3I/ATLAS Explained, Forensic Fingerprints & Alzheimer’s Breakthrough (EP. 18)

Hosted by Lester Nare and Krishna Choudhary, this episode spans astrophysics, forensic chemistry, and neuroimmunology. We begin with a deep dive into 3I/ATLAS, only the third confirmed interstellar object to ever pass through our solar system — larger and stranger than ‘Oumuamua and Borisov, with new imagery released as NASA reopened operations. Then we break down a true-crime forensic breakthrough from Maynooth University that reveals how to recover fingerprints from fired bullet casings — a technique that could radically accelerate criminal investigations. And we close with a Max Planck Institute discovery identifying a regulatory microglial state in the brain that may finally clarify why Alzheimer’s develops — and how immune dysfunction, not just plaques, drives the disease. Summary The third interstellar visitor — 3I/ATLAS joins ‘Oumuamua and Borisov as only the third object ever observed entering the solar system from interstellar space, with new NASA imagery revealing structure, trajectory, and compositional clues. A forensic chemistry breakthrough — researchers at Maynooth University develop a technique to retrieve latent fingerprints from fired shell casings, combining heat-stable organic residues with spectroscopic imaging. A new model of Alzheimer’s — Max Planck Institute scientists uncover a microglial “regulatory” state (a T-reg–like analogue) activated through CD28-dependent pathways, reshaping how the field thinks about plaques, neuroinflammation, and therapeutic targets. Show Notes 3I/ATLAS — Interstellar Object Updates (NASA / JPL) Forensic Chemistry: Fingerprints on Fired Casings (Maynooth University) Alzheimer’s Microglia Study — Max Planck Institute / Univ. of Cologne

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Lester Nare?

  Hello, Internet. This is your captain speaking, Lester Nare, joined as always by my co-host and our resident PhD Krishna Choudhary. My friend, how are you?

• 0:10Krishna Choudhary?

  Pretty good.

• 0:11Lester Nare?

  You have any exciting Thanksgiving plans for the week?

• 0:14Krishna Choudhary?

  Uh, yeah, I'm actually, I'm gonna go to Maui with, um, my parents. It's gonna be great. Yeah.

• 0:20Lester Nare?

  That's awesome.

• 0:21Krishna Choudhary?

  Yeah. Hopefully, I'm gonna get to see the, the, the Daniel K. Anyway, telescope.

• 0:26Lester Nare?

  I was actually gonna ask if you're gonna make a trip out to the.

• 0:28Krishna Choudhary?

  Yeah, yeah. We're definitely gonna make a trip out. I don't know if the telescope is operating, but, um, you know, it'd be nice to see whatever I can.

• 0:36Lester Nare?

  Absolutely, absolutely. And it's, uh, an interesting dovetail, at least on the observatory piece for

• 0:42Krishna Choudhary?

  Yeah.

• 0:42Lester Nare?

  the story we're gonna spend a lot of time on today, which is, we're gonna talk about the 3I Atlas. We now have the observations.

• 0:49Krishna Choudhary?

  Yep.

• 0:49Lester Nare?

  We've had time to put it together. We did touch this on this once before.

• 0:53Krishna Choudhary?

  Yes.

• 0:54Lester Nare?

  So we're doing a little bit of an update based on all of the latest.

• 0:58Krishna Choudhary?

  Yeah.

• 0:58Lester Nare?

  and greatest. Uh, it's been in high demand. We're gonna start off with 3I Atlas today, followed up by a new story that's gonna be out of my youth university in Ireland. It was in forensic chemistry around a new technique for taking fingerprints off of fired bullet casings. So this is a, a new forensic technique that will, uh, help us catch the bad guys even better. Ending with a, a, a new Alzheimer's, uh, sort of discovery around microglia, uh, or immune cells that are in our brain.

• 1:28Krishna Choudhary?

  Yeah.

• 1:28Lester Nare?

  This is a combination of a couple of universities in nature, Icahn School of Medicine at Mount Sinai, Max Planck Institute of Biology and Aging, and the University of Cologne. So three incredible stories. We're gonna touch on all the details.

• 1:42Krishna Choudhary?

  Yep.

• 1:42Lester Nare?

  This is from First Principles.

• 2:01Lester Nare?

  So our first story of the day is 3I Atlas.

• 2:04Krishna Choudhary?

  Yes.

• 2:05Lester Nare?

  This is the one that obviously everyone keeps asking us about because the government is back open.

• 2:10Krishna Choudhary?

  Yeah.

• 2:11Lester Nare?

  And so NASA has now released new imagery.

• 2:15Krishna Choudhary?

  Yes.

• 2:16Lester Nare?

  So let's sort of just start right from, from the top here.

• 2:20Krishna Choudhary?

  Yeah, I mean, it's, it's a, it's an interstellar visitor, as we all know. It's the third interstellar object. There's been two predecessors that it's had. The first one was Oumuamua. The second one was 2I Borisov, and this is the third and the largest one that we have by far.

• 2:39Lester Nare?

  Okay.

• 2:39Krishna Choudhary?

  Okay. Oumuamua was a really strange watch. It was an inert, highly elongated object that was flying through. Then we had 2I Borisov, which was basically just like a normal comment, comet, like any other comet that we'd seen. The only thing that was really different was that it was moving so fast that it wasn't trapped by the sun's gravity. Right? And then now we've got finally this guy, 3I Atlas. The I stands for interstellar. The 3 stands for the fact that it's the third. And the Atlas stands for the fact that it was discovered by the Atlas system, which is the asteroid terrestrial impact last alert system. These are a bunch of telescopes all over the world. The one that actually discovered this was in Chile.

• 3:24Krishna Choudhary?

  And the whole point of this telescope system is to find near earth objects or objects that are coming through and gonna be a little bit close.

• 3:33Lester Nare?

  Right.

• 3:33Krishna Choudhary?

  Right? In our solar system.

• 3:34Lester Nare?

  Right.

• 3:35Krishna Choudhary?

  It preferentially looks in the plane of the planets.

• 3:39Lester Nare?

  Okay.

• 3:40Krishna Choudhary?

  Right? So.

• 3:41Lester Nare?

  Meaning?

• 3:42Krishna Choudhary?

  Meaning, so if the sun is here.

• 3:44Lester Nare?

  Yeah.

• 3:44Krishna Choudhary?

  All of the planets revolve around the sun in the same sort of plate.

• 3:49Lester Nare?

  Got it.

• 3:50Krishna Choudhary?

  It's not like the Big Bang Atom.

• 3:52Lester Nare?

  Okay.

• 3:53Krishna Choudhary?

  From the, from the show where it's like, you know, there's one going this way, there's another going the other way. They're all sort of along the same plane.

• 4:00Lester Nare?

  Makes sense.

• 4:00Krishna Choudhary?

  Right?

• 4:00Lester Nare?

  Yes.

• 4:01Krishna Choudhary?

  And that's because when the solar system first formed, there was some, some angular momentum of that cloud. So when it collapsed, you know, everything has to be on that plane to preserve the angular momentum.

• 4:12Lester Nare?

  Makes sense.

• 4:13Krishna Choudhary?

  So that's actually why we discovered this thing. And one of the reasons why it's sort of taking a tour of the planetary systems, right? It's kind of by design that Atlas finds objects that are along this plane, right? So it begs the question, there might be other objects that are not in the plane that we're not really sensitive to.

• 4:34Lester Nare?

  Right.

• 4:34Krishna Choudhary?

  But perhaps with the new Verarubin telescopes and things like that, we will be. But in any case, that's how it got its name, right? It's inbound, it's got an extremely hyperbolic orbit. So an eccentricity of approximately 6.2. The earth is basically at a one, it looks like a circle, right? But this thing is extremely hyperbolic. You can see that it's going so fast, 58 kilometers per second, that it barely even changes its orbit.

• 5:05Lester Nare?

  As it?

• 5:06Krishna Choudhary?

  As it passes the sun, right?

• 5:07Lester Nare?

  Right.

• 5:08Krishna Choudhary?

  Unlike the, you know, the Wicked movie, there's that, one of my favorite songs is like, like a comet pulled from orbit. As it passes the sun, this is not doing that. It has not changed in any, in any real sense, for the better or the worse. But it's 58 kilometers per second, right? That's a, that's a velocity that's three times higher than what's expected for a usual star encounter.

• 5:35Lester Nare?

  So this thing's moving extremely, extremely quick.

• 5:38Krishna Choudhary?

  Yeah, yeah, and it begs the question, like, what even gave it its speed?

• 5:42Lester Nare?

  How did it reach that?

• 5:43Krishna Choudhary?

  Yeah, how does, how does something move that fast through the solar system? And the orientation is, it's also retrograde. The other weird thing is, you know, in the Milky Way, the sun is moving around the Milky Way, right?

• 5:58Lester Nare?

  Yeah.

• 5:58Krishna Choudhary?

  And the plane of the planets is about perpendicular to the motion.

• 6:05Lester Nare?

  So are the, were our entire sort of solar system is moving through the Milky Way galaxy like, let's say on the X axis? But then the orbit of the planets in that context while we're doing that is on the Y axis?

• 6:18Krishna Choudhary?

  Isn't this Y, right? And so, and so. When, when 3I Atlas, when we say that it's taking a tour of the solar system, what it's really doing is it's like going piercing through the Milky Way in some sense, right? It's not moving, I mean, obviously it has some direction along the Milky Way's rotation as well, but it's going through the plate of the Milky Way as well. That's why it's going through all the planets in the plane of our ecliptic.

• 6:45Lester Nare?

  Which, which is, which is sort of a cosmic, the cosmic serendipity there is, is, is.

• 6:53Krishna Choudhary?

  Yeah, it's, it's kind of a mystery where it came from and things like that. And we're going to get into some of that later. So, um, there's been some milestones that have happened since the last time we talked. It flew by Mars on October 3rd, 2025. That was when it got as close as it possibly could. And that was a really cool way of providing a local observation, right? Because we have the Mars Reconnaissance Orbiter around Mars. The ESA, the European Space Agency has a bunch of stuff around there. And it's about 28 million kilometers away from these guys. So you can get some, at least some closeups, you know, it's still far away.

• 7:32Lester Nare?

  28 million kilometers.

• 7:33Krishna Choudhary?

  Yeah, yeah, yeah. It's still, it's like, it's close enough, right?

• 7:36Lester Nare?

  Yep.

• 7:37Krishna Choudhary?

  And then on October 30th, 29th, it had its closest approach to the sun, which was a, which was at a distance of 1.36 astronomical units. One astronomical unit is the orbit of the earth. So it didn't even get closer than earth is to the sun.

• 7:53Lester Nare?

  Got it.

• 7:53Krishna Choudhary?

  Okay. Um, a lot of comets, you know, the, the really bright ones get within earth's orbit, sometimes even like as close as Mercury, right? As close as like between Venus and Mercury. And those are the ones that glow and you can see with your naked eye. This one, not so much, right? It, it wasn't that, it wasn't that close. And then finally, in December 19th, it's going to be well outside the earth's orbit, but that's when it's actually going to be the closest to earth. It's going to be 80% of the distance between earth and the sun, but it's going to be in the other side.

• 8:25Lester Nare?

  Yep.

• 8:26Krishna Choudhary?

  Right? So the sun will be in front of us, the comet will be kind of behind us.

• 8:31Krishna Choudhary?

  That's when it's going to get closer.

• 8:32Lester Nare?

  Okay.

• 8:32Krishna Choudhary?

  So. I told you that it's it's got a really weird orbit, right? It's it's coming through really fast and it's going along the plane of the planets. It's unclear whether it's coming from a part of our Milky Way called the thin disk, which is really what you see when you look out in the night sky and you see the Milky Way, or from the thick disk. Because if you trace back, the yellow trajectory here shows where the the comet is, and the red trajectory is where we are, where the sun is. And it's sort of like playing tag and go with our sun because it's about the same distance away from the center of the Milky Way as we are. And so it's going to be kind of sharing our orbit, the same way that, you know,

• 9:16Krishna Choudhary?

  you can imagine the Trojan asteroids outside of Jupiter. They share the same orbit with Jupiter and they move around with Jupiter. The James Webb Telescope is orbiting the sun with the Earth, right? Because it's it's feeling the same gravitational pull from the sun that the Earth is and the moon is. So the question is, where where did it come from?

• 9:37Lester Nare?

  The the idea is as we are traveling through the Milky Way, we're going on a particular orbit and the the way that 3A Atlas moves through the Milky Way is in that similar similar circular orbit. In in in the radius of that orbit is

• 9:54Krishna Choudhary?

  Yeah.

• 9:54Lester Nare?

  almost identical.

• 9:55Krishna Choudhary?

  It's almost identical, right? I mean, hence it's right here.

• 9:58Lester Nare?

  Right.

• 9:58Krishna Choudhary?

  And the Milky Way is just has a gravitational potential because of all the stars and gas in it.

• 10:04Lester Nare?

  Yep.

• 10:04Krishna Choudhary?

  And the sun is feeling the same gravitational potential that the comet is.

• 10:08Lester Nare?

  Yep.

• 10:09Krishna Choudhary?

  And because of Newton's law of gravitation, the acceleration that we feel is independent of our mass. So even though the comet 3A Atlas is really, really small compared to the sun, all objects fall at the same rate, according to Galileo, right? So it doesn't like in terms of the orbit, it's not really going to matter if it's the sun or or a star, right?

• 10:33Lester Nare?

  Yep, that's a that's a good.

• 10:34Krishna Choudhary?

  That's the that's the point.

• 10:35Lester Nare?

  Yep.

• 10:36Krishna Choudhary?

  That's why the James Webb Telescope is moving around the sun the same way that we are.

• 10:40Lester Nare?

  Right, even though it's obviously smaller than

• 10:42Krishna Choudhary?

  than than the Earth, right? So the first paper that tried to answer this was from Oxford in the Astrophysical Journal Letters. This was in July, and they said that it's from the thick disk. The thick disk is the part of the Milky Way that's just above all of the stars and the real gas. So the stuff that we see in the night sky when we look up, there's a, that's the thin disk. The thick disk is the part that's right above or below. That's an old population of stars. We know that because we can look at the spectral signatures of the stars that are above there. And, um, you know, there are these very red, um, long lasting stars with, um, lots of metal, which means they've been doing fusion for a while.

• 11:25Krishna Choudhary?

  Um, actually, um, it depends, actually, but it depends on whether it's high metal or low metal. High metal could also mean that you're, you've, you're the second or third generation of stars that, that are coming from the, the ashes of the older stars that have made the metal. And then low metallicity could mean that, okay, you just have hydrogen and helium. So like, it's like from the big bang, you've got nothing else, you know? But, uh, so there, there's ways of quantifying it. But in any case, they've quantified that a lot of these stars are between seven to 14 billion years old, right? So it's, it's much older than the sun, which is about five billion years old, right? Right. So that, that was the first one. Then there's some new work that came out in September. Um, this is not in a journal, but it's, it's on the archive.

• 12:10Krishna Choudhary?

  And it was from the Tenerife Observatory, a bunch of, um, people there in Spain. They were trying to trace back the object's origins in a similar way. And they showed that, uh, they, they used this, um, Python package called Milky Way Potential 2022, which basically what, what it can do is it can take your object and then run back the clock for however long that you want, given the Milky Way Potential. And what they found was that if you integrate over the millions of stars in that database and you go back, at least in the last 10 million years, there's no close encounter

• 12:50Krishna Choudhary?

  that's going to cause this giant velocity. Okay? If you, if you go through all of the, and those are the stars that the, the, that it had close encounters with. Yep. And none of them were close enough to really add any velocity to this thing.

• 13:09Lester Nare?

  The, the point being, Three Eye Atlas had to get its acceleration from an encounter with some celestial object at some point in its history.

• 13:18Krishna Choudhary?

  Yeah.

• 13:19Lester Nare?

  And.

• 13:19Krishna Choudhary?

  But it can't be the recent history.

• 13:21Lester Nare?

  But it can't be the recent history.

• 13:22Krishna Choudhary?

  Yeah.

• 13:23Lester Nare?

  Okay. And then when we look in this Milky Way potential 2022, and trace back the journey that it had made and the stars that it would have passed, these celestial objects would have passed on the way.

• 13:36Krishna Choudhary?

  Yeah.

• 13:36Lester Nare?

  None of those are of sufficient mass and size.

• 13:40Krishna Choudhary?

  Yeah, and, and it wasn't close enough.

• 13:42Lester Nare?

  To generate the acceleration that we're seeing. That's what the paper is trying to say.

• 13:46Krishna Choudhary?

  That's what the paper is trying to say. Right. So then they say, okay, what we can do is we can really just run back the clock, right? And we can say, okay, if it's not in our recent history, let's just treat the Milky Way as this like potential landscape and ask, how far does it deviate away from the thin disk? Right? Because what it could do, what the original paper was saying was that, you know, because it's got such a high velocity perpendicular to the disk, it must be coming from up there.

• 14:15Lester Nare?

  Yeah.

• 14:15Krishna Choudhary?

  Right? But the potential landscape is such that when it goes above the disk, the disk is going to start pulling back. And so there's going to be some oscillation through the disk, right? It's going to go up and then it's going to come back down and it's going to go down. Then it's going to get pulled back up again.

• 14:30Lester Nare?

  Yes.

• 14:30Krishna Choudhary?

  Right? So how big is that amplitude?

• 14:32Lester Nare?

  Right.

• 14:33Krishna Choudhary?

  Of that oscillation?

• 14:34Lester Nare?

  Basically, how, how high, how far above and below the thin disk?

• 14:38Krishna Choudhary?

  Yes.

• 14:39Lester Nare?

  Is it, is it?

• 14:39Krishna Choudhary?

  Is it going, right? Is it going all the way to the thick disk? Because we also have velocity profiles of the stars that are up there. There's some typical trajectories that those guys take and there's some typical trajectories that the, that the thin disk takes. Which one does this thing belong to?

• 14:56Lester Nare?

  Got it.

• 14:56Krishna Choudhary?

  Right? And so that's what they did. And what they think is happening is that it stayed basically within the thin, thin disk and. They're ruling out the fact that it could be in that upper thick disk.

• 15:08Lester Nare?

  Okay.

• 15:09Krishna Choudhary?

  They found where the velocity profile of this comet is compared to the stars in these two regions. And it's more aligned with the thin disk.

• 15:17Lester Nare?

  Interesting.

• 15:18Krishna Choudhary?

  Right. So this is kind of a clapback to the Oxford paper.

• 15:22Lester Nare?

  Which was that original?

• 15:23Krishna Choudhary?

  Which was that original one. So we're gonna have to see if Oxford comes back and says nah.

• 15:28Lester Nare?

  This is good because when we first covered this, the Oxford paper was the only one.

• 15:33Krishna Choudhary?

  Was the only one and everyone was like, okay, that's gotta be it.

• 15:35Lester Nare?

  Right.

• 15:36Krishna Choudhary?

  But the process of science is extremely dynamic, you know? There's a bunch of researchers vying for the spotlight.

• 15:42Lester Nare?

  Right.

• 15:42Krishna Choudhary?

  So, you know, someone's gonna, someone's gonna say this, the other person's gonna say that.

• 15:47Lester Nare?

  This is very good. So we now, we now are in a position in terms of the locational origin of the RiA Atlas, which initially was believed to be coming from above where we are on the thin disk and in the thick disk. But there's at least now a rebuttal.

• 16:05Krishna Choudhary?

  Yes.

• 16:05Lester Nare?

  There's at least now a rebuttal to that that can explain away the thickness origin hypothesis.

• 16:11Krishna Choudhary?

  Yeah, yeah, exactly. And now it calls into question whether it is as old as they say they are. Because it used to be, we were really excited, right? This is gonna be the oldest thing in the solar system.

• 16:21Lester Nare?

  Right.

• 16:21Krishna Choudhary?

  It's gonna be older than seven billion years old because all of the the stars that are up there are super old. And if it came from there, then it's gotta be super old too. Now, well, if it's just one of these thin disk populations that just got bumped maybe a bunch a long, long time ago, right? It's no longer maybe that old.

• 16:40Lester Nare?

  Right.

• 16:40Krishna Choudhary?

  Maybe it is, it is quite contemporary. So there's a bunch of, you know, very cool science that is still happening, trying to figure this out.

• 16:49Lester Nare?

  Trying to trace back its location, origin, location.

• 16:52Krishna Choudhary?

  Yeah. So, so that's, that's, that's the origin story. It's still in question.

• 16:56Lester Nare?

  Yes.

• 16:57Krishna Choudhary?

  Now let's talk about what it actually is and why it is so interesting. It is quite a bizarre comet.

• 17:03Lester Nare?

  Okay.

• 17:03Krishna Choudhary?

  Okay. If we're completely honest, there's a typical comet that we see in our solar system. And this is a pretty bizarre one. It's not unprecedented. We have seen comets that do the weird things that this thing is doing, but it's been like one or two.

• 17:16Lester Nare?

  Got it.

• 17:16Krishna Choudhary?

  Okay. So it's, it's rare, but it's not like totally

• 17:19Lester Nare?

  unprecedented.

• 17:20Krishna Choudhary?

  Unprecedented.

• 17:21Lester Nare?

  Yep.

• 17:21Krishna Choudhary?

  Okay.

• 17:21Lester Nare?

  Yep.

• 17:23Krishna Choudhary?

  So it's got a nucleus. The radius is about anywhere between 0.22 kilometers to 2.8 kilometers. That's how we constrained it.

• 17:33Krishna Choudhary?

  There's a lot of activity on this thing. Hyperap, it's called a hyperactive comet. Okay, there's, as the comet gets closer and closer to the sun, the solar radiation and the photons from the sun start creating chemical reactions and physical reactions on the comet's surface. And that's gonna just make it glow and do all of the cool things that it does. And a lot of the weird stuff that it does has, it's been implied that, you know, maybe there's something weird going on. If there's a techno signature, blah, blah, blah. A lot of this actually came from Avi Loeb at Harvard. But then in September, or sorry, October of this year, he came out with this model, which is a physical model for the ice coma of 3I Atlas

• 18:16Krishna Choudhary?

  with Avi Loeb and one of his collaborators, Eric Kito. And this one is trying to suggest how the physics of a comet could produce all of the weird stuff that we're seeing. Just normal comet, maybe not a normal comet, kind of a weird comet, but just ordinary physics, stuff that we know. Okay, one of the things that it tries to explain is something called the anti-tail. This was very weird, right? There was a, if you can see over there, this is from the Hubble Space Telescope. On the right is where the sun is. And there's some projection, there's like a jet from the comet coming out towards the sun.

• 18:54Lester Nare?

  Which, which is, which is counterintuitive because the idea would be if the comet is traveling at high velocity towards the sun, you would imagine the quote unquote jet would be pointing in the opposite direction.

• 19:08Krishna Choudhary?

  And there is one, yeah, and there is one. There is an anti-sun tail. And because of the way that we're looking, right? It's coming at us. So the anti-sun tail is kind of behind the comet. And the sun facing one is towards us. So because of our vantage point, it looks like the sun facing emission is that much brighter. But that's not actually true. But in any case, there is a sun facing emission, right? Okay. And then when it. Went past post peri Helion, so it went past the sun on the other side. Now there's no anti sun tail. Sorry, now there's no towards the sun tail. There's only the anti sun tail. Okay, so it disappeared. This is from the very large array. Sorry, the very large telescope, the V L T in Chile.

• 19:48Krishna Choudhary?

  So the nucleus has been, has done this thing where it had jets pointing in both directions. Yes. And then on the other side of the sun, it no longer has that. Yes. So what's going on? The model that um Kito and Lo proposed is the following, okay? So when, when the comet is coming towards the sun, there's gonna be something called sublimation. Sublimation is what happens with dry ice, where you go directly from a solid form to gas form. There's no in between of liquid because the temperature, the, the energy is enough to cause these, the C O two molecule to just free itself from the, from the gas, not transition through that liquid phase. Now, when it's happening and it's coming towards us,

• 20:33Krishna Choudhary?

  that sublimation is actually gonna cause chunks of C O two to sort of shoot out from the comet. Okay? And if you're far enough away, those chunks of C O two are gonna shoot out, but they're gonna follow with the comet because of the same thing that I said earlier, right? They're falling towards the sun the same way the comet is, even though the comet is this giant mountain Yes. of stuff. Yes. And let's say a chunk of C O two is, you know, centimeters to meters, to maybe tons of meters big. That thing is still feeling the sun's gravity. So it's gonna follow in the same sort of path. Yeah. But maybe a little bit ahead because it got shot towards the sun. Yep, yep, got it, got it. And the solar radiation out there, far away,

• 21:16Krishna Choudhary?

  is not enough to quickly melt these chunks. Okay? So it's sort of like the comet is here. You've got these chunks of, of C O two. Ahead and it's moving along the sun, right? Now, as it gets close to the sun, there's going to be so much pressure, radiation pressure and ionization pressure, that these chunks, as soon as they get out of the comet, they're just going to immediately evaporate. And so that's why we're seeing that loss.

• 21:43Lester Nare?

  Yeah, that makes sense. Yeah.

• 21:44Krishna Choudhary?

  Of the, of the front facing tail. Right? Because the closer you get, the more, the, the, the shorter the lifespan of the stuff that's getting ejected.

• 21:54Lester Nare?

  At, when it, at distance, we're seeing these large chunks break off, right? But they're in such large size and the pressure's not high enough yet. And they maintain its structure.

• 22:06Krishna Choudhary?

  Yeah, and they just follow along.

• 22:07Lester Nare?

  Right? At this slightly, you know, again, because it's basically getting

• 22:13Lester Nare?

  broken off from the front side.

• 22:16Krishna Choudhary?

  Yeah.

• 22:16Lester Nare?

  As it's making its way over, but as you get so close, the heat, the, the radiation is so high that that, the lifespan of that tail that is appearing in front doesn't, basically it's not, doesn't have a long, enough time to exist before it evaporates into going from that sublimation process. Yeah. From solid to liquid, which if I recall correctly, was also part of the original walkthrough we did about where the origins of this could have been, where it could have been around a star that had this accumulation.

• 22:45Krishna Choudhary?

  Yes, exactly.

• 22:46Lester Nare?

  Things and then, then it broke up. So there, in that first episode, it's interesting, that same process was discussed well before even this keto low paper came out.

• 22:56Krishna Choudhary?

  Yeah, and that was, that was in how it formed.

• 22:58Lester Nare?

  And how it formed.

• 22:59Krishna Choudhary?

  In the snow line.

• 23:00Lester Nare?

  Yes.

• 23:00Krishna Choudhary?

  In that ice line, right? Where the CO2 goes from gas to being able to freeze. So there's a, there's a bunch of frozen stuff right at this ice line. And maybe the comet formed there, which is why there's so much CO2 compared to water.

• 23:15Lester Nare?

  And, and which, and that's, it's basically the opposite process on the formation.

• 23:19Krishna Choudhary?

  Yes, now we're seeing it on the other side.

• 23:21Lester Nare?

  If we, if you go back and watch that episode, it does a good job. We go into detail about the concept of sublimation and that formation process. That actually kind of dovetails to what you just talked about quite nicely.

• 23:31Krishna Choudhary?

  Exactly, yeah. So, so that's the, that's sort of, um, The keto lobe hypothesis.

• 23:38Lester Nare?

  Right.

• 23:38Krishna Choudhary?

  For why we're seeing a tail sometimes and not other times.

• 23:41Lester Nare?

  The sunward extension.

• 23:43Krishna Choudhary?

  Yeah.

• 23:44Lester Nare?

  Specifically.

• 23:44Krishna Choudhary?

  Yeah.

• 23:45Lester Nare?

  The thing that was weird.

• 23:46Krishna Choudhary?

  Yeah, yeah. So I wanted to highlight that, um, that paper because I thought that was a quite interesting physical model.

• 23:51Lester Nare?

  Yep.

• 23:51Krishna Choudhary?

  That's out of Harvard astronomy. So now let's get into some of the observations that have been happening.

• 23:57Lester Nare?

  Yes.

• 23:57Krishna Choudhary?

  So the James W.

• 24:00Krishna Choudhary?

  Space Telescope.

• 24:03Krishna Choudhary?

  Infrared chemical frank fingerprinting. So this is in the infrared range. The Space Telescope took that photo. The coma is highly dominated by emission that's coming from CO2 and H2O. And one can see that the mixing ratio between the CO2 and H2O is 7.6. Which is way higher.

• 24:25Lester Nare?

  Oh, yeah.

• 24:26Krishna Choudhary?

  Than the typical solar system comets, right? The typical solar system comets are at 0.1 to 0.2. Three Atlas is all the way up there.

• 24:34Lester Nare?

  So yeah, so we're looking at this, this.

• 24:37Krishna Choudhary?

  It's a plot.

• 24:38Lester Nare?

  It's a plot. And then we, we see basically that three Atlas is well above.

• 24:43Krishna Choudhary?

  The trend line.

• 24:44Lester Nare?

  The trend line, well, well above.

• 24:45Krishna Choudhary?

  Yeah, there are a few that like the C 2016 R2. That's another comet that's local. And that's even more above than three Atlas. But these are exceptions. That's the point.

• 24:55Lester Nare?

  Yes.

• 24:55Krishna Choudhary?

  These are very much exceptions. And the fact that, you know, we've had two interstellar visitors. One is typical, the other is crazy. Of course, like N equals two is a very small. Sample size, but it begs the question, are most interstellar comets atypical?

• 25:12Lester Nare?

  Right.

• 25:12Krishna Choudhary?

  Right?

• 25:12Lester Nare?

  Right, right, right.

• 25:13Krishna Choudhary?

  It's kind of an interesting question because we don't know where they formed and how they formed, around what stars they formed and things like that. The other thing that's kind of weird about three Atlas is there's a lot of nickel. And there's not a lot of iron. This is very strange because those two usually come side by side together. Okay, they're, they're formed at the core of stars during explosions, things like that. And one can imagine that whenever they form in a dust cloud and they're in summer environment, they have typically the same kind of elemental mass. So they're going to be forming together. It's not unprecedented again, but it's definitely unusual. That there's a lot of nickel, there's not a lot of iron.

• 25:53Lester Nare?

  The ratio between these two is so.

• 25:55Krishna Choudhary?

  Yeah.

• 25:55Lester Nare?

  Uh, the, the delta is so large.

• 25:57Krishna Choudhary?

  Yeah, yeah, yeah. So, so that again, there's another question mark there. How did you get a lot of nickel on a comet, but no iron?

• 26:04Lester Nare?

  So, so we, the, the one of, one of the questions is like the velocity question, which goes to origin. One of the questions is the, uh.

• 26:12Krishna Choudhary?

  CO2.

• 26:13Lester Nare?

  The sunward extension, CO2 piece.

• 26:15Krishna Choudhary?

  Yeah.

• 26:15Lester Nare?

  And, and then, and then this is now like the, the, like a third question, which is the, um, the composition itself.

• 26:21Krishna Choudhary?

  Yeah.

• 26:21Lester Nare?

  Just to try to like quickly summarize those, those three key points that are quote in question.

• 26:26Krishna Choudhary?

  Yeah, exactly. Um, another really cool local view that we got, I was telling you about the Mars fleet that we had.

• 26:32Lester Nare?

  Yes, yes.

• 26:33Krishna Choudhary?

  So the Maven, um, probe, which is on Mars imaged through Atlas. We found a massive neutral hydrogen corona using the Lyman Alpha line, which is one of the spectral lines of hydrogen that this Maven instrument actually had access to. So from that, we can actually derive a water production rate. And there's a lot of water sublimation that's happening on that comet. Okay? Which is kind of cool, but that's not really that unprecedented. Comets have a lot of water. It used to be thought actually that, um, and it still is thought that a lot of the Earth's water came from comets because when Earth was forming, probably all the water just got evaporated.

• 27:12Krishna Choudhary?

  And then comets came and deposited their water during the early bombardment of Earth when it was forming. And one can actually look at the isotopic ratios of different isotopes in water and comets and in the ocean, and they're the same. So that suggests that there is a link. Um, the, the, the last piece from Mars that I want to highlight is the Mars Reconnaissance Orbiter High Rise. This confirmed that there is a nuclear diameter, which is probably less than 30 kilometers. That's the limit of the high resolution imager. I mean, we've had tighter constraints before. Actually, um, I saw a interview of Avi Loeb on like NBC where he was just like this, this like.

• 27:57Krishna Choudhary?

  There's nothing new here. Like, the data kinda sucks. It's like, you know, I mean, give them a break. They were supposed to, they were supposed to image Mars with this thing. They didn't know that they were gonna have like a comet on their hand that's like a astronomical unit away. But I just thought it was funny because like, everybody's like really excited about this data. But because the orbiters around Mars are built for Mars, right? As, as like, you know, within hundreds of kilometers to thousands of kilometers. Now you're asking them to image something that's thirty million kilometers away, that's much smaller than Mars. They're not gonna have a good time.

• 28:34Lester Nare?

  This, I think this is, this was, this is an important sort of side note because this, I think this has been the one thing that a lot of people have been like leaning on, which is like, we spend billions of dollars and like, you know, why is it that, you know, we can't capture imagery that is, you know, equivalent to like this? And they just bring up an example of something else. And I think for the Mars specific, for the Mars orbiter specifically, you know, it would be like asking you to take a picture of someone holding a penny on the Empire State Building from Los Angeles with your iPhone. You know, and it's like, it's not built for that.

• 29:08Krishna Choudhary?

  It's not built for that, yeah.

• 29:09Lester Nare?

  You know, maybe you could use a specialized tool to do so, but that just wasn't what was up there at the time.

• 29:13Krishna Choudhary?

  Yeah, exactly. Like wildlife photographers use giant telephoto lenses, right?

• 29:18Lester Nare?

  To get those shots.

• 29:19Krishna Choudhary?

  They, they spend thousands of dollars on that. They don't just all go up with an iPhone.

• 29:23Lester Nare?

  I, as someone who's had to take photos of my little brother at sports games and having video lenses, not a telephoto lens, uh, yeah.

• 29:31Krishna Choudhary?

  Yeah, yeah. There's a reason why the lens matters. Like, it's, it's a hardware problem at some point, right? The other really cool way of monitoring this thing was with something called Stereo A, which is solar conjunction monitoring. This is a really cool set of satellites we have on two. Sides of Earth's orbit that monitor the sun all the time. Because the Earth only sees the side of the sun that it's seeing. Right. Right? Right. What we'd like to do is see all of the sun all the time. Right. So what they do is as the Earth is revolving around the sun, they have two satellites that share Earth's orbit,

• 30:14Krishna Choudhary?

  but are on 180 degrees away from each other. So they're imaging the sun from two different sides. One is leading the Earth, the other is trailing behind us. Yep. And so with this, we can actually track 3A Atlas as it goes behind the sun. Right? Because when it was coming towards Earth, it actually went behind the sun and we could no longer see it. Well, with these two satellites, we can, we can track it. Yep. And we were tracking it and the object kept its structural integrity. Okay. Again, this thing is built for imaging the sun, not comets. Yes. But at least it could see that, okay, this thing still exists on the other side. Right. It didn't like totally disintegrate like some comets sometimes do. Yep, yep. Um, and then finally, I want to mention that ISRO, the Indian Space Research Organization,

• 31:00Krishna Choudhary?

  did some observations with the 1.2 meter Mount Abu Infrared Observatory. I have actually been to that observatory because my dad used to work there. It was, yeah, that's, that's me when I was probably like nine, nine or 10 years old. Um, taking a photo with that 1.2 meter telescope. Yes, yes. So, um, that was pretty cool that I saw that, you know, one of these observatories that my dad did a lot of research at, back when we were in India, um, did some things. They've got a really nice spectrometer there. So they found some key molecules in that spectrum. They found the swan bands, which are C2 and C3. That's two carbons and three carbons. And they also found cyanogen, which is carbon and nitrogen. Like those bonds have very specific spectra.

• 31:45Krishna Choudhary?

  And from that spectrum, we can actually find that, okay, these, these molecules do exist. And it sort of refutes any lingering claims that there's some like inert or artificial composition because again, comets are very typically have these kinds of carbon spectral lines. So that's sort of where we're at in terms of.

• 32:06Krishna Choudhary?

  3I Atlas, the, the current data, all of the current observations, not all of them. I mean, we, we still keep doing a bunch. There's a lot of actually amateur astronomers that are taking really great photos of this thing.

• 32:20Lester Nare?

  Yep.

• 32:21Krishna Choudhary?

  Which, um, which I find really awesome.

• 32:23Lester Nare?

  Yep.

• 32:25Krishna Choudhary?

  It's, it's a weird comet for sure. Probably came from a metal-rich star system. That's why it's got a bunch of nickel. The fact that it doesn't have a lot of iron is kind of weird. Um, but there, there's a lot of, there's a lot of stuff that we can do with it, right? I'm really excited for the Vera Rubin Observatory that's gonna come online.

• 32:43Lester Nare?

  Yes.

• 32:44Krishna Choudhary?

  I'm also really excited for an ESA mission called the Comet Interceptor. It's, it's this new type of mission where it's scheduled for 2029. It's gonna, it's designed for high speed flybys. Okay? And this thing is the highest speed possible, right?

• 33:01Lester Nare?

  Right.

• 33:01Krishna Choudhary?

  So now we've got sort of a parameter space on how high we think flybys can, should, should be capable of.

• 33:07Lester Nare?

  Right, right, right, right. Because, because we have a real-world data point now.

• 33:10Krishna Choudhary?

  Yeah.

• 33:10Lester Nare?

  3I Atlas of knowing like, okay, we, we are going to see objects that are moving this quickly.

• 33:14Krishna Choudhary?

  Yeah, yeah, yeah. And, and so now we need to meet those expectations of, okay, we found this thing in July, or in, uh, yeah, in July, we found it. We've got like a few months to scramble the fighter jets, to scramble the, the rockets and get this thing going. That's the capability that we need.

• 33:31Lester Nare?

  Right.

• 33:32Krishna Choudhary?

  In order to really like study these things really up close.

• 33:35Lester Nare?

  Yep.

• 33:35Krishna Choudhary?

  So, so now we have some data points to actually, you know, give us that ballpark estimate.

• 33:41Lester Nare?

  It, it, it basically gives like a sort of a mission orientation.

• 33:45Krishna Choudhary?

  Yes.

• 33:45Lester Nare?

  Uh, for, for the like, you know, what, how, how fast do we need to set up a rapid response?

• 33:52Krishna Choudhary?

  Yeah.

• 33:52Lester Nare?

  Uh, and what are the sort of implement, like what are the keys to implementation in order to be able to accomplish it and do so?

• 33:58Krishna Choudhary?

  Yeah.

• 33:58Lester Nare?

  Um, with, and I cannot wait for, I keep thinking about how with Vera Rubin, uh, the number of these interstellar objects is gonna just, uh, balloon and explode.

• 34:11Krishna Choudhary?

  Yeah.

• 34:12Lester Nare?

  If, if they're, if they are there to be, if they are there to be discovered.

• 34:16Krishna Choudhary?

  Yeah.

• 34:16Lester Nare?

  It will be discovered.

• 34:17Krishna Choudhary?

  It will be discovered by the Vera Rubin.

• 34:19Lester Nare?

  Yeah.

• 34:19Krishna Choudhary?

  100%. Um, the Vera Rubin would have discovered this thing.

• 34:23Lester Nare?

  Right.

• 34:24Krishna Choudhary?

  Had it gone online three weeks earlier.

• 34:26Lester Nare?

  Which is so crazy.

• 34:27Krishna Choudhary?

  Right?

• 34:28Lester Nare?

  It's so crazy. And would the, the, the quality of that data would have been?

• 34:31Krishna Choudhary?

  Yeah.

• 34:33Lester Nare?

  Fantastic. Again, this being a tool that is built for that type of observation.

• 34:38Krishna Choudhary?

  Yeah.

• 34:39Lester Nare?

  In contrast to the Mars orbiters, which just happen to be closer in proximity. And also able to see it at a time where we are on the other side of the sun. Uh, so very would have been, would not have been helpful during that window of time.

• 34:51Krishna Choudhary?

  Yeah, yeah, definitely not.

• 34:52Lester Nare?

  Just that window of time. Fascinating. So we still, jury's still out on origins.

• 34:59Krishna Choudhary?

  Yep.

• 35:00Lester Nare?

  Uh, locationally, like where it is coming from.

• 35:02Krishna Choudhary?

  Yeah.

• 35:03Lester Nare?

  We have.

• 35:03Krishna Choudhary?

  And that's jury's still out on age.

• 35:05Lester Nare?

  Uh, which.

• 35:06Krishna Choudhary?

  Because location is tied to age.

• 35:08Lester Nare?

  So we still don't know like where and how old.

• 35:10Krishna Choudhary?

  Yeah.

• 35:11Lester Nare?

  Um, we have an interesting explanation for the sunward extension.

• 35:15Krishna Choudhary?

  Mm hmm.

• 35:16Lester Nare?

  But that still is being developed.

• 35:18Krishna Choudhary?

  Yeah.

• 35:18Lester Nare?

  Um, it's.

• 35:19Krishna Choudhary?

  Again, that's on archive. That's not been, um, peer reviewed and published.

• 35:23Lester Nare?

  Right, right. Um, and we, you know, uh, don't quite have the explanation for the nickel iron ratio.

• 35:32Krishna Choudhary?

  No.

• 35:33Lester Nare?

  So these are still open questions.

• 35:35Krishna Choudhary?

  Yeah, yeah.

• 35:35Lester Nare?

  Um, which is fair and understandable. And it's interesting to see the.

• 35:38Krishna Choudhary?

  I mean, this thing's a few months old.

• 35:40Lester Nare?

  Right.

• 35:40Krishna Choudhary?

  Right. So. Right now, we're, we're still in the capture all the data you can. It's going to, it's in December. It's going to be close to Jupiter.

• 35:48Lester Nare?

  Right.

• 35:49Krishna Choudhary?

  So that'll be interesting. We have some probes there that perhaps can go, um, you know, orient and, and take a look. Well, I don't know what the plans are there.

• 35:57Lester Nare?

  I think what's, what is interesting is it's, you know, there has, it hasn't been clear. Or we haven't had a lot of these. So we, we've never had the opportunity to say, hey, we have all these instruments in our solar system now. Which we didn't have before.

• 36:10Krishna Choudhary?

  No.

• 36:11Lester Nare?

  We have a ton of stuff that's just out there.

• 36:12Krishna Choudhary?

  Mm hmm.

• 36:13Lester Nare?

  And when there is a, these, these ephemeral events, these events that happen, you know, in a moment in time, where are these tools going to be used to capture this data or not? And this is like proof positive that like everyone understands the import and the unique opportunity and chose to do so. So, uh, another update on 3A Atlas. I'm sure we'll do another one.

• 36:35Krishna Choudhary?

  Yep.

• 36:35Lester Nare?

  Once.

• 36:36Krishna Choudhary?

  Once it's all gone.

• 36:37Lester Nare?

  Once it's all gone and everyone's really doing that deep dive.

• 36:40Krishna Choudhary?

  Or once it, once it, um, puts probes in Jupiter.

• 36:43Lester Nare?

  Yeah, right, right. Apparently.

• 36:44Krishna Choudhary?

  We'll know in a month.

• 36:45Lester Nare?

  Uh, December 19th. It's still not done yet. So we're waiting for, uh, quote unquote, whatever, December 19th. Um, that was our story number one, uh, which was again, a quick update on 3A Atlas. Uh, we're gonna now move on to story number two, which is a very different context.

• 37:04Krishna Choudhary?

  Yes.

• 37:04Lester Nare?

  Going into a forensic story.

• 37:06Krishna Choudhary?

  Yeah, we've never done a forensic.

• 37:07Lester Nare?

  I was gonna say, I think it's our first, uh, it's our first.

• 37:09Krishna Choudhary?

  But I thought this was really cool.

• 37:11Lester Nare?

  A true crime. Uh, so if you're a fan of true crime, you're gonna love this one.

• 37:14Krishna Choudhary?

  Yeah.

• 37:14Lester Nare?

  Uh, this is out of forensic chemistry, uh, research out of Maynooth University in Ireland for fingerprints from fired bullet casings. So I think the, the top line is there's a new technique.

• 37:26Krishna Choudhary?

  Yeah.

• 37:27Lester Nare?

  That is making it more efficient to figure out who done it.

• 37:29Krishna Choudhary?

  Yeah, yeah. And from fired bullet casings, which is, which is really quite something because, um, it's kind of the holy grail of modern forensics. Okay. Is to find fingerprints from bullet cases that have already been fired.

• 37:44Lester Nare?

  Mm hmm.

• 37:45Krishna Choudhary?

  Right? Because then you can tie a suspect to actually loading the gun rather than just possession of the firearm.

• 37:52Lester Nare?

  That's actually, that's an important decision. Yeah.

• 37:54Krishna Choudhary?

  That's, that's, that's pretty big.

• 37:56Lester Nare?

  Yes.

• 37:56Krishna Choudhary?

  Um, it's a, it's a really cool methodology involving electro deposition. Um, the paper is out in forensic chemistry by Maynooth University in Ireland. The fingerprints are typically destroyed whenever a firearm discharges, right? Because you have stuff like 500 degrees Celsius, pressures of 50,000 pounds per square inch. Um, and this method exploits some organic residue that's, that remains even after all of the stress.

• 38:24Lester Nare?

  Hmm.

• 38:25Krishna Choudhary?

  And it like amplifies that organic residue to create a fingerprint.

• 38:29Lester Nare?

  Alright.

• 38:30Krishna Choudhary?

  And it's, it's very cool that the electro, the electrochemical techniques that they're using to do this. Okay. And the significance is, as I was saying, right? The print on the casing links individuals to the act of loading the gun. And before we really only have the possession of the firearm. But it could, somebody else could have done it. Somebody could have taken the firearm and done something.

• 38:51Lester Nare?

  Yep, yep, yep.

• 38:52Krishna Choudhary?

  And the prevailing consensus is the violent process of actually firing a bullet would destroy the fingerprint on the casing.

• 39:01Lester Nare?

  Right. The, the, the, the, the theory of the case is you're never gonna get the fingerprint off of the fired bullet.

• 39:06Krishna Choudhary?

  Exactly. Yeah. And it is a pretty violent process, right? Of fire. I've, I fired a gun only once. I went to a shooting range and it was like. One of the crazy, craziest exhilarating experiences I've ever had. I've never done it again. So I don't, I don't, I had to do a lot of research on how the gun works and the physics of the gun. But this is my two minute summary of the process.

• 39:29Lester Nare?

  Yes.

• 39:29Krishna Choudhary?

  This whole thing happens in under two milliseconds. You've got a casing that has gunpowder. And then you've got the bullet, which is the projectile in the front. You've got a firing pin. And when you hit the firing pin with the, the trigger, that causes a chemical reaction, which raises the temperature inside of the casing. All of that gunpowder or whatever, goes up in temperature around something like you can, you can get as much as 2,000 degrees Celsius. And then that's going to expand a lot of air, which is going to shoot the gun forward. Okay? That's not the end though, because afterwards you have to take out the casing and replace it with the next one. Right? So there's like a thing that grabs the case, pulls it back,

• 40:13Krishna Choudhary?

  throws it away and then loads up the next one. Right? So all of that stuff is going to mess with the fingerprint that's on the outside. Because when the bullet is fired, that expansion of the air is also gonna, first of all, it's going to heat up everything. So any organic residue that you have, like the proteins or any carbon, that's just going to burn up. Then the, the casing itself is going to expand into the chamber. And when it, and when you pull it back, that friction is going to then again destroy any residue of a fingerprint that's on the outside.

• 40:47Lester Nare?

  Yep.

• 40:48Krishna Choudhary?

  Right? So there's all of these different things that are happening that will completely mess with the fingerprint that's on the outside.

• 40:54Lester Nare?

  Right.

• 40:54Krishna Choudhary?

  Okay. So the recovery relies on some persistence of like a decomposition product that's on the outside. Okay? And what this particular paper is focusing on is the carbonized ash. So there's going to be some inorganic salts that are left by our sweat and our oils that is going to remain, it's going to get burned up, but the ash is going to remain on the outside.

• 41:19Lester Nare?

  There's the, the idea being, the theory of the case is there's no organic residue that will be left after the bullet is fired because it's just going to get burned.

• 41:30Krishna Choudhary?

  Yeah. Like the proteins, the oils and the lipids, it's gone. But.

• 41:35Lester Nare?

  Their hypothesis was there's gonna be a little indicator still left despite all of that.

• 41:41Krishna Choudhary?

  Mm hmm. Yeah. And it should be the burned up ash of all of that stuff.

• 41:46Lester Nare?

  Of all of that stuff.

• 41:46Krishna Choudhary?

  Right. And there should be a little bit left, right? And if there's even a little bit left, there's a chance.

• 41:52Lester Nare?

  So you're saying, so you're saying there's a chance.

• 41:55Krishna Choudhary?

  Exactly. And so, and so that's, that's what they're doing here. This isn't completely unprecedented. Okay? So in 2008, there was a guy, Dr. John Bond. He came up with a mechanism to actually figure out these casings.

• 42:10Lester Nare?

  There's, that's crazy that his name is Bond.

• 42:12Krishna Choudhary?

  Yeah, yeah. And I, I, I thought it was like part of the bond when I was reading it because my summary just had bond. And even the, the, the news articles about this just have bond. And I'm like, like James Bond? Like, like this is, you know, maybe this is one of, um, cues, like the weird techniques that he's made. But no, this is Dr. John Bond. And he came up with a way of using really high voltage, 2.5 kilovolts, right? And what you do is you realize that most of these casings are made out of brass, which is, um, copper and zinc. Okay? And the zinc and the copper are going to react with the oils on my finger in different ways.

• 42:56Lester Nare?

  Okay.

• 42:56Krishna Choudhary?

  Okay. So where the fingerprint was, that's actually going to create a chemical reaction and a corrosion of the zinc part, not the copper part.

• 43:04Lester Nare?

  Okay.

• 43:04Krishna Choudhary?

  Okay. So there's going to be different resistance. There's going to be different tiny layer of different metals. And what I'm going to do is subject this casing to really high voltage.

• 43:17Lester Nare?

  People are crazy.

• 43:18Krishna Choudhary?

  And then put a fine conducting powder on top. And then that powder is going to be attracted to the corrosion sites because that's going to be high, more conductive than the rest, right? And then I can, I can make a fingerprint out of that.

• 43:29Lester Nare?

  That's so brilliant.

• 43:31Krishna Choudhary?

  It's, it's pretty brilliant. So in 2008, this has already happened. This is going one step further, further. Okay?

• 43:36Lester Nare?

  Okay.

• 43:37Krishna Choudhary?

  And so the, the, we've, we've identified that we can basically put.

• 43:42Lester Nare?

  Like current into a substrate and it will basically reveal this red like this pattern which is the fingerprint we're looking for because the zinc interacts.

• 43:55Krishna Choudhary?

  Yeah, the metal itself.

• 43:56Lester Nare?

  The metal itself interacted differently with the organic, you know, residue, which is just us touching.

• 44:01Krishna Choudhary?

  Yeah.

• 44:01Lester Nare?

  Outside of the brass bullet casing.

• 44:03Krishna Choudhary?

  Yeah.

• 44:03Lester Nare?

  Where he's like, let's just pump it and then it just shows up.

• 44:06Krishna Choudhary?

  Yeah.

• 44:06Lester Nare?

  That's so, I know that's like a bastard, but that's so.

• 44:09Krishna Choudhary?

  I think that's pretty cool.

• 44:10Lester Nare?

  That's pretty cool.

• 44:10Krishna Choudhary?

  Yeah.

• 44:10Lester Nare?

  In and of itself.

• 44:11Krishna Choudhary?

  Yeah, the problem is it works on brass because it requires this alloy, right, of copper and zinc.

• 44:16Lester Nare?

  Yep.

• 44:17Krishna Choudhary?

  Well, now, I mean, I think there are now casings made out of steel, stainless steel and things like that. It's not going to work.

• 44:22Lester Nare?

  It's not a universal solution.

• 44:23Krishna Choudhary?

  The chemistry is not going to work with the iron.

• 44:25Lester Nare?

  Yep.

• 44:25Krishna Choudhary?

  And the, and the carbon that's in the steel.

• 44:27Lester Nare?

  Okay.

• 44:28Krishna Choudhary?

  So what these guys did was use a process called cyclic voltometry. So you start with an electrochemical cell, which is a three electrode setup. You've got a working electrode. In this case, this is going to be our brass casing, the thing that we want to actually test on. There's going to be a counter electrode, which basically completes the circuit. And then there's a reference electrode that keeps the circuit at a certain voltage. And you've got, so imagine you, you take your brass casing, you put it in a chamber.

• 44:58Lester Nare?

  Yes.

• 44:58Krishna Choudhary?

  With a bunch of electrolyte around it.

• 45:00Lester Nare?

  Yes.

• 45:00Krishna Choudhary?

  So chemically conducting water effectively. You attach a electrode lead to it. You have other leads. And now what you can do is start turning on the voltage very gradually. Okay? And that's called cyclic voltometry. You turn on the voltage extremely gradually and what you do is you measure the current. There's going to be a blip in the current. There's going to be a peak in the current and that corresponds to something called the oxidation potential. Effectively, there's some current that is going to allow a chemical reaction to take place on that surface. Okay?

• 45:33Krishna Choudhary?

  Once you tune it to that peak current. You can keep that current as low as possible. So you don't make any other weird chemistry that's happening. And really tune it to that residue that you want. Right? And this is the ash that's been left over after the casings come out. Right?

• 45:54Lester Nare?

  Yep.

• 45:54Krishna Choudhary?

  So you're at a low enough voltage where you're not destroying any. You're not causing anything else to start destroying the ash that's there. You're only tuning it barely to that ash.

• 46:05Lester Nare?

  Ash itself.

• 46:06Krishna Choudhary?

  Okay. Barely to that ash itself. And what ends up happening is you get these two polymers called E dot and P E dot. Doesn't matter what they are. The effect, the effect is they're polymers that are long chains, but still really, really small. In terms of, you know, every day.

• 46:24Lester Nare?

  Every day.

• 46:24Krishna Choudhary?

  But they're like a single chemicals. And what those single chemicals are going to do is when this chemical reaction is happening, this oxidation reaction, the chemicals are going to get deposited on the ash.

• 46:38Krishna Choudhary?

  Okay. Oh, actually, no, sorry. They're going to get deposited on the metal and they're going to leave the ash alone. Because the ash is going to be insulating.

• 46:47Lester Nare?

  I got you.

• 46:47Krishna Choudhary?

  I should say that, I should say that again. You, you, you stick the electrode in, you charge up the casing.

• 46:53Lester Nare?

  Yes.

• 46:53Krishna Choudhary?

  That's going to have a bunch of carbon ash and residue on it. That ash is going to be insulating compared to the metal. So the chemicals are going to get deposited on the metal, but leave holes where the ashes.

• 47:05Lester Nare?

  It's, it's like the opposite of the tracer stuff that they put in mice when they're trying to test them to follow it. It's like the opposite imprint of like that concept.

• 47:12Krishna Choudhary?

  Exactly, exactly.

• 47:14Lester Nare?

  Like what's, what's left is what we're looking for.

• 47:16Krishna Choudhary?

  Yes, exactly. And so now we have a way of, of actually doing this, right? Now, why is this better than the 2008 method?

• 47:25Lester Nare?

  Okay, yeah.

• 47:25Krishna Choudhary?

  For one, I can do this on steel.

• 47:28Lester Nare?

  Okay.

• 47:29Krishna Choudhary?

  Right? I don't need the brass zinc and all that stuff. The other is you get a lot higher resolution on this, okay? This E dot thionine method consistently yields grade three visualization. I didn't know this about fingerprints. With fingerprints, there's level one pattern, which is the fingerprint itself. The level two pattern is the detail on the ridges. And the level three pattern is within each of our ridges, there's little pores.

• 47:57Lester Nare?

  That's crazy.

• 47:57Krishna Choudhary?

  Where the, the pattern of that pore is also unique.

• 48:01Lester Nare?

  Okay.

• 48:02Krishna Choudhary?

  To each individual.

• 48:03Lester Nare?

  Okay.

• 48:03Krishna Choudhary?

  Right? And so to really like start getting something that I can admit in court.

• 48:09Lester Nare?

  Right.

• 48:09Krishna Choudhary?

  And all of this other kind of stuff. It'd be really nice to get level three patterns because sometimes level two patterns, like let's say you have like just the edge of someone's fingerprint. Well, that edge could maybe match to somebody else's fingerprint and things like that. But if you have the edge of someone's fingerprint and you have the pattern of the holes.

• 48:25Lester Nare?

  Yes.

• 48:25Krishna Choudhary?

  That's now extremely hard to, to match to erroneously.

• 48:30Lester Nare?

  Yeah, yeah, yeah.

• 48:30Krishna Choudhary?

  Right? And so this current method actually lets you resolve those pores with these micro deposits. Right? You've got, you've got a mechanism to now actually visualize those pores with those electrolyte contacts. And this is from the paper. You can see very clearly the pores and the ridges.

• 48:50Lester Nare?

  Yeah.

• 48:51Krishna Choudhary?

  Right?

• 48:51Lester Nare?

  Yeah.

• 48:51Krishna Choudhary?

  And this is at tens of microns of resolution. That's the other key that's very different. In the 2008 method from Dr. Bond, he used a conductive powder. That powder, the size of the powder.

• 49:06Lester Nare?

  Is your.

• 49:06Krishna Choudhary?

  Is bigger than the pores.

• 49:07Lester Nare?

  Yeah, that's your limiting factor for resolution.

• 49:10Krishna Choudhary?

  Here we're doing single molecule deposition.

• 49:12Lester Nare?

  Right, right, right.

• 49:13Krishna Choudhary?

  Right?

• 49:13Lester Nare?

  Right, right. So it makes total sense. The, this is so, I'm just like bent out of shape at how clever.

• 49:22Krishna Choudhary?

  Yeah.

• 49:23Lester Nare?

  Conceptually, like people think about this stuff.

• 49:25Krishna Choudhary?

  Yeah, yeah, yeah, yeah.

• 49:26Lester Nare?

  Put it in a, and then put some electrolytes around it.

• 49:29Krishna Choudhary?

  Yeah.

• 49:29Lester Nare?

  And then we know, because we know the other aspects of this chemistry, we can just intuit, right?

• 49:35Krishna Choudhary?

  Yeah, that it should, this should probably.

• 49:37Lester Nare?

  Probably work.

• 49:38Krishna Choudhary?

  Yeah.

• 49:38Lester Nare?

  And then when you do it and you see, you know, the example image we just looked at.

• 49:42Krishna Choudhary?

  It's a sick image.

• 49:43Lester Nare?

  Getting the, the, the level of detail, oh, sorry, not this one, but not number eight, where we now see in the real world, that detail difference.

• 49:50Krishna Choudhary?

  Yeah.

• 49:50Lester Nare?

  Um, I mean, like again, even as, as sort of someone who's maybe not in France, you, you could understand why you would want something with this, the level of fidelity on the right.

• 49:57Krishna Choudhary?

  Yeah.

• 49:58Lester Nare?

  Versus on the left.

• 49:59Krishna Choudhary?

  Yeah, yeah, exactly. And then it, it's, it's pretty awesome.

• 50:02Lester Nare?

  It's pretty cool.

• 50:02Krishna Choudhary?

  Yeah. Um, the other cool thing that they did was actually like, so you know, your casing goes in.

• 50:09Lester Nare?

  Yep.

• 50:09Krishna Choudhary?

  Um, in order to maintain a uniform electric field around that casing during this electrochemical reaction, they had a custom built cylindrical chamber that would sort of. Make a uniform electric field.

• 50:22Lester Nare?

  Okay.

• 50:22Krishna Choudhary?

  Because if you put it inside a box, then the edges, the edge effects are going to be different. And you're not going to get the complete fingerprint around the thing, you know? So now it moves to a place where, okay, if we want to implement this in industry, for each different size of casing, we should have different sized chambers to actually do this reaction. The other cool thing about this is the Dr. Bond method took 2.5 kilovolts. That's not something that I can like hook up to my car battery and like, right? This thing takes less than 1.1 volts. So this could be handheld by the crime fighting units.

• 51:02Lester Nare?

  Yeah, yeah, yeah. I would think if you could do it onsite, you wouldn't necessarily have to send it to a lab.

• 51:06Krishna Choudhary?

  Yes. And then, you know, with that stuff, timing is everything, right? So, so there's a lot of really new stuff that's happening. Now, before it actually gets implemented, it needs to pass something called the Dobert standard, which is the standard that they have in forensics before you can admit something in court.

• 51:27Lester Nare?

  Okay.

• 51:28Krishna Choudhary?

  Like DNA testing had to go through this, things like that. It relies on testability. You gotta have peer review. They already have peer review with this paper. You gotta figure out what the error rates are among a general population, like not just, let's say, white males, but okay, how does it work with women? How does it work with different races?

• 51:47Lester Nare?

  Yep.

• 51:47Krishna Choudhary?

  Things like that. And generally to accept everything, all of these things have to be checked. So that's the next step.

• 51:53Lester Nare?

  It's sort of like the regulatory process or the governing standard.

• 51:57Krishna Choudhary?

  Yeah.

• 51:57Lester Nare?

  This moving from being something that is interesting and people could utilize, but not then have be admissible in court to it being be able, being able to be used to actually say, you know, as evidence that someone is the shooter.

• 52:11Krishna Choudhary?

  Yeah, exactly. And one last thing that I want to talk about is the fact that they can actually do old casings as well. They tried to do a fingerprint from a 16 month old casing, and they were actually able to recover a fingerprint. Which is, uh, you know, so this isn't like just now. They could be going back.

• 52:30Lester Nare?

  This is okay.

• 52:31Krishna Choudhary?

  Yeah.

• 52:31Lester Nare?

  Look.

• 52:32Krishna Choudhary?

  So.

• 52:32Lester Nare?

  Look.

• 52:33Krishna Choudhary?

  If you thought you got away, I don't know. Yeah.

• 52:36Lester Nare?

  That's actually very, a very important detail.

• 52:40Krishna Choudhary?

  Yeah, yeah.

• 52:40Lester Nare?

  Because it kind of, you know, I think because, for example, if, for all the fans of true crime podcasts, etc., with the advent of DNA.

• 52:48Krishna Choudhary?

  Yeah.

• 52:49Lester Nare?

  Testing, a lot of cold cases have effect, have been reopened.

• 52:52Krishna Choudhary?

  Yeah.

• 52:53Lester Nare?

  And, you know, people have started to, you know, uh, get caught for stuff they did ages ago.

• 52:58Krishna Choudhary?

  Yeah.

• 52:59Lester Nare?

  Uh, this is another.

• 53:00Krishna Choudhary?

  There's another one.

• 53:01Lester Nare?

  Another lever that could unlock a lot of stuff there.

• 53:03Krishna Choudhary?

  Yeah.

• 53:03Lester Nare?

  I mean, there's a lot of recent cases I can think of where this existing, uh, would have been valuable. I mean, Meg Thee Stallion and had a case with, uh, that little rapper that I can't remember his name right now, who's in jail. And like, it has this issue of, they fingerprinted the gun, but, uh, they, they, not the casings.

• 53:25Krishna Choudhary?

  Oh, okay, yeah.

• 53:26Lester Nare?

  And so like, that would be a case where it would be interesting. Another one is obviously the recent unfortunate assassination of Charlie Kirk, like.

• 53:32Krishna Choudhary?

  Yes.

• 53:33Lester Nare?

  That would be an example.

• 53:34Krishna Choudhary?

  Yeah.

• 53:35Lester Nare?

  Where like, this would really go a lot, because there's a lot of issue.

• 53:39Krishna Choudhary?

  Right.

• 53:40Lester Nare?

  About the weapon.

• 53:41Krishna Choudhary?

  Mm-hmm.

• 53:41Lester Nare?

  And the suspect and all of the kind of, the timeline doesn't.

• 53:45Krishna Choudhary?

  Yeah, quite, yeah, yeah.

• 53:47Lester Nare?

  So, I mean, this would be another.

• 53:48Krishna Choudhary?

  Trying to sell something.

• 53:48Lester Nare?

  Yeah, you know, an empirical thing that would be, um, valuable in that context.

• 53:56Krishna Choudhary?

  Yeah, I think, I think, uh, it's, it's a very cool use of just fundamental electrochemistry for a problem that's been around for ages.

• 54:03Lester Nare?

  Uh, Tory Lanez, I had to say the name because I was gonna be mad if I couldn't remember it. That was Meg Thee Stallion and Tory Lanez.

• 54:10Krishna Choudhary?

  Yeah, okay.

• 54:11Lester Nare?

  I didn't forget, guys, it's a little brain fart. I got it, I got it, I got it.

• 54:14Krishna Choudhary?

  I don't know who either, I, I don't know who either of those people are.

• 54:19Lester Nare?

  It's funny because it was very, on TikTok, it was a very, anyway, um, story number two, our first forensic story, we should do more of those.

• 54:26Krishna Choudhary?

  Yeah, we should do, yeah.

• 54:27Lester Nare?

  That was, that was, um.

• 54:28Krishna Choudhary?

  That was cool.

• 54:29Lester Nare?

  That was a nice little true crime vibe. Um, and so again, we have now a new way to identify fingerprints from fired bullet casings. This is out of my new university in Ireland, and it was in forensic chemistry. We're gonna move on to our last story.

• 54:45Krishna Choudhary?

  Mm-hmm.

• 54:46Lester Nare?

  Um, we've done a lot of, uh, uh, health-related or healthcare-related stories, um, just because science is having an absolute.

• 54:56Lester Nare?

  Just tear, I think on just these, some of these new, new models, new detection mechanisms. And so this last story is about Alzheimer's.

• 55:05Krishna Choudhary?

  Yes.

• 55:06Lester Nare?

  And we have sort of a, so paper in nature, Icahn School of Medicine at Mount Sinai, Max Planck Institute for Biology of Aging, and the University of Cologne seem to have a new detection.

• 55:19Krishna Choudhary?

  Yeah, it's a new type of immune system, or it's a new type of immune cell that they found.

• 55:25Lester Nare?

  That they found.

• 55:25Krishna Choudhary?

  In, in the brain. And even that is kind of, let me, let me be very careful. It's not a new type of immune cell, because we already knew the microglia existed, but it's a state that the cell is in that is very important for mitigating Alzheimer's. And we're honing in on what exactly that cell needs to be in order to help Alzheimer's not happen.

• 55:52Lester Nare?

  Interesting, okay.

• 55:52Krishna Choudhary?

  Okay.

• 55:53Lester Nare?

  Got it.

• 55:53Krishna Choudhary?

  Alzheimer's is an incredibly difficult disease, okay? Incredibly difficult. There used to be this thing called the amyloid hypothesis, where the basic idea was there's a protein in our brain called beta amyloid that misfolds, starts aggregating, and then starts creating clumps. And then those clumps are what get in the way of neurons, they start killing neurons, they start killing synapses, and then that is what leads to Alzheimer's. That's been sort of shut out by a lot of recent evidence suggesting that that might not actually be the case. Okay?

• 56:32Lester Nare?

  So the hypothesis was basically there's a blockage that starts growing.

• 56:36Krishna Choudhary?

  Yeah.

• 56:36Lester Nare?

  And then that's what impacts the brain activity.

• 56:38Krishna Choudhary?

  Yes.

• 56:39Lester Nare?

  This growth of this blockage.

• 56:40Krishna Choudhary?

  Exactly. And now we're slowly shifting from, there's this like protein blockage to there's, might be an innate immune system in the brain that might be failing at doing its job.

• 56:52Lester Nare?

  Oh, this, okay.

• 56:53Krishna Choudhary?

  So that's the shift that we're, we're sort of in the middle of, actually, right now, as more and more papers come out.

• 56:58Lester Nare?

  I think I know where this is going.

• 56:59Krishna Choudhary?

  Okay. And, um, so.

• 57:03Krishna Choudhary?

  The core study that came out in Nature, first author Ayata, "Lymphoid gene expression supports neuroproductive microglia function." What they've, what they found is a novel immune-like microglial state that, and they've identified exactly the transcription factor that is required. They've identified exactly the genes that are involved in this microglial state. And they've identified how those genes and those transcription factors create the downstream effect of mitigating Alzheimer's. So it's top-down, all the way. They have a full map. They have a full map of how it's happening. And it's very, very cool. Very interesting.

• 57:47Krishna Choudhary?

  Okay, so let's start with Alzheimer's, right? It's an evolving landscape. Alzheimer's, 1906, described these senal plaques and neurofibrillary tangles. And the field of neurodegradation has been intellectually sort of focused on these plaques. You can see the really dark plaque in the middle of brain tissue. That's gonna just get in the way of stuff, right? Then we started targeting immunotherapies that would, that were capable of stripping the brain of these amyloid plaques, right? And those had only modest effects on cognitive decline. And that suggests that these plaques are like kind of a match that starts a much larger fire, okay?

• 58:29Krishna Choudhary?

  There's something else downstream of the plaques that's really the cause. There's something more fundamental. Yes, exactly. And that thing that is more fundamental, people thought, could be neuroinflammation, which is the inflammation of the brain because of stress, because of an immune response. Effectively, it's kind of like an autoimmune response, but local to our brain. Okay. Okay, there's, the immune system itself, that's supposed to be cleaning everything, is now in a stage where it's just attacking all the time, okay? So there's some genetic evidence for this. Because a vast majority of the late onset Alzheimer's genetic risk, like, we can, we can tell because some people have Alzheimer's and others don't. We can look at what the genetic mutations are.

• 59:14Krishna Choudhary?

  All of those are targeted on these things called microglia, not neurons. Okay. Those genetic loci are...

• 59:24Krishna Choudhary?

  Activated in microglia and not in neurons. So that's telling us that the riskiness of the Alzheimer's, at least from a genetic standpoint, is happening in the cells that are the microglia, not on the neurons. Right. Not on the computation, but on these housekeeping cells. Yeah, okay. That might be acting up. Yep, yep, yep. Right? Yep. Microglia are a specific type of cell. They actually originate in the yolk sac, the stem cells in the yolk sac, back when we're in embryo. They colonize the brain before the blood-brain barrier forms. Oh, okay. So they get inside and then the blood-brain barrier forms and then they maintain themselves within the blood-brain barrier. So they don't come from the bone marrow like other immune cells do.

• 1:00:06Krishna Choudhary?

  Okay, they're sort of innate in the brain and they stay in the brain. Okay. Okay, so another big reason why it's hard to access these things is they're inside the blood-brain barrier, right? Right. So you can't really poke it with drugs and things like that. And a lot of times, they're basically in homeostasis. So they're doing their normal thing where they're moving around, they're cleaning up byproducts, they have these things called processes, which are, if you've ever seen immune cells like in, in real time, they'll like protrude out. They'll have these arms that stick out and they're basically just surveying, right? They don't have eyes. So they're, they're using these protrusions to increase their surface area and sense

• 1:00:50Krishna Choudhary?

  the chemical environment. And if they sense something that's bad, then they go into a state of response where they try to eat whatever thing is bad or they try to deal with the plaques and stuff like that. But if you have too much of that, then that's going to destroy the neurons around you as well. Hmm. Right? So if you have too much upregulation of that state, that's pretty bad. Mm hmm. Right? And what ends up happening is you've got this aggressive amyloid deposition that happens in, let's say, mice models, right? Yep. This is, this is something that mimics the Alzheimer's. So you've got a neuron in the middle and all of these plaques that are sort of getting in the way of the neuron trying to do everything.

• 1:01:35Krishna Choudhary?

  Yes. And if you're...

• 1:01:40Krishna Choudhary?

  Microglial cell like actually senses some of these plaques, senses too much of the plaques, or just has this up regulation and can't down regulate, then it's a runaway reaction of immune stuff that's happening in our brain.

• 1:01:53Lester Nare?

  So what we're sort of getting at here is this idea that these immune cells might be overactivated based on some stimuli.

• 1:02:04Krishna Choudhary?

  Yeah.

• 1:02:04Lester Nare?

  And that overactivation is actually the driver for the neurodegeneration.

• 1:02:12Krishna Choudhary?

  Yeah, it could be one of the drivers.

• 1:02:13Lester Nare?

  One of the drivers.

• 1:02:15Krishna Choudhary?

  Yeah.

• 1:02:15Lester Nare?

  Of the decline in cognition, because now it's these arms that are going to pick up stuff.

• 1:02:25Krishna Choudhary?

  Yeah.

• 1:02:26Lester Nare?

  Are just everywhere.

• 1:02:28Krishna Choudhary?

  Yeah, there's too much.

• 1:02:29Lester Nare?

  Too much. Doing too much.

• 1:02:30Krishna Choudhary?

  Yeah, yeah.

• 1:02:31Lester Nare?

  Picking up too many people off the street.

• 1:02:32Krishna Choudhary?

  Yeah, and when they're doing too much, they're not doing their original job. Of like.

• 1:02:37Lester Nare?

  Cleaning.

• 1:02:38Krishna Choudhary?

  Cleaning the plaque and like compacting it and all this other kind of stuff.

• 1:02:41Lester Nare?

  It's like if the janitor became a vigilante at night.

• 1:02:44Krishna Choudhary?

  Yeah.

• 1:02:45Lester Nare?

  At the building. And so instead of doing the normal janitor.

• 1:02:47Krishna Choudhary?

  Yeah, now the building's.

• 1:02:48Lester Nare?

  The building's falling apart while the janitor's going to be a vigilante.

• 1:02:51Krishna Choudhary?

  Yeah, yeah, and he's not good at vigilante either.

• 1:02:56Krishna Choudhary?

  You know?

• 1:02:57Lester Nare?

  Okay.

• 1:02:57Krishna Choudhary?

  So, so they had a bunch of different methodologies that they used, which was, which was quite cool. They used a mouse model and the mouse model mimics the, the adult Alzheimer's. They also have this Creelox recombination system, which what you can do is you can induce gene deletion four to six weeks after they're born.

• 1:03:19Lester Nare?

  Yeah.

• 1:03:19Krishna Choudhary?

  Right? Usually you imagine with gene deletion, the deletion needs to happen and then you create the life form.

• 1:03:25Lester Nare?

  Yes.

• 1:03:25Krishna Choudhary?

  But then you have problems because like, what if the development is perturbed?

• 1:03:31Lester Nare?

  Yeah.

• 1:03:31Krishna Choudhary?

  Right? Then you've created this defective life form, you're making conclusions and you don't know if it's the development or the actual gene that's happening in the adult population. So here, this is a way to delay deleting a gene and then it ensures that any phenotypes that are observed and anything that we observe in the experiment is due to a loss of the gene function in the adult deceased brain, because Alzheimer's is the adult.

• 1:03:53Lester Nare?

  Yeah, right, right, right.

• 1:03:54Krishna Choudhary?

  It's not, it's not something that, you know, it's this gene is doing something bad once you're getting old.

• 1:03:59Lester Nare?

  Right.

• 1:04:00Krishna Choudhary?

  Right?

• 1:04:00Lester Nare?

  Right.

• 1:04:00Krishna Choudhary?

  And so that's what we want to mimic. So they were able to do that. They also have this.

• 1:04:06Krishna Choudhary?

  They, the other really cool thing that they could do was something called TRAP, which is translating ribosome affinity purification. The idea is I want to prove that the, the transcripts, the mRNA that's, that's getting translated in the microglia. Like, so the instructions from the DNA into making protein, those instructions that the microglia is paying attention to, it's coming from the actual microglia and not because the microglia is like, let's say, eating another immune cell, right? Because if the microglia eats another immune cell, well, that immune cell is going to have its own mRNA. And when I sequence, I don't know if this mRNA came from me doing my own thing

• 1:04:50Krishna Choudhary?

  or me eating something else and then that food is what's getting transcribed, right? So how do we, how do we make that distinction? There's this incredible way of doing it called GFP tagging, where you take this green fluorescent protein, you tag a ribosome with it. Okay, so the ribosome has attached this green fluorescent protein. And now the ribosome is going along and it's transcribing your mRNA. You take that, you take those cells in that culture, and you have another part that attaches to the GFP, that green fluorescent protein. But that thing is attached to a magnetic bead.

• 1:05:29Lester Nare?

  Okay.

• 1:05:29Krishna Choudhary?

  Okay, and now with a magnetic field, I can rip only the ribosomes from the, from the microglia, right? Because the magnetic bead is something I can use a force on.

• 1:05:41Lester Nare?

  Right, right, right, right.

• 1:05:42Krishna Choudhary?

  And then, and then, and then I have, and the ribosome is going to have an mRNA attached, right? Because it's in the middle of doing some job.

• 1:05:49Lester Nare?

  Right.

• 1:05:50Krishna Choudhary?

  Now, all of a sudden, you like pick it up, so it's like dragging the mRNA with it. And then you're like, okay, now I'm gonna, I'm gonna sequence this mRNA.

• 1:05:58Lester Nare?

  Right.

• 1:05:58Krishna Choudhary?

  That gives me an insight into the actual transcriptome of the, of the immune cell, rather than all of the mRNA in the immune cell.

• 1:06:06Lester Nare?

  That makes more sense.

• 1:06:06Krishna Choudhary?

  Right, I'm actively looking at only the mRNA that is being transcribed into protein, that's actually being put

• 1:06:14Lester Nare?

  Yes.

• 1:06:14Krishna Choudhary?

  through this machinery.

• 1:06:15Lester Nare?

  Yes, yes.

• 1:06:16Krishna Choudhary?

  Right, I thought that's a really cool technique.

• 1:06:18Lester Nare?

  I, I, I just. Who the the way that folks think about us. As like the solution to the problem. Because like it it makes sense. You want to be able to know what is actively being translated.

• 1:06:34Krishna Choudhary?

  Yeah, yes.

• 1:06:35Lester Nare?

  And so you need to be able to track like in order to be able to validate. Like, what is your process by which you can actually do validation? And it's a very clever way.

• 1:06:47Krishna Choudhary?

  It's very clever. It's like just like.

• 1:06:48Lester Nare?

  Do that.

• 1:06:48Krishna Choudhary?

  Yeah, basically tag the factory.

• 1:06:51Lester Nare?

  Right.

• 1:06:51Krishna Choudhary?

  That's making the stuff.

• 1:06:52Lester Nare?

  Right. And so any product.

• 1:06:54Krishna Choudhary?

  And then drag the factory out.

• 1:06:55Lester Nare?

  Right, right, right, right.

• 1:06:56Krishna Choudhary?

  And then see what's inside the factory. Right? So if you want only the cars in that particular, like, let's say, city, and you don't want all the cars that are.

• 1:07:05Lester Nare?

  Right.

• 1:07:06Krishna Choudhary?

  Being ridden around by the by the general population, you just tag the factory, drag out the factory.

• 1:07:12Lester Nare?

  Now, yeah, that's, oh, that's really good.

• 1:07:14Krishna Choudhary?

  You know?

• 1:07:14Lester Nare?

  That's really good.

• 1:07:16Krishna Choudhary?

  It's it was it was very cool. So now let's get into.

• 1:07:20Lester Nare?

  Funny they call it trap, too.

• 1:07:21Krishna Choudhary?

  Yeah, they literally call it trap. Yeah, yeah. A lot of times with these acronyms, they come, they, I'm pretty sure they start with the acronym. And then they're like, OK, what are the words?

• 1:07:32Lester Nare?

  Hundred percent.

• 1:07:33Krishna Choudhary?

  That like can make it happen.

• 1:07:35Lester Nare?

  I like trap.

• 1:07:36Krishna Choudhary?

  Yeah. Then they put down, OK, in the lab meeting, trap.

• 1:07:39Lester Nare?

  Translating. OK, that works. Ripe it so there's an R.

• 1:07:44Krishna Choudhary?

  Yeah, exactly.

• 1:07:47Krishna Choudhary?

  So let's let's get into what they actually found.

• 1:07:51Lester Nare?

  OK.

• 1:07:51Krishna Choudhary?

  OK, they focused on.

• 1:07:55Krishna Choudhary?

  A transcription factor called PU1. OK, a transcription factor is basically something that.

• 1:08:03Krishna Choudhary?

  Gets attached to the DNA and promotes RNA polymerase, which is the factory that creates mRNA.

• 1:08:10Krishna Choudhary?

  To actually transcribe a gene. Okay, so this is how we get from gene to mRNA to protein. That first step, you need something called a transcription factor to get where that DNA is, bring in an RNA polymerase and be like, alright, you need to start here, look for that start code on, and then, and then start transcribing.

• 1:08:29Lester Nare?

  The transcription factor is like identifying like where the things need to happen, like where the polymerase needs to come in to do stuff.

• 1:08:36Krishna Choudhary?

  Yes, and each gene usually has different transcription factors. So this particular one, this gene SPI1, has a transcription factor PU1. Okay, and different genes have different transcription factors. These transcription factors have different affinities, right? There's some that'll bind immediately. So even at low concentration, it's gonna find that bit of DNA and bind. Those are usually the housekeeping genes that you can't live without. Okay, those are the ones that like, it's like, how do I, how do I make sure that I stay alive as a cell? Okay, then there's stuff that have to do with function, specific states. Like this PU1 gene is, is the one that is controlling whether microglia go are chilling,

• 1:09:20Krishna Choudhary?

  or if they're doing the vigilante stuff, right? And what they found was that when microglia were in the plaque environment, that plaque environment actively enforces low PU1.

• 1:09:32Lester Nare?

  Ah, okay.

• 1:09:33Krishna Choudhary?

  It's very counterintuitive.

• 1:09:34Lester Nare?

  Okay.

• 1:09:35Krishna Choudhary?

  You would think that, you know, I want like super, a lot of inflammation and a lot of policing around my plaques. That's not what's happening. What's happening is, near the plaques, there's a downregulation of PU1, of that transcription factor, which is already a first clue that perhaps we don't fully understand this ecosystem of what's happening, right? So then, they actually used, they used a bunch of tools to figure out, what is the signal transduction pathway that goes from, I sense a myeloid, I sense my plaques, to I downregulate PU1? And they used some knockout versions of mice to actually link all of these signal transduction pathways together.

• 1:10:21Krishna Choudhary?

  They also had, they also showed that there is an upregulation of a T-cell associated gene.

• 1:10:28Lester Nare?

  Okay.

• 1:10:28Krishna Choudhary?

  Okay, in those low PU1 populations.

• 1:10:32Lester Nare?

  So, so when, when there's low PU, right?

• 1:10:34Krishna Choudhary?

  Yeah.

• 1:10:35Lester Nare?

  Right, there's this, uh, there's a T-cell gene.

• 1:10:39Krishna Choudhary?

  There's a T-cell gene.

• 1:10:41Lester Nare?

  That now more frequently arises.

• 1:10:44Krishna Choudhary?

  Yes.

• 1:10:44Lester Nare?

  Or, or is.

• 1:10:45Krishna Choudhary?

  Yes.

• 1:10:45Lester Nare?

  Um, or it proliferates because of that low population environment.

• 1:10:51Krishna Choudhary?

  Exactly. And, and what, what they think is happening is when you don't have that transcription factor, or when you don't have a lot of that transcription factor, the chromatin around that, that, that part sort of relaxes and it exposes some of the genes. And one of these genes that is exposes is CD28, which is a neuroprotective master switch. You might recognize CD28 from our Nobel Prize videos.

• 1:11:15Lester Nare?

  I was literally gonna say.

• 1:11:16Krishna Choudhary?

  Okay, CD28 is the gene that sort of regulates T-cells from becoming normal T-cells to T-regulatory cells.

• 1:11:24Lester Nare?

  Yeah, yeah, yeah.

• 1:11:26Krishna Choudhary?

  Right? So that same gene, that same part of the gene is also be, having a role in microglia in the brain.

• 1:11:34Lester Nare?

  That's actually crazy.

• 1:11:36Krishna Choudhary?

  So it's like the brain is, the, these cells are borrowing a motif from innate immunity elsewhere in the body and saying, well, I can actually use this for my own gains over here.

• 1:11:46Lester Nare?

  Right, right. For this, this, this function, which, which ultimately sort of generates this neuroprotective master switch.

• 1:11:51Krishna Choudhary?

  Yeah.

• 1:11:51Lester Nare?

  And so, so the idea is because if we come back at it, cause I just want to make sure I'm tracking here.

• 1:11:57Krishna Choudhary?

  Yeah.

• 1:11:57Lester Nare?

  So we have this, we have this mechanism by which the, the microglia is, we, we don't want it, when it's close to these plaque regions.

• 1:12:12Krishna Choudhary?

  Yeah.

• 1:12:13Lester Nare?

  It is less active.

• 1:12:15Krishna Choudhary?

  Yeah, it's the PU1.

• 1:12:17Lester Nare?

  The PU1 is less, is less active.

• 1:12:19Krishna Choudhary?

  There's not enough PU1 in the cell.

• 1:12:21Lester Nare?

  Right. And that, because of that, that induces.

• 1:12:25Krishna Choudhary?

  Yeah, then the chromatin sort of relaxes. And now parts of the DNA get exposed and one of the parts that gets exposed is the CD28.

• 1:12:33Lester Nare?

  And, and that, and that one is sort of, uh, that, this is that neuroprotective master switch.

• 1:12:38Krishna Choudhary?

  Which is, it's sort of like, we can sort of, it's like the Tylenol button.

• 1:12:41Lester Nare?

  It's like, go fix and make all my problems go away. Right? And, and because of that low PU, it is what helps to release more of that.

• 1:12:49Krishna Choudhary?

  Yeah.

• 1:12:49Lester Nare?

  And so. What you don't want to happen is that process to get prevented.

• 1:12:56Krishna Choudhary?

  Yes.

• 1:12:57Lester Nare?

  Because that is potentially then what is causing the neurodegeneration.

• 1:13:00Krishna Choudhary?

  Exactly.

• 1:13:01Lester Nare?

  Because we're not basically, and you know, releasing the Tylenol response.

• 1:13:05Krishna Choudhary?

  Yep, yeah. And so, exactly, that master switch is the switch that is controlling the cell fate of these microglia. That's turning it vigilante janitor.

• 1:13:16Lester Nare?

  That, yeah, that's okay.

• 1:13:17Krishna Choudhary?

  You know?

• 1:13:17Lester Nare?

  Yeah.

• 1:13:18Krishna Choudhary?

  And, and so, and so if we can control that and we can have therapies that now, now that we understand this entire chain.

• 1:13:24Lester Nare?

  Right.

• 1:13:24Krishna Choudhary?

  Of, of all of the stuff that's happening, we can actually, you know, maybe do something.

• 1:13:29Lester Nare?

  Right.

• 1:13:30Krishna Choudhary?

  Right? And, and so these microglia are now, you know, they're calling it the T regs of the brain. T regs being again, the thing that won these three scientists, the Nobel Prize.

• 1:13:42Lester Nare?

  The, the military police.

• 1:13:43Krishna Choudhary?

  Yes.

• 1:13:44Lester Nare?

  Uh, the police of the police, right? The system that by which that regulates the things that regulate your body. Can in its, in and of itself, break down.

• 1:13:54Krishna Choudhary?

  Exactly. And maybe that's what's happening in these Alzheimer's brains, which is causing this, these runaway effects that we see as symptoms. But maybe this is the cause, right? This is, or one of the causes. Obviously Alzheimer's is extremely.

• 1:14:08Lester Nare?

  Sure.

• 1:14:08Krishna Choudhary?

  Complicated, right? And there's probably multifaceted genes that are happening all in an environment. But, you know, the step by step, we're getting, you know, closer to understanding what is really going on. And they are called the T regs of the brain because it's very similar. They've got a very small population, just like regulatory T cells, dominant suppressive effect. So they suppress immune responses, just like the T, T regs. And then they're also dependent on the CD28, the same gene.

• 1:14:34Lester Nare?

  Yeah.

• 1:14:35Krishna Choudhary?

  The same gene is in both, right?

• 1:14:36Lester Nare?

  I'm, I'm, this, this is, I understand the, the connection to T regs because the deep dive we did.

• 1:14:43Krishna Choudhary?

  Yeah.

• 1:14:43Lester Nare?

  For the Nobel Prize, we went really, really deep on, and it is definitely worth watching in the context of, we have so many, uh, throwback connections to pass.

• 1:14:50Krishna Choudhary?

  Yeah.

• 1:14:50Lester Nare?

  Episodes in this one.

• 1:14:51Krishna Choudhary?

  Yeah.

• 1:14:52Lester Nare?

  Because it, I can now much more intuitively translate in my head, the idea of it being T regs of the brain. Because of understanding the function of regulatory T cells and the immune response. And why a breakdown in the regulatory T cells.

• 1:15:14Lester Nare?

  Can sort of be a driver for like problems that we see arise. So like you can map, it's a very direct.

• 1:15:21Krishna Choudhary?

  Very directly.

• 1:15:22Lester Nare?

  Map to this.

• 1:15:23Krishna Choudhary?

  Yeah.

• 1:15:23Lester Nare?

  Problem set.

• 1:15:24Krishna Choudhary?

  Yes.

• 1:15:24Lester Nare?

  Just in terms of the framework of how to think about it.

• 1:15:26Krishna Choudhary?

  Yep.

• 1:15:27Lester Nare?

  Obviously, understanding it's a combinatorial problem set.

• 1:15:30Krishna Choudhary?

  Yeah.

• 1:15:30Lester Nare?

  Multiple blah, blah, blahs.

• 1:15:31Krishna Choudhary?

  Exactly, yeah.

• 1:15:32Lester Nare?

  Very, very interesting.

• 1:15:33Krishna Choudhary?

  But it is, it is very cool. And they, they, they use not only mouse models, they also had a human brain tissue.

• 1:15:38Lester Nare?

  Okay.

• 1:15:38Krishna Choudhary?

  And the same results.

• 1:15:41Lester Nare?

  Mm hmm.

• 1:15:41Krishna Choudhary?

  Were, were in the human brain tissue, which is very important. Obviously, you can't do the in vivo effects and things like that. But um, on, on the tissue, as much as you can sort of express one thing, express the other thing. All of this stuff tracks, even in humans, right? The one really cool thing that, that I thought they did was they used hippocampal tissue. And they looked at something called LTP, which is long-term potentiation. This is the idea that synapses will grow and shrink based on how they're, how the neurons are talking to one another. This is the, the, you know, physical mechanism by which we learn. Like when we say our, the connections are strengthening. Literally, what's happening is the size of the, the synapses, the connections, is getting bigger and smaller.

• 1:16:24Krishna Choudhary?

  It's increasing in surface area and that's causing the connection to get strengthened. This is something that doesn't happen in Alzheimer's.

• 1:16:33Lester Nare?

  Okay.

• 1:16:34Krishna Choudhary?

  So, so what they did was they used, they used these brain slices. And they showed that if they have these manipulations where they down-regulate PU1 using the, and then the CD28 comes on, stuff like that. You can restore this LTP. You can restore this ability of the hippocampus to start forming connections and have a dynamic way of expanding connections, contracting connections, so on and so forth.

• 1:16:58Lester Nare?

  That is very.

• 1:16:59Krishna Choudhary?

  So, so there was a mechanistic link here.

• 1:17:01Lester Nare?

  Right, right.

• 1:17:02Krishna Choudhary?

  To straight up learning.

• 1:17:03Lester Nare?

  Right, that, that is, that is tied to.

• 1:17:06Krishna Choudhary?

  And like, and the hippocampus is the center for consolidation of memories, right? And the access to the long-term memories and things like that, right? So having this happen in hippocampal slices is also super, super important to show that, you know, this, this is, this could be a target for therapies in the future.

• 1:17:25Lester Nare?

  And, and because, you know, the idea would be you want to try to target. To the lowest level of abstraction possible.

• 1:17:33Krishna Choudhary?

  Yeah.

• 1:17:34Lester Nare?

  And because of like this, again analogy of T regs for the brain, this seems to be an interesting place to target because it has so many derivative. Like it's like, it's like, it's at the foundation and then that is going to impact processes that happen at a higher, higher orders and all that. So that is interesting.

• 1:17:51Krishna Choudhary?

  Yeah. Yeah. So now when we look at translational horizons, it's promising, but we have to be very, very careful. Okay. One way to think about it was, okay, what if we just, okay, it depends on CD 28, right? What if we just like stimulate CD 28 and we boost these populations? That sounds simple and biology is never that simple. There's actually this really famous disaster that happened in 2006 when it went to phase one trials of doing exactly this. This wasn't in the brain, but this was in the body. They were trying to stimulate CD 28 to get the autoimmunity to go away and things like that, get the T regs to come back. This is called the TGN 1412 disaster.

• 1:18:32Krishna Choudhary?

  Six patients, it resulted in cytokine release syndrome in all six volunteers. Multiple organ failures because basically all the T cells just got activated. And then they didn't care that usually the T cell is presented with some kind of antigen and then, and then they act. This is, they just like started acting and it was really bad. Right? So we have to be very careful with messing with the immune system. Right? And you could have something called specific antibodies, like bispecific antibodies, where it targets not just CD 28, but it also targets something that is very specific to microglia. And you need both. It's an and not an or that like makes this thing.

• 1:19:14Lester Nare?

  Yeah. Activate.

• 1:19:15Krishna Choudhary?

  Activate.

• 1:19:16Lester Nare?

  Yep.

• 1:19:16Krishna Choudhary?

  Perhaps that's one way of doing it. You have brain penetrating vectors that go through the blood brain barrier. That's always like, if you know, now something's in my brain. I don't like, the brain is, if, if, if, if that thing also matches in shape to some other random thing in my neurons, then what's gonna happen? So like. Trying to create translational therapies is one thing, and that's, that's its own like can of worms.

• 1:19:42Lester Nare?

  Yeah.

• 1:19:43Krishna Choudhary?

  Yeah, can of worms. Um, but understanding the mechanism itself is the first step, right? The fundamental science needs to happen first before we start saying, okay, what part of this pathway can I poke?

• 1:19:54Lester Nare?

  We, we have to figure first to find the treasure map and then we can figure out the plan of how we're gonna go get the treasure.

• 1:19:59Krishna Choudhary?

  Yeah.

• 1:19:59Lester Nare?

  And now we have an interesting treasure map.

• 1:20:01Krishna Choudhary?

  Mm hmm.

• 1:20:01Lester Nare?

  Uh, that is specific to issue that again, also might have insights that are connected to other related topics. This is, ah, this is such a great piggyback off of our T regs episode.

• 1:20:15Krishna Choudhary?

  Yeah. Yeah, I think, I think it's a, it's, it's a pretty good story, right? It's, it, it shows just how complicated the brain is.

• 1:20:25Lester Nare?

  Right, right.

• 1:20:25Krishna Choudhary?

  Like, like the brain is not just neurons, it's the blood vessels, it's immune cells. Those immune cells have been there since forever, since we were born, right? All of these microglia are just hanging out in our brain. And we're not getting any new ones.

• 1:20:39Lester Nare?

  Right, right.

• 1:20:39Krishna Choudhary?

  Because, and they can't go through the blood brain barrier.

• 1:20:42Lester Nare?

  Right, right, because it stops at some point in that.

• 1:20:44Krishna Choudhary?

  Yeah.

• 1:20:45Lester Nare?

  It's so good. This is, this is so good. This, so this, this was a, and, and kudos to, you know, another multi-institution.

• 1:20:54Krishna Choudhary?

  Yes.

• 1:20:54Lester Nare?

  Nature paper.

• 1:20:55Krishna Choudhary?

  Yeah, multi-institution, multi-country.

• 1:20:57Lester Nare?

  Multi-country.

• 1:20:58Krishna Choudhary?

  Yeah.

• 1:20:58Lester Nare?

  Um, you know, again with, um, Icahn School of Medicine at Mount Sinai, Max Planck Institute for Biology of Aging, and the University of Cologne. I mean, this is, again, people are working really hard. Like, obviously, we lose a lot of people to.

• 1:21:13Krishna Choudhary?

  Yeah.

• 1:21:14Lester Nare?

  Alzheimer's every year.

• 1:21:15Krishna Choudhary?

  Yeah.

• 1:21:15Lester Nare?

  It is a.

• 1:21:16Krishna Choudhary?

  It's the next frontier.

• 1:21:17Lester Nare?

  It's the next frontier. Um, it's gonna be hugely impactful if we can sort of take this and continue to iterate to the point where hopefully we, like, and we don't wanna have another TN, you know.

• 1:21:29Krishna Choudhary?

  Yeah, disaster.

• 1:21:30Lester Nare?

  Disaster, but we have better tools now, we have better understandings.

• 1:21:35Krishna Choudhary?

  Yeah, and I think we learned a lot from that disaster on how to start phase one trials for immunology. Maybe we do a lot more testing.

• 1:21:42Lester Nare?

  Right.

• 1:21:42Krishna Choudhary?

  In vitro.

• 1:21:43Lester Nare?

  Right.

• 1:21:44Krishna Choudhary?

  Before going in vivo into a human at least, you know? But that, the other thing with, with this kind of stuff is it's incredibly hard to, because this is such a unique sort of late-stage evolution.

• 1:21:58Krishna Choudhary?

  Uh, problem. And what I mean by that is a lot of these problems with Alzheimer's are is something that happens because the brain, the human brain is the most recent organ to be to have evolved, right? A lot of the mutations that are different that make us different from the chimpanzees have to do with neurodevelopment. I mean, uh, duh, right? But what that also means is the locations, the location, the part of our genome and the, and the part of our brain that is so new also means there's a lot of stuff that can go wrong, right? Because it's kind of by design. We're still evolving this thing, right? All of a sudden, we kind of put evolution on pause

• 1:22:39Krishna Choudhary?

  because survival of the fittest isn't the same in the classical sense anymore. We're not having 20 kids and then the smartest ones like, you know, we're, we're a completely different animal now. Where are the evolution that's happening in humans is now not something that is in Darwin's origin of the species, but the genetics doesn't know that, right? Right? Our, our genome doesn't know that. And so the mutation rate is still really high and the, the genome is still kind of experimenting with what the brain is doing, right? And, and that's going to cause all of these failure mechanisms. Right? So it's really hard to find, you know, you can't just with heart disease, you can, you can sometimes even take a pig's heart, put it into a human and it'll work,

• 1:23:24Krishna Choudhary?

  right? Can't do that with, with the brain, right? It's like, it's actually a really good, like it's, you know, it's, it's, it's because it's by design, the most recent organ, it's going to have these failure modes that are just way more complicated than normal. Yeah.

• 1:23:40Lester Nare?

  And, and also the accessibility problem, right? Like it's kind of hard to get in there.

• 1:23:45Krishna Choudhary?

  Yes. Yeah.

• 1:23:46Lester Nare?

  As compared to the rest of the body. Um, that's just another layer of complexity. Um, three great stories this week. Um, we touched on a review of three I Atlas, uh, which was the most demanded story. Yeah. Yeah. And it is what

• 1:24:02Krishna Choudhary?

  I hope you're happy now. Another wicked reference.

• 1:24:07Lester Nare?

  And it is very similar to what we said in our original coverage of it.

• 1:24:11Krishna Choudhary?

  Yeah.

• 1:24:12Lester Nare?

  It basically.

• 1:24:12Krishna Choudhary?

  It's a weird comment.

• 1:24:13Lester Nare?

  It's panned out exactly the way we described it the first time. What are the things that were gonna be weird? What were the areas that still needed more information?

• 1:24:21Krishna Choudhary?

  Yeah.

• 1:24:21Lester Nare?

  We discussed about the, why we would be able to get stuff on from the Mars orbiters? Why it wouldn't be that good?

• 1:24:27Krishna Choudhary?

  Yeah, we talked about. Even the guys were like, guys, you guys know it's not gonna be that good, right?

• 1:24:32Lester Nare?

  We brought it up, this was months ago at this point, but again, still so much to be learned.

• 1:24:38Krishna Choudhary?

  Yeah.

• 1:24:39Lester Nare?

  We followed that up with the fingerprint story, which is so clever.

• 1:24:42Krishna Choudhary?

  Yeah, that's clever.

• 1:24:43Lester Nare?

  That one is just clever. We can now pull fingerprints off of fired bullet casings.

• 1:24:48Krishna Choudhary?

  Yeah.

• 1:24:49Lester Nare?

  And it works retroactively. Old stuff does, works for that too, so.

• 1:24:56Krishna Choudhary?

  At least 16 months.

• 1:24:58Lester Nare?

  At least 16 months.

• 1:24:59Krishna Choudhary?

  And they, I don't know, we haven't pushed it.

• 1:25:02Lester Nare?

  And they're gonna push it.

• 1:25:03Krishna Choudhary?

  Yeah, they are, yeah.

• 1:25:04Lester Nare?

  They're gonna push it. And then we finally ended with a great story about a better understanding of the different states that are helping us better understand how Alzheimer's, sort of the process by which it begins and a potential pathway for us to think about therapeutics to try to address what is one of the most prevalent neurodegenerative diseases that we're seeing.

• 1:25:30Krishna Choudhary?

  Yeah.

• 1:25:31Lester Nare?

  In the human population. I'm ready for some good food this week. I'm gonna eat a lot. Thanksgiving is always, you know, my birthday is the same week as Thanksgiving and so it's always a little bit of, I have to be thankful when we're supposed to be celebrating me.

• 1:25:53Krishna Choudhary?

  Right.

• 1:25:56Lester Nare?

  Like, why am I, this week is supposed to be about me? But I get food.

• 1:25:59Krishna Choudhary?

  They should be thankful for you.

• 1:26:00Lester Nare?

  Yeah, that's exactly right. But it'll be, it'll be good.

• 1:26:05Krishna Choudhary?

  I'm excited to travel.

• 1:26:07Lester Nare?

  You're gonna have a little.

• 1:26:07Krishna Choudhary?

  To Hawaii.

• 1:26:08Lester Nare?

  Good time in Hawaii.

• 1:26:09Krishna Choudhary?

  That's gonna be great.

• 1:26:10Lester Nare?

  After three weeks of rain here or whatever it was. Yeah. To get to some nice weather for a little bit. As always, we really appreciate the listeners, especially those of you. Who get to the banter at the end, who reach us all the way here. We are going to have a couple of more episodes through the end of the year, and we may do some best of coverage for the end of year wrap up. So if you're interested in us choosing our favorite stories from the year and doing like a huge summary, kind of top 10, top five kind of video in the comments, wherever you see this, put that we want to see best of.

• 1:26:48Krishna Choudhary?

  If you made it this far, you know, put some stuff in the comments.

• 1:26:51Lester Nare?

  Yeah.

• 1:26:52Krishna Choudhary?

  Give us ideas for the next month.

• 1:26:54Lester Nare?

  We want to try to do something for the holidays. We think we want to do top 10 or a top best of kind of list to wrap up the year. But let us know in the comments. I'm your host, Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary for another fantastic episode. This is from First Principles.