2026 Nobel Prize Predictions: Medicine, Physics & Chemistry

The science that could win a Nobel Prize

0:00Well, I received a phone call at uh 9 minutes past 2 my morning and I thought, well, this is obviously a junk call. And >> 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 a.m. to find out who

0:42gets the call. Today, we're making our picks. This is from first principles and this is our 2026 Nobel Prize preview.

Hello Internet: our 2026 predictions

0:57Hello internet. This is your captain speaking Lester Nar joined as always by my co-host and our resident PhD Krishna Chowdery. We are back from our trip to Washington DC 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 quite nice. >> That's quite nice. It's quite nice. And we are going to do the same this week. We're going to keep it nice and light

1:39and tight because we have an action-packed week coming up for you. As always, we are going to talk about the science from the ground up today because this is from first principle.

Medicine: GLP-1 and the science behind Ozempic

2:03Next 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. 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

2:46Angeles and America and the world because the GLP-1 drugs like Ompic and Wiggoi have been used as a treatment for diabetes but also as a treatment for weight loss. Um 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 prolucagon, but it's really cut up into different products in 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

3:28by a bunch of pioneers. We're going to go through some of them whom I think are going to be involved if GLP1 gets the Nobel Prize. So the first one is Svet Lana Majavv. She identified and synthesized the active form of GLP-1 and she helped establish its intestinal origin and the fact that it insulates it 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 Jen's Jewel Holtz. his group independently helped establish those same properties. So frequently the

4:09Nobel Prize will be given to both if it happened like concurrently at the same time. And that's why I think he's probably in the contention. University of Copenhagen is his home. And finally, Daniel Duker, he contribute 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 um at the University of Toronto and also he's affiliated with Massachusetts General Hospital in Harvard. >> Now that's already three, right? >> Yeah. >> Um and the Nobel Prize very famously is only given to three. maxes out >> maxes out at three. The trouble with

4:53GLP-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. Lahi Vieri Nudson she was at Novo Nordisk and she's part of the team that attached a fatty acid chain to the GLP1 analoges and this is what turned it into a drug. Mhm. >> 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 mediary that helps it do the types of regulation that we know from the GLP1 associated drugs. So, um, she's a strong possible recipient. She's the chief scientific adviser for

5:35research and development at Nova Nordisk right now. And um you know the the there was a breakthrough prize I believe in 2024 or 2025 that was given to all four of them. >> Interesting. >> Okay. Yeah. >> 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. >> The practical application. >> Yeah. Yeah. So, if GLP1 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? >> Uhoh. Uh-oh. And for listeners of the

6:16pod, you will recall that we discussed uh GLP1 in the context of uh also having been a former winner of the Golden Goose Award. >> That's right. uh based on some research as it relates to Gila Monsters, >> not Gila Monsters. >> Gila, thank you Monsters. Thank you for everyone correcting our American uh pronunciation. And it's obviously something that people get inundated with with ads on Instagram, etc. Yeah. >> 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

6:57many. Um but it does again start with some fundamental understanding that then leads to the practical application. Uh this I think was the mo one of the is one of the most popular um >> predictions out there >> predictions on all of the markets and all this other stuff. >> Yeah. Yeah. The only reason why I think it's a far-fetch is because there's four involved. You know, I think this is one of those where um 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, >> which if you watch our last year's Nobel

7:38coverage, we talk about that that context which

Medicine: optogenetics and controlling neurons with light

7:42>> is a classic move for the uh Nobel committee. >> Yep. All right. So the second prediction that I have is something that I've recycled from last year's predictions. This is optogenetics. Um 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 redopsin. It's a in it's a channel protein meaning that it's um it lets ions through. It sits on the membrane between the outside and the inside of the cell. And

8:24it's rodopsin because that reminds you of the rods and cones, the rods in your eyes. 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

9:05is not the first time that we've been able to write stuff obviously like Neurolink for example is read and write as well 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

9:46to 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, whether it be parameal neurons or like inhibitory neurons, whatever I want, I can sort of engineer and make happen within a living breathing animal. Right? I 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 uh and using the existing mechanics >> of you know how biology works generally and just manipulating it for an outcome

10:27that we want that's controllable and uh the again not to continue to >> pump up last year's coverage We had a deeper dive on channel adoption at the time. Yeah. And so if you're curious to learn more about it, uh, check our preview episode from last year. Yeah. I mean, it's absolutely incredible because it's been used it's used in every single university. There is a research lab actually usually several that use optogenetics. Um, and the key idea is we 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

11:09all the way down to behavior because we have this control knob. 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 Hegman. >> Um he is the professor of experimental biohysics at Humbult 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 Daiseroth and Edward Bdon in 2005 and all of their collaborators at Stanford they demonstrated precise optical control of mamalian neurons

11:50using channel redopsin. So you know having it in algae is one thing but modifying it a certain way making it compatible with mamalian 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. Um 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. >> Right. We're taking a second bite at the apple here. >> Yeah. Yeah. I really think this could happen. Um there's one other guy um Garham Misenbach. He's also predicted if they give it to Misenbach, they're probably not going to give it to Bdon because Bdon was a PhD

12:31student at the time. >> Um but Ed at at Ed Bdon 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? I this is so I think you know like many things uh it's a little bit subjective >> uh there is obviously backing to it. >> Yeah. >> But when you have the limitation of saying only three >> Yeah. >> Someone's got to sit on the bench. Yeah. Not everyone can be a starting player. >> Exactly. Yeah. >> Um and that's tough. And a lot and and all four of these guys are quite young. >> Yeah. And so like so you can't really

13:11wait, you know. >> Right. Uh can't wait for them to

Medicine: optical coherence tomography

13:16>> 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 crapshoot, 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

13:58nice. 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. >> Okay. So getting that timing is going to be insane >> with Google Maps at the micron level for tissue. >> 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 comes in and out and then depending on you know >> the timing >> there's going to be phase

14:40>> 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. >> That's clever. >> Um this one's actually >> kind of clean. There's three that are involved. Okay. >> They published their paper in 1991. So it's also, you know, 30 years now, 35 years since >> Sweet Spot. 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

15:20that I think are going to get it are James Pujimoto, David Hang and Eric Swanson. They had their foundational paper in 1991. Their early retinal images led to imaging living eyes and the practical clinical instruments. Um, Fujioto is the professor of electrical engineering and computer science at MIT. Guang is at the Oregon Health and Science University in Portland. And Swanson is also at MIT's research lab of electronics. >> As you can tell, this year we're toning down the MIT hate a little bit. Uh, >> look, if they win though, it's it's going to happen. >> We got very lucky last year that we had two alma modders win between both

16:01Princeton and UCLA >> and all three were University of California. >> Yeah. All Yeah. >> Right. All like the physics prize. Physics prize was all University of California. >> The um the medicine prize had one UCLA graduate and the Omar Yagi obviously was a professor at Berkeley at the time. At the time, California forever goodbye. Um, it's not looking good. based on these predictions this year. >> It's not looking good. >> No, but physics is coming up.

Golden Goose Awards and FFP updates

16:28>> Okay, we're still getting early. We're still early. >> Uh 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. Um real big thank you to all the team at AAS and GSG who were extremely helpful in setting up all of our interviews and taking care of us uh throughout the day. All of the

17:08awardees uh you guys were fantastic. We look forward to continuing the conversation. Uh that episode again will come out after Nobel Week where we have our interviews for those who watched our last episode where we walk 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 uh 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

17:48favorite podcast platforms. Video is available on Spotify and YouTube. Uh Apple podcast coming soon. We have not forgot about you all. Uh 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 ffpod.com has all those research papers, several other cool science related interactive things you can do. Uh it's quite nice.

18:30And with that, the shilling is over and we're gonna get to the most important Nobel Prize. >> I didn't say it.

Physics: the Aharonov–Bohm effect and geometric phase

18:39Uh, the physics Nobel Prize. And so we have, I believe, two predictions. >> 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 Aranov and the Arnov bomb effect which he and David Bomb described in 1959. David Bomb 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.

19:20Neils Boore ran him out of um Copenhagen when bomb went over to like try to pitch 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 Arnoff bomb effect people have said that this is the biggest development in quantum mechanics since

20:02Drock's um prediction of antimatter okay >> pretty good >> 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 Arnov 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 um >> 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

20:43quantum mechanics. So now imagine actually if we can bring that >> yes um photo 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 paths 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

21:23magnetic field is zero because you can run ampier's law outside the solenoid. There's no current that's involved because there's net current going in, net current coming out in in those directions. 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

22:04potential 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. >> The the I think the example you talked to me about one time is like imagine a hill >> and you have someone you're at the top of the hill or the bottom of the hill and your gravitational potential at the top of the hill is greater and then it could do the so >> 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

22:46Whitney or at sea level, >> the dynamics on my cardboard mesh thing is going to be exactly the same. Yeah. >> Right. Because the only thing that matters is the difference in the potential. >> Okay, that's fine. Um 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 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

23:29potential is just a trick, right? It's supposed to be a mathematical trick. >> 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. So it shouldn't affect the two paths. That ends up not being true. If I turn on the magnetic field on and off, that changes my interference pattern. >> Right. >> So this is very strange. >> Yeah. Right. Right. Because the the the the institutional understanding was there should not be an effect on your beam. >> Yeah. >> Outside of the solenoid. >> 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

24:10thing. 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 Drock'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? It turns out that you know what you have to do is the quantum interference depends

24:51on the complete path geometry not just on these two paths but like you you do a sum over paths on every single one and perhaps maybe there's some that go through it's still like you know is that is that really what's happening right and wavy >> yeah um like but the the the local force along the path is not the only thing that matters that's the key right >> there's there's like >> it's it's it's a global thing it's a global phenomenon >> I I and One of the things that always trip not trips me up but um is so interesting when we talk about these quantum mechanical stories is this idea that >> you have it's not just everything

25:31matters >> even the things that are not what you end up seeing experimentally. >> Exactly. >> Um and that uh is a brain teaser. >> 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 um the physicality is not that we can engage in at the human scale is not the only thing >> not the only thing yeah it's an it's I mean it's a trip every time you dive too deep into it you know um so David Bomb died in 1992 and so Yakir Arnov would be the only recipient he's actually a professor of theoretical physics at Chapman university in Southern California. Ah, look at that. Right. So

26:13th this would be a long time coming I think. Um 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 the amount of time it took >> right from like 1959 till now. Um that would be a big one. Um, Michael Barry. We were just on the Instagram live before taping this and someone >> said Barry. This is who they're referring to. >> Michael Barry is a natural possible co-reient. 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

26:55the Arnoff bomb effect, but not exactly the same. Um again topological physics is something that is incredibly deep, complex and yet simple. Um so you know if if the Nobel Prize committee decides to award topological physics another Nobel Prize um I'll have a field day explaining it. That'll be that'll be really fun. >> Does this relate to when we had these conversations about gradient descent >> and and related and the >> related concepts? I can't remember what episode it was. Um, we had one where we went really deep on it. Um, but it's it's escaping me right now. However, if there's a win, we will cover it.

27:36>> Yeah, we will cover it for sure. Uh,

Physics: atomic force microscopy

27:38Physics 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. >> This one is so crazy. >> Yeah, this one is huge. Um, 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. I I want to just double click on

28:19this. We're talking about ex very very very very very small. >> Yeah. Like you see those hills and valleys there? Those are like those are like at on the orders of tens of atoms like that. It's >> right to now I think I think people are doing like single atoms straight up >> which is so ridiculous. >> It's so ridiculous how we can sense such tiny tiny perturbations right. Um it's it's completely led to the the advent of precision nanotechnology. >> Um a lot of really nice applications like if we want to understand the stress and strain of materials at that scale, right? Um if we want to understand for

29:01example even biological membranes in 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 um under suitable conditions, they can even resolve single atoms. It's >> so nuts. >> It it's it's huge. >> I mean, there's manufacturing, you know, benefits. There's biological health medicine, clinical benefits, >> research. It just applies literally everywhere. >> Yeah. Exactly. Um and so the original inventors were Jared Binig, Calvin Kuate, and Kristoff Gerber. They all received the 2016 Kavi Prize in

29:42nanocience. Kuate died in 2019. So if the Nobel honors them, it's going to be um only Binig and Gerber. >> Binig is a retired physicist from IBM's IBM's Zurich research lab. And Gerber is the department of physics professor at the University of Bassel. So this would be two Swiss recipients. Europe's on the board. >> Yep. >> Europe's on the board. It's not just California forever goodbye. I I I remember when we first when we first talked about these and um it was so early in the show >> and there were a lot of fundamental

30:23concepts 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. >> Yeah. >> And so a we've come a long way. Okay. 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. >> Yeah. This was 1986. >> Imagine what we're doing now, >> right? So this was exactly 40 years ago. >> Yeah. >> Um and because of the AFM, we have such a we we have a much more finer understanding of nanotechnology. Right.

31:04Without 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. It's like opposite world JWST. >> Mhm. >> Yeah. >> In the other direction. >> In the other direction. Exactly. 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. Actually, um can I just caveat that? Um peace and literature are real Nobel prizes because

31:46um Alfred Nobel put it in his will that he wanted peace and >> sure >> literature. So, there's really five real Nobel prizes because that's what was in Alfred Nobel's will. >> But what about economics? >> Yeah, >> I didn't I don't You guys hear something?

Chemistry: biomolecular condensates

32:04>> Chemistry. Let's talk about chemistry. >> This is an inside joke for those who are new. Um, but yes, let us proceed to to the chemistry. Noel, >> the first one, this is a recycling from last year because I do think this deserves it. Biomolelecular condensates. I'm going to say it again. These things are everywhere in biology and they were discovered by chemists for um 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

32:45membrane 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 ukarotes because you want to compartmentalize all of your DNA, all of your chromosomes. 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

33:26compartment 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 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. >> The membraneless compartment. Exactly. And the underlying physics is just phase

34:08separation. 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 a oil and water mixture that is pushing the oil together, right? 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

34:48chemistry happening and that's what causes this phase separation. >> So who are the people involved? 2009 I would say Clifford Bragwine and Tony Heyman and their colleagues. They showed that these PE 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. So you got a protein that's got multiple little magnetic sites where stuff can stuff can like

35:29bind and depending on the interactions you can have those proteins coales into a compartment without any um without anything on the outside. So where are these people? Regine is at Princeton University. >> Oh we're on the board baby. >> So um he is a professor in the bioengineering institute. Hyman is at EML, which is the European Molecular Biology Laboratory that's based in H Highidleberg. It's kind of like a Maxplank, but like not. I don't know if they win. I'm going to go into like what exactly that thing is, but it seems something like that. And then Rosen is a professor at UT Southwestern Medical

36:10Center in Dallas. >> Okay, so Texas is on the board. >> Yep. >> Uh okay, so fingers crossed. Fingers crossed for biomolelecular condensates. I really think that that's a because that one's another clean like sort of three people. >> Yeah. Yep. You know, >> so um >> and related to the most important academic institution, >> of course. So yeah, of all time. So it's not close. It's not close. >> That would be great. Um chemistry 2.

Chemistry: Buchwald–Hartwig coupling

36:36>> Yes. >> This one's catalytic carbon nitrogen bond formation. It's called the Bukwald Hartwig coupling and it's named after the two people that I think might get it if this is the thing that gets it. Um, 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 molecules charge, the solubility, the interaction with proteins. Um and this reaction is super important for creating drug therapies, right? Um in this case, what

37:17Hartwig and Bquall did was they combined a mechanistic understanding with liand design. Ligen is the molecule that bounds to some kind of catalyst. In this particular case, the catalyst that they always use is palladium. >> Mhm. which I think is the same um it's the same metal that was used by Iron Man in the cave >> to create the >> He did this in a cave. >> Yeah, he did this in a cave. >> Yeah. Yeah, that was palladium. Um 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

37:59where 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. So Bwald is a professor of chemistry at MIT and Hartwig is a professor of chemistry at use University of California Berkeley. So California on the board again. >> I I don't know what to tell you guys. >> I think I think we're going to have some fun. >> Yeah. And those are those are my

38:39predictions. Let's see. Uh we wanted to

Your predictions and our Nobel week plans

38:42keep 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, uh, for those who like long episodes, tune in next week. We're definitely going to get into the weeds. Um, but please let us know for those who have finished, which should be most of you, cuz 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. Uh so uh we're super excited. It's going to be

39:23a lot of fun and uh maybe we'll do a little bit of a little live preview uh for those on Instagram. We did a couple of lives for fun at the uncction as the kids say because we don't understand how to use these things anymore. >> Um, but it's great to be able to interact with many of you. Um, but with that we are going to end nice and quick this week. Well under an hour. This is shocking levels. >> The first time in a while. >> Shocking levels. >> Probably in a year. The last time was when we did the Nobel Prize episodes. Uh, we know you guys like the long form. We wanted to get you our predictions before we get into the good stuff. My

40:03name is Lester Nar, joined as always by my co-host and our resident PhD Krishna Chowy. We will see you all next week for the Nobel Prizes.