Latest / From First Principles / 2026 Nobel Prize Predictions: Medicine, Physics & Chemistry (EP 60)

Transcript

2026 Nobel Prize Predictions: Medicine, Physics & Chemistry (EP 60) · From First Principles

• 0:00
  Well, I received a phone call at nine minutes past two in my morning, and I thought, well, this is obviously a junk call.
• 0:11
  Every October, somewhere in the world, a phone rings before sunrise.
• 0:18
  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.
• 0:36
  Next week, for the second year running, we'll be up at 2 a.m. to find out who gets the call.
• 0:44
  Today, we're making our picks.
• 0:47
  This is From First Principles, and this is our 2026 Nobel Prize Preview.
• 0:57
  Hello, Internet.
• 0:58
  This is your captain speaking, Lester Nare, joined as always by my co-host and our resident PhD, Krishna Chowdhury.
• 1:07
  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.
• 1:19
  For those of you who have been here since last year, we did a huge weekly special, Daily Drops, and beforehand,
• 1:26
  We did a predictions episode in which our resident PhD had one out of three.
• 1:32
  Quite nice.
• 1:33
  That's quite nice.
• 1:33
  It's quite nice.
• 1:35
  And we are going to do the same this week.
• 1:37
  We're going to keep it nice and light and tight because we have an action-packed week coming up for you.
• 1:43
  As always, we are going to talk about the science from the ground up today because this is From First Principle.
• 2:03
  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.
• 2:14
  So the first prediction for medicine is something that a lot of people have been calling GLP-1.
• 2:21
  This is the glucagon-like peptide 1.
• 2:24
  It's a hormone that's released by the intestinal cells after a meal.
• 2:28
  It helps stimulate insulin secretion in the pancreas when glucose is elevated, and it coordinates communication between the gut and the pancreas.
• 2:36
  It also, importantly, affects appetite and the movement of food throughout the stomach,
• 2:43
  It's been all the craze lately in Los Angeles and America and the world because the GLP-1 drugs like Ozempic and Wegovi have been used as a treatment for diabetes, but also as a treatment for weight loss.
• 3:00
  Yeah.
• 3:01
  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.
• 3:10
  The big protein is called pro-glucagon, but it's really cut up into different products and different tissues.
• 3:16
  So you can imagine...
• 3:17
  You can't just look at the gene because the gene is going to give you the giant protein.
• 3:21
  I want the peptide, which is the smaller part of the protein.
• 3:24
  And that was a big challenge.
• 3:26
  And the significant challenge was solved by a bunch of pioneers.
• 3:30
  We're going to go through some of them whom I think are going to be involved if GLP-1 gets the Nobel Prize.
• 3:36
  So the first one is Svetlana Majsov.
• 3:40
  She identified and synthesized the active form of GLP-1, and she helped establish its intestinal origin and the fact that it stimulates insulin.
• 3:52
  So she's a research professor at the Rockefeller University in New York.
• 3:55
  She did her PhD there also at Rockefeller.
• 3:59
  The next one that I think would probably be involved is Jens-Jule Holtz.
• 4:05
  His group independently helped establish those same properties.
• 4:09
  So frequently, the Nobel Prize will be given to both if it happened concurrently at the same time.
• 4:14
  And that's why I think he's probably in the contention.
• 4:16
  University of Copenhagen is his home.
• 4:19
  And finally, Daniel Drucker, he contributed experiments showing that the glucose-dependent insulin secretion and the broader physiology...
• 4:31
  is in fact these glocogon-like peptides.
• 4:34
  So he's a professor at the University of Toronto, and also he's affiliated with Massachusetts General Hospital and Harvard.
• 4:42
  Now, that's already three, right?
• 4:44
  Yeah.
• 4:45
  And the Nobel Prize very famously is only given to three.
• 4:48
  Max is out.
• 4:49
  Max is out at three.
• 4:51
  The trouble with GLP-1, which is why I think this is kind of a far chance, because there is a fourth involved that is very heavily involved.
• 5:01
  Lottie Bieri-Gnutzen.
• 5:05
  She was at Novo Nordisk, and she's part of the team that attached a fatty acid chain to the GLP-1 analogs.
• 5:12
  And this is what turned it into a drug.
• 5:15
  It went from just a peptide that's found normally, but if you just inject GLP-1, you're going to throw up.
• 5:20
  You need a kind of mediary that helps it...
• 5:23
  do the types of regulation that we know from the GLP-1 associated drugs.
• 5:29
  So she's a strong possible recipient.
• 5:32
  She's the chief scientific advisor for research and development at Novo Nordisk right now.
• 5:37
  And, you know, the...
• 5:42
  there was a breakthrough prize, I believe in 2024 or 2025, that was given to all four of them.
• 5:49
  Interesting.
• 5:50
  Okay?
• 5:50
  Yeah.
• 5:51
  So there were the three scientists, and then there was this person who really pushed it to become the kind of treatment option that it's available today.
• 5:59
  The practical application.
• 6:01
  Yeah, yeah.
• 6:01
  So if GLP-1...
• 6:04
  is something that the Nobel Prize Committee deems worthy.
• 6:07
  It's going to be interesting how they distribute it.
• 6:09
  Like, who are the three out of the four that they choose?
• 6:12
  Uh-oh.
• 6:13
  Uh-oh.
• 6:14
  And for listeners of the pod, you will recall that we discussed GLP-1 in the context of also having been a former winner
• 6:27
  Of the Golden Goose Award.
• 6:28
  That's right.
• 6:30
  Based on some research as it relates to Gila Monsters.
• 6:34
  Not Gila Monsters.
• 6:35
  Gila.
• 6:36
  Thank you.
• 6:36
  Gila Monsters.
• 6:36
  That's right.
• 6:37
  For everyone correcting our American pronunciation.
• 6:42
  And it's obviously something that people get inundated with with ads regularly.
• 6:45
  on Instagram, et cetera.
• 6:47
  Yeah.
• 6:47
  And I think the through line is, yes, great.
• 6:51
  You know, we have something that is attacking an issue that impacts a lot of people and has been beneficial to many.
• 6:58
  But it does, again, start with some fundamental understanding that then leads to the practical application.
• 7:05
  This, I think, is one of the most popular things
• 7:09
  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-fetched 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
• 7:29
  Or they do the classic thing where they wait for one of them to die.
• 7:33
  And then immediately give it to the three that are left standing.
• 7:36
  Which, if you watch our last year's Nobel coverage, we talk about that context, which is a classic move for the Nobel Committee.
• 7:45
  Yep.
• 7:46
  All right, so the second prediction that I have is something that I've recycled from last year's predictions.
• 7:52
  This is optogenetics.
• 7:56
  Optogenetics is...
• 7:58
  an incredible technology that is now used not only in neuroscience, but all over cellular biotechnology assays.
• 8:07
  The idea is that there's a specific protein that has been discovered called channel rhodopsin.
• 8:13
  It's a channel protein, meaning that it lets ions through.
• 8:20
  It sits on the membrane between the outside and the inside of the cell.
• 8:24
  And it's rhodopsin, because that reminds you of the rods and cones, the rods in your eyes.
• 8:29
  It is light sensitive.
• 8:31
  This is a protein that was originally identified in green algae, and it forms an ion channel on the membrane.
• 8:38
  The idea is...
• 8:40
  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.
• 8:55
  Crucially, this gives us the ability to not only read,
• 8:59
  but also write into the neurons, right?
• 9:02
  We can now actively affect what the neurons are doing.
• 9:05
  This is not the first time that we've been able to write stuff.
• 9:07
  Obviously, Neuralink, 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?
• 9:20
  Here, on the other hand, you can very specifically tag...
• 9:24
  specific types of neurons.
• 9:26
  So you can have a virus, for example, that is modified, obviously.
• 9:32
  And this virus has the DNA for channel rhodopsin.
• 9:35
  And it's also got a marker that lets it only infect certain types of neurons and not others.
• 9:40
  So it's going to infect those neurons, put in this DNA for channel rhodopsin.
• 9:45
  The cell is going to make channel rhodopsin and express it on its outside.
• 9:49
  And then I can shine light on it and turn on and off
• 9:53
  Only those specific types of cells, whether it be pyramidal neurons or like inhibitory neurons, whatever I want, I can sort of engineer and make happen within a living, breathing animal.
• 10:06
  I remember when we talked about this the first time and it was such a mind-blowing concept.
• 10:10
  Again, the ways in which we are so clever in how we try to have impacts on our biology.
• 10:17
  and using the existing mechanics of how biology works generally and just manipulating it for an outcome that we want that's controllable.
• 10:29
  Again, not to continue to pump up last year's coverage, but we had a deeper dive on channel adoption at the time.
• 10:39
  And so if you're curious to learn more about it, check our preview episode from last year.
• 10:44
  Yeah, I mean, it's absolutely incredible because it's been used, it's used in every single university.
• 10:49
  There is a research lab, actually usually several, that use optogenetics.
• 10:54
  And the key idea is when we can manipulate circuits like this, we can then turn them on and off.
• 11:01
  We can couple them to behavior experiments.
• 11:04
  and then we can see what specific circuits are doing, right?
• 11:07
  In terms of all the way from the genetics all the way down to behavior.
• 11:11
  Right.
• 11:11
  Because we have this control knob.
• 11:12
  Right.
• 11:12
  So it's been incredible for the bio-research community at large.
• 11:18
  So there are a few people that are involved here.
• 11:20
  First one, I would think, is Peter Hageman.
• 11:23
  He is the professor of experimental biophysics at Humboldt University at Berlin.
• 11:28
  He studied the chemistry of this protein itself, and...
• 11:33
  His research was basically on how algae responded to light.
• 11:36
  He's the guy who discovered the protein in the first place.
• 11:39
  After that, Carl Diceroth and Edward Boyden in 2005 and all of their collaborators at Stanford, they demonstrated precise optical control of mammalian neurons using channelrhodopsin.
• 11:52
  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.
• 11:59
  And that is what has led to the boom for over the past 20 years of using this as an experiment.
• 12:06
  It's been absolutely massive.
• 12:10
  I think this has contention, which is why I'm recycling it from last year.
• 12:16
  Right, we're taking a second bite at the apple here.
• 12:18
  Yeah, I really think this could happen.
• 12:20
  There's one other guy, Garam Misenbach.
• 12:25
  He's also predicted...
• 12:27
  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.
• 12:33
  But Ed Boyden at MIT now has really taken this to the next level.
• 12:37
  So, again, this is going to be one of those where it's interesting.
• 12:39
  If they give it to optogenetics, which three are they going to choose?
• 12:44
  This is so – I think, like many things, it's a little bit subjective.
• 12:51
  There is obviously backing to it.
• 12:53
  Yeah.
• 12:54
  But when you have the limitation of saying only three, someone's got to sit on the bench.
• 13:01
  Yeah.
• 13:01
  Not everyone can be a starting player.
• 13:02
  Exactly.
• 13:03
  Yeah.
• 13:04
  And that's tough.
• 13:06
  And all four of these guys are quite young.
• 13:09
  Yeah.
• 13:10
  And so you can't really wait.
• 13:12
  Right.
• 13:12
  You can't wait for them to die.
• 13:16
  So that one's going to be interesting if that goes.
• 13:19
  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.
• 13:26
  But again, honestly, it's a crapshoot, so probably not, right?
• 13:29
  But the last one that I have is optical coherence tomography, or OCT.
• 13:35
  This produces a cross-sectional image of tissue using light.
• 13:40
  It's a major, major medical application, right?
• 13:43
  Usually we use this on the retina where there's thin layers that can become distorted.
• 13:48
  They can lose cells.
• 13:49
  They can accumulate fluid.
• 13:51
  OCT reveals that internal structure without actually cutting into the eye.
• 13:55
  So this non-invasive imaging is really, really nice.
• 13:59
  The challenge always is like determining depth.
• 14:02
  Like here, over here, we're seeing a cross-section, right?
• 14:05
  And we're using this optical...
• 14:08
  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 goes in and out and then depending on you know
• 14:36
  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.
• 14:46
  Right?
• 14:46
  It's quite clever.
• 14:47
  That's clever.
• 14:48
  This one's actually kind of clean.
• 14:51
  Okay.
• 14:51
  There's three that are involved.
• 14:52
  Okay.
• 14:53
  They published their paper in 1991.
• 14:55
  So it's also, you know, 30 years now, 35 years since... Sweet spot.
• 15:00
  So it's a sweet spot of like, okay, and it's been used for so much because...
• 15:05
  Like OCT now helps clinicians track glaucoma and retinal disease.
• 15:10
  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.
• 15:17
  Well, this is pretty clearly for the benefit of mankind.
• 15:20
  So the three that I think are going to get it are James Fujimoto, David Huang, and Eric Swanson.
• 15:26
  They had their foundational paper in 1991.
• 15:29
  Their early retinal images led to imaging living eyes and the practical clinical instruments.
• 15:36
  Fujimoto is the professor of electrical engineering and computer science at MIT.
• 15:41
  Huang is at the Oregon Health and Science University in Portland.
• 15:46
  And Swanson is also at MIT's research lab of electronics.
• 15:50
  As you can tell this year, we're toning down the MIT hate a little bit.
• 15:55
  Look, if they win, though, it's going to happen.
• 15:57
  We got very lucky last year that we had two alma maters win between both Princeton and UCLA.
• 16:03
  And all three were University of California.
• 16:06
  Yeah.
• 16:06
  Yeah.
• 16:06
  Right?
• 16:07
  Like the physics prize.
• 16:09
  Physics prize was all University of California.
• 16:11
  The medicine prize had one UCLA graduate.
• 16:15
  And Omar Yagi, obviously, was a professor at Berkeley at the time.
• 16:19
  At the time.
• 16:20
  California forever goodbye.
• 16:23
  It's not looking good based on these predictions this year.
• 16:26
  It's not looking good.
• 16:26
  No, but physics is coming up.
• 16:28
  Okay.
• 16:28
  We're still getting early.
• 16:29
  We're still early.
• 16:30
  Yeah.
• 16:31
  And so those are the three predictions for medicine.
• 16:34
  We're going to take a quick break for some housekeeping.
• 16:37
  As we said, it's been, we've had several episodes in a short period of time.
• 16:42
  We love you so much.
• 16:43
  We want to get you the best content as much as possible.
• 16:45
  I do want to touch on briefly a few thank yous from our last week to our trip to DC for the golden goose award.
• 16:57
  Real big thank you to all the team at triple AS and GSG who were our
• 17:02
  extremely helpful in setting up all of our interviews and taking care of us throughout the day.
• 17:08
  All of the awardees, you guys were fantastic.
• 17:11
  We look forward to continuing the conversation.
• 17:14
  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 on
• 17:25
  that received a golden goose award this year.
• 17:28
  And, um, it's, you know, it's a community that makes this stuff happen.
• 17:34
  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, um,
• 17:40
  For those who may be new to From First Principles, welcome to the best science show on the planet.
• 17:45
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• 17:50
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• 17:53
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• 17:55
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• 17:57
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• 18:05
  It helps us grow so people know that this is the best and helps us continue to be able to provide feedback.
• 18:12
  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 uh it's quite nice and with that the shilling is over and we're going to get to the most important nobel prize i didn't say it
• 18:40
  the physics Nobel Prize.
• 18:41
  And so we have, I believe, two predictions.
• 18:44
  Yes, we've got two predictions.
• 18:46
  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.
• 18:54
  This is also a recycle from last year, because I am fully convinced that this guy deserves it.
• 19:02
  This is Yakir Aronoff and the Aronoff-Bohm effect, which he and David Bohm described in 1959.
• 19:09
  David Bohm is the very famous physicist behind the pilot wave theory, or the pilot wave interpretation of quantum mechanics.
• 19:16
  This was the first non-Copenhagen interpretation of quantum mechanics.
• 19:20
  Niels Bohr ran him out of Copenhagen when Bohm went over to try to pitch.
• 19:27
  And then he was run out, very sadly, of the country, because this was the McCarthy era, and he was ideologically a communist.
• 19:36
  So he had to go to Brazil for the rest of his career, which, you know, given his stature, he could have done a lot more in some of the bigger universities.
• 19:47
  But he went to Brazil.
• 19:50
  He had a nice time there.
• 19:52
  The Arnav-Bom effect...
• 19:54
  People have said that this is the biggest development in quantum mechanics since...
• 20:02
  Dirac's prediction of antimatter.
• 20:07
  Okay?
• 20:07
  Pretty good.
• 20:08
  That's pretty good.
• 20:09
  The Arnoff-Bomb effect is so fundamental, it doesn't make sense why it hasn't gotten a Nobel Prize.
• 20:15
  Seriously.
• 20:15
  So here's the idea.
• 20:16
  The Arnoff-Bomb effect, and 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.
• 20:23
  But I'm going to give you a real quick...
• 20:27
  justification of the whole thing.
• 20:28
  So remember the double-slit experiment?
• 20:31
  The idea was that 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.
• 20:41
  And this is key to quantum mechanics.
• 20:45
  So now imagine, actually, if we can bring that photo 11.
• 20:50
  So now imagine we've got
• 20:54
  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?
• 21:06
  and in the middle, in between these two paths is a solenoid
• 21:11
  that has a current going through it.
• 21:13
  And because it has a current going through it, inside the solenoid, there's going to be a magnetic field.
• 21:18
  But if you remember from your undergraduate physics, outside the solenoid, the magnetic field is zero.
• 21:24
  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.
• 21:34
  And so there's no actual current
• 21:36
  which means there's no magnetic field outside the solenoid.
• 21:39
  The magnetic field is localized inside of the solenoid, okay?
• 21:45
  Now, for all intents and purposes in physics, the field is the real thing.
• 21:49
  But you can construct fields out of potentials.
• 21:52
  For example, the gravitational field is the real thing, but in order to sort of do mathematics with the gravitational field...
• 22:00
  We can invent something like a gravitational potential and say that, you know, the potential here is something.
• 22:06
  The potential here is a little bit more.
• 22:08
  And so the amount of energy it takes for me to go against the field is just the difference in the potential.
• 22:13
  And it's always the difference in the potential.
• 22:15
  I think the example you talked to me about one time is like imagine a hill.
• 22:19
  And you have someone that you're at the top of the hill or the bottom of the hill.
• 22:22
  Exactly.
• 22:22
  And your gravitational potential at the top of the hill is greater.
• 22:25
  And then it could do that.
• 22:27
  And then you can figure out how fast a ball would roll down the hill based on the difference.
• 22:30
  Yeah.
• 22:31
  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.
• 22:52
  Yeah.
• 22:53
  Right?
• 22:53
  Because the only thing that matters is the difference in the potential.
• 22:57
  Okay, that's fine.
• 22:58
  Um...
• 23:00
  For magnetic fields, we can also construct a potential that describes a magnetic field.
• 23:04
  But instead of a scalar potential, which in this case is just height, so there's no vector, right?
• 23:09
  It's just a number.
• 23:10
  For a magnetic field, it requires a scalar potential.
• 23:13
  I mean, sorry, for the magnetic field, it requires a vector potential, not a scalar potential.
• 23:18
  Now, that introduces some interesting things.
• 23:21
  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.
• 23:27
  But the potential is just a trick, right?
• 23:30
  It's supposed to be a mathematical trick.
• 23:32
  The field is the real thing.
• 23:34
  And in the Arnav-Bohm effect, my electron is moving one way and the other way.
• 23:38
  The field is in the middle.
• 23:39
  The solenoid is in the middle.
• 23:41
  And the field is localized inside the solenoid.
• 23:43
  So it shouldn't affect the two paths.
• 23:46
  that ends up not being true.
• 23:47
  If I turn on the magnetic field on and off, that changes my interference pattern.
• 23:52
  So this is very strange.
• 23:54
  Yeah, right, right.
• 23:54
  Because the institutional understanding was there should not be an effect on your beam outside of the solenoid.
• 24:03
  Outside of the solenoid, because the field is the real thing.
• 24:06
  Here, we're saying perhaps the potential could be a real thing.
• 24:09
  It's not just a bookkeeping thing, right?
• 24:11
  There are multiple interpretations of how this thing works.
• 24:14
  But the fact that it works and that I can experimentally do it introduces a lot of nuance into how we understand quantum mechanics.
• 24:23
  And that's why it's one of the biggest developments since Dirac's equation and his prediction of antimatter.
• 24:30
  So this was in 1959.
• 24:31
  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...
• 24:42
  understand from a philosophical and metaphysical level.
• 24:45
  Okay?
• 24:46
  We can do the calculations, right?
• 24:47
  It turns out that, you know, what you have to do is the quantum interference depends on the complete path geometry.
• 24:53
  Not just on these two paths, but like you do a sum over paths on every single one, and perhaps maybe there's some to go through.
• 24:59
  it's still like you know is that is that really what's happening and wavy yeah um like but the the local force along the path is not the only thing that matters that's the key right yeah there's there's like it's it's it's a global thing it's a global phenomenon i and i one of the things that always trip that trips me up but um is so interesting when we talk about these quantum mechanical stories is this idea that
• 25:28
  You have, it's not just everything matters, even the things that are not what you end up seeing experimentally.
• 25:35
  Exactly.
• 25:35
  And that is a brain teaser.
• 25:39
  Yeah.
• 25:40
  Yeah.
• 25:40
  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.
• 25:49
  The physicality is not, that we can engage in at the human scale is not the only thing.
• 25:55
  It's not the only thing.
• 25:55
  Yeah.
• 25:56
  It's, I mean, it's a trip.
• 25:57
  Every time you dive too deep into it.
• 25:59
  Yeah.
• 26:00
  Yeah.
• 26:01
  So David Baum died in 1992.
• 26:03
  And so Yakir Aronoff would be the only recipient.
• 26:07
  He's actually a professor of theoretical physics at Chapman University in Southern California.
• 26:11
  Oh, look at that.
• 26:12
  Right?
• 26:12
  So this would be a long time coming, I think.
• 26:17
  He published that paper in the late 1950s when he was a doctoral student.
• 26:22
  So this would be one of the record holders for the amount of time it took.
• 26:28
  To get it.
• 26:28
  From 1959 until now.
• 26:31
  That would be a big one.
• 26:31
  Yeah.
• 26:33
  Michael Berry, we were just on the Instagram live before taping this, and someone said Berry.
• 26:39
  This is who they're referring to.
• 26:41
  Michael Berry is a natural possible co-recipient.
• 26:44
  In 1984, he showed that a quantum state can acquire an additional phase when the parameters slowly trace some type of closed loop.
• 26:52
  It's a topological argument.
• 26:54
  It's related to the Arnav-Bomb effect, but not exactly the same.
• 26:59
  Again, topological physics is something that is incredibly important.
• 27:03
  Deep, complex, and yet simple.
• 27:06
  So, you know, if the Nobel Prize Committee decides to award topological physics another Nobel Prize, I'll have a field day explaining it.
• 27:15
  That'll be really fun.
• 27:18
  Does this relate to when we had these conversations about gradient descent?
• 27:21
  Kind of.
• 27:23
  And relate in the...
• 27:24
  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 escaping me right now however if there's a win we will cover it yeah we will cover it for sure uh physics 2 i'm gonna 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
• 27:51
  This one is so crazy.
• 27:52
  Yeah, this one is huge.
• 27:55
  Here's the idea.
• 27:56
  With the AFM, the Atomic Force Microscope, you can scan a sharp tip that is like...
• 28:03
  At the level of angstrom's thick at its tip.
• 28:06
  Like this is like something that is like at the atomic resolution.
• 28:10
  And what you do is you run a surface across it and it measures the interaction between the tip and the sample.
• 28:17
  I want to just double click on this.
• 28:20
  We're talking about very, very, very, very, very, very small.
• 28:25
  Yeah, like you see those hills and valleys there?
• 28:28
  Those are like on the orders of tens of atoms.
• 28:32
  Right?
• 28:33
  To now, I think people are doing like single atoms straight up.
• 28:35
  Which is so ridiculous.
• 28:37
  It's so ridiculous how we can sense such tiny, tiny perturbations.
• 28:43
  Right?
• 28:44
  It's completely led to the advent of precision nanotechnology.
• 28:51
  Yeah.
• 28:52
  A lot of really nice applications, like if we want to understand the stress and strain of materials at that scale, right?
• 29:00
  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?
• 29:09
  We can use AFMs.
• 29:11
  It's an absolutely revolutionary technology, I think.
• 29:15
  Under suitable conditions, they can even resolve single atoms, right?
• 29:21
  So nuts.
• 29:23
  It's huge.
• 29:23
  I mean, there's manufacturing benefits.
• 29:26
  There's biological health medicine, clinical benefits.
• 29:28
  Research benefits, yeah.
• 29:29
  It just applies literally everywhere.
• 29:31
  Yeah, exactly.
• 29:33
  And so the original inventors were Jerd Binig...
• 29:37
  Calvin Kuwate and Christoph Gerber, they all received the 2016 Kavli Prize in nanoscience.
• 29:43
  Kuwate died in 2019, so if the Nobel honors them, it's going to be only Binnig and Gerber.
• 29:52
  Binnig is a retired physicist from IBM's Zurich Research Lab.
• 29:59
  And Gerber is the Department of Physics professor at the University of Basel.
• 30:04
  So this would be two Swiss recipients.
• 30:08
  Europe's on the board.
• 30:09
  Yep.
• 30:11
  Europe's on the board.
• 30:11
  It's not just California forever.
• 30:13
  Goodbye.
• 30:13
  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.
• 30:31
  I mean, these things are not new.
• 30:33
  Yeah.
• 30:33
  And so we've come a long way.
• 30:36
  So when we talk about frontier research stories, you know,
• 30:38
  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.
• 30:49
  Yeah, this was 1986.
• 30:50
  Imagine what we're doing now.
• 30:51
  Right.
• 30:52
  So this was exactly 40 years ago.
• 30:54
  Yeah.
• 30:55
  And because of the AFM, we have such a...
• 30:59
  we have a much more finer understanding of nanotechnology, right?
• 31:04
  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.
• 31:16
  It's like opposite world JWST.
• 31:19
  Yeah.
• 31:20
  In the other direction.
• 31:20
  In the other direction, exactly.
• 31:23
  We are going to move now to the final category.
• 31:26
  Again, we are going to be having coverage every day for the first three days for the only real Nobel Prizes.
• 31:35
  Medicine, physics, and our final category, chemistry.
• 31:40
  Actually, can I just caveat that?
• 31:42
  Peace and literature are real Nobel Prizes because Alfred Nobel put it in his will that he wanted peace and...
• 31:52
  Literature.
• 31:52
  So there's really five real Nobel Prizes because that's what was in Alfred Nobel's will.
• 31:58
  But what about economics?
• 32:00
  I didn't, I don't, you guys hear something?
• 32:04
  Chemistry.
• 32:05
  Let's talk about chemistry.
• 32:06
  This is an inside joke for those who are new.
• 32:09
  But yes, let us proceed to the chemistry Nobel Prize.
• 32:14
  The first one, this is a recycling from last year because I do think this deserves it.
• 32:18
  Biomolecular condensates.
• 32:20
  I'm going to say it again.
• 32:22
  These things are everywhere in biology, and they were discovered by chemists for a very good reason.
• 32:31
  The idea is in biology...
• 32:34
  You need to bring particular molecules together in the right places at the right time.
• 32:39
  You need compartmentalization.
• 32:41
  Biology usually does this using membranes.
• 32:44
  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 cells.
• 32:53
  That's nice in eukaryotes because you want to compartmentalize all of your DNA, all of your chromosomes.
• 32:59
  You don't want all of the cellular machinery running around trying to get to your DNA, right?
• 33:03
  And that's why we have the wall around our DNA.
• 33:08
  We keep that safe.
• 33:09
  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.
• 33:17
  But look inside the nucleus, right?
• 33:19
  There is that blob, that orange arrow it's pointing to.
• 33:22
  Mm-hmm.
• 33:23
  That is the nucleosome.
• 33:25
  It's a compartment inside the nucleus itself.
• 33:29
  Some people like to call it the nucleus of the nucleus.
• 33:32
  And that's where a lot of the ribosome-making machinery happens.
• 33:36
  The ribosome is the protein-making factory of our cells, and the ribosomes are created in that nucleosome.
• 33:43
  But there's no membrane around that nucleosome, okay?
• 33:47
  The proteins just kind of aggregate there.
• 33:49
  The ones that are important for that particular process are just aggregating there.
• 33:53
  This is an example of a biomolecular condensate.
• 33:58
  It shows how compartments can form without actual membranes around them.
• 34:03
  The membrane-less compartment.
• 34:05
  Exactly.
• 34:06
  And the underlying physics is just phase separation.
• 34:09
  Okay?
• 34:09
  You can have proteins and RNA, and they can make weak contacts.
• 34:13
  And then those things can mix with other stuff.
• 34:16
  And you can kind of get, you know how oil separates from water very naturally?
• 34:21
  Yeah, yeah, yeah.
• 34:21
  Kind of the same way.
• 34:24
  These molecular condensates can separate from other dilute phases in a very natural way.
• 34:29
  And this is a purely physically driven entropic system.
• 34:32
  Like it's not, there's no active, like stuff is pushing, there's nothing active in an oil and water mixture that is pushing the oil together, right?
• 34:42
  Just the oil wants to be together and the water wants to be together because of the different chemistry.
• 34:47
  The same thing is happening here.
• 34:48
  There's different chemistry happening and that's what causes this phase separation.
• 34:52
  So who are the people involved?
• 34:54
  2009, I would say Clifford Bregwein and Tony Hyman and their colleagues, they showed that these pea granules in roundworm embryos behave like liquids.
• 35:03
  And those granules could accumulate at one end of the embryo through dissolution in just one region and then condensation in another.
• 35:11
  So it's the same substance, but it would exhibit different chemistry because of its environment.
• 35:15
  which was very nice.
• 35:16
  And then in 2012, Michael Rosen and his colleagues, they showed how proteins with multiple binding sites could assemble into droplets.
• 35:24
  So you got a protein that's got multiple little magnetic sites where stuff can, stuff can like bind.
• 35:30
  And depending on the interactions, you can have,
• 35:33
  Those proteins coalesce into a compartment without anything on the outside.
• 35:40
  So where are these people?
• 35:41
  Bregwine is at Princeton University.
• 35:44
  Oh, we're on the board, baby!
• 35:46
  So he is a professor in the Bioengineering Institute.
• 35:50
  Hyman is at...
• 35:52
  EMBL, which is the European Molecular Biology Laboratory, that's based in Heidelberg.
• 35:57
  It's kind of like a Max Planck, but not.
• 36:00
  I don't know.
• 36:01
  If they win, I'm going to go into what exactly that thing is.
• 36:05
  But it seems something like that.
• 36:06
  And then Rosen is a professor at UT Southwestern Medical Center in Dallas.
• 36:12
  okay so texas is on the board yep uh okay so fingers crossed fingers crossed for biomolecular condensates i really think that that's a because that one's another clean like sort of three people yeah yeah you know yeah so um and related to the most important academic institution of course so yeah of all time of all time so it's not that would be great um chemistry two yes this one's
• 36:41
  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.
• 36:50
  This is a widely used method for making carbon-nitrogen bonds.
• 36:54
  Nitrogen-containing groups are common in medicines.
• 36:57
  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.
• 37:10
  reaction is super important for creating drug therapies, right?
• 37:16
  In this case, what Hartwig and Buchwald did was they combined a mechanistic understanding with ligand design.
• 37:24
  Ligand is the molecule that bounds to some kind of catalyst.
• 37:28
  In this particular case, the catalyst that they always use is palladium, which I think is the same...
• 37:36
  It's the same metal that was used by Iron Man in the cave to create the...
• 37:40
  He did this in a cave.
• 37:41
  Yeah, he did this in a cave.
• 37:42
  The pot's scratch.
• 37:43
  Yeah, yeah, that was palladium, I'm pretty sure.
• 37:46
  In any case, that metal is kind of an intermediary that bridges this gap between the carbon...
• 37:52
  removing, like, let's say the bromine in this case, and then attaching a nitrogen there.
• 37:57
  And you can use this to control exactly where to attach the nitrogen in a convoluted organic molecule.
• 38:04
  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.
• 38:14
  So they actually shared the 2019 Wolf Prize.
• 38:19
  They were recognized for their catalytic work.
• 38:22
  So Buchwald is a professor of chemistry at MIT, and Hartwig is a professor of chemistry at University of California, Berkeley.
• 38:30
  So California on the board again.
• 38:32
  I don't know what to tell you guys.
• 38:35
  I think we're going to have some fun.
• 38:38
  Yeah, and those are my predictions.
• 38:40
  Let's see.
• 38:41
  Let's see.
• 38:42
  We wanted to keep it quick and tight today.
• 38:44
  We have a lot to prepare for next week for a fast turnaround after having just come back and still working through our interviews.
• 38:52
  And so for those who like long episodes, tune in next week.
• 38:57
  We're definitely going to get into the weeds.
• 38:59
  But please let us know for those who have finished, which should be most of you because this week's episode is very short.
• 39:06
  Let us know in the comments before Monday.
• 39:10
  What do you think is going to win a Nobel Prize in these categories?
• 39:14
  And then we'll see what happens.
• 39:16
  And if you end up being right, we'll make sure we comment back.
• 39:20
  So we're super excited.
• 39:22
  It's going to be a lot of fun.
• 39:24
  And maybe we'll do a little bit of a little live preview for those on Instagram.
• 39:29
  We did a couple of lives.
• 39:30
  We did a couple of lives.
• 39:31
  For fun.
• 39:32
  At the unction, as the kids say.
• 39:34
  Because we don't understand how to use these things anymore.
• 39:38
  But it's great to be able to interact with many of you.
• 39:41
  But with that, we are going to end nice and quick this week.
• 39:46
  Well under an hour.
• 39:48
  This is shocking levels.
• 39:49
  It's the first time in a while.
• 39:50
  Yeah.
• 39:51
  shocking levels probably in a year the last time was when we did the nobel prize episodes oh we know you guys like the long form we want 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 chowdhury we will see you all next week for the nobel prizes