louis pasteur -- 3/20/24

20 Mar 2024

louis pasteur -- 3/20/24

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Today's selection -- from Elixir by Theresa Levitt. The transformational discoveries of the young Frenchman Louis Pasteur:

“Louis Pasteur was working in Jerome Balard's laboratory when the revolution broke out in February. He could hear the gunshots from the barricades and was thrilled by the fight for liberty and justice. ‘It is a great and a sublime doctrine that is now being unfolded before our eyes,’ he wrote home, ‘and if it were necessary, I would fight heartily for the holy cause of the Republic.’ He joined the National Guard, which had emerged in the wake of the revolution as the primary defenders of the Republic. ‘What a transformation of our whole being!’ he exclaimed, seeing France born anew as the land of free men. One day in April, while crossing the Place du Pantheon, he saw a wooden structure with ‘Altar of Our Country’ written on it. Someone explained that it was for accepting donations to the Republic, so Pasteur went back to his lodgings at the Ecole Normale, emptied his drawers, and returned to place the entirety of his savings—150 francs—on the altar.

“Nor was his excitement for his work in the chemistry lab dampened by this revolutionary upheaval. If anything, it paralleled the sense of a world being born anew. He had completed his dissertation the previous fall and was now engaged in a new project that probed the very contours of life. A notebook lay open on his workbench, the phrase ‘Tartrates (Questions to resolve)’ written across the top. The substance in question was simple enough, being a common by-product of making wine. Vintners usually found tartar in the bottom of the barrels after emptying them, and had taken to scraping it out, grinding it up, and purifying it to sell as cream of tartar, a kitchen staple used for making baking powder. But anyone who opened a bottle of wine could see tartar, accreted in large crystals on the underside of the cork. For red wines, the crystals could take on a deep, amethyst-like purple. For white wines, they were clear, sparkling like diamonds.' Indeed, ‘wine diamonds’ was the name used by oenophiles.

“Pasteur had, like Laurent, grown up among the vineyards of Eastern France. His two closest friends, Jules and Altin Vercel, were the sons of the neighboring vintner, and he spent his days playing there and helping with the annual harvest. His own family had run a tannery, and they collected the tartrates from the spent mash to treat leather. At fifteen, he was sent to Paris to study, together with the vintner's son, Jules. But the shock was too great. He missed his home, the contour of the land, its smells. ‘If I could only get a whiff of the tannery yard,’ he confided in Jules, ‘I feel I should be cured.’ He lasted scarcely a month.

“He tried again at the age of eighteen, finding lodging in Paris above a public bathhouse. His parents wrote him solicitous letters encouraging healthy habits. ‘Take some nice baths,’ his mother wrote, although she insisted they should not be too hot, as his heavy workload might lead to overheating. His father suggested he put some drops of cologne water in his hair to prevent headaches and strengthen his eyesight. He also told him that he should avoid running around Paris late at night, and instead of going out to see plays, he would do better to stay home and read them himself, and would likely come away with a better understanding of them, anyway.

“One of the first things Pasteur did in Paris, before his own classes even started, was to sit in on a lecture by Jean-Baptiste Dumas at the Sorbonne. ‘You cannot believe how many people there are at this course,’ he wrote home. Some 600 or 700 people filled the immense room, and you needed to get there half an hour early to get a good seat. He compared it to an evening at the theater, complete with thunderous applause at the end. Dumas's soaring rhetoric, he explained, ‘could set fire to the soul,’ and appears to have lit something in Pasteur, who was soon accepted in the sciences section of the École Normale, where he haunted the chemistry labs every chance he got. When he graduated in 1846, he wrote to Dumas asking if he could work as his teaching assistant at the École Centrale. The answer was no, but Pasteur was hired by Balard, who needed an assistant for his clandestine lab at the Ecole Normale, the one where Pasteur would meet Laurent.

“Pasteur never forgot the moment Laurent first called him over to peer into his microscope at some sodium tungstate crystals. It had looked perfectly pure at first glance, but Laurent showed him that if you looked at the structures of the crystals, you could divide them into three distinct kinds. The two men shared an artistic bent. Pasteur had even thought of becoming an artist before discovering science, and they both continued to draw constantly in their lab notebooks—caricatures and grotesque physiognomies. Perhaps that is why they liked to visualize the arrangements of atoms and think about how a molecule's structure might look, when so much of the chemistry community dismissed this as dangerous speculation. In any case, Pasteur was hooked, and Laurent began teaching him how to work with crystals. He had been working on his thesis to earn a doctorate in chemistry, but he now abandoned his old project and began a new one with Laurent. Pasteur kept his new activity largely under wraps, writing only to a friend to convey his excitement but urging him not to tell anybody. In the end, Pasteur submitted two separate theses in August 1847. One was in chemistry, which consisted of a straightforward chemical analysis of arsenious acid and its salts, confirmed with crystallographic methods. The other was in physics, and made precisely the point that Laurent had been arguing to the chemical community, to an indifferent response: substances of the same crystalline form had the same optical activity. It was a powerful claim that pointed, both Laurent and Pasteur were convinced, to some aspect of the molecule's physical organization. But these were not the kinds of ideas by which someone earned a doctorate in chemistry at the time.

“Now, in the spring of 1848, doubly doctored and with the tocsin of liberty sounding around him, Pasteur turned to the heart of the question: was there something special about the organization of the molecules of living things? Could a study of tartrates hold the key? Chaptal, in his study of wine, had seen a close congruence between tartrates and the ‘vegeto-animal principle’ that he proposed as a vital force particular to living things. Biot had been virtually obsessed with tartrates, studying them for decades in his effort to use optical activity to distinguish between the living and non-living. And now there was another wrinkle to the story. In addition to the ‘natural tartrate’ that formed in the process of fermentation, when acid in the grapes reacted with a potassium salt, there was also an ‘artificial tartrate’ created as a by-product of industrial production. An industrialist, Karl Kestner, had first noticed this substance as a waste product of his chemical factory in Thann, Alsace, in the 1820s. He showed it to Gay-Lussac when the famous chemist came for a visit, who gave it the name racemic acid. As analytical techniques improved in the 1830s, chemists noticed that it had the exact same ratios of carbon, oxygen, and hydrogen as tartaric acid, prompting Berzelius to rename it paratartaric acid, to indicate it was an isomer of tartaric acid. By this time there were several cases of isomers that had the same number of carbons and hydrogens. Isomers could usually be distinguished by different properties. Berzelius, hoping to find differences, asked Mitscherlich, at the University of Berlin, to prepare salts of the compounds and compare the resulting crystals.

Pasteur experimenting in his laboratory

“Mitscherlich had, like Laurent, published his first scientific paper on mineralogy, and he was one of the few other chemists who was skilled with a goniometer. He put it to use now, comparing the salts made with grape tartrates with some made from paratartrates he got from a factory in Saxon. Not finding any differences, he put the work aside for several years, until he heard of Biot's demonstration that tartaric acid was optically active and racemic acid was not. He repeated his experiments, once again finding a remarkable identity: they had the same crystalline form, with the same angles, the same specific weight, the same double refraction, and the same angles between their optic axes. Dissolved in water, their refraction was the same. One difference alone distinguished them: the natural substance was optically active and the artificial substance was not. Mitscherlich sent a note of his findings to Biot, who pronounced his experiments ‘beautiful’ and his results ‘curious.’ Mitscherlich had provided him with samples of his material, which Biot investigated relentlessly, hoping to uncover some clue about the organization of living bodies.

“This was the challenge that Pasteur picked up. He was able to borrow a bit of the paratartaric tartrate Mitscherlich had sent to Paris, and then made crystals of both it and some normal tartrate by reacting them with potassium, ammonia, or the like to produce salts. He looked at the normal tartrates first. At first glance, the crystals they formed seemed perfectly symmetric, but after a while he noticed something entirely new: what he called ‘little faces that betrayed its asymmetry,’ that is, tiny protrusions that jutted out of one side but not the other. There was a word for the asymmetry that Pasteur was seeing: hemihedral. This type of asymmetry was well known among crystallographers and usually associated with the crystal quartz. This seemed to Pasteur an important clue. Quartz was an inorganic mineral that was nonetheless optically active. Although it was symmetric at a molecular level, it crystallized into an asymmetric form, and this seemed to be what ‘pulled’ the light to one side in optical activity. Pasteur thought a similar process might be responsible for the optical activity of the tartaric acid.

“His next step was to look at the crystals of the ‘artificial’ paratartrates. Since these were not optically active, he thought they would perhaps be perfectly symmetrical, thus finally finding the distinguishing feature Mitscherlich had missed. But what he actually found was much stranger. They, too, were hemihedral, but unlike the tartrates, whose faces were all on one side, the paratartrates had some faces to the left and others to the right. When he first observed this phenomenon, he recounted, ‘my heart skipped a beat.’ He felt on the edge of solving the mystery. Slowly, painstakingly, he separated out the two groups by hand: one whose crystalline structure was identical to the plant-derived tartrates and one whose crystals were mirror images of those. He tested each batch in a polarimeter and found that they had now become optically active. The one identical to the tartrates deviated the plane of polarization about 7 degrees to the right, while the mirror-image batch deviated it the same amount to the left, which explained why they cancelled each other out and looked inactive when combined. Pasteur ran out of his room like Archimedes, threw his arms around the first person he saw, and dragged him to the

Luxembourg Garden, explaining his discovery along the way.

“He took his news to Balard, who would be able to report it at the Academy of Sciences for him. Balard did not even wait for an official session but instead gossiped loudly about it in the corner of the library where academics came to socialize. Dumas was present, and listened seriously. Biot overheard and approached Balard, asking, ‘Are you quite sure of it?’ He wanted to meet the young man who had solved the problem he could not, and investigate his results. That was how Pasteur came to be knocking on Biot's door at the College de France one morning in the early spring of 1848. Pasteur reported that he sensed suspicion in the old man's voice and gestures. Biot demanded that Pasteur prepare the paratartrate salt in front in him, supplying him materials from his own stores—soda, ammonia, and most crucially, some of the racemic acid he had himself been working with. He watched over Pasteur as he went through the manipulations, then placed the liquid in a quiet corner of his apartment, where it could crystallize undisturbed, and told Pasteur he would send for him when the crystals were ready.

“Several days later, summoned again, Pasteur sorted the crystals into the two types, hunting down the best specimens, wiping off the eau-mere that adhered to them. This experiment has proved devilishly difficult for the many who have tried to repeat it. The difference between the two crystals is normally hard to see, and it seems Pasteur's dogged care resulted in particularly large crystals. There was also some luck involved, when Pasteur cooled his tartaric acid on the windowsill. The left- and right-handed crystals only separate below 26° C and would not have revealed themselves in a warmer month. But he was able to get them again for Biot, and at this point, the older man took over. He prepared the salts in a solution that he placed in a polarimeter. When he verified what Pasteur had seen, he took him by the arm in delight and proclaimed, ‘My dear boy, I have loved science so much during my life, that this touches my very heart.’ After working on the question for thirty years, he finally had an answer. Natural products were optically active because they possessed a fundamental asymmetry that artificial ones did not. And it further entrenched his suspicion that it was folly to try to replicate these natural substances by artificial means.”