay.
7:45 Lester Nare? Right. So we sort of have, instead of seeing a fuzzier image of things kind of blending, there's more discreteness in what we're looking at because it's, we're not limited to light has to travel and things are getting squished at these these scales. Sorry, stretched at these scales. And so we need to expand what we're looking at in order to capture just more clarity.
8:07 Krishna Choudhary? Yes.
8:07 Lester Nare? And understanding what.
8:08 Krishna Choudhary? Yeah, we want to be sensitive to that correct part of the of the spectrum, right?
8:13 Lester Nare? That makes sense.
8:13 Krishna Choudhary? And so that's where these little red dots come in. And they're literally called little red dots. Okay. Weird thing about them is they they show up all over the place, about 600 million years to 800 million years after the Big Bang. But then they vanish out of existence 1.5 billion years after the Big Bang. And we don't see any of them. It's kind of like dinosaurs where like dinosaurs were alive for, you know, 300 million years to 65 million years before us.
8:40 Lester Nare? Yeah.
8:40 Krishna Choudhary? And then they're just gone.
8:41 Lester Nare? Yeah.
8:42 Krishna Choudhary? So it's got these little red dots are like dinosaurs from the early universe that are no longer there in any nearby galaxies.
8:50 Lester Nare? Interesting.
8:50 Krishna Choudhary? So it's very weird.
8:51 Lester Nare? Yes.
8:52 Krishna Choudhary? Right?
8:52 Lester Nare? That is curious.
8:53 Krishna Choudhary? The other thing about them is they're really small. Okay, they're really, really small. If you look on the right hand side, on the left hand side, we've got one of the JWST deep fields and on the right hand side, we have a close up of one of these red dots. And if you look really closely, that red dot has a sort of hexagonal hue around it. That hexagonal hue is an artifact of the James Webb Space Telescope's design because the James Webb has a primary mirror and then a secondary mirror. That's sort of the light comes in primary, goes to the secondary and then goes to the detector. And the scaffolding that is holding up that secondary mirror has three sort of rods that holds it up.
9:38 Krishna Choudhary? So those rods are going to cause something called diffraction spikes.
9:42 Lester Nare? Okay.
9:42 Krishna Choudhary? They're just artifacts of the fact that the secondary mirror has these three rods holding it up. In the Hubble, there's four. And so you see for the Hubble photographs, the diffraction spikes are
9:55 Lester Nare? Yeah, right.
9:55 Krishna Choudhary? in diamond shape.
9:56 Lester Nare? Diamond shape.
9:57 Krishna Choudhary? But in the James Webb, they'll be in hexagonal shape.
9:59 Lester Nare? Makes sense.
10:00 Krishna Choudhary? Okay. So, but the fact that we're seeing those diffraction spikes for those little red dots means that they're localized point sources. And we can actually calculate how big they are and they'd be about 150 to 500 light years across. That's really light, light years across.
10:15 Lester Nare? Light years.
10:16 Krishna Choudhary? Right? The Milky Way is on the order of 100,000 light years.
10:21 Lester Nare? Okay.
10:21 Krishna Choudhary? Okay? The Milky Way is much bigger
10:23 Lester Nare? Okay.
10:24 Krishna Choudhary? than these things by a factor of 100 to 1,000.
10:27 Lester Nare? Okay.
10:27 Krishna Choudhary? So perhaps they are just like black holes. This is the first clue that maybe they're black holes. They're really compact objects, right? They have a lot of activity and a lot of mass. So, yeah, seems like a black hole.
10:39 Lester Nare? Tracks.
10:39 Krishna Choudhary? Okay, so if it's a black hole, we'd like to calculate its size.
10:44 Lester Nare? Right.
10:45 Krishna Choudhary? Okay? How do we calculate a black hole size? Well, in the Milky Way, the way we calculated the black hole sizes, we had Andrea Guz from UCLA. She watched the black hole for about 20 years and charted the Path of stars that were nearby. And then you just do Newton's laws.
11:02 Lester Nare? Right.
11:02 Krishna Choudhary? And you figure out how big is the compact object on the inside. Now, if we've got a black hole that is at the edge of the universe, 13 billion light years away, how are we going to do it? Well, we use something called the Doppler broadening of spectral lines. Okay. Effectively, what's happening is this. We look at a certain spectra. Let's say H alpha, which is an intrinsic piece of light that comes out of hydrogen. Okay. Now, if the hydrogen is not moving at all and it's static, that line is going to be really sharp. But in a black hole, there's going to be stuff moving around in an accretion disk. Right? So there's going to be hydrogen that's moving away from us.
11:41 Lester Nare? Yes.
11:41 Krishna Choudhary? And hydrogen that's moving towards us.
11:43 Lester Nare? Yes.
11:44 Krishna Choudhary? So there's going to be some bits of H alpha, the light, that is going to be blue shifted. So the wavelength will be shorter. And then there's going to be some bits that are red shifted because it's moving away. And the wavelength is going to be longer. And what's that going to, what that's going to cause is my H alpha line, which used to be just a really well-defined frequency. It's going to broaden.
12:03 Lester Nare? I see.
12:03 Krishna Choudhary? Right? And that's called Doppler broadening.
12:05 Lester Nare? This is what we're seeing here.
12:07 Krishna Choudhary? And that's what we're seeing here. We get a nice Gaussian profile.
12:10 Lester Nare? Yes.
12:10 Krishna Choudhary? Of our spectral line. And that Gaussian profile, from there, we can then back calculate, how fast does the gas need to be moving around to create that broadening? Right? And then you can apply the virial theorem, which is something in basic physics. The mass is proportional to the velocity squared. And from that, you get something like a number that is 10 to the 7 to 10 to the 9 times the mass of the sun. So it's like, you know, a billion to 100 million, tens of million times the mass of the sun. This is for something that is moving at 2,000 kilometers per second. That's what we can calculate back from the broadening is the velocity. And from the velocity, we calculate back the mass.
12:51 Lester Nare? Got it.
12:51 Krishna Choudhary? Okay. So we're getting 10 to the 7 times, or 10 to the 9, mass of the sun.
12:56 Lester Nare? As the, as the scale of these, of...
12:58 Krishna Choudhary? Of how big these black holes should be.
13:00 Lester Nare? Should be.
13:01 Krishna Choudhary? Right?
13:01 Lester Nare? How big they should be.
13:03 Krishna Choudhary? Okay. So you would think that, okay, we're good, right? Like, they're not galaxies, they're just black holes.
13:08 Lester Nare? Mm-hmm.
13:09 Krishna Choudhary? Not so fast.
13:10 Lester Nare? Okay.
13:11 Krishna Choudhary? Okay? There's two problems with these masses. For one thing, these black holes are way too big for... Whatever galaxy this little red dot is, if this little red dot is a galaxy and at the center is this active galactic nuclei, that's, you know, churning up a bunch of mass and then spewing it out as radiation, then those black holes are about 10 to 100% the host stellar mass. Okay. In contrast, for our Milky Way, the center of the galaxy where the black hole is, that black hole is only 0.1% of the entire mass of the Milky Way.
13:48 Lester Nare? So this is, the math is not math.
13:50 Krishna Choudhary? The math is not mathing. Okay. Sagittarius A star at the center of our Milky Way is only 0.1% of the total mass of the Milky Way. And here I'm getting 10% to 100% the total mass. Like the whole thing is a black hole.
14:02 Lester Nare? They're way too massive.
14:03 Krishna Choudhary? Yeah. It doesn't make any sense. Okay. Yeah. The second thing is, okay, so you're, you're telling me that these black holes are 100 million times the mass of the sun, right? How did it get that big? Well, the way that black holes get big is through accretion, right? It's like taking in mass and it's eating up mass. And as it eats up all this matter, it gets bigger and bigger. There's a caveat to it though. Okay. It can't just like eat endlessly.
14:31 Lester Nare? It's not like those video games where you just eat the whole city around you.
14:34 Krishna Choudhary? Yeah. And like a single, yeah. And like a single moment, you can't do that. You've got to take your time with your meal. That's the point. There's something called the Eddington limit. Okay. And it says there's a maximum luminosity to accretion rate before I'm eating too much. And when I eat all that much, I'm going to spew out radiation. That radiation is going to shock all of the rest of my food away. You see what I'm saying? It's the same argument of hydrostatic equilibrium that we've been visiting a lot on this podcast.
15:06 Lester Nare? Yes.
15:07 Krishna Choudhary? The idea is, If I eat too fast, then the radiation from all of that eating, because the black hole is gonna accrete all this mass, the mass is gonna start heating up, that's gonna cause radiation. That radiation is gonna be enough to shoo all of the rest of my mass away.
15:25 Lester Nare? Yes.
15:26 Krishna Choudhary? So there's a maximum limit at which I can grow.
15:29 Lester Nare? 3,000 calories a day, max.
15:31 Krishna Choudhary? Max, right? And if you do too much, then there's no food around you.
15:34 Lester Nare? Right, right.
15:35 Krishna Choudhary? Okay, that's the idea.
15:36 Lester Nare? Look, that's very interesting.
15:37 Krishna Choudhary? Okay, so that's something called the Eddington limit. It's named after Arthur Eddington, who's a amazing man of science in history, also a bit problematic, and by a bit, I mean a lot, but that's...
15:50 Lester Nare? For another episode.
15:50 Krishna Choudhary? For another episode. In any case, he finds this sort of limit to how much stars can grow, what's the luminosity of these stars, and you can apply that same logic to black holes.
16:01 Lester Nare? Got it.
16:02 Krishna Choudhary? Okay, so from that, we get an accretion rate. It's like, how much am I eating?
16:07 Lester Nare? Yes.
16:08 Krishna Choudhary? And from that, I can have a characteristic growth time scale of like, how much time do I need to grow by a certain factor?
16:16 Lester Nare? Because you know what your limit on eating is, and so you'll know if I'm trying to gain 10 pounds or lose 10 pounds.
16:21 Krishna Choudhary? Yeah, how long is that gonna take? Right?
16:23 Lester Nare? Because you have a max.
16:24 Krishna Choudhary? Yeah, and for this, by a factor of E, because everything is an exponential, exponential to the E, so if I wanna grow by a factor of E, which is like 2.7-ish, I need to wait 50 million years.
16:35 Lester Nare? Yeah.
16:36 Krishna Choudhary? All right?
16:36 Lester Nare? Sure.
16:37 Krishna Choudhary? 50 million years to grow by a factor of 2.7. All right. Now, these red dots that we see in the universe, they're at a redshift of 7, which means they're approximately 800 million years after the Big Bang.
16:49 Lester Nare? Mm-hmm.
16:51 Krishna Choudhary? 800 million years is not a lot of time.
16:53 Lester Nare? No.
16:54 Krishna Choudhary? Even, especially for growing at only 50 million years per factor of 2.7.
17:00 Lester Nare? Right.
17:01 Krishna Choudhary? Okay?
17:01 Lester Nare? Right.
17:01 Krishna Choudhary? So there's two possibilities. One is you've got these light seeds, light as in like, light instead of heavy.
17:09 Lester Nare? Okay.
17:09 Krishna Choudhary? You have the first stars. These are population 3 stars. They're the remnants of... The very first stars, when the very first stars that are, you know, about, let's say a hundred mass, a hundred times the mass of the sun, or a thousand times the mass of the sun, very, very old stars, when they blow up, they're gonna make a black hole. And that black hole is gonna be about a hundred times the mass of the sun. And so in order to reach 10 to the nine times the mass of the sun, in 800 million years, you gotta be continuously eating at the addington limit.
17:40 Lester Nare? I see, stuffing your face.
17:42 Krishna Choudhary? Stuffing your face for like hundreds of millions of years. You gotta, you gotta be going like, like the, the hot dog eating competition. Have you seen those?
17:52 Lester Nare? Kobayashi.
17:53 Krishna Choudhary? Yeah, dude. So, so you got, like, you gotta be in the zone.
17:57 Lester Nare? Yes.
17:57 Krishna Choudhary? For hundreds of millions of years.
18:00 Lester Nare? Constantly.
18:00 Krishna Choudhary? Constantly. Very improbable.
18:03 Lester Nare? Seems, yeah.
18:05 Krishna Choudhary? Seems improbable to just be going at it.
18:07 Lester Nare? Yes.
18:07 Krishna Choudhary? Right? Okay. So the second possibility is there's heavy seeds, which is this direct collapse. You don't make a star, you just got a gas cloud, the gas cloud maybe runs into another gas cloud, reaches critical mass, and then the whole thing just falls inside the Schwarzschild radius, you get a black hole, no star needed. For that, the advantage is, you, you can reach that high mass, 10 to the nine mass of the sun, you can reach that. But the conditions gotta be perfect. You gotta have really pristine gas, it's gotta be like sort of spherically symmetric, and you need a lot of UV background, so that the, the gas doesn't cool down to form stars.
18:47 Lester Nare? Right.
18:47 Krishna Choudhary? It has to like really just be focused on making a black hole.
18:50 Lester Nare? Which is.
18:50 Krishna Choudhary? Again, improbable.
18:52 Lester Nare? Right, right.
18:53 Krishna Choudhary? Right?
18:53 Lester Nare? So the idea is the current, the, the light seed and heavy seed options, uh, don't pass the sniff test.
18:59 Krishna Choudhary? Yeah, they, they really don't. It's like both are like super improbable. On the one hand, you have, you have like a black hole that is just eating max out, like in the zone. And then the second, the, the conditions to create that first black hole are like perfect. Okay? And the number of these little rodas that we're seeing, it just doesn't make sense.
19:18 Lester Nare? There's too many.
19:19 Krishna Choudhary? There's too many for all of them to have just this perfect. Like condition.
19:24 Lester Nare? The idea is we're seeing so many of them. So you're saying this thing that's improbable is happening
19:28 Krishna Choudhary? Like.
19:28 Lester Nare? Frequently.
19:29 Krishna Choudhary? Yeah.
19:29 Lester Nare? Which is the whole. The whole point.
19:31 Krishna Choudhary? Yeah. So what are we doing? All right. So, so this was the big conundrum, right?
19:35 Lester Nare? Yes.
19:36 Krishna Choudhary? So what can we do? Well, let's point an X-ray telescope at it. So they had the Chandra X-ray telescope pointed at it. No X-rays. That's weird.
19:44 Lester Nare? Okay.
19:44 Krishna Choudhary? Black holes spew a lot of X-rays.
19:47 Lester Nare? Okay.
19:47 Krishna Choudhary? Because stuff gets really hot. And if stuff gets really hot, it's gonna like spew out very high energy radiation. It also, there's no radio emissions. You look at, you look at it from the earth with really nice radio telescopes that can localize that point source. No radio emissions. Black holes should have radio emissions because there's high magnetic fields. And if charged particles are spinning around in that high magnetic fields.
20:11 Lester Nare? It's gonna shoot off.
20:12 Krishna Choudhary? They, they're gonna shoot off at radio waves. So no X-rays, no radio waves. What do we have? Well, let's look at the photo.
20:19 Lester Nare? What do, what do we?
20:20 Krishna Choudhary? What do we have? Well, the James Webb Space Telescope has a really nice spectrograph, right? So we can look at the photometric spectra. And this is from a particular little red dot called the cliff.
20:30 Lester Nare? The cliff.
20:31 Krishna Choudhary? And the cliff, you can see the cliff, right?
20:33 Lester Nare? Yeah.
20:34 Krishna Choudhary? So at shorter wavelengths, you've got a little bit of light coming through in the ultraviolet.
20:38 Lester Nare? Yeah.
20:38 Krishna Choudhary? And then right at about 300 and like 380 nanometers, you get a, you get a really high spike. Everything that's over that 365, sorry, 365 nanometers, you get a lot of light coming in.
20:56 Lester Nare? Yeah.
20:56 Krishna Choudhary? Okay. So you get this like distinct V shape.
20:59 Lester Nare? Yeah.
20:59 Krishna Choudhary? This particular one is called the cliff because it's such a nice spectra.
21:03 Lester Nare? Yeah.
21:03 Krishna Choudhary? Okay. So the question is, what would actually cause a spectral like this? Where you've got a little bit of ultraviolet, but right at 365, there's nothing, almost nothing. And then for any wavelength longer than 365, you've got a lot of light coming through. Well, 365 nanometers, and this is in the rest frame. So they had to, you know, shift everything to suppose I was, suppose this thing wasn't moving away. Because in reality, that light is gonna be somewhere in the infrared, right? Because it's moving away. But you can shift it back into the rest, rest frame. And you can say, okay, at 365, there's nothing. And then anything higher than 365 nanometers, which means lower in energy, because higher wavelength, lower energy.
21:48 Krishna Choudhary? We're getting a lot of light.
21:49 Lester Nare? Let there be light at 365.
21:51 Krishna Choudhary? So 365 nanometers is something called the Balmer limit. Okay, this is what happens because any piece of light that is higher energy than the 365 nanometer wavelength, it ionizes hydrogen. That photon has enough energy to kick out an electron if the electron is in the second shell of hydrogen. Okay, so any photon that is in lower energy, meaning longer wavelength, that's not going to be able to kick out that hydrogen and it's not going to be able to ionize. And this is actually something that we see a lot in stellar atmospheres because stellar atmospheres have a lot of ionized hydrogen. This is a blueprint of a blue supergiant spectrum.
22:36 Krishna Choudhary? And there you can see right at about that Balmer limit, you're going to get a massive discontinuity.
22:43 Lester Nare? Yes.
22:44 Krishna Choudhary? Where there's a bunch of stuff at a higher wavelength because those photons don't have enough energy to ionize hydrogen. But the stuff that's with a smaller wavelength, so higher energy, those things ionize hydrogen, no problem. And the electron goes off and does whatever it wants to do. Right? So that's the key. The key here is that the ionized hydrogen around a star could be causing this.
23:11 Lester Nare? Okay.
23:12 Krishna Choudhary? Okay.
23:12 Lester Nare? Yeah.
23:13 Krishna Choudhary? So the key insight of this paper is to say, all right, suppose I were to take that ionized hydrogen idea and I were to put that ionized hydrogen envelope around a black hole.
23:26 Lester Nare? I see.
23:27 Krishna Choudhary? What would that mean?
23:28 Lester Nare? What would that mean?
23:29 Krishna Choudhary? Okay. And that's the key insight of this paper.
23:33 Lester Nare? It's funny because we've been talking about reionization and hydrogen
23:39 Krishna Choudhary? Yeah.
23:39 Lester Nare? in in astrophysics, cosmology and space in a couple of our previous episodes. So folks will have a good grounding for this conversation based on several of our past.
23:49 Krishna Choudhary? Exactly.
23:49 Lester Nare? Stories.
23:50 Krishna Choudhary? Yeah, and and this paper came out in, I think it was Nature. We have the.
23:55 Lester Nare? Yes, it was in Nature, January. Thirteenth twenty twenty six.
23:58 Krishna Choudhary? Right. So, so very recently, and this is photo thirteen, just to show
24:02 Lester Nare? Yes.
24:03 Krishna Choudhary? Our folks what the, what the paper looks like. Little red dots as young, supermassive black holes in dense ionized cocoons. That's where the ionized cocoons comes in. It's an ionized cocoon of stuff around my black hole.
24:16 Lester Nare? That, okay.
24:17 Krishna Choudhary? And the key is that that hypothesis then lays to rest all of the different conundrums that we've had.
24:24 Lester Nare? I see.
24:25 Krishna Choudhary? Okay.
24:25 Lester Nare? I see. Like when we talked about earlier about it's over massive.
24:29 Krishna Choudhary? Yeah.
24:29 Lester Nare? And
24:30 Krishna Choudhary? The thing is too big.
24:32 Lester Nare? Uh, the Eddington limit. So we can't accrete enough to like be able to get to that size. But the, the, the note here is that this, the, the ionized hydrogen envelope that's around it is what is making what we're measuring or seeing look the way.
24:48 Krishna Choudhary? Look the way it is. And so perhaps these black holes aren't as big
24:52 Lester Nare? Hmm.
24:52 Krishna Choudhary? As we thought they were.
24:53 Lester Nare? I see. I see.
24:55 Krishna Choudhary? That's the idea.
24:56 Lester Nare? Okay.
24:56 Krishna Choudhary? Okay.
24:56 Lester Nare? Okay.
24:57 Krishna Choudhary? So the inside of the ionized gas cloud means we can, we can now recalculate the mass of these black holes. Because the line broadening, before we thought the line broadening just had to do with the, uh, the hydrogen spinning around the black hole. And then from that, we calculate what the mass should be for it to spin around at that rate. Okay. Well, if there's ionized hydrogen, then what we're gonna see is not the actual photons from the accretion disk, but we're gonna see those photons get released. And then they're gonna bounce around in the ionized hydrogen because the ionized hydrogen is just plasma.
25:32 Lester Nare? Mm hmm.
25:32 Krishna Choudhary? And plasma means that light doesn't really have a free path to travel all the way to us.
25:38 Lester Nare? Mm hmm.
25:38 Krishna Choudhary? Right? It's going from here to there. And so the photons undergo this random walk of free electrons in a highly ionized environment. So you've got the black hole in the center.
25:50 Lester Nare? Mm hmm.
25:50 Krishna Choudhary? And it releases a Gaussian profile.
25:52 Lester Nare? Yes.
25:53 Krishna Choudhary? Because of the accretion, but by the time it gets to us.
25:56 Lester Nare? Yes.
25:56 Krishna Choudhary? By the time it gets to the James Webb, it's gonna be bouncing around this hydrogen atom, then this electron, then this hydrogen, then this electron, electron, blah, blah, blah. And you're gonna get this Thompson scattering. The electron, the free electrons are gonna scatter around.
26:12 Lester Nare? Yes.
26:13 Krishna Choudhary? Okay?
26:13 Lester Nare? Yes.
26:14 Krishna Choudhary? And when that happens, the Gaussian profile is actually gonna resemble more of an exponential decay on both sides. So the way to test this. And in physics and in science, really, a lot of times what it comes down to is can you get good enough data to discern one theory from another? So the two theories that are competing in this case are it's a Gaussian profile, so it's a bell curve, and the other one is it's a exponential decay.
26:43 Lester Nare? Yes.
26:44 Krishna Choudhary? The James Webb style telescope is giving us good enough data where we can discern between those two theories. And that's why it's so important to get really good data.
26:54 Lester Nare? And which, which means we have to build really great instruments.
26:57 Krishna Choudhary? Yeah, and the James Webb is just a phenomenal instrument. And so here you can see from their paper, they fit an exponential and then they fit a Gaussian. And the errors when it comes to fitting an exponential are basically zero. That's the teal color. And then if you look at the purple, there's plenty of error.
27:16 Lester Nare? Yeah, yes.
27:17 Krishna Choudhary? The exponential fits this profile a lot better.
27:21 Lester Nare? The model, the exponential model of the theory to explain why we're seeing the, what we believe to be these, you know, black holes look the way they do, this ionization of hydrogen, which then ends up having this exponential decay on this, that, that we did theoretically on paper.
27:44 Krishna Choudhary? Yeah, yeah, we're like, we're like, okay, if there's a cocoon of hydrogen that's ionized, so a bunch of plasma that's like diffuse.
27:51 Lester Nare? Yes.
27:51 Krishna Choudhary? What would it look like? Well, it would look like an exponential. So let's fit an exponential.
27:54 Lester Nare? And then we got the experimental data of high fidelity from JWST that now is like, oh yeah, that's exactly what we're seeing.
28:00 Krishna Choudhary? That's exactly right, yeah. And now, instead of 2,000 kilometers per, per second.
28:05 Lester Nare? Yes.
28:05 Krishna Choudhary? That the accretion disk is going around.
28:07 Lester Nare? Yes.
28:08 Krishna Choudhary? Instead, it's something like 300 kilometers per second.
28:12 Lester Nare? Right.
28:13 Krishna Choudhary? So actually, the accretion disk isn't moving all that fast. The broadening is happening because of the plasma that's all around.
28:20 Lester Nare? Surrounding it, not the actual internal structure of the black hole itself.
28:23 Krishna Choudhary? Exactly.
28:24 Lester Nare? So it, I guess to, the intuition is then that means the black holes are much smaller and much younger.
28:29 Krishna Choudhary? Yes.
28:30 Lester Nare? Because they're not supermassive and they're not going very, very quickly. That's all being sort of obfuscated by the amount of. Plasma ionized hydrogen that's around this really young, small black hole.
28:43 Krishna Choudhary? That's exactly right.
28:44 Lester Nare? Okay.
28:45 Krishna Choudhary? Yeah. And so when you redo the estimate for the mass, you get something like 10 to the five, which is, you know, several orders of magnitude, but below
28:53 Lester Nare? Right.
28:54 Krishna Choudhary? what we had earlier.
28:55 Lester Nare? Right.
28:55 Krishna Choudhary? And now this makes sense.
28:56 Lester Nare? Yeah, now it's now fits.
28:57 Krishna Choudhary? Now it fits. It's like now you can have that light seed of the population three stars. But this thing, this guy doesn't have to constantly eat like a hot dog contest for hundreds of millionaires. He can take breaks, you know, he can go sub Eddington limit and like he'll be fine. He'll make it, he'll make it to this far.
29:14 Lester Nare? Yes.
29:14 Krishna Choudhary? You know?
29:15 Lester Nare? So and given the volume of these that we're seeing, it then also matches the like frequency of its appearance. Like, okay, these are.
29:24 Krishna Choudhary? This is probable now.
29:25 Lester Nare? Yes.
29:26 Krishna Choudhary? You know, and then, and then now it's kind of explains why there's so many of them. The missing X rays also makes sense because all of these X rays are now going to get absorbed by the plasma.
29:35 Lester Nare? Right.
29:35 Krishna Choudhary? So we don't see the X rays. The red color makes sense because the cocoon absorbs the high energy light and then re emits it in the lighter part of the spectrum, the redder part of the spectrum.
29:46 Lester Nare? I was gonna ask earlier, I'm like, I thought black holes were like black holes of light, but I get the accretion disk and then stuff happens. I'm like, why is it, why was it red was kind of.
29:54 Krishna Choudhary? Yeah. Yeah. But it's just, I mean, the, the stuff around the black hole is so hot that it's releasing a bunch of, a bunch of light, right?
30:00 Lester Nare? Which makes sense.
30:01 Krishna Choudhary? And then it also explains the black hole mass problem because now you don't need this accretion. And the host mass, you know, before we used to think, oh, this thing is like 10% to 100% of the, of the host galaxy.
30:13 Lester Nare? As opposed to the point one we see.
30:14 Krishna Choudhary? Yeah. Yeah. And now you can see in the, the final figure in their paper is actually showing, so the, the, the gray circles
30:23 Lester Nare? Yes.
30:23 Krishna Choudhary? are what it would be without their hypothesis. And you can see the masses decreasing.
30:28 Lester Nare? Yes.
30:29 Krishna Choudhary? Because they use this exponential fit and they're saying, actually, these black holes are not that massive. And the blue line is what the theory says.
30:36 Lester Nare? Right. So it's.
30:37 Krishna Choudhary? And it's like lining up very nicely.
30:38 Lester Nare? Yeah, yeah, yeah, yeah.
30:39 Krishna Choudhary? Right?
30:40 Lester Nare? Yep. Yes.
30:41 Krishna Choudhary? Now, there's caveats. They only analyzed 12 of these and we've seen, you know, several hundred.
30:48 Lester Nare? Okay.
30:48 Krishna Choudhary? So it could be that there's a bunch of different things. And not, it's not like a one, um, one answer fits all little red dots, right? Some of them could be young galaxies and then there's always more questions. But this at least puts a lot of the black hole theories.
31:05 Lester Nare? Yes.
31:07 Krishna Choudhary? To rest. Like it's making sense now.
31:10 Lester Nare? Yes.
31:10 Krishna Choudhary? Okay, the universe did, the big bang did start three point, 13.6 billion years ago. And right after the big bang, within a billion years, there were black holes, but they weren't that big. It's fine, but because there was so much gas around at the time,
31:24 Lester Nare? Yes.
31:25 Krishna Choudhary? You could have these ionized cocoons. Nowadays you can't because the gas is so sort of diffuse.
31:30 Lester Nare? Yeah, we have Pepto Bismol now, so.
31:32 Krishna Choudhary? Exactly. The universe is 13.6 billion years old. The universe needs some Pepto Bismol, you know? But I thought, I thought that was really cool. Just the way that, you know, it, it's, it's a recurring theme in astrophysics research, actually, that the closer you measure something, the better you can discern between two competing theories.
31:53 Lester Nare? Right, right, right.
31:54 Krishna Choudhary? And like, it goes all the way back to Kepler and Tycho Brahe. Tycho Brahe was this really rich guy who had a very nice observatory, not with lenses and stuff, but an observatory to point out locations of planets. And he tracked the locations of planets to a really high degree of accuracy. And then Kepler, who was the mathematician, was able to. Took that data and he was trying to fit Copernicus's model of circles.
32:22 Lester Nare? Yep.
32:23 Krishna Choudhary? And he's like, the circles don't fit, but the ellipses do fit. And the difference between the ellipse and the circle was really small because the, the orbits of the planets are basically circles.
32:34 Lester Nare? For sure.
32:35 Krishna Choudhary? But they're more ellipses than there are circles, right? But there's a very famous quote by Tycho Brahe, I'm going to paraphrase. He said that this error is too big.
32:45 Lester Nare? Yeah.
32:46 Krishna Choudhary? For Tycho Brahe to make.
32:47 Lester Nare? Yeah, yeah.
32:49 Krishna Choudhary? Right? Like the error between the circle and the ellipse is big enough that I'm pretty sure Tycho Brahe's error bar is smaller than the difference between these theories. So I'm pretty sure these things are ellipses.
33:00 Lester Nare? Mm hmm.
33:01 Krishna Choudhary? Yep. And then he came up with Kepler's three laws and then, you know, Newton ran with it. So it's, it's an amazing like sort of, it's, the tradition holds true. The better data you get, the more you can discern between one or the other theory.
33:13 Lester Nare? This is why we need to continue to support and invest in frontier research.
33:19 Lester Nare? It's not necessarily tied to commercial impact.
33:22 Krishna Choudhary? No.
33:23 Lester Nare? Because the better instruments will eventually somehow, some way, it always is dual use.
33:28 Krishna Choudhary? Yeah.
33:28 Lester Nare? It's always dual use. Our better, the better we understand the world around us, the better we can get all the conveniences we love every day.
33:34 Krishna Choudhary? Yeah.
33:35 Lester Nare? And this is, this was.
33:36 Krishna Choudhary? I mean, it was just so cool that now we know that there were black holes.
33:41 Krishna Choudhary? You know, 800 million, like, like an infant universe.
33:44 Lester Nare? Yes.
33:44 Krishna Choudhary? Had just a bunch of black holes.
33:46 Lester Nare? Yes.
33:47 Krishna Choudhary? That were just like going gangbusters.
33:48 Lester Nare? Yes. Yes. And then started all spinning out and creating all of this. And again, and we can see it, we can literally see it now.
33:57 Krishna Choudhary? Yeah.
33:57 Lester Nare? Um, I still get so, my mind still gets so weirded out by the idea that because of the speed of light, when we look far enough, it's like looking in the past.
34:07 Krishna Choudhary? Oh dude, it's still, it's still weird to me.
34:09 Lester Nare? It's very.
34:10 Krishna Choudhary? It's weird to me.
34:11 Lester Nare? Very hard for my brain.
34:12 Krishna Choudhary? Yeah.
34:13 Lester Nare? Um, like it makes logical sense.
34:14 Krishna Choudhary? Yeah, of course, but like.
34:16 Lester Nare? Then you're like, are you sure?
34:20 Lester Nare? That's our astrophysics story of the day. I think we're almost averaging one per, one per week at this point.
34:26 Krishna Choudhary? Yeah.
34:26 Lester Nare? Um, great story one. Um, we're gonna move now into the rundown, uh, before we get to story two. We can't cover every story happening in the frontiers of research labs, not only in the U S, but across the globe. It's an incredible time. And it's really important that we kind of keep track of what's going on because these things are eventually gonna impact our lives one way or another. And we're gonna start the rundown. These are some fun stories this week, covering a couple of different areas. Our first story in the rundown is about a prehistoric wolf's gut.
35:03 Krishna Choudhary? Yeah.
35:04 Lester Nare? Frozen in time and revealed an ice age giant. This is from the center of paleogenetics in Stockholm, Sweden, and Stockholm University that was published in Genome Biology and Evolution. The summary is here is that a wolf pup that died 14,000 years ago, close to when the woolly rhino.
35:28 Krishna Choudhary? Yeah.
35:28 Lester Nare? Went extinct.
35:29 Krishna Choudhary? Went extinct.
35:29 Lester Nare? And there's some hair and stuff.
35:31 Krishna Choudhary? Yeah, that's still in the stomach.
35:33 Lester Nare? It's still in the gut and which means that the DNA apparently is well preserved.
35:38 Krishna Choudhary? Yeah, because apparently the wolf died like pretty soon after having dinner. This wolf pup, okay, and they don't think that it like died from predation or something like that. They think a landslide just came and like knocked its home. And so it had just had dinner and then the wolf pup died along with its sister. And it was found like right next to each other. And what's really cool is the, the hair and all of this biological material was actually intact in the, the gut of this wolf pup. Okay, so from there we can, we can do genetic sequencing.
36:12 Lester Nare? Yes.
36:12 Krishna Choudhary? And find the genetic remnants of this woolly rhino. And the key thing is if the woolly rhino went out because the population dwindled, right? And there were not that many viable individuals in the population. Then what you would expect is a lot of inbreeding. And that would leave markers in the genomics. But what they found was there was no evidence of inbreeding, which means that there was a healthy population, even as recent as 14,000 years ago. And that's right around the time when all of them died off. And that's also right around the time when the ice age ended.
36:49 Lester Nare? Right.
36:49 Krishna Choudhary? So it's probably due to climate change that this massive, massive species that used to roam Siberia and Canada is now, is now gone.
36:59 Lester Nare? I didn't even know the woolly rhino was a thing.
37:02 Krishna Choudhary? Yeah, it's pretty crazy. It's a rhino, but like.
37:05 Lester Nare? Like hair.
37:05 Krishna Choudhary? With hair. Yeah, I mean, it's a mammal, so it's got hair, but this has a lot of hair because it lives in the, you know, the winter.
37:12 Lester Nare? This, I just found, this might be totally nonsense. A pig can become a wild boar if you leave it in the wild? Like, like, like, like, there's, it's, it's about the environment that transitions them from being like a generic.
37:30 Krishna Choudhary? Domesticated.
37:31 Lester Nare? Domesticated pig versus like what we think of as a wild boar. Like they're not necessarily different geni or whatever.
37:36 Krishna Choudhary? Oh, really?
37:37 Lester Nare? I, this, look, someone in the comments, please correct me if I'm wrong.
37:41 Krishna Choudhary? Yeah.
37:42 Lester Nare? I saw it scrolling and I was like, this makes.
37:45 Krishna Choudhary? That's pretty crazy. That means, that means that like certain genes turn on and off based on environment.
37:49 Lester Nare? Right.
37:50 Krishna Choudhary? Wow.
37:50 Lester Nare? Which. Story for another day.
37:52 Krishna Choudhary? Yeah.
37:53 Lester Nare? Uh, number two in the rundown, uh, and we're gonna be doing a lot of this Artemis story because we're coming up on our return to the moon. NASA rolled out an 11 million pound moon rocket in preparations for the astronauts' launch. There's no journal or institution here, just one of our favorite government agencies. NASA moved a 322 foot tall rocket out to the launch pad on Saturday. A key step as the agency prepares for its long awaited mission to send four astronauts around the moon on the widest orbit it's been around the moon. Not on the moon. We have been to the moon, but not at this widest orbit. There were so many.
38:34 Krishna Choudhary? Oh, yeah, yeah. Guys, it's, it's fine.
38:39 Krishna Choudhary? We've, we've been to the moon, but now we're going really far away. That's the idea.
38:43 Lester Nare? That's, that's the idea here. Uh, we did, I think, see, have someone in our comments that was mentioning that they were, uh, a rocket scientist and they were actually driving down.
38:53 Krishna Choudhary? Yes.
38:54 Lester Nare? To, to basically get ready for the.
38:56 Krishna Choudhary? Yeah, it was really cool that, uh, some of them, like they worked at Huntsville.
38:59 Lester Nare? Yes.
38:59 Krishna Choudhary? Alabama, which, which is involved with the Artemis program.
39:02 Lester Nare? Yes.
39:02 Krishna Choudhary? It's very cool to get feedback like that.
39:05 Lester Nare? Um, sorry for not immediately being able to pull the name, but comment again and we'll make sure to get your name next time. Uh, we will have a deep dive on, uh, the Artemis launch and everything soon, so we will take care of all the moon people. Want more moon info. Story number three is about teenagers.
39:23 Krishna Choudhary? Yeah.
39:24 Lester Nare? Uh, scientists have found hidden synap hotspots in the teen brain. This is out of Kyushu University in Japan. It was published in Science Advances. Scientists have discovered that the adolescent brain does more than prune old connections. During the teen years, it actively builds dense, new clusters of synapses in specific parts of neurons. These clusters emerge only in adolescence and may help shape higher level thinking. When the process is disrupted, it could play a role in conditions like schizophrenia.
39:59 Krishna Choudhary? Yeah, this was, this was very exciting to me because, you know, by normal neurological dogma, we grow a lot of synapses as we get into our teenage years. So like when we're children, when we're toddlers. And then during teenage years, the, the sort of main understanding is the synapses that don't have a lot of traffic, synapses are ways to connect from one neuron to another. And when those synapses don't have a lot of traffic, those synapses get deleted. Right? This is saying that actually in certain parts of the brain, new synapses form, not new neurons, but neurons are making new connections while we're teenagers. This
40:38 Krishna Choudhary? kind of tracks with how I was as a teen, you know? Specifically, they looked at layer five neurons in the cerebral cortex. Cerebral cortex is the, the neocortex part of our brain. That's the newest evolved for us mammals. The experiments were done in mice and layer five neurons are very cool because these are the neurons that collect a lot of data from the other layers and then send it out to other different parts of the brain. So this is very important for trafficking information and making sense of different sensory stimuli or different ideas and so on and so forth. The, the authors do mention that this is experiments in mice and, you know, not everything that happens in mice translates to primates
41:19 Krishna Choudhary? and humans, but it's something to look into. Even in mice, I think it's a pretty big deal because this kind of stuff I would assume is conserved across the mammalian lineage.
41:29 Lester Nare? Yep.
41:30 Krishna Choudhary? Right? Something as deep as making new synapses.
41:33 Lester Nare? Yeah.
41:34 Krishna Choudhary? I wouldn't be surprised if we found it now in primates, but this, this is, you know, something that we can study further on. I think it's, I think it's very cool.
41:41 Lester Nare? It definitely maps on to the behavior we see in teenagers.
41:44 Krishna Choudhary? Yeah, that's for sure.
41:45 Lester Nare? Uh, from a, from a purely non-scientific perspective, it tracks.
41:50 Krishna Choudhary? Yeah. Uh, story number four is from Penn, University of Pennsylvania and University of Michigan. Penn and Michigan create the world's smallest programmable autonomous robots. Uh, because we need more robots. Uh, this was published in Science Robotics and Proceedings of the National Academy of Sciences. Uh, researchers at UPenn and University of Michigan have created the world's smallest, fully programmable autonomous robots. Microscopic swimming machines, little Michael Phelps is running around that can independently sense and respond to their surroundings independently. Hmm. And operate for months and cost just a penny each.
42:35 Lester Nare? Not going to take off in the US.
42:37 Krishna Choudhary? No way. We don't got pennies anymore.
42:39 Lester Nare? We don't even have.
42:40 Krishna Choudhary? Yeah. Yeah. You gotta buy in bulk now. But, okay, uh, jokes aside, this is pretty crazy. Okay.
42:47 Lester Nare? This is very crazy.
42:48 Krishna Choudhary? You saw the photo, right?
42:49 Lester Nare? Yes.
42:49 Krishna Choudhary? These, these things are smaller than a grain of salt. They're powered by light and they've got a little computer that can let it move in sophisticated ways. This thing is, this thing is insane and they operate at the biological level. So, you know, they say you can monitor individual cells, you can have it go inside your body. Um, you can help with small scale manufacturing, like imagine a, a laboratory that's the size of like, you know, microns by microns. I think it's definitely, uh, look, it's, it's a cool technological advance, but all those people who are like, there's a chip in my body. Like, this is a, this is weird. It's a little bit weird.
43:27 Lester Nare? Now there's some experimental research.
43:29 Krishna Choudhary? Yeah. Now there's, yeah. And, and they operate, you know, with just light.
43:34 Lester Nare? Meaning.
43:34 Krishna Choudhary? So they've got little tiny solar panels and then they've got a computer that lets them figure out where they want to go and things like that. Um, one thing that I thought was really cool is how do you, how do you make something that's small move around?
43:45 Lester Nare? Yeah.
43:45 Krishna Choudhary? Water. Okay. Because you run into the low Reynolds numbers, right? The Navier-Stokes equations, when you go down to that scale, water is basically like honey. And so it's really hard to move around. So how are they actually doing it? Well, if you have movable parts like little. Flippers and stuff. One, that's a really inefficient way to move around in honey because like as I move this way and then I retract my flippers. I'm all actually going to go backwards. The other thing is movable parts are really bad because they're not durable.
44:14 Lester Nare? Yes.
44:14 Krishna Choudhary? They can break, especially if you're moving around in honey.
44:16 Lester Nare? There's no nano bio, not nano robotic auto zone.
44:19 Krishna Choudhary? Yeah, yeah, yeah. And these things are lasting for months on end, right? The way they do it is they generate electric fields around their chip. And then the electric fields then move around ions. Because our body has a bunch of ions and then that moves around water, which propels, propels them forward. So there's no moving parts.
44:39 Lester Nare? I just am so mad at how clever that is.
44:41 Krishna Choudhary? That it's pretty clever. I gotta say. It's a bit weird that that's what we're going for, but at the end it is pretty clever. And I think for the right use cases.
44:50 Lester Nare? For sure.
44:50 Krishna Choudhary? It can be huge, right? For delivering, let's say, medical cargo for to one specific site.
44:56 Lester Nare? Yep.
44:56 Krishna Choudhary? Of the body versus another, things like that, it could be very useful.
44:59 Lester Nare? We've been hearing about the potential of nanotechnology since I think I was like in middle school.
45:05 Krishna Choudhary? Yeah.
45:05 Lester Nare? How it's the next frontier and all these things. This is a real practical. You know, it reminds me of the programmable protein story we covered from Yale in last season. We're doing greater and greater things at smaller and smaller scales. And again, the, the applications, you know. Eat your heart out.
45:26 Krishna Choudhary? Yeah.
45:26 Lester Nare? It's, it's endless. That's a really, really good story. Our last story for the rundown today is about Leonardo DiCaprio. Genetic clues.
45:37 Krishna Choudhary? Da Vinci.
45:38 Lester Nare? Oh, excuse me. It's Golden Globes. Excuse me. I saw that clip of him talking about K-pop demon hunters. Da Vinci, the one from the 1500s.
45:49 Krishna Choudhary? Yeah.
45:50 Lester Nare? Genetic clues may be hiding in his artwork. There were many institutions involved in this one. The Venter Institute, Vanderbilt, Vanderbilt University Medical Center and the University of Maryland. This was out in Bio Archive. And the idea here is that. The artist inventor and all around genius Da Vinci was sort of the definition of the Renaissance man. Obviously, we have the Da Vinci Code, all these books, all this stuff. And scientists have been aiming to unlock the secrets of his genius on a genetic level. But there's just one small problem. More than 500 years after his death, his DNA has proved virtually impossible locate.
46:32 Krishna Choudhary? Yeah.
46:33 Lester Nare? No kids, his grave was destroyed during the French Revolution.
46:36 Krishna Choudhary? Yeah, that's not the only thing that was destroyed in the French Revolution. Let me tell you that. But, you know, that's my jab at the French. There's gonna be another one later in the episode. In any case, I don't know why, but like, there's this thing called the Leonardo Project. And they're obsessed with all things Leonardo and they really want his DNA. Okay, they want to sequence his DNA. What the project's team did was they swabbed letters that were written by a distant Leonardo relative. And they also swabbed something called the Holy Child, which is a drawing that was possibly created by Leonardo. And they found a Y chromosome.
47:12 Lester Nare? Okay.
47:13 Krishna Choudhary? Which is the chromosome that is in all males.
47:17 Lester Nare? Yes.
47:17 Krishna Choudhary? And there's not a lot of mutations.
47:19 Lester Nare? Yes.
47:19 Krishna Choudhary? So if there's a distant Leonardo relative and then this swab from the letter is actually matching, then it's very highly likely that it is Leonardo. And this kind of reminded me of, there was this documentary called The Lost Leonardo. It was about this painting Salvator Mundi. That was apparently the lost Leonardo da Vinci painting. He only made a handful of paintings, something like 10 or 15, less than 15. And each one of his paintings are masterpieces. The first painting that I ever saw was Madonna with Child in the gallery in London. And it is, it is like quite amazing, just the way that he shades painting, paint together and.
48:01 Krishna Choudhary? The faces that he makes are just like incredible. This particular painting, the Salvator Mundi, it sold for $450 million. It's the most expensive painting to have ever been sold by Christie's. And it is currently owned by Mohammed bin Salman of Saudi Arabia. He's trying to open a new art gallery in Saudi Arabia. And this is going to be the big masterpiece there. It's debated whether Salvator Mundi is from Leonardo.
48:31 Lester Nare? Okay.
48:31 Krishna Choudhary? Okay. But if we could figure out like a scientific way to say this is Leonardo or not, then you know, you could actually see whether he made the bet was correct or not.
48:43 Lester Nare? We are giving new meaning to the common phrase, the Da Vinci Code.
48:49 Krishna Choudhary? Yeah. Oh, yeah. Nice one.
48:53 Lester Nare? I do this professionally.
48:56 Lester Nare? Great five stories on the rundown today. Prehistoric woolly rhino. The rollout of an 11 million pound rocket in preparation for Artemis II launch. We figured out why teens get to communicate better in their brain because of all these new synaptic connections. Nanobots are here.
49:19 Krishna Choudhary? Yeah.
49:20 Lester Nare? And we may finally have the DNA of Leonardo da Vinci so that we can genetically replicate him and have a bunch of geniuses running around. We are now going to move into our next story, which is about something very fascinating that I've never heard of, which is time vaults.
49:40 Krishna Choudhary? Yeah.
49:41 Lester Nare? So in a new paper out in Science from both Harvard and the Broad Institute of MIT, is this new genetically encoded device for transcriptome storage, information storage in mammalian cells.
50:00 Lester Nare? This, this story is super interesting.
50:01 Krishna Choudhary? Yeah, this is, this is pretty incredible because I think it is going to, dare I say, if this is what it purports it to be, this might be something that is Nobel Prize worthy.
50:12 Lester Nare? Okay, wow.
50:12 Krishna Choudhary? Okay, that's, I'm gonna start there.
50:14 Lester Nare? Oh.
50:15 Krishna Choudhary? There's something called the measurement problem.
50:16 Lester Nare? Yes.
50:17 Krishna Choudhary? In biology and physics, we have the measurement problem, right? Which is like you measure something and then that destroys the system. Well, in biology, we've got something very similar, which is the destructive nature of observation. If I want to measure what is happening inside of a cell, I basically have to kill the cell, get all of its contents out and then do RNA sequencing to figure out what kind of RNAs inside and all that other kind of stuff. So we can never observe the same cell twice. And what we have to do is we have to infer biological dynamics using static snapshots of stuff, right? You gotta break down and then you gotta break down here and then you gotta sort of connect the dots in time.
50:55 Lester Nare? That's, I actually did not know that. That's interesting.
50:57 Krishna Choudhary? But if you think about it, that kind of makes sense, right? How am I gonna observe a cell? Well, I gotta break all of its contents. I gotta get all the proteins and then sequence the proteins. Oh, there's this much amount of this protein. There's this much amount of this. This is the mRNA profile, this, that, which is the transcriptome. So it's like super nonlinear. And if you have stuff like cancer and embryonic development, which is nonlinear and non-ergotic, these systems, you can't really piece together a time sequence that confidently.
51:25 Lester Nare? You can't really understand what's happening in time. You can understand what's happening in snapshots of time.
51:31 Krishna Choudhary? Exactly. So there's a lot of information loss, right? There's cellular decisions that happen, let's say now.
51:37 Lester Nare? Yes.
51:37 Krishna Choudhary? And then the result of that cellular decision is only gonna come forward in a few days.
51:43 Lester Nare? Yes.
51:43 Krishna Choudhary? Right? So how do I connect?
51:45 Lester Nare? Right.
51:45 Krishna Choudhary? Those two things.
51:46 Lester Nare? Right.
51:46 Krishna Choudhary? And that, the existing solutions are something like DNA editing. In 2014, there was this CRISPR-based tape recorder.
51:54 Lester Nare? Okay.
51:54 Krishna Choudhary? That what you could do is you could say, okay, I wanna watch these specific genes and how they're transcribed. And there was a tape recorder that you could literally like be like, oh, okay, this thing was transcribed, but this time I'm gonna like keep it and save it in some sort of memory. But you had to choose beforehand what to record.
52:11 Lester Nare? Ah, it wasn't, okay.
52:13 Krishna Choudhary? Right?
52:13 Lester Nare? Yeah.
52:14 Krishna Choudhary? And, and there's only a few events that you could record before the memory went out. Okay, and that's where the breakthrough comes in here. It's called time vaults, okay genetically encoded molecular archives. It's a time capsule for cells cells that stores the secret experiences of their past. It's very, very cool and it's repurposing something called the vault particle. Okay, physically encapsulate mRNA and store it as the cell just goes about its daily business.
52:43 Lester Nare? We created almost a cellular backup system like time machine on your Mac.
52:47 Krishna Choudhary? Yeah, dude, it's exactly that. It's a time machine on your Mac, but now at the cellular level.
52:54 Lester Nare? That's incredible.
52:54 Krishna Choudhary? It's insane.
52:55 Lester Nare? That's incredible. It's especially given before we were only getting snapped like the
52:59 Krishna Choudhary? Yeah.
52:59 Lester Nare? The order, the, the scale of difference of capability.
53:03 Krishna Choudhary? Yeah.
53:04 Lester Nare? Okay.
53:04 Krishna Choudhary? It's, it's very cool. Okay, so let's talk about like, why this is important, right?
53:08 Lester Nare? Yeah.
53:09 Krishna Choudhary? So in physics, we like to think of systems as state vectors. Like all of the particles in a room are going to have position and momenta. And if we know those position and momenta, then we'll know everything about that system. Well, in biology, the state vector is really something called the transcriptome, which is the mRNA counts. There's about 20,000 genes that are getting expressed in the human body. And if you could count which genes and how much of that gene is getting expressed in a cell, you could have something like a state vector for that cell. It could be like, what is the cell state in? The, the cells in our skin will have a bunch of genes that express for the proteins that are responsible for our skin.
53:52 Krishna Choudhary? The cells in our blood will have the blood genes expressed. The DNA is the same, but how much of which gene is expressed is what matters in terms of what that cell is doing.
54:03 Lester Nare? It's, it's what differentiates how cells have this multi, have these different functions.
54:08 Krishna Choudhary? Exactly, yeah. And so in nature, you can think of DNA as like a stable read only memory. So that's your ROM. And then your mRNA is a volatile, random access memory, right? That's your RAM. Now mRNA has a half life that's about five to nine hours, which, which means. In about every five to nine hours, half of the amount of mRNA that was there is gonna be gone. It's gonna be degraded. And this is a feature and not a bug, because the cell can then quickly respond to an environment and forget what it was doing five hours ago. You wanna be able to, you know, quickly change what you're doing in case there's some outside stress that comes along, right?
54:45 Lester Nare? It's sort of this adaptive property.
54:47 Krishna Choudhary? Exactly. And there were ways that we could tag the new mRNA to be like, okay, I wanna, I wanna check how much of this new mRNA is going through. You could tag it with something called fourthiouridine, which is a specific type of nucleotide that goes into the mRNA and it kind of saves stuff. But that signal was limited by about 17 hours. So it's like undetectable after 24 hours. So your memory was only really 24 hours, because you've got these things called exosomes in your cell that are basically the trash collectors. And they collect all the trash and then they, they put it out. Okay? So, okay, how do we, how do we extend the recording window? Well, one naive way to do it is just be like, delete all the exosomes, all the trash collectors.
55:29 Krishna Choudhary? That's a really bad idea. Imagine a city without trash collectors.
55:33 Lester Nare? Yeah, we don't want that.
55:34 Krishna Choudhary? We don't want that. We don't want that.
55:35 Lester Nare? Some people say that's what LA is today. I will have you know, we still have trash and recycling running.
55:41 Krishna Choudhary? Yeah, and it's not that bad. It's not that bad. But you can imagine that's, that's a really bad way of doing things. You can't stop degradation, because that stuff is essential for life to keep moving around. So instead, what if we could spatially segregate the mRNA and keep it away from the trash collectors?
55:57 Lester Nare? Okay.
55:58 Krishna Choudhary? Right? We could put it in a vault.
56:00 Lester Nare? Uh huh, I see.
56:02 Krishna Choudhary? Although, although the name vault is actually not for, like, you know, a vault to store stuff. It actually comes from this 1986 paper by Khedashia and Rome at UCLA in the Journal of Cell Biology. This was 1986. Okay? What they were doing was studying coated vesicles, which are like just transport spheres that like... Package a bunch of stuff and then and then move it around the cell and they kept coming up with this contaminant. Okay, there was a contaminant in their sample all the time. And when they looked really closely at this contaminant, there were these large barrel shaped organelles.
56:36 Lester Nare? Okay.
56:36 Krishna Choudhary? Okay. And when you went into a electron microscope and took a look at them, these organelles resembled vaulted ceilings of Gothic cathedrals. So they named them vaults and these things are massive. Okay. If you look at the scale bar there, that's 100 nanometers. That's like the size of some cells and these organelles are that big, right? Okay. And they're the largest non-viral ribonucleic protein complex. They've got a mass of approximately 13 mega daltons, which is three times the size of a ribosome. The ribosome is the factory that makes proteins out of mRNA and they're pretty big.
57:17 Lester Nare? They're factories.
57:18 Krishna Choudhary? For just like for just like single units.
57:20 Lester Nare? Right.
57:20 Krishna Choudhary? Of stuff, right? Not not really single units. There's like subunits that form together to create a ribosome. But at the end of the day, it's not a fully fledged organelle with like a membrane and like a full like, you know, inside and outside. This thing, 13 mega daltons at the dimensions of tens of nanometers. And there's a bunch of them in our cells, 10,000 to 100,000 per cell.
57:43 Lester Nare? Jesus.
57:44 Krishna Choudhary? Okay. A lot of our immune system cells have overexpression of this stuff.
57:49 Lester Nare? Okay.
57:49 Krishna Choudhary? And what's weird is we still don't really know what they're there for. And they're not essential because if you knock them out in mice, like you just get rid of the protein that makes these vaults, the mice are fine.
58:03 Lester Nare? So there's some, you know, there's a variety of things. It's either, you know, evolutionarily over time, we've, you know, no longer need these things.
58:10 Krishna Choudhary? Yeah.
58:11 Lester Nare? They're still around.
58:11 Krishna Choudhary? Yeah.
58:12 Lester Nare? Or there is some functionality.
58:13 Krishna Choudhary? That we just haven't figured out.
58:14 Lester Nare? Don't really quite know.
58:15 Krishna Choudhary? And it's more likely the latter because there's a lot of stuff that, you know, our DNA is made up of introns and exons. So there's stuff that the DNA keeps inside the nucleus and then there's stuff that gets expressed. This stuff is getting expressed, right? If you have 10,000 to 100,000 per cell, clearly like. Evolution by now should have figured out if there's no use for this, why waste time and energy like making this stuff? Yeah. But it's being expressed. So there is some reason. We just haven't quite figured out what that is. But the advantage is because it's not critical for function, you can use it as this kind of ideal, robust, non-toxic chassis for stuff. Mm hmm. Okay? So let's get into this vault protein. What does it look like? There's a single protein that makes it up.
59:00 Krishna Choudhary? This called a major vault protein. You get 78 copies of this protein and it self-assembles. It doesn't need like something to come in and assemble it. It's like a bunch of tiny little magnets, 78 of them come together and make this barrel shape. Beautiful structure, right? This very beautiful symmetric barrel-like structure. They're all just coming together. There's these two subunits that come together, one on each side, 39 on each of them. And the Young's modulus of this thing, like the stress and strain, like how hard it is, it's about as hard as like some plastics or like viral capsules. Oh, wow. Which is very good because it's, you know, it's quite sturdy. Yeah, yeah.
59:42 Krishna Choudhary? And the other thing is unlike viral capsules, when you like poke them, the viral capsules are kind of, they're gonna go all over the place and they're not really gonna be able to recover. With these major vault proteins, there's interactions with that protein, the way it's sort of just magnetically locks into place with all of the others, that ensures that if I were to like poke it with, let's say, a little tip, like an AFM tip or something like that with atomic force microscopy tip, the vault protein will break and then when I remove the stress, it'll just form back up. Just naturally, biology has figured out this exact design to make this beautiful barrel-like
1:00:25 Krishna Choudhary? structure that is resistant to stress. Mm hmm. It's incredible and we still don't know what it does. What it does. Like 40 years later. But it's. 1986, 40 years later, we still quite don't know what it does.
1:00:37 Lester Nare? But it is clearly fantastically engineered through evolutionary biology.
1:00:42 Krishna Choudhary? Yeah, it's absolutely amazing, right? So how do we get from vaults to now time vaults?
1:00:48 Lester Nare? Yes.
1:00:49 Krishna Choudhary? This is a really funny story, okay? So one of these students at the Harvard lab found Leonard Rome's YouTube channel. He's called the Vault Guy.
1:00:57 Lester Nare? The Vault Guy.
1:00:58 Krishna Choudhary? On YouTube, and he makes a bunch of YouTube videos about vault proteins and just like molecular biology in general.
1:01:05 Lester Nare? Shout out to the Vault Guy.
1:01:06 Krishna Choudhary? And yeah, I guess one of these grad students in the Harvard lab found the YouTube channel and was like, yo, this vault guy is making some pretty cool stuff. Maybe we could use him for our purposes, right? And that's where they got the idea of time vaults. And then this paper has come out in Science. A genetically encoded device for transcriptome storage in mammalian cells. The idea is we're going to use these vaults as our Mac time machine.
1:01:32 Lester Nare? Yes.
1:01:32 Krishna Choudhary? Right?
1:01:33 Lester Nare? Yes.
1:01:34 Krishna Choudhary? Very cool. So how do we do that? How exactly mechanistically does it work? Because, you know, on this podcast, we like to focus on just the Lego blocks.
1:01:43 Lester Nare? Yes.
1:01:43 Krishna Choudhary? Of biology.
1:01:44 Lester Nare? Yes.
1:01:44 Krishna Choudhary? And how you put together a bunch of Lego blocks that actually work the way that they're supposed to.
1:01:49 Lester Nare? Because the concept of what they're trying to accomplish and the reason why makes total sense.
1:01:56 Krishna Choudhary? Yeah.
1:01:57 Lester Nare? And then the entry point of, you know, these vaults being a possible conduit.
1:02:05 Krishna Choudhary? Yeah.
1:02:05 Lester Nare? To an engineered kind of functionality is interesting, but there's a big gap between those two things.
1:02:12 Krishna Choudhary? Yeah, like how am I going to get the mRNA inside?
1:02:15 Lester Nare? Yes.
1:02:15 Krishna Choudhary? And then how does it stay inside and all this other kind of stuff, right? This is again, at the molecular level.
1:02:20 Lester Nare? Yes.
1:02:20 Krishna Choudhary? Okay, well, at the molecular level, everything is Lego blocks. So let's talk about mRNA. One of the properties of mRNA is when it comes out, it has something called a poly A tail, which means at the end of the mRNA, after it gets transcribed from the DNA, there's a bunch of AAA, the adenine, there's just repetition of adenine. And that poly A tail. Is kind of like a handle for figuring out where to take this mRNA and things like that. You need to be able to grab it without messing with the genetic information that's later, right? So you need some kind of handle for the sword.
1:02:55 Lester Nare? It's, it's, yeah, it's, yeah, I was gonna say, it's like on a knife.
1:02:58 Krishna Choudhary? Yeah.
1:02:58 Lester Nare? You don't want the end to be a blade that you're grabbing.
1:03:00 Krishna Choudhary? Yeah, yeah, because then you'll mess with the blade or you'll like kill yourself, you know? So, so the poly A tail is there and the stuff that interacts with the poly A tail is something called the poly A binding protein, P A B P. And what these guys figured is we could have a container and a bait. Okay, the container is my vault protein shell. And my bait would be this protein that interacts with the poly tail. And also has a little domain on the protein that interacts with the vault. Okay, so the P A B P that binding protein is gonna grab the poly A tail. And then part of it is gonna get stuck to the vault.
1:03:42 Lester Nare? Yes.
1:03:42 Krishna Choudhary? Okay, and all of this, we can put in a single piece of DNA such that when it gets transcribed, the vault protein gets transcribed to make the vault and also the poly A binding protein.
1:03:54 Lester Nare? Goodness.
1:03:56 Krishna Choudhary? You see?
1:03:56 Lester Nare? That is so.
1:03:57 Krishna Choudhary? And so when I turn this thing on, it, it makes the whole package. It makes my vault and it makes the thing that grabs the mRNA and puts it inside the vault.
1:04:05 Lester Nare? We've created a vertically integrated stack at this molecular level to effectively go through the creation of the individual component parts necessary.
1:04:17 Krishna Choudhary? Yeah.
1:04:17 Lester Nare? We don't have to hijack something existing. We're literally able to say, no, we want the time vault. We want the grab, the transporter.
1:04:24 Krishna Choudhary? Yeah.
1:04:25 Lester Nare? And so it's fully self-contained as a process.
1:04:28 Krishna Choudhary? Yeah, fully self-contained.
1:04:29 Lester Nare? Fascinating.
1:04:30 Krishna Choudhary? Amazing, right? And then what you can do is this entire genetic circuit, you can turn on and off based on this tet on tet off mechanism, which is effectively what you do is you introduce an antibiotic called doxycycline. And then when you introduce it on, this genetic pathway gets triggered. So it makes the vault protein and it makes the interaction protein, right?
1:04:50 Lester Nare? Yeah.
1:04:50 Krishna Choudhary? And then, and then there's another called docs off where I can introduce docs off. And then it's gonna stock, stop the vault protein. And so now I have a controlled time window.
1:05:01 Lester Nare? Yes.
1:05:01 Krishna Choudhary? Where I can make this. Time machine, I can trigger it.
1:05:05 Lester Nare? Yes.
1:05:06 Krishna Choudhary? It can turn on, it can make all this stuff and it'll just grab a bunch of mRNA, stick it inside the vault protein and then I'll, I can make it stop.
1:05:14 Lester Nare? For so many listeners may have heard of doxy cycling before because it's like a, it's an antibiotic you'll get for any like a variety of use cases. So I'm like, it's simply just doxy triggers the initialization of the storage. That's again, it's, it's, you're not inventing like we're taking things that are already there.
1:05:31 Krishna Choudhary? Yeah, but just putting these Lego blocks together in a really clever way.
1:05:35 Lester Nare? Yeah.
1:05:36 Krishna Choudhary? And then now you can see if this time vault stuff works, right? So you can, you can show that there's no new capture this time vault. The half-life of the mRNA in the time vault is now 132 hours, which is five days instead of the five hours that we had before. So the mRNA is sticking around because it's been captured.
1:05:55 Lester Nare? Right.
1:05:55 Krishna Choudhary? And if I now lice the cells, it's still in there.
1:05:59 Lester Nare? Mm hmm.
1:06:01 Krishna Choudhary? Right?
1:06:01 Lester Nare? Yes, this is good.
1:06:03 Krishna Choudhary? So you, you can now, you can now basically tell a cell.
1:06:06 Lester Nare? Yes.
1:06:07 Krishna Choudhary? I want you to save all your memory right now.
1:06:09 Lester Nare? Yes. Yes. Simply by introducing doxy cycling.
1:06:12 Krishna Choudhary? Yeah, yeah. It'll save all the memory. And then you can just have the cell go on its merry way because all of the stuff is inside the vault protein.
1:06:18 Lester Nare? Right.
1:06:19 Krishna Choudhary? It's not interacting with the stuff outside and we know that the vault protein is not toxic.
1:06:23 Lester Nare? Yes.
1:06:24 Krishna Choudhary? To the cells themselves because it was already there in the first place.
1:06:26 Lester Nare? So it can just hang around doing the function we want it to because it's non-toxic and it's self-contained, meaning like the mRNA inside cannot escape. And also if it gets poked, it'll reconstruct. So it's, it sort of has security in that context. So the, the point be, you want to be careful when you start doing things like this to not introduce, you know, new variables that the system will attack or are not prepared for. But the, the, the structure we've already walked through really identifies that this is not going to interrupt regularly scheduled programming.
1:06:57 Krishna Choudhary? Exactly.
1:06:58 Lester Nare? While still enabling the capability of capturing the memory of a cell over this long, much longer period of time.
1:07:03 Krishna Choudhary? Exactly. And so now you can ask this, the mRNA that's inside the vault protein, right? How long does that last? Well, the thing is lasting for about 17 days. Okay, the stuff that's inside the vault protein. And you ask, okay, why is it lasting that long? Well, that's actually the inherent physics of RNA.
1:07:21 Lester Nare? Okay.
1:07:22 Krishna Choudhary? Okay, RNA is ribonucleic acid versus DNA is deoxyribonucleic acid. The, one of the big differences is, of course, the DNA is double stranded and RNA is single stranded. So DNA is a bit more stable, obviously, because you've got, you know, a fully fledged ladder that's sort of protecting the inner bases. The other big thing is that the ribos, sugar, which RNA has, and DNA has deoxyribosugar. The ribosugar has an extra OH, okay? It's got an extra hydroxyl group on the, on the two of that pentagon.
1:07:54 Lester Nare? Yeah, okay.
1:07:54 Krishna Choudhary? Right?
1:07:55 Lester Nare? Yep.
1:07:55 Krishna Choudhary? And that extra OH, that oxygen, oxygen is always just bad. Okay, it just attacks random crap. And so the RNA, that extra oxygen goes and attacks the phosphate backbone. And that process has a characteristic timescale of 17 days. So we're reaching the theoretical limit of how long RNA can just hang around before the chemical RNA itself starts attacking itself.
1:08:22 Lester Nare? We're, we're, we're literally at the, what did we call the, the Ed, the Eddington limit of your, of your.
1:08:28 Krishna Choudhary? Yeah, but in this case it would be the thermodynamic limit of, of RNA stability. But what it's, what it's showing is that there's no enzymatic degradation of mRNA. Right? There's no other stuff, there's no exosomes that are coming in, trying to like take it out. This is just pure physics. It's gonna last about 17 to 18 days.
1:08:46 Lester Nare? It's locked down, but for the fact that the structure of ribos itself will degrade.
1:08:53 Krishna Choudhary? Will degrade the RNA.
1:08:55 Lester Nare? Which we, that's a bigger, that's a whole other thing.
1:08:56 Krishna Choudhary? Yeah, that's like, I don't know, I don't know what to do with that. Yeah, so, so here you can show that like, you know, this. This is really happening, right? So the critical step is, once you have, once you have like, the RNA that's present in the cytosol, let's say, versus RNA that's present in the time vault. How do you tell the two apart?
1:09:18 Lester Nare? Right, okay.
1:09:19 Krishna Choudhary? Right? Because if I were to now take the cell and I were to say, okay, I want you to record now. And then in five days, I want to read it. Right? How do I, how do I tell what's already there versus what's in the vault? Well, I can introduce something called RNase, which is an enzyme that eats RNA. If I make it eat RNA, the stuff that's inside the time vault is protected from this enzymatic degradation.
1:09:44 Lester Nare? Oh, my God, bro. This is so good.
1:09:47 Krishna Choudhary? It's so good.
1:09:48 Lester Nare? This is so good.
1:09:49 Krishna Choudhary? And so now, the, if you add RNase, the only stuff that we're going to be able to read afterwards is the stuff that's inside the vault protein.
1:09:56 Lester Nare? God, that's so good.
1:09:57 Krishna Choudhary? It's so good.
1:09:59 Lester Nare? This is, this is, this is, you're watching masters at work here.
1:10:04 Krishna Choudhary? Yeah, this is great.
1:10:05 Lester Nare? I can see why you started off with such a high, high bar.
1:10:09 Krishna Choudhary? High bar, right? There are some, there are some caveats. For example, it's not gonna, it's not gonna take in mitochondrial RNA, because the mitochondrial RNA is inside the mitochondria. Right? And it's not going to take in any RNase that lack a poly-A tail. There's some, there's always some that are exceptions to the rule. And so, you know, the, the interaction protein is not going to be able to grab that mRNA, because there's no poly-A tail to actually grab. The capture efficiency is also quite low. It only takes in about 3% of the total mRNA. Right? Because there's so much mRNA. So it's only going to take in a small sample. And so that low capture rate means that you really need to pool together thousands of cells to prevent this statistical bias.
1:10:54 Krishna Choudhary? Right? Where if you were to do just one cell, how do you know that you got all of it? If it's only taking 3%. But if you do 1,000 cells, then you're pretty sure that you've got all of the mRNA covered.
1:11:03 Lester Nare? That's, well, that's a solvable. We'll solve that problem.
1:11:05 Krishna Choudhary? Yeah, and, and there's, there's ideas later that'll, that'll help you solve it. But I just want to let you know that in, at least in the first iteration of this, this is still pretty damn good.
1:11:14 Lester Nare? This is, this is, right? Now that this base is there, like, I, I'm just shocked at how clever that is.
1:11:20 Krishna Choudhary? Yeah, it's, it's really nice, okay? And so the way, so how do we know that it works? Well, they did a really simple experiment. What they did was heat shock these cells after.
1:11:33 Krishna Choudhary? And then, right after the heat shock, they had the RNA go into the vault proteins. Okay, and then they compared the vault proteins right after the heat shock to when you and then, you know, you wait five days and you sequence the mRNA that's in the vault proteins and then you compare that to the heat shock and then right after you you license it and then you do it, right? If this whole thing worked, then the mRNA that's in the vault proteins right after the heat shock should match normal cells right after the heat shock. The transcriptomes should match. And that's exactly what they found, right? Is that the present transcriptome, if you look at five days later, the present transcriptome forgot that it was heat shock. But the stuff that's inside the vault remembers that it got heat shock because you did the
1:12:16 Krishna Choudhary? time machine thing and you did the backup right then, right? Very beautiful. And the figures, I gotta say, the aesthetics of the figures are also really nice. Like the color coordination of the blue and the red, I liked it.
1:12:28 Lester Nare? Look, we like design and aesthetic, both experimental and visual.
1:12:34 Krishna Choudhary? Yeah, yeah, so I thought this was really cool. So now, applications, right? They actually went further and went into applications. This is the one where people talk about, you know, real world applications. So Harvard, when it came out with the story in their press, they talked about how did that cancer cell become drug resistant? One of the first things you can do is apply this thing to cancer cells, okay? Whenever you do cancer cells and you treat the cancer cells with a drug, there's always 1% of cancer cells that are drug tolerant persisters. You know how like you have like the soap that's like kills 99% of germs? Well, there's always 1% of germs that get away, right? And the same thing happens with cancer.
1:13:13 Krishna Choudhary? If you target therapy with something called osimertinib, which is a drug for cancer, 1% of these cancer cells survive. Now, the debate is the following: Were these cancer cells pre-adapted? Or was the fact that I introduced the drug causing them to adapt? This is a debate that goes all the way back to Charles Darwin and Jean Baptiste Lamarck. There was the idea of how do organisms gain traits? The Darwinian model was the one at the top that you see, which is let's take a population of giraffes, right? Why do giraffes have long necks? Where, well, you could have a population that has a bunch of different neck sizes. And then the longer necks could reach the trees and eat the trees.
1:13:59 Krishna Choudhary? And so then the shorter necks died off. And then the subsequent populations got longer and longer necks. That's actually the one at the bottom. Okay, now the Lamarckian hypothesis is the
1:14:15 Krishna Choudhary? hereditary nature of acquired characteristics. Meaning the giraffes like kept stretching their necks. And then that stretching of the necks made the subsequent population stretch their necks. And so now that's why we have longer necked giraffes.
1:14:31 Lester Nare? Would it be almost like an epigenetic kind of?
1:14:34 Krishna Choudhary? Yeah, yeah, yeah.
1:14:34 Lester Nare? Like more of an epigenetic theory?
1:14:36 Krishna Choudhary? Exactly, yeah. And for what we know from large scale populations, it's really a Darwinian thing. But the Lamarck hypothesis is not completely off ground, right? At the cellular level, we have examples of that. For example, with bacteria, when we heat shock bacteria, the bacteria just start taking in DNA from their environment. Right? So that's kind of Lamarckian because I've been introduced to stress. And then that stress is causing the genetics to change. So the question is, what's happening with these cancer cells, right? And currently, we can only record the bulk population, which is mostly dead. And then we can record the survivors, which is after the fact. So to answer this question in cancer biology, you have to be able to record what's happening before the drug was introduced.
1:15:18 Lester Nare? Yes.
1:15:18 Krishna Choudhary? And then probe what the survivors were doing.
1:15:23 Lester Nare? Yeah, yes.
1:15:23 Krishna Choudhary? Does that make sense? And this is perfect for the time vault. So what they did was they had a protocol where you record for 24 hours with no drug. And then you introduce this cancer drug, osimertinib. You record this cancer drug for four days, 99% die.
1:15:40 Lester Nare? Yes.
1:15:40 Krishna Choudhary? And then the ones that survive, let's read out what's inside their vaults.
1:15:45 Lester Nare? Yes, yes.
1:15:46 Krishna Choudhary? And it was definitive evidence for the selection model, meaning that these cancer cells had previously adapted. The cancer cells have a very high mutation rate.
1:15:54 Lester Nare? Yes.
1:15:54 Krishna Choudhary? And so they're exploring all of these different possibilities. And the 1% of cancer cells that survived had a distinct transcriptional signature before the drug treatment.
1:16:03 Lester Nare? Mm hmm.
1:16:03 Krishna Choudhary? Right? And so now the focus for therapeutics can shift from adaptation to targeting that pre-existing state. And what they did was they, they looked at some of the genes that were expressed in those vaults. Specifically FN1. They knocked that out. And then now none of the cancer cells survived that drug.
1:16:20 Lester Nare? This is
1:16:21 Krishna Choudhary? So it's like literally working.
1:16:22 Lester Nare? This, this is actually unreal. I want people to understand how unreal this is.
1:16:27 Krishna Choudhary? Yeah.
1:16:27 Lester Nare? Because now you're, because we can now DVR our cells.
1:16:33 Krishna Choudhary? Yeah, yeah, yeah.
1:16:35 Lester Nare? We can Mac time machine back up our cells. It means we can actually see what happens before, like, we can understand after you introduce some external factor, like what the changes are. And particularly in the cancer research example you just brought up, this is so fascinating. You have all of them. You, you, you do the recording in the time vault. You're doing it over 24 hours. You have all of them there. Then you introduce the current treatment.
1:17:01 Krishna Choudhary? Yeah, 99% die.
1:17:03 Lester Nare? 99 are gone, 1% are left over. You can look at the 1% that are left over and say, what is it about these guys? That's different. And then now we can attack the thing like the FN1. That's different because we are able to now actually see over time, do it again, and now they all die.
1:17:19 Krishna Choudhary? Yeah.
1:17:19 Lester Nare? That's incredible.
1:17:21 Krishna Choudhary? Yeah.
1:17:22 Lester Nare? That's incredible. Do you understand what we can do with that?
1:17:24 Krishna Choudhary? Yeah, that's so cool. You can, you can use this for like, and the fact that these vault proteins are just ubiquitous in mammalian cells.
1:17:31 Lester Nare? Yes.
1:17:32 Krishna Choudhary? Means that you can just apply this all over the place.
1:17:34 Lester Nare? Exactly. This almost feels structural, conceptually, as I try to put it into my brain. It feels CRISPR-esque as being a platform.
1:17:44 Krishna Choudhary? Yeah.
1:17:44 Lester Nare? Versus a single point solution.
1:17:45 Krishna Choudhary? Exactly, yeah.
1:17:47 Lester Nare? This is a really big deal.
1:17:48 Krishna Choudhary? It's a really big deal.
1:17:49 Lester Nare? Once it, you know, once it percolates and people poke hole, review or two pokes a hole.
1:17:54 Krishna Choudhary? Yeah, no, but people, people are very excited.
1:17:56 Lester Nare? Excited about this.
1:17:57 Krishna Choudhary? From the press coverage that I've seen, people are very excited.
1:17:59 Lester Nare? This is, I mean, holy moly.
1:18:01 Krishna Choudhary? Yeah, it's very cool.
1:18:03 Lester Nare? And what a great name, Time Vaults.
1:18:04 Krishna Choudhary? Yeah, yeah.
1:18:05 Lester Nare? Great name.
1:18:05 Krishna Choudhary? Well done.
1:18:06 Lester Nare? Great name.
1:18:07 Krishna Choudhary? Well done on that one.
1:18:07 Lester Nare? Whoever was doing the branding, right?
1:18:09 Krishna Choudhary? Yeah, the branding on that one was great. So what's the future? Well, we want to overcome this 3% capture efficiency.
1:18:16 Lester Nare? Sure.
1:18:16 Krishna Choudhary? Right? So one thing that I thought was really cool, the idea was you can put in inside the vault protein, you can put in something called reverse transcriptase. And what that's going to do is take the mRNA that's getting stuck inside the vault protein and reverse transcribe that into DNA. Now, the DNA is going to last much longer than the 17 days. That's the thermodynamic limit for RNA. And so you could like have weeks of time vaults, right?
1:18:42 Lester Nare? It's almost like there's a short-term memory in the mRNA storage that gets, and then it's sort of like how we record. We record onto a small hard drive and then we dump it onto our archive drive for long-term storage.
1:18:53 Krishna Choudhary? Yeah, it's exactly that. Yeah. The other thing could be like you could have molecular identifiers per vault, per cell. And then it's kind of like a barcode for each cell. And then you could be like, these mRNA came from this cell and these mRNA came from this cell. So you get the aggregate, but you also get single cell resolution. Kind of cool, right? To think about. You could combine this time vaults with super resolution and expansion microscopy. So then you could locate where the time vaults were in a cell. Right now, they're just sort of lysed and in a test tube. But imagine, you know, you stick it under a microscope, you could locate where in the cell it is. Is it next to the nucleus? Is it next to the endoplasmic reticulum, so on and so forth? Is it next to the cell membrane?
1:19:36 Krishna Choudhary? Synthetic organelles, you could have programmable delivery vehicles that will just like go through. I think it's, it's, it's very, very cool.
1:19:44 Lester Nare? My mind is just.
1:19:46 Krishna Choudhary? Yeah, there's so much that you can do with this.
1:19:48 Lester Nare? This, this, this was a go. Again, we don't always like to give credit to our, two of our arch rivals in Harvard and MIT. But kudos, guys, you know.
1:19:59 Krishna Choudhary? This was a good one.
1:20:00 Lester Nare? Still not Princeton, but you know.
1:20:04 Lester Nare? Credit where credits due.
1:20:05 Krishna Choudhary? This one's a good one. I thought that was really cool.
1:20:08 Lester Nare? That was, that was fantastic. Time vaults storing, oh, my, my brain. Every week, I know for those of you who watch and listen, my brain's constantly being, my mind's constantly being blown. But like the, the implications of some stuff we talk about is just insane. We're gonna go to our last main story of the day, which is going to be about ancient mathematics. Ancient maths.
1:20:31 Krishna Choudhary? Yeah.
1:20:31 Lester Nare? As they say, uh, over, over the, across the pond, which right now we're having some sibling rivalry with. This story is in the Journal of World Pre-History. Uh, the dawn of art and mathematics, ancient Mesopotamian pottery reveals early mathematical thinking.
1:20:52 Krishna Choudhary? Yes.
1:20:53 Lester Nare? So we've been thinking about math, the maths.
1:20:55 Krishna Choudhary? For quite a while.
1:20:56 Lester Nare? Quite a while.
1:20:57 Krishna Choudhary? And it, it used to be that we thought math from the fourth millennium B.C., right? The Sumerian city-states, they had these like tablets that had stuff like the Pythagorean theorem. They even had the quadratic formula like figured out, which I think is very, very cool, right? And they had a base sixty system, which we still use today when we talk about like, uh, minutes to an hour, seconds to a minute. Um, angles, things like that. We still use base sixty. This is a new discovery that says that Hallophian pottery, which is six thousand B.C.
1:21:32 Krishna Choudhary? It's in northern Mesopotamia. This might contain geometric sequences. And the first evidence of humans doing math, this is a thousand to two thousand years before the Sumerian city-states. Okay. And it's a pretty cool study and we're gonna get into it. I have some.
1:21:49 Krishna Choudhary? I don't know much about anthropology and so maybe I'm maybe I'm not getting it, but I think it's still a really cool study and we'll get into some of the qualms that I have later on, but it's not much. Okay, so this time period is sixth millennium B.C. Late Neolithic Revolution, right? The Halafians were this culture that were widely dispersed in a network in northern Iraq and Syria. So this is above the Euphrates and the Tigris rivers. Sixth century, sixth millennium B.C. Way, way back. Okay. So this is right when we're coming out of the post-Ice Age stabilization. The climate is becoming sort of stabilized and the world population is about 40 million. It's quadrupling. It's like growing really fast. Humans are, you know, getting better.
1:22:34 Krishna Choudhary? They used to live in these distinctive circular toloï dwellings, mud brick dwellings, agricultural villages. They used to have dry farming, so no irrigation as of yet. They were just relying on the rains to make wheat and barley. They used to have herding for sheeps and goats. And before the Halafians, the most of the art was dominated by animals. Okay, this is an example of cave paintings from 40,000 years ago from Lascaux, France. I believe that's how they pronounce it over there. That's how it's spelled anyways. So I don't know any better, but 40,000 years ago,
1:23:15 Krishna Choudhary? they were making a bunch of cave paintings that were a bunch of really beautiful animals and things like that. Right? Halafian pottery comes in 6,000 B.C. Very beautiful, first of all. The pottery itself is like really, really nice. Okay? And this pottery contains a shift between just focusing on animals to now also focusing on the botanical world.
1:23:39 Lester Nare? Okay.
1:23:39 Krishna Choudhary? Okay, so if you go to the next slide, there's examples of plants on pottery, plant art, and this is a really fundamental cognitive shift from this hunter-gatherer, animal-centered view to now farmers and plant-centered.
1:23:56 Lester Nare? The vegetarians, man.
1:23:57 Krishna Choudhary? Yeah, I mean, because farming becomes the way of life, right? To create civilization.
1:24:02 Lester Nare? Hundred percent.
1:24:03 Krishna Choudhary? To create population. So.
1:24:06 Krishna Choudhary? The idea with this paper is maybe this change is what's creating now mathematics and the need for mathematics, right?
1:24:13 Lester Nare? Because you're shifting into this system that naturally benefits from some foundational
1:24:21 Krishna Choudhary? mathematics. Right? Because now you have like communal stuff.
1:24:24 Lester Nare? Yeah.
1:24:25 Krishna Choudhary? That you need to split up.
1:24:26 Lester Nare? Yeah.
1:24:27 Krishna Choudhary? Okay? So let's get into the history of human mathematical thought, right? Paleolithic, there was this thing called the Ishango Bone, which was discovered in the Congo in 1960. This is, it's thought that the first example of mathematics, now it's in a Belgian museum because of course the Belgians.
1:24:44 Lester Nare? Boo.
1:24:45 Krishna Choudhary? Yeah. The Belgians did great things for the Congo, right? And for those who are listening, my face is very sarcastic. Okay? The Belgians were probably the worst colonizers of all the colonizers. So, but they got the bone and now it's in one of their museums. Great. So why do we think this is a mathematical tool? Well, it's got all these like notches on it that happen to be prime numbers, which is very cool.
1:25:12 Lester Nare? Yeah.
1:25:13 Krishna Choudhary? Right? Like 20,000 years ago, they're putting in these notches that are prime numbers. It could be like a counting tool. This is very advanced, right?
1:25:19 Lester Nare? Yeah, for 20, anyway.
1:25:21 Krishna Choudhary? 20,000 years ago, right? There's some criticism that maybe it's just a tally stick or like the notches are for better grip, but the prime numbers are kinda.
1:25:32 Lester Nare? Specific.
1:25:33 Krishna Choudhary? Specific, right? So I like that one. Okay? I'm just gonna go ahead and say I like that one. There's, there's an understanding about Neanderthal yarn. This came out and what, what they were doing was microscopic analysis of yarn that they found in a Neanderthal cave and it showed evidence of an intertwined three ply cord.
1:25:54 Lester Nare? Okay.
1:25:55 Krishna Choudhary? And if it's intertwined like that, you know, where it's like you're doing braids, then there's some understanding of mathematics, right? You gotta do three and then one under and then two and then one under, so on and so forth. So maybe the Neanderthals had basic mathematical concepts, right? Then we get into about 8,000 B.C. There's something called the token system, which is again in Mesopotamia. These early farmers used geometric clay tokens like triangles, cones, spheres for one-to-one accounting. And there's evidence that three cones would mean three measures of barley, and so on and so forth, right? And amidst this is where we get the Halafian gap, which is where this paper sort of fits in. Okay, it's a paper that was out very recently, and it's showing that the Halafian period,
1:26:40 Krishna Choudhary? which is about 6,000 to 5,000 B.C., it predates the Sumerian writing. And perhaps the pottery is evidence that it's not just aesthetics that they were going for, but they were going for some kind of mathematical codification for their agricultural society.
1:26:58 Lester Nare? Okay.
1:26:58 Krishna Choudhary? Okay? And this is, we're getting into something called cognitive archaeology, which is reconstructing ancient thought. It's always very hard to do.
1:27:06 Lester Nare? Yes.
1:27:07 Krishna Choudhary? Ethnomathematics, which is inferring math from indirect indications, like we did with that bone.
1:27:13 Lester Nare? Yes.
1:27:13 Krishna Choudhary? From the Congo. So it's very hard to do. All right? So this is not an exact science, but I still think it's incredibly cool because I love thinking about how we got here.
1:27:23 Lester Nare? How do we get out of the cradle of civilization?
1:27:25 Krishna Choudhary? Yeah, yeah. And how do we form this kind of amazing society, right?
1:27:29 Lester Nare? Yes.
1:27:29 Krishna Choudhary? To think about something that happened 8,000 years ago is, I think, very, very cool.
1:27:33 Lester Nare? Yes.
1:27:33 Krishna Choudhary? So let's get into the paper. They did a survey of pottery from 29 different agricultural sites across northern Mesopotamia.
1:27:41 Lester Nare? Archaeological sites.
1:27:42 Krishna Choudhary? Yes, yes. What did I say?
1:27:44 Lester Nare? Agriculture.
1:27:45 Krishna Choudhary? Oh, yeah, yeah. Archaeological sites. I guess they were agricultural, but you're right. This is archaeological sites where they analyzed tens of thousands of painted shards of pottery. Okay? So they have, one thing that's very important is they have a very large statistical sample. This is quite rare.
1:28:01 Lester Nare? I was gonna say, that's, I was literally gonna say, I can't imagine there's a lot of archaeological sites where we have that volume.
1:28:06 Krishna Choudhary? Yes.
1:28:07 Lester Nare? Of stuff.
1:28:07 Krishna Choudhary? Yes. So this is a lot of data from tens of thousands of shards from all over this geography. And what we find. What they find is vegetal motifs, so motifs of plants that are a shared cultural language. The entire Halafian territory had this language. If you look at pottery from one end all the way to the other, you've got plants. So that means this isn't like a one-off thing.
1:28:32 Lester Nare? Right.
1:28:33 Krishna Choudhary? Okay, this is a kind of cultural language that goes across the entire civilization, right? And there's an average frequency of these motifs, which is pretty significant. About four to six percent of all of the pottery has this. And given the amount of data that we have, we can actually be very confident that this is there, right? Now, the motifs are classified into four basic categories, and there's a critical subgroup. There's a bunch of large flowers, okay? And these flowers are on big bowls, and the basis of these bowls, and they happen to be in radial patterns.
1:29:07 Lester Nare? Yes.
1:29:07 Krishna Choudhary? Here you can see there's four, then you have eight, so you get this doubling, right?
1:29:11 Lester Nare? Yes.
1:29:12 Krishna Choudhary? You get four, which is a cross, and then you have each of the crosses, so you get a doubling and you get eight.
1:29:17 Lester Nare? Yes.
1:29:17 Krishna Choudhary? And then these radial encodings don't just stop at eight, they keep going on and on. So then you get sixteen, you get thirty-two, and the one that's really crazy for me is all the way to sixty-four.
1:29:29 Lester Nare? Yeah.
1:29:30 Krishna Choudhary? Okay?
1:29:30 Lester Nare? Yeah, yeah.
1:29:31 Krishna Choudhary? Getting thirty-two petals, I can imagine you do four, then you, you know, you do the pizza cut for eight, and then you do another pizza cut for sixteen, then you do another pizza cut for thirty-two. But if you've ever cut pizzas for like a large group of people and you've only got one pizza, which happened to me once, it was the worst party ever, you can't get to sixty-four, because then at that point, it's like you're doing like atoms of bread, you know? And so what they did with the sixteen, with the sixty-four is they divided it into four quadrants, and then they had sixteen in each, a four by four sort of, a four by four grid in each of the four quadrants to give sixteen times four, which is sixty-four.
1:30:10 Lester Nare? Yes.
1:30:10 Krishna Choudhary? This is pretty convincing that there is some mathematics.
1:30:14 Lester Nare? Yes.
1:30:14 Krishna Choudhary? That's happening, right?
1:30:15 Lester Nare? Yeah, that level, the complexity, once you start getting to that size, I mean, also, these designs are beautiful.
1:30:20 Krishna Choudhary? These designs are beautiful for eight thousand years ago.
1:30:22 Lester Nare? Yeah, they're not just like-
1:30:23 Krishna Choudhary? Like, the patterns are amazing. The checkerboard, the radially outward, like, even in terms of symmetry.
1:30:32 Lester Nare? Yes.
1:30:32 Krishna Choudhary? Eight thousand years ago, this is incredible symmetry.
1:30:35 Lester Nare? I totally agree. I'd say, I mean, I- Can barely get that out of ChatGPT today.
1:30:40 Krishna Choudhary? Yeah, exactly. So, so the the authors argue that there's some kind of consistent use of these two to the power of two, two to the power of three. So you have four, eight, sixteen, thirty two and sixty four. And these are not, these are not by coincidence. There's some kind of having logic, right? Where the sequence emerges because of some intuitive geometric operation, we are dividing a circle into a bunch of parts, right? And now comes the theoretical side of things, that these Halafian villages used to have communal sharing economy, and then the crops, like grain or barley, had to be shared out fairly to everyone in the population.
1:31:23 Lester Nare? So they had, they had the sharing economy. What do we call it now with the Uber and the Instacart?
1:31:29 Krishna Choudhary? Oh, yeah. What are those called?
1:31:30 Lester Nare? It's not sharing economy. It's, is it?
1:31:32 Krishna Choudhary? Uber pool?
1:31:33 Lester Nare? No, the creator economy. Anyway.
1:31:35 Krishna Choudhary? Yeah.
1:31:36 Lester Nare? They used to have that.
1:31:37 Krishna Choudhary? They used to have that. Yeah, all the way back then, right? And there's, there's more, there's more evidence that there used to be complex geometric subdivisions, because if you look at the stamp seals from the Halafian period, the stamp seals also have this very nice geometric pattern. And these were seals that were used to mark property and secure trade items. So it supports this idea that there's some sophisticated economic administration.
1:32:00 Lester Nare? Yes.
1:32:00 Krishna Choudhary? And perhaps this kind of economic administration would require basic mathematics of two to the power of whatever.
1:32:07 Lester Nare? Yes.
1:32:08 Krishna Choudhary? Right?
1:32:08 Lester Nare? Okay.
1:32:09 Krishna Choudhary? Now, there are examples of other numbers.
1:32:14 Lester Nare? Okay.
1:32:15 Krishna Choudhary? Okay, like there are examples of six or seven.
1:32:19 Lester Nare? Six.
1:32:20 Krishna Choudhary? Or like twelve, thirteen. And what the authors argue is that these show less meticulous craftsmanship. This is where I'm like. I don't know, that still looks pretty good to me.
1:32:32 Krishna Choudhary? Right, six, seven, 12, 13, these still look very beautiful. So, I don't know, I'm not a anthropologist. Maybe there's some way to quantify, right? That these are less beautiful than the ones that were 16 and 32. There's also some pushback in the CNN article. There was a professor Jens Heyrup from Roskildeik University in Denmark. He specializes in Mesopotamian mathematics. And he was not convinced. He said that the symmetry is just an isolated incident of mathematical technique, rather than the evidence of a broader mathematical reasoning. If you've just got to divide the circle nicely, of course, you're going to get powers of two. Now, he's an expert in Mesopotamian mathematics,
1:33:16 Krishna Choudhary? which tells me that he's probably of the Sumerian city-states camp. And he wants the Sumerian city-states to be first. So, you know, there, obviously with science, there's a lot of like human tension.
1:33:28 Lester Nare? Yes.
1:33:29 Krishna Choudhary? And it's worth something to think about, like, you know, is this just symmetry? Or is consistently dividing a circle into 32 equal parts and then 64, it's inherently performing a mathematical operation without written symbols? Right?
1:33:47 Lester Nare? Yeah.
1:33:47 Krishna Choudhary? It's an open question. I, I think it's, the symmetry is clear to me.
1:33:51 Lester Nare? Yes.
1:33:51 Krishna Choudhary? And to me, we've had a lot of discussions about symmetry on this podcast. And so symmetry is inherently a mathematical principle.
1:33:57 Lester Nare? Yes.
1:33:58 Krishna Choudhary? So, to me, I, I think this is pretty cool, right?
1:34:02 Lester Nare? If you have not listened to it, check out our Chen Yang episode. I think it's episode 18 or 19.
1:34:07 Krishna Choudhary? From season one, yeah.
1:34:08 Lester Nare? From season one, where we go deep into the concept of symmetry. And, and it's, it's, that was a lot of fan favorite episodes. I, what's interesting here is I do, I think, get the tension of, like, there's, it looks aesthetically good versus understanding a broader mathematical context of why it looks so good.
1:34:28 Krishna Choudhary? Yeah.
1:34:29 Lester Nare? That feels fair to me.
1:34:31 Krishna Choudhary? Yeah, yeah.
1:34:31 Lester Nare? Like, I can sort of see, like, yeah, like, you know, I make things that look good all the time. I don't know the maths behind it.
1:34:36 Krishna Choudhary? Yeah.
1:34:38 Lester Nare? But given how early it is, even being able to compute aesthetic value.
1:34:44 Krishna Choudhary? Yeah, and have it all over the civilization, right?
1:34:47 Lester Nare? And clearly, it was a part of some aspect of culture, whether it's economics or otherwise.
1:34:53 Krishna Choudhary? Yeah.
1:34:53 Lester Nare? That it's not just for.
1:34:57 Krishna Choudhary? It's clearly a shared visual language.
1:34:59 Lester Nare? Yes.
1:34:59 Krishna Choudhary? Right?
1:34:59 Lester Nare? Yeah. Yes, yes. And so this is interesting. So what is your, what is your conclusion here?
1:35:07 Krishna Choudhary? My conclusion is that I do think that they were doing something mathematical because of the 64.
1:35:12 Lester Nare? Okay.
1:35:12 Krishna Choudhary? Bowl.
1:35:13 Lester Nare? Yeah.
1:35:13 Krishna Choudhary? The 64 bowl with the four quadrants and then the four by four grid in each of them, that was like, that was, that was pretty like, oh, okay, that's like, you know, they're doing something.
1:35:22 Lester Nare? Yeah, no.
1:35:23 Krishna Choudhary? You know, but again, it could just be symmetry. I like to think that there's mathematics because I just like to find the beauty in things, but you know, who knows?
1:35:34 Lester Nare? For those who have stayed this long and worked through mathematics, which you've always said, we're never going to cover mathematics. And you broke your rule because it's so good. And it was kind of light mathematics.
1:35:46 Krishna Choudhary? Yeah.
1:35:46 Lester Nare? A little light, you know, mathematics, light. What do you guys think? Do you think this Halafi work on the pottery and stuff, do you think it's math? Do you think it's art? Do you think it's art math, math art? Let us know in the comments. As always, we like to know how folks get to the end of the episode. And it just helps us with that little comment. We are going to wrap up here today with a follow up from the cloud nine story.
1:36:19 Krishna Choudhary? Yeah.
1:36:20 Lester Nare? Potential for a dark matter gas cloud from the last episode. I'll let you take it away here.
1:36:25 Krishna Choudhary? Yeah. I mean, we, at the end of the last episode, we asked our audience, what do you guys think? Cause the name Cloud Nine. And, you know, some of the authors of the episode that we sent the link to, they actually made it that far as well, which is great.
1:36:42 Lester Nare? Yes.
1:36:42 Krishna Choudhary? And they were asking, they actually let us know.
1:36:46 Lester Nare? Yes.
1:36:46 Krishna Choudhary? What is the story behind the name Cloud Nine? So this particular response comes from Alejandro Lombe, but actually, most of the authors of that study responded with very similar takes. I'll just sort of paraphrase how he put it. So back in February 2023, he read a paper about a potential dark galaxy candidate that was identified by the FAST telescope, which is the big Arecibo-like telescope in China. And the authors were initially unaware of Alejandro's earlier paper, where he had described this idea of relics.
1:37:18 Lester Nare? Yes.
1:37:18 Krishna Choudhary? He was one of the original authors of that relics paper, being like, hey, there should be something like this out there.
1:37:23 Lester Nare? Yes.
1:37:24 Krishna Choudhary? So he emails them, the gas cloud that he emailed them about turned out to actually be a galaxy. So when you point at optical telescope, you see stars and it's just a galaxy. Then, the same FAST guys.
1:37:35 Lester Nare? Yes.
1:37:36 Krishna Choudhary? In China, they look at this object, Cloud Nine. And Cloud Nine was named Cloud Nine because it was the ninth object that they had seen in that direction. Okay, so it was just the Cloud Nine. And in China, there's no sort of cultural meaning for the phrase Cloud Nine. The FAST guys then emailed Alejandro back, being like, hey, this could be a new candidate. And this was the ninth cloud in their radio survey. The authors were aware of Alejandro, and then they sort of teamed together. They went, looked at the analysis from the VLA. The VLA actually could pinpoint where Cloud Nine was, because the FAST telescope is this giant thing that's just sort of like stuck to the earth, right? So it doesn't have very good angular resolution on where this thing is coming from. VLA could
1:38:20 Krishna Choudhary? then pinpoint and be like, it's actually right there.
1:38:22 Lester Nare? Right.
1:38:23 Krishna Choudhary? Once you have those coordinates, then you can go to the Hubble guys at NASA and be like, hey, look. I actually know where it is and I'd really like to look at it. The Hubble guys gave the author some time and that's where we get that paper from Cloud Nine. They kept the name because you know, if it turns out that Cloud Nine is a relic, then the authors would be on Cloud Nine. So they kept that name for that reason. But that's, that's, that's what's behind it, which is, which is very cool.
1:38:50 Lester Nare? We always love naming conventions on this show.
1:38:53 Krishna Choudhary? Yeah.
1:38:54 Lester Nare? And it was great to get outreach from everyone on the team.
1:38:56 Krishna Choudhary? Yeah, that was awesome.
1:38:57 Lester Nare? If you, if we happen to cover, if you're listening now and you happen to be in a lab, on a research team, having had a story by us covered at some point and there is a correction, you can always make sure you reach out to us to, to facilitate that correction in a future episode. We do our best to cover it as accurately as possible, but there's no one better than the experts. And so we are really grateful that the team for the relics paper were just so enthusiastic and providing feedback and loving the coverage. This was a fantastic episode 23.
1:39:35 Krishna Choudhary? Yep.
1:39:36 Lester Nare? The time vault story is still so nuts to me. Wrapping notes for housekeeping, again, if you want us to cover a paper, you can go to ffpod.com backslash submissions. We have a Reddit style upvote, downvote ranking board on there that can help you in the community, provide us stories you want to cover, us to cover in the future. As we mentioned earlier in the pod, we do have a, an Artemis special coming up next week. So that will be a one story deep dive. We will probably still do a rundown as well, but just if you're listening this far, you're a fan, just be aware of that. So you're not disappointed when you tune in next week. We're going to enter a bunch of weeds.
1:40:20 Lester Nare? I am your host, Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary. This is From First Principles.
Previous Cloud9 Dark Matter Halo, Jellyfish Sleep, and String Theory Hidden in Nature (EP. 22) Next Artemis II, Apollo, and the Physics of Going Back to the Moon (EP. 24) Page updated October 31, 2026 · transcript and summary are machine-generated