2026 Nobel Prize Predictions: Medicine, Physics & Chemistry (EP 60)

Who could win the 2026 Nobel Prizes? From the science behind Ozempic to quantum interference and droplets inside living cells, Lester Nare and Krishna Choudhary make their picks for Medicine, Physics and Chemistry, and explain the discoveries behind them. In Episode 60 of From First Principles, we explore seven research areas with a case for Nobel recognition: GLP-1, optogenetics, optical coherence tomography, the Aharonov–Bohm effect, atomic force microscopy, biomolecular condensates and Buchwald–Hartwig coupling. We also discuss Michael Berry’s geometric phase and the awkward question of how a prize limited to three people recognizes discoveries built by larger teams. These are our predictions, recorded before the 2026 announcements. Medicine, Physics and Chemistry will be announced October 5–7. Which discovery, and which researchers, would you pick? Tell us in the comments, then join us for our Nobel week breakdowns. CHAPTERS 00:00 The science that could win a Nobel Prize 00:57 Hello Internet: our 2026 predictions 02:03 Medicine: GLP-1 and the science behind Ozempic 07:41 Medicine: optogenetics and controlling neurons with light 13:16 Medicine: optical coherence tomography 16:28 Golden Goose Awards and FFP updates 18:39 Physics: the Aharonov–Bohm effect and geometric phase 27:37 Physics: atomic force microscopy 32:04 Chemistry: biomolecular condensates 36:36 Chemistry: Buchwald–Hartwig coupling 38:42 Your predictions and our Nobel week plans RESEARCH & FURTHER READING Foundational papers and background for the discoveries discussed: GLP-1: Mojsov, Weir & Habener (1987) https://doi.org/10.1172/JCI112855 Optogenetics: Boyden et al. (2005) https://doi.org/10.1038/nn1525 Optical coherence tomography: Huang et al. (1991) https://doi.org/10.1126/science.1957169 Aharonov–Bohm effect (1959) https://doi.org/10.1103/PhysRev.115.485 Berry’s geometric phase (1984) https://doi.org/10.1098/rspa.1984.0023 Atomic force microscopy: Binnig, Quate & Gerber (1986) https://doi.org/10.1103/PhysRevLett.56.930 Biomolecular condensates: Brangwynne et al. (2009); Li et al. (2012) https://doi.org/10.1126/science.1172046 https://doi.org/10.1038/nature10879 Buchwald–Hartwig coupling: Paul et al. (1994); Guram et al. (1995) https://doi.org/10.1021/ja00092a058 https://doi.org/10.1002/anie.199513481 Official Nobel announcement schedule: https://www.nobelprize.org/prizes/about/prize-announcement-dates/ EDITORIAL NOTES 19:30 David Bohm later held a professorship at Birkbeck, University of London (1961–1987); he did not spend the rest of his career in Brazil. 33:23 The ribosome-producing compartment discussed is the nucleolus, not the nucleosome. These corrections also appear on screen. WATCH & EXPLORE YouTube: https://youtu.be/MgOpbh5VUGE Episode page and research library: https://ffppod.com/episodes/ep60 Support: https://ffppod.com/donate Follow @FFPPod on X / Instagram / TikTok / Facebook Breaking down science news so it makes sense to curious people everywhere.

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

• 0:00Speaker 00

  Well, I received a phone call at nine minutes past two in my morning. And I thought, well, this is obviously a junk call.

• 0:11Lester Nare?

  Every October, somewhere in the world, a phone rings before sunrise. Last year, the call went to scientists who showed how the immune system keeps itself in check, who built molecular frameworks full of open space, and who made an electric circuit behave like a single quantum particle. Next week, for the second year running, we'll be up at 2:00 a.m. to find out who gets the call. Today, we're making our picks. This is from First Principles, and this is our 2026 Nobel Prize preview.

• 0:57Lester Nare?

  Hello, Internet. This is your captain speaking, Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary. We are back from our trip to Washington, D.C. for the Golden Goose Awards, and we are preparing for one of the biggest weeks in science, Nobel Prize week. For those of you who have been here since last year, we did a huge weekly special, daily drops. And beforehand, we did a predictions episode in which our resident PhD had one out of three. Quite nice.

• 1:33Krishna Choudhary?

  That's quite nice.

• 1:33Lester Nare?

  It's quite nice. And we are going to do the same this week. We're going to keep it nice and light and tight because we have an action-packed week coming up for you. As always, we're going to talk about the science from the ground up today because this is from First Principle.

• 2:03Lester Nare?

  Next week, the Nobel Prizes start on Monday with medicine and physiology, and we're going to jump right in to our first prediction for medicine.

• 2:14Krishna Choudhary?

  So the first prediction for medicine is something that a lot of people have been calling GLP-1. This is the glucagon-like peptide 1. It's a hormone that's released by the intestinal cells after a meal. It helps stimulate insulin secretion in the pancreas when glucose is elevated, and it coordinates communication between the gut and the pancreas. It also importantly affects appetite and the movement of food throughout the stomach. It's been all the craze lately in Los Angeles and America and the world because the GLP-1 drugs like Ozempic and Wegovy

• 2:54Krishna Choudhary?

  have been used as a treatment for diabetes, but also as a treatment for weight loss. There was an early scientific challenge in identifying what the active peptide is because you can't just look at what the big protein is. The big protein is called proglucagon, but it's really cut up into different products and different tissues. So you can imagine, you can't just look at the gene because the gene is going to give you the giant protein. I want the peptide, which is the smaller part of the protein. And that was a big challenge. And the significant challenge was solved by a bunch of pioneers. We're going to go through some of them whom I think are going to be involved if GLP-1 gets the Nobel Prize.

• 3:36Krishna Choudhary?

  So the first one is Svetlana Majsov. She identified and synthesized the active form of GLP-1, and she helped establish its intestinal origin and the fact that it insulates, the fact that it stimulates insulin. So she's a research professor at the Rockefeller University in New York. She did her PhD there also at Rockefeller. The next one that I think would probably be involved is Jens Jule Holst. His group independently helped establish those same properties. So frequently, the Nobel Prize will be given to both if it happened concurrently at the same time. And that's why I think he's probably in the contention. University of Copenhagen is his home.

• 4:19Krishna Choudhary?

  And finally, Daniel Drucker. He contributed to, he contributed experiments showing that the glucose-dependent insulin secretion and the broader physiology is in fact these glucagon-like peptides. So he's a professor at the University of Toronto, and also he's affiliated with Massachusetts General Hospital in Harvard. Now, that's already three, right?

• 4:44Lester Nare?

  Yeah.

• 4:45Krishna Choudhary?

  And the Nobel Prize very famously is only given to three.

• 4:48Lester Nare?

  Maxes out.

• 4:49Krishna Choudhary?

  Maxes out at three. The trouble with GLP-1, which is why I think, you know, this is kind of a far chance because there is a fourth involved that is very heavily involved. Lottie Bieri Knudsen. She was at Novo Nordisk, and she's part of the team that attached a fatty acid chain to the GLP-1 analogs. And this is what turned it into a drug. Okay? It went from just a peptide that's found normally, but if you just like inject GLP-1, you're going to throw up. You need a kind of intermediary that helps it do the types of regulation that we know from the GLP-1-associated drugs. So she's a strong possible recipient.

• 5:32Krishna Choudhary?

  She's the chief scientific advisor for research and development at Novo Nordisk right now. And, you know, the, there was a breakthrough prize, I believe in 2024 or 2025, that was given to all four of them.

• 5:49Lester Nare?

  Interesting.

• 5:50Krishna Choudhary?

  Okay?

• 5:50Lester Nare?

  Yeah.

• 5:51Krishna Choudhary?

  So there were the three scientists, and then there was this person who really like pushed it to become the kind of treatment option that it's available today.

• 5:59Lester Nare?

  The practical application.

• 6:00Krishna Choudhary?

  Yeah, yeah. So if GLP-1 is something that the Nobel Prize Committee deems worthy, it's going to be interesting how they distribute it. Like, who are the three out of the four that they choose?

• 6:12Lester Nare?

  Uh-oh, uh-oh. And for listeners of the pod, you will recall that we discussed GLP-1 in the context of also having been a former winner of the Golden Goose Award.

• 6:28Krishna Choudhary?

  That's right.

• 6:30Lester Nare?

  Based on some research as it relates to Gila monsters.

• 6:34Krishna Choudhary?

  Not Gila monsters.

• 6:35Lester Nare?

  Gila, thank you. Thank you for everyone correcting our American pronunciation. And it's obviously something that people get inundated with, with ads on Instagram, et cetera.

• 6:47Krishna Choudhary?

  Yeah.

• 6:47Lester Nare?

  And I think the through line is, yes, great. You know, we have something that is attacking an issue that impacts a lot of people and has been beneficial to many. But it does again start with some fundamental understanding that then leads to the practical application. This, I think, was the, is one of the most popular.

• 7:09Krishna Choudhary?

  Predictions out there.

• 7:10Lester Nare?

  Predictions on all of the markets and all this other stuff.

• 7:13Krishna Choudhary?

  Yeah, yeah. The only reason why I think it's a far-fetched is because there's four involved. You know, I think this is one of those where maybe they'll have a deal with the chemistry people to like give some of it to the chem and some of it to bio or something like that. You know, or they do the classic thing where they wait for one of them to die. And then, and then immediately give it to the three that are left standing.

• 7:36Lester Nare?

  Which, if you watch our last year's Nobel coverage, we talk about that.

• 7:40Krishna Choudhary?

  Yeah.

• 7:40Lester Nare?

  That context, which is a classic move for the Nobel Committee.

• 7:45Krishna Choudhary?

  Yep. All right. So the second prediction that I have is something that I've recycled from last year's predictions. This is optogenetics. Optogenetics is an incredible technology that is now used not only in neuroscience, but all over cellular biotechnology assays. The idea is that there's a specific protein that has been discovered called channel rhodopsin. It's a, it's a channel protein, meaning that it's, it lets ions through. It sits on the membrane between the outside and the inside of the cell. And it's rhodopsin because that reminds you of the rods and cones, the rods in your eyes.

• 8:29Krishna Choudhary?

  It is light-sensitive. This is a protein that was originally identified in green algae, and it forms an ion channel on the membrane. The idea is. You can shine light on it of a particular frequency. The protein is going to absorb that photon and then use the energy of that photon to change its shape and open up or close, depending on what this specific protein is trying to do. Crucially, this gives us the ability to not only read, but also write into the neurons, right? We can now actively affect what the neurons are doing. This is not the first time that we've been able to write stuff. Obviously, like Neuralink, for example, is read and write as well.

• 9:10Krishna Choudhary?

  And that uses electrodes that are going right next to the neurons. And if you send out a voltage pulse, then that's going to affect the molecular environment, right? Here, on the other hand, you can, you can very specifically tag specific types of neurons. So you can like have a, you can have a virus, for example, that is modified, obviously. And this virus has the DNA for channel redopsin. And it's also got a marker that lets it only infect certain types of neurons and not others. So it's going to infect those neurons, put in this DNA for channel redopsin. The cell is going to make channel redopsin and express it on its outside. And then I can shine light on it and turn on and off only those specific types of cells,

• 9:55Krishna Choudhary?

  whether it be peramidal neurons or like inhibitory neurons. Whatever I want, I can sort of engineer and make happen within a living, breathing animal, right?

• 10:07Lester Nare?

  I remember when we talked about this the first time and it was such a mind blowing concept again, the ways in which we are so clever in how we try to have impacts on our biology and using the existing mechanics of, you know, how biology works generally and just manipulating it for an outcome that we want that's controllable. And again, not to continue to pump up last year's coverage, but we had a deeper dive on channel redopsin at the time.

• 10:39Krishna Choudhary?

  Yeah.

• 10:40Lester Nare?

  And so if you're curious to learn more about it, check our preview episode from last year.

• 10:44Krishna Choudhary?

  Yeah, I mean, it's absolutely incredible because it's been used, it's used in every single university. There is a research labs, actually usually several, that use optogenetics. And the key idea is when we can manipulate circuits like this, we can then turn them on and off. We can couple them to behavior experiments and then we can see what specific circuits are doing, right? In terms of all the way from the genetics, all the way down to behavior.

• 11:11Lester Nare?

  Right.

• 11:12Krishna Choudhary?

  Because we have this control knob.

• 11:13Lester Nare?

  Right.

• 11:14Krishna Choudhary?

  So it's been incredible for the bio research community at large. So there are a few people that are involved here. First one, I would think is Peter Hegeman. He is the professor of experimental biophysics at Humboldt University at Berlin. He studied the chemistry of this protein itself. And he, his research was basically on how algae responded to light. He's the guy who discovered the protein in the first place. After that, Carl Deisseroth and Edward Boyden in 2005 and all of their collaborators at Stanford, they demonstrated precise optical control of mammalian neurons.

• 11:50Lester Nare?

  Yeah.

• 11:51Krishna Choudhary?

  Using channel redopsin. So, you know, having it in algae is one thing, but modifying it a certain way, making it compatible with mammalian neurons, that was something else. And that is what has led to the boom for, over the past 20 years of using this as an experiment. It's, it's been absolutely massive. So I think, I think this has contention, which is why I'm recycling it from last year.

• 12:15Lester Nare?

  Right, right, right. We're just taking a second bite at the apple here.

• 12:18Krishna Choudhary?

  Yeah, yeah, I really think this could happen. There's one other guy, Gareum Misenbach. He's also predicted, if they give it to Misenbach, they're probably not going to give it to Boyden, because Boyden was a PhD student at the time. But Ed Boyden at MIT now has really taken this to the next level. So again, this is going to be one of those where it's interesting. If they give it to optogenetics, which three are they going to choose?

• 12:44Lester Nare?

  This is so, I think, you know, like many things, it's a little bit subjective. There is obviously backing to it.

• 12:53Krishna Choudhary?

  Yeah.

• 12:54Lester Nare?

  But when you have the limitation of saying only three.

• 12:58Krishna Choudhary?

  Yeah.

• 12:59Lester Nare?

  Someone's got to sit on the bench.

• 13:01Krishna Choudhary?

  Yeah.

• 13:02Lester Nare?

  Not everyone can be a starting player.

• 13:03Krishna Choudhary?

  Exactly, yeah.

• 13:04Lester Nare?

  And that's tough.

• 13:05Krishna Choudhary?

  And a lot, and, and all four of these guys are quite young.

• 13:09Lester Nare?

  Yeah, and so like.

• 13:10Krishna Choudhary?

  So you can't really wait, you know?

• 13:12Lester Nare?

  Can't wait for them to die.

• 13:15Krishna Choudhary?

  Yeah. So that one's going to be interesting if that goes. And the last prediction I have for medicine, medicine is the only one where I have three, because I think it could be either one of these three. But again, honestly, it's a crap shoot, so probably not, right? But the, the last one that I have is optical coherence tomography, or OCT. This produces a cross sectional image of tissue using light. It's a major, major medical application. Usually we use this on the retina where there's thin layers that can become distorted, they can lose cells, they can accumulate fluid. OCT reveals that internal structure without actually cutting into the eye. So this non-invasive imaging is really, really nice.

• 13:59Krishna Choudhary?

  The challenge always is like determining depth. Like here, over here, we're seeing a cross section, right? And, and we're using this optical coherence tomography to, to look at what the depth is in a tissue. You would think that the depth you can just find by shining light and then seeing when the light bounces back, but this is at the micron level.

• 14:18Lester Nare?

  Yeah.

• 14:19Krishna Choudhary?

  Okay, so getting that timing is going to be insane.

• 14:22Lester Nare?

  With Google Maps at the micron level for tissue.

• 14:25Krishna Choudhary?

  Yeah, yeah. And you can't really look at delays in light. So what they do here instead is they use interference. They have a reference light and then they have light that goes in and out. And then depending on, you know, the timing, there's going to be phase accumulation. And then that is going to interfere with the reference light and that's going to give you a kind of timing signal at the end of the day, right? It's quite clever.

• 14:47Lester Nare?

  That's clever.

• 14:48Krishna Choudhary?

  This one's actually kind of clean.

• 14:51Lester Nare?

  Okay.

• 14:52Krishna Choudhary?

  There's three that are involved.

• 14:53Lester Nare?

  Okay.

• 14:54Krishna Choudhary?

  They published their paper in 1991. So it's also, you know, 30 years now, 35 years since.

• 14:59Lester Nare?

  Sweet spot.

• 15:00Krishna Choudhary?

  So it's a sweet spot of like, okay. And it's been used for so much because, um, like OCT now helps clinicians track glaucoma and retinal disease. So it's been used in treatment, which kind of goes back to Nobel's original will, where he said, you know, for the benefit of mankind. Well, this is pretty clearly for the benefit of mankind. So the three that I think are going to get it are James Fujimoto, David Wang, and Eric Swanson. They had their foundational paper in 1991, their early retinal images led to imaging living eyes and the practical clinical instruments. Fujimoto is the professor of electrical engineering and computer science at MIT. Wang is at the Oregon Health and Science University in Portland.

• 15:45Krishna Choudhary?

  And Swanson is also at MIT's research lab of electronics.

• 15:49Lester Nare?

  As you can tell, this year, we're toning down the MIT hate a little bit.

• 15:54Krishna Choudhary?

  Yeah. Look, if they win though, it's, it's going to happen.

• 15:57Lester Nare?

  We got very lucky last year that we had two alma maters win between both Princeton and UCLA.

• 16:03Krishna Choudhary?

  And all three were University of California.

• 16:06Lester Nare?

  Yeah, oh, yeah.

• 16:07Krishna Choudhary?

  Right? Like the physics prize, physics prize was all University of California. The, um, the medicine prize had one UCLA graduate and Omar Yagi obviously was a professor at Berkeley at the time.

• 16:19Lester Nare?

  At the time, California forever goodbye. Um, it's not looking good based on these predictions this year. It's not looking good.

• 16:27Krishna Choudhary?

  No, but physics is coming up.

• 16:28Lester Nare?

  Okay, we're still getting early, we're still early.

• 16:30Krishna Choudhary?

  Yeah.

• 16:31Lester Nare?

  And so those are the three predictions for medicine. We're going to take a quick break for some housekeeping. Um, as we said, it's been, we've had several episodes in a short period of time. We love you so much, we want to get you the best content as much as possible. I do want to touch on briefly, um, a few thank yous from our last week to our trip to DC for the Golden Goose Award. Real big thank you to all of the team at AAAS and GSG who were extremely helpful in setting up all of our interviews and taking care of us throughout the day. All of the awardees, uh, you guys were fantastic. We look forward to continuing the conversation.

• 17:14Lester Nare?

  That episode again will come out after Nobel week, where we have our interviews, for those who watched our last episode, where we walked through the background of all of the folks that received a Golden Goose Award this year. And, um, it's, you know, it's a community that makes this stuff happen. And I think it's important that we continue to find ways to take the folks doing the work and giving them a platform. For those who may be new to, from First Principles, welcome to the best science show on the planet. You can listen to us on YouTube, as well as all of your favorite podcast platforms. Video is available on Spotify and YouTube, Apple Podcasts coming soon. We have not forgot about you all.

• 17:57Lester Nare?

  If you enjoy the show, one of the best ways you can help us out is engaging, like, comment, share, subscribe, five star review on the podcast networks. It helps us grow so people know that this is the best and helps us continue to be able to provide value for all of you. If you're interested in any of the research papers or background information that we talk about, our website, ffppod.com, has all those research papers, several other cool science related, interactive things you can do. It's quite nice. And with that, the shilling is over and we're going to get to the most important Nobel Prize.

• 18:37Krishna Choudhary?

  I didn't say it.

• 18:39Lester Nare?

  The physics Nobel Prize. And so we have, I believe, two predictions.

• 18:44Krishna Choudhary?

  Yes, we've got two predictions. The first one, I think is really a no brainer and I cannot believe that the Nobel Committee still hasn't given him a Nobel Prize. This is also a recycle from last year, because I am fully convinced that this guy deserves it. This is Yakir Aronoff and the Aronoff-Bohm effect, which he and David Baum described in 1959. David Baum is the very famous physicist behind the pilot wave theory or the pilot wave interpretation of quantum mechanics. This was the first non-Copenhagen interpretation of quantum mechanics. Niels Bohr ran him out of Copenhagen when Baum went over to like try to pitch.

• 19:27Krishna Choudhary?

  Um, and then he was run out very sadly of the country because this was the McCarthy era and he was ideologically a communist. So he had to, he had to go to Brazil for the rest of his career, um, which, you know, given his stature, he could have done a lot more in some of the bigger universities. But, um, he, he went to Brazil, he had a nice time there. The Aronoff-Bohm effect, people have said that this is the biggest development in quantum mechanics since.

• 20:01Krishna Choudhary?

  Dirac's prediction of antimatter. Okay?

• 20:07Lester Nare?

  Pretty good.

• 20:08Krishna Choudhary?

  That's pretty good. The Arnoff Bomb Effect is so fundamental, it doesn't make sense why it hasn't gotten a Nobel Prize. Seriously. So here's the idea, the Arnoff Bomb Effect, and you know, hopefully, I really hope they do give him the Nobel Prize, because then I get to do a deep dive on it for 45 minutes. But I'm going to give you a real quick justification of the whole thing. So remember the double slit experiment? The idea was that, you know, you have two paths that the photon can go through, or the electron can go through, and then it interferes in the back, and you get an interference pattern. And this is key to quantum mechanics. So now imagine, actually, if we can bring that

• 20:47Lester Nare?

  Yes.

• 20:49Krishna Choudhary?

  For to 11. So now imagine we've got a beam splitter of electrons this time. The electron follows one path to the left, one path to the right, and it meets back up, recombined at a detector in the back, right? And in the middle, in between these two pads, is a solenoid that has a current going through it. And because it has a current going through it, inside the solenoid, there's going to be a magnetic field. But if you remember from your undergraduate physics, outside the solenoid, the magnetic field is zero. Because you can run Ampere's law outside the solenoid, there's no current that's involved, because there's net current going in, net current coming out in those directions.

• 21:34Krishna Choudhary?

  And so there's no actual current, which means there's no magnetic field outside the solenoid. The magnetic field is localized inside of the solenoid. Okay? Now, for all intents and purposes, in physics, the field is the real thing. But you can construct fields out of potentials. For example, the gravitational field is the real thing. But in order to sort of do mathematics with the gravitational field, we can invent something like a gravitational potential, and say that, you know, the potential here is something, the potential here is a little bit more. And so the amount of energy it takes for me to go against the field is just the difference in the potential. And it's always the difference in the potential.

• 22:16Lester Nare?

  The, I think the example you talked to me about one time is like, imagine a hill. And you have someone that you're at the top of the hill or the bottom of the hill.

• 22:22Krishna Choudhary?

  Exactly.

• 22:22Lester Nare?

  And your gravitational potential at the top of the hill is greater, and then it could do the, so.

• 22:26Krishna Choudhary?

  And then, and then you can figure out how fast a ball would roll down the hill, based on the difference. Now, the key thing is, if I had the hill down at sea level, but then I took the same like cardboard landscape, let's say, of the balls rolling, and I've got a cardboard landscape, and I took it up to Mount Whitney, as long as the gravitational field is exactly the same, it doesn't matter if I'm at Mount Whitney or at sea level, the dynamics on my cardboard mesh thing is going to be exactly the same.

• 22:52Lester Nare?

  Yeah.

• 22:53Krishna Choudhary?

  Right? Because the only thing that matters is the difference in the potential. Okay, that's fine. For magnetic fields, we can also construct a potential that describes a magnetic field. But instead of a scalar potential, which in this case is just height, so there's no vector, right? It's just a number.

• 23:10Lester Nare?

  Yeah.

• 23:10Krishna Choudhary?

  For a magnetic field, it requires a scalar potential. I mean, sorry, for the magnetic field, it requires a vector potential, not a scalar potential. Now, that introduces some interesting things. Because if you've got a vector potential, then all of a sudden, direction matters in terms of like, which way you're traversing this potential. But the potential is just a trick, right? It's supposed to be a mathematical trick.

• 23:32Lester Nare?

  Right.

• 23:32Krishna Choudhary?

  The field is the real thing. And in the Arnoff Bomb Effect, my electron is moving one way and the other way, the field is in the middle, the solenoid is in the middle, and the field is localized inside the solenoid.

• 23:43Lester Nare?

  Yeah.

• 23:43Krishna Choudhary?

  So it shouldn't affect the two pads. That ends up not being true. If I turn on the magnetic field on and off, that changes my interference pattern. So this is very strange.

• 23:54Lester Nare?

  Yeah, right, right. Because the, the institutional understanding was there should not be an effect on your beam.

• 24:02Krishna Choudhary?

  Yeah.

• 24:02Lester Nare?

  Outside of the solenoid.

• 24:03Krishna Choudhary?

  Outside of the solenoid, because the field is the real thing. Here, we're saying perhaps the potential could be a real thing. It's not just a bookkeeping thing, right? There are multiple interpretations of how this thing works. But the fact that it works, and that I can experimentally do it, introduces a lot of nuance into how we understand quantum mechanics. Right? And that's why it's one of the biggest developments since Dirac's equation and his prediction of antimatter. So this was in 1959. It's quite late in terms of fundamental quantum theory. And here, yet you have something that is so fundamental and so in your face, and something that we don't really quite understand from a philosophical and metaphysical level. Okay? We can, we can, we can do the calculations, right?

• 24:47Krishna Choudhary?

  It turns out that, you know, what you have to do is the quantum interference depends on the complete path geometry. Not just on these two pads, but like, you do a sum over pads on every single one, and perhaps maybe there's something to go through. It's still like, eh, you know, is that, is that really what's happening?

• 25:02Lester Nare?

  Hand wavy.

• 25:03Krishna Choudhary?

  Yeah. Like, but the, the, the local force along the path is not the only thing that matters. That's the key, right?

• 25:10Lester Nare?

  Yeah.

• 25:11Krishna Choudhary?

  There's, there's like, it's, it's, it's a global thing. It's a global phenomenon.

• 25:16Lester Nare?

  I, and I, one of the things that always trip, not trips me up, but is so interesting when we talk about these quantum mechanical stories, is this idea that you have, it's not just, everything matters. Even the things that are not what you end up seeing experimentally.

• 25:35Krishna Choudhary?

  Exactly.

• 25:36Lester Nare?

  And that is a brain teaser.

• 25:39Krishna Choudhary?

  Yeah.

• 25:40Lester Nare?

  Yeah. In terms of how your frame, your mental framework about what it is, all this stuff around us, and reality and the physicality of it, the physicality is not, and it's that we can engage in at the human scale, is not the only thing.

• 25:54Krishna Choudhary?

  It's not the only thing. Yeah. It's, it's, I mean, it's a trip every time you dive too deep into it. So David Bohm died in 1992. And so Yakir Arnoff would be the only recipient. He's actually a professor of theoretical physics at Chapman University in Southern California.

• 26:11Lester Nare?

  Oh, look at that.

• 26:12Krishna Choudhary?

  Right? So this would be a long time coming, I think. He, he published that paper in the 19, late 1950s, when he was a doctoral student. So this, this would be one of the record holders for like, the amount of time it took. Right? From like 1959 till now, that would be a big one.

• 26:33Krishna Choudhary?

  Michael Berry, we were just on the Instagram Live before taping this.

• 26:37Lester Nare?

  Yeah.

• 26:37Krishna Choudhary?

  And someone said, Barry, this is who they're referring to. And Michael Berry is a natural possible co-recipient in 1984. He showed that a quantum state can acquire an additional phase when the parameters slowly trace some type of closed loop. It's a topological argument. It's related to the Arnoff Bomb Effect, but not exactly the same. Again, topological physics is something that is incredibly deep, complex, and yet, simple. So, you know, if, if the Nobel Prize Committee decides to award topological physics another Nobel Prize,

• 27:14Krishna Choudhary?

  I'll have a field day explaining it. That'll be, that'll be really fun.

• 27:17Lester Nare?

  Does this relate to when we had these conversations about gradient descent?

• 27:22Krishna Choudhary?

  Kind of.

• 27:22Lester Nare?

  And related, and the related concepts? I can't remember what episode it was. We had one where we went really deep on it.

• 27:32Lester Nare?

  But it's, it's escaping me right now. However, if there's a win, we will cover it.

• 27:36Krishna Choudhary?

  Yeah, we will cover it, for sure. Physics 2, I'm going to be honest, this is also a recycle from last year. Because I really do think AFM is something that deserves it. Okay? This is the atomic force microscope.

• 27:51Lester Nare?

  This one is so crazy.

• 27:52Krishna Choudhary?

  Yeah, this one is huge. Here's the idea, with the AFM, the atomic force microscope, you can scan a sharp tip that is like, at the level of Angstrom's thick at its tip. Like, this is like, something that is like, at the atomic resolution. And what you do is, you run a surface across it, and it measures the interaction between the tip and the sample.

• 28:17Lester Nare?

  I, I want to just double click on this. We're talking about it's very, very, very, very, very, very small.

• 28:25Krishna Choudhary?

  Yeah, like, you see those hills and valleys there? Those are like, those are like, on the orders of tens of atoms.

• 28:31Lester Nare?

  Like, that, it's.

• 28:32Krishna Choudhary?

  Right? To now, I think, I think people are doing like, single atoms, straight up.

• 28:35Lester Nare?

  Which is so ridiculous.

• 28:37Krishna Choudhary?

  It's so ridiculous, how we can sense such tiny, tiny perturbations. Right? It's, it's completely led to the, the advent of precision nanotechnology.

• 28:51Lester Nare?

  Yeah.

• 28:52Krishna Choudhary?

  A lot of really nice applications, like if we want to understand the stress and strain of materials at that scale, right? If we want to understand, for example, even biological membranes and biological tissue, what is the type of force that biology goes under at the molecular scale? We can use AFMs. It's, it's an absolutely revolutionary technology, I think. Under suitable conditions, they can even resolve single atoms.

• 29:20Lester Nare?

  So nuts.

• 29:22Krishna Choudhary?

  It's it's huge.

• 29:23Lester Nare?

  I mean, there's manufacturing, you know, benefits. There's biological health, medicine, clinical benefits.

• 29:28Krishna Choudhary?

  Research benefits.

• 29:29Lester Nare?

  Like, it just applies literally everywhere.

• 29:31Krishna Choudhary?

  Yeah, exactly. And so the original inventors were Gerard Binig, Calvin Kuaté and Christoph Gerber. They all received the 2016 Kavli Prize in Nanoscience. Kuaté died in 2019, so if the Nobel honors them, it's gonna be only Binig and Gerber. Binig is a retired physicist from IBM's Zurich Research Lab. And Gerber is the Department of Physics professor at the University of Basel. So this would be two Swiss recipients.

• 30:08Lester Nare?

  Europe's on the board.

• 30:09Krishna Choudhary?

  Yep.

• 30:10Lester Nare?

  Europe's on the board. It's not just California forever goodbye. I I remember when we first, when we first talked about these and it was so early in the show. And there were a lot of fundamental concepts that have stuck with me since in terms of being able to build further understanding in our future stories, just in terms of like, again, what's even possible? I mean, these things are not new.

• 30:33Krishna Choudhary?

  Yeah.

• 30:33Lester Nare?

  And so we've come a long way. So when we talk about frontier research stories, we're talking about much more evolved applications, not necessarily of these concepts specifically, but just if you can imagine we were doing these things such a long time ago.

• 30:49Krishna Choudhary?

  Yeah, this was 1986.

• 30:50Lester Nare?

  Imagine what we're doing now.

• 30:51Krishna Choudhary?

  Right? So this was exactly 40 years ago.

• 30:54Lester Nare?

  Yeah.

• 30:55Krishna Choudhary?

  And because of the AFM, we have such a, we have a much more finer understanding of nanotechnology, right? Without the AFM, a lot of the nanotechnology that we use in day to day lives wouldn't be possible because the AFM gives us a way to probe that scale and understand what's going on down there.

• 31:16Lester Nare?

  It's like opposite world JWST.

• 31:19Krishna Choudhary?

  Yeah.

• 31:20Lester Nare?

  In the other direction.

• 31:20Krishna Choudhary?

  In the other direction, exactly.

• 31:23Lester Nare?

  We are going to move now to the final category. Again, we are going to be having coverage every day for the first three days for the only real Nobel prizes, medicine, physics, and our final category, chemistry.

• 31:39Krishna Choudhary?

  Actually, can I just caveat that? Peace and literature are real Nobel prizes because Alfred Nobel put it in his will that he wanted peace and literature. So there's really five real Nobel prizes because that's what was in Alfred Nobel's will.

• 31:58Lester Nare?

  But what about economics?

• 32:00Krishna Choudhary?

  I didn't, I don't, you guys hear something? Chemistry. Let's talk about chemistry.

• 32:06Lester Nare?

  This is an inside joke for those who are new. But yes, let us proceed to the chemistry Nobel.

• 32:14Krishna Choudhary?

  The first one, this is a recycling from last year because I do think this deserves it. Biomolecular condensates. I'm gonna say it again. These things are everywhere in biology and they were discovered by chemists for a very good reason. The idea is in biology, you need to bring particular molecules together in the right places at the right time. You need compartmentalization. Biology usually does this using membranes. For example, this outer membrane that you're seeing here, that's the nuclear membrane and that is separating the nucleus on the inside from the outside of the cell. That's nice in eukaryotes because you want to compartmentalize all of your DNA, all of your chromosomes.

• 32:59Krishna Choudhary?

  You don't want all of the cellular machinery running around trying to get to your DNA, right? And that's why we have the, the wall around our DNA. We keep that safe. And then we have RNA, mRNA that goes outside and is kind of like hanging out with the plebs on the outside of the cell, trying to make everything work. But look inside the nucleus, right? There is that blob, that orange arrow it's pointing to. That is the nucleosome. It's a compartment inside the nucleus itself. Some people like to call it the nucleus of the nucleus. And that's where a lot of the ribosome making machinery happens. The ribosome is the protein making factory of our cells and the ribosomes are created in that nucleosome.

• 33:43Krishna Choudhary?

  But there's no membrane around that nucleosome. Okay? The proteins just kind of aggregate there. The ones that are important for that particular process are just aggregating there. This is an example of a biomolecular condensate. It shows how compartments can form without actual membranes around them.

• 34:03Lester Nare?

  The membraneless compartment.

• 34:05Krishna Choudhary?

  Exactly. And the underlying physics is just phase separation. Okay, you can have proteins and RNA and they can make weak contacts and, and then those things can mix with other stuff. And you can kind of get, you know how oil separates from water very naturally? Kind of the same way, these molecular condensates can separate from other dilute phases in a very natural way. And this is a purely physically driven entropic system. Like it's not, there's no active, like stuff is pushing, there's, there's nothing active in an oil and water mixture that is pushing the oil together, right?

• 34:42Lester Nare?

  Right.

• 34:42Krishna Choudhary?

  Just the oil wants to be together and the water wants to be together because of the different chemistry. The same thing is happening here. There's different chemistry happening and that's what causes this phase separation. So who are the people involved? 2009, I would say Clifford Bragwine and Tony Hyman and their colleagues. They showed that these pea granules in roundworm embryos behave like liquids. And those granules could accumulate at one end of the embryo through dissolution in just one region and then condensation in another. So it's the same substance, but it would exhibit different chemistry because of its environment, which was very nice. And then in 2012, Michael Rosen and his colleagues, they showed how proteins with multiple binding sites could assemble into droplets.

• 35:24Krishna Choudhary?

  So you got a protein that's got multiple little magnetic sites where stuff can, stuff can like bind. And depending on the interactions, you can have those proteins coalesce into a compartment without any, without anything on the outside. So where are these people? Bragwine is at Princeton University.

• 35:44Lester Nare?

  Oh, we're on the board, baby.

• 35:46Krishna Choudhary?

  So he is a professor in the Bioengineering Institute. Hyman is at EMBL, which is the European Molecular Biology Laboratory that's based in Heidelberg. It's kind of like a Max Planck, but like not, I don't know. If they win, I'm gonna go into like what exactly that thing is, but it seems something like that. And then Rosen is a professor at UT Southwestern Medical Center in Dallas.

• 36:12Lester Nare?

  Okay, so Texas is on the board.

• 36:14Krishna Choudhary?

  Yep.

• 36:16Lester Nare?

  Okay, so fingers crossed.

• 36:18Krishna Choudhary?

  Fingers crossed for biomolecular condensates. I really think that that's a, because that one's another clean, like sort of three people.

• 36:24Lester Nare?

  Yeah, yeah.

• 36:25Krishna Choudhary?

  You know?

• 36:26Lester Nare?

  Yeah.

• 36:26Krishna Choudhary?

  So.

• 36:27Lester Nare?

  And related to the most important academic institution.

• 36:30Krishna Choudhary?

  Of course, so.

• 36:31Lester Nare?

  Yeah, of all time.

• 36:32Krishna Choudhary?

  Of all time.

• 36:32Lester Nare?

  So, so yeah.

• 36:33Krishna Choudhary?

  It's not close.

• 36:33Lester Nare?

  That would be great.

• 36:35Krishna Choudhary?

  Chemistry two.

• 36:36Lester Nare?

  Yes.

• 36:36Krishna Choudhary?

  This one's catalytic carbon nitrogen bond formation. It's called the Buchwald-Hartwig coupling. And it's named after the two people that I think might get it if this is the thing that gets it. This is a widely used method for making carbon nitrogen bonds. Nitrogen containing groups are common in medicines. You know, you attach the nitrogen to a certain position of a carbon ring and that can change the molecular's charge, the molecule's charge, the solubility, the interaction with proteins. And this reaction is super important for creating drug therapies, right? In this case, what Hartwig and Buchwald did was they combined a mechanistic understanding

• 37:22Krishna Choudhary?

  with ligand design. Ligand is the molecule that bounds to some kind of catalyst. In this particular case, the catalyst that they always use is palladium, which I think is the same, it's the same metal that was used by Iron Man in the cave to create the.

• 37:40Lester Nare?

  He did this in a cave.

• 37:41Krishna Choudhary?

  Yeah, he did this in a cave. Yeah, yeah, that was palladium. I'm pretty sure. In any case, that metal is kind of a intermediary that, that bridges this gap between the carbon, removing like, let's say the bromine in this case, and then attaching a nitrogen there. And you can use this to control exactly where to attach the nitrogen in a convoluted organic molecule. This is huge because for drug discovery, this lets chemists make families of related molecules and then you can test how different nitrogen groups affect biological activity. So they actually shared the 2019 Wolf Prize. They were recognized for their catalytic work.

• 38:21Krishna Choudhary?

  So Buchwald is a professor of chemistry at MIT and Hartwig is a professor of chemistry at US University of California, Berkeley. So California on the board again.

• 38:32Lester Nare?

  I don't know what to tell you guys. I think, I think we're gonna have some fun.

• 38:38Krishna Choudhary?

  Yeah, and those, those are my predictions. Let's see.

• 38:42Lester Nare?

  We wanted to keep it quick and tight today. We have a lot to prepare for next week for a fast turnaround after having just come back and still working through our interviews. And so for those who like long episodes, tune in next week. We're definitely gonna get into the weeds. But please let us know for those who have finished, which should be most of you, because this, this week's episode's very short. Let us know in the comments before Monday. What do you think is going to win a Nobel Prize in these categories? And then we'll see what happens. And if you end up being right, we'll make sure we comment back. So we're super excited.

• 39:22Lester Nare?

  It's gonna be a lot of fun and maybe we'll do a little bit of a little live preview. For those on Instagram, we did a couple of lives for fun at the unction, as the kids say, because we don't understand how to use these things anymore.

• 39:38Lester Nare?

  But it's great to be able to interact with many of you. But with that, we are going to end nice and quick this week, well under an hour. This is shocking levels.

• 39:49Krishna Choudhary?

  It's the first time in a while.

• 39:51Lester Nare?

  Shocking levels.

• 39:52Krishna Choudhary?

  Probably in a year. The last time was when we did the Nobel Prize episodes.

• 39:58Lester Nare?

  We know you guys like the long form. We wanted to get you our predictions before we get into the good stuff. My name is Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary. We will see you all next week for the Nobel Prizes.