Louis Pasteur discovered molecular handedness in the mid-1800s while studying tartaric acid crystals from wine production. Noticing that colleagues reported the substance sometimes bent polarized light right and sometimes left, he grew and examined the crystals under a microscope and found two mirror-image forms, which he separated by hand with tweezers. Dissolved in liquid, one form rotated polarized light right and the other left, showing the handedness was a property of the molecules themselves, not an artifact of the crystal. In 1857 he also found that fermenting bacteria would consume one tartrate form but not its mirror twin, an early clue that life's chemistry favors one hand, later confirmed when naturally occurring amino acids were found to all rotate light left (L-amino acids) while DNA's sugars and helix are right-handed.
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Pasteur's original substance was tartaric acid, familiar from wine sediment known as wine diamonds or potassium bitartrate crystals.
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The experiment used a polarizer to produce polarized light and a second polarizer (analyzer) on the far side to measure how much the sample rotated the light's axis.
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The bacteria fermentation test specifically used the tartrate form found naturally in grapes and wine, which bacteria readily consumed, versus the mirror form, which they would not grow on at all.
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This work predated atomic theory, so Pasteur's crystal-level discovery pointed to an invisible molecular property without the conceptual framework of molecules as we understand it today.
1,229 words · auto-generated from the episode video
12:12especially 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. When we 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.
12:53He 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. (Laughing) 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 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
13:33take 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 colleagues 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
14:14you 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. 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 with a light microscope that there are these
14:55two 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 went 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
15:39that 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, you know, 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
16:21the 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 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.
17:06So 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, like the left-hand side of the Petri dish has some temperature on 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
17:50growth 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, Pasteur kind of started this process by separating these different types of crystals, which are at a macro-sized 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
18:31time these invisible molecules. Yes exactly. And at that point, atomic theory was new. There wasn't really a sense of 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 L-alanine that we were talking about earlier, leucine, valine, every single amino acid that is chiral, life uses only a particular type of chirality.
19:13And 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 enzymes fit the right-handed version, things like that. And this insight
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