From First Principles - Nobel Prize in Chemistry 2026 Explained: Mirror Molecules (EP 63)

Episode Date: October 7, 2026

Why does life favor one molecular mirror image? The 2026 Nobel Prize in Chemistry honors Henri B. Kagan and Kenso Soai for nonlinear effects and autocatalysis in asymmetric organic synthesis.Lester Nare and Krishna Choudhary unpack the science from first principles: chirality, Pasteur's crystals, enantiomeric excess, and how a tiny imbalance can grow into an overwhelming preference for one molecular hand.We connect Kagan's catalyst discoveries and the Soai reaction to medicines, the origins of biological handedness, and the serious concerns around hypothetical mirror life. Plus: symmetry in physics, Frances Oldham Kelsey and thalidomide, and our interpretation of a Nobel illustration.CHAPTERS00:00 Why life has a molecular handedness01:33 Hello Internet02:49 The 2026 Chemistry laureates06:24 Chirality and mirror-image molecules12:10 Pasteur and the history of handedness19:36 Why is life's chemistry one-handed?24:35 Frank and the origin-of-life puzzle29:14 Enantiomeric excess explained30:30 Kagan and nonlinear effects38:58 FFP and symmetry in physics42:20 Soai and asymmetric autocatalysis51:28 Why chirality matters for medicine58:21 What this does and does not explain about life1:00:25 Mirror life and biological risk1:10:37 Examining the Nobel illustration1:14:10 Recap and Nobel week reflectionsRESEARCH & FURTHER READINGOriginal papers and supporting context:Frank's model (1953): https://doi.org/10.1016/0006-3002(53)90082-1Puchot, Kagan et al. (1986): https://doi.org/10.1021/ja00269a036Soai et al. (1995): https://doi.org/10.1038/378767a0Sato et al., amplification (2003): https://doi.org/10.1002/anie.200390105Mirror-life risks (2024): https://doi.org/10.1126/science.ads9158Nobel announcement: https://www.nobelprize.org/prizes/chemistry/2026/press-release/EDITORIAL NOTESIntro: the 50:50 example describes an unbiased synthesis, not all chemistry. The Soai reaction is a clue to amplification, not proof of how life began.On-screen clarifications:04:38 B-DNA is right-handed; Z-DNA can form a left-handed helix.13:56 Pasteur separated sodium ammonium tartrate crystals.18:48 L/D configuration does not specify optical rotation.19:10 Proteins mainly use L-amino acids; DNA/RNA use D-sugars.22:55 Mentos mainly triggers CO2 bubble nucleation.27:18 Asymmetric catalysis and autocatalysis are distinct.34:07 0.25 × 0.25 = 0.0625 = 6.25%.36:31 Inactive mixed catalyst pairs are a simplified model.37:55 The normalized product-ratio curve need not be parabolic.42:04 Wu: preferential emission opposite spin; antineutrinos also emitted.45:30 5-pyrimidyl alkanol; an alkanol is an alcohol.47:10 The tiny-imbalance result is Sato et al. (2003), cited above.47:40 A demonstration of symmetry breaking by asymmetric autocatalysis.49:09 Above 99.5% ee means above 99.75% majority form, not exactly 100%.49:57 0.00005% excess is 1 part in 2,000,000.52:44 Thalidomide enantiomers interconvert in the body.53:36 Merrell applied in the U.S.; Kelsey withheld approval. Trial exposure occurred.1:02:09 Mirror-life catastrophe is a serious risk, not an observed outcome.1:03:28 Antibodies are adaptive immunity, not innate immunity.1:03:53 Impaired recognition does not mean proven total immune invisibility.1:04:27 Some treatments might work; ecosystem protection is very difficult.1:04:56 No reproducing mirror organism has been reported.1:09:19 Chimeras and genetic modification are not interchangeable.1:10:37 The Nobel-diagram critique is our interpretation, not an official correction.1:11:51 Solid wedge: toward; hashed wedge: away; ordinary line: neither.WATCH & FOLLOWFull video: https://youtu.be/Wdapv1hFT4wEpisode notes: https://ffppod.com/episodes/ep63Follow @FFPPod on Instagram, TikTok, X and Facebook.Breaking down science news so it makes sense to curious people everywhere.

A chemist in Paris and a chemist in Tokyo who cracked one of life's oddest habits. Look at your hands. Mirror images. But a left glove won't fit your right hand. Many molecules come in left and right versions too. One smells like spearmint. Its mirror twin smells like rye bread. But chemistry in a flask always makes both.

50-50. In 1986, Henri Gaga found something odd. A catalyst that was only a little right-handed made products that were mostly right-handed. Picture six right-handers and four lefties on a dance floor. Each lefty pairs off with a right-hander and sits down. Who's still dancing?

Only right-handers. Then, Kenzo Soai built, a molecule that copies itself and all, like a rumor that spreads. A head start of one molecule in 2 million became more than 99% in just three rounds. Life builds itself from just one hand. This is a clue to how that happened and a sharper way to make medicines. And this is the 2026 Nobel Prize in Chemistry. internet, this is your captain speaking, Lester Nare, joined as always by my co-host and our resident PhD,

Krishna Chowdhury. We are on day three and our final day of Nobel Prize week. We are going to go from the search for ghostly particles in Antarctica to the winner of the chemistry Nobel Prize. And this one is interesting and it reminds me of one of my favorite episodes that we did at the end of last year. We have left and right hands, and similarly, there are left and right molecules, but life overwhelmingly prefers one specific type. Today's prize is about how chemistry can make that asymmetry happen. It connects the way we make medicines to a much older question. Why did life settle on particular molecular building blocks in the first place. This is going to be interesting.

As always, we are going to talk about the science from the ground up today, starting with who won. The 26th Nobel Prize in Chemistry has been awarded to Henri B. Kagan of the former University Peresud in France and Kenzo Soai of Tokyo University of Science. in Japan. And the official citation is, for the discovery of nonlinear effects and autocatalysis in asymmetric organic synthesis. Talk about a mouthful. Yeah. But by the end of the episode, we will have unpacked that statement. And there's a hint in the words nonlinear and asymmetric auto catalysis. For anyone familiar with biochemistry, this should immediately ring a bell because

that's kind of what life is. Okay? It's a nonlinear phenomenon because, you know, reproduction happens. And if you've ever seen the bacterium sort of expand in a petri dish, from one, you get two to four to eight, and there's this doubling factor. So obviously that's nonlinear. And it's a kind of auto-catalysis because it's a bunch of chemical reactions that make themselves, right? The DNA makes more DNA, makes more DNA. Obviously, there are multiple steps in the process, but at the end of the day, is nonlinear and it is autocatalysis. It's also asymmetric because of the kinds of molecules that life prefers. Even though the molecules in life can exist in symmetric parts, life is remarkably consistent with which one it uses. DNA is a great example of this. DNA is right-handed,

meaning if I were to put my thumb on the axis of a DNA molecule, the curve is always the way that my fingers wrap around. It's always going to go right-handed, sort of clockwise, if I were looking up the axis of DNA. But you can make DNA that is left-handed, right? It's just that life never does it. So the two Loretz contributions fit together here because Kagan showed that a small imbalance in a catalyst can produce a substantially greater imbalance in the product. If you start out with a little bit more right-handed than left-handed, then you can make that non-linear effect. And so I found a reaction in which the product becomes the catalyst

for making more product. That's that autocatalysis part. Okay, so before we unpack the chemistry, what is the surprising part here? Why wouldn't a small advantage naturally just become a big advantage? Right. And that's actually what I was asking when I was researching this kind of stuff. It turns out that making more material and increasing its purity are two different achievements.

Okay. So if you repeatedly double, let's say you've got a mixture of 51, 49, okay? But the 51% of molecules start making their own version and the 49% make their own version. The ratio is going to remain exactly the same, right? So there's something in the chemistry that has to favor the majority. disproportionately for the imbalance to grow. And that is what this Nobel Prize is about. That's the key distinction. It matters for making useful molecules, including pharmaceutical intermediates. It also gives us an experimental way to investigate the Holy Grail of biochemistry, which is how a world of molecules, an abiotic world, without a consistent handedness, could give rise to the life that we have on the planet earth, which is all one particular handedness. So we've talked a lot about handedness and it's not just an analogy. So what does it mean for a molecule to be left or right-handed?

Yeah, we went into detail with our Yang Mills episode, but we'll do it again. So let's hold our hands. This is my left hand. This is my right hand. There is no transformation. that I can do to my right hand, like rotating-wise, that will give me my left hand. Even if I rotate it, right? Sure, they meet up to form like a prayer hand or a clap. But these are two separate things, right? Because in this case, the hand is facing me. The thumb is to the left, but the hand is facing me, my palm is facing me.

And here, the back of my hand is facing me. The front is facing the camera. So even though the thumb is pointing in the same direction, these are not the same, right? So it requires this 3D point of view to really understand this. And the chemistry world has a word for this. It's called chirality from the Greek word or hand. And so we would say that our hands are chiral. Now let's look at some of the building blocks of life itself.

This is aline. It's an amino acid. Sometimes you can buy it in a powder if you want to like get swall or whatever. Right. And on the left hand side, we see the chemical diagram. of this thing. There's a carbon at the center. It's an amino acid, so it's got an amine group, an H2 to its left, a carboxyl group to its right, that's a C-O-O-H, and then the R group, which is the thing that changes for every single amino acid. In this case, it's just a methyl group,

CH3. If you look at that diagram itself, you don't find anything funny. But if you look at the 3D picture, you find that there are two versions. There's the left-handed alamine and the right-handed alamine, which in chemistry they call D alamine. L-alamine is the left-hand version. And these are chiral molecules because there's just how with our hand, there's no way to rotate one hand to make it the other. There's no way to rotate the right-handed an antioamer, which is the right-handed version of this molecule, to make it the left. It's the same atoms. It's the same bonds even, right? The carbons are bonded to the oxygen in exactly the same way and the nitrogen in exactly the same way. But in one case, the oxygen is coming out of the page and in the other case, the oxygen is going into the page.

Just like how, like our hands, in one case, the palm is facing me, but in the other case, the back of my hand is facing me. Right? This is what we talk about when we're talking about mirror image molecules and why they're chemically alike in some environments, but in other environments, you can actually distinguish them. And that last detail is what matters. If you look at the left-hand side, the flat diagram does not give you the information. You need the 3D information to distinguish between the left and the right-handed version. Okay?

Now, not everything in life is chiral. You can have achyral molecules. For example, there is the glycerol molecule, which is just carbons with a bunch of OH groups attached. that is achyrol. If I take a mirror image of that, it's the same. Faty acids like butyric acid, again, if I take a mirror image of that, it's going to be exactly the same. Glucose, on the other hand, is chiral. So it's ribos. That's why actually DNA and RNA have a particular handedness, because ribonucleic acid in RNA, we only use a particular handedness, and that's what causes the spiral. Deoxyribose, again, has a particular

handness, in this case right-handed, which is why DNA is right-handed. So in biology, you have a mixture of both, but this has crucial implications for biochemistry in general. Because imagine trying to fit a right-handed glove into your left hand. It's just not going to work, right? And this has implications in biochemistry because the glove, you can imagine, is an enzyme that has particular handness, and it is expecting the same handedness of whatever thing that it's going to bind to, right? If you give it the other handedness, things are going to get funny. One of the big implications of this is, for example, the left-handed carvone, which is the odor that we get from spearmint, right? We've got a photo of that where we show the left-handed

version of Carvone is how we get spearmint. That's the odor that we get from, you know, when we smell mint. The right-handed version of the same molecule, our receptors in our nose get confused. They start smelling something completely different. It's the odor of Carraway. The same chemistry, the same, I shouldn't say the same chemistry. The chemist will get mad. The same atoms, the same arrangement of atoms. But in the same chemistry, but in the same chemistry, the same The 3D world, they look entirely different because there are mirror images. And that has an effect on how we actually sense this molecule. Right?

And so these two forms, they differ in activity, metabolism, side effects. Sometimes both are useful, sometimes not. And the point is that their behavior can be measured and you can infer it by looking at their activity. This is incredible. And so I think the next natural question here, now that we kind of, kind of understand this idea of handness, especially that you can look at a 2D diagram versus a 3D diagram, and there's different implications based on how you're looking at it. How did we, in chemistry, even get to the point where we discovered this idea of left and

right-handedness? Yeah, I mean, the Nobel Prize in Chemistry in this year, 2026, the results form from a long chain of ideas, as is classic in all of science. And the first result really goes back to the mid-19th century. It all began with Louis Pasteur. He was investigating a substance that is important from wine production. We all like wine here in California. He was investigating tartaric acid. He was French, so obviously, you know, they're obsessed with wines. Let me just say, it's been shown in international competitions that California wines are better than French wines. I heard he's from the French region of Tartaria. Is that a thing?

No, it should be. But in any case, tartaric acid is the stuff that you might recognize from wine diamonds. This is the like particulates that kind of settle at the bottom of a glass

or sometimes they form in the cork as you see on the upper right-hand side. These are little crystals of potassium bipartite and they take on the form, they take on the color of whatever wine is in there. They're harmless, and sometimes they're actually manufactured in wine barrels because they'll settle at the bottom, right?

Now, Louis Pasteur heard about tartaric acid, and his colleague said that sometimes they bent polarized light to the right, and sometimes the crystals bent polarized light to the left. And that really piqued his interest. So he grew crystals of tartaric acid and examined them under a microscope. and he discovered they exist in two different variants. On the left-hand side, we actually see some of the drawings that he made of these crystals. And you can see they're mirror images of one another. So the crystals themselves came in these two different forms. And one of the geniuses of Louis Pasteur is to look under the microscope and notice that difference.

Yeah. Under a microscope, it's very easy to be like, oh, they're the same crystal. but the mind of Louis Pasteur, the genius that he was, he noticed that subtle difference that actually, if you arrange them, because in the drawing, they come out in this nice arrangement, right? But that's because he's drawing it that way. Presumably, on the Petri dish where he's looking under the microscope,

they're in all these different arrangements. And he was able to notice, right, with a light microscope, that there are these two versions. And there, we have actually the Louis Pasteur Institute still has little vials of the bipartite that he made in these vials, which is absolutely incredible, right? So he discovered that there's these two variants, each that are mirror images, and then using little tweezers, he separated out samples of one-handedness

and samples of another handedness. But this is at the aggregate crystal level, okay? Now, from that aggregate crystal, he dissolved each thing in liquids, and he found that one of them, bent light to the right and the other one bent light to the left. This is a classic experiment that we see in like when we talk about chirality and molecules that are chiral, what you do is you have a light source that brings out unpolarized light, unpolarized light meaning the electric field of your light wave is in every direction. You put that through a polarizer,

which is like the stuff, you know, the sunglasses that we have with the polarized sunglasses. that's literally a polarizing filter that selects for a particular orientation of electromagnetic field. Like the light is oscillating in all these different directions, and the polarizer preferentially selects one particular orientation. So now that you have polarized light that's gone through this set of glasses, you put that through your sample, which is a dissolved liquid that has either the left-hand-side version of the crystal or the right-hand-side version of the crystal. And what he noticed was the axis of polarization would rotate as the light propagated through the medium.

And you can tell that by putting another polarizer on the right-hand side and seeing how much comes out. Depending on the angle, you would get a lot of absorption or not absorption at all. This is interesting. It's both kind of like a control mechanism on the left-hand side as the polarizer and then like a sensor on the right-hand side as an analyzer. Exactly. And this is a classic experiment now that we use in a lot of. of chemistry labs. The striking part is that the distinction between the left and right crystals survived dissolving stuff into the liquid and then putting it into this polarizer. Okay? So that's

telling you that the things that make up the crystal have that property of left and right-handedness. This was the key observation. It's not an artifact of the experimental setup. Yeah, yeah, yeah. It's not like the crystal is growing in some weird, you know, like the left-hand side of the petri dish has some temperature in the right-hand side. No, it's like literally the things that make up this crystal are left and right-handed, right? And this property matters because when it came to these tartate crystal molecules, the next experiment that he did was whether bacteria preferred one or the other. And he saw that indeed they did. This was in 1857. He investigated what happened if bacteria fermented on tartaric acid preferred growth on one medium versus the

other. He saw that bacteria willingly fermented. The bacteria were great at eating one particular type of tartaric acid. This is the same type that was found in grapes and found in wine bottles. But the other type, they did not eat at all. The bacteria did not grow at all. And this is the first indication that life's chemistry is somehow chiral. So Pastor kind of started this process by separating these different types of crystals, which are at a macro size level, because they had some differences in it. But the thing he really discovered was this underlying property of what would have been at the time these invisible molecules. Yes, exactly. And at that point, you know, atomic theory was new. Like there wasn't really a sense of like atoms and

molecules in the sense that we now take for granted, right? But that was the key conceptual leap. And later when researchers began studying life's building blocks, they discovered that naturally occurring amino acids all bend polarized light to the left. So all of the naturally occurring amino acids, you dissolve them into a solution, the polarized light always bends towards the left. And this is where we get left-handed amino acids like al-alinin that we were talking about earlier, lucine, valine, every single amino acid that is chiral, life uses only a particular type of chirality. And that's why we call life homo chirality, because homo is the same. Chirality meaning this handedness. Subsequent experiments in sugars found that DNA helix is the opposite. It's actually right-handed.

And the sugars are actually right-handed. And that's because the glove kind of fits the, you know, the enzymes fit the right-handed version, things like that. And this insight is pretty incredible, right? And the next question, obviously, is what happened at the dawn of life to make life? chemistry one-handed. Because Pasteur was able to create both versions in his lab. If you grow tartaric acid abiotically, you'll get both versions of the crystal. But everywhere that we see in life, they prefer only one-handedness. And when you try to figure that out, the main question is, why do living organisms only use one mirror image of the amino acids? Like, how can this preference

even arise. Now, some chemists just claim that chiral chemistry is unique to life, right? Maybe it could be that, like, there's like, you know, some woo-woo thing. Hand-wavy. Yeah, hand-wavy, woo-woo thing of, like, vitalism where, like, the life has some, like, force, right? That is beyond the laws of physics as of now that we haven't seen. But in the 1900s, a German chemist, Willie Markwald, he showed that, no, I can actually make a reaction that prefers one way or the other. This is the first time that we've found a reaction like this. He used a catalyst. A catalyst is basically an intermediary in a chemical reaction that facilitates a chemical reaction.

He figured out that actually if the catalyst itself has a particular handedness, then it will prefer to make products of that same handedness versus the other handedness. Well, sometimes the other way around. But in any case, you've got two different products that you can make, the left and the right-handed version. If the thing that is making the product is itself right or left-handed, then you can skew the chances one way or the other, right? And this particular experiment here, this is from the Nobel Committee, the visualizations that they put out. here the key thing is you've got a metal ion that is marked M in black that is associated with a chiral molecule and then that thing attaches to a substrate and that entire complex starts creating one particular

side of products versus the other right now in this case both are being created but one is preferred over the other in physical terms what this really means is that both pathways have different activation energies. We've got a little diagram that kind of shows this where if we talk about reaction progress on the x-axis, that means like going from reactants to products, you can think about it as a time axis. It's not exactly, but let's just say for this visual,

it's a time axis. The Gibbs free energy is on the y-axis. That tells you effectively what is the energy of the chemicals that are involved here. The reactants have a higher energy and the products have a lower energy. That's why, just like in physics, you go from high to low energy. But in order to get there, you have to go through this hill,

which is the activation energy. That's why every time you put reactants into a vial, they're not going to immediately go to products. A lot of times they're going to stay reactants because you have this energy barrier. When I put my Mentos into my Coca-Cola, it doesn't immediately explode. There's a little buffer time.

There's a little buffer time, and that's because, you know, the jiggling is getting over that activation energy. But as you know, the stuff is a runaway reaction because the jiggling creates higher temperature, which then creates more jiggling, which creates more jiggling. And so more and more stuff go over the activation energy. What's happening with the chiral catalyst is that the activation energy is decreased for the ones that are preferred, like let's say the right-hand side, has a lower activation than the left-hand side, because the catalyst is preferring that one over the other. And that's why there's more right-hand side reactants,

or products, I should say, versus the other, right? There's more right-hand-side products versus the other because the activation energy is lowered because that catalyst itself is right or left-handed. Depending on its handedness of the catalyst, the entry point for the end product of that same hand-diveness has a lower barrier to entry. Exactly.

And this was in the early 1900s. The difference was small, but the mere existence of it is revolutionary, because this means that it's not just life. We can create organic stuff in our petri dish, in our vial, that creates this asymmetry. So there's the potential. You're saying there's a chance.

The woo-woo, it's not the vitality. And there's a way to fundamentally understand what life is doing to make it homo-chiral. Like this is now where we are like, okay, there's a path that we can go down to understand that fundamental question. Exactly. And this is where the theoretical physicists come in. Oh, yes.

Right? This brings us to 1953. There's an article by Charles Frank from the University of Bristol. I should say, sir, Charles Frank, because he was knighted. He's a fellow of the Royal Society. And he is a theoretical physicist who a colleague describes to him the fact that chemistry and chemists can't really understand why life's asymmetry arose. And maybe a mathematical solution,

or like at least a roadmap to understanding this problem, would be nice. And so Charles Frank writes this paper, and it's kind of a, it's a classic, like, theoretical physicist paper of like, this is trivial. He's the kind of theoretical physicist that everyone hates, especially the experimentalist. Okay? Like in his introduction, he talks about how like, you know, this is guys.

Why are you wasting my time? Yeah. Yeah. And he responds with three categories that we need to establish in order to make something like an asymmetry like this happen. The first one is that there is a chiral catalyst and an asymmetric reaction. That's the kind that was that we had just discussed from Willie Markwald. The second stipulation is that the formation of one of the mirror images is somehow enhanced and the other is dampened. This means that there's an inhibition of types.

You're not just making both. Somehow the presence of one is making the other one worse. And the third is that the chemical reaction has to form the catalyst itself. You need a runaway reaction. You need the product itself to go back into the reaction and feed in. So you get this nonlinear effect. So he's putting out a roadmap, okay? That last part is called autocatalysis,

and that's the self-reinforcing effect. And Frank concludes his report by just laconically noting that a laboratory demonstration may not be impossible. Like, really? This is something that classic theoretical physicists do. It's like, oh, why don't you just figure it out? Just go do it. Yeah.

Like, what are you asking me for? Yeah, it's like, oh, really? Okay, nice. Well, his paper does make waves because now we've got kind of a roadmap on how to get there, right? And it's spread widely among chemists. It becomes kind of a chemical puzzle that university lecturers present to their students. Like, this is an open problem. Let's see if you guys can figure it out. Now, Mark Wald, as I said, had already succeeded in the first condition at the start of the 20th century. And autocatalysis, asymmetric catalysis, is also something, that has been figured out. The 2001 Nobel Prize in Chemistry recognized William Knowles, Rioji Noyori, and Barry Sharpless for important chiral catalytic reactions. This is the autocatalysis that we're talking about. And that led to the industrial route to L. Dopa,

which is a pharmaceutical that's used pretty widely. And in 2021, the Nobel Prize recognized Benjamin List and our favorite chemist on the podcast, David Macmillan from Princeton University. Go tigers. They created asymmetric organocatalysis. So organic chemistry that preferred one way or the other, right? All of that is fine. The Nobel Prize in Chemistry this year recognizes the fulfillment of the remaining two conditions,

Meaning you need inhibition and you need that inhibition paired with catalysis, this runaway reaction. Okay? So in nature, there's this 50-50 thing where it happens naturally where it's not asymmetric. And through 2021, we had all of these different ways to artificially create an asymmetry. But the thing was to fulfill sort of the ultimate vision, we still had two missing variables. And those specifically are the difference between the past Nobel Prizes and this Nobel Prize. Exactly. In this particular Nobel Prize, we are establishing the nonlinear effect, which is this sort of property that, like, I can get more asymmetry from underlying asymmetry and the fact that we can

have a runaway reaction, that autocatalysis part. Okay. So to make that question measurable, there's one scientific sort of, there's one scientific like parameter that I need to introduce to everyone. And this is the idea of an antiomeric excess, abbreviated EE. This is the difference between the amount of left-handed stuff and the amount of right-handed stuff. If I have exactly 50% left and right, that's a zero percent excess, right? Because I have exactly the same. If I have all of one percent, all of one type, if I have all of like left-handed and no right-handed, that means I have 100% excess of left-handed stuff, right? This is a key thing, a key parameter that we're going to have to deal with as we move on. Okay, so a 50-50% mixture, that's a zero. If I have a

60-40 mixture, that's a 20% excess because it's really the difference between how much of one I have and how much of the other I have. And that distinction is essential as we get to talking about how a small starting imbalance is going to create a large ending imbalance. So 2% excess is almost a coin flip. Yeah. And then 51, 49 of the other. That's 2%. That's 2%.

Yeah. And that's almost a coin flip. Okay, okay. Okay. Yeah. Okay. Yeah. So I think we now are getting to our Nobel laureates.

Yes. We know this setup. And, you know, as a fan of Tieri Henri, the French footballer, although he was an Arsenal player, this is a Chelsea house, we will start with Henri Cagan. And so what was it that he discovered as a part of now this setup we've created? Right. So now we get to our actual Nobel laureates. Henri Kagan tries to tackle the nonlinear part of the Nobel description. Okay. Let's suppose that we start with a pure right-handed catalyst that favors right-handed products, right-handed products. Mark Wald has already shown that. If you start with, like, the catalyst itself has a particular geometry,

then the products are going to favor some particular geometry. Okay. So let's say the right-handed catalyst favors the right-handed product, and the left-handed catalyst favors the left-handed product. The prevailing wisdom at the time was that if each of these catalysts work independently, then if I start out with, let's say, a 60-40 mixture of catalysts, the ending reactants are also going to be 60-40 because 60% of the catalysts created the 60% products, the 40% of the right-handed stuff created the 40% and the ratio is going to remain the same, right?

The slope in this case is going to be one. Like if I start out with some ratio, I'm going to end up with some ratio. The slope could also be something different. For example, like, you know, if I start out with 60%, I could end up with 30% of something. But the line is going to be linear. Because maybe, like, you know, there's some, like weird effect that happens and, like, one type goes one way and the other type goes the other way. The line, if I increase the asymmetry on the catalyst side, I will just only linearly increase the asymmetry on the reality. react inside. Okay? Because these things are working independently. Right. Okay. That is the assumption

that Kagan starts to question. Okay. Okay. Everyone believed this at the time. Kagan's like, well, you know, um, if you think about the catalyst itself, we don't actually know how it works. Okay. And during a chemical reaction, we've got this metal atom, right? That's like doing a lot of the work. But the metal atom could be doing different things if there are multiple agents in involved, okay? Metal atoms normally react and interact with several molecules simultaneously. They're not just like, oh, I'm going to stick to this guy. They're recruiting all sorts of other stuff. And that's why metals like zinc and things like that are very important for our body as cofactors, because they actually help proteins recruit all sorts of other types of

stuff. Now, here's what he considers, right? Suppose we've got two chiral molecules. that are catalysts. There's a left-handed version and a right-handed version, and we combine it with a metal atom, right? Now, this metal atom is going to recruit two of these to create mixtures. So we're going to get three possibilities. We're going to get a right-right mixture, a left-right mixture, and then a left-left mixture, right? But because of combinatorics, if I start out with a certain asymmetry, that asymmetry is only going to grow because of my mixtures. For example, if I saw a lot of my mixtures. For example, if I start out with 25% and 75%, I'm going to end up with 6% and 56%. Like if I start out with 25% left, the commentatorics there is going to be 0.25 squared, which is going to be 0.625. So these guys are rounding to...

Boo! They should say 6.25%, but this is the popular information and they don't want to deal with decimals like for the plebs. But it should really be 6.25%. That makes sense. If you guys are taking the GRE, don't round. Don't do that. Okay. So you get 6.25% of the left-hand side.

You get something like, I think it's 56.25%, or I don't know what the, you know what I mean, of the right, right? And then the mixture is going to be about 38%. It's really 37. Something something percent. But that's the key distinction now, right? So you've made these mixtures of molecules that have a different ratio. than what you started. It's not that same linear ratio we just talked about previously. Exactly. And now, if you create this type of multi-molecular interaction and you try to run your

reaction through, what are the products going to look like? This is the big paper that comes out in 1986 in the Journal of Chemical Society, the Journal of the American Chemical Society, he shows that actually, for a particular type of reaction called the sharpless epoxidation of geronial, which is depicted on the lower there, we don't get a line. We get a non-linear effect. If I increase the amount of asymmetry or I increase the amount of right-handed versus left-handed, I don't get a straight line. I actually get a difference.

I get a slope that is very, very much a non-linear effect. The type of reaction here is the Sharpless epoxidation that's named after Barry Sharpless, who won the Nobel Prize in 2001. So this is building on some of the asymmetric oxidation stuff that Barry Sharpless had done earlier on. The left-right catalyst behaves differently. And that is the key distinction that he's trying to make. So theoretically, what's happening, he actually tries and figures it out. Now we have the complete picture, right? We've created these left-right catalysts, and we've created the left-left and the right-left.

Sorry, left-left and the right-right, right. What ends up happening is the left-right catalyst, the mixture, can't do anything. It is completely useless. Inert? Yeah, in some sense. Yeah, it can't react with anything because I guess, you know, it's getting confused about which type of reactant to make. And now, at the very end, you're taking out that middle 38 portion.

Yeah. Yeah. And you get a huge asymmetry. Yeah. Yep. Yep. Right? Before we had 6%, 38%,

58%, 56%. But the 38% is not creating any reactants. And so if we look at the reactant distribution, we only get 10% of reactants and 90% of the right version. 10% of the left version, 90% of the right version. which is basically taking up all of the product that would have come out of the left right because effectively it cannot it cannot can't do anything catalyze yeah there's no catalysis happening and so this is nonlinear yeah because you're starting yeah with 25% 75% and you're

ending up with a 10% and a 90% and specifically this mixing mechanism is a multiplicative thing right which is why we're getting that slope right right If it was just an additive thing, that the slope would just change, but like, it would still be a straight line. The fact that it's multiplicative means that I'm getting a parabola, right? Yep. And that's why you've got a curve in that reaction kinetics. Yep. That's the key distinction that's happening.

This is the positive nonlinear effect. And this is the nonlinear part of the Nobel Prize discovery. Exactly. So if we go back to the top here. Right. The official citation is for the discovery of nonlinear effects and autocatalysis and asymmetric organic synthesis. So now we've identified, this is the first piece. Yeah, the nonlinear effects. Right. And this is a historic breakthrough.

It's historic because many chemists didn't think it was possible. And now they start exploring this new phenomenon. Everyone in chemistry who cares anything about asymmetric catalysis starts exploring this. One of these chemists is Kenzo-Soai at the Tokyo University of Science. And he comes up with the final link in that Nobel Prize citation. And before we get to that, let's do some housekeeping, because we haven't done that in a while, and I think we deserve it. A quick opportunity to shill, a quick pause.

So you can find all of the papers that we talk about and go through on the show at our website, at FFPpod.com. We do short clips and little bite-sized takes of some of the best science that we talk about on our socials at FFP pod. And, you know, one of the best ways to help this show get seen by more people, to like, share a comment, share it with somebody you think would find it interesting. Five-star on Spotify or any of the podcast networks really helps us get the best science show on the planet out to more people.

And I just want to note, I was so excited when I saw the announcement this morning because one of the, and you mentioned this earlier, one of the biggest unlock episodes for me in terms of my mental framework around the sciences was when we talked about, due to the unfortunate passing of Chenning Young at the end of last year, we have an episode, The Man Who Unlocked Symmetry. If any of these concepts are super interesting to you and you want to know more, whether it's about parity violation or the birth of Yang Mills, that episode is an absolute banger. Yeah, it really is. And the one thing that I want to mention about that episode and its distinction with this one is the fact that physics does care about the mirror world. Yes. In chemistry, as we said, you can create a petri dish of both left-handed and right-handed stuff. And you might be thinking, well, you know, does everything? in physics care about left-handed or right-handed or not? Like in chemistry, it clearly doesn't.

In physics, in fact, there is a way to tell between left-handed and right-handed stuff. And we do this great analysis that Richard Feynman actually originally did, where he talked about, you know, if we were to call up an alien, how would we tell him left versus right hands, right? We can't use chemistry. We can't be like grow some glucose and then make it go through light and see which way the light turns because the glucose on earth, sure, it's turning to the right-hand side because glucose is right-handed here on earth. But the alien is going to grow crystals and then like Louis Pasteur, he's going to be like, well, there's two different types of crystals and like this type of crystal is going left-hand, this type of crystal is going

right-hand. Or in the worst-case scenario, the alien has a left-handed version of life, right? He's still somehow eating glucose, but his version of glucose is all left-hand. candid. And so he goes the other way, and he thinks his left is our right. Chemistry cannot make that distinction. Physics, on the other hand, can. Chen Ning Yang was one of the key people who understood that. And CS Wu, the very famous Chinese physicist, she did not win the Nobel Prize very controversially, but she proved that that was in fact a fact of the universe, that parity violation exists in beta decay where neutrons spit out a proton and an electron, but the electron only spins in one direction versus the other. It's an incredible episode. It's actually one of my

favorites as well. It's so good. And beta decay coming up again. Yeah, we talked about beta decay yesterday. So yeah. Okay. So with that said, we now have the nonlinear part of this 2026 chemistry. Nobody The next word in the Nobel description is autocatalysis. How do we get there? Yes. This is where we get into autocalysis. The idea of autocatalysis is that the product participates in catalyzing the reaction that produces more of the product,

that then catalyzes more of the reaction that produces more of the product. So as the product accumulates, you get this runaway reaction. And a signature of this type of reaction in reaction kinetics is, As time goes on, you get kind of a sigmoid, where the first half is like exponential, because the more and more products you get, you start blowing up. But as you start running out of the reactants, you reach a baseline where all of the reactants are finally taken care of. Life has a bunch of this type of autocatalysis.

For example, there's several cycles that we have in life where, you know, you create a particular product and then that particular product feeds back into the cycle itself. The Krebs cycle in mitochondria is a great one. The Calvin cycle in photosynthesis is a great one. So life does this all the time, right? And you can imagine like, kind of makes sense, right? If you've got a workshop that builds tools and then the tools build themselves, then you've got this thing going. If you want a $3,000 a month payday for life, what would you feel free to do? Maybe take a long weekend every weekend or try a bunch of new hobbies. Would you feel free to upgrade and listen ad-free?

Don't worry, we get it. Every $20 ticket could win you $3,000 a month for life and supports life-saving cancer research at the Princess Margaret. Feel free to buy your payday for life ticket today. Raffle number RAF 157-3916. Please play responsibly. This is not recursive self-improvement and we're not talking about AI. Yeah, we're not talking about AI.

although that is also a runaway effect that we should be certainly concerned about. In any case, so So I and his collaborators, they start exploring reactions in which organo-zinc reagents add to aldehydes to make alcohols. Let's take this particular reaction here. This is an asymmetric catalytic addition of dimethyl zinc, which is the ME-2-ZN. ME is the methyl, so dimethyl group. this is being attached to a chiral ligand on the left-hand side, the pH is a phenol group.

That's a C6H5, okay? When you scrutinize this thing, look at the product. The product also has a fennel with OH. It's a bit different from the reactant, but it's also kind of similar to the thing that is catalyzing the reaction at the very top because it's got a phenol group and OH group and extra carbon.

And the carbon, if you can somehow attach it, to the N-benzine feridine, the NBN over there, then perhaps you could make more of this stuff. Okay? So this is kind of like, you know, maybe there's something here. This sparks an idea, right? Perhaps you can design a reaction where the catalyst forms itself. Now, at this time, early 1990s,

there's several known examples of auto-catalytic reactions, but none that are asymmetric, okay? There's several reactions of this thing doing it, but we need something that prefers one hand over the other, right? And by experimenting with many different molecules, so I succeeds in finding a chiral substance called five pyramidal alkalinol. I almost said alcohol and chemists with their, dude, I remember organic chemistry, like if you put down alcohol and not alcanol,

which by the way, the H kind of looks like an N, like you get a zero. Oh my God, I hate it, Orgo. But in any case, five-paramidal alkynol is a chiral substance that so I finds that can create itself. And in a publication in 1995 in nature, he describes this revolutionary experiment, asymmetric autocatalysis and the amplification of inantiomeric excess of a chiral molecule. Bangor title. For anyone who is in the field, like this is like, oh, you did it. Right.

And this is literally like the word for word, some of the stuff that the Nobel Committee is citing, right? Asymmetric autocatalysis. So a great title, 1995. It's not the end of his work because this is kind of halfway there. It starts with a 2% excess of one in Antiochomer and ends up with an excess of 87%. That's pretty good. But, you know, the reaction is not what life does because in life, you start with a little bit of excess and you've got to get to 100%. It's the Riemann hypothesis. We got to rule out all of the non-trivial zero.

Yeah, yeah, yeah. Even when you get to 100%, yeah. A little different. A little different. A little different. But at least this is like some statistical type thing, right? We're getting close. We're getting close, right? So another eight years, Soey's Lab just continues their search. And they finally find the ultimate auto-catalytic process. In 2003, they published in the American Chemical Society Journal. This journal, by the way, is just one of the goats for chemistry. In last year's episode, if you look back, a lot of the MOFs, the metal organic framework papers came out in the American Chemical Society Journal. So, like, kind of goes under the radar compared to, like, nature, science, but this thing... We see you?

Yeah, we see. This thing is a heavy hitter. This is the first time that anyone had successfully created chirality from non-chiral combinations of molecules since the dawn of life. This is where he got to 100% pyro. Unbelievable. Okay. Since the dawn of life.

Yeah. Since the dawn of life, this is the first time. It's called the So-I reaction, and it is considered by chemists as the most elegant chemical experiment ever conducted by some chemists. I just want to note the pronunciation of the last name, So-I, being the one that, like, created this, is also just like a sort of aesthetically. interesting naming convention. It's like, so I and I only.

Yeah, anyway. Yeah, I think that is quite funny. I mean, it's considered one of the most elegant chemical experiments ever conducted, which that is a high bar, you know, to meet. So here's what's happening. When you start the catalytic process, you've got both an antiumers that are present, but a tiny excess of just one creates 100% excess of that one. And that's because...

Effectively, what's happening is one enantiomer takes over the entire reaction. The left-hand side creates only left-hand catalysts, and the right-hand side creates only right-hand catalysts. But if you've got a tiny imbalance, the left-hand sides create way more than the right-hand side, which is going to then create way more, which is then going to create way more. So you start out with something like 0.000-0-0-0-05 percent. after the first run, you get all the way to 57%. Unbelievable.

After the second run, you get to 99%. And after the third run, you get to 99.5%. It's a runaway reaction because of auto catalysis. That is the key. The thing is creating itself, which is then creating itself, right? This is, I remember seeing this image in the Nobel materials. And without necessarily connecting the dots, understanding, like looking at this runaway, in three runs, in three runs,

with how small your starting point was in terms of the imbalance, clearly was going to be important. Yeah. Now the connection as to how and why is fascinating. Yeah, and it's like one part in, what, 10,000, I think, if I'm doing the math right? One part in 10,000 is leading to, in three runs, 99.5%, almost at 100, right? Just one of them is just dominating. just because of the chance beginning asymmetry.

And the small scale of that chance asymmetry at the beginning is very small. Yeah, yeah. It could have gone the other way, right? And then in which case, we would have had a lot of the left-hand side. This is so good. And so now we've kind of gotten to the point where we understand now all of the component parts. Yes, exactly. And just to say it one more time, the non-linear.

effects. That was Kagan. That was Kagan. Kagan. Kagan. Yeah. No, no. And then if it's not, you can let us know in the comments.

Yeah, please. And then autocatalysis, which is what creates this runaway in asymmetric organic synthesis, which means the inputs have that slight asymmetry. And it only, it doesn't always have to have a slight asymmetry, but it only requires a slight asymmetry in this example. To then create this 100% runoffer. way. And this is fascinating for a lot of reasons.

Obviously, we made the connection earlier to how, you know, a couple of things. But one of the notes was that this changes how we make medicines. Yes. Or pharmaceutical. So how does that connect to the impacts now that we have this understanding? Yeah. And this leads to like, you know, some of why chemists are so motivated by this. The aim is to produce an antem tumors that are as pure.

pure as possible. For example, in pharmaceutical manufacturing, you want a particular type of handedness for the drug that you're making. You don't want to do Louis Pasteur, where you've got both sides. The importance of achieving this has been shown by the thallidomide, the thallidomide scandal of the 1960s. I don't know if you're aware of this. I was not. But this is an incredibly dark time in chemistry, in pharmaceuticals, and in the world at large. Like, aside from war, this is one of the worst disasters in history that I hadn't really heard about, which I was really surprised by. So this is the thalidomide scandal of the 1960s when thousands of children were affected

by birth defects caused by a sedative thalidomide. It was widely given to pregnant women to treat morning sickness. It's actually incredible that, like, there's so little testing on pregnant women to create such a tragedy, tens of thousands of people were affected. And when researchers analyzed what had happened, they'd realized that it was an active substance. The mirror image was causing the harm. Both mirror images were in the drug.

And while one of the mirror images was actually creating the sedative version, the other mirror image was causing these defects. And I want to take a brief note here and talk about, Why the world at large was very much affected by the thallidomai scandal, tens of thousands. I'm talking literally tens of thousands of birth defects. The U.S. was spared because of Francis Oldham Kelsey. And if you go back to that photo that we had, Francis Oldham Kelsey is the hero in our story for America.

Because she was a pharmacologist working for the U.S. Food and Drug Administration. she blocked the drug's approval in the United States, despite heavy pressure from the manufacturer, Grunenthal, which was a German pharmaceutical company, they were trying to pressure the FDA to approve this thing. She saw the writing on the wall in early clinical studies that others had kind of just handwaved as like, oh, that's just a hand of God, like, chance stuff.

She was looking at the data going, no, no, no, there's clearly an effect here. I don't know what you guys are talking about. She received a lot of pressure from lobbyists, from, like, you know, I can imagine, like, as a woman at the time in the 1960s in the Food and Drug Administration as a scientist trying to block approval. But, you know, it took her and it largely spared the U.S. from this crisis. There are several other countries that are still dealing with this. Japan, Australia, a lot of Europe. These are developed nations that have their own versions of the Food and Drug Administration. But somehow the pressure from Grunenthal, like actually, you know, they succumb to that pressure.

We did not because of her. And, you know, there's a photo of President John F. Kennedy giving her the president's award for distinguished federal civilian service. It highlights why the FDA is important. I want to bring this up in today's climate where apparently we're just making decisions with the FDA that, don't make sense to me. Don't make sense to a lot of trained scientists. I just wanted to show that this is one of those situations where you really need independent thinkers in our government

to make informed decisions. America was spared from that crisis. When the next crisis comes, we need someone like Francis Oldham Kelsey to do that again. And just to piggyback on that, I think this also highlights the importance of not allowing commercial influence in sort of public health decisions, as well as research and R&D decisions.

There needs to be a healthy tension there. And this is a perfect example of you don't want it to become too late because you've allowed sort of this runaway corporatism to infect civic institutions. to their own benefit for the sake of shareholder value at the expense of a potential catastrophe that can last generations. And that's, these decisions can last generations. Right. And these countries are still dealing with it to this day. I think it was only the last decade when, um, decade. Decade. Yeah. Very good. Yeah, but only in the last decade was that company actually apologizing for what they did, which is like 50 years later. Yeah. Yeah. Really? And a lot of, I was, I,

I mean, I went in a deep dive on this. A lot of like the original scientists and shareholders and the CEO of that company in the 1960s that was peddling this thing, they were just trying to, you know, avoid any sort of responsibility. They avoided responsibility for most of their life until most of them had passed away. And then they had the repercussions. It's, if you guys want to like, you know, go into a deep dive about, like, how badly things can go wrong, you should look up the thalidomide scandal of the early 1960s. But I think this highlights something about drug development,

which is chirality is a practical design and quality control issue, right? If two mirror images interact differently with the body, then the manufacturer needs to understand which form is being made, how much of it is being made, and how we can actually create asymmetric synthesis where we can build a preference of one over another, right? Understanding these non-linear effects helps researchers interpret experiments, identify active species, and decide how to actually improve

selectivity. So this year's Nobel Prizes, the work that they've done is very much important for drug development at large. This is, it's so interesting. I think, you know, I've talked about this previously. You know, my dad has worked in stage one drug discovery for quite some time. and this is one of those things where, you know, even in the course of his career, the change of understanding has impacted what he's been able to do and work on. And it's always touching on stories that have a tangential connection to allow me to understand his work a little bit better. I always find gratifying.

And I know you feel the same when we talk about stuff in the other category for you as well. But I think this now brings us back to the last missing piece from the, beginning of the episode set up, which comes back to this age-old question about life. So how does this now, you know, what does all of this say about why biology is homo-chiral? It only has one chirality. Like, how does this now connect to that bigger question? Right, right. And you might think that this sort of answers it, right? Because the So-I reaction shows that you can start with a small asymmetry and get, you know, 100% one way or the other. Now, that is certainly true, and it has a lot of compounding effects for drug development,

as we talked about, in fundamental chemistry questions at large. But at the end of the day, the so-eye reaction is artificial, and it is a bit different from the chemistry of life. It still awakens a new enthusiasm in chemists who want to understand life's origins, but the connection to life is limited in some sense, because these experiments demonstrate that the chemical route from little or no handedness to a very strong preference for handedness that is certainly possible. Whether the mechanism four billion years ago was exactly the soy reaction or some other part,

it's not entirely clear, right? I mean, there's the extreme case where life came from outer space, and that already had a handedness. So then, you know, that answers the question. So, so origin of life is a very, is a very different question. But this certainly gets to things that are possible, right? You know, it tells you that you don't need like an outside, like agent. Invisible hand.

Yeah, invisible hand, vitalism, like some mysterious force that's in life that creates these building blocks one way or the other. Now, around the world, researchers are taking the next step and they're trying to repeat so-wise achievement, but with the aim of producing homo-chiral amino acids and sugars. Right now, we've done simple molecules. We'd like to make even more complicated molecules, but we need to be careful. Okay. Okay? We do not want to make mirror life.

And in the recent times, we've had a lot of, like, alarmist news coming out about dumer's? We have more dupers? We have a lot of dupers. There's AI dupers. The mirror life dupers have been around for a while. Why? Okay, ever since we figured out that life is chiral and we've been able to make asymmetric

catalysis happen, there have been AI, there have been mirror life domers that are telling us not to do it. This is just a few of the headlines. Mirror life is still hypothetical. Here's why it should probably stay that way. There was a news article in nature that said, how should mirror life research be restricted? The debate heats up. My favorite one is mirror life is a mass extinction risk.

we don't need to take. Okay? I want to go a little bit into some of this because, so what is mirror life? What it means is the molecules and the proteins that make up these organisms would be completely mirrored from the ones that we have. This would require mirrored sugars, mirror DNA, mirror proteins, like everything, literally everything that this particular life form that we create would have the opposite version. Okay?

Now, this has issues if it is created and if it escapes the lab. Some really, really bad issues, okay? Because suppose you create a mirror bacterium, like a bacteria where everything is the opposite chirality from normal life. Okay? So that means the amino acids are right-handed. That means the sugars are left-handed. Everything is opposite.

What that means is that you can have a bacteria that proliferates, but there is no defense mechanism on the earth that is suited to combat this thing. The viruses, like the bacteriophages that prey on the bacteria, they require chiral mechanisms to get into the bacteria. Well, if the bacteria has the opposite-handedness, the virus can't really screw itself into the bacterium and kill it. You can't. The Lego blocks don't. Yeah. A lot of our antibiotics are chiral in nature. And they require the specific chirality of the bacterial proteins to attach and then destroy. Now you've got, you know, there's no predation. There's no effective predation.

And the accompanying increase in the bacteria would create this runaway reaction because the bacteria would just start eating. Suppose it's photosynthetic, right? It doesn't, it would just. like all it needs is water which is not chiral carbon dioxide which is not chiral and sunlight which is not chiral and it would just create the opposite type of glucose the opposite type of proteins boom you get a runaway reaction right um in humans we've got an innate human immune system and the first line of human defense in the immune system against microbial threats relies on a pattern of recognition where you've got antibodies reacting to the inviating to the invioms

or you've got antigens. No, the antigens are the invaders. The antibodies react to them, recognize, and then you've got the second line of defense that characterizes, okay, we need to start an immune response. Well, if our antibodies do not recognize the antigens and they have no hope of recognizing the antigens. Because you can't.

Because you literally can't make the opposite chirality antibody. Yeah, that's dangerous. Right? That's dangerous. Yeah, it's, this is. is getting weird, right? So immune systems will go bad. Instead of causing standard infections,

the mirror pathogen is going to act more like a cancer. Because we're not going to even have an immune response to this thing. The mirror pathogen is just going to go in, and it's going to start occupying space. It's going to start reproducing and creating a runaway reproductive reaction that's going to use bodily energy resources, and there's going to be no existing countermeasures.

This is a very scary prospect. Yeah. Right. So image mirror life is really quite a danger. OG doomers might be on to something there. Yeah, yeah. This is from way back, and they've been calling for bans on this thing for a very long time. Now, what's the current status?

Now, mirror life does not exist, and it can't form naturally because natural biology prefers one-handedness, and mirror life is necessarily the other-handedness. put a qualifier there that says on earth? On earth. We should. Not that it's, yeah, we haven't seen extraterrestrial life at this point in time. But that's also a reason why bringing stuff back is not a good idea. It's not a good idea as well. Yes, exactly. And and that's also a reason why bringing stuff there is not a good idea as well, right? So that's why when we go to places like Europa to look for life, we better know that like all of our equipment is sterilized in some sense, right? Because Europa could have the other handedness of life. Now, it's challenging to build

mirrored life, right? You need to create a central dogma that is a mirrored central dogma. Like, for example, nobody's created a mirrored ribosome where all of the amino acids and all of the RNA are exactly the opposite type, let alone some major components like the TRNAs that are required for protein synthesis and things like that. You would need a mirrored DNA. You would need a mirrored RNA. You would need mirrored RNA polymerases. So all of this stuff needs to happen. And like, you'd really need to like try. Yeah, yeah, yeah. Yeah. You know? Um, it, it, it, there's so many similarities with the ongoing AI safety conversation just in terms of like, they're being two camps. People are like, this shouldn't happen. Uh, and then other folks saying, well, we don't even,

we're not even close. Yeah. Right. It has that same, uh, dynamic. Um, part of the challenge with things like this is because we are increasing in our ability to do scientific innovation generally, AI enabled or not, the gap time between we don't have any of the component parts to having the component parts, it's not necessarily the time compression there is non-trivial. Exactly. Yeah. And so right now, the best we've got is like a scientific moratorium. Okay, in 2024, there was an international coalition of 38 leading scientists, including some Nobel laureates. they published this landmark call for a halt. And what they're effectively doing is like a taboo strategy.

Like I'm not going to review papers that, you know, forward mirror life. Maybe we don't fund research that forwards mirror life. There's major international bodies that recently issued critical reports like the UNESCO International Bioethics Committee, the World Health Organization, the UNS Secretary General's scientific advisory. But like, you know. Yeah, we've seen how. In the current world environment, geopolitically and otherwise, unfortunately, these entities that are meant to create collective action have struggled.

Yeah. Yeah. And we've seen a breakdown, unfortunately, and the ability to get global collaboration on a lot of different things. Yeah. So we're kind of in a tough spot. Yeah. And it's complicated by the fact that not everyone even agrees that we should just like sweepingly ban this thing. There's some synthetic biologists that argue that a blanket ban would be premature.

because we're so far away from it. And, you know, mirror image peptides and biomolecules, they can currently be used to design safer, highly stable drugs. You know, beneficial mirror molecules can make better drugs effectively. And that's very far away from living, self-replicating mirror cells. Sounds a lot like Sam Altman. Right. Yeah. I don't think there's a whole like USA versus China debate here, right?

Because I think everyone agrees that let's not do this. but there's no like supremacy, mirror-life supremacy going on. But there's some like debate about, you know, maybe not a blanket ban. It kind of reminds me of, you know, when we were talking about what, Sudiparik, the CEO of AAAS, he was talking about how some of the advice that he gave the Senate Scientific Advisory Committee was used on the floor of Congress to like steer legislation. One of the examples that he gave us,

and we'll have the interview coming out soon, he said that, you know, there was a ban for any chimeras of human animal or animal animal organisms. Well, the blanket ban would stop any genetic modification from happening, right? And that's a huge ban. Yeah. Right? So there's like room to do this.

But at the same, at the same time, like, like animal, animal chimeras are not an existential risk for all life on Earth. So the fact that, like, right now we're just, we're just, oh, it's taboo. Like, let's not do it, guys. I think we should have a little, I think we should get our act together here, guys. Like, the more I researched this, I was like, how are we just, how are we just like, let's not do it, guys? That's like our best strategy. doesn't make any sense. And it's fascinating because once you get into the details to understand what's

functionally happening, it's clear where the risk comes from. Exactly. It's a lot easier to see the risk than some of the RSI debate, although I am more dumer than non-dumer on recursive self-improvement, but I think it requires more infrastructure around it. This is like once it's created and it's out. No, it's like, it's really bad. It's really bad.

It's really bad. All you need is like one bacteria. Right. Exactly. Right. Yeah. Exactly. So I'm going to end on a lighter note than existential dread.

Before we end, I want to mention that I'm pretty sure I caught a mistake by the Nobel Committee's press material. Uh-oh. Okay. So on the left-hand side is the popular science background. That's an image of the Sawai chemical reaction. The intermediary is the left and right. versions of the catalyst that then, you know, auto-catalyze themselves and create the runaway reaction. And if you notice on the left-hand side, the colored versions, this is

the popular signs. So, you know, they got some graphic artists to like make this version. They're showing the left version of it and then the right version of it. It's flipped. Yes. Right. Okay. But let's look at the, let's look at the molecule in a little bit greater detail. If this molecule was completely flat, then all I'd have to do is just flip the left into the right. And then I would, those two are not in antiumers if they're completely flat. The fact that they're not flat comes from the fact that on the left, there's a dotted line that's attaching the zinc group to the organic molecule. And on the right hand side, there's a solid line that is attaching the zinc to the solid molecule. Now, in chemistry, the convention is dotted line means it's moving.

moving away, and solid line means it's moving towards. But if you're flipping it, then the zinc that's away on the left-hand side, as I turn it and flip it, the zinc is going to come towards me on the right-hand side. Those two are the same molecule. Right? In the scientific background, they were a bit more careful because I think they just copy and pasted the image from the paper itself. And there, it's showing the left and the right versions of that molecule.

It's not flipped. Right. And one of them is dotted going away. One of them is solid going towards. Uh-oh. Right? I see it. Yeah.

So on the left-hand side, what would have been correct is both of them are either dotted or you don't flip and one of them is dotted, one of them is solid. Yep. You see what I'm saying? I see exactly what you're saying. Because by having it flipped in this orientation, you're actually changing. the in and outness of the zinc group. The zinc is going away from me on the left,

but if I flip it to the right, it would be coming towards me. It's the same molecule. On the other hand, if it's the opposite version, then as I flip it, it would be a dotted line on the right as well. We're awaiting comment. If there's any chemists out there that have some justification for this,

let me know, but I'm pretty sure the Nobel Committee made a mistake here. The Nobel Committee has been very quiet since this tweet. You know? But given what we've gone through, it makes total sense. Yeah, yeah, yeah. Why these are representing different things. Yeah, yeah.

On the right-hand side, we're seeing true chirality, right? We're seeing the anantiumers that are left-handed and right-handed. On the left-hand side, we're actually seeing the same molecule. Yeah, yeah. Because all you're doing is rotating it. Oh, that's a good one. In case people didn't think we did our homework. Yeah.

This is proof positive. that we spend the time. So in the comments, right? FFP pod greater than Nobel committee. Let's go. Or I'm wrong and let me know. We have spent a lot of time this week, waking up early, putting all these materials together

so we could have had daily drops with the detailed understandings of each of the moving parts. I just want to quickly kind of go through what we've talked about today. So we started with two hands that can not, not be made identical by rotating them. From that small geometric difference, we reached a problem that connects the molecules in medicine to the building blocks of life.

Pasteur, we pastore, made molecular symmetry experimentally visible. This was our wine example earlier. Kagan showed why the behavior of mixed-handed catalyst need not be a simple average. And so I demonstrated a reaction in which self-production and amplification work together. This non-linearity, we talked about then this autocatalysis. A tiny starting imbalance does not always stay tiny. Fascinating. Under the right chemical conditions, it can shape almost the entire outcome.

That is the idea behind this year's Chemistry Nobel, and it leaves an excellent question open, which other chemical systems can turn a small beginning into a strongly ordered result, which is what we just ended on. Maybe we need to be a little bit careful when it comes to some of the mirror life stuff. If there's a step in the story that you would like us to unpack further, in addition to the FFP

Greater Than No about Committee in the comments, please let us know. Again, all the papers and the sources are available at fFPod.com on socials. You can get all of our clips at FFP pod. Oh, look, our little give it a like just popped up on the screen for those watching on YouTube. That timing was quite nice. Look, that was no hands. Look, no hands. I want to take a, but I know this is running a little long, but I want to just take a last moment, since this is going to be our last episode from the no bells.

I want to give a huge, big shout out to our resident PhD, Krishna Chowdhury this week, who's been an absolute champion. These are extremely dense and complex issues. As I mentioned, we are up all morning, recording first thing after several hours to deliver a deeply technical but conversational and a problem. approachable episode right when it happens so you can really get this immediately. Krishna is a big part, not only in every episode, but especially in Nobel Prize Week, for us to be able to deliver the correct and accurate and still enjoyable result here. And I really just want to give you some flowers. It's a hugely challenging thing for us to accomplish this in this time period.

with just the two of us and to get it out to you with high production value, making us look pretty. So, you know, in the comments, if you made it to the end of the episode, please give Krishna a big shout out because this is real work. And it's a pleasure to be able to produce this show alongside one of my favorite science communicators. My name is Lester Nare, alongside, again, one of my favorite people, Krishna. Is there anything from the week that you want to just end on before we let the people go here? I want to end on the fact that, you know, I think Nobel, I think in a grand scheme, if we zoom out, the Nobel prizes are a great way to recognize scientists for a lifelong career in advancing a particular field. But prizes aren't everything.

And science is so much bigger than the few individuals. that get the Nobel Prize. Even in today's episode, we talked about all of the stuff that led up to it in the Ice Cube episode. I mean, there's 450 people involved in Ice Cube. Only one person got the Nobel Prize. It was his baby, and it kind of makes sense. But let's not forget about all of the scientists that work for creating science. They're just as much heroes as the Nobel Prize winners.

And that's why a big part of the show is just highlighting science as it happens throughout the year. It's a team sport. This is not tennis. And again, we do always try to, for example, when we show the papers, show the whole author byline. So everyone gets that recognition. Because I think it's a really good point. We are trying to create an entry point into this to make it enjoyable. But we are extremely grateful to the entire research community.

and we are trying to elevate your stories in this love letter to science. And one thing I will also say is that, you know, the getting up at 2.30 in the morning, it's not just me. You're doing it too. And, you know, the fact that we can, like, produce this thing, release a day of, release a bunch of social clips the day of, that's all Lester. And, you know, be sure to look at, like, all of the advancements that we've had in our automatic caption creation and things like that. Pretty cool stuff. We are one of the best teams in science entertainment,

and we are trying to build off the shoulders of giants of the many researchers who don't get their stories told as often as other things. And so it's a pleasure for us both. To be able to bring the show to you for many of the new listeners, we have a great back catalog. Check it out. We are going to go get some rest.

next episode will be our interview episode from the Golden Goose Awards, which was, I can't believe that was last week. When we were in D.C., we'll have three interviews with all of the awardees that won this year and that will be followed up by our interview with AAAS CEO, Sudip Parikh. And we may do a Halloween special,

but we haven't decided we're going to take a couple days for a breather. We appreciate you all in FFP Nation for joining us, and we will see you all next week. If you want a $3,000 a month payday for life, what would you feel free to do? Maybe take a long weekend, every weekend, or try a bunch of new hobbies. Would you feel free to upgrade and listen ad-free?

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