From Cells to Circuits to Crystals — 2025 Nobel Prizes Unpacked

0:01Ladies and gentlemen, good morning and >> okay, we are here live for Nobel Prize week day one which is medicine. Looks like the presentation is starting. >> My name is Thomas and I'm Secretary General of the Nobel Assembly. >> I will first read the announcement in Swedish followed by English. We will then uh as usual present some background to the prize and open up for questions. Okay, here we go. Yep.

0:48Mary Bronl Fred Ramon Sakaguchi. >> Okay. So the predictions so the predictions are wrong. Okay. The Nobel Assembly at Karolinsky Institute has today decided to award the 2025 Nobel Prize in Physiology or Medicine jointly to Mary Bronco, Fred Ramstelle and Shimon Sakaguchi for their discoveries concerning peripheral immune tolerance. >> Okay. Okay. >> Immune tolerance >> are the three laurates. Mary Bronco was born in 1961 in uh and received a PhD

1:31from Princeton University in the United States. >> The work for which she's awarded was performed at a biotech company, Celtech Cyrocience in both Washington. >> She's currently a senior program manager at the Institute for Systems. >> It's not even an academic institution. >> Oh, interesting. Fred Ramstell was born in 1960 and received a PhD in 1987 at the University of California in Los Angeles. >> The work for which he's awarded was performed at the same biotech company Celtech Cyrocience. >> He's currently a scientific advisor at

2:13the company he he himself founded. So no mark therapeutics in San Francisco and in Seattle. Shimon 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 II cancer Center Research Institute in Nagoya. He's currently a distinguished professor at the iminology frontier research center at Osaka University.

2:55>> Okay. At Osaka University. Okay. So, we got two private people and and Osaka University. I think we need a wardrobe change. >> Yeah. No. I mean, what between I'm going to do some research and we'll dive in. >> Yeah. And and then we'll be right back. We'll be right back. >> Hello, internet. This is your captain speaking Lester Narre joined as always by my co-host and our resident PhD Krishna Chowdery. 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. Uh as you can see we have a little bit of Princeton representation. We are back on the board with one of the Laur uh uh Nobel winners who just won being a PhD

3:37at Princeton. >> Yeah. >> Uh but let's dive right in. peripheral immune tolerance just won in medicine. Why? Like let's let's start with like why this prize matters. Yeah, this prize is 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 tea cells come in. Okay. And that's why I

4:18think it's kind of like the military police. And these three Nobel laureates in slide one um Shimon Sakajuchi, Mary Bernau, and Fred Ramdell. They are responsible for doing a lot of the research 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,

5:01which is what you see on the left over there. Yes, >> that's require learning. That's in our genetics. We're wired to recognize viruses. We're wired to recognize bacteria. We're wired to recognize 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 TE-C

5:42cells. >> Okay. >> Okay. TE- 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 white blood cells, which are our immune system, right? And the ones that we're going to focus on today are called TE-C cells. They develop in the thymus, um, which is an organ of our body, hence the name 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

6:24macrofasages come in. macrofasages like big eaters that like come in and like actually actually like eat things and digest it like within the cell. Um and then >> they're like scouts, >> right? >> Yes. The helper tea cells are exactly like scouts. >> Okay. And then and then you've got your killer tea cells, right? And the killer tea cells like the one you're seeing over there that's attacking the the smaller one is the killer tea cell and it's taking on this giant cancer tumor cell, right? And it's attacking it. So killer tea cells can kill infected cells. They can kill cancerous cells directly and the mechanism by which they understand whether something requires

7:05killing or not >> is the focus of this problem. >> Got it? Okay. >> Does that make sense? Because imagine right you're >> again you're a cell. >> The senses that you have are just lock and key. >> Mhm. 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? Right? And to get into that, we're going to have to go into um exactly how these tea cells actually find, you know, which one is

7:47wrong, which one is right. >> How does our first line of defense >> know >> Mhm. Yeah. >> what to go after. >> Yeah. And effectively like, you know, in in a normal society, the police come over and they check your ID. >> Mhm. >> These guys are doing kind of the same thing. Okay. So, in slide five, you'll see >> this is from the Nobel Prize Committee. they they released these like um you know things for the press. >> Yes. >> To 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

8:28outside of their surface >> that actually take whatever is inside the cell and display it. >> Got it. >> 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 going to take little parts of that protein and they're going to put it out. Got it? 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 up cell that's sort of center screen. >> Yeah. That's that's that's sort of attached to that receptor, that T- cell has recognized something that is quite bad. And so it's going to elicit a

9:09immune response. That's that lock and key model that I was talking about. Yes. Right. >> Yes. I think there's a literal scene in the movie Osmosis Jones that that walks with T- cells going and checking ID. Oh, really? As the metaphor for >> Dude, that's literally what this is. Yeah. Yeah. Yeah. And so the way that the ID check happens is if you go to um photo 6, this is a picture of the human lucasy 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 like right over here, that red thing is maybe it's a viral fragment or maybe it's a part of

9:50our own DNA that or 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- cell's job is to come in and try to figure out if that little fragment is self or not. >> Yep. >> Understood? Yes. >> Okay. >> So the this human lucasite antigen, it's part of the MHC major hystocompatibility complex. It's basically it's found in like you know animals and so on and so forth. Um 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? Yeah. Yeah.

10:32>> And that's why you're like more attracted to them. That's this stuff. >> That's interesting. >> Okay. That's the that's the humanite 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 >> because the the the idea is you have there's less of of these uh potential threats threat vectors that you are going to be susceptible to because you're so different. >> Yeah. Yeah. Exactly. And and so like you have like a broader Yeah. immunity 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

11:15organ is like that's not me. >> Right. >> Right. Like and I don't I don't want that as part of this body. And so people who were actually studying this organ transplant problem, they won the Nobel Prize in 1980, Jean Dat and George Snell for discovering this um human luccoside 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. >> Understood. Understood. So now we've we figured out how cells in our body display their ID, >> 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

11:56not >> or not. Yeah. Now the next thing next part of the clue is how do the TE-C cells which are the police or the military in this case um how do they decide whether that ID is okay or not? >> Okay. And so this >> one thing is the display of the ID. The second thing is like running it through the like is like actually scanning it to be like are you in the database? >> 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. >> Got it? >> 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,

12:38then that means you're a bad person. If they sort of match it in a good way, then you're fine, right? >> So 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 like and if that then happens, >> then they know we need to now have our appropriate immune response. >> Exactly. Yeah. And it's actually kind of an insane thing to think about, right? Because as a TE-C cell, you're going to have to come up with a bunch of different keys. >> Right. Right. right? For all >> that means 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

13:19shapes in your protein. That means you need different sequences of amino 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 cuz we have like something like 10 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? Um because it's three for one. So I'm doing some really crude math here. 10 of the 14 >> different sequences of of DNA. That's a lot of DNA. That's larger than our genome right? >> Okay. So >> how does that happen? H how how are we

14:01actually storing the memory and facilitating the creation of the T- cell receptors in this wide uh this massive scale that is necessary for us to survive in the way we >> exactly and if you go to photo 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 okay >> right and it's trying to generate all of these different shapes and the and the the challenge is how do you generate so many different protein sequences without blowing up on the genetic side of things. Correct. Right. And that was made possible by something called V DJ, variable diversity and joining locuses.

14:43They'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. And now you can come up with a combinatorally much larger outfit. Yes. >> Right. That's exactly what these tea cells are doing. Okay. And this process was discovered by um Susumu Tony and and he won the Nobel Prize in 1987. He's now at MIT. He's doing actually optogenetics stuff which is the prediction. Um 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. Um, so

15:25good luck to him on that. And then the the the last part of it was, so this is so um Tony Gawa figured out how to make all of these different um proteins, right? All of these different shapes that without blowing up, right? Genetic. The the final key was in um 1996 they won the Nobel Prize Peter Deari and Ralph Zincernagle and they were the ones who showed that actually the that human leosite antigen the part that was displaying the ID that's crucial for the T-C cell lock and key model the T- cell isn't just locking in on everything >> everything it's doing it >> it's doing it specifically on the stuff

16:07that this thing is putting out and displaying >> instead of doing no knock warrants at every door they check the the the ID at the door and only do the you know the the the bust when there's a match there which then decreases the like volume of the activity itself. >> Exactly. Yeah. Now you can be a lot more specific. You can manage like >> the whole actually scale to complex >> to a complex organism like us with like billions of cells. Right. So, so that's the background behind how TE-C cells >> do their job if they're doing it correctly, >> right? >> Okay. >> Okay. >> Now, some TE-C cells are inevitably going to recognize your own body.

16:49>> Okay. Because these guys are making, as I said, 10 to the 15 possible receptors, right? Some of these receptors are going to match to like the stuff that we have, right? How do we make sure that those guys don't just like go off? Right. Right. >> Because each TE-C cell is expressing a specific shape. >> Yes. >> 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 um commit cell death 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

17:31do is they can bind this photo 10 they can bind strongly to self-p proteins and whenever they do that the process that happens in the thymus when we're very very young is those tea cells go off and they don't they don't proliferate to the rest of the body >> okay >> 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 >> after that first sort of uh purge, there's still some remaining leftover tea cells that recognize our own bodies >> as as invad as as invaders incorrectly. >> Incorrectly. Yeah. >> And so now there's a second after the

18:12first filter which you just talked through, there's a second line of defense here. >> Yes. Yeah. And that's photo 11. If you go there, these are called regulatory TE-C cells. So on the left hand side, what you're seeing is um 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 TE-C cell and what that does is it's going to suppress the immune response of that incorrect T- cell. >> Okay? >> And this regulatory TE- cell is what stops the autoimmune response from happening. Autoimmune being meaning it's a immune response on yourself. It's

18:54almost 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 >> that are problematic. And so if only that actually happened, but you know, um >> it's that's exactly what's going on is like you've got you've got like the the ones who regulate the cops, right? And and they and if they do a good job like in most of us, we don't have those, right? And so most in mostly it works and where it doesn't we need to figure out how what's going on with the regulatory tea cells and if there's ways to prevent that from happening. >> So we have our first filter and then you know once we get past the first filter there's still some remaining uh uh tea

19:36cells that are attacking our own body. So then regulatory tea cells come in to suppress that immune response but that's not there that doesn't happen 100% of the time still even at that second layer. >> 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 this system existed in the first place discovering the fact that there are such things as regulatory tea cells that are uniquely different from the rest of the tea cells from helper tea cells from killer tea

20:16cells this is totally different class of immune cells that come out of the phalamus. Right? >> So you have the ID system, you have the T- cells that are ID system, you have the T- cells are going out and actually doing the work. And then now there's this third bucket which is the police of the police. >> 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 um 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.

20:57>> Okay. So the thymus is key. I mean this was already known but now you've got sort of test bed. 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 leion the thymus. the the guy's sick. >> 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 going to 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 going to be fine. Right? So what you've done is

21:38transfer this um tolerance, right? You've transferred this mechanism. >> Yes. >> Okay. >> And this was back when like >> they didn't have like monoconal antibodies. They didn't have any of this stuff. So they they used to use like blood serum to basically classify like what was in the thing that I injected which was like very coarse grain. 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 monoconal antibodies, right? And with monoconal antibodies now what I could do is I could start identifying a subop of

22:22tea cells that have a specific thing like a specific surface marker because monoconal 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 and the numbers 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- rags right and without these cells the mice developed autoimmunity but with them they they

23:03were fine right and he finally published his paper in the journal journal of immunology this was the first sort of seminal paper got it in 1995 Okay. >> Okay. The first one with the alos 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. Right. All right. >> Right. >> So, there's there's there's a level of higher fidelity um to to get to the answer. >> 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

23:44the gene level that is expressing a difference between these regulatory tea cells and the normal tea cells because even normal tea cells like the conventional activator tea cells they also have CD25 which is this marker that he had identified. Sure fine it's like a little bit lower density but it's still there. Right. So it's not as convincing. >> Right. Right. Right. And so >> what we're saying is like what is the actual mechanism? >> Yes. >> That allows the differentiation in when these tea cells are you know when they get created like what what makes it know I'm a helper. >> Oh a killer versus a regulatory. Is >> that exactly exactly like the courses

24:25that they took in the training academy like but what exactly did they read? >> Right. Right. Yeah. How did they get to Yeah. >> Exactly. You know what I mean? >> So, >> yes. >> So, that was um Shimon Sakaguchi. >> Yes. >> He he had sort of come into the 4A. Now, we're going to get to our next two Nobel Prize winners, Mary Broncow and Fred Ramdell. Their story um is is pretty interesting. So, actually to get to their science, we first need to talk about 1940s Oakidge National Lab. I think you've got a photo of that there. Yeah, that's the that's where we um enriched uranium for the atomic bombs. Um, and you know, there's a lot of radiation there. And in the 1940s, um,

25:05researchers found a mutant mouse strain in Oakidge that had scaly skin, swollen lymph nodes, early death. And, you know, as scientists do, they're like, "Oh, let's study this thing." Okay, they called it the scurfy mouse strain. Okay, they called it the scurfy mouse strain. And what they noticed was only male mice developed this disease 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, but females are fine, that means that it has to be an XL disorder. X- linked meaning that

25:46whatever genetic thing is making this thing happen >> is happening on the X chromosome, right? because females have two copies of the X chromosome. 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 >> Yeah, that makes sense. >> So So they figured out that it's got to be on the X chromosome. They did a lot of um different tests to figure out and they narrowed it down to 500 base pairs. Okay. >> Okay. and their job what what Broncow and Ramsdale did, they were these basically gene hunters at Celtech um Chyrocience. Um Mary Brunow had finished her PhD at Princeton.

26:28>> We got another one baby. And then Fred Ramdell at UCLA, which is where I went for P for a PhD. So that's kind of cool that today um both my institutions >> I was going to say but both >> they got a plus one plus one, baby. Yeah. Um so after they the after they're done with that and they're done with their posttos they they join Celtech Chyroscience which is um 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 that's on the X chromosome okay >> now back then we don't have the kind of high throughput DNA technology like 23 and me where I can like mail a sample

27:10and then and then like just get back all my all my DNA results, right? Back then, this is in the '9s. So, this is before Human Genome Project was >> like this is when in the heyday of that. So, we've got these like really really old technologies. One of them is called BAC cloning, bacterial artificial chromosomes. What you do is you take a segment of whatever um whatever part of DNA that you're trying to sequence, 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

27:50a 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 100 bucks and a laptop right like but but back then this is like several PhDs. is just like figuring out what are these 500 kilobase stretch of DNA doing. And so if you go to photo 19, we've got a photo from their um from their paper on the top there, that's the 500 kilobase stretch of DNA, okay, from the X chromosome. 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

28:32genes. 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 scurfy mouse strain. Okay? It was a two base insertion. And if there's an insertion of two bases, remember, >> um, >> it's three base pairs to a single amino acid, 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. >> 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

29:14>> my reading for all of the rest is going to be completely off. It's it's not a point mutation. Right. >> Right. And so and so this twobase insertion created like a um ma made the gene effectively shorter 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 it's it's completely wrecked. And so they named this um gene the forkhead box protein P3 or or fox P3. Okay. And it turned out that it was a transcription factor. And they published this in nature genetics 2001. That was

29:56their first big paper with the two of them together. Again, this is Brunca and Ramsdale. Yes. Um they also published another one in nature of genetics where they linked this mutation the scurfy mice mutation to um diabetes and other autoimmune disorders specifically IPEX ipex which is immune dysregulation polyendocrronopathy >> entropathy and it's also XL which is 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. You know, we'd like to think that we're very different, but like you know,

30:37at a real molecular biology level, we're very similar, especially for for old systems like the immune system, right? The immune system is is is a very old system for mammals. So, >> a lot of the same mechanisms are happening across the mamalian 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, three papers in paper in nature genetics and this was the nail in the coffin. What they did was crossbreeding of um scurfy mice with people that had the wild type and they could show a

31:18recovery of function. And so it's really like it's like it's like definitely it's that that's the location >> that's causing all of this. >> 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 where perhaps this regulation is happening. >> Yes. >> Okay. >> And this is when Sakaguchi gets back. >> Yes. >> So in 2003 he publishes um this work which basically combines those two papers. He combines the Sakaguchi paper from earlier which showed that these T te T- cell regulators were um were functioning in this way to suppress this autoimmune response and then it's combining this um FOX P3 gene thing

32:02that's happened in 2001 to show that actually >> the if you add the FOX P3 gene to normal TE-C cells they'll turn into regulatory T- cells >> it's like a retraining >> okay that's like you send them back to the training to to relearn what what may have been missed. >> Yeah. So you can you can insert this FOXP3 genome >> and it'll actually like turn them into regulatory cells. >> That's very okay. >> 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. >> Works. Yes. You know. >> Yes. No. 100 100%. I Yeah.

32:43>> It's it's really cool. So he published this in 2003 in science. I think that's um 24 you can see and this is sort of the last um last of the papers that we're going to review. Okay. And so 2003 and then now it's been what about 20 years? 20 plus years that they get the Nobel they get the Nobel Prize for it which is so >> but Sakaguchi has been at it since the 1980s. Right. >> Right. >> He's been at it like for a while. >> That'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. And in photo 25 I

33:24have 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 you've got um the T-reg the regulatory cell the regulatory T- cell which which is like the spaceship I guess and it's got this the receptor the T- cell receptor that's trying to identify if there's been an incorrect immune response and then the alien or whatever is inside >> that has a Fox P3 cap on >> you know so that's the DNA >> that is uh I don't know how they come up with this >> that's that's but that that's Having walked through because I saw this image at the beginning >> it meant nothing

34:05>> and now having walked through I actually can point to each of the identify what's what's going on and why it matters. >> Yeah. So so the T- rag outside that's that's um Sakaguchi and then the Fox P3 gene that is responsible for that that is Brun and Ramdell you know and so congrats to the the three laurates. >> Yes. Yes. you know they're they did amazing work and now there's in current frontiers there's a lot of stuff going on. So I'm actually going to 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 crisper this was more of an understanding of a functional >> functional processes in a way that

34:46unlocks a whole variety of implications. >> 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, right? Cuz that's when we get these autoimmune disorders like IPEX and diabetes. >> The reason it's among other things, the reason it's so important is because it's so directly related to this autoimmune disorder problem. >> Exactly. Yeah. This is one of the ways in in which an autoimmune disorder manifests >> which is very a very pernicious. >> 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

35:26then there's, um, induced T-regs that are induced in peripheral tissues after antigen exposure. So, there's like normal tea cells. Yes. >> That like get induced to become >> T-regs. Yeah. >> Because of their environment, they they they decide to go back to the their own cuz the gene is already in there, right, in their DNA. It's just been repressed. 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. Mhm. >> 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 um >> there needs to be people have found that

36:09>> in inflamed tissues where there is an there there is an immune response you'll find that the T-regs actually need stronger FOXP P3 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 >> box3, right? And then if you block the repressor, >> then this thing is no longer inhibited and you can actually get regulation. So, so that's one way that you can actually

36:50do therapy. >> Yes. >> 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 other episode. Um, there's like 200 plus clinical trials that are happening right now >> related to related to T-R related to TAG as a general. Yeah. Yeah. So, so you know it's a ubiquitous now um like method by which the people are trying to >> tune the immune system and then fight disease >> in in this way and it wouldn't wouldn't be possible without like fundamentally understanding all of these mechanisms >> right >> down to the molecular level of like how

37:31this stuff works. Yes. >> You know. >> Yes. 100 100%. Yeah, >> this this is a um the imu I mean obviously you know the immune system and all of the medicine in particular I I think it's been postco there has been a very interesting discussion about how the body works >> that is not necessarily informed from first principles. >> Yeah. >> Right. Because there's a lot of these fundamental processes >> Yeah. >> that just are what they are. >> Yeah. And there's there is a benefit to having an understanding of what those are. >> Yeah. I mean, I love thinking about the body as just a bunch of Lego blocks. >> Lego blocks, >> right, that are just trying to find each

38:11other. And like all of the complicated decision-m is happening at that Lego block level, right? At the molecular level. It's kind of insane, >> dude. That we're it's such a complicated >> set of things, >> right? >> Where like tiny things go wrong and it just totally wrecks you, right? And now we're getting to understanding things at such a level when those tiny things go wrong, we can go in and fix it >> and and even just one very very tiny small aspect of this combinatorial process that has so many implications. So it it seems like this has solved sort of this >> 100year mystery >> of like how the immune system >> Yeah. >> restrains itself.

38:52>> Yeah. Exactly. Yeah. Pretty cool. >> This this is this is this is very cool. Uh this is day one. So, this is the medicine. Yep. >> We did. We I I said in our predictions Princeton was going to get on the board. >> Yeah. I didn't know it was going to be the first day. >> We're on the board. >> Yeah. I mean, at least my predictions were wrong, but we got on the board. >> We got on the board. We'll take that. >> Directionally accurate, but tactically wrong. Uh so, tomorrow we're going to be doing physics. Um >> same time, y >> same place. >> Uh congratulations to the winners. Uh and we're going to 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

39:33Nar as always joined by my co-host our resident PhD Krishna Chowdery. This is from first principles. We'll see you guys tomorrow. >> Okay, here we go. Yep. >> This year's prize is about encountering quantum mechanics on a new scale. >> Okay. >> Okay. So, not atomic force microscopy or topological physics.

40:03Y Clark, University of California at Berkeley USA. >> Okay. Michelle Berkeley on the board. >> University Oak University of California at Santa Barbara. >> Okay. Oh, UCSB on the board. >> Martinez University of California, Santa Barbara. >> That's also UCSB. >> Okay.

40:33The 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. Michelle Devore, Yale University and University of California at Santa Barbara USA. >> Santa Barbara. Unbelievable. >> And Yon Machinis University of California at Santa Barbara, USA. >> I wonder where they got their >> for the discovery of microscopic quantum mechanical tunneling and energy quantization in an electric circuit. >> Microscopic quantum tunneling. Okay.

41:13>> Hello internet. This is your captain speaking Lester Nar joined as always by my co-host and our resident PhD Krishna Chowdery. 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 uh very much still important. So what what what matters about this macroscopic quantum tunneling winning the Nobel for physics this year? >> Um you might have heard of quantum computers. >> Yes. >> Right. Um actually I just I just looked

41:55it up. Um John Martineis 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. >> Oh interesting. Okay. >> In UCSB. Yes. So, it's kind of a 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 four experiments that were done in the 1980s and that has sort of started a whole new field of quantum devices,

42:35quantum 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, Michelle 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 a episode on the fact that 2025 is >> the year of quantum, right? According to the UN. >> Yes. And that's because a 100 years ago is when the first seminal papers in quantum mechanics by Verer Heisenberg

43:16were published. Um 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 um 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. Um photo three is a nod to the 2025 year of quantum physics.

43:57That's a photo of um three of some of my favorite scientists. >> We've got Verer Heisenberg in the middle. On the left is Pi. And on the right is Enrio Fairmy. >> Yes. >> Three seinal um figures in quantum mechanics. Um and on the left is a letter from Verer Heisenberg to Wolf Gang Pi talking about his 1925 paper and how everyone else is wrong. Pi was also of the opinion of Warner Heisenberg where you know we needed a new paradigm to do everything quantum related. Um 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

44:39the back chatter that happens. >> 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 going to 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 Schroinger equation, you'll have a probability that that particle goes through the barrier. And if you look at

45:20this description here on that's that's the Schroinger equation 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. Yes. 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.

46:00>> Yes. >> But crucially, >> notice that the winess of the of the wave function on the right >> 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. 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 throughout this energy barrier. That's very not classical. >> Right. Right. >> Right. 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

46:41would 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 that's the that's the magic of quantum mechanics there. Okay. So >> historically, it's actually been seen in all sorts of um different phenomenon like for example with radioactive decay. This is the idea where nuclei like large nuclei like the uranium atom can decay and 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 a you've got the nucleus of the atom and the nucleus of the atom has a bunch of

47:23particles 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. Then it's going to find itself on the other side of that barrier and it's going to be going >> with pretty high energy. >> Yes. >> Right. That's and and the probability with which that tunneling happens tells you the halflife >> of your material. >> If it's a high probability then the halflife is lower. If it's a really low probability that means it's a very stable nucleus and the halflife is much larger. Right? And that is why half-life

48:04and 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 and it's rooted in this quantum mechanical probability stuff. Okay, >> does that make sense? >> 100%. >> So like we know that quantum tunneling happens, right? also in the core of like the reason why we're all alive on Earth and Earth has been going for 4 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 C um and you know at that speed I mean at that temperature

48:45the nuclei inside the sun are moving extremely fast right and the idea is two hydrog 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. And so the coolum barrier, which is basically repulsion, positive positive, don't like to be next to each other >> is going to 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

49:27because sometimes these guys tunnel past that energy barrier that's created by the kulam 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 that we see. Right? Yes. >> So quantum tunneling is we we can we can thank quantum tunneling for the light from the sun. >> Literally the light that powers everything that entire ecosystem. >> Yeah. And so quantum tunneling has always been um something that is wellnown but it's been well known for small numbers of particles right with even with nucleons um and alpha decay

50:07that'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. >> Interesting. >> Okay. So, it's it's several orders of magnitude above that sort of undergraduate level >> understanding >> like problem sets that we used to do. Right. Right. Right. It's it's it's very cool. I think um so in order to really understand the the the experimental setup >> Yes. >> Right.

50:47>> Um we got to talk about superc conductivity. 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. >> It was not a room temperature. >> 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 stuff around it. Right. And with superc conductivity you have this amazing phenomenon where at low temperatures you have zero resistance >> to um electrical current. Okay. And by zero I don't mean near zero. >> You mean >> or like a little bit. I mean literally

51:28>> literally zero. >> Literally zero. >> Literally zero. There are there are superconducting um currents that have been kept alive just by the fact that they've been kept cold for like decades now. >> Interesting. Okay. >> In um experimental physics labs because like it's it because there's no resistance. You can keep this state, >> right, >> for decades and it'll be the same exact current value cuz no current is leaving, no current is entering. It's the same amount of energy that's locked into this >> apparatus that you have. Yeah. So for for 20 years, you can experiment on the same exact thing, right? And make your make everything else bigger and bigger.

52:08But like the thing that you're you're messing with is exactly the same. Yeah. 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 here. 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, >> right, >> is is just going to stay forever, right? It's it's that's the magic of superc conductivity. And the physics behind superc conductivity is quite interesting. It was um discovered by three people Bardin Cooper and Schiffer at the University of Illinois in Urbana Champagne and it comes from the fact that electrons can interact with the lattice of atoms in a

52:52superconductor 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? 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 going to do is deform the lattice in a way that the positive nuclei are going to kind of get smudged towards the electron. Okay. Now, what is

53:34that going to create? That's going to create a localized positive charge where the electron is because usually that electron and all the positive charges would perfectly cancel out, >> right? 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 >> which this in that sort of slightly pink area. >> Yes. Exactly. There's a slight positiveness >> to it. Okay. And that is going to couple with the negative electron >> that's in the lice, right? Yes. Exactly. And these two

54:15these two particles, they obey um the Pali exclusion principle, meaning that you can't have the quantum states right on top of each other. They they they don't want to they don't want to sort of like talk to each other all that much. Okay? But because they're two different electrons, you can have them obey the pi exclusion principle within themselves >> and create something called a Bzon. Okay? Like these two are firmians meaning that they obey the poly exclusion principle but together they they they they use their dis disagreement to sort of cancel each other out and create a Bzon. Okay. And this Bzon is something that

54:55can have quantum states that are right on top of each other. Interesting. >> And so you have very different physics. You can have something I mean you might have heard of something called a Bose Einstein condensate. >> I was literally going to just ask that. Yes. >> Exactly. So the bzon and condensate is this idea that all like when you get something really really cold they start behaving like bzons 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 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

55:36is about the same. >> Interesting. Okay. Yeah. Yeah. Yeah. >> And what that means is these these this condensate can now move around like a single quantum state. >> It's it's almost has a shared state across these independent electrons. Yes. >> Um that act that act in unison as an as an emergent effect of this these parameters that you just described. >> Yeah. Exactly. Exactly. And so they can it's like multiple play pairs. They 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. Right? Does that make sense? >> 100%.

56:17>> So the Cooper pairs are are talking nice to each other and they're moving. >> Yes. >> And >> without without any without any bumping >> and and that lack of resistance creates like there's opportunity that gets created from that low resistance environment. >> Yeah. Zero resistance. Z zero resistance environment. Um >> zero resistance environment. And once you have zero resistance, then you have stuff like the misner effect, which is where you get the levitation over a magnetic field and you get mag lev train. I was going to say that's how magv works. >> 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 firmians are pairing up to create a bzon and then those bzzons

56:57become 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 Bardin Cooper and um Schifer and it was at the University of Illinois, Urbana Champagne. Bardin actually um um alumni of Princeton University and he's the only person to have won the physics prize twice. >> Oh, okay. >> Yeah. once for inventing the transistor at Bell Labs and no big deal. And then he came over here and like did the seminal work for superc conductivity. Yeah. What a life dude. BCS theory. Um >> so now we understand how um

57:37superconductors work. Right now there's this guy Brian Josephson. He predicted that what superconductors can do is they can actually tunnel across a insulating barrier >> together. Before we used to talk about how particles individually tunnneled 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. Um on the top there, that's a normal current, right? All the electrons

58:17are 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 um 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 a Josephson junction. Okay. So that was Brian Josephson. The bottom rung is what the Nobel prizes >> now are doing. I I >> which is we're we're going from Cooper pairs >> to now a giant current. That is one thing. >> That is one thing. >> Okay. That is that is tunneling across the barrier. Right. >> Okay. So we're going from like two particles to now 10 to the 9.

58:58>> Right. >> Okay. >> Right. Yes. And um Joseph he won the he won the Nobel Prize in 1973 for um 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 barrier, you can have Cooper pairs go through >> and there's going to be some max amount

59:39of critical current that you can get from those Cooper pairs >> pairing up and moving through. Okay? 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 going to become a classical um system, right? Okay. So that's how Josephson junctions work. Now in 1978, Anthony Leget, who is another Nobel Prize winner, um he

1:00:21started asking, well, can I make a macroscopic tunneling experiment happen where instead of doing um Cooper pairs that are tunneling the and and and like each little thing is treated like a like a a quantum mechanical state. What if the entire circuit is a quantum machine, right? It's like a it's like a the entire circuit is an atom >> in some sense >> that's doing this quantum mechanics. Okay. And what he considered was a current biased Josephson's injunction and that's that's what we're going to see over here. So >> what we're looking at is that Joseph's injunction that we had earlier, right?

1:01:02And he's asking now what is the energy landscape of the current in that Joseph's injunction? Okay, you can ask the Josephson junction can be parameterized 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

1:01:42the energy minima, right? So, so when when you start putting the language of the Josephson's 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 if if you don't apply a current remember this is a current bias Joseph's injunction. 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 the particle is sort of going to get stuck in one of those, >> right? 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 where the

1:02:25>> the the the energy landscape gets completely tilted. Yes. Right. 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- energy minima thing >> right where on 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

1:03:07a 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. So that is the experimental question right? >> Right. >> And Leot 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

1:03:48today. 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 um >> junction >> biased. >> Yeah. Yeah. It's it's got this like biased um it's got this biased current that goes in um can I make the entire circuit a quantum object? Right? >> That's the idea, right? And the entire circuit is made up of like 10 the nine

1:04:29things, right? And can all of those 10 the nine things >> move as a single quantum object, right? That tunnels and does all of the stuff that I want it to do >> as a result of this sort of concept we just walked through around how quantum tumbling fundamentally works. The thing is how can we scale it up from a single like there's a particle which is a single Lego block. Then 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 like the complete like the completed Lego structure behind you um and have that entire system >> uh operate as this single >> a single quantum object >> quantum object like um that has

1:05:09well-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 uh 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. Um that's the building where plutonium was discovered. Several Nobel prizes. And actually now they got a plus three on a single day. >> That's unbelievable. Unbelievable because >> we were excited yesterday. >> Yeah, we were excited with plus one. Um

1:05:51but yeah, in a single day UC Berkeley has a plus three because John Clark at the time after his PhD at Cambridge he um became a professor at UC Berkeley. He was joined by Michelle Devore who was a posttock in his lab and Jean Martinez who was a PhD student. All three of them were in the same lab in 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 the 9 particles are acting like a single quantum particle >> right >> yes

1:06:31>> can we do this >> okay so 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. >> Oh, okay. Okay. >> Imagine writing a PhD thesis. >> Yeah. >> And then like a figure is like in the Nobel cartoon, >> you know, so legendary. >> It's so legend, dude. Like this is literally in his thesis. Um >> that's unbelievable. >> Yeah. Yeah. In 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

1:07:13the right hand side all the way over here I guess for 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 like I thought copper was electrically conductive. 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 shielding. All right. So, so but but the idea is, you know, you want to get this

1:07:55thing really cold. >> Mhm. >> And and so and you want to shield it from all sorts of electrical noise, all sorts of every type of noise. Okay. So muchter. 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? 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'd fit parameters >> right >> and be like >> see it's kind of working and that's not

1:08:36convincing 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 >> we're good >> right >> it's not like if these numbers are this then it makes sense >> that's not I mean it it's It's still like fundamentally good science. It's just not >> sort of closing the the book. >> It's it's not a complete It's not like a sort of the the complete circle complete loop, right? You're you're arbitrarily creating. >> It's not closed logic, right? It's like >> Exactly. >> Yeah. It's it's like there's too many free parameters. >> Yes. >> Okay. So, they they they make this thing, they put it inside of Cryostat, and on the top,

1:09:16you see that little antenna there? >> 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 >> with some copper in the middle for shielding. >> Yes. With a 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

1:09:56get 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 on the on the on the right hand side what you can see is a 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. >> Mhm. >> What we're seeing is the current is is

1:10:36stabilizing. Right. There there's some some like minimum amount of current that's happening. >> Right. >> 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 >> oh tells you >> and and the and the little the the the >> the plateau is happening right at that tick. >> Right at that tick >> on the x-axis. It's also telling you where the plateau should start according to theory. And that's also lining up with the experiment. >> We love to see it. >> Right. And you love to see that experiment um theory confirmation happening. And so on the left hand side um I don't really like this cartoon. I >> It's like a switch that is like turning

1:11:18on and off. Um and that's it. So I I don't know how that's like quantum. Anyways, that 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. Okay. And the way they did that was remember that microwave antenna. >> They used a micro the microwaves to excite the system >> and they observed energy levels that were quantized. So if you go to the the next slide, what what they're on the

1:12:00left, this is this is the cartoon of quantized energy levels, right? That are like discrete. 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, right? According to that's like Eisenberg's uncertainty principle actually, like energy and time are both related by that quantity where the product has to be less than something. So if you increase the energy, you're going to have to decrease the amount of time that it stays within that state. Um so it's consistent with quantum mechanics and on the on the on the upper panel you can see this quantized energy landscape, right? Mhm. >> So, so this was kind of the nail in the

1:12:42coffin >> of like this entire thing of 10 the 9 billions of Cooper pairs are >> behaving as a single >> quantum thing that is like going between one state or another >> another in unison. >> In unison. That's exactly right. >> Right. >> Yeah. >> Pretty it's pretty it's pretty cool. And um this was in the 1980s. So they they waited I guess 40 years >> to give it to them. >> To give it to them. Yeah. But in those 40 years, a lot of advancement has happened. >> I I mean I can imagine. >> Yeah. Yeah. A lot of stuff has happened. So the way the way it's made me think just like the implications of understanding because obviously with

1:13:22quantum everything quantum related, it's always there's always it's a little handwavy. It's a little like don't look in the corner over here. You know, we haven't figured that part out yet. Um, but this feels like a really solid root that has a lot of branches that can come from having experimental confirmation. >> Yeah. Yeah. And it's like, dude, 10^ the 9 particles that are behaving in a quantum way is like pretty insane. >> Yeah. >> 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 0 Kelvin, but like >> we're not talking about room temperature. >> Yeah. Yeah. because there's too much noise in room temperature. But even down

1:14:02there, >> 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 cubits and that's one of the um applications that we can focus on. So this is a photo of IBM's quantum computer. The cubit so the the photo

1:14:43what 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 got to get really cold. >> All these quantum systems have to look so bizarre. >> 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. Yeah. >> It's like a lot of it's just like the refrigerator. Um but the the cubit itself is the next photo that I have and that is the um transm cubit. The arrow that you're seeing, that little square in the middle, that's the Josephson junction. >> Okay. and the little like uh radiator type things on the on the right hand

1:15:24side of that that's like a microwave cavity >> that's being used to talk to the Josephson's injunction so it's they've basically miniaturaturized um >> this work >> 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 multi-million dollar deal of course it was >> 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. >> I I think I texted you about it because I was like hey is is is it is this it is

1:16:06it happening? >> And it's like you know in the in the in the quantum community it's like maybe I mean it's certainly very impressive that they have so many cubits that are running. John Martinez is that team right? So, I bet Google's um like press is gonna like have a field day. >> They're gonna have a field day. >> They're having a field day. >> They're gonna have a field day. We told you we're on the board. >> Yeah. Yeah. Now Google has >> Google's on this cuz we're going to start a scoreboard for the the institutions with the most Nobels. And so now Google's >> Yeah. Google's getting up there with the with private >> um institutions, right? I don't think anyone's ever going to beat Bell Labs. Bell Labs has like eight, which is insane. That's that's pretty that's

1:16:47pretty >> um but yeah like 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 um PhD at Cambridge and then he was a professor at Berkeley Michelle um Devore he got his u PhD in Paris and then came to the states now at UC UC Santa Barbara and Yale. And then finally, Jean Martinez who's at Google and UC Santa Barbara. >> Unbelievable. What a fantastic that that that's actually a really helpful explanation cuz I've I've heard I think

1:17:28actually one one of uh 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. >> Yeah. And it's one of those words that I hear all the time tossed around, especially with some of the the UAP stuff that people always like to throw the word without the actual first principles understanding. >> Quantum tunneling for sure. >> That's that's how the they're doing all the crazy flight movement. But this is this is super fascinating. And I think it's interesting because you you your view is is it's somewhat unexpected. I thought it was somewhat unexpected because usually like Nobel prizes um go for

1:18:10things that have like act that have actually worked. I wouldn't say that quantum computing has really worked. >> 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. Is it would you say that in part some of the understanding related to

1:18:50understanding quantum tunneling and energy quantization like it it helps to elucidate this like the unification problem >> with classical and quantum mechanics or is it >> certainly does I mean I mean the I think personally I think the the more the larger we push quantum systems that's kind of the thought >> the the the weirder it gets, right? Um, but fundamentally actually I don't I don't think like doing these kinds of experiments will really solve the measurement problem. You're just making the measurement problem bigger in in terms of like you know now it's no longer I'm observing a photon. It's like

1:19:31okay now I'm observing 10 the 9 particles but philosophically the problem is still the same right which is like how does the how does the Josephson's injunction know whether to um you know be in one state or the other >> which we which we talked about this last >> quantum 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 um these Josephson junction type superconducting circuits to get at Bell's inequality. And Belle'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

1:20:13the measurement of the other, right? There's like correlations that wouldn't be possible unless these two were actually entangled across that distance. Um so there have been there have been um experiments that use these cubits to do that and I think they did it over 30 m right which is um which is a pretty big a pretty big distance when it comes to like particles right >> um >> so I I there there's going to 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 weird even when you get really big. >> Big. Uh day two's conclusion. The world

1:20:54is really weird. >> Yeah. >> Uh and we are rewarding those who help us see that it is in it is indeed quite curious. >> Yeah. It's really weird. >> So this was day two for the Nobel Prizes. We have macroscopic quantum tunneling. John Clark, Michelle Devare, John Martinez. We'll be back tomorrow for day three. Yep. The last of the sciences, chemistry. Yeah, >> bright and early again. Be sure to tune in. I'm your host, Lester Nar, joined as always by my co-host and our resident PhD, Krishna Chowdery. This is from first principles. See you guys tomorrow.

1:21:35This year's prize is about creating new rooms for chemistry. What does that even mean? New rooms. New rooms for chemistry.

1:21:56University. >> All right. >> Richard Robson, University of Melbourne. >> Omar Yagi, dude prediction. I knew it. That's amazing. >> I told you. >> Yep. Yep. >> Yes. I called >> it called it on Sunday. >> Called it on from first principles podcast baby. >> That's so funny. Hello, internet. This is your captain speaking Lester Nar joined as always by my co-host and our resident PhD Krishna Chowdery. 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 reticular chemistry. And so

1:22:37we're going to dive right into understanding what is what are metal organic frameworks and why this is so important. >> Yeah. I mean, so the the chair of the Nobel Committee said new rooms for chemistry, right? 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. Um on the left there, that's the cartoon from the Nobel Committee. Yes. And on the right is the actual one one of the examples of a chemical compound that exhibits this

1:23:20metal organic framework. Okay. >> 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. >> Yes. >> 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, right? Suppose you want to like get water from thin air. The porous material can now do that, right? Cuz you're making holes that are the size of the chemical compounds you're looking >> 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

1:24:01it's it's like you can tune the building material, right? Right. using using these metal organic frameworks. >> It's like I built a resort and each room is customuilt for each guest that I have at the resort. >> Yeah. And you can now build each each thing. Yeah. >> Right. Because because it's it's effectively like really really complicated Lego blocks. 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. >> That makes sense. >> And make like buildings. >> Yes. that can fit whatever molecule that you want. Right? >> Okay. >> It's really cool. So, the award was given to these three individuals for basically starting this field. Okay. And

1:24:43like 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 >> okay this um back in the 1980s. And then there's um Susumu Kitagawa from Kyoto University and Omar Yagi. a 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 cuz I did have the prediction, but um but it was still it was still like getting into getting into the weeds. It was really cool to see how the history progressed, right? Okay. So, >> chemistry has been really good for a very long time with something called

1:25:24zerodimensional 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 cuz they're pointlike. >> Okay. >> Right. And that's a zero dimension. >> Then we got started getting really good at 1D, right? Polymers. That's a carbon nano tube. And >> 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

1:26:04nerd like you know those nerd ropes it's like that it's like relatively easy okay compared to the 2D and 3D stuff that this Nobel Prize is going for. Um >> but there was a precedent to try and find these things. Okay, there are these um minerals that are found naturally. They're called zeolytes. It was discovered by um the Swedish minologist Alex Pronstead in 1756. And what he did what he did was he observed that like if you take this material, >> right, which in this case it's still bite. Zeolyte 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.

1:26:45>> 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? And there's like holes inside where this water molecule is going. >> Right? And that's why he he coined it zeolyte because zeo is Greek for boil and lithos for stone. And these lights became a big character.

1:27:27Berlin 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 2 and iron 3. That means it's either two electrons are gone or three electrons are gone. And then inside they're linked by these um carbon nitrogen bonds. Okay. >> Okay. And now we're starting to get into metal >> organics, right? Metal the iron organics. Anything that has carbon. This is the like like day zero. >> Okay. And on the left, that's the famous um great wave off Kanagawa. Yes. The print um by Hokusai in the in the 1800s.

1:28:10Yes. Right. That blue pigment is the Berlin blue. Berlin blue, right? The Japanese um print makers would like import this from Europe because making blue was incredibly difficult. >> Like the Egyptians used to make blue, but then we forgot how to do it because like the Egyptians >> such that's such a crazy like I mean knowledge is forgettable. >> Yeah, knowledge is very fragile, dude. If you're not if you're not careful, >> 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. >> 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

1:28:51of led to all of the developments and then uh created the Nobel Prize today. So, >> we know that these things are possible, >> right? >> Right. They occur in nature. >> Yeah. They occur in nature. The idea is we want to we want to be able to engineer >> and very specifically put stuff together. Okay. >> In order to basically get themer like the emergent properties what we're looking for. >> Yeah. Yeah. And in order to figure out exactly how we're going to do this engineering, we need to do a little bit of basic chemistry. Always you got to start from first principles. >> So um we go to 1913. Alfred Wernern wins the Nobel Prize in 1913. He basically starts this field of coordination chemistry. Okay. He starts he starts

1:29:31thinking about metal ions and how metals can bond covealently with other atoms and he characterizes these tetrahedral tetrahedral complexes. Tetrahedral meaning the the like four yes >> you know tetra meaning four. So four bonds that are in this like sort of nice crystalline parameal structure. >> Um 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 covealent bond. So if you go to the next slide, I'll show you what the difference is. So in in a normal covealent bond, you've got shared electrons, right? In O2 for example, oxygen and oxygen, each oxygen is sort

1:30:14of donating an electron to the bond to create the O2 molecule. Same thing with CO2 H2O. With a coordinate covealent 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 covealent bond. Okay? And this is going to be the sort of >> building block of the chemistry that

1:30:56we're about to talk about that won the Nobel Prize. Okay? Because metals metals make ions, right? And what ions usually with metals the the outer electrons which are in the Dshells that are like far away from the nucleus, they're just going to go away. So you're going to get like a copper ion which is C++ that means one electron left. Or the ones we were talking about, iron 2, iron 3, 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 covealent bond. Right? And that's going to 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 noble laureates. So first we got Richard Robson. >> He is in the University of Melbourne.

1:31:37He's teaching classes in 1974. And this is a great example of how teaching actually leads to >> discovery. >> Discovery. Okay. So, he's teaching and um he needs you you've probably seen these in like high school chemistry, right? The balls that have like holes and then he put 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 going to 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

1:32:18the atoms tell me the geometry of the the bond right but these holes can be on the outside of bigger molecules and those holes will still preserve the geometry >> right on the outside. >> Mhm. >> 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 tetrahedrin. 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 parameal ones on the bottom. And then you can connect all of these together to create a tetrahedral crystal 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

1:33:01>> a diamondlike thing, 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+ 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? I'm it's the molecule is called 444 tetracyano tetraenolmethane. >> Okay. This is one of the reasons why I never really got into chemistry in high school is like the names were just ridiculous. But the the main idea behind

1:33:43this molecule is it's pretty rigid, right? >> Okay, it's a rigid molecule and on the ends of that pyramid, the top and the three ends, there's something called a nitral group, which is this CN carbon and nitrogen. 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 a metal

1:34:23crystalline structure using metal ions and other stuff in between. Yes. And it had a bunch of holes, >> right? >> Remember, right? It had a bunch of holes. And and he and he published this in um the American societ, the American Chemical Society in 1989 and 1990. And this was very unexpected at the time, >> right? >> Okay. This was like this was like very very cool because people used to think like, oh, like if I just put together um if I just put together metals with this other kind of stuff, I'm going to get a molecular bird's nest. You know, bird's nest is like very kind of disorganized. It like maintains its shape, >> but it's not this kind of regular sort of thing, right? >> Yes.

1:35:04>> So, this was this this was very cool when it first came out. Um, 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. Mhm. >> Okay. He also at at the time he he started talking about the future of applications. He's like this could be used in the absorption of gases, catalytic reactions. So he was very forward thinking, right? And it sort of started a lot of people along this and two Yeah. And two of those people are the >> the other he opened the door.

1:35:44>> Yep. >> Uh for other people to think in this direction as like oh there's there's a there there. Yes. >> Uh that's worth study and exploration. >> Exactly. Yeah. Um 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. Yes. So >> now we're going to go to our second um Nobel Prize winner, Suzumu Kitagawa. And he makes this. Okay. So this is um in about in I think 1995 he publishes this and it's a tongue and groove where he's using cobalt, nickel, and zinc ions in a 3D framework. And this is really stable. >> Okay. >> Okay. This is the first sort of like

1:36:25nice stable thing. You make this in water. Okay. In a soluble sort of chemistry. That's how that's how 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. >> It's not a single use or like or like a limited end number of use. It is structurally going to repeat the same process every time.

1:37:06>> Exly. Yeah. And it's it's stay it's it's sturdy for that kind of thing. Right. So this is the first demonstration of a reversible gas absorption. Okay. Okay, absorption 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. Absorption means like um like a 2D kind of thing. Yep. >> 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 stuffing because people were like, "Oh, zeites already exist." Mhm. >> They weren't really convinced that the stuff that um >> Robson was doing was going to work

1:37:46because it was so rickety, right? It was 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. The porest crystal that he made and that's um Kitagawa on the right. The porest 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. >> Okay. So, so now this is something that zeolytes can't do. >> Right. >> Right. The natural occuring occurring mineral are extremely rigid. Right.

1:38:27>> 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. Yeah. Yes. Yes. I know exactly what I mean. Yes. >> 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. >> Ah this and and again the the the dynamic structural behavior is the key difference here to the naturally occurring >> to the naturally occurring. Yeah. Yeah. And so this was this was this was the first clue that it was like new chemistry, >> right? That there's something fun there

1:39:07was a more fundamental understanding that could be gleaned from continuing to go down this thought. >> Yes. Yeah. And and creating like way new material that you definitely can't find >> which so the the material science implication became more obvious. >> Mhm. Yeah. >> Fascinating. >> Pretty cool. And in parallel, we've got Omar Yagi. >> Yes. >> Okay. Omar Yagi has an incredible life story. >> We which we talked about a bit on Sunday. >> Yeah. It's uh he um he was a Palestinian refugee in Jordan. Okay. >> 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

1:39:50higher studies. got his PhD at University of Illinois or Bana Champagne and then he started really getting into um these metal organic frameworks. Okay, he was like this this could be something, right? He got really interested in that and at Arizona State University that was his first um faculty appointment. That's when he publishes this 2D molecule that can hold stuff >> and it can remain stable up to 350° C. >> Oh wow. you can heat this thing up and it can still hold its stuff >> and and not get completely degraded. He published that in nature. Okay, so this was the first sort of big >> big thing, right? He starts he starts making a name for himself

1:40:31>> and um in 1999 he publishes the big one. >> Okay, this is the big 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 Ivory Chemistry Department. Okay. Okay. This is called MOF5, metal organic framework 5. It's got a zinc at its center, >> then oxygen molecules in a in a par in a pyramid. Okay? That creates a little pyramid. >> You attach four of those pyramids together with carbons on the end, right? And you get the

1:41:12middle thing which is uh four pyramids together to create one giant sort of diamond type thing. >> Yes. >> With carbons at the end. >> 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 MOF5 um molecule. Okay. And this thing was insane. This thing was like 3,000 m squared of surface area per gram. That's the thing I was when we were talking about on our predictions, right? It's a single gram of this substance is going to have enough surface area

1:41:53>> for of like a football field or like several football fields, right? It can absorb a lot more than zeolyte can because of that because of that thing. And also >> it's again stable until 300°, right? So it's it's resilient. >> Yes. >> It's pretty simple to make. >> Yes. >> And it's >> you know hugely functional, right? 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 lises, right? It was Yagi and Kitagawa together that sort of figured this this

1:42:35whole thing out. And Yagi went even further. 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 molecules, between those carbon >> they're 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. 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.

1:43:15>> Yes. And what you can do is you can have customizable size of the pore. >> Yes. >> By by saying, okay, I have three carbon rings, 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, >> do you see that? 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. >> Yeah. >> Uh in order to get to the again the outcome that you're looking for. >> Yes. Exactly. >> Fascinating. >> 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

1:43:57papers that won the Nobel Prize. Got it. Okay. It's the It's the papers from um Robson, Kitagawa, and finally the nature and science papers. >> 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 that's usable. >> Yeah. Yeah. Yeah. It's it becomes totally customizable now. Right. Now you literally have >> it's programmable. >> Yeah. Link like things >> you can engineer properly. >> You can engineer completely properly. Okay. And um so he started out at University of Arizona. >> Yes. >> And then he moved actually to UCLA. Yes. In 2012 because by this point

1:44:38>> I think everyone knew he was going to win. >> Yeah. Right. Right. Right. Right. >> The Nobel. Okay. So So now institutions are like >> Berkeley. >> No, no, no. First he moved to UCLA. >> First he moved to UCLA. Um actually no, you're right. So I I got the year wrong. I think it was 2005 or six when he moved to UCLA. Okay. >> That's how he got to California. >> Yeah. And then and then that's how we got to California. And then he was he was in the chemistry department at UCLA. And then in 2012, Berkeley was like offered him a you know an offer in campus because Berkeley was like was like okay he's definitely winning by now >> and and and we want we want that plus one%. >> Um so so he moved to um Berkeley in 2012. He became the director of the

1:45:20molecular foundry at the Lawrence Berkeley National Lab, co-director of the Cavi Energy Nanosciences Institute and just in 2025, earlier this year, he became the a university professor, which is the top honor in the University of California reserved for like the highest >> um distinction. So, so he he was working his way up to like everyone sort of that's that's why it was like kind of easy to predict >> predict that it was going to be him because the signals were there. the signals were all there and um but you know UCLA first poached him and then Berkeley poached it from >> UCL that's ours >> like you said the little brother of Berkeley in this context >> exactly yeah so so I was like okay now I'm going to keep that one um and yeah

1:46:00now 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 um metal organic frameworks we're just going to 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. >> Okay. >> Okay. The one in the middle, that's that can be used to um catalyze the decomposition of crude oil. >> Oh, very interesting. >> Right. Which is which is very nice for like environmental people. Um on the right, that's something that can absorb um PFAS, which is perluo alkal. It's one of these like forever chemicals. The EPA always talks about it like they never

1:46:40degrade. get into our bodies, get into the environment. Um, that's something that can absorb those forever chemicals from water. So, and so the one of the the ideas here is that we can begin to create these chemical compounds that we can then use for things like, you know, uh, controlling emissions issues, dealing with uh Oh, beautiful. Yes. >> Yeah, you're you're exactly right. Um, the the one on the left, that's for mining rare earth metals from wastewater. >> Oh, okay. Yeah. Right. Cuz like waste, industrial waste is going to have a bunch of metals. >> Yes. >> You don't want it to go into the >> That's a hu that's a huge application. That's an unbelievable application. >> Right. And then in the middle, that's to absorb CO2.

1:47:20>> There you go. >> There you go. That's what you were talking about. >> Yep. >> And then on the right, that one's actually my my favorite. Um that one can store and release hydrogen at normal pressure. >> Oh, really? >> Okay. At at So you don't need a tank of compressed hydrogen. That's really >> and that's huge because compressed hydrogen is how you get the Hindenburg in your car, >> right? And like everything explodes. So, nobody wants hydrogen fuel cells. Well, now with this kind of stuff, you can get hydrogen fuel cells. >> I can understand why this won the Nobel, >> right? Yeah. And and what you what you saw there is like all of these things have like pretty similar, you know, the the you can see that they're the same

1:48:02chemistry. Yes. You know what I mean? >> Yeah. Yeah. Yeah. They have the share they share sort of a similar substrate of structure. >> Yeah. Yeah. Yeah. It's 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 the holes can be can be giant in the world of atoms, these things are giant, right? You can do nanometers, tens of nanometers. >> This is interesting because it's it's kind of similar conceptually to yesterday's prize in physics around this idea of scaling up to larger sizes uh with the quantum tunneling. uh but in this case with metal organic frameworks. >> 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

1:48:42got AI going to they have a chat they have a chat. >> Really? >> Yeah. A chat metal organic framework. You like chat with it and then it'll like generate like it's like I want I want a you know chemical compound that does this and then it'll like spit out like oh you should try these things. chat. Yeah, they got they have a generative framework there um for like you know generative AI can make photos while it can also if you train it on the chemistry 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

1:49:22came up with like 15 molecules in six months again just accelerating this process right >> yes yes yes >> pretty cool this is what we talk about a lot which is again a lot of generative AI conversation etc 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 crisper we have it for there's also things like alphafold uh where LIGO >> oh that wasn't generative but still still AI sort of uh assisting and accelerating the process of research and discovery and it has like real world implications Yeah. >> Um in terms of us getting to these things quickly with fewer human capital

1:50:04resources with less uh financial capital resources. >> Yeah. It's also like a democratization process 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. >> Yes. can I do it with? And the chat will be like, yeah, actually just make this, this, this, and this, and and then put it in this way. >> It's so crazy. I I think there's this conversation happening uh CEO of OpenAI, Sam Alman, 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 and there's usually two sides of where people are like,

1:50:45we're nowhere close. Other 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 for some people's defined as like being able to have novel insight. >> Um and there are a couple now cases in these again research contexts where the models are actually having novel insights that are working um and not just working like working 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

1:51:25generate novel insights even at small scales. There's that's hugely huge. That's hugely important. >> Yeah. That's going to be crazy. >> Fascinating. >> Yeah. Well, and that was the that that was the chemistry prize. >> So, so and and I think there's >> there's so many implications for this more broadly moving forward. >> Yeah, dude. It's it's it's going to be yeah >> it's going to be very cool. >> I want to take a moment. So we've talked about this is our day three of >> the last >> Nobel Prize week. Uh so many of you thousands of you have sort of joined us for this journey. It's been an incredible week. 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

1:52:06about the winners. >> All right. >> Right. We're going to break this down in sort of two two categories, institutions and countries. This is like our ESPN top 10. Um, so on the institution side, we had some some unsurprising uh number one winner. So at the top with uh four Nobels is uh Berkeley, >> three for physics, one for chemistry. Kyoto had two. Uh UCSB unexpectedly for me, two, UCLA won. Princeton got on the board. >> We got on the board. >> We got on the board with one. Yale with one. Uh Princeton we're printing before Yale cuz we came first. Um and then we have a University of Illinois or Brana Cherain with one Oxford, Melbourne,

1:52:46Cambridge and Paris University all with a single Nobel. >> Yeah. >> And if we look at it by country, >> number one, >> big old America, >> USA baby, >> six universities in the US, uh two from the UK, >> Mhm. >> one from Japan, one from France, and one from Australia. >> Yeah. >> So great representation. Yep. >> The UC system run ran the board. ran the board, dude. California, baby. >> California is is continues to lead in sort of fundamental research. >> Yeah. >> And this was the public institutions in California, right? Not not the >> I guess Stanford and Caltech didn't didn't show up this year. >> Maybe maybe next year, guys. >> Maybe next year. >> Neither did MIT or Harvard,

1:53:27>> but Princeton's there. >> Princeton's there. Oh, goodness. Um, again, another just great episode. We talked about metal organic frameworks, a branch of reticular 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. Um, but just an unbelievable. We'll definitely do this next year again. >> Oh, yeah. >> Uh, we'll probably have a little bit more more going. We'll maybe get the Nobel uh society to uh help us get some inside access. >> Yeah. >> Um, I'm Lester Nar, your host, joined as always by my co-host and our resident PhD, Krishna Chowy. Thank you all again for joining us for Nobel Prize Week. It's been an incredible week. We will see you all next week.

1:54:10[Music] >> Nice. All right. [Music]