From Cells to Circuits to Crystals — 2025 Nobel Prizes Unpacked (EP. 11)

Hosted by Lester Nare and Krishna Choudhary, this one-episode special brings all three 2025 Nobel Prizes in the sciences into a single listen: Medicine (immune tolerance and FOXP3), Physics (macroscopic quantum tunneling in superconducting circuits), and Chemistry (metal–organic frameworks and “new rooms for chemistry”). Summary Medicine: Regulatory T cells and the FOXP3 gene that prevent autoimmune disease. Physics: Macroscopic quantum tunneling and energy quantization in electrical circuits — the bridge to today’s qubits. Chemistry: Metal–Organic Frameworks (MOFs) — modular porous crystals enabling CO₂ capture, water harvesting, and hydrogen storage. Show Notes Nobel Prize Press Release (2025 Medicine) Nature Genetics (2001) — FOXP3 mutation and IPEX link Nature Genetics (2001) — FOXP3 Mutation Causes Dysregulation Nature Genetics (2001) — FOXP3 Gene Cause IPEX Syndrome Science (2003) — FOXP3 function in regulatory T cells German Journal of Immunology (1995) — Sakaguchi’s first Treg paper Nobel Prize Press Release (2025 Physics) Physical Review Letters (1980s) — Macroscopic Quantum Tunneling Experiments (UC Berkeley) BCS Theory (1972 Nobel) — Bardeen, Cooper & Schrieffer, University of Illinois Josephson Effect (1973 Nobel) — Brian D. Josephson Google Quantum AI Lab — Quantum Supremacy Paper (Nature, 2019) Nobel Prize Press Release (2025 Chemistry) Nature (1999) — MOF-5 Discovery (Omar Yaghi et al.) Science (2003) — Reticular Chemistry Foundations Journal of the American Chemical Society (1989, 1990) — Richard Robson’s Early Frameworks Lawrence Berkeley National Laboratory — ChatMOF and AI-Assisted Materials Discovery

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

• 0:01Speaker 00

  Lady and gentlemen, good morning.

• 0:04Lester Nare?

  Okay, we are here live for Nobel Prize Week, day one, which is Medicine. Looks like the presentation is starting.

• 0:11Speaker 00

  My name is Thomas Hjalmann and I am the Secretary General of the Nobel Assembly. I will first read the announcement in Swedish, followed by English. We will then, as usual, present some background to the prize and open up for questions.

• 0:31Lester Nare?

  Okay, here we go.

• 0:33Speaker 00

  Nobelörsamlingen vid Karolinska Institutet har idag beslutat att Nobelpriset i fysiologi eller medicin år 2025 ska delas lika mellan Mary Branco, Fred Ramsdell och Shimon Sakaguchi för deras upprichter rörande peripheral immuntolerans. The Nobel Assembly at Karolinska Institutet has today decided to award the 2025 Nobel Prize in Physiology or Medicine jointly to Mary Branco,

• 1:12Speaker 00

  Fred Ramsdell and Shimon Sakaguchi for their discoveries concerning peripheral immune tolerance.

• 1:21Lester Nare?

  Okay.

• 1:22Speaker 00

  Here are the three laureates. Mary Branco was born in 1961 and received a PhD from Princeton University in the United States. The work which she's awarded was performed at a biotech company, Celtech Chiroscience, in Bothell, Washington. She is currently a senior program manager at the Institute for Systems Biology in Seattle.

• 1:52Lester Nare?

  Oh, interesting.

• 1:52Speaker 00

  Fred Ramsdell was born in 1960 and received a PhD in 1987 at the University of California in Los Angeles. The work which he's awarded was performed at the same biotech company, Celtech Chiroscience. He's currently a scientific advisor at the company he himself founded, Sonoma, biotherapeutics in San Francisco and in Seattle.

• 2:23Speaker 00

  Shimone Sakaguchi was born in 1951, earned an MD in 1976, and a PhD degree in 1983 from Kyoto University in Japan. The work for which he is awarded was initiated at Ichi Cancer Center Research Institute in Nagoya. He's currently a distinguished professor at Immunology Frontier Research Center at Osaka University.

• 2:55Krishna Choudhary?

  Okay, at Osaka University. Okay, so we got two private people and Osaka University. I think we need a wardrobe change.

• 3:02Lester Nare?

  Yeah, no, I mean, what?

• 3:03Krishna Choudhary?

  Yeah, that's crazy.

• 3:04Lester Nare?

  Okay, okay, okay.

• 3:05Krishna Choudhary?

  All right, I'm gonna do some research.

• 3:06Lester Nare?

  And we'll dive in.

• 3:07Krishna Choudhary?

  Yeah, and then we'll be right back.

• 3:09Lester Nare?

  We'll be right back. Hello, Internet. This is your captain speaking, Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary. We are now doing a deep dive on day one of the Nobel Prizes. We had the Medicine Award for Peripheral Immune Tolerance just go out. As you can see, we have a little bit of Princeton representation.

• 3:30Krishna Choudhary?

  Yeah.

• 3:30Lester Nare?

  We are back on the board with one of the Nobel winners who just won being a PhD at Princeton.

• 3:37Krishna Choudhary?

  Yeah.

• 3:38Lester Nare?

  But let's dive right in. Peripheral immune tolerance, just one in medicine. Why, like, let's start with like, why this prize matters?

• 3:47Krishna Choudhary?

  Yeah, this prize matters because it's effectively, if you go to slide two, it's the military police for our body, okay? The military, you can think of as the immune system. They're the ones that are fighting the invaders, right? But every once in a while, some people might act up, okay? And then what ends up happening is you need to control parts of the immune system that might be attacking the self. And that's where these regulatory T-cells come in, okay? And that's why I think it's kind of like the military police. And these three Nobel laureates in slide one, Shimone Sakaguchi, Mary Brunkow, and Fred Ramsdell, they are responsible for doing a lot of the research

• 4:31Krishna Choudhary?

  that elucidated this system of regulation of our immune system. Basically answering the question like, why doesn't everyone have an autoimmune disorder? Okay, and that sounds like kind of crazy, but it'll become a non-trivial problem once I get into some of the details about exactly how our immune system works, okay? So... With the immune system, there's two different kinds of basic immunity that we have. So in, um, we've got the innate immunity, which is what you see on the left over there. Yes. That's stuff that doesn't require learning. That's in our genetics. Right. We're wired to recognize viruses. We're wired to recognize bacteria. We're wired to recognize

• 5:13Krishna Choudhary?

  outside pathogens that are coming in. Okay. Then there's something called adaptive immunity. These are our T cells and our B cells. Okay. They're specialized to have a kind of memory of stuff. They're specialized to really, um, recognize things at a molecular level. And these things are slower and it involves a lot of different molecular mechanisms that we're going to try and get into. What we're really going to focus on are something called T cells. Okay. Okay. T cells, they're a type of white blood cell. Um, you know, our blood has basically three types of cells. We've got the red blood cells, which carry oxygen. We've got platelets, which do a lot of the clotting and like tissue repair. And then finally, we've got

• 5:58Krishna Choudhary?

  white blood cells, which are our immune system. Right. And the ones that we're going to focus on today are called T cells. They develop in the thymus, um, which is an organ of our body, hence the name T cell. T cell. Okay. Um, there's two types of T cells. There's the helper T cell, which coordinates an immune response. It doesn't actually do the killing. Yep. But it like tags stuff and then makes other help, other like B cells come in or macrophages come in, macrophages like big eaters that like come in and like actually, actually like eat things and digest it. Yes. Like within the cell. Yes. And then. They're like scouts, right? Yes. The helper T cells are exactly like scouts. Yep. Yeah. And then, and then you've got your killer T cells, right? And the killer T

• 6:41Krishna Choudhary?

  cells, like the one you're seeing over there, that's attacking, the, the smaller one is the killer T cell and it's taking on this giant cancer tumor cell. Okay. Right? And it's attacking it. So killer T cells can kill infected cells. They can kill cancerous cells directly.

• 6:59Krishna Choudhary?

  And the mechanism by which they understand whether something requires killing or not.

• 7:06Lester Nare?

  Yes.

• 7:07Krishna Choudhary?

  Is the focus of this problem.

• 7:08Lester Nare?

  Got it. Okay.

• 7:09Krishna Choudhary?

  Does that make sense?

• 7:10Lester Nare?

  Yes.

• 7:10Krishna Choudhary?

  Because imagine, right, you're, again, you're a cell. The senses that you have are just lock and key. That's like at the cellular level, you're worried about concentrations of certain molecules. Like, how many of this molecule do I see around here? Is that a red flag? Or on the other hand, like, you know, you go, you go to another cell. How do you know if that cell is healthy? Or it's been taken over by something?

• 7:35Lester Nare?

  Right.

• 7:35Krishna Choudhary?

  Right? And to get into that, we're gonna have to go into exactly how these T cells actually find, you know, which one is wrong, which one is right.

• 7:48Lester Nare?

  How does our first line of defense?

• 7:50Krishna Choudhary?

  Know.

• 7:50Lester Nare?

  Know.

• 7:51Krishna Choudhary?

  Yeah.

• 7:52Lester Nare?

  What to go after.

• 7:53Krishna Choudhary?

  Yeah. And effectively, like, you know, in a normal society, the police come over and they check your ID. These guys are doing kind of the same thing.

• 8:00Lester Nare?

  Okay.

• 8:00Krishna Choudhary?

  Okay? So in slide five, you'll see, this is from the Nobel Prize Committee. They, they release these like, um, you know, things for the press.

• 8:09Lester Nare?

  Yes.

• 8:10Krishna Choudhary?

  To sort of explain and understand. It's a really good cartoon. So on the left-hand side, you've got a healthy body cell that's been infected by a pathogen. Right? That's the stuff that's coming in. And what these cells do is they've got, they've got these receptors on the outside of their surface that actually take whatever is inside the cell and display it.

• 8:36Lester Nare?

  Got it.

• 8:37Krishna Choudhary?

  It's like an ID card for everything that's inside your cell. Okay? Every little protein that's been degraded or like broken down, they're gonna take little parts of that protein and they're gonna put it out.

• 8:50Lester Nare?

  Got it.

• 8:51Krishna Choudhary?

  And then what the T cell does is they've got receptors that actually come in and bind. And if one of the receptors matches, like it does over there, then it's like, oh, that's bad.

• 9:00Lester Nare?

  That's sort of center screen.

• 9:01Krishna Choudhary?

  Yeah. That's, that's, that's sort of attached to that receptor. That T cell has recognized something that is quite bad.

• 9:07Lester Nare?

  Yes.

• 9:08Krishna Choudhary?

  And so it's gonna elicit. A immune response. That's that lock and key model that I was talking about.

• 9:13Lester Nare?

  Yes, yes. I think there's a literal scene in the movie Osmosis Jones that that walks through T cells going and checking ID.

• 9:20Krishna Choudhary?

  Oh, really?

• 9:21Lester Nare?

  As the metaphor.

• 9:22Krishna Choudhary?

  Dude, that's literally what this is. Yeah, yeah, yeah. And so the way that the ID check happens is if you go to photo six. This is a picture of the human leukocyte antigen, okay? And this is the protein that is responsible for taking whatever is inside the cell and displaying it. So that red part that you see at the very top.

• 9:44Lester Nare?

  Yes.

• 9:44Krishna Choudhary?

  Like right over here.

• 9:45Lester Nare?

  Yes.

• 9:46Krishna Choudhary?

  That red thing is, maybe it's a viral fragment, or maybe it's a part of our own DNA. That our own, sorry, protein complexes inside. What they've done is they've broken down the the proteins and they display them. In little tiny segments outside, okay? And the T cells job is to come in and try to figure out. If that little fragment is self or not. Understood?

• 10:11Lester Nare?

  Yes.

• 10:11Krishna Choudhary?

  Okay.

• 10:11Lester Nare?

  Yes.

• 10:12Krishna Choudhary?

  So the this human leukocyte antigen, it's part of the MHC major histocompatibility complex. It's basically, it's found in like, you know, animals and so on and so forth. This is the thing that's actually involved in like mate selection. So like. You know, have you have you heard about that research where it's like people with different immune systems smell better?

• 10:31Lester Nare?

  Yeah.

• 10:32Krishna Choudhary?

  And that's why you're like more attracted to them. That's this stuff.

• 10:35Lester Nare?

  That's interesting.

• 10:36Krishna Choudhary?

  Okay, that's the that's the human leukocyte antigen, okay? Like, everyone has different versions of this of this antigen. And really, only like your identical twin has the same one, okay? And the more different you are, the better, you know, it is for the kid.

• 10:51Lester Nare?

  Because the the the idea is you have, there's less of of these potential threats. Vectors that you are going to be susceptible to because you're so different.

• 11:00Krishna Choudhary?

  Yeah, yeah, exactly. And so like you have like a broader.

• 11:03Lester Nare?

  Broader, yeah.

• 11:04Krishna Choudhary?

  Yeah. And the other reason, like, you know, organ transplant rejection, a lot of times that happens because your. HLA, this this antigen complex is different. And so the organ is like, that's not me.

• 11:16Lester Nare?

  Right.

• 11:16Krishna Choudhary?

  Right? Like, and I don't, I don't want that as part of this body. And so people who are actually studying this organ transplant problem. They won the Nobel Prize in nineteen eighty, Jean Desaut and George Snell for discovering this. Human leukocyte antigen, this like idea of like these, these proteins that actually take what's inside the cell and display it out. And the fact that they're different is what causes all of these rejections. Okay. So that was our first clue as to like how this stuff works.

• 11:45Lester Nare?

  Understood, understood.

• 11:47Krishna Choudhary?

  So now we've, we figured out how cells in our body displayed their ID.

• 11:51Lester Nare?

  Right. In order for the T cells to be able to identify whether or not it's something that they need to deal with or not.

• 11:56Krishna Choudhary?

  Or not. Yeah. Now, the next thing, next part of the clue is how did the T cells, which are the police, or the military in this case, how do they decide whether that ID is okay or not? Okay. And so this is-

• 12:10Lester Nare?

  One thing is the display of the ID.

• 12:12Krishna Choudhary?

  Yeah.

• 12:12Lester Nare?

  The second thing is like running it through the, is like actually scanning it to be like, are you in the database?

• 12:17Krishna Choudhary?

  Are you in the database or not? And that's where T cell receptors come in. Okay. So T cell receptors are, they look like that. Okay. They're the ones on the outside and you can think of this as the key.

• 12:28Lester Nare?

  Got it.

• 12:28Krishna Choudhary?

  If the HLA things that we were talking about earlier, where the cells are displaying it, that's the lock. Okay. And these keys have to match the lock. And if they match the lock in a bad way, then that means you're a bad person. If they sort of match it in a good way, then you're fine. Right?

• 12:44Lester Nare?

  The idea is these T cell receptors are sort of protruding, looking to be able to fit into the lock of a matching, you know, person on the bad list.

• 12:53Krishna Choudhary?

  Yeah.

• 12:53Lester Nare?

  And if that then happens, then they know we need to now have our appropriate immune response.

• 12:58Krishna Choudhary?

  Exactly. Yeah. And it's actually kind of an insane thing to think about, right? Because as a T cell, you're going to have to come up with a bunch of different keys.

• 13:09Lester Nare?

  Right.

• 13:09Krishna Choudhary?

  Right?

• 13:10Lester Nare?

  Right.

• 13:11Krishna Choudhary?

  For all the stuff. For all of the stuff that's out there. And if you want to have a bunch of different keys, you want to have a diversity, this is in the protein, you want, you want different shapes in your protein. That means you need different sequences of amino acids. You want different sequences of amino acids. That means you need a different sequence of DNA creating that amino acid. And for the longest time, it was like a really big challenge to figure out, because we have like something like 10 to the 15 different receptors. Okay? To code for 10 to the 15 different receptors, you would need like 10 to the 13 amino acids at least, or 10 to the 14, right? Because it's three for one. So I'm doing some really crude math here. 10 to the 14 different sequences of, of DNA, that's a lot of DNA.

• 13:54Lester Nare?

  Right.

• 13:55Krishna Choudhary?

  That's larger than our genome.

• 13:56Lester Nare?

  Right.

• 13:56Krishna Choudhary?

  Okay. So- How does that happen?

• 13:59Lester Nare?

  How are we actually storing the memory and facilitating the creation of the T-cell receptors in this wide, this massive scale that is necessary for us to survive in the way we survive?

• 14:14Krishna Choudhary?

  Exactly. And if you go to photo 8, that's a pretty good depiction of it. Like, on the right-hand side, you've got all these different shapes, right? That the T-cell receptor can be, right? And it's trying to generate all of these different shapes. And the challenge is, how do you generate so many different protein sequences without blowing up on the genetic side of things?

• 14:34Lester Nare?

  Right, correct.

• 14:34Krishna Choudhary?

  Right? And that was made possible by something called VDJ, Variable Diversity and Joining Locuses. They're different gene segments. And what ends up happening is the cell mixes and matches. So it's like you have like 10 different pairs of socks, you know? 20 different shirts, 20 different pants.

• 14:54Lester Nare?

  Yes.

• 14:55Krishna Choudhary?

  And now you can come up with a combinatorially much larger outfit.

• 14:59Lester Nare?

  Yes.

• 14:59Krishna Choudhary?

  Right? That's exactly what these T-cells are doing.

• 15:02Lester Nare?

  Got it.

• 15:02Krishna Choudhary?

  Okay? And this process was discovered by Susumu Tonigawa, and he won the Nobel Prize in 1987. He's now at MIT. He's doing actually optogenetic stuff.

• 15:13Lester Nare?

  Ah, which we had as the prediction.

• 15:15Krishna Choudhary?

  He's actually chasing his second Nobel, I'm pretty sure. He's trying to, he does like optogenetics on the hippocampus, which is the center for learning and memory in our brain. So, good luck to him on that. And then, the last part of it was, so this is, so Tonigawa figured out how to make all of these different proteins, right? All of these different shapes.

• 15:40Lester Nare?

  Without blowing up the genetic base.

• 15:42Krishna Choudhary?

  The final key was, in 1996, they won the Nobel Prize, Peter Deherity and Rolf Zinkernagel. And they were the ones who showed that actually, that human leukocyte antigen, the part that was displaying the ID, that's crucial for the T-cell

• 16:00Krishna Choudhary?

  Lock and key model. The T cell isn't just locking in on everything.

• 16:03Lester Nare?

  It's doing it.

• 16:04Krishna Choudhary?

  It's doing it specifically on the stuff that this thing is putting out and displaying.

• 16:10Lester Nare?

  Instead of doing no knock warrants at every door. They check the ID at the door and only do the, you know, the bust.

• 16:18Krishna Choudhary?

  Yeah.

• 16:19Lester Nare?

  When there's a match there, which then decreases the like.

• 16:21Krishna Choudhary?

  Exactly.

• 16:22Lester Nare?

  Of the activity itself.

• 16:23Krishna Choudhary?

  Exactly. Yeah. Now you can be a lot more specific. You can manage like, you know, the whole.

• 16:28Lester Nare?

  You actually scale to a complex.

• 16:29Krishna Choudhary?

  To a complex organism like us with like billions of cells, right? So, so that's the background behind how T cells do their job if they're doing it correctly.

• 16:42Lester Nare?

  Right.

• 16:42Krishna Choudhary?

  Okay.

• 16:43Lester Nare?

  Okay.

• 16:43Krishna Choudhary?

  Now, some T cells are inevitably gonna recognize your own body. Okay. Because these guys are making, as I said, 10 to the 15 possible receptors, right? Some of these receptors are gonna match to like the stuff that we have, right? How do we make sure that those guys don't just like go off?

• 17:04Lester Nare?

  Right.

• 17:04Krishna Choudhary?

  Right?

• 17:04Lester Nare?

  Right, right, right.

• 17:05Krishna Choudhary?

  Because each T cell is expressing a specific shape.

• 17:08Lester Nare?

  Yes.

• 17:08Krishna Choudhary?

  Okay. Each individual T cell is expressing a specific shape. So what we basically want to do is the ones that are recognizing our body, we should just get rid of them. We should tell them to commit cell death.

• 17:21Lester Nare?

  Yes.

• 17:21Krishna Choudhary?

  And then we don't have to deal with that anymore. So that first line is called central tolerance. That's the first filter. It happens in the thymus. Okay? So these, these T cells, what they do is they can bind, this is photo 10, they can bind strongly to self proteins. And whenever they do that, the process that happens in the thymus when we're very, very young is those T cells go off and they don't, they don't proliferate to the rest of the body.

• 17:47Lester Nare?

  Okay.

• 17:47Krishna Choudhary?

  Okay?

• 17:48Lester Nare?

  Okay.

• 17:48Krishna Choudhary?

  The, the filter is not perfect though. And there's some that get through. Okay. That second line of defense, that is what this Nobel Prize is about.

• 17:59Lester Nare?

  After that first sort of purge, there's still some remaining leftover T cells that recognize our own bodies.

• 18:06Krishna Choudhary?

  As, as invaders.

• 18:08Lester Nare?

  As invaders. Incorrectly.

• 18:09Krishna Choudhary?

  Incorrectly. Yeah.

• 18:10Lester Nare?

  And so now there's a second, after the first filter, which you just talked through. There's a second line of defense.

• 18:15Krishna Choudhary?

  Yes. Yeah. And that's photo 11. If you go there, these are called regulatory T cells. So on the left hand side, what you're seeing is. You know, um, are this rogue T cell that's misbehaving, that's recognized our own body and a protein fragment in our own body as something that needs to be taken care of. Now comes a regulatory T cell. And what that does is it's going to suppress the immune response of that incorrect T cell. Okay. And this regulatory T cell is what stops the autoimmune response from happening. Autoimmune being, meaning it's an immune response on yourself.

• 18:53Lester Nare?

  It's, it's almost like Internal Affairs in those cop movies. When the cops do something bad and they come in and they investigate their own people to make sure that it gets taken care of. And you remove the people from the force that are problematic.

• 19:04Krishna Choudhary?

  That are problematic. And so, yeah, if only that actually happened, but you know, um, it's, that's exactly what's going on. It's like you've got, you've got like the, the ones who regulate the cops.

• 19:14Lester Nare?

  The cops, yeah.

• 19:15Krishna Choudhary?

  Right. And, and they, and if they do a good job, like in most of us, we don't have those.

• 19:19Lester Nare?

  Yes.

• 19:19Krishna Choudhary?

  Right. And so most, and mostly it works. And where it doesn't, we need to figure out how, what's going on with the regulatory T cells. And if there's ways to prevent that from happening.

• 19:29Lester Nare?

  So we have our first filter. And then, you know, once we get past the first filter, there's still some remaining, uh, uh, T cells that are attacking our own body. So then regulatory T cells come in to suppress that immune response. But that's not, there's, that doesn't happen a hundred percent of the time still, even at that second layer.

• 19:47Krishna Choudhary?

  Yeah. And so, and so now there's ongoing, ongoing work, even, even today. Like I was looking today at, when I was like researching this stuff, even today, there's, there's papers coming out about how do we make this system better? But the first step is always understanding how the system works. And that's what our three Nobel Prize winners did. Okay. Was just figuring out that the system existed in the first place.

• 20:07Lester Nare?

  Okay.

• 20:07Krishna Choudhary?

  Discovering the fact that there are such things as regulatory T cells that are uniquely different from the rest of the T cells. From helper T cells, from killer T cells. This is a totally different class of immune cells that come out of the thalamus. Right?

• 20:21Lester Nare?

  So you have the ID system, you have the T cells that are ID system. You have the T cells that are going out and actually doing the work. And then now there's this third bucket, which is the police of the police.

• 20:30Krishna Choudhary?

  Police of the police. Exactly. Yeah. And these guys are the ones who like solved it. Okay. So now we're going to get into actually what these three, um, researchers did. We're going to start with, um, Shimon Sakaguchi. He got his PhD at Kyoto University. And then he started getting really into these autoimmune disorders. So the first thing he did was figure out that actually if I lesion the thymus of an animal in the lab, then the animal develops an autoimmune disorder. Okay, so the thymus is key. I mean, this was already known, but now you've got sort of testbed. Yep. Okay. And the key thing that he did was he injected a fraction of immune cells. Like over there, on the top row, you see just you lesion the thymus. The guy's sick.

• 21:13Krishna Choudhary?

  But if you take a fraction of immune cells from a healthy mouse and you inject that into this guy who doesn't have a thymus, he's gonna be fine. Interesting. So what you've done is there's something in the mature immune cells of a healthy individual that when you transfer to someone who does have this no thymus defect, he's gonna be fine, right? So what you've done is transfer this tolerance. Yes. Right? You've transferred this mechanism. Yes. Okay. Yes. And this was back when like, they didn't have like monoclonal antibodies. They didn't have any of this stuff. So they, they used to use like blood serum to basically classify

• 21:57Krishna Choudhary?

  like what was in the thing that I injected, which is like very coarse grained, right? Now, nobody uses it, but back then that was cutting edge. And so you just knew that in whatever cocktail that I injected it, there was something magic. Okay? Then came the introduction of monoclonal antibodies, right? And with monoclonal antibodies, now what I could do is I could start identifying a subpopulation of T cells that have a specific thing, like a specific surface marker. Because monoclonal antibodies will then go and attach to that surface marker. And then you can say, oh, this thing has the CD4 plus or the CD425. CD is just like a naming convention for like the proteins that are on the outside. Yep.

• 22:40Krishna Choudhary?

  And the number is just like the number in which that it was discovered. So. You can now start saying that this specific T cell that mattered actually had this very specific type of protein. And so it's different from all the rest that we've been looking at, right? And he started calling these regulatory T cells or T regs, right? And without these cells, the mice developed autoimmunity. But with them, they they were fine, right?

• 23:04Lester Nare?

  Yes.

• 23:04Krishna Choudhary?

  And he finally published his paper in the Journal Journal of Immunology. This was the first sort of seminal paper.

• 23:11Lester Nare?

  Got it.

• 23:12Krishna Choudhary?

  In 1995.

• 23:13Lester Nare?

  Okay.

• 23:13Krishna Choudhary?

  Okay. The first one with the Alice with the serum was published in the 1980s. Everyone was like, yeah, probably. But at the time, you know, that's the best you can do. Now we've gotten to like this resolution of like, now we've got cells.

• 23:24Lester Nare?

  Right.

• 23:25Krishna Choudhary?

  All right.

• 23:25Lester Nare?

  Right.

• 23:25Krishna Choudhary?

  So.

• 23:26Lester Nare?

  There was a there was a level of higher fidelity.

• 23:28Krishna Choudhary?

  Yes.

• 23:29Lester Nare?

  To get to the answer.

• 23:30Krishna Choudhary?

  Exactly, exactly. And so, fine, now you've got these cells. We still need a little bit more convincing, right? You got to get to the genetic level to really see if there's something that is changing at the gene level that is expressing a difference between these regulatory T cells and the normal T cells. Because even normal T cells, like the conventional activator effector T cells, they also have CD25, which is this marker that he identified. Sure, fine. It's like a little bit lower density.

• 24:00Lester Nare?

  Yep.

• 24:01Krishna Choudhary?

  But it's still there, right?

• 24:02Lester Nare?

  Right.

• 24:02Krishna Choudhary?

  So it's not as convincing.

• 24:04Lester Nare?

  Right.

• 24:04Krishna Choudhary?

  Right?

• 24:04Lester Nare?

  Right.

• 24:05Krishna Choudhary?

  And so.

• 24:06Lester Nare?

  What we're saying is, what is the actual mechanism?

• 24:08Krishna Choudhary?

  Yes.

• 24:08Lester Nare?

  That allows the differentiation in when these T cells are, you know, when they get created, like what what makes it know I'm a helper.

• 24:19Krishna Choudhary?

  Oh, I'm a killer.

• 24:20Lester Nare?

  Killer.

• 24:21Krishna Choudhary?

  Or regulatory.

• 24:22Lester Nare?

  Yeah, yeah.

• 24:22Krishna Choudhary?

  Is that? Exactly, exactly. Like the courses that they took in the training academy.

• 24:27Lester Nare?

  Yeah, yeah, yeah.

• 24:27Krishna Choudhary?

  Like, but what exactly do did they read?

• 24:31Lester Nare?

  Right, right. Yeah. How did they get to?

• 24:33Krishna Choudhary?

  Yeah, exactly. You know what I mean?

• 24:34Lester Nare?

  Yes.

• 24:34Krishna Choudhary?

  So.

• 24:35Lester Nare?

  Yes.

• 24:36Krishna Choudhary?

  So that was Shimon Sakaguchi.

• 24:39Lester Nare?

  Yes.

• 24:40Krishna Choudhary?

  He had sort of come into the fore. Now we're going to get to our next two Nobel Prize winners, Mary Brunkow and Fred Ramsdale. Their story is is pretty interesting. So actually, to get to their science, we first need to talk about 1940s Oak Ridge National Lab. I think you've got a photo of that there. Yeah, that's the that's where we enriched uranium for the atomic bombs.

• 25:00Lester Nare?

  Yes.

• 25:01Krishna Choudhary?

  And, you know, there's a lot of radiation there. And in the 1940s, researchers found a mutant mouse strain.

• 25:09Krishna Choudhary?

  In Oak Ridge that had scaly skin, swollen lymph nodes, early death. And you know, as scientists do, they're like, oh, let's study this thing. Right, right, right. They called it the scurfy mouse strain. Okay, they call it the scurfy mouse strain. And what they noticed was only male mice developed this disease. Okay. Of like, having this like, sort of autoimmune type of disorder. Right? And so if you look at photo 17, if only male mice display this disease. Yes. But females are fine. Yes. That means that it has to be an X-linked disorder. X-linked meaning that whatever genetic thing is making this thing happen is happening on the X chromosome. Right? Because females have two copies of the X chromosome.

• 25:54Krishna Choudhary?

  So if one of them is defective, the other one is still going to print the correct protein and you're going to be fine. But if you're an XY and this thing is defective, then you're just totally screwed. Yeah, that makes sense. So, so they figured out that it's got to be on the X chromosome. They did a lot of different tests to figure out and they narrowed it down to 500 base pairs. Okay. Okay? And their job, what, what Brunkow and Ramsdale did, they were these basically gene hunters at Cell Tech Chiroscience. Mary Brunkow had finished her PhD at Princeton. We got another one, baby. We got it, we're on the board. And then Fred Ramsdale at UCLA, which is where I went for PhD. So that's kind of cool that today, both my institutions.

• 26:38Krishna Choudhary?

  I was gonna say, but both undergrad and. Plus one, baby. Yeah. So after they, after they're done with that and they're done with their postdocs, they, they joined Cell Tech Chiroscience, which is, I think it's, it's kind of like a bioscience startup in Seattle at the time. And what they want to do is if you go to number 18, they, they want to identify this mutation. Right. That's on the X chromosome. Right. Okay? Now, back then, we don't have the kind of high throughput DNA technology like 23andMe, where I can like, mail a sample and then. So crazy. And then like, just get back all my, all my DNA results. Right? Back then, this is in the 90s, so this is before Human Genome Project. Was, yeah. Right? Like, this is when, in the heyday of that.

• 27:21Krishna Choudhary?

  So we've got these like, really, really old technologies. One of them's called BAC cloning, bacterial artificial chromosomes. What you do is you take a segment of whatever, whatever.

• 27:33Krishna Choudhary?

  Part of DNA that you're trying to sequence. Yes. You stick that into the bacterial chromosome and then have the bacterial replicate it. And then, you know, you can then start testing each, each, each little part. There's also called shotgun sequencing where you break up the DNA into different parts. You sequence each part and then you play a jigsaw puzzle where you're trying to see how they overlap. And it's like, an intensive process requires like, you know, two or three years from like, two or three researchers nowadays, it's like a day. Yeah, right. A hundred bucks and a laptop, right? Like, but, but back then, this is like several PhDs. Right. It's just like figuring out what are these 500 kilo base stretch of DNA doing? And so if you go to photo 19, we've got a photo from their, um, from their paper.

• 28:18Krishna Choudhary?

  On the top there, that's the 500 kilo base stretch of DNA. Okay. Okay, from the X chromosome. Yep. And they figured out that they've got 20 candidate genes that they need to sequence. So one by one, they're sequencing the 20 candidate genes. And it was their 20th gene. Of course it is. Of course it is. They could have given up, but they didn't. They're like, let's just do all 20. Finally, on their 20th gene, they found the mutation that was responsible for this scurvy mouse strain. Yes. Okay, it was a two base insertion. And if there's an insertion of two bases, remember,

• 28:54Krishna Choudhary?

  it's three base pairs to a single amino acid. Yes. Right? So if I put in two, not only have I made a mutation right there, I've also done what's called a frame shift. Yeah, yeah, yeah. Right? Yep. Like, like if you're, if you're reading music, like I've just made each measure. Like now, half of this guy is in the other measure. And so my reading for all of the rest is going to be completely nuts. It's, it's not a point mutation. Right. Right? Right. And so, and so this two base insertion created like a, um, made, made the gene effectively shorter. Yes. Because later on, there was part of that frame shift was like, oh, this is a stop code on, which means I'm going to stop making my protein. Well, the protein is supposed to be so long. So like now, it's just completely wrecked, right?

• 29:39Krishna Choudhary?

  It's, it's completely wrecked. And so they named this, um, gene, the fork head box protein P3 or Fox P3. Fox P3. Okay. And it turned out that it was a transcription factor. And they published this in Nature Genetics 2001. That was their first big paper with the two of them together. Again, this is Brunkow and Ramsdale. Yes. Um, they also published another one in Nature Genetics where they linked this mutation, the scurfy mice mutation to diabetes and other autoimmune disorders, specifically IPEX, IPEX, which is immune dysregulation, polyendocrinopathy, enteropathy, and it's also X-linked, which is,

• 30:23Krishna Choudhary?

  which is crazy, right? Because like the, on the mouse chromosome, it was also on the X chromosome. And in humans, it's also on the X. This sort of also shows why it's, um, why we do animal studies in the first place. Right. You know, we'd like to think that we're very different, but like, you know, at a real molecular biology level, we're very similar, especially for, for old systems like the immune system. That makes sense. The immune system is, is, is a very old system for mammals. So a lot of the same mechanisms are happening across the mammalian, um, species. Yes. So the, the final, um, paper that they published was also in Nature Genetics. I guess the editor there really liked it or something. Um, but all in 2001, all in 2001,

• 31:06Krishna Choudhary?

  three papers and paper in Nature Genetics. And this was the nail in the coffin. What they did was cross breeding of, um, scurfy mice with people that had the wild type and they could show a recovery of function. And so it was really like, it's like, it's like, definitely it's that, that's the location that's causing all of this. Yes. And so now we've got a mechanism in, in the DNA that is, that is perhaps where we've got a location in our DNA. Right. Where perhaps this regulation is happening. Yes. Okay. Yes. And this is when Sakaguchi gets back. Yes. So in 2003, he publishes, um, this work, which basically combines those two papers.

• 31:48Krishna Choudhary?

  He combines the Sakaguchi paper from earlier, which showed that these two T-cell regulators were, um, We're functioning in this way to suppress this autoimmune response.

• 31:57Lester Nare?

  Yes.

• 31:58Krishna Choudhary?

  And then it's combining this Fox P3 gene thing that's happened in 2001.

• 32:04Lester Nare?

  Yes.

• 32:04Krishna Choudhary?

  To show that actually, the, if you add the Fox P3 gene to normal T cells, they'll turn into regulatory T cells. It's like a retraining.

• 32:16Lester Nare?

  Okay.

• 32:16Krishna Choudhary?

  You know, it's like you send them back to the training academy.

• 32:19Lester Nare?

  To relearn what, what it may have been missed.

• 32:22Krishna Choudhary?

  Yeah, so you can, you can insert this Fox P3 genome, and it'll actually like turn them into regulatory T cells.

• 32:29Lester Nare?

  That's, that's very, okay.

• 32:30Krishna Choudhary?

  Okay, so that's, it's, it's so cool, like the mechanistic way in which we can, we can manipulate these things to really be convinced that this is how it works.

• 32:40Lester Nare?

  Yes.

• 32:40Krishna Choudhary?

  You know?

• 32:40Lester Nare?

  Yes, no, hundred, hundred percent, I, yeah.

• 32:43Krishna Choudhary?

  It's, it's really cool. So he published this in 2003 in Science. I think that's 24, you can see.

• 32:49Lester Nare?

  Yes.

• 32:49Krishna Choudhary?

  And this is sort of the last, last of the papers that we're gonna review.

• 32:52Lester Nare?

  Okay.

• 32:53Krishna Choudhary?

  Okay, and so 2003, and then now it's been what, about 20 years? 20 plus years that they get the Nobel Prize for it.

• 33:00Lester Nare?

  Right, but Sakaguchi's been at it since the 1980s.

• 33:03Krishna Choudhary?

  Right, right. He's been at it like for a while.

• 33:06Lester Nare?

  Right.

• 33:06Krishna Choudhary?

  It's crazy. Yeah, um, and so that's, that's effectively what this Nobel Prize is about. It's completely characterizing this, um, military police kind of narrative, or the police of the police.

• 33:22Lester Nare?

  Yes.

• 33:22Krishna Choudhary?

  And in Photo 25, I have like, the, they always make a cartoon of, um, of like what the Nobel Prize is about. So here, you've got like, the, you've, you've got, um, the T reg.

• 33:35Lester Nare?

  Yeah, the regulatory T cell.

• 33:36Krishna Choudhary?

  The regulatory T cell, which, which is like the spaceship, I guess.

• 33:39Lester Nare?

  Yes.

• 33:40Krishna Choudhary?

  And it's got this, this, the receptor, the T cell receptor.

• 33:43Lester Nare?

  Yeah.

• 33:43Krishna Choudhary?

  That's trying to identify if there's been an incorrect immune response.

• 33:46Lester Nare?

  Yes.

• 33:47Krishna Choudhary?

  And then the alien or whatever is inside.

• 33:49Lester Nare?

  Yes.

• 33:50Krishna Choudhary?

  That has a Fox P3 cap on. You know, so that's the DNA.

• 33:54Lester Nare?

  Yeah, yeah, yeah.

• 33:55Krishna Choudhary?

  That is, uh, I don't know how they come up with this.

• 33:58Lester Nare?

  That's cool, that's cool. But that, that's actually, having walked through, because I saw this image at the beginning. It meant nothing.

• 34:04Krishna Choudhary?

  Yeah.

• 34:05Lester Nare?

  And now having walked through, I actually can point to each of the things.

• 34:08Krishna Choudhary?

  Exactly, yeah, yeah.

• 34:08Lester Nare?

  And identify what's, what's going on and why it matters.

• 34:12Krishna Choudhary?

  Yeah, so, so the T reg outside, that's, that's Sakaguchi. And then the Fox P3 gene that is responsible for that, that is Brunt, Calvin Ramsdale. You know, and so. Congrats to the the three laureates.

• 34:25Lester Nare?

  Yes, yes.

• 34:26Krishna Choudhary?

  You know, they're they did amazing work. And now there's in current frontiers, there's a lot of stuff going on.

• 34:31Lester Nare?

  So I was actually gonna ask, like, so now now knowing that we have that understanding, because this was like a rather than like the implementation of a tool necessarily like CRISPR, this was more of an understanding of a functional.

• 34:44Krishna Choudhary?

  Yeah.

• 34:44Lester Nare?

  Functional processes.

• 34:45Krishna Choudhary?

  Yeah.

• 34:45Lester Nare?

  In a way that unlocks a whole variety of implications.

• 34:48Krishna Choudhary?

  Yeah, now now we can now we can start getting into how do we um? How do we understand when T regs themselves don't do their job?

• 34:56Lester Nare?

  Mm hmm.

• 34:56Krishna Choudhary?

  Right? Because that's when we get these autoimmune disorders like IPEX and diabetes.

• 35:00Lester Nare?

  The reason it's among other things, the reason at some point is because it's so directly related to this autoimmune disorder.

• 35:05Krishna Choudhary?

  Yes.

• 35:06Lester Nare?

  Problem.

• 35:06Krishna Choudhary?

  Exactly. Yeah, this is one of the ways in which an autoimmune disorder manifests.

• 35:10Lester Nare?

  Which is very a very pernicious.

• 35:11Krishna Choudhary?

  Yes, exactly. And it's something that we need to solve. And at the end of the day, it is a Nobel Prize for medicine. Right? And so um now there's been so much research about it, dude. Like now there's subsets of T regs. There's something called the natural T regs. And then there's um induced T regs that are induced in peripheral tissues after antigen exposure. So there's like normal T cells.

• 35:34Lester Nare?

  Yes.

• 35:35Krishna Choudhary?

  That like get induced to become T regs.

• 35:38Lester Nare?

  Yeah.

• 35:39Krishna Choudhary?

  Because of their environment.

• 35:40Lester Nare?

  Yeah.

• 35:40Krishna Choudhary?

  They they decide to go back to the their own because the gene is already in there.

• 35:43Lester Nare?

  Yes.

• 35:44Krishna Choudhary?

  In their DNA, it's just been repressed.

• 35:45Lester Nare?

  Yes.

• 35:46Krishna Choudhary?

  They can they can take out that that repressor. And then um there's you can also induce them in vivo and use them in cell therapy.

• 35:52Lester Nare?

  Mm hmm.

• 35:54Krishna Choudhary?

  Um, you know, it's right now we've got we've got um work in 2025. I was just reading some of the some of the work that's come out now.

• 36:04Lester Nare?

  Yes.

• 36:04Krishna Choudhary?

  Um, there needs to be people have found that in inflamed tissues where there isn't there where there isn't an immune response, you'll find that the T regs actually need stronger Fox P three expression. So they need they need more expression of that magic gene in order to actually remain stable. Um, they've identified repressors, transcriptional repressors, which are literally like little proteins that come in and sit on your DNA and prevent that stretch of DNA from getting transcribed, right? And so you've they've discovered um repressors that can inhibit Fox P three.

• 36:41Lester Nare?

  From expressing.

• 36:41Krishna Choudhary?

  And then if you block the repressor, then this thing is no longer inhibited.

• 36:46Lester Nare?

  Yeah.

• 36:46Krishna Choudhary?

  And you can actually get regulation.

• 36:48Lester Nare?

  Yeah.

• 36:48Krishna Choudhary?

  So so that's one way that you can actually do therapy.

• 36:52Lester Nare?

  Yes.

• 36:53Krishna Choudhary?

  You know, they've discovered enhancers which go in and actually do the volume control on that Fox P3 gene that we talked about on another episode.

• 37:01Lester Nare?

  Yes.

• 37:02Krishna Choudhary?

  Um, there's like 200 plus clinical trials that are happening right now.

• 37:06Lester Nare?

  Related to.

• 37:06Krishna Choudhary?

  Related to T reg.

• 37:08Lester Nare?

  Related to T reg as a general.

• 37:09Krishna Choudhary?

  Yeah, yeah. So, so you know, it's a ubiquitous now.

• 37:15Krishna Choudhary?

  Like method by which the people are trying to tune the immune system and then fight disease in this way. And it wouldn't, wouldn't be possible without like fundamentally understanding all of these mechanisms.

• 37:28Lester Nare?

  Right.

• 37:29Krishna Choudhary?

  Down to the molecular level.

• 37:30Lester Nare?

  Yes.

• 37:31Krishna Choudhary?

  Of like how this stuff works.

• 37:32Lester Nare?

  Yes.

• 37:32Krishna Choudhary?

  You know?

• 37:33Lester Nare?

  Yes. Hundred, hundred percent.

• 37:35Krishna Choudhary?

  Yeah.

• 37:35Lester Nare?

  This, this is a, um.

• 37:39Lester Nare?

  The immune, I mean, obviously, you know, the immune system and all of the, the medicine in particular, I think, I think it's been post COVID, there has been a very interesting discussion about how the body works.

• 37:52Krishna Choudhary?

  Mm hmm.

• 37:53Lester Nare?

  That is not necessarily informed from first principles.

• 37:55Krishna Choudhary?

  Yeah.

• 37:56Lester Nare?

  Right? Because there's a lot of these fundamental processes.

• 37:58Krishna Choudhary?

  Yeah.

• 37:58Lester Nare?

  That just are what they are.

• 38:00Krishna Choudhary?

  Yeah.

• 38:01Lester Nare?

  And there's, there is a benefit to having an understanding of what those are.

• 38:05Krishna Choudhary?

  Yeah. I mean, I love thinking about the body as just a bunch of Lego blocks.

• 38:09Lester Nare?

  Lego blocks.

• 38:10Krishna Choudhary?

  Right? Which are just trying to find each other and like all of the complicated decision making is happening at that Lego block level, right? At the molecular level.

• 38:18Lester Nare?

  Right.

• 38:18Krishna Choudhary?

  It's kind of insane.

• 38:19Lester Nare?

  It, it.

• 38:19Krishna Choudhary?

  That we're, it's such a complicated set of things.

• 38:24Lester Nare?

  Right.

• 38:25Krishna Choudhary?

  Where like tiny things go wrong and it's just totally wrecks you, right?

• 38:28Lester Nare?

  Yeah.

• 38:29Krishna Choudhary?

  And now we're getting to understanding things at such a level when, when those tiny things go wrong, we can go in and fix it.

• 38:35Lester Nare?

  And, and even just one very, very tiny, small aspect of this combinatorial process that has so many implications. So it, it, it seems like this has solved sort of this 100 year mystery.

• 38:48Krishna Choudhary?

  Mm hmm.

• 38:48Lester Nare?

  Of like how the immune system.

• 38:50Krishna Choudhary?

  Yeah.

• 38:51Lester Nare?

  Restrains itself.

• 38:52Krishna Choudhary?

  Exactly. Yeah, pretty cool.

• 38:54Lester Nare?

  This is, this is, this is, this is very cool. This is day one, so this is the medicine.

• 38:59Krishna Choudhary?

  Yep.

• 38:59Lester Nare?

  We did, we, I, I said in our predictions Princeton was gonna get on the board.

• 39:02Krishna Choudhary?

  Yeah, I didn't know it was gonna be the first day.

• 39:04Lester Nare?

  We're on the board.

• 39:05Krishna Choudhary?

  Yeah, I mean, at least my predictions were wrong, but we got on the board.

• 39:08Lester Nare?

  We got on the board.

• 39:09Krishna Choudhary?

  Yeah.

• 39:09Lester Nare?

  We'll take that. They're actually accurate, but tactically wrong.

• 39:12Krishna Choudhary?

  Yeah.

• 39:12Lester Nare?

  Uh, so tomorrow, we're gonna be doing physics. Um, same time.

• 39:17Krishna Choudhary?

  Yep.

• 39:18Lester Nare?

  Same place. Uh, congratulations to the winners. Uh, and we're gonna, again, make sure we put all these out across all the socials, etc. So be sure to tune in, but we will be back tomorrow for day two of Nobel Prize week. My name is Lester Nare, as always, joined by my co-host and resident PhD Krishna Choudhary. This is from First Principles. We'll see you guys tomorrow. Scott. Okay, here we go.

• 39:43Krishna Choudhary?

  Yep.

• 39:44Speaker 03

  This year's prize is about encountering quantum mechanics on a new scale.

• 39:51Krishna Choudhary?

  Okay, so not atomic force microscopy.

• 39:54Lester Nare?

  Or topological physics.

• 39:55Speaker 03

  Kungli vetenskapakademin har i dag beslutat att utdela 2025 års Nobelpris i fysik till John Clark, University of California at Berkeley, USA.

• 40:08Krishna Choudhary?

  Okay.

• 40:09Speaker 03

  Michelle DeBoreille.

• 40:10Krishna Choudhary?

  Berkeley on the board.

• 40:11Speaker 03

  Yale University, and University of California at Santa Barbara, USA.

• 40:15Krishna Choudhary?

  Okay. Oh, UCSB on the board.

• 40:17Speaker 03

  John Martinez, University of California, Santa Barbara, USA.

• 40:21Krishna Choudhary?

  That's also UCSB, okay.

• 40:23Speaker 03

  For uptake of macroscopic quantum mechanics, funding and energy quantizing in an electric current. The Royal Swedish Academy of Sciences has today decided to award the 2025 Nobel Prize in Physics to John Clark, University of California at Berkeley, USA.

• 40:48Speaker 03

  Michel Devoret, Yale University and University of California at Santa Barbara, USA.

• 40:55Lester Nare?

  Santa Barbara, unbelievable.

• 40:56Speaker 03

  And John Martinez, University of California at Santa Barbara, USA.

• 41:02Krishna Choudhary?

  I wonder where they got their PhDs.

• 41:03Speaker 03

  For the discovery of macroscopic quantum mechanical tunneling and energy quantization in an electric circuit.

• 41:10Lester Nare?

  Macroscopic quantum tunneling. Okay. Hello, Internet. This is your captain speaking, Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary. We are on day two of Nobel Prize week for the Physics Prize. We just watched the live press conference. Macroscopic quantum tunneling was the winner. We're going to dive in and understand what exactly this all means. So, interestingly, not AFM, not topological physics.

• 41:39Krishna Choudhary?

  Yep, yep.

• 41:40Lester Nare?

  Very much still important. So, what matters about this macroscopic quantum tunneling winning the Nobel for Physics this year?

• 41:49Krishna Choudhary?

  You might have heard of quantum computers.

• 41:52Lester Nare?

  Yes.

• 41:52Krishna Choudhary?

  Right? Actually, I just, I just looked it up. John Martinez, who's the, who's one of the winners of the Nobel Prize today, he's actually the head of the Google Quantum AI lab.

• 42:04Lester Nare?

  Oh, interesting, okay.

• 42:05Krishna Choudhary?

  In UCSB.

• 42:06Lester Nare?

  Yes.

• 42:07Krishna Choudhary?

  So, it's kind of, it's kind of a win for large devices that have these quantum mechanical properties that can then go on to do all sorts of stuff. It's, it's a bit surprising to me that something like as adjacent to quantum computing as this got the Nobel Prize, but I think it's, it, I mean, it's for experiments that were done in the 1980s.

• 42:31Lester Nare?

  Okay.

• 42:31Krishna Choudhary?

  And that has sort of started a whole new field of quantum devices, quantum experiments, things like that. So, it's not just for, you know, quantum computing, but it's sort of a foundational prize. So, it was given to three people. It was given to John Clark. Michel Devore and Jean Martinez for the discovery of macroscopic quantum mechanical tunneling and energy quantization. And I think it's a bit of a nod to what happened 100 years ago. We did an episode on the fact that 2025 is the year of quantum, right? According to the UN. Yes. And that's because 100 years ago is when the first seminal papers in quantum mechanics by Werner

• 43:15Krishna Choudhary?

  Heisenberg were published. We did a whole episode on that paper itself. And in photo two, you can see that's a it's a oh, okay, never mind. Photo two is actually just about the quantum tunneling itself. This is the this is the Nobel Prize cartoon. They always have a Nobel Prize cartoon, right? About about what's actually happening. So this is a cartoon of on the left hand side, you see like electrons and it's turning into this giant current. Yes. It's because it's one giant quantum state. Okay. Okay. And we're going to sort of get into like what this thing means as we go on in the story. Photo three is a nod to the 2025 year of quantum physics. That's a photo of three of

• 44:00Krishna Choudhary?

  some of my favorite scientists. We've got Werner Heisenberg in the middle. On the left is Paul Lee and on the right is Enrico Fermi. Yes. Three seminal figures in quantum mechanics. And on the left is a letter from Werner Heisenberg to Wolfgang Pauli, talking about his 1925 paper and how everyone else is wrong. Pauli was also of the opinion of Werner Heisenberg, where, you know, we needed a new paradigm to do everything quantum related. And so I really think that this year's Nobel Prize goes to quantum because of the fact that it's the year of quantum, you know, I think that was definitely part of the back chatter. That makes sense. Okay.

• 44:42Krishna Choudhary?

  So to get into like what exactly is going on in the physics? We need to understand something called quantum tunneling. Okay, so if we have like a classical particle and you've got like, let's say a wall, like a brick wall. And I like throw stuff at it, it's gonna bounce right back. In no world is a ball that's the size of my hand ever gonna go through. Right in quantum, in the quantum world, that's no longer the case. Right, you can have a barrier and then have a single particle go through. And this is something that you can solve in undergraduate physics. Um, just using the Schrodinger equation. You'll have a probability that that particle goes through the barrier. And if you look at this description here on, that's, that's the Schrodinger equation.

• 45:25Krishna Choudhary?

  Getting solved for this potential landscape. The potential landscape is zero everywhere. And then you've got this high potential region, what that, that's basically the barrier. And then you've got some particle with initial energy going from left to right. Okay, notice that on the right hand side. You've got, the wave function is highly diminished. So what that means is that the probability of finding the particle on that side. Is way smaller than finding the particle on the left side, which makes sense, right? I'm going from the left side, so the probability of tunneling is low. Yes. But crucially, notice that the waviness of the, of the wave function on the right.

• 46:07Krishna Choudhary?

  Is the same as on the left, meaning the wavelength hasn't changed. Yes. And what that means is the energy hasn't gone down. Right. So if I were to find a particle with low probability, fine. But if I were to find that low probability outcome of a particle on the right hand side. The energy has not gone down. It's almost as if the particle just teleported through this energy barrier. Yes. That's very not classical. Right, right, yes. That is, that is very much like not a classical thing. Yes. Right, in a classical thing. Even if it like somehow went through, it would be slowed down by the barrier. But here it's a probabilistic outcome. But if it happens that the particle goes through, it's going to be moving with the same energy. That's so interesting. That's the that's the magic of quantum mechanics there.

• 46:52Krishna Choudhary?

  Right. Okay. Right. So historically, it's actually been seen in all sorts of different phenomenon. Like, for example, with radioactive decay. This is the idea where nuclei, like large nuclei, like the uranium atom, can decay when they spit out an alpha particle, right? And it happens with a certain probability. That can actually be modeled using this quantum tunneling landscape. What you can imagine is you've got you've got the nucleus of the atom. And the nucleus of the atom has a bunch of particles that are kind of moving around. Right? Each of these nucleons are moving around either the protons or the neutrons. And if the proton or neutron tunnels itself outside of that little well. Yes. Right?

• 47:37Krishna Choudhary?

  Then it's going to find itself on the other side of that barrier. And it's going to be going. Yes. With pretty high energy. Yes. Right? That's and and the probability with which that tunneling happens tells you the half-life of your material. If it's a high probability, then the half-life is lower. Yes. If it's a really low probability, that means it's a very stable nucleus. And the half-life is much larger. Mm hmm. Right? And that is why half-lives and like the the fact that half of your nuclei are going to decay with a certain amount of time. That's a very probabilistic thing to say. Yes. And it's rooted in this quantum mechanical probability stuff. Okay. Does that make sense? Hundred percent. So and like, we know that quantum tunneling happens. Right.

• 48:22Krishna Choudhary?

  Also, in the core of like, the reason why we're all alive on Earth. And Earth has been going for four billion years with life on Earth is because the Sun has been doing quantum tunneling in its nucleus. Right? You would imagine that the Sun's nucleus is like, I think it's something like a million Kelvin, a million degrees Celsius. And you know, at that speed, I mean, at that temperature, the nuclei inside the sun are moving extremely fast, right? And the idea is two hydrogen nuclei, just protons, are moving so fast that they bump into each other. But what's preventing them from bumping into each other is the fact that they're both positive charges.

• 49:02Krishna Choudhary?

  And so the Coulomb barrier, which is basically repulsion, positive, positive, don't like to be next to each other, is gonna make them not bump into each other, right? And they're actually not moving fast enough to get over that energy barrier, okay? The reason why sometimes they get stuck right next to each other and the strong nuclear force takes over and fuses them into a single nucleus is because sometimes these guys tunnel past that energy barrier that's created by the Coulomb potential. And so all of a sudden, sometimes you'll have the proton tunnel through that barrier, find itself right next to the other proton, and then you'll have the fusion happen that creates the light that we see.

• 49:44Lester Nare?

  That we see.

• 49:45Krishna Choudhary?

  Right?

• 49:45Lester Nare?

  Yes.

• 49:46Krishna Choudhary?

  So quantum tunneling is, we can, we can thank quantum tunneling for the light from the sun.

• 49:51Lester Nare?

  Literally the light that powers everything, that entire ecosystem.

• 49:55Krishna Choudhary?

  Yeah, and so quantum tunneling has always been something that is well-known, but it's been well-known for small numbers of particles, right? With, even with nucleons and alpha decay, that's like four protons, right? Four sort of, it's a pretty small mass, right? Um, with the, with the stuff in the sun, again, few nucleons. What this year's Nobel Prize winners did was experimentally confirm quantum tunneling and quantum behavior for like, on the order of a billion individual particles, all acting together and quantum tunneling together.

• 50:30Lester Nare?

  Interesting.

• 50:31Krishna Choudhary?

  Okay, so it's, it's several orders of magnitude above that sort of undergraduate level.

• 50:36Lester Nare?

  Understanding.

• 50:37Krishna Choudhary?

  Like problem sets that we used to do.

• 50:39Lester Nare?

  Right, right.

• 50:39Krishna Choudhary?

  Right? It's, it's, it's very cool, I think. So in order to really understand the, the, the experimental setup.

• 50:46Lester Nare?

  Yes.

• 50:46Krishna Choudhary?

  Right? We gotta talk about superconductivity, okay? This was made very famous with the whole LK99 scam that happened from the, the Korean scientists. It was not, it was not real.

• 51:00Lester Nare?

  It was not a room temperature.

• 51:01Krishna Choudhary?

  It was not a room temperature superconductor. Yeah, this is, this is an example of an actual superconductor that's been cooled down. That's why it's like condensing all the. The stuff around it, right? And with superconductivity, you have this amazing phenomenon where at low temperatures, you have zero resistance to electrical current. Okay? And by zero, I don't mean near zero. You mean. Or like a little bit. I mean, literally zero. Literally zero. Literally zero. There are, there are superconducting currents that have been kept alive just by the fact that they've been kept cold for like decades now. Interesting. In experimental physics labs.

• 51:43Krishna Choudhary?

  Because like, it's, because there's no resistance, you can keep this state. Right. For decades and it'll be the same exact current value. Cause no current is leaving, no current is entering. It's the same amount of energy that's locked into this apparatus that you have. Black box. Yeah, so for, for 20 years, you can experiment on the same exact thing, right? And make your, make everything else bigger and bigger, but like the thing that you're, you're messing with. Right. Is exactly the same. Yeah. It's, it's been decades. Yeah, all you have to do is keep it cold. Right. Okay, so it's not a perpetual motion machine. Okay, do not get me wrong, right? It takes a lot of electricity to keep this thing that cold. Okay? But if you can keep it cold, then this little state.

• 52:28Krishna Choudhary?

  Right. Is, is just gonna stay forever, right? It's, it's, that's the magic of superconductivity. And the physics behind superconductivity is quite interesting. It was discovered by three people, Bardeen, Cooper and Schiefer, at the University of Illinois in Urbana-Champaign. And it comes from the fact that electrons can interact with the lattice of atoms in a superconductor in a very specific way. So I think we, we've got a, we've got a picture here that we can show. Here's what's going on, okay? So you've got two electrons, okay? They're the little tiny blue dots. And then you've got a lattice of, of atoms, which are these, which are these positive charges, right?

• 53:09Krishna Choudhary?

  Um, well, they're really neutral, but they've got positive neutral nuclei and then and then electron clouds around them. Right? So so the the positive is the the teal color. Okay? What happens is when there's an electron in that lattice, what it's gonna do is deform the lattice in a way that the positive nuclei are gonna kind of get smudged towards the electron. Okay, now, what is that gonna create? That's gonna create a localized positive charge where the electron is, because usually that electron and all the positive charges would perfectly cancel out.

• 53:44Lester Nare?

  Right.

• 53:45Krishna Choudhary?

  But because all the all the positive charges are now sort of scrunched up and localized, there's a higher density of positive charge there than the electron is able to cancel out. So there's a slight positive charge there.

• 53:57Lester Nare?

  Which this is in that sort of slightly pink area.

• 53:59Krishna Choudhary?

  Yes, exactly. There's a slight positiveness to it.

• 54:04Lester Nare?

  Yes.

• 54:04Krishna Choudhary?

  Okay, and that is gonna couple with the negative electron.

• 54:09Lester Nare?

  That's in the lattice, right?

• 54:11Krishna Choudhary?

  Yes, exactly. And these two, these two particles, they obey the Pauli exclusion principle, meaning that you can't have the quantum states right on top of each other. They they they don't wanna, they don't wanna sort of like talk to each other all that much, okay? But because they're two different electrons, you can have them

• 54:34Krishna Choudhary?

  obey the Pauli exclusion principle within themselves and create something called a boson. Okay, like, these two are fermions, meaning that they obey the Pauli exclusion principle, but together, they they they they they use their disagreement to sort of cancel each other out and create a boson. Okay, and this boson is something that can have quantum states that are right on top of each other.

• 54:58Lester Nare?

  Interesting.

• 54:59Krishna Choudhary?

  And so you have very different physics. You can have something, I mean, you might have heard of something called a Bose-Einstein condensate.

• 55:05Lester Nare?

  I was literally gonna just ask that, yes.

• 55:06Krishna Choudhary?

  Exactly. So the Bose-Einstein condensate is this idea that all, like, when you get something really, really cold, they start behaving like bosons, and then they start going on top of each other, and they obey like one giant quantum function. Okay, that's what these Cooper pairs can now do. These are called Cooper pairs.

• 55:23Lester Nare?

  Yes.

• 55:24Krishna Choudhary?

  And the pairs can act like quasi-particles that can stack on top of each other, and you can have this kind of Bose-Einstein condensate in your. Superconductor, right? The mathematics is about the same.

• 55:38Lester Nare?

  Interesting.

• 55:38Krishna Choudhary?

  Okay?

• 55:39Lester Nare?

  Yeah, yeah, yeah.

• 55:39Krishna Choudhary?

  And what that means is these, these, this condensate can now move around like a single quantum state.

• 55:45Lester Nare?

  It's almost has this shared state across these independent electrons.

• 55:49Krishna Choudhary?

  Yes.

• 55:49Lester Nare?

  Um, that act at, that act in unison as an, as an emergent effect of this, these parameters that you just described.

• 55:59Krishna Choudhary?

  Yeah, exactly, exactly. And so they can, it's like multiple pairs, they occupy the same quantum state and because they're occupying the same quantum state, they can move as one. And so the electrical resistance, which is what you usually get when all these electrons are bumping into each other, is no longer there.

• 56:14Lester Nare?

  Right.

• 56:15Krishna Choudhary?

  Does that make sense?

• 56:16Lester Nare?

  A hundred percent.

• 56:16Krishna Choudhary?

  So the Cooper pairs are, are talking nice to each other.

• 56:20Lester Nare?

  Yes.

• 56:20Krishna Choudhary?

  And they're moving.

• 56:21Lester Nare?

  Yes.

• 56:22Krishna Choudhary?

  And without, without any, without any bumping.

• 56:24Lester Nare?

  And that lack of resistance creates, like, there's opportunity that gets created from that low resistance environment.

• 56:30Krishna Choudhary?

  Yeah, zero resistance.

• 56:31Lester Nare?

  Zero resistance environment.

• 56:33Krishna Choudhary?

  Zero resistance environment. And once you have zero resistance, then you have stuff like the Meissner effect, which is where you get the levitation over a magnetic field.

• 56:40Lester Nare?

  Yes.

• 56:40Krishna Choudhary?

  And you get maglev trains.

• 56:42Lester Nare?

  I was gonna say, that's how maglev works.

• 56:43Krishna Choudhary?

  Yeah, yeah. So, so that's, that's how, um, that's how superconductors work, okay? Fundamentally, the physics is you've got these Cooper pairs that are pairing up, they, the two fermions are pairing up to create a boson, and then those bosons become like one giant thingy that like moves in the, in the superconductor, right? And it was, um, they won the Nobel Prize for it in 1972. This is Bardeen, Cooper, and Schaeffer, and it was at the University of Illinois, Urbana-Champaign. Bardeen, actually, um, alumni of Princeton University, and he's the only person to have won the physics prize twice.

• 57:19Lester Nare?

  Oh, okay.

• 57:20Krishna Choudhary?

  Yeah, once for inventing the transistor at Bell Labs.

• 57:23Lester Nare?

  No big deal.

• 57:24Krishna Choudhary?

  And no big deal. And then he came over here and like, did the seminal work for superconductivity.

• 57:29Lester Nare?

  What a life.

• 57:30Krishna Choudhary?

  Yeah, what a life, dude. BCS theory.

• 57:33Krishna Choudhary?

  So now we understand how Superconductors work. Right now, there's this guy, Brian Josephson. He predicted that what superconductors can do is they can actually tunnel across an insulating barrier together. Before, we used to talk about how particles individually tunneled, right? Across barriers. Yes. What Josephson figured out is actually these Cooper pairs that are that are acting like particles. They can tunnel across a barrier as well. As one. As one. As one. As one, right? So on the top there, this is again, a cartoon from the Nobel Prize Committee. On the top there, that's a normal current, right?

• 58:16Krishna Choudhary?

  All the electrons are pissed off and they're like fighting each other. And being disagreeable. Yeah, they're being disagreeable. And then in the middle, that's your superconductor. So all of the electrons are paired up. They've got little smiles. I don't know if you can see that from here, but they got little smiles and they're paired up. And they're moving across that barrier. That's called the Josephson junction. Okay, so that was Brian Josephson. The bottom rung is what the Nobel Prizes now are doing. Which is we're going from Cooper pairs. Right. To now a giant current. Right. That is one thing. That is one thing. Okay. Yes. That is that is tunneling across the barrier. Right. Okay. Yes. So we're going from like two particles to now 10 to the 9. Right. Okay. Right. Yes.

• 59:00Krishna Choudhary?

  And Josephson, he won the he won the Nobel Prize in 1973 for for that. And this is a depiction of a Josephson junction, which is the the sort of theoretical thing that he was he was trying to look at. Okay, so on the left hand side, you've got two superconducting regions. Okay, that is separated by an insulator. Yes. Okay. And the idea is that when even when there's zero voltage across this.

• 59:33Krishna Choudhary?

  Barrier, you can have Cooper pairs go through. Go through. And there's gonna be some max amount of critical current that you can get from those Cooper pairs pairing up and moving through. Yes. Okay? Yes. And you can, you can sort of imagine the Josephson junction as like a schematic on the right, where you've got a capacitor, you've got a resistor that holds all of the resistance of the entire circuit somehow. And then you've got a current in the middle, and that's your critical current, and that's the maximum amount of current you can do with zero voltage. If you apply more voltage, then it's just gonna become a classical system, right? Okay, so that's how Josephson junctions work.

• 1:00:13Krishna Choudhary?

  Now, in 1978, Anthony Leggett, who is another Nobel Prize winner,

• 1:00:21Krishna Choudhary?

  he started asking, well, can I make a macroscopic tunneling experiment happen? Where instead of doing Cooper pairs that are tunneling, and, and, and like each little thing is treated like a, like a quantum mechanical state, what if the entire circuit is a quantum machine? Right. Right? It's like a, it's like a, the entire circuit is an atom. Yes. In some sense. Yes. That's doing this quantum mechanics, okay? And what he considered was a current biased Josephson junction. And that's, that's what we're gonna see over here. So what we're looking at is that Josephson junction that we had earlier, right?

• 1:01:02Krishna Choudhary?

  And he's asking, now, what is the energy landscape of the current in that Josephson junction? Okay? You can ask, the Josephson junction can be parametrized by something called the phase, which is like if you have an alternating current, the phase difference between the two sides is like a parameter that describes the position of this circuit. You can imagine the circuit is like a particle, and the position of that circuit is the phase, okay? Like, and in physics, when you do that, and you go to the equations, then it like starts obeying kind of like Newton's laws kinds of stuff, right? Where you've got like a potential landscape, and you've got the energy minima, and like it wants to move towards the energy minima, right?

• 1:01:44Krishna Choudhary?

  So, so when, when you start putting the language of the Josephson junction into this sort of mathematics, you get these potential landscapes. And the idea is, on the top... You've got on the left, if you don't apply a current, remember, this is a current bias Josephson junction. So I'm applying an external current, right? And if I apply very little current, then the energy states look like on the top left where I've got these energy minima. Right? And the particle is sort of going to get stuck in one of those. The circuit is going to get stuck in one of those states. If I apply too much current, then you're going to get this effect. Yes. Where the the the the energy landscape gets completely tilted. Yes. Right?

• 1:02:28Krishna Choudhary?

  And then you have no energy minima. Okay, so the the question was, the experimental question was, is there a macroscopic degree of freedom? Such that the entire circuit behaves like the this multi

• 1:02:51Krishna Choudhary?

  energy minima thing, right? Where on the bottom, if there's no such macroscopic degree of freedom, where stuff can get quantum at a big level, then you're going to have the stuff in C, which is a very continuous energy landscape. And the it's just like a particle on a hill. Okay, a ball rolling down a hill. It can be in any of those positions on the hill. Right? If it's quantum, on the other hand, then in that potential barrier, right? In that little well. Yes. Where where the particle is sitting, where this current particle is sitting, there's going to be discrete energy levels. Within that. Within that, within that well. Right? And there's going to be discrete quantum states. But that is the experimental question, right? Right.

• 1:03:35Krishna Choudhary?

  And Leggett says that there should be, but this is this is going to be notoriously hard to actually make. Right? You can imagine, uh, this is in the 1980s. So again, we don't have the technology that we have today. Today, we have all of the upgrades from this to create like giant super, um, like superconductors and giant quantum computers. This is so fascinating. With that, with that setup, the fact that you like, the question is, I've got a, I've got a circuit now. That's that's made, that's it's a fancy Josephson. This is the junction biased. Yeah, it, yeah, it's it's got this like biased, um. It's got this biased current that goes in.

• 1:04:20Krishna Choudhary?

  Can I make the entire circuit a quantum object?

• 1:04:23Lester Nare?

  Right.

• 1:04:24Krishna Choudhary?

  That's the idea, right? And the entire circuit is made up of like 10 to the nine things.

• 1:04:29Lester Nare?

  Right.

• 1:04:30Krishna Choudhary?

  And can all of those 10 to the nine things move as a single quantum object, right? That tunnels and does all of the stuff that I wanted to do.

• 1:04:40Lester Nare?

  As a result of this sort of concept, we just walked through around how quantum tumbling fundamentally works.

• 1:04:44Krishna Choudhary?

  Yes.

• 1:04:44Lester Nare?

  The thing is, how can we scale it up from a single? Like there's a particle, which is a single Lego block. And we talked about Cooper pairs, which is like imagine components of a whole Lego structure. But it's like larger than a block. And now we're saying, can we make it the whole?

• 1:04:57Krishna Choudhary?

  The whole.

• 1:04:58Lester Nare?

  Like the completed Lego structure behind you.

• 1:05:00Krishna Choudhary?

  Yeah.

• 1:05:01Lester Nare?

  And have that entire system operate as this single.

• 1:05:05Krishna Choudhary?

  A single quantum object.

• 1:05:06Lester Nare?

  Quantum object, right?

• 1:05:08Krishna Choudhary?

  Like that has well-defined quantum states. Okay, so that is where we get to UC Berkeley. Okay, one of my favorite universities in California. So we're in the physics building. This is a photo 12. That's the physics building of UC Berkeley, legendary building, right in the center of campus, right next to the giant tower that UC Berkeley campus is well-known for. That's the building where, you know, Oppenheimer's been in. That's the building where plutonium was discovered, several Nobel prizes. And actually now they got a plus three on a single day.

• 1:05:45Lester Nare?

  That's unbelievable.

• 1:05:46Krishna Choudhary?

  Unbelievable because.

• 1:05:47Lester Nare?

  We were excited yesterday.

• 1:05:48Krishna Choudhary?

  Yeah, we were excited with plus one. But yeah, in a single day, UC Berkeley has a plus three because John Clark, at the time, after his PhD at Cambridge, he became a professor at UC Berkeley. He was joined by Michel Devore, who was a postdoc in his lab, and Jean Martinez, who was a PhD student. All three of them were in the same lab and the same building together. And they start asking if they can create a superconducting electrical circuit with a Josephson junction that has this property, where billions of these Cooper pairs, 10 to the nine particles, are acting like a single quantum particle, right?

• 1:06:31Lester Nare?

  Yes.

• 1:06:31Krishna Choudhary?

  Can we do this? Okay, so.

• 1:06:35Krishna Choudhary?

  Um, we get to, we, we get there and now this is their setup. Okay. This is actually a photo that's adapted from John Martinez's thesis. Okay, okay. Imagine writing a PhD thesis. Yeah. And then like a figure is like in the Nobel committee's cartoon.

• 1:06:55Krishna Choudhary?

  You know, it's so legendary. It's so legend, dude. Like this is literally in his thesis. That's unbelievable. Yeah, yeah. And his PhD thesis. So this is the, um, the current that they came up with. This, the circuit that they came up with. On the left-hand side, you've got the power that's coming in. Okay. And on the right-hand side, all the way over here, I guess, from my, my left, um, all, all the way over there. That's the Josephson junction part. In the middle, you've got, um, like copper in the middle. And this is the part I, I actually still don't understand is how they're, they're saying the copper is like shielding. But I like, I thought copper was electrically conductive.

• 1:07:38Krishna Choudhary?

  They didn't really go into it and I didn't really have time to like figure out how. So if somebody in the comments who knows how this works, like, I don't know how copper is shielding. Okay. Anyways, but somehow they're saying it's shield. So, so, but, but the, the idea is, you know, you want to get this thing really cold. And, and so, and you want to shield it from all sorts of electrical noise, all sorts of every type of noise. Okay. So much so. Yeah, all of these external factors. And what you want to do is also measure the resistance and the capacitance of this entire circuit independently at that temperature. So that then you can fit everything to the, you can, you can plug everything into the equation and then see if the properties are making sense. Right?

• 1:08:23Krishna Choudhary?

  So before this group, before this group was doing all that, what people would do is they would like, do these kinds of experiments, but they fit parameters. Right. And be like, See, it's kind of working. That's not convincing, right? What you want to do is say, this is the equation. This is this number. This is this number. This is this number. This should be this number. This is what I measured. We're good.

• 1:08:45Lester Nare?

  We're good.

• 1:08:46Krishna Choudhary?

  Right?

• 1:08:46Lester Nare?

  Yes.

• 1:08:46Krishna Choudhary?

  It's not like if these numbers are this, then it makes sense.

• 1:08:50Lester Nare?

  Right.

• 1:08:50Krishna Choudhary?

  That's not, I mean, it's, it's still like fundamentally good science.

• 1:08:54Lester Nare?

  Yes.

• 1:08:55Krishna Choudhary?

  It's just not sort of closing the, the book.

• 1:08:58Lester Nare?

  It's, it's not a complete, it's not like a sort of the, the complete circle, complete loop. Right? You're arbitrarily creating.

• 1:09:04Krishna Choudhary?

  It's not closed logic, right?

• 1:09:06Lester Nare?

  Yeah, exactly.

• 1:09:07Krishna Choudhary?

  Yeah, it's, it's like, there's too many free parameters.

• 1:09:10Lester Nare?

  Yes.

• 1:09:10Krishna Choudhary?

  Okay, so they, they, they make this thing. They put it inside a cryostat. And on the top, you see that little antenna there?

• 1:09:18Lester Nare?

  Mm hmm.

• 1:09:18Krishna Choudhary?

  That's a little microwave antenna. That's going to get really important later on. Okay? But this is effectively the setup. You've got a power source. You've got the Josephson junction. And then you've got a microwave antenna that like kind of talks to it.

• 1:09:29Lester Nare?

  With some copper in the middle for shielding.

• 1:09:30Krishna Choudhary?

  Yes, with the copper in the middle for shielding, which I still don't quite understand how that works. Um, I thought they were trolling when I, when I read it and I was like, okay, whatever. I guess, yeah, there's always some weird physics, you know, that, that, um, I just didn't have time to figure out. So they, they make this thing. And what they do is they want to see if the current, if they feed a weak current, am I going to get, um, the system, can the system tunnel out of this state? With a sudden voltage that comes up in that, in that power thing that I put in. Okay? And that's what they actually find. What they find is if they repeat this experiment thousands of times,

• 1:10:12Krishna Choudhary?

  on the, on the, on the right-hand side, what you can see is a photo from their paper, which was in the Physical Review. And this is the one that like, you know, finally won the Nobel Prize. So you've got this macroscopic tunneling happening because the diagonal is what the classical circuit should do. And you see this nice uptick as you decrease the temperature.

• 1:10:34Lester Nare?

  Mm hmm.

• 1:10:34Krishna Choudhary?

  What we're seeing is the current is, is stabilizing.

• 1:10:37Lester Nare?

  Yes.

• 1:10:37Krishna Choudhary?

  Right? There's, there's some, some like minimum amount of current that's happening.

• 1:10:41Lester Nare?

  Yes.

• 1:10:41Krishna Choudhary?

  Right?

• 1:10:41Lester Nare?

  Yes.

• 1:10:42Krishna Choudhary?

  At that, and, and the amount of current on, on the, on the Y-axis, there's a little tick that says where the theory.

• 1:10:49Lester Nare?

  Oh, tells you.

• 1:10:51Krishna Choudhary?

  And, and the, and the little, the, the plateau is happening right at that tick. On the X-axis, it's also telling you where the plateau should start according to theory.

• 1:11:02Lester Nare?

  Hmm.

• 1:11:02Krishna Choudhary?

  And that's also lining up. With the experiment. We love to see it. Right? And you love to see that experiment. Theory confirmation happening. And so on the left hand side, I don't really like this cartoon. It's like a switch that is like turning on and off. And that's it. So I don't know how that's like, anyways, that was the Nobel Committee's best, best attempt. They were like, this quantum stuff is tough. Let's just put a switch on there. Yeah, let's put a switch, make it two states. We're good to go. Okay, so now we've shown that there's like this current. Right. The killer is that this thing is quantized. This state is quantized.

• 1:11:46Krishna Choudhary?

  Okay. And the way they did that was, remember that microwave antenna? They use a microwave, the microwaves to excite the system. And they observed energy levels that were quantized. So if you go to the next slide, what they're, on the left, this is, this is the cartoon of quantized energy levels. Right? That are like discreet. It's not continuous like it would be in classical, classical physics. And on the right, what you're seeing is that the tunneling would occur faster if you were in the higher energy state, which makes sense. Yes. Right? According to, that's like Eisenberg's uncertainty principle, actually. Like, energy and time. Yes. Are both related by that quantity where the product has to be less than something. So if you increase the energy, you're gonna have to decrease the amount of time that it stays

• 1:12:29Krishna Choudhary?

  within that state. So it's consistent with quantum mechanics. And on the, on the, on the upper panel, you can see this quantized energy landscape. Right? So, so this was kind of the nail in the coffin. Of like this. Of like this entire thing of 10 to the night, billions of Cooper pairs are behaving as a single quantum thing that is like going between one state or another. In unison. In unison. That's exactly right. Right? Pretty, it's pretty, it's pretty cool. And this was in the 1980s. So they, they waited, I guess 40 years.

• 1:13:08Lester Nare?

  To give it to them.

• 1:13:08Krishna Choudhary?

  To give it to them. Yeah. But in those 40 years, a lot of advancement has happened.

• 1:13:12Lester Nare?

  I mean, I can imagine.

• 1:13:13Krishna Choudhary?

  Yeah, yeah. A lot of stuff has happened. So.

• 1:13:16Lester Nare?

  The way, the way it's made me think, just like the implications of understanding, because obviously with quantum, everything quantum related, it's always, it's always, it's a little hand wavy. It's a little like, don't look in the corner over here. You know, we haven't figured that part out yet.

• 1:13:31Krishna Choudhary?

  Yeah.

• 1:13:31Lester Nare?

  Um, but this feels like a really solid root that has a lot of branches that can come from having experimental confirmation.

• 1:13:42Krishna Choudhary?

  Yeah, yeah. And it's like, to 10 to the nine particles that are behaving in a quantum way is like, pretty insane.

• 1:13:49Lester Nare?

  Yeah, yeah.

• 1:13:50Krishna Choudhary?

  It's pretty insane. It's an entire circuit that is like an atom, right? I mean, sure, it's like cold. It's like near, near zero Kelvin, but like.

• 1:13:58Lester Nare?

  We're not talking about room temperature.

• 1:13:59Krishna Choudhary?

  Yeah, yeah. Because there's too much noise in room temperature, but even down there, like, the fact that the noise is so low and the quantum connections are so robust that, that it's able to like maintain coherence and maintain this single state, right? Across, across these transitions from one state to another. It's not like losing stuff. Pretty crazy. And, you know, it's, it started a whole field of quantum devices. Superconducting circuits are now used as quantum qubits. And that's one of the, um, applications that we can focus on. So this is a photo of IBM's quantum computer.

• 1:14:40Krishna Choudhary?

  The qubit, so the, the photo, what you're seeing is like the chandelier type design. That's because this whole thing is inside a dilution refrigerator that like gets you down to that temperature, right? So you gotta get really cold.

• 1:14:52Lester Nare?

  Quantum systems have to look so bizarre.

• 1:14:55Krishna Choudhary?

  Yeah, it's because it's the, the cooling apparatus is like half of it, right? In terms of the, in terms of the actual like mass of the stuff.

• 1:15:02Lester Nare?

  Yeah.

• 1:15:02Krishna Choudhary?

  It's like, a lot of it's just like the refrigerator. Um, but the, the qubit itself is the next photo that I have. And that is the, um, Transmom.

• 1:15:12Krishna Choudhary?

  Quantum qubit, the arrow that you're seeing, that little square in the middle, that's the Josephson junction.

• 1:15:18Lester Nare?

  Ah, okay, okay.

• 1:15:19Krishna Choudhary?

  And the little like radiator type things on the, on the right hand side of that.

• 1:15:25Lester Nare?

  Yes.

• 1:15:25Krishna Choudhary?

  That's like a microwave cavity.

• 1:15:26Lester Nare?

  Okay.

• 1:15:27Krishna Choudhary?

  That's being used to talk to the Josephson junction. So it's, they've basically miniaturized.

• 1:15:34Lester Nare?

  This work.

• 1:15:35Krishna Choudhary?

  The, this work, right? And John Martinez is actually now, he's in 2014, he, Google poached him from UC Santa Barbara. And they, I think it was a multimillion dollar deal.

• 1:15:48Lester Nare?

  Of course it was.

• 1:15:48Krishna Choudhary?

  Um, and like now Google's quantum AI lab is headed by John Martinez. And I, I don't know if you remember a few years ago, there was that quantum supremacy paper, maybe like two years ago.

• 1:16:02Lester Nare?

  I think I texted you about it because I was like, hey, is, is, is this it?

• 1:16:05Krishna Choudhary?

  Yeah, yeah, yeah. And it's like, and you know, in the, in the, in the quantum community, it's like, yeah, maybe. I mean, it's certainly very impressive that they have so many qubits that are running. John Martinez is that team, right? So I bet Google's, um, like press is gonna like have a field.

• 1:16:22Lester Nare?

  They're gonna have a field day.

• 1:16:23Krishna Choudhary?

  They're having a field day.

• 1:16:24Lester Nare?

  They're gonna have a field day. We told you, we're on the board.

• 1:16:27Krishna Choudhary?

  Yeah, yeah, now Google has.

• 1:16:29Lester Nare?

  Google's on those, cause we're gonna start a scoreboard for the, the institutions with the most Nobels.

• 1:16:34Krishna Choudhary?

  Yeah.

• 1:16:34Lester Nare?

  And so now Google's.

• 1:16:35Krishna Choudhary?

  Yeah, Google's getting up there with the, with a private, um, institutions, right? I don't think anyone's ever gonna beat Bell Labs. Bell Labs has like eight, which is insane.

• 1:16:46Lester Nare?

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

• 1:16:47Krishna Choudhary?

  Um, but yeah, like it's, it's, it's a pretty profound contribution. And now, you know, the Nobel celebrates that this collective behavior of many particles is doing it, right? We've got John Clark, he got his PhD at Cambridge and then he was a professor at Berkeley. Michelle, um, Devore, he got his PhD in Paris and then came to the States.

• 1:17:15Krishna Choudhary?

  Now at UC Santa Barbara and Yale, and then finally, Jean Martinez, who's at Google and UC Santa Barbara.

• 1:17:22Lester Nare?

  Unbelievable. What a fantastic, that's actually a really helpful explanation. Yeah. I've heard, I think actually, one of the people in our comments on our predictions video, talked about how they thought that the quantum tunneling was going to be the one that won.

• 1:17:37Krishna Choudhary?

  Yeah.

• 1:17:37Lester Nare?

  And it's one of those words that I hear all the time tossed around, especially with some of the UAP stuff, that people always like to throw the word.

• 1:17:46Krishna Choudhary?

  Oh, yeah.

• 1:17:46Lester Nare?

  Without the actual first principle of understanding.

• 1:17:48Krishna Choudhary?

  Quantum tunneling.

• 1:17:51Lester Nare?

  That's how they're doing all the crazy flight movement. But this is, this is super fascinating. And I think it's interesting because you, your view is somewhat unexpected.

• 1:18:01Krishna Choudhary?

  I thought it was somewhat unexpected because usually like Nobel prizes,

• 1:18:07Krishna Choudhary?

  go for things that have like, that have actually worked. I wouldn't say that quantum computing has really worked.

• 1:18:16Lester Nare?

  That's fair.

• 1:18:17Krishna Choudhary?

  Okay, but it has worked in the sense that I like, you know, I am creating giant things that are entangled in a quantum way. Right? So in that sense, it's definitely worked. And so maybe, maybe, maybe given that, this thing makes sense. Because like, this is the first sort of experiment that showed that in principle, I could create billions of particles that are, that are behaving together in a quantum way.

• 1:18:44Lester Nare?

  Is it, would you say that in part, some of the understanding related to understanding quantum tunneling and energy quantization, like it helps to elucidate this like, the unification problem with classical and quantum mechanics?

• 1:19:03Krishna Choudhary?

  Or is it? Certainly does. I mean, I mean, the, I think, personally, I think that the more, the larger we push quantum systems.

• 1:19:10Lester Nare?

  Right, that's kind of the.

• 1:19:13Krishna Choudhary?

  The weirder it gets, right? But fundamentally, actually, I don't, I don't think like doing these kinds of experiments will really solve the measurement problem.

• 1:19:24Lester Nare?

  Okay.

• 1:19:24Krishna Choudhary?

  You're just making the measurement problem bigger in terms of like, you know, now it's no longer I'm observing a photon. It's like, okay, now I'm observing 10 to the nine particles. But philosophically, the problem is still the same, right? Which is like, how does the, how does the Josephson junction know whether to, you know, be in one state or the other?

• 1:19:44Lester Nare?

  Which we talked about this.

• 1:19:46Krishna Choudhary?

  Yeah, yeah. So, so it's, it's, it's an interesting problem. I mean, I also saw there was a paper, I think, two years ago that used these Josephson junction type superconducting circuits to get at Bell's inequality. And Bell's experiment is the one where you, you take two entangled particles, you put it on either side, and then you measure one and that sort of affects the measurement of the other, right? There's like correlations that wouldn't be possible unless these two were actually entangled across that distance. So there have been, there have been experiments that use these qubits to do that. And I think they did it over 30 meters, right?

• 1:20:30Krishna Choudhary?

  Which is, which is a pretty big, a pretty big distance when it comes to like particles, right?

• 1:20:36Lester Nare?

  Yeah.

• 1:20:36Krishna Choudhary?

  So there's gonna be like fundamental physics experiments that you can do with these things too. But I think, yeah, fundamentally, this is just showing that the world is really weird, right? And the world gets weird even when you get really big.

• 1:20:52Lester Nare?

  Day two's conclusion, the world is really weird.

• 1:20:55Krishna Choudhary?

  Yeah.

• 1:20:56Lester Nare?

  And we are warning those who help us see that. It is, it is indeed quite curious.

• 1:21:02Krishna Choudhary?

  Yeah, really weird.

• 1:21:04Lester Nare?

  So this was day two for the Nobel Prizes. We have macroscopic quantum tunneling.

• 1:21:12Lester Nare?

  John Clark, Michelle Devore, John Martinez, we'll be back tomorrow for day three.

• 1:21:19Krishna Choudhary?

  Yep.

• 1:21:19Lester Nare?

  The last of the sciences, chemistry.

• 1:21:21Krishna Choudhary?

  Yeah.

• 1:21:22Lester Nare?

  Bright and early again. Be sure to tune in. I'm your host, Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary. This is From First Principles. See you guys tomorrow.

• 1:21:35Speaker 03

  This year's prize is about creating new rooms for chemistry.

• 1:21:41Lester Nare?

  What does that mean?

• 1:21:42Krishna Choudhary?

  New rooms?

• 1:21:43Lester Nare?

  New rooms for chemistry.

• 1:21:46Speaker 03

  Kungli vetenskapakademin har idag beslutat att utdela 2025 års Nobelpris i kemij till Sosomo Kitagawa Kiotto University Japan.

• 1:21:58Lester Nare?

  Alright.

• 1:21:59Speaker 03

  Richard Robson, University of Melbourne, Australia.

• 1:22:03Krishna Choudhary?

  Omar Yagi dude, from the prediction. I knew it.

• 1:22:06Lester Nare?

  That's amazing.

• 1:22:07Krishna Choudhary?

  I told you.

• 1:22:08Lester Nare?

  Yep, yep, yep.

• 1:22:09Krishna Choudhary?

  Yes, I called that.

• 1:22:10Lester Nare?

  Called it on Sunday.

• 1:22:11Krishna Choudhary?

  Called it on From First Principles podcast, baby.

• 1:22:14Lester Nare?

  That's so funny. Hello, internet. This is your captain speaking, Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary. We are day three of Nobel Prize week, chemistry. We just watched the live stream and the winner is Metal Organic Frameworks, which was part of our prediction on Sunday, a branch of particular chemistry. And so we're going to dive right into understanding what is, what are Metal Organic Frameworks and why this is so important?

• 1:22:44Krishna Choudhary?

  Yeah, I mean, so the, the chair of the Nobel Committee said, new rooms for chemistry.

• 1:22:49Lester Nare?

  New rooms for chemistry.

• 1:22:50Krishna Choudhary?

  We're like, what, what, what are you talking about? Well, it, it's a pretty good way of talking about Metal Organic Frameworks. Okay. What, what we're doing is we're making new rooms for chemistry that have custom sizes, custom doors, and they're made out of custom walls. So they've got a, they've got a cartoon, as they always do. On the left there, that's the cartoon from the Nobel Committee.

• 1:23:10Lester Nare?

  Yes.

• 1:23:10Krishna Choudhary?

  And on the right is the actual, one, one of the examples of a chemical compound that

• 1:23:19Krishna Choudhary?

  Exhibits this metal organic framework.

• 1:23:21Lester Nare?

  Okay.

• 1:23:22Krishna Choudhary?

  And the idea is these things are exceptionally useful mainly because they got a bunch of holes. Okay, they have a bunch of like vacancies.

• 1:23:32Lester Nare?

  Yes.

• 1:23:32Krishna Choudhary?

  That you can use to do really cool things. For example, suppose you want to filter out carbon dioxide from exhaust. Right, this porous material can now do that.

• 1:23:42Lester Nare?

  Yeah.

• 1:23:42Krishna Choudhary?

  Right, suppose you want to like get water from thin air. The porous material can now do that.

• 1:23:48Lester Nare?

  Right.

• 1:23:48Krishna Choudhary?

  Yes. Cause you're making holes that are the size of the chemical compounds.

• 1:23:52Lester Nare?

  You're looking to.

• 1:23:53Krishna Choudhary?

  Or like that are going to interact with the chemical compounds that you're trying to extract. Or you're trying to catalyze, things like that. So it's, it's, it's like you can tune the building material.

• 1:24:04Lester Nare?

  Right.

• 1:24:04Krishna Choudhary?

  Right, using, using these metal organic frameworks.

• 1:24:07Lester Nare?

  It's like I built a resort and each room is custom built for each guest that I have at the resort.

• 1:24:12Krishna Choudhary?

  Yeah, and you can now build each, each thing.

• 1:24:14Lester Nare?

  Yeah.

• 1:24:15Krishna Choudhary?

  Right, because, because it's, it's effectively like really, really complicated Lego blocks.

• 1:24:20Lester Nare?

  Okay.

• 1:24:21Krishna Choudhary?

  Okay, if the Lego blocks individually are like atoms and small molecules. Now we're creating like structures that you can then just like attach.

• 1:24:30Lester Nare?

  That makes sense.

• 1:24:31Krishna Choudhary?

  And make like buildings.

• 1:24:32Lester Nare?

  Yes.

• 1:24:33Krishna Choudhary?

  That can fit whatever molecule that you want.

• 1:24:35Lester Nare?

  Okay.

• 1:24:36Krishna Choudhary?

  Right?

• 1:24:36Lester Nare?

  Okay.

• 1:24:37Krishna Choudhary?

  It's really cool. So the award was given to these three individuals for basically starting this field. Okay, and like bringing it to its heyday. So the first one is Richard Robson. He's the one in the middle from the University of Melbourne. He's the guy who sort of founded.

• 1:24:50Lester Nare?

  Okay.

• 1:24:51Krishna Choudhary?

  This back in the 1980s.

• 1:24:53Lester Nare?

  Okay.

• 1:24:53Krishna Choudhary?

  And then there's Susumu Kitagawa from Kyoto University and Omar Yagi. They in parallel brought the field forward to where now it's like so many industrial applications. Right? It's, I think it's, it's very cool. I've been doing a lot of research. I was a little bit better prepared this time because I did have the prediction. But it was still, it was still like getting into, getting into the weeds. It was really cool to see how the history progressed.

• 1:25:18Lester Nare?

  Right.

• 1:25:19Krishna Choudhary?

  Okay, so chemistry has been really good for a very long time with something called zero dimensional chemistry. Okay, zero dimensional chemistry is like something that is localized. Okay, like even the Bucky ball or like small molecules. Right, those things are in some sense zero dimensional because they're point like.

• 1:25:37Lester Nare?

  Okay.

• 1:25:38Krishna Choudhary?

  Right, and that's a zero dimension.

• 1:25:39Lester Nare?

  Right, right.

• 1:25:40Krishna Choudhary?

  Then we got, started getting really good at 1D. Right, polymers, that's a carbon nanotube. And.

• 1:25:47Krishna Choudhary?

  We wanted to get to 2D and 3D, okay? But that was known as kind of a synthetic wasteland. Because it was really hard to figure out how to create stable 2D and 3D structures. 1D, you can imagine, right? You just like, you know, add, like in a chain of like nerd, like, you know, those nerd ropes? Yes. It's like that. It's like relatively easy, okay? Compared to the 2D and 3D stuff that this Nobel Prize is going for. But there was a precedent to try and find these things, okay? There are these minerals that are found naturally. They're called zeolites. It was discovered by the Swedish mineralogist Alex Tronstedt in 1756. And what he did, what he did was he observed that like,

• 1:26:31Krishna Choudhary?

  if you take this material, right? Which in this case, it's still bite. Zeolite is the class of materials. What he discovered was this particular one. This thing could absorb water, okay? And then when he heated it up, steam would come out. Okay, very simple observation. But what does that mean? That means inside the chemistry, it's trapping water molecules, right? And then as you heat it up, those water molecules are going away in the form of steam. So what that means is there's like some, there's some ability of this thing to absorb chemical compounds and then put them out, right? Right. And there's like holes inside where this water molecule is going, right? And that's why he coined it zeolite, because zeo is Greek for boil and lithos for stone.

• 1:27:16Krishna Choudhary?

  It's like a boiling stone. And these zeolites became like a big passion of chemists because they're found naturally and you want to try to characterize them. The next thing that kind of gets into this is the Berlin Blue, which is this pigment that was discovered in the 18th century. It's got a relatively complex structure. Like on the right hand side, you're seeing the structure, which is basically a bunch of iron, which is iron ions. So iron two and iron three, that means it's either two electrons are gone or three electrons are gone. And then inside, they're linked by these carbon nitrogen bonds. Okay. Okay? And now we're starting to get into metal organics, right? Metal, the iron, organics, anything that has carbon.

• 1:27:59Krishna Choudhary?

  This is the like, like day zero, okay? And on the left, that's the famous Great Wave of Kanagawa. Yes. The print by Hokusai in the 1800s, right? That blue pigment. Is the Berlin blue.

• 1:28:14Lester Nare?

  Berlin blue.

• 1:28:15Krishna Choudhary?

  Right? The Japanese printmakers would like import this from Europe because making blue was incredibly difficult. Like, the Egyptians used to make blue, and then we forgot how to do it. Because like the Egyptians.

• 1:28:30Lester Nare?

  That's such, that's such a crazy, like, I mean, knowledge is forgettable.

• 1:28:33Krishna Choudhary?

  Yeah, knowledge is very fragile, dude, if you're not, if you're not careful.

• 1:28:36Lester Nare?

  Right, and actively keeping it up. It's funny, that same blue wave, my wife has a Snoopy bag she got from the Snoopy store in Japan with that blue, blue wave on it, so I'll tell her that fun fact.

• 1:28:45Krishna Choudhary?

  Yeah, yeah, it's, it's, it's pretty cool. So, and that is like the, you know, day zero metal organic framework that sort of led to all of the developments and then created the Nobel Prize today. So, we know that these things are possible.

• 1:28:58Lester Nare?

  Right.

• 1:28:59Krishna Choudhary?

  Right?

• 1:28:59Lester Nare?

  Because they occur in nature.

• 1:29:00Krishna Choudhary?

  Yeah, they occur in nature. The idea is, we wanna, we wanna be able to engineer and very specifically put stuff together, okay?

• 1:29:07Lester Nare?

  In order to basically get the, like, the emergent properties, what we're looking for.

• 1:29:10Krishna Choudhary?

  Yeah, yeah. And in order to figure out exactly how we're gonna do this engineering, we need to do a little bit of basic chemistry. Always, you gotta start from first principles. So, we go to 1913, Alfred Werner wins the Nobel Prize in 1913. He basically starts this field of coordination chemistry, okay? He starts, he starts thinking about metal ions and how metals can bond covalently with other atoms. And he characterizes these tetrahedral complexes, tetrahedral meaning the, like, four, you know, tetra meaning four.

• 1:29:46Lester Nare?

  Yeah.

• 1:29:47Krishna Choudhary?

  So, four bonds that are in this, like, sort of nice crystalline pyramidal structure.

• 1:29:52Krishna Choudhary?

  And these bonds between the metal atom and the other atom is what's called a coordinate bond, okay? And this is different from a covalent bond. So, if you go to the next slide, I'll show you what the difference is. So, in, in a normal covalent bond, you've got shared electrons, right?

• 1:30:09Lester Nare?

  Yes.

• 1:30:09Krishna Choudhary?

  In O2, for example, oxygen and oxygen, each oxygen is sort of donating an electron to the bond to create the O2 molecule. Same thing with CO2, H2O. With a coordinate covalent bond, there's only one donor. Okay, the other guy's kind of leeching. Okay. Okay, so over here, you've got, you know, on the left hand side, you've got the yellow atom that's got a full um, shell with eight electrons. Yes. And then on the, the pink atom has two, the two holes. Right. So the, the yellow atom goes in and donates. Now everyone has full electron shells and everyone's happy. This is called a coordinate covalent bond. Okay. And this is going to be the sort of

• 1:30:54Krishna Choudhary?

  building block of the chemistry that we're about to talk about. The one, the Nobel Prize, okay? Because metals, metals make ions, right? And what ions usually with metals, the, the outer electrons, which are in the d shells. Yes. That are like far away from the nucleus. They're just gonna go away. Right. So you're gonna get like a copper ion, which is C plus. That means one electron left. Or the ones we were talking about, iron two, iron three. That means two or three electrons left. So they got these holes. But now other atoms can come in and fill that gap. And you get a coordinate covalent bond. Right? And that's gonna be the building block for the chemistry that we're about to talk about. Yes. Okay. So with that in mind, let's go into our Nobel laureates. So first we got Richard Robson. He is in the University of Melbourne. He's teaching classes in 1974.

• 1:31:39Krishna Choudhary?

  And this is a great example of how teaching actually leads to discovery. Okay, so he's teaching and um, he needs, you, you've probably seen these in like high school chemistry. Hundred percent. Right? Yes. The balls that have like holes. And then he puts sticks in it to make molecules. So he's trying to get those um, made in the wood shop. Okay. Okay, so he's sending over instructions on where to put the holes. Because each atom is gonna have specific geometry on where the holes go and where the atoms are being made. And as he's doing that, he needs to mark out where the holes are. He gets, he gets inspired by this and he's like, wait. If the holes in the atoms tell me the geometry of the bond, right?

• 1:32:21Krishna Choudhary?

  But these holes can be on the outside of bigger molecules. And those holes will still preserve the geometry, right? On the outside. And he was inspired by the diamond, which is, we've talked about. Um, in the next slide, we, we can look at the crystal structure of the diamond. That's a tetrahedron. It's carbon. Right. With the carbon, you've got four holes that you make, right? Which is one on the top and then three sort of parametal ones on the bottom. And then you can connect all of these together to create a tetrahedral crystal. Yes. Of carbon, and that's what a diamond is. So he was inspired by this. And he's like, okay, if I, if I want to create a diamond-like thing,

• 1:33:03Krishna Choudhary?

  but I want to do it with bigger building blocks. Right. Right? Right. Can I do that? Right. Okay. So he was, he, he, he decided to try the copper ion, which is um, Cu plus. And with the copper ion, he made a, he, he attached copper ions, so four copper ions. He attached that to a molecule that already had this tetrahedral geometry. Right. Um, it's, the molecule is called 4444 tetrasyano tetraphenyl methane. Okay? This is one of the reasons why I never really got into chemistry in high school. It's like, the names were just ridiculous. But the, the, the main idea behind this molecule is it's pretty rigid. Right. Okay?

• 1:33:46Krishna Choudhary?

  It's a rigid molecule and on the ends of that pyramid, the top and the three ends, there's something called a nitrile group, which is this Cn, carbon and nitrogen. Yes. And those things really like bonding with copper. Okay? So what you can do is put four copper ions at the, at the points of this pyramid. And then those four copper ions can then bind to the next pyramid and the next pyramid. And what you get is this very nice crystalline framework. This is the first metal organic, it's not really organic. But it's the first sort of idea behind like creating a metal crystalline structure.

• 1:34:24Lester Nare?

  Yes.

• 1:34:25Krishna Choudhary?

  Using metal ions and other stuff in between.

• 1:34:27Lester Nare?

  Yes.

• 1:34:28Krishna Choudhary?

  And it had a bunch of holes.

• 1:34:30Lester Nare?

  Right.

• 1:34:31Krishna Choudhary?

  Remember?

• 1:34:31Lester Nare?

  Right.

• 1:34:31Krishna Choudhary?

  It had a bunch of holes and he published this in the American society, the American Chemical Society in 1989 and 1990. And this was very unexpected at the time.

• 1:34:41Lester Nare?

  Right.

• 1:34:42Krishna Choudhary?

  Okay.

• 1:34:42Lester Nare?

  Right.

• 1:34:43Krishna Choudhary?

  This was like, this was like very, very cool because people used to think like, oh, like if I just put together, if I just put together metals with this other kind of stuff, I'm going to get a molecular bird's nest.

• 1:34:56Lester Nare?

  Right.

• 1:34:57Krishna Choudhary?

  You know, bird's nest is like very kind of disorganized. It like maintains its shape.

• 1:35:00Lester Nare?

  Right.

• 1:35:00Krishna Choudhary?

  But it's not this kind of regular sort of thing, right?

• 1:35:03Lester Nare?

  Yes.

• 1:35:04Krishna Choudhary?

  This, so this was, this, this was very cool when it first came out.

• 1:35:08Krishna Choudhary?

  And at the same time, he also started talking about the predictive framework in how to design these 3D molecules. Right? Like what are the rules that are, that are sort of needed to, to put these Lego blocks together and have them be sort of stable? Okay. He also, at, at the time, he, he started talking about the future of applications. He's like, this could be used into the absorption of gases, catalytic reactions. He was very forward thinking, right? And it sort of started a lot of people along this.

• 1:35:40Lester Nare?

  Along the.

• 1:35:40Krishna Choudhary?

  Right? And two, yeah, and two of those people are the.

• 1:35:42Lester Nare?

  The other, he opened the door.

• 1:35:44Krishna Choudhary?

  Yep.

• 1:35:45Lester Nare?

  Uh, for other people to think in this direction as like, oh, there's, there's a there, there.

• 1:35:48Krishna Choudhary?

  Yes.

• 1:35:49Lester Nare?

  Uh, that's worth study and exploration.

• 1:35:51Krishna Choudhary?

  Exactly. Yeah. It was still, the, the stuff that he made was still kind of rickety and it tended to fall apart. Right? And this is where Kitagawa and Yagi come in. All right?

• 1:36:01Lester Nare?

  Yes.

• 1:36:02Krishna Choudhary?

  So now we're going to go to our second Nobel Prize winner, Susumu Kitagawa, and he makes this. Okay?

• 1:36:09Lester Nare?

  Okay.

• 1:36:09Krishna Choudhary?

  So this is in about, in, I think, 1995, he publishes this. And it's a tongue in groove where he's using cobalt, nickel and zinc ions in a 3D framework. And this is really stable.

• 1:36:23Lester Nare?

  Okay.

• 1:36:24Krishna Choudhary?

  Okay?

• 1:36:24Lester Nare?

  Yes.

• 1:36:24Krishna Choudhary?

  This is the first sort of like nice, stable thing. You make this. In water, okay, in a soluble sort of chemistry, that's how I saw this thing is manufactured. You've got like these grooves that are like, like crossing, cross linking to each other. And the trick is, if you dry it up, it's still stable. And it can also be used and reused to absorb gases and then let them out and then absorb more. So it's a stable compound. It's not like, um, it's, it's a true catalyst in that sense, right? It's, it's not, um, getting used up.

• 1:36:58Lester Nare?

  It's not a single use or like a, like a limited N number of use. It is structurally going to repeat the same process every time.

• 1:37:06Krishna Choudhary?

  Yeah. And it's, it's, it's sturdy, that kind of thing, right? So this is the first demonstration of a reversible gas adsorption.

• 1:37:14Lester Nare?

  Okay.

• 1:37:15Krishna Choudhary?

  Adsorption, meaning like at the surface, you're, you're taking in the gas. As opposed to absorption with a B, which is just like a volume absorbing. Okay. Adsorption means like, um, like a 2D kind of thing, right? Um, and so, so he gets, he gets really big on that. Um, at this point, it's still, he's, um, he actually had a lot of trouble trying to get funding to do this kind of stuff.

• 1:37:38Lester Nare?

  Interesting.

• 1:37:38Krishna Choudhary?

  Because people were like, oh, zeolites already exist. They weren't really convinced that the stuff that, um, Robson was doing was gonna work because it was so rickety.

• 1:37:47Lester Nare?

  Yes.

• 1:37:48Krishna Choudhary?

  Right? It was just this, it was just this kind of like fringe thing. But he was at Kyoto University at the time, got his PhD, and then he got a lab there. And he finally started making these things work. Okay? And the thing that really convinced people was the porous crystal that he made. That's the next one.

• 1:38:04Lester Nare?

  Okay.

• 1:38:04Krishna Choudhary?

  The porous crystal that he made, and that's Kitagawa on the right. The porous crystal that he made was soft in the sense that it deformed and changed its shape based on whether it had stuff inside in those cavities.

• 1:38:18Lester Nare?

  Hmm.

• 1:38:18Krishna Choudhary?

  Okay? So, so now this is something that zeolites can't do.

• 1:38:22Lester Nare?

  Right.

• 1:38:23Krishna Choudhary?

  Right? The natural occurring, occurring mineral are extremely rigid.

• 1:38:26Lester Nare?

  Right.

• 1:38:27Krishna Choudhary?

  But you've got this thing where like it can like, the bonds are flexible. So if there's nothing inside, now you can imagine, right? Like creating these, the, you know, those, um, those, those toys where the, you got a magnet, magnetic ball and like the stick.

• 1:38:41Lester Nare?

  Yeah. Yes. Yes. I know exactly what you're talking about. Yes.

• 1:38:43Krishna Choudhary?

  Yeah. Yeah. It's like, those things can like move around, right? And this is doing the same thing. So this was very big, right? It was, it was expanding and contracting like a lung.

• 1:38:53Lester Nare?

  Ah, this and and again, the the the dynamic structural behavior is the key difference here to the naturally occurring.

• 1:38:59Krishna Choudhary?

  To the naturally occurring stuff.

• 1:39:00Lester Nare?

  Yeah, yeah.

• 1:39:01Krishna Choudhary?

  And so this was, this was, this was the first clue that it was like new chemistry.

• 1:39:05Lester Nare?

  Right. There, there, there's something fundamental. There was a more fundamental understanding that could be gleaned from continuing to go down this thought.

• 1:39:11Krishna Choudhary?

  Yes, yeah. And and creating like way new materials that you definitely can't find.

• 1:39:17Lester Nare?

  Which so the the the material science implication became more obvious.

• 1:39:20Krishna Choudhary?

  Mm hmm. Yeah.

• 1:39:22Lester Nare?

  Fascinating.

• 1:39:23Krishna Choudhary?

  Pretty cool. And in parallel, we've got Omar Yagi.

• 1:39:28Lester Nare?

  Yes.

• 1:39:28Krishna Choudhary?

  Okay, Omar Yagi has an incredible life story.

• 1:39:31Lester Nare?

  We, which we talked about a bit on Sunday.

• 1:39:33Krishna Choudhary?

  Yeah, it's a, he, um, he was a Palestinian refugee in Jordan.

• 1:39:38Lester Nare?

  Okay.

• 1:39:38Krishna Choudhary?

  With his family, like, very poor. They, the, the entire family lived in a single room, but he got really into chemistry at the age of 10. Um, he came to the States for higher studies, got his PhD at University of Illinois or Benham Champagne. And then he started really getting into, um, these metal organic frameworks. Okay, he was like, this, this, this could be something, right? He got really interested in that. And at Arizona State University, that was his first faculty appointment, that's when he publishes this 2D molecule that can hold stuff and it can remain stable up to 350 degrees Celsius.

• 1:40:15Lester Nare?

  Oh.

• 1:40:16Krishna Choudhary?

  You can heat this thing up and it can still hold its stuff and and not get completely degraded.

• 1:40:22Lester Nare?

  Right.

• 1:40:22Krishna Choudhary?

  He published that in Nature.

• 1:40:24Lester Nare?

  Yes.

• 1:40:24Krishna Choudhary?

  So this was the first sort of big, big thing, right? He starts, he starts making a name for himself. And, um, in 1999, he publishes The Big One.

• 1:40:36Lester Nare?

  The Big One.

• 1:40:38Krishna Choudhary?

  This is the, this is the sort of classic example of metal organic frameworks. Okay? Um, and there's, there's posters of this in every chemistry department.

• 1:40:50Lester Nare?

  Okay.

• 1:40:50Krishna Choudhary?

  Okay, this is called MOF5, Metal Organic Framework 5. It's got a zinc at its center, then oxygen molecules in a, in a print, in a pyramid. Okay? That creates a little pyramid. You attach four of those pyramids together with carbons.

• 1:41:09Krishna Choudhary?

  On the end, right? And you get the middle thing, which is uh, four pyramids together to create one giant sort of diamond. Yes. Type thing. Yes. With carbons at the end. Right. And that carbon is key because now we're getting into the organic. Okay. With those carbons at the end, you can now start attaching linkages to other diamonds, other blue diamonds and start creating cavities. This was the MOF five um, molecule, okay? And this thing was insane. This thing was like 3,000 meters squared of surface area per gram. That's the thing I was uh, when we were talking about on our predictions. Right, right. Right? It's a single gram of this substance is going to have enough surface area. Right.

• 1:41:53Krishna Choudhary?

  For of like a football field or like several football fields. So crazy. It can absorb a lot more than zeolite can because of that. That. Because of that thing. Yes. And also it's again, stable until 300 degrees Celsius. Right. So it's resilient. Yes. It's pretty simple to make. Yes. And it's, you know. Hugely functional. Hugely functional. Yeah. Yeah, exactly. The, the possibilities are endless, right? And this is the field that introduced sort of reticular. Chemistry. This is the beginnings of it. This is, yeah, it's like using modular components to make these crystalline lattices, right? It was Yagi and Kitagawa together that sort of figured this, this whole thing out. And Yagi went even further.

• 1:42:37Krishna Choudhary?

  So in, in photo 16, you'll see he takes the MOF, which is the one on the left. And he figures those linkages, right? Between the carbon molecule. Yes. Between those carbon atoms. On there on the edges. That are on the edges, that are creating this cubic cavity. Those linkages, I can just make those linkages bigger. Okay. Right? And then I'm going to have more space. Oh, on the, uh, yes, yes. It's so simple. Yes. The linkages are organic molecules that are made out of carbon rings, attached to carbon rings, attached to carbon rings. Well, I can just start adding more and more carbon rings. And now you're actually increasing the, the, that surface area of, of available space. Yes. And what you can do is you can have customizable size of the pore. Uh, yes.

• 1:43:21Krishna Choudhary?

  By, by saying, okay, I have three carbon rings. Yes. The pore is going to be this size. I add six, then it's going to be a little bit bigger. So whatever chemistry you want to do.

• 1:43:30Lester Nare?

  Right.

• 1:43:31Krishna Choudhary?

  Do you see now?

• 1:43:31Lester Nare?

  You can build for exactly the size and like exactly the parameters that you need. And so this, this is really the like the, the dial that you can turn.

• 1:43:40Krishna Choudhary?

  Yeah.

• 1:43:41Lester Nare?

  Uh, in order to get to the, again, the outcome that you're looking for.

• 1:43:45Krishna Choudhary?

  Yes, exactly.

• 1:43:46Lester Nare?

  Fascinating.

• 1:43:47Krishna Choudhary?

  Right? And now, now this, this is when, um, this is when things got really big. He published those two papers in Nature and Science and those are basically the papers that won the Nobel Prize.

• 1:43:58Lester Nare?

  Got it.

• 1:43:58Krishna Choudhary?

  Okay. It's the, it's the papers from, um, Robson, Kitagawa, and finally the Nature and Science papers.

• 1:44:05Lester Nare?

  That's, and, and I totally get your point about the implications of the linkages being malleable in terms of, uh, their size and how that creates more available potential space.

• 1:44:17Krishna Choudhary?

  Yeah.

• 1:44:18Lester Nare?

  That's usable.

• 1:44:18Krishna Choudhary?

  Yeah, yeah, yeah. It's, it becomes totally customizable now, right?

• 1:44:21Lester Nare?

  Yeah.

• 1:44:21Krishna Choudhary?

  Now you literally have.

• 1:44:22Lester Nare?

  It's programmable.

• 1:44:23Krishna Choudhary?

  Yeah. Link like things.

• 1:44:25Lester Nare?

  You can engineer properly.

• 1:44:27Krishna Choudhary?

  You can engineer completely properly. Okay. And, um, so he started out at University of Arizona.

• 1:44:32Lester Nare?

  Yes.

• 1:44:32Krishna Choudhary?

  And then he moved actually to UCLA.

• 1:44:35Lester Nare?

  Yes.

• 1:44:35Krishna Choudhary?

  In 2012.

• 1:44:36Lester Nare?

  Yes.

• 1:44:36Krishna Choudhary?

  Because by this point, I think everyone knew he was gonna win.

• 1:44:39Lester Nare?

  Yeah, right, right, right, right.

• 1:44:41Krishna Choudhary?

  The Nobel. Okay. So, so now institutions are like.

• 1:44:44Lester Nare?

  Berkeley.

• 1:44:45Krishna Choudhary?

  No, no, no. First he moved to UCLA. First he moved to UCLA.

• 1:44:49Lester Nare?

  Okay.

• 1:44:50Krishna Choudhary?

  Um, actually, no, you're right. So I, I got the year wrong. I think it was 2005 or six.

• 1:44:54Lester Nare?

  He moved.

• 1:44:54Krishna Choudhary?

  When he moved to UCLA. Okay.

• 1:44:56Lester Nare?

  That's how he got to California.

• 1:44:57Krishna Choudhary?

  Yeah. And then, and then that's how he got to California. And then he was, he was in the chemistry department at UCLA.

• 1:45:02Lester Nare?

  Yes.

• 1:45:02Krishna Choudhary?

  And then in 2012.

• 1:45:03Lester Nare?

  Yes.

• 1:45:03Krishna Choudhary?

  Berkeley was like, offered him a, you know, an offer he can't refuse.

• 1:45:06Lester Nare?

  Of course.

• 1:45:07Krishna Choudhary?

  Because Berkeley was like, was like, okay, he's definitely winning by now.

• 1:45:10Lester Nare?

  Right.

• 1:45:11Krishna Choudhary?

  And, and, and we want, we want that plus one.

• 1:45:14Lester Nare?

  A hundred percent.

• 1:45:14Krishna Choudhary?

  Um, so, so he moved to, um, Berkeley in 2012. He became the director of the molecular foundry at the Lawrence Berkeley National Lab, co-director of the Kavli Energy Nanoscience Institute. And just in 2025, earlier this year, he became the, a university professor, which is the top honor in the University of California.

• 1:45:34Lester Nare?

  Hmm.

• 1:45:34Krishna Choudhary?

  Reserved for like the highest.

• 1:45:35Lester Nare?

  Mm hmm.

• 1:45:36Krishna Choudhary?

  Distinction. So he was working his way up to like everyone sort of that's that's why it was like kind of easy to predict.

• 1:45:42Lester Nare?

  That was gonna be him because the signals were there.

• 1:45:44Krishna Choudhary?

  The signals were all there and but you know UCLA first poached him and then Berkeley poached it from UCLA.

• 1:45:50Lester Nare?

  That's ours.

• 1:45:51Krishna Choudhary?

  Yeah.

• 1:45:52Lester Nare?

  Like UCLA, the little brother of Berkeley.

• 1:45:54Krishna Choudhary?

  Yeah, exactly. Yeah. So so it's like, okay, now I'm gonna keep that one. And yeah, now now he's won the Nobel Prize, right? And so these three people won the Nobel Prize. Right now, there's so many different applications to this metal organic frameworks. We're just gonna go through a couple, a few of them. So this first one, these are three molecules, the one on the left, that's used to capture water vapor.

• 1:46:19Lester Nare?

  Okay.

• 1:46:20Krishna Choudhary?

  Okay, the one in the middle, that's that can be used to catalyze the decomposition of crude oil.

• 1:46:26Lester Nare?

  Oh, very interesting.

• 1:46:26Krishna Choudhary?

  Right? Which is which is very nice for like environmental people.

• 1:46:29Lester Nare?

  Hundred percent.

• 1:46:30Krishna Choudhary?

  On the right, that's something that can absorb PFAS, which is perofluoroalkyl. It's one of these like forever chemicals.

• 1:46:38Lester Nare?

  Yes.

• 1:46:38Krishna Choudhary?

  The EPA always talks about it like they're they never degrade, get into our bodies, get into the environment. That's something that can absorb those forever chemicals from water.

• 1:46:49Lester Nare?

  And so the one of the ideas here is that we can begin to create these chemical compounds that we can then use for things like, you know, controlling emissions issues.

• 1:47:00Krishna Choudhary?

  Yeah.

• 1:47:00Lester Nare?

  Dealing with forever chemicals. Oh, beautiful. Yeah.

• 1:47:03Krishna Choudhary?

  Yeah, you're exactly right. The one on the left, that's for mining rare earth metals from wastewater.

• 1:47:10Lester Nare?

  Oh, okay.

• 1:47:10Krishna Choudhary?

  Right? Because like waste, industrial waste is gonna have a bunch of metals.

• 1:47:13Lester Nare?

  Yes.

• 1:47:14Krishna Choudhary?

  You don't want it to go into.

• 1:47:15Lester Nare?

  That's a huge, that's a huge application.

• 1:47:16Krishna Choudhary?

  Yeah.

• 1:47:16Lester Nare?

  That's an unbelievable application.

• 1:47:18Krishna Choudhary?

  Right. And then in the middle, that's to absorb CO2.

• 1:47:20Lester Nare?

  There you go.

• 1:47:21Krishna Choudhary?

  There you go. That's what you were talking about.

• 1:47:23Lester Nare?

  Yep.

• 1:47:23Krishna Choudhary?

  And then on the right, that one's actually my my favorite. That one can store and release hydrogen at normal pressure.

• 1:47:31Lester Nare?

  Oh, really?

• 1:47:33Krishna Choudhary?

  So you don't need a tank of compressed hydrogen.

• 1:47:36Lester Nare?

  That's really crazy.

• 1:47:38Krishna Choudhary?

  Huge.

• 1:47:38Lester Nare?

  Yeah.

• 1:47:39Krishna Choudhary?

  Because compressed hydrogen.

• 1:47:40Lester Nare?

  Yes.

• 1:47:40Krishna Choudhary?

  Is how you get the Hindenburg in your car.

• 1:47:42Lester Nare?

  Right.

• 1:47:43Krishna Choudhary?

  Right? And like everything explodes. So nobody wants hydrogen fuel cells. Well, now with this kind of stuff, you can get hydrogen fuel cells.

• 1:47:50Lester Nare?

  I can understand why this won the Nobel.

• 1:47:51Krishna Choudhary?

  Right? Yeah. And and what you what you saw there is like all of these things have like pretty similar, you know, the. You can see that they're the same chemistry.

• 1:48:02Lester Nare?

  Yes.

• 1:48:03Krishna Choudhary?

  You know what I mean?

• 1:48:03Lester Nare?

  Yeah, they have to share, they share sort of a similar substrate of structure.

• 1:48:06Krishna Choudhary?

  Yeah, yeah, yeah. It's repetitive, it's crystalline, but each of the little tiny crystals, instead of being a single atom, now they're these giant building blocks, right? And the holes can be, can be giant. In the world of atoms, these things are giant, right? You can do nanometers, tens of nanometers.

• 1:48:23Lester Nare?

  This is interesting because it's kind of similar conceptually to the Yesterdays Prize in Physics around this idea of scaling up to larger sizes with the quantum tunneling.

• 1:48:32Krishna Choudhary?

  Yeah.

• 1:48:32Lester Nare?

  Uh, but in this case with metal organic frameworks.

• 1:48:35Krishna Choudhary?

  Yeah, it's, it's, it's, it's an incredible, incredible field. And I just wanted to see what was happening nowadays. So they, they got AI going to know this too.

• 1:48:44Lester Nare?

  Of course.

• 1:48:44Krishna Choudhary?

  They, they have a chat, they have a chat MOF.

• 1:48:47Lester Nare?

  Really?

• 1:48:48Krishna Choudhary?

  Yeah, a chat metal organic framework where you like chat with it. And then it'll like generate, like it's like, I want them, I want a, you know, chemical compound that does this. And then it'll like spit out like, oh, you should try these things.

• 1:49:00Lester Nare?

  Chat MOF.

• 1:49:01Krishna Choudhary?

  Yeah, they got, they have a generative framework there. For like, you know, generative AI can make photos. Well, it can also, if you train it on the chemistry, it can start making, you know, these, these metal organic frameworks. And on the right, that's a news article from Berkeley. Omar Yagi in his lab, he's actively using AI. And like, um, one of his students, I think, came up with like 15 molecules in six months. Again, just accelerating this process, right?

• 1:49:28Lester Nare?

  Yes, yes, yes, yes, yes.

• 1:49:29Krishna Choudhary?

  It's pretty cool.

• 1:49:30Lester Nare?

  This is what we talk about a lot, which is again, a lot of generative AI conversation, et cetera, revolves around consumer use cases, understandably, because that's where most people are actually using it currently. But there's not as much chat. I mean, just, we've talked about this, there's, you know, generative AI for CRISPR. We have it for MOF. There's also things like AlphaFold.

• 1:49:50Krishna Choudhary?

  LIGO.

• 1:49:51Lester Nare?

  LIGO.

• 1:49:51Krishna Choudhary?

  Oh, that wasn't generative, but still AI.

• 1:49:53Lester Nare?

  Still AI sort of assisting and accelerating the process of research and discovery. And it has like real world implications.

• 1:50:00Krishna Choudhary?

  Yeah.

• 1:50:00Lester Nare?

  Um, in terms of us getting to these things quickly with fewer human capital resources, with less, uh, financial capital resources.

• 1:50:07Krishna Choudhary?

  Yeah, it's also like a democratization process.

• 1:50:10Lester Nare?

  Yep.

• 1:50:10Krishna Choudhary?

  Because people who maybe, you know, chemistry labs who want to do something, right? But don't have the expertise of the metal organic framework can go to this chat thing and be like, hey, like, this is the thing that I want to accomplish.

• 1:50:23Lester Nare?

  Yes.

• 1:50:23Krishna Choudhary?

  Can I do it with MOFs? And the chat will be like, yeah, actually just make this, this and this.

• 1:50:28Lester Nare?

  And then put it in this way. It's so crazy. I, I think there's this conversation happening. Uh, CEO of OpenAI, Sam Altman, uh, yesterday or the day before, did an interview where he was asked about AGI. Okay. Um, because there's this whole AGI is near conversation. Yeah. And there's usually two sides of where people are like, we're nowhere close. Uh, people are like, we're very close. And the signal that's being alleged as like, why we're getting close is in these kind of research use cases, there is, you know, AGI and for some people is defined as like being able to have novel insight. Mm hmm. Um, and there are a couple now cases. Yeah. In these, again, research contexts where the models are actually having novel insights. Yeah.

• 1:51:11Lester Nare?

  That are working. Um, and not just working, like working really, really, really well. It's not AGI in the way I think people imagine it from the movies. Yeah. But, you know, there's a glimmer, if these models can truly generate novel insights, even at small scales, there's, that's hugely. That's huge. That's hugely important. Yeah. That's gonna be crazy. Fascinating. Yeah. Well, and that was the, that was the chemistry prize. So, so, and, and I think there's, there's so many implications for this more broadly. Yeah. Moving forward. Yeah, dude. It's, it's, it's gonna be, yeah. It's gonna be very cool. I want to take a moment. So we've talked about, this is our day three of. The last day. Prize week. Uh, so many of you, thousands of you have sort of joined us for this journey.

• 1:51:56Lester Nare?

  It's been an incredible week. Yeah. So thanks everyone for tuning in. We did medicine on Monday, physics on Tuesday, and then chemistry today. I wanted to do a quick tally, uh, about the winners. All right. Right? We're gonna break this down in sort of two, two categories, institutions and countries. This is like our ESPN top 10. Yeah, yeah. So on the institution side, we had some, some unsurprising. Yeah. Number one winner. So at the top with, uh, four Nobels is, uh, Berkeley. Yep. Three for physics, one for chemistry. Kyoto had two, uh, UCSB unexpectedly for me, two, UCLA one, Princeton got on the board. We got on the board. We got on the board with one, Yale with one, uh, Princeton were putting before Yale because we came first. Yeah.

• 1:52:41Lester Nare?

  Um, and then we have University of Illinois, our, our Banister Payne with one, Oxford, Melbourne, Cambridge, and Paris University, all with a single Nobel. Yeah. And if we look at it by country. Number one, big old America.

• 1:52:56Krishna Choudhary?

  USA, baby.

• 1:52:57Lester Nare?

  Six universities in the US, two from the UK, one from Japan, one from France, and one from Australia.

• 1:53:05Krishna Choudhary?

  Yeah.

• 1:53:05Lester Nare?

  So, great representation.

• 1:53:06Krishna Choudhary?

  Yep.

• 1:53:07Lester Nare?

  The UC system ran the board.

• 1:53:09Krishna Choudhary?

  Ran the board, dude. California, baby.

• 1:53:12Lester Nare?

  California continues to lead in sort of fundamental research.

• 1:53:15Krishna Choudhary?

  Yeah, and this was the public institutions in California.

• 1:53:19Lester Nare?

  Right, right.

• 1:53:19Krishna Choudhary?

  Right?

• 1:53:19Lester Nare?

  Not the.

• 1:53:20Krishna Choudhary?

  Yeah, I guess Stanford and Caltech didn't show up this year.

• 1:53:24Lester Nare?

  Maybe, maybe next year, guys.

• 1:53:25Krishna Choudhary?

  Maybe next year.

• 1:53:25Lester Nare?

  Neither did MIT or Harvard. But Princeton's there.

• 1:53:28Krishna Choudhary?

  Princeton's there.

• 1:53:29Lester Nare?

  Oh, goodness. Again, another just great episode. We talked about metal organic frameworks, a branch of particular chemistry. We did talk a little bit more about this also in our Sunday preview. So if you're interested, go back and take a listen to that. But just an unbelievable, we'll definitely do this next year again.

• 1:53:47Krishna Choudhary?

  Oh, yeah.

• 1:53:48Lester Nare?

  We'll probably have a little bit more, more going. We'll maybe get the Nobel Society to help us get some inside access.

• 1:53:55Krishna Choudhary?

  Yeah.

• 1:53:57Lester Nare?

  I'm Lester Nare, your host, joined as always by my co-host and our resident PhD, Krishna Choudhary. Thank you all again for joining us for Nobel Prize week. It's been an incredible week. We will see you all next week.

• 1:54:12Krishna Choudhary?

  Nice.

• 1:54:12Lester Nare?

  All right.