From Princeton to the Nobel Prizes — How FFP Started + 2025 Nobel Recap (EP. 12)

After a packed week of Nobel Prize coverage, Lester and Krishna look back on how From First Principles began and why they built it as an “ESPN for Science.” They revisit 2025’s Medicine, Physics and Chemistry winners and discuss why fundamental research and immigration policy are core to America’s scientific edge. Quick note: this week’s episode is in vertical format because of a technical hiccup during recording — back to widescreen next week! Summary Origin Story — Two Princeton friends from different continents unite around a shared love of science and storytelling. The Mission — Creating an “ESPN for Science” that celebrates research and the people behind it. Nobel Follow-ups — Medicine (Tregs and non-immune roles), Physics (macroscopic quantum tunneling and quantum supremacy), Chemistry (MOFs and industrial scaling). Funding + Immigration — Why public research grants and curating global talent are vital to scientific leadership. Show Notes Nobel Prize Press Release (2025 Medicine) Nobel Prize Press Release (2025 Physics) Nobel Prize Press Release (2025 Chemistry) Nature Genetics (2001) — FOXP3 Mutation Causes Dysregulation Nature (1999) — MOF-5 Discovery (Omar Yaghi et al.) Google Quantum AI Lab — Quantum Supremacy (Nature, 2019)

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

• 0:00Lester Nare?

  Konichi waguan, internet. This is your captain speaking, Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary. This is from First Principles, also known as FFP Pod. We are joining you here in our post Nobel Prize week episode. Unbelievable week, super interesting.

• 0:21Krishna Choudhary?

  Amazing.

• 0:21Lester Nare?

  We did three days in a row. We put out the full episode. The engagement has been unbelievable. Clearly, people liked our sort of ESPN-style coverage.

• 0:32Krishna Choudhary?

  Waking up at, waking up at 2:30 was worth it.

• 0:36Lester Nare?

  Super interesting stuff. We're gonna do a follow-up this episode. But before we start, one of the questions that kept coming up in a lot of the comments as more and more people started watching the show was, who are you guys? Which is a fair question, given we just started the podcast.

• 0:52Krishna Choudhary?

  Yeah.

• 0:52Lester Nare?

  Our first episode was July 31st of 2025.

• 0:55Krishna Choudhary?

  Yep.

• 0:56Lester Nare?

  So we're only a couple of months in.

• 0:57Krishna Choudhary?

  Yep.

• 0:58Lester Nare?

  And we thought it would be a good time to kind of talk about our origin story, which is not dissimilar from any other podcasts. But it all starts at one place we talk about a lot on the podcast, which is Princeton. We both sort of were at Princeton at the same time, became best friends. And at that time, you were in one of the most illustrious programs on the planet.

• 1:21Krishna Choudhary?

  Yeah.

• 1:22Lester Nare?

  In the Princeton Physics Program.

• 1:23Krishna Choudhary?

  Yes. And boy, that was a doozy, wasn't it?

• 1:26Lester Nare?

  So we, we met sophomore year.

• 1:29Krishna Choudhary?

  Yeah.

• 1:29Lester Nare?

  Which was 2011. So we've been friends for about 14 years now.

• 1:32Krishna Choudhary?

  Yeah.

• 1:33Lester Nare?

  Our wives are very close at this point, which is another interesting variable. But at the time, you know, I played soccer and I was moving from economics to Program 2, which was Shirley Tillman's pet project for creating a arts program at the school.

• 1:50Krishna Choudhary?

  Right.

• 1:51Lester Nare?

  And you were busy doing the hard sciences.

• 1:53Krishna Choudhary?

  Yeah, I was pretty set on physics right when I got there.

• 1:56Lester Nare?

  I remember asking you one day, oh, like, you know, physics, like, was that hard? And you were like, mate.

• 2:02Krishna Choudhary?

  Mate, you have no idea.

• 2:06Krishna Choudhary?

  Programs started with like twenty, two hundred freshmen being like, I'm gonna be a physics major. And then slowly, it just ended up being like the twenty of us being like, bro.

• 2:17Krishna Choudhary?

  This is ridiculous.

• 2:19Lester Nare?

  So we have a long friendship and a long history. And a lot of the times, even back in the day, you know, I would always come to you about, you know, one of the interesting overlaps in both of our lives is that we both come from immigrant families.

• 2:32Krishna Choudhary?

  Yes.

• 2:33Lester Nare?

  Indian and Zimbabwean, both of whom have two parents that are heavily involved in the sciences.

• 2:39Krishna Choudhary?

  That's right. Yeah.

• 2:40Lester Nare?

  Between the two of us, we have three PhD parents.

• 2:42Krishna Choudhary?

  Yeah.

• 2:43Lester Nare?

  We have physics, botany, parasitology, and clinical trials as the sort of verticals that our parents work in. And so I think part of the initial, like, substance of why this show works is we both grew up in science-based households.

• 2:59Krishna Choudhary?

  Yeah.

• 3:00Lester Nare?

  That were very academic focused.

• 3:03Krishna Choudhary?

  Yeah.

• 3:03Lester Nare?

  In terms of us.

• 3:05Krishna Choudhary?

  Exactly. And like, the stories that I would hear growing up about, like, the heroes.

• 3:10Lester Nare?

  Right.

• 3:10Krishna Choudhary?

  Would, for me, would be like scientists.

• 3:12Lester Nare?

  Hundred percent.

• 3:13Krishna Choudhary?

  You know, my dad would tell me stories about Feynman and Einstein and Chandrasekhar, you know, and so instead of sports, we got, I got at least a lot of just science heroes to look up to.

• 3:27Lester Nare?

  I mean, it's very similar in Zim culture, where, you know, your path out, a lot of times, people don't know a lot about Zimbabwe. The number one thing most people know about Zimbabwe is we had a trillion dollar note because of hyperinflation.

• 3:38Krishna Choudhary?

  Yeah.

• 3:39Lester Nare?

  In like, the two thousand, two thousand or two thousand and one. But one thing that's not well-known is we have an incredible academic infrastructure in the country. And when you grow up, you're built to be in the sciences.

• 3:53Krishna Choudhary?

  Yeah.

• 3:54Lester Nare?

  Be a doctor, be in mathematics. Because that was your way to sort of salve, that was your way out.

• 3:59Krishna Choudhary?

  Yeah, yeah.

• 3:59Lester Nare?

  Of poverty.

• 4:00Krishna Choudhary?

  Yeah.

• 4:00Lester Nare?

  And I.

• 4:01Krishna Choudhary?

  Same in India.

• 4:01Lester Nare?

  I was gonna say, it's very similar.

• 4:03Krishna Choudhary?

  Education was your lottery ticket.

• 4:05Lester Nare?

  Exactly.

• 4:06Krishna Choudhary?

  Yeah.

• 4:06Lester Nare?

  And so we have sort of shared background, both family and college-wise. You know, there's an LA connection as well.

• 4:14Krishna Choudhary?

  That's right.

• 4:15Lester Nare?

  You born here, me moving here after college.

• 4:17Krishna Choudhary?

  I wasn't born here.

• 4:18Lester Nare?

  Not born?

• 4:19Krishna Choudhary?

  Yeah. I was born in India, but I did grow up. This is the most I've grown up in. This is the place that I've most grown up in.

• 4:25Lester Nare?

  Most, the most normal home.

• 4:27Krishna Choudhary?

  Yeah.

• 4:28Lester Nare?

  And what's interesting is I remember when I was trying to decide.

• 4:32Lester Nare?

  Between New York, San Francisco and LA, which is the classic three choices that you have.

• 4:37Krishna Choudhary?

  Yeah.

• 4:38Lester Nare?

  After school.

• 4:38Krishna Choudhary?

  Yeah.

• 4:39Lester Nare?

  I really wanted to come to LA and you were so, you were just like, yeah, mate.

• 4:46Krishna Choudhary?

  Yeah. LA is the place.

• 4:48Lester Nare?

  LA is the best. We both ended up back here.

• 4:50Krishna Choudhary?

  Yeah.

• 4:52Lester Nare?

  A little bit of different paths. I went straight to the private sector. I've worked in sort of entertainment and tech for the last 10 years, which is kind of where I've acquired a lot of the equipment that it now enables this podcast. It's been sort of 10 years of working in influencer, marketing and gaming and, and now running a tech company. You stayed in academia.

• 5:14Krishna Choudhary?

  Yeah.

• 5:14Lester Nare?

  For a little bit.

• 5:15Krishna Choudhary?

  Yeah. Went to UCLA for graduate school, got my PhD there. Ended up first at, in the physics department, of course, and you know, at Princeton, I got really interested in the emerging field of biological physics, which is the idea of

• 5:34Krishna Choudhary?

  trying to figure out how life even like exists in a, in a world where physics is king.

• 5:41Lester Nare?

  Right.

• 5:42Krishna Choudhary?

  In a world where, um, where the second law of thermodynamics is an axiom, where everything needs to go to soup and everything needs, entropy needs to increase and everything needs to be uniform and at equilibrium. We are clearly like highly non-equilibrium beings that are just creating podcasts and not just us, but like plants, bacteria, all of these little things are hacking physics at a fundamental level to stay alive. And that was always so fascinating to me that, you know, in a world where the second law of thermodynamics is an axiom, you can have so much stuff that is just like visibly breaking that rule somehow, but it's not. You know, it's definitely not breaking the rule, but it's very clever.

• 6:27Lester Nare?

  How?

• 6:27Krishna Choudhary?

  In how it circumnavigates that rule, you know? And I, I thought that was awesome. So at Princeton, I did some research in like theoretical physics of DNA confinement, like polymer physics, how DNA bends and curves and stuff like that. And protein aggregation and stuff like Alzheimer's where these mi load proteins like aggregate and then neurons. So what are the statistics of that? And then finally for my senior thesis, I did a little bit on, um, this thing called the omitted stimulus response, which is. A way in which the retina in your eye literally acts like a little microcircuit controller that sends compressed data to your brain in a very cool way. So that's where I got really into neural computation.

• 7:12Lester Nare?

  Right.

• 7:13Krishna Choudhary?

  Of like, how does a neural network that is biological and running at 300 Kelvin in this hot and soupy environment able to compute stuff? And so that's where I got into that. And then when I came to UCLA, I did my PhD in neuroscience and physics. But it was in the physics department and most of my, most of my scientific inquiry was physics based, although the experiments were biological because they had to do with like real, you know, neurons in real brains. But it was, it was a really cool synthesis of like the two fields. Got my PhD in physics at UCLA, did a postdoc, and now I'm working as a scientist in the private sector.

• 7:54Lester Nare?

  I think while you were, one of, some of your work, correct me if I'm wrong, while you were at UCLA, did get pub, some sort of press coverage.

• 8:03Krishna Choudhary?

  Oh, yeah, yeah.

• 8:03Lester Nare?

  As being pretty, pretty important.

• 8:05Krishna Choudhary?

  Yeah, yeah, that was, that was cool. I, my first, like first author paper came out in Nature Communications and a lot of the press really, really took it up. You know, as the press do, there are some things I was like, that's not quite right. But hey, I'm happy you're, you're talking about it. Yeah. It got some international coverage too. That was really cool. There was like a, a news article in Iran. There's a news article in Japan. So that was, it was pretty cool to see like, you know, people responding to my work.

• 8:34Lester Nare?

  So how do we get from this soup of backgrounds to deciding to do a

• 8:39Krishna Choudhary?

  To this.

• 8:40Lester Nare?

  To deciding to do a science podcast? It's not our first rodeo. You know, in my work, I've previously done solo podcasts that were more focused in the tech space, given that I have a production background. Again, all the technical implementation of lights, cameras, switchers, editing, distribution. That was kind of the learning curve there. Around COVID, we had actually, you know, one of the things I'd always pushed on was even early on back when we were at Princeton, I was like, I, I think, I think you have the gift of gab around science communication that. Has potential, you know, and we tried it with the Dark Matters Podcast

• 9:25Lester Nare?

  right around when COVID started. And I think in part, the inspiration was the clear lack of like, sort of, the public health communication during that time period was maybe, let's say, lacking. Yeah, severely. And there was not really an understanding of the basics around a lot of the things related to vaccines, the immune system. We'll actually touch on the immune system in this episode a little bit. And so a little bit of the inspiration to try it then was that it just didn't work at the time for a number of reasons. Then we tried again earlier, like last year, you doing a solo, me running production. And, you know, it just, there wasn't the Yeah, the magic dust.

• 10:06Lester Nare?

  The magic dust wasn't there. And then I finally decided, let me come out from behind the camera. I had actually done a little bit of a UAP, unidentified anomalous phenomenon, content creation and podcasts over the last two years. Yeah. And in that process, you set up this The studio as a part of that and found success there and kind of figured out, I think, the way in which we need to structure a show. So I came back and was like, let's try again. Yeah, let's do it. And that's how we got to where we are today with From First Principles. And so just a little bit of background on, you know, where we're coming from. And ultimately, we've built this show with sort of two component ideas.

• 10:47Lester Nare?

  One is it's meant to be a love letter to the scientific community, academics, researchers, especially who give us the incredible life we have today where every device, every convenience that we take for granted is the result of some researcher toiling away years ago. Yeah. And ultimately that getting into industrial production and then into end consumer products. And I think the the second reason, and this is more of my reason, is when I look around and I'm looking for content to consume, I'm like, why is there not an ESPN for science? Like, why isn't there something that is doing the same kind of analysis and promotion and hyping around the thing that makes all of our lives so much better?

• 11:31Krishna Choudhary?

  Yeah.

• 11:32Lester Nare?

  And so this combination of love letter to the scientific community and building the ESPN for science is a lot of the like thesis and theory of the case for for why we've built the pod. And with all of that being said, one other question that came up was, how did you guys get sponsored by a beverage company? If you're if you're so new, so many of you probably have seen, the show is presented by Standard Model Beverages, which has been conveniently placed, for those who are listening, if you watch on the video, it's always in the podcast as the drink of choice.

• 12:08Krishna Choudhary?

  That's right.

• 12:08Lester Nare?

  And what is the what is the history behind Standard Model Beverages?

• 12:12Krishna Choudhary?

  So Standard Model Beverages also has a history in science. It was started by me and a friend of mine, Cameron Bravo. He was a PhD friend from UCLA. He worked in particle physics at CERN, experimental particle physics, and he got really good at making drinks.

• 12:31Lester Nare?

  Oh, my God. I remember the bachelor party was, it was incredible. The brew he made was incredible. I remember talking to him, like, are you gonna do something with this?

• 12:38Krishna Choudhary?

  Yeah, exactly. At the bachelor party was when we started thinking like, hey, maybe we could like do this. And then after my wedding, he brought more beer, and then it was a hit there. And then we were like, you know, let's just, let's make a, let's make a science centric company, a beverage company that celebrates science and scientists and the experimental method of how we create these things. Because he's, he's a man of science as well, and he uses the scientific method to get the best sort of ingredients and the best flavors. And so we called it the Standard Model Beverage Company, after the standard model of particle physics, which we're huge fans of, and maybe we'll get into in some of the later episodes. It's, right now, we make non-alcoholic soda from agave sugars.

• 13:23Krishna Choudhary?

  And on the back of every can, you'll find a featured scientist that you can learn about. So this one has Galileo Galilei, it'll tell you all about his life and the science that he's known for. Other cans have other scientists. So it's really, again, just as this show is a love letter to scientists and science, this drinks company is a love letter to science and scientists. Even you can go on our website and learn about the quantum mechanics behind our logo, which is a visual depiction of the Dirac equation, which is the equation for an electron or any relativistic particle. And it gives you a prediction of matter and antimatter, the antimatter being the hole in a sea.

• 14:04Krishna Choudhary?

  Again, something that we can go into in later episodes, because that's one of the greatest achievements of theoretical physics is to literally predict antimatter based on the fact that a square root can be positive and negative. Right? And that's what, that's what sort of, so all of our artwork, all of our branding is around this love for science. And check us out, our website should be on the links.

• 14:29Krishna Choudhary?

  We're working towards our alcohol license from the ABC office of California, and pretty soon we'll, we'll be offering more.

• 14:36Lester Nare?

  And I think what's so funny is if you listen to this podcast, you'll be one of the few people that understands the secret of the logo that goes on the front of the can.

• 14:43Krishna Choudhary?

  Exactly, yeah.

• 14:43Lester Nare?

  And shout out to Snapple Facts, which if you grew up in the 90s and drank Snapples. You turned the cap and there's a little fun fact on the underneath, and that was a little bit of inspiration for featuring a scientist on every can.

• 14:58Krishna Choudhary?

  Yeah.

• 14:58Lester Nare?

  And so with all of that procedural nonsense out of the way, we can get back to regularly scheduled programming. Also, not industry plants, by the way. We're not industry plants.

• 15:10Krishna Choudhary?

  Yeah, yeah, yeah.

• 15:11Lester Nare?

  That would make my finances a lot easier to manage.

• 15:13Krishna Choudhary?

  Yeah, yeah, this is all self-funded.

• 15:15Lester Nare?

  It's, it's, it's just.

• 15:17Krishna Choudhary?

  It's just the two of us. We don't have like a team.

• 15:19Lester Nare?

  There's no production crew. Everything is done, processed, edited, produced, output, just by the two of us. So all the support that you guys give us is really, really meaningful.

• 15:28Krishna Choudhary?

  Yeah.

• 15:29Lester Nare?

  As we try to again, grow this into a network and again, build that ESPN for science, which in the times we live in today is more important than ever.

• 15:38Krishna Choudhary?

  Yeah.

• 15:39Lester Nare?

  And with that, we will now pivot into. Our quick Nobel recap.

• 15:45Krishna Choudhary?

  Yeah.

• 15:45Lester Nare?

  Uh, so we, last week, we did coverage of all of the three science Nobels. Chemistry, uh, medicine, chemistry and physics.

• 15:53Krishna Choudhary?

  Yep.

• 15:53Lester Nare?

  And we want to do a quick follow up on a couple of the discoveries, starting with the medicine follow up on non-immune roles in regulatory T cells, uh, or T regs.

• 16:04Krishna Choudhary?

  Yeah.

• 16:04Lester Nare?

  And so we'll start with that quick recap now.

• 16:06Krishna Choudhary?

  Yeah, it's, um, you know, the, the 2025 Nobel Prize was given to three individuals, Shimon Shaka-Guchi, Fred Ramsdell and Mary Brunkow. Um, Shimon Shaka-Guchi was at the University of Osaka in Japan and Fred Ramsdell and Mary Brunkow were, um, two individuals at private research companies in Washington in America. They were given for basically discovering T regs, which are regulatory T cells. This is the, it, it's a cartoon that the Nobel Prize committee came up with. It's got, uh, alien, I guess, inside of a police ship. And the police ship is the T reg, which is the T cell that is a regulatory T cell.

• 16:51Krishna Choudhary?

  And inside the alien has a cap on and the cap says Fox P3 because the Fox P3 is the gene that sort of creates and regulates the T reg itself and, and, and makes the T reg different from all the other T cells in our body. Um, and just as a quick review for what these T regs do, right? Their basic role is to act as the police of the police. The police being our greater immune system that targets viruses, targets antigens, targets other human cells that have been affected by a virus or an antigen and are now falling apart.

• 17:33Krishna Choudhary?

  So T cells are normally involved with identifying those guys and then gearing them up for.

• 17:42Krishna Choudhary?

  Greater immune like therapy, greater immune attack from macrophages, from all these other kinds of things that come in. And once the T cell has identified that bad cell, the other guys come in and sort of take care of business, right? But every once in a while, the T cell is gonna, is gonna identify one of your own as a bad cell, because all it is, is a lock and key method. And sometimes the locks and the keys don't work like they're supposed to. And so what these regulatory T cells do is they inhibit that immune response, right? And that's what these three individuals showed. Shaka Gucci was the guy who found T regs and showed that they were completely different from normal T reg, T reg cells, I mean, from normal T cells. And then Fred Ramsdell and Mary Brunkow found the Fox P3 genome

• 18:27Krishna Choudhary?

  that actually makes these T regs what they are.

• 18:31Lester Nare?

  So it was both the discovery of the function of this special class of T cells, in addition to understanding how they are actually created.

• 18:40Krishna Choudhary?

  At a genomic level.

• 18:41Lester Nare?

  At a genomic level. It's both, both aspects.

• 18:43Krishna Choudhary?

  Yeah. And, and that's why there were, there were three that got the Nobel Prize, right? But since then, it's been, you know, 40 years of research, since this, all, all of this has been happening. And now we figured out that T regs aren't just about controlling immunity, right? They can also directly influence non-immune tissue function in, in a way that previously we hadn't really seen immune cells do. Okay. So one of the things in, in today's topic, there's so many different ways that T regs are doing this, where they're doing this non-immune function. But the thing that we'll focus on today was discovered in 2013. And it shows that T regs are really involved in muscle repair and regeneration. We've got

• 19:28Krishna Choudhary?

  a, that's the, that's the paper that came out of Harvard Medical School by Burzine and others in Nature Medicine in 2013. They're the ones who found a population of T regs in damaged muscle cell tissue that can actually promote repair of those muscles. Okay. And the way it works is in photo four, you go, these T regs, they actually sit in your muscles. So they're tissue resident. Instead of sort of circulating in the blood, a lot of times we think of immune cells as just circulating in the bloodstream, right? And they go and they find stuff to take care of. These are tissue resident T cells, T regs, that are found in our muscle

• 20:08Krishna Choudhary?

  tissue. And what they do is they modulate the action of stem cells. Stem cells are the cells that don't really have an identity yet, but they lead to progenitor cells that lead to some kind of tissue cell. So in this case, they would become muscle progenitor cells that would then become new muscle cells and repair and damage the tissue there. Does that make sense?

• 20:31Lester Nare?

  Yes.

• 20:31Krishna Choudhary?

  Yeah. And they, and these kinds of, of stem cells are found all over. They're found in our bone marrow, they're found in our muscles, they're found in our hair follicles. And that's actually the other thing that I wanted to highlight. That's kind of cool is another, this was pretty recent. Another way that these T cell, T regs are doing stuff that's outside of the immune system is they become onsite repair forman for like stem cells in our hair follicles. So they, they promote hair growth in our hair follicles by actually influencing the stem cells that are in there that are called hair follicle stem cells. And those stem cells promote the growth of hair in those hair follicles,

• 21:15Krishna Choudhary?

  right? So without the T regs actually like mediating that interaction, you're not going to get

• 21:22Lester Nare?

  Hair growth.

• 21:22Krishna Choudhary?

  Hair growth in those hair follicles.

• 21:24Lester Nare?

  So we can thank the cellular military police for our wonderful

• 21:28Krishna Choudhary?

  Yeah, they do a bunch of side jobs too.

• 21:31Lester Nare?

  Right.

• 21:31Krishna Choudhary?

  Where they're like just maintaining a lot of the tissue resident stem cells or doing whatever job that they're doing.

• 21:40Lester Nare?

  So they get deployed into local cities across your body to maintain order.

• 21:46Krishna Choudhary?

  Yeah, there it is. There it is. Don't listen. Let's not, let's not get too triggering. But in, this was, um, this was work that was done by UC Santa San Francisco, and this was a paper in Cell in 2023 that showed that T regs can actually help hair follicle regeneration. They use something called the notch signaling pathway, which is just another, it's, it's, it's one of these other lock and key signaling pathways where the T cell locks and keys into a stem cell and then the stem cell is like, oh, okay, I need to start doing whatever I need to do.

• 22:19Lester Nare?

  This is fascinating. So not only the Nobel discovery was around the like, the existence of this specific T cell type and its genomic origins.

• 22:29Krishna Choudhary?

  Yeah.

• 22:30Lester Nare?

  And then now, since those early discoveries, we've now begun to understand that these regulatory T cells, these T regs, have multiple functions.

• 22:41Krishna Choudhary?

  Yeah.

• 22:42Lester Nare?

  They're not just in the highway of the bloodstream.

• 22:44Krishna Choudhary?

  Yeah.

• 22:44Lester Nare?

  They can be in the tissue cells and actually facilitate other aspects, other processes that are independent of the immune response, which is its primary responsibility.

• 22:52Krishna Choudhary?

  Yeah, exactly. Yeah. And that's how they were discovered. But now it turns out they've got a much larger role in our body. Right? So it's, it really shows why something like that deserves the Nobel Prize, like discovering this whole new class that is actually doing so much more than than just an autoimmune response.

• 23:09Lester Nare?

  Sort of.

• 23:09Krishna Choudhary?

  Yeah, like curtailing the autoimmune response. Now it's doing all sorts of stuff.

• 23:13Lester Nare?

  The other thing that's interesting, and this goes back to kind of what you always talk about with biology as compared to physics where it's like the here, like, there's a lot of complexity still that we are continuing to better understand.

• 23:24Krishna Choudhary?

  Yeah.

• 23:25Lester Nare?

  In terms of biological systems.

• 23:27Krishna Choudhary?

  Yeah.

• 23:28Lester Nare?

  And there's complexity there.

• 23:31Krishna Choudhary?

  There's complexity at every level. It's insane. Biology is, is somehow this like hodgepodge stack of cards that is just like staying alive because everyone is, is making sure the cards don't, you know, fall, right? At every level, at the molecular level, at the cellular level, at the organism level, then you can go into like ecosystems and there's population dynamics. It's, it's an incredible like hierarchy of.

• 23:59Krishna Choudhary?

  Of being, it's very cool.

• 24:01Lester Nare?

  The combinatorial problem set there is

• 24:03Krishna Choudhary?

  Yeah, yeah.

• 24:04Lester Nare?

  Is, uh, one to behold.

• 24:05Krishna Choudhary?

  Yeah.

• 24:06Lester Nare?

  And, and so that was again, the, the medicine Nobel from last week. If you haven't watched last week's episodes, we have both individual stories for each of the individual awards, as well as a collective episode with all of them. So you can zoom in to the subject you care about, or zoom out and listen to them all. They're all fascinating. And then so day two, which was Tuesday,

• 24:28Krishna Choudhary?

  Yep.

• 24:28Lester Nare?

  Was, was physics.

• 24:30Krishna Choudhary?

  Mm hmm.

• 24:31Lester Nare?

  This one was for macroscopic quantum tunneling.

• 24:35Krishna Choudhary?

  Yep.

• 24:35Lester Nare?

  I, I will note, uh, you know, there was some commentary about the use of the word macroscopic.

• 24:42Krishna Choudhary?

  Yeah.

• 24:42Lester Nare?

  And understandably, in this context, it is macroscopic.

• 24:46Krishna Choudhary?

  Yeah.

• 24:46Lester Nare?

  But in our everyday lived life, when we say macroscopic, we don't mean laptop macroscopic.

• 24:52Krishna Choudhary?

  Yeah, yeah.

• 24:52Lester Nare?

  Um, it's still quite, quite small.

• 24:54Krishna Choudhary?

  This thing is still quite small, yes.

• 24:55Lester Nare?

  But it's still.

• 24:56Krishna Choudhary?

  It's at the nano-micro scale.

• 24:58Lester Nare?

  But it's still meaningfully different than where we were before.

• 25:01Krishna Choudhary?

  Yeah, it's still 10 to the nine, you know, one billion things, quantum tunneling. That's not a joke, right? Um, it was given to John Clark, Michelle Deveray and John Martinez for their discovery of macroscopic tun- quantum tunneling. It was a experiment that they had done in the 1980s at Berkeley. John Clark was the principal investigator at Berkeley. Uh, Michelle Deveray was a postdoc in his lab and John Martinez was a PhD student in his lab.

• 25:27Lester Nare?

  I will be remiss to say, we also call it Cal on this podcast.

• 25:32Krishna Choudhary?

  Yeah, but guys, Berkeley is fine.

• 25:35Lester Nare?

  But for the sake of the international audience, uh, we will refer to it as Berkeley.

• 25:39Krishna Choudhary?

  Yeah, yeah. We, I mean, in, I think in science, I've almost never heard it called Cal. Okay, I'm sorry. I've been around circles in, in science. It's called Berkeley, okay?

• 25:49Lester Nare?

  Go Bears in athletics.

• 25:51Krishna Choudhary?

  Yeah.

• 25:52Lester Nare?

  Cal, yes.

• 25:52Krishna Choudhary?

  Cal, yeah.

• 25:53Lester Nare?

  But in science, well, you know, we'll stay with Berkeley.

• 25:56Krishna Choudhary?

  I don't, I don't think anyone from Berkeley is pressed about it, honestly.

• 26:00Lester Nare?

  Okay, anyways.

• 26:00Krishna Choudhary?

  Let us know in the comments.

• 26:01Lester Nare?

  Yeah, let us know. Um, and in any case, like what they did was they showed that you could build and customize this kind of artificial atom in some sense, right? That, that even though it was 10 to the nine different things that were doing this quantum tunneling, all of them collectively are obeying the Schrodinger equation. And so one could use this as a substrate to simulate things.

• 26:26Krishna Choudhary?

  That do quantum mechanics, for example, atoms. And this is the central idea behind a quantum computer, right? It was actually first hypothesized by Richard Feynman, one of our favorite physicists, in a 1981 talk. The talk became a 1982 paper in the International Journal of Theoretical Physics. And the paper was titled "Simulating Physics With Quantum Systems," right? It's an incredible paper that's so forward-thinking, and it's something very much in the style of Feynman. He builds it from first principles. And he asks like, "Okay, what if I want to simulate a quantum system?" Right. Okay? What would that take? And here's the math that he does.

• 27:11Krishna Choudhary?

  He says, "Suppose I have an interacting system of N quantum particles, okay? And I want to simulate all of that. Can I do this with a classical computer?" Pretty soon, it gets way, way out of hand. Okay, and here's why. Consider just two quantum particles that can be in two states. Okay? They can be in a 0 or a 1, right? In a classical computer, well, you would just have one thing be the first state and one thing be the second state. And then you can decide whether it's a 0 or a 1, and you have four bits, right? But you can just keep track of each of the bits. And as you grow the number of bits, like, it just grows linearly

• 27:54Krishna Choudhary?

  in terms of how much stuff you need to save. You need to store N bits, that's N different transistors that are storing a 0 or a 1. If you want to start doing quantum systems now, combinatorically, it goes insane, right? Because just, let's imagine two quantum systems, right? Like, two electrons that are spin up or spin down. You actually have to keep track of four different complex numbers. Okay, each complex number is actually two numbers. One, how much of the numbers on the real axis? How much of the numbers on the imaginary axis? And what you have to do is you have to keep track of the spin up, spin down. You have to keep track of the spin down, spin down, and then spin up, spin down, spin down, spin up. Right?

• 28:38Krishna Choudhary?

  That's four different complex numbers that you gotta keep track of. So that's eight different things. With three, now I gotta keep track of all eight of these spin systems. Yes. Right? And with N, it becomes two to the N. Two to the N different numbers that I gotta keep track of to really fully characterize a quantum system. Because each of these, each of these individual spin states are themselves distinct. And so I need a number for each of these distinct spin states. And so pretty much what ends up happening is if you, if you scale with the number of bits, the amount of stuff that you can store in a classical computer becomes linear. But the amount of stuff you can store in a quantum computer becomes exponential. Right?

• 29:20Krishna Choudhary?

  Because a quantum computer by design is storing all of the little values for each of the superposition of these states. So it was a very simple, simple argument that Feynman made. And he did this back of the envelope calculation. He's like, well, if you need two to the N numbers to keep track of a quantum state that has N things, each of those things having two states, then you know, with, um, if you want just like 40 interacting particles with two states, that's two to the 40. And one real quick trick to convert two to the something into 10 to the something is to know that two to the 10 is 1024, which is about 10 to the 3. So two to the 40 becomes about 10 to the 12.

• 30:03Krishna Choudhary?

  That's a trillion, that's a trillion bits that you need in your RAM. Not in your hard disk.

• 30:09Lester Nare?

  Right, right.

• 30:09Krishna Choudhary?

  You need in your RAM because you're messing with all of those numbers, right? And in terms of computation, this isn't data that's being stored on a permanent basis.

• 30:19Lester Nare?

  Right.

• 30:19Krishna Choudhary?

  This is stuff in the middle of your computation that you're using to then calculate the new state and the new state and the new state. So that's a terabyte of stuff in your RAM, right? Which is already a lot.

• 30:29Lester Nare?

  It's already a lot.

• 30:29Krishna Choudhary?

  A terabyte of RAM is quite a bit.

• 30:31Lester Nare?

  I wish I had a terabyte of RAM on the computer. We'd have to render the episodes.

• 30:34Krishna Choudhary?

  Yeah, yeah. It would be, it would take, that's, that's reaching at the level of like, supercomputers. Right? But 40 different things is not really what we're even talking about. We're trying to do like 200, 200 or 400 qubits, right? Because in, in modern, like for a protein, for example, a protein will have like, on the order of 100 to 400 atoms, that many interacting quantum states, right? For each of the little configurations that the electrons can do. And already at like 2 to the 200, you're getting to 10 to the 66.

• 31:04Lester Nare?

  It's an insane number.

• 31:05Krishna Choudhary?

  Which is, which is an insane number because there's only about 10 to the 80 atoms in the universe, right? So like, what? Each atom in your universe is now, you know, like you can't make transistors.

• 31:15Lester Nare?

  Yeah, it's not feasible.

• 31:16Krishna Choudhary?

  It's not feasible anymore. So that was the main impetus and it was sort of introduced by Feynman in, in the 1980s to start thinking about what if, what if we wanted to do quantum simulations? We would really need a quantum computer.

• 31:32Lester Nare?

  Right.

• 31:32Krishna Choudhary?

  In order to do it.

• 31:33Lester Nare?

  Classical systems don't have basically the, the horsepower, the, to be able to sustain as you get to more complex.

• 31:42Krishna Choudhary?

  Yeah.

• 31:42Lester Nare?

  Systems.

• 31:43Krishna Choudhary?

  Exactly. And so we need, we need a computer that's made out of quantum bits, right? And this is where the superconducting circuits that won the Nobel Prize, they sort of became a leading platform because the, the superconducting circuit itself can now have these quantum behaviors. And so you can use that as your two-state system that encodes a 0 and a 1. And that's what sort of I want to get into is just a little bit of background. We can't cover all of it because that's going to be an episode in itself that maybe we can do. But I just wanted to give you a little bit of, a starter on why superconducting qubits became like this sort of. Ubiquitous method of making a quantum computer.

• 32:27Lester Nare?

  And this is the Josephson junction circuit.

• 32:29Krishna Choudhary?

  Yeah, yeah, this is this. Yeah, this is exactly the Josephson junction stuff that we talked about on the episode that became a qubit in itself.

• 32:37Lester Nare?

  So a good primer, if you haven't already watched our Nobel Prize episode on physics, would be to watch that because we go into very good detail from first principles about like, what is?

• 32:47Krishna Choudhary?

  Yeah, a Josephson junction.

• 32:48Lester Nare?

  Uh, which is important to understand, like, why this fundamentally is a workable solution to the problem.

• 32:55Krishna Choudhary?

  Exactly. Yeah. Yeah. But we'll, we'll give you a tiny primer here. Um, we'll start with just an LC circuit. Okay. An LC circuit is something that I think anyone who's taken an undergrad physics class, the second semester, you go into AC circuits, um, which is analog circuits. And an LC circuit is very simple. There's a capacitor and there's an inductor. A capacitor is a, is a configuration of metals, basically, that lets you store charge. And an inductor is like a coil of stuff that lets you create magnetic fields and you can charge it up and you can de-charge the magnetic field. It becomes, um, a little battery in some sense.

• 33:35Krishna Choudhary?

  Okay. And if you hook up a capacitor to an inductor and you charge up the capacitor and then you turn on the switch, what's going to end up happening is the, the capacitor is going to discharge because it's storing a bunch of charge, but then the circuit is going to be like, oh, there's a way for me to, for me, for the charge to rebalance. As it, as it rebalances, that's going to create a current in my loop. That current is going to turn on and then create a, a magnetic field in my inductor, which is going to become like a kind of battery that's going to reverse the circuit and the circuit is going to go the other way. And then it's going to go one way and then it's going to go the other way. And this charging and discharging of the capacitor and the charging and discharging of the inductor

• 34:17Krishna Choudhary?

  becomes a sort of simple harmonic oscillator. This is ubiquitous in physics. We love simple harmonic oscillators. Okay. Because everything is a pendulum in some sense, right? Everything is around some energy minima and you, and it oscillates as it goes from one part to the other part of that energy minima. And that's what an LC circuit becomes. It becomes a simple harmonic oscillator. Now, you take anything at the classical level, in this case, an LC circuit, which is a simple harmonic oscillator, and you cool it down. First of all, this circuit is going to become superconducting, meaning that there's going to be no resistance, which means this guy, this circuit is just going to keep going. There's no joule heating involved, and so it's not going to lose any energy.

• 35:02Krishna Choudhary?

  So this thing can keep going as an oscillation, right? And in, anyone who's taken first semester quantum mechanics usually goes through the Griffith's quantum mechanics textbook. And this is the cartoon they have. They show Schrodinger's cat going up and down a ladder. And all the ladders, the rungs of the ladders are equally spaced. And what this guy is doing is going up and down the energy states of a quantum harmonic oscillator. In a classical harmonic oscillator, you can, in a classical harmonic oscillator, my pendulum can be in any state, right? It can go up, and if I push the pendulum more, it'll have a higher amplitude. This is like you on a swing, right? You can have arbitrarily low amount of energy.

• 35:45Krishna Choudhary?

  You can just sit on the swing stationary with no swinging. Or you can have a little bit. If you push a little bit more, you can have a little bit more. In a quantum harmonic oscillator, though, quantum mechanics takes over, and there are discrete energy levels, where the quantum harmonic oscillator will have a certain frequency, or it'll have a little bit more frequency, or it'll have a little bit more frequency. And each of those frequencies of oscillation is tied to a energy, just by h bar omega, right? And the key with a quantum harmonic oscillator is the rungs of that ladder are equally spaced. Now, this is cool for a quantum harmonic oscillator. It becomes a problem if we want to make a quantum computer out of it.

• 36:28Krishna Choudhary?

  Because what we want are just two states. And we want to be able to reliably go between one state and the other. But imagine if the energy difference between 0 and 1 is the same as the energy difference between 1 and 2. When I'm poking it, and this thing is at the 1, it could go to 2. Right. We don't want that. Right. We want it to be... Fixed within 0 and 1. And so what we do is we add a Josephson junction to our superconducting circuit. And what that does is, so on the left, we've got a perfect parabola. That's our omega, omega x squared, which is a perfect parabola. That's our simple harmonic oscillator. Okay, that's like Hooke's law, you know, a spring and a mass on a spring.

• 37:13Krishna Choudhary?

  The energy of that thing is 1/2 k x squared. Similarly, if you have a parabola, then you get a perfect pendulum. That's what we don't want. So when we add a Josephson junction to our LC circuit, then what ends up happening is you add a cosine term to that parabola. And that cosine is very much like a parabola on, in the bottom, right? If you, if you zoom in close to its minima, it's going to be like a parabola. But it's going to add a little bit of wiggle on the outside. And that's what's called an anharmonicity, which means we've gone from a harmonic, simple harmonic oscillator to an anharmonic oscillator that has a tiny bit of a difference in that parabola. And what that does is now our ladders,

• 37:58Krishna Choudhary?

  it's still, it's still a ladder, but the rungs of the ladder are no longer equally spaced in energy. And so what I can do is now tune my poking, right? So that it only resonates to that 0, 1 transition. Right. And it doesn't resonate with anything else. Above. And so I can reliably now control whether it's in a 0 and a 1, and I can switch it from 0 to a 1. And that's where this Josephson junction comes in, okay? It adds that little cosine magic that turns my perfect quantum harmonic oscillator into, into something that I can manage as a two-state system. Which is, which is required in order to make a quantum computer operate in the way in which we needed to, to get like tangible versus like Yes. To have it operational.

• 38:41Krishna Choudhary?

  Yeah, we want a two-state system at all times for a quantum. We want to, I mean, we like bits, right? Yeah. And, and a lot of the, the simplest logic you can do is with a bit, a two-state system. This was first actually implemented at Tokyo by Nakamura and his colleagues in a Nature paper in 1999. And that's what sort of started the field of superconducting qubits. And it's come a long way, right? And now, one of the, one of the papers that I wanted to highlight was the big paper in 2019 by the Google team. John Martinez was involved in the hardware leadership.

• 39:17Krishna Choudhary?

  And they published in Nature in October 2019 with an experiment titled Quantum Supremacy, Using a Programmable Superconducting Processor. This was a very big deal. They're claiming quantum supremacy. Quantum supremacy is the idea that we have done something now with a quantum computer that cannot be done with a classical computer, no matter how long you wait. Okay? Not no matter how long. They said something like, um, the age of the, like a million years. Okay? Something crazy. And they were like, we did this in 200 seconds that would have taken a million years to do.

• 39:55Lester Nare?

  The point is, in a classical system, it would be so far beyond the life cycle of of humans, that it's irrelevant if it could do it in a million years.

• 40:04Krishna Choudhary?

  Yeah, yeah. It's like, it's something that we could not do. Okay?

• 40:10Krishna Choudhary?

  Now, what they did was, they designed a random quantum circuit sampling task. And this is where their claim met some scrutiny. Okay? Because the task that they're saying they did, that a classical computer couldn't do, was itself a quantum task, in some sense. So you're, maybe you're gearing the problem for the hardware that you have. And that's not completely out of precedent, but you can understand if their competitors were like, yeah, you know?

• 40:40Lester Nare?

  Doesn't count.

• 40:41Krishna Choudhary?

  Yeah, yeah, it doesn't count. But in any case, they said that this is like, you know, the, the burden of proof is, I've done something that a classical computer can't do. Right? Quantum simulation is another thing that Feynman came up with, that is obviously by design, something a classical computer can't do.

• 40:59Lester Nare?

  Yes.

• 40:59Krishna Choudhary?

  Right? So it's not, it's not that like weird for me. Um, they've got a 53 qubit computer, okay? 54 physical, physical qubits. That's, um, in a, in a sort of nice chessboard pattern. Each of the qubits talks to four of its neighbors, using a coupler. And it's all in a 2D grid. Their chip was called the Sincamore chip. It's

• 41:27Krishna Choudhary?

  54 physical qubits, tiny, tiny chip that's inside of a giant dilution refrigerator, like those chandelier stuffs that we were talking about. It's got to be cooled down to where these things can be superconducting and they can do all of those things. And their claim was that this quantum device could sample, i.e. could like produce these bit strings from a quantum distribution, from a probability distribution that was inherently quantum. And in 200 seconds, they could produce enough bit strings to totally characterize this probability distribution. Okay? And they estimated that a classical supercomputer, like this is a big supercomputer, would require 10,000 years to do the same. Okay?

• 42:08Krishna Choudhary?

  And they did some cross-entropy benchmarking to show like for smaller number of qubits that this would work and how that thing would scale. Okay? And so that was their main thing. They were like, look, we did this in 200 seconds. This would require 10,000 years on a supercomputer, a million years on a normal computer, like blah, blah, blah. Okay. It's, it's sort of outperforming these classical algorithms, right? IBM claps back because IBM is the other big competitor in the field of superconducting circuits. So shortly after the Google announcement, they published this blog post that, you know, eh, it's not, it's not that hard.

• 42:48Krishna Choudhary?

  Their first thing was like 10,000 years and they, they made a better classical simulation. They outlined a better way to do that classical simulation that would take 2.5 days, not 10,000 years.

• 43:03Lester Nare?

  So they kind of undercut, they were like, well...

• 43:05Krishna Choudhary?

  Yeah, yeah. It's like, it's like, well, you didn't use the latest sort of classical algorithm to benchmark how good your quantum computer was, you know? 2.5 days is still not 200 seconds, which is what Google did.

• 43:17Lester Nare?

  Right.

• 43:18Krishna Choudhary?

  But it's not, also not 10,000 years. So they were saying, you know, you shouldn't say quantum supremacy, you should say quantum advantage. At this point, yeah, it's like they're, I mean, they're, they're pressed because like this is a big deal still, right?

• 43:30Lester Nare?

  And if you think about just also just economically from the business context, IBM has been struggling to survive both in chips, in its, in its clientele base in terms of being dominated. They are being pressed by Google, by Nvidia, by AMD in all avenues of their business. So just from a purely...

• 43:52Krishna Choudhary?

  And they made a big push in the quantum... Place, you know?

• 43:55Lester Nare?

  And so they had to say something.

• 43:57Krishna Choudhary?

  Yeah, they had to. Yeah. And I mean, the other things that they did talk about is like, the paper itself is quite self-aggrandizing. Like, the 2019 paper in Nature says, "Quantum processors have thus reached the regime of quantum supremacy. We expect that their computational power will continue to grow at a double exponential rate." I mean, that's, that's, you know, that's, that's a lot. That's saying a lot that maybe you shouldn't say in a scientific paper, and maybe the press should say that, right? But so there's, there's still ongoing scrutiny. There's some papers that say that they've improved the quantum, the classical simulation algorithms to increase that, to decrease that gap even further.

• 44:39Krishna Choudhary?

  There's philosophical critiques about like, well, should, should we really say supremacy and all this other kind of stuff? So it's still an ongoing debate. And meanwhile, the, the field of quantum computing just like forges forward, you know, with these superconducting circuits. It's going to be very exciting.

• 44:55Lester Nare?

  I think the, the implications of, you know, stepping back from some of the corporate intransigence, the, the implications are that we now have computing systems that have a capability set to simulate massively complex concepts, environments, at a degree that we don't have the capability for in classical systems. And there are a variety of use cases that you can imagine. A lot of times people talk about, oh, it's going to break encryption because you can just, you know, brute force hack, blah, blah. That's like the low hanging fruit.

• 45:30Krishna Choudhary?

  Yeah, yeah.

• 45:31Lester Nare?

  Of implications, but you can imagine, you know, simulating biological systems.

• 45:35Krishna Choudhary?

  That's what I'm most excited about.

• 45:37Lester Nare?

  Right?

• 45:37Krishna Choudhary?

  Right? It's like, the, the breaking encryption is like, fine, I guess, from a national security point of view or whatever. But for me, it's like doing quantum simulation, the, the dream that Feynman had originally.

• 45:48Lester Nare?

  Right?

• 45:48Krishna Choudhary?

  Right? Of like, now, imagine you, you've got a new idea for a material. It's incredibly hard to simulate the physics of a material now because of this problem of exponential blow up. Well, now, what if we could just, you know, put in, we know where the positions of all the electrons are. We can create this molecular Hamiltonian that tells you how the physics of that molecule is going to work. And then we put that into a computer and we try to see things like, okay, what is the, what is the base energy? What is the conductivity of this thing? Imagine finding a room temperature superconductor by just hypothesizing all of the different materials that it could be, putting it into the quantum computer and having it tell us, hey, is this thing superconducting or not?

• 46:29Lester Nare?

  There's huge implications in material science and drug discovery, in personalized healthcare, like you can, it's hard, it's hard to like make a list.

• 46:40Krishna Choudhary?

  Yeah.

• 46:41Lester Nare?

  You know, it is, it is as fundamental as, you know, vacuum tubes giving us computing for the first time. It's as fundamental as the move to mobile, as the internet, it just in terms of, you can only, it's hard to even imagine.

• 46:54Krishna Choudhary?

  Yeah, all the things that we could do.

• 46:56Lester Nare?

  We could do with it because it's, it's sort of an infinite canvas of opportunity.

• 47:01Krishna Choudhary?

  Yeah.

• 47:02Lester Nare?

  I always find the quantum space so fascinating.

• 47:05Krishna Choudhary?

  Yeah. And then, I guess the last one we did was chemistry.

• 47:09Lester Nare?

  Yes, the last follow up was for, for chemistry. This was on metal organic frameworks and the, you know, it was our third day.

• 47:18Krishna Choudhary?

  Yeah.

• 47:19Lester Nare?

  Of waking up at 2:30 in the morning.

• 47:21Krishna Choudhary?

  Yeah.

• 47:22Lester Nare?

  But it was equally as interesting and it was one that I had the least amount of basis for understanding. I think someone made an interesting comment that was like, chemistry never gets the love that it deserves for how like important and crazy.

• 47:35Krishna Choudhary?

  Yeah.

• 47:36Lester Nare?

  The stuff we do and it is. So we're making sure that, shout out to all the chemists out there.

• 47:40Krishna Choudhary?

  Yeah.

• 47:41Lester Nare?

  That chemistry.

• 47:42Krishna Choudhary?

  Some of the most important sort of Nobel prizes have come in chemistry.

• 47:44Lester Nare?

  Chemistry. Right? We're going to make sure you guys get your just desserts here. And so, yes, so chemistry was our, our last prize that we covered last week.

• 47:52Krishna Choudhary?

  Yes, this was for metal organic frameworks. It was given to Susum Kitagawa at Kyoto, Richard Robson at Melbourne, and Omar Yagi at Berkeley. Omar Yagi is someone that I called.

• 48:03Lester Nare?

  Yes.

• 48:04Krishna Choudhary?

  I totally predicted that.

• 48:05Lester Nare?

  And next year, we're gonna do a more, a more crazy prediction show. We're gonna try to get some, some partnerships with, I don't know, maybe we'll do, what is it? Polymarket.

• 48:15Krishna Choudhary?

  Yeah.

• 48:15Lester Nare?

  Maybe we'll get Kalshi.

• 48:17Krishna Choudhary?

  Yeah.

• 48:18Lester Nare?

  One of the prediction markets out there.

• 48:19Krishna Choudhary?

  Yeah, that'll be hilarious. But Omar Yagi specifically, we're gonna focus on some of his follow-ups. He made MOF5, which was the really big deal. Metal Organic Framework, right? This thing had a single gram, had several football fields worth of surface area. And we got a lot of questions in the comments, actually, about like, what does that even mean? For a molecule to have surface area? And this was something that I sort of had an idea what they were talking about, but I wanted to dig deeper. So, you know, my, my initial inclination was that they're basically talking about how much area is available for interactions at a molecular level, right?

• 49:03Krishna Choudhary?

  When we think about adsorption of molecules, this is a 2D surface interacting with molecules and absorbing it and making it stick, right? Instead of absorption with a B, which is a 3D way of absorbing molecules. So at a 2D level, how much surface area is available for interaction with other chemistry? That's the idea. And the analogy you can use is like a parking garage, right? It's a single building, but it has an insane amount of surface area. It's packing like five or six parking lots into a single 3D structure. And so you can park a bunch of cars there, right? And in this case, we're calculating the surface area.

• 49:45Krishna Choudhary?

  We're using how much surface area is available, available for parking other chemical stuff. Okay? One of the ways that they do this to calculate the actual surface area is by using liquid nitrogen and nitrogen gas adsorption. So here, what they do is they, they, they take your sample and they, and they cool it down with liquid nitrogen so that it's super cold. And then they run nitrogen gas over it. And they see how much nitrogen gas is gone from the sample and gone into the sample.

• 50:20Krishna Choudhary?

  And from that, you get this curve where on the X axis, you vary the amount of nitrogen that you're putting in, that you're exposing that MOF to. And on the Y axis, you get, okay, how much nitrogen gas, volume wise, was absorbed by this, by this compound. And then you can fit something called the Brauner-Emett-Teller equation, the BET equation, which then calculates how much volume has been absorbed to create a mono layer, a single layer of, of N2 on this thing, right?

• 50:49Lester Nare?

  Which would be the equivalent of a single level of the parking garage?

• 50:52Krishna Choudhary?

  Yeah, exactly. It's like a single, it's the amount of stuff, exactly. And then, and then the more pressure you put in, the more molecules are going to get absorbed. And then from this, you can figure out, all right, what is the constant amount of surface area that is needed to show this dynamics of how much is being absorbed? And that's where you get in, get this, you know, 3,000 square meters per gram.

• 51:15Lester Nare?

  Per gram.

• 51:16Krishna Choudhary?

  Like several football fields per gram. It's because the amount of stuff that this one gram of thing is absorbing, the amount of nitrogen that this thing is absorbing, would be equivalent of if I had a football field of nitrogen absorbing area, and that's how much nitrogen was absorbed.

• 51:37Lester Nare?

  And so part of the idea here is like, you know, we've maximal, we've, we've engineered the space of the parking garage to be maximally efficient for the number of cars that can park.

• 51:49Krishna Choudhary?

  Yeah.

• 51:50Lester Nare?

  At any given level.

• 51:51Krishna Choudhary?

  Mm hmm.

• 51:52Lester Nare?

  At any given time.

• 51:53Krishna Choudhary?

  Yeah.

• 51:54Lester Nare?

  So you can imagine a parking garage with double wide spaces.

• 51:55Krishna Choudhary?

  Yeah.

• 51:56Lester Nare?

  And we've created the minimal amount of space.

• 51:59Krishna Choudhary?

  Yeah.

• 52:00Lester Nare?

  For any individual molecule.

• 52:01Krishna Choudhary?

  Mm hmm.

• 52:02Lester Nare?

  Car to be able to park to maximize the amount of cars that can be parked at each level.

• 52:08Krishna Choudhary?

  Yeah, exactly. And sometimes maybe you do want the double wide spaces, so then there's MOFs that do that.

• 52:13Lester Nare?

  Right.

• 52:14Krishna Choudhary?

  That only work for larger.

• 52:15Lester Nare?

  Right.

• 52:16Krishna Choudhary?

  Like for CO2, right? CO2 slightly larger than N2, but you want to absorb that and not the N2. Then there's other ways of doing it. But exactly, it's tunable. The, the, the space of the parking garage is tunable. It's, it's very cool. And the other question that we were getting a lot, and this is something that I was also... Interested in is, you know, how do you make these things in a lab? Right. How do you make these things? And I was briefly in a chemistry lab at UCLA when I was doing rotations from one lab to the other to figure out what I want to do my PhD physics in. This was a lab that was actively doing cryo electron microscopy to find, you know, the structures of giant proteins.

• 52:59Krishna Choudhary?

  And in that, my advisor at the time, she said, you know, chemistry is a lot like cooking. Okay. In that there's only, there's, there's a few techniques that you have, and you have to be extremely good at figuring out which techniques you want to do. And the order in which you want to put them in order to actually make your chemistry happen. But it is really like cooking because you've got standard tools, right? You've got heat, you can heat up stuff, you can cool down stuff. You can mix stuff together and you can stir stuff together. Every once in a while, you have like fancy techniques, like if you want to do creme brulee or whatever that thing is with like a blowtorch, right? And you're like, you know, every once in a while, or like you want to electrically shock stuff for some reason.

• 53:43Krishna Choudhary?

  But most of, most of it is basically mixing, heating, letting it sit. All of the techniques that we use in the kitchen to make a really good meal. Right. And that's what's happening in chemistry, like in the lab. That's, that's what you have. And so MOFs are created by this process called solvothermal synthesis. Okay. Effectively, what you're doing is you're mixing together metal salts. Think like zinc nitrate, you've got copper, zirconium and chlorine together. You mix that in with your organic linker, which is the linker between the things that makes that cube happen. And these can be like carboxylates, organic, organic molecules.

• 54:25Krishna Choudhary?

  You've got some kind of solvent, usually that's DMF, which is dimethyl formamide. This is a pretty toxic solvent. You can also now there's techniques that are using ethanol or water. And then what you do is you mix them up, you heat them in a sealed vessel. For, you know, 250 degrees Celsius, you can heat them up for hours to days in these vessels that are like Teflon lined autoclaves. Autoclaves are like ways to, to make high pressure, high temperature reactions happen. And then you can cool them slowly. The idea is to cool them very slowly so that that promotes the crystalline growth, right? As you cool, the, the chemicals are now going to start forming in this energetically favorable way

• 55:09Krishna Choudhary?

  where the organic linkers are going to find the metal and then the metal are going to find more organic linkers and you're going to grow this MOF out of a, out of a tiny seedling of stuff.

• 55:18Lester Nare?

  It's, the mix has the prerequisites such that when you apply heat and then apply cooling, the end result is what is planned for based on the amount of heat applied, the period of time the heat is applied, the amount of cooling that's applied, the period of time that the cooling is applied. So it's going to fall into place based on just the mix, how it's mixed, the, the proportions of each component part and that sort of healing, heating and cooling cycle.

• 55:45Krishna Choudhary?

  Exactly. And that, that's why I'm telling you, it's like a lot like cooking, right? Because like if the bread is like underproofed, if, if people watch the Great Britain Bake, which I love, you know, if the bread is underproofed or overproofed, it becomes like stodgy and, and whatever, and, and you know, so, so everything has to go perfect for all of this to happen, right? And, and so it really is like a, a cooking thing. And after all of that's done, now you've got these crystals. And what you have to do is now wash out the solvent and then you have a naked MOF, right? And you get these crystals, which they kind of look like this under the microscope. They're tiny, tiny amounts, you know, grams at a time. The, the real challenge now is scaling this thing industrially.

• 56:30Lester Nare?

  I do remember one comment saying like, well, can you produce it at industrial scale?

• 56:35Krishna Choudhary?

  Yeah. Yeah. And it's, it's difficult. There's a lot of difficulty here. First of all, the DMF, which is a common solvent that's used, this thing is toxic and it's expensive. So we'd rather use stuff like ethanol or water. The yield is pretty small. We're getting like, you know, grams of stuff at a time. And if you scale up, then you can imagine the crystals are less good because the environment is not completely uniform. The bigger the vessel there's going to have, you're going to have like edge effects, right? Where the edge temperature is different from the central temperature, the pressures are different.

• 57:06Krishna Choudhary?

  You know, and removing that solvent is pretty hard at larger and larger scales because what you have to do is basically vacuum pump all of that stuff out. And, you know, producing a big enough vacuum pump for the, for industrial scale is pretty hard. I did find a company, there are several companies, but there's one company I wanted to highlight, Novo MOF. They're a company out of Switzerland. We're not sponsored by them or anything, okay? But it's, it's a cool company that I found. They, they made 300 kilograms of their NMOF and that 300 kilograms has 240 kilometers squared of surface area, which is like the size of cities.

• 57:41Lester Nare?

  Right.

• 57:42Krishna Choudhary?

  And they're using this for carbon capture in factories, right? But they, they've, they've, they, on their website, they talk about the challenges that comes with trying to scale these up at industrial level and some of the techniques that they're using to go through and actually mitigate those, those things.

• 58:00Lester Nare?

  So what's interesting is the, the, the concept of metal or like, like most of the Nobels, the discoveries have been made quite some time ago.

• 58:07Krishna Choudhary?

  Yeah.

• 58:08Lester Nare?

  And, you know, with metal organic frameworks, we're at a place now where they've been experimentally proven, there's a variety of different methodologies that have kind of been identified.

• 58:18Krishna Choudhary?

  There's been the, also the, the rulebook on how to make stuff, right? The cookbook is now pretty well established.

• 58:25Lester Nare?

  And so now the challenge is, is going from making a meal for me, you.

• 58:30Krishna Choudhary?

  Yeah.

• 58:31Lester Nare?

  Of the spouses.

• 58:32Krishna Choudhary?

  To like McDonald's level.

• 58:33Lester Nare?

  To McDonald's.

• 58:34Krishna Choudhary?

  Yeah.

• 58:34Lester Nare?

  How do you, how do you make this man, you know, enterprise, industrial grade, volume, size, scale, uh, which again is non-trivial, but is, is the tail end of this sort of fundamental research to end consumer product cycle.

• 58:49Krishna Choudhary?

  Exactly, exactly. Um, and it really shows how science benefits us as a society, right? It's like, the process is always fundamental science needs to happen first to show the base case, it's possible.

• 59:07Krishna Choudhary?

  And it's worth it. Once you have that, then you go into, okay, how do I industrially scale this thing? How do I make it better? How do I make it cheaper? Blah, blah, blah, blah, blah, you know?

• 59:17Lester Nare?

  This is an important context in understanding like how the public and private sector work in terms of innovation. A lot of times, especially in the modern tech era, innovation is framed as the private sector is the only location in which innovation can arise because in the public sector, there's too much bureaucracy.

• 59:36Krishna Choudhary?

  Oh, yeah.

• 59:37Lester Nare?

  All this other stuff. And the, the challenge with that viewpoint is so much of the innovation, big I innovation that gets talked about has a basis that was publicly funded for fundamental research that dictates it. There are some exceptions to this rule where the private sector will look at an area and it'll usually it'll be a founder-led company where the founder has super voting shares to be able to dictate what happens and it doesn't matter. And they have a conviction about something and then they'll go and do that fundamental research, acquire all, we've seen this particularly, for example, in AI, which again is still based on decades of fundamental research.

• 1:00:15Krishna Choudhary?

  Even every private company that is doing this fundamental research, they're standing on the shoulders of giants, right? And those giants are always funded by public institutions and by our taxpayer dollars.

• 1:00:30Lester Nare?

  Because there's not a profit incentive.

• 1:00:32Krishna Choudhary?

  No.

• 1:00:33Lester Nare?

  For the private sector to do fundamental research where they can't tie it to quarterly earnings or shareholder value in a time cycle that is reasonable for the sort of stock market system that we have today.

• 1:00:45Krishna Choudhary?

  I mean, if, if we look at AI, right? Like John Hopfield in the 1980s, working on neural networks was NSF funded. Everybody thought he was just like doing some weird biophysics like stuff. Okay. Like you made, you made an Ising model out of the brain. Cool. And then, you know, Geoffrey Hinton saying that, guys, neural networks are the future and everybody else was going for the algorithmic AI. He's the one who was like, no, let's just make it bigger and bigger. And with backprop, it's going to work. No one believed him, but he got funding because some people were like, eh, it might work. Let's, let's give him some funding for it. And now we have all of AI, right?

• 1:01:25Krishna Choudhary?

  The PhD students of Geoffrey Hinton that went and started OpenAI and all this stuff, they were supported by grants from taxpayer dollars.

• 1:01:34Lester Nare?

  And now it's a multi-trillion dollar global issue that is-

• 1:01:37Krishna Choudhary?

  Neuralink, the PhD students that started Neuralink were supported by grants from the American government.

• 1:01:43Lester Nare?

  Hundred percent.

• 1:01:43Krishna Choudhary?

  Right? Like, there's no, there's no world where this isn't happening because of funding from our taxpayer dollars. And this is one thing that I really feel really strongly about is like, when I pay taxes, I want it to go for this kind of stuff.

• 1:01:58Lester Nare?

  One of the things that has created this strategic advantage for the US, where we have been a dominant global power, driven not only by our military, but by our technology, both of which are fundamentally where they are because of our investment in fundamental science research.

• 1:02:19Krishna Choudhary?

  Yeah.

• 1:02:20Lester Nare?

  We would not have dominance in air and sea with the Navy and the Air Force. We would not have dominance where all of the biggest technology companies on the planet-

• 1:02:28Krishna Choudhary?

  Yeah, are here.

• 1:02:29Lester Nare?

  Are here. We would not have that without the early investments in these arenas that were perceived as not being commercially viable at the time.

• 1:02:40Krishna Choudhary?

  Yeah, yeah, yeah, exactly. It's like, it doesn't make any sense to me because this used to be, this used to be a bipartisan thing.

• 1:02:48Lester Nare?

  That's what's so interesting.

• 1:02:49Krishna Choudhary?

  This used to be a very bipartisan thing. We're gonna be the best when it comes to science, okay? George Bush funded the NASA's re-going to Mars and stuff like that. There's so many, so many things that have happened now, especially with the current administration, that is just like totally, totally bankrupting us when it comes to our supremacy in the sciences. And it's really, really rather unfortunate.

• 1:03:18Lester Nare?

  We have sort of photo seven here-

• 1:03:20Krishna Choudhary?

  Yeah.

• 1:03:20Lester Nare?

  Which is-

• 1:03:22Lester Nare?

  You know, we're leading in Nobel prizes.

• 1:03:24Krishna Choudhary?

  Yeah.

• 1:03:24Lester Nare?

  Our universities are at the top.

• 1:03:26Krishna Choudhary?

  But the current administration is just running scientists out of our country.

• 1:03:31Lester Nare?

  Which is like another problem, which is like, if you look at the Nobel prizes from the US.

• 1:03:36Krishna Choudhary?

  Yeah, even this year.

• 1:03:38Lester Nare?

  And who led and who they are.

• 1:03:39Krishna Choudhary?

  Yeah.

• 1:03:40Lester Nare?

  And how they got to be American.

• 1:03:43Krishna Choudhary?

  Yeah. Omar Yagi, he was an immigrant from Jordan, Palestinian refugee, came in, embraced this country, was supported by the DOE, was supported by the NSF, did an NSF postdoc fellowship at Harvard, and the NSF postdoc fellowship is now completely gutted. The NSF postdoc fellowship used to be this thing that would take graduate students that were stars and put them at these top institutions to do postdoc research and gear them up for becoming top faculty members at our leading institutions. And now that thing is gutted.

• 1:04:16Lester Nare?

  You know, what's funny is the only reason that I am able to be in the US is, you know, my dad did his postdoc at Harvard and was funded. He not only got in through a newly created visa program that was specific to Zimbabwe.

• 1:04:30Krishna Choudhary?

  Okay.

• 1:04:30Lester Nare?

  Right? And it was the first round and he won the lottery the first round. He similarly got to be able to do, that's how he got to McGill, where he did grad school. And then he got to do the Harvard postdoc because of a similarly federally funded grant program around postdoc research. And like, you know, he's been in Science and Nature, published multiple times, has multiple patents that are accruing value to

• 1:04:56Krishna Choudhary?

  Yeah.

• 1:04:57Lester Nare?

  multiple American companies, you know, he's been a director of biology at a biotech that sold for millions of dollars. And like, all of that value creation is because of these systems that existed.

• 1:05:09Krishna Choudhary?

  Yeah. I mean, same for my dad. My dad came on a, I think it was an NOA fellowship or an NSF fellowship. We first came to Huntsville, Alabama from India. We stayed there for two years. He was working at the Marshall Space Flight Center for NASA. And then he got a tenure track position here in LA. And that's how he moved here. But even throughout his position as a professor here in LA, he's gotten funding from the NSF. And now all of that is going down. It's just really, really quite insane to me that this is happening at a countrywide scale. And it's not something that I think we should take lightly. Because, you know, Germany.

• 1:05:47Krishna Choudhary?

  I hate to bring up Germany as an example, but it really is such a great example because before the 1920s and 1930s, Germany won almost every Nobel Prize in chemistry, in biology. And then afterwards, they haven't won a lot. It took them a while to crawl back. And we're seeing that happening with American institutions. The UC system has a hiring freeze.

• 1:06:11Lester Nare?

  Right.

• 1:06:12Krishna Choudhary?

  JPL has let go of 500 of their staff.

• 1:06:16Lester Nare?

  Right. And that's just right around the corner from us here.

• 1:06:19Krishna Choudhary?

  I mean, it's just, it's just nuts, dude. Like, it's gonna take us, I fear that it's gonna take us decades to, to come back from this. And I think, I think, you know, we should really be thinking about this as, as a nation, about like, what is important to us? Like, if American exceptionalism is important to us, which it should be, certainly important to me. Like, you know, I got my American citizenship and I love the fact that America is exceptional at a lot of things, right? And it's perhaps more so than any other profession, I think scientists understand what that means.

• 1:06:56Lester Nare?

  Yep.

• 1:06:57Krishna Choudhary?

  To have American exceptionalism, right? We have the greatest research infrastructure in the world and we shouldn't be so casually letting that go.

• 1:07:05Lester Nare?

  Hundred, hundred, hundred percent. I mean, and it's one of those things that takes a long time to see transpire and it's why ringing the alarm sooner rather than later matters. Because the Nobel Prizes that went out last week were for discoveries from decades ago.

• 1:07:23Krishna Choudhary?

  Uh huh.

• 1:07:24Lester Nare?

  And so there's like an inertia.

• 1:07:26Krishna Choudhary?

  Yeah.

• 1:07:26Lester Nare?

  Right?

• 1:07:26Krishna Choudhary?

  Exactly.

• 1:07:27Lester Nare?

  To see it show up in the system.

• 1:07:28Krishna Choudhary?

  Yeah, yeah.

• 1:07:29Lester Nare?

  And so, just because-

• 1:07:30Krishna Choudhary?

  Yeah, we don't want to be in the 2050s now and then all the Nobel Prizes are being won by countries outside of the US. There's several stories of scientists now leaving the US because of what's happening, right? Other countries are salivating.

• 1:07:46Lester Nare?

  At the opportunity.

• 1:07:46Krishna Choudhary?

  At the opportunity to just poach all of our scientists. And this is happening now in real time. This is something that needs to stop.

• 1:07:53Lester Nare?

  It's, it's, this is an important subject we've covered before.

• 1:07:56Krishna Choudhary?

  Yeah, but I really, yeah, I think the, the recent Nobel Prizes like really made me think about it, right? Because, you know, Omar, like, we're also doing this whole anti-immigration thing, which I totally get.

• 1:08:09Krishna Choudhary?

  Right? Like with the illegal immigration and all that, like there's, there's arguments to be made there. But I'm, I think both sides of the aisle should agree that curating exceptional international talent is something that America should be doing.

• 1:08:24Lester Nare?

  It's what we've been doing for hundreds of years.

• 1:08:27Krishna Choudhary?

  Yeah.

• 1:08:28Lester Nare?

  And it, we've done it through multiple world wars.

• 1:08:31Krishna Choudhary?

  Yeah, we've done it since the 1800s. Andrew Carnegie was a, was a immigrant. And look what he did for our nation, right? All, Albert Einstein was an immigrant. Enrico Fermi was an immigrant. Like, oh, come on, guys. Tesla was an immigrant.

• 1:08:44Lester Nare?

  If you look at most of the top, uh, companies in the S and P 500,

• 1:08:52Lester Nare?

  if you look at Fang, most of these, you know, Facebook, Amazon, Netflix, Google, et cetera, et cetera. The Nvidia, the biggest companies that the US has right now, the majority of them are founded by immigrants.

• 1:09:08Krishna Choudhary?

  Yeah, yeah. And I mean, even this year's Nobel prizes, right? Four out of the six Americans are immigrants. You've got, actually, no, sorry, three out of the six. John Clark, he's an immigrant from the UK, did his PhD at Cambridge and then came here to Berkeley. Michel Devore did his PhD at Paris Sud, came here to Berkeley. We've got Omar Yagi, obviously, um, from Jordan, came here. So it's worked, guys.

• 1:09:37Lester Nare?

  Even if you look at our math Olympiad team.

• 1:09:39Krishna Choudhary?

  Yeah.

• 1:09:39Lester Nare?

  It's a, I think it's a hundred percent Chinese.

• 1:09:42Krishna Choudhary?

  Yeah, no, there's, there's an Indian guy and there's an American guy.

• 1:09:44Lester Nare?

  Okay.

• 1:09:44Krishna Choudhary?

  There's a US guy, like a white guy.

• 1:09:46Lester Nare?

  That's fair.

• 1:09:46Krishna Choudhary?

  But I mean, I love that, dude. Like, I love the fact that, like, our country curates talent from all over the world and we just, we just create the A-team.

• 1:09:56Lester Nare?

  Yes.

• 1:09:57Krishna Choudhary?

  Right?

• 1:09:57Lester Nare?

  Yes.

• 1:09:57Krishna Choudhary?

  I, I absolutely love that.

• 1:09:59Lester Nare?

  And we should continue to do so.

• 1:10:01Krishna Choudhary?

  Yeah.

• 1:10:01Lester Nare?

  Um, so.

• 1:10:02Krishna Choudhary?

  We're getting the plus ones, right?

• 1:10:03Lester Nare?

  Right.

• 1:10:03Krishna Choudhary?

  It's our scoreboard.

• 1:10:04Lester Nare?

  Right. Hundred, hundred percent. Uh, this is, this is an important issue. We need to continue to fund fundamental science in the United States. Uh, we need to continue to bring the best and brightest from the world here to continue to facilitate the life and the lifestyle that we have facilitated and also give the gift of what we create to the rest of the world. Uh, we have the infrastructure to do so. We have the sort of. Cultural dynamics to do so.

• 1:10:34Krishna Choudhary?

  Yeah.

• 1:10:34Lester Nare?

  Irrationally confident.

• 1:10:35Krishna Choudhary?

  Yeah.

• 1:10:37Lester Nare?

  And.

• 1:10:38Krishna Choudhary?

  And it works.

• 1:10:38Lester Nare?

  And it works.

• 1:10:39Krishna Choudhary?

  And it works. We are irrationally confident and we just do it. And we just do it and we, and if it doesn't work, we try again and we try again because we're so confident that it's gonna work, you know, and that's how we get stuff like

• 1:10:53Krishna Choudhary?

  M O F five that has a football field size surface area in a gram.

• 1:10:58Lester Nare?

  Or, or.

• 1:10:59Krishna Choudhary?

  Everybody else was like, what are you talking about?

• 1:11:01Lester Nare?

  Right, right.

• 1:11:02Krishna Choudhary?

  He's like, no, this thing literally has a football field.

• 1:11:07Lester Nare?

  It's, it's been a really fascinating two weeks with the Nobel Prizes.

• 1:11:10Krishna Choudhary?

  Yeah.

• 1:11:11Lester Nare?

  We want to thank all of you who are listening, whether it's on YouTube, Spotify, Apple Podcasts, TikTok, Instagram, X, Facebook.

• 1:11:22Lester Nare?

  You guys really are powering the show.

• 1:11:24Krishna Choudhary?

  Yeah.

• 1:11:25Lester Nare?

  Continue to send over questions. We'll try to touch on them as much as possible. We may introduce a listener question section.

• 1:11:32Krishna Choudhary?

  Yeah, we might.

• 1:11:33Lester Nare?

  In future episodes. But this is, uh, this is one of the most important subjects to all of our lives. Our everyday lives, our family, our careers and everything. And we're going to try to continue to do it justice by covering it from first principles. I am your host, Lester Nare, joined as always by my co-host and our resident PhD Krishna Choudhary. This is from first principles. We'll see y'all next week.