The mysteries of Louis Pasteur’s mislaid lab books

Louis Pasteur is one of the world’s most famous scientists, acclaimed for his work on the germ theory of disease, for developing rabies and anthrax vaccines, and for inventing a technique to prevent bacterial contamination of milk and wine—his eponymous pasteurization process. But Pasteur has a special place in chemists’ hearts for some sleuthing he did early in his career to help define the concept we now call chirality.

For the past year, Gregory S. Girolami and Joseph Gal have been doing some Pasteur-related sleuthing of their own. Girolami, a chemistry professor at the University of Illinois, Urbana-Champaign, and Gal, a Pasteur historian and professor of medicine at the University of Colorado, Denver, have been trying to trace the journey of two of Pasteur’s notebooks from 1847 and 1848. It was in these books that the renowned scientist recorded his experiments and insights on chirality.

“Amazingly, these two notebooks were lost for many decades and were not found again until the 1930s. Since then, they’ve been lost again and found again,” said Girolami during a talk about his and Gal’s detective work at the American Chemical Society national meeting in Boston in August. Gal organized the symposium in the Division of the History of Chemistry to celebrate the 170th anniversary of Pasteur’s landmark discovery of chirality. When he started to put his list of speakers together in 2017, many Pasteur scholars thought the notebooks—important artifacts for chemists—were lost.

In 1847, when Pasteur earned his doctoral degree in chemistry and physics, a mystery concerning salt crystals of tartaric acid puzzled scientists. When dissolved in solution, tartrate crystals, which form naturally in old wine barrels during storage, would rotate polarized light. On the other hand, solutions made from what was known at the time as paratartrate, a related compound that was also a by-product of wine production, did not. Scientists knew tartrate and paratartrate had the same chemical composition, but they had different physical properties.

Although he was only 25 years old and had just received a mediocre grade on his thesis, Pasteur noticed something that had escaped everybody else’s attention: When he looked closely at the paratartrate crystals, he observed there were actually two types of crystals with shapes that were nonsuperimposable mirror images. The crystals of tartrate were all of a single type. Pasteur painstakingly separated the right- and left-handed paratartrate crystals using a microscope and tweezers. Sure enough, solutions of these separated crystals rotated polarized light in opposite directions. Paratartrate, we now know, was a racemic mixture of tartrate and its enantiomer.

“The importance of the discovery was in part the solution of this mystery, but more importantly, it was the first evidence that there was something in chemical substances that had left- and right-handed character,” Girolami said. That knowledge led to the concept of stereochemistry.

Pasteur gave a talk on his discovery to the French Academy of Sciences in May of 1848, and a short summary of the discovery was published in the academy’s proceedings (C. R. Hebd. Seances Acad. Sci.1848,26, 535). In another publication later that year, “he wrote he observed with ‘surprise and delight’ that the crystals that had facets to the left rotated light to the left, and the crystals that had facets to the right rotated light to the right,” Girolami said. “It’s a very poetic statement—a rare admission of emotion in a scientific paper.”

At the time, Pasteur was working as a laboratory assistant at the École normale supérieure (ENS) in Paris. But he moved several times during his career—briefly to a school in Dijon, then to the University of Strasbourg, to the University of Lille, back to ENS, then to the Sorbonne, and finally to the Pasteur Institute, where he was director until his death in 1895.

When Pasteur died, his wife, Marie, inherited all his scientific notebooks—all but the two from 1847 and 1848 containing his discovery of chirality. We know this, Girolami explained, because they were not among the vast collection of notebooks Pasteur’s grandson, Louis-Pasteur Vallery-Radot, donated to France’s national library, the Bibliothèque nationale de France (BnF), in 1964. They were also not among Pasteur’s notebooks that Vallery-Radot sold to rare-book dealers in Paris, which have wound up in other collections.

“It’s a mystery as to why the two notebooks were separated from Pasteur’s library, which his family inherited when he died,” Gal said. But the notebooks did turn up at the Sorbonne. Perhaps Pasteur forgot them when he left there, Gal suggested, or perhaps he loaned them to a colleague, and they were never returned. Regardless, the notebooks surfaced at the Sorbonne in the 1930s. Marie-Laure Prévost, former curator of Pasteur’s papers at BnF, told Gal that they were fortuitously discovered in a closet in one of the laboratories where Pasteur worked. And for many years the notebooks remained in the care of Jean Wyart, a crystallographer at the university.

But the notebooks would disappear again. Before that happened, though, their existence was documented by University of London crystallographer J. D. Bernal. In 1946, Bernal gave a talk in Paris to commemorate the 50th anniversary of Pasteur’s death. The day before his lecture, Bernal examined Pasteur’s 1847 and 1848 notebooks, still in Wyart’s care, and included information from them in his talk.

“Bernal’s talk was the first time that the world at large knew that these notebooks existed,” Girolami said. Bernal published this lecture seven years later in his book “Science and Industry in the Nineteenth Century,” including black-and-white images from the notebooks.

Years later, in 1971, Seymour Mauskopf, a science historian at Duke University, read Bernal’s 1953 book and wrote to Wyart asking to see the notebooks. Wyart did not reply. Months later, in 1972, Mauskopf tried Wyart again. This time Wyart answered, confessing to Mauskopf that when he received the first letter he couldn’t find the notebooks and was too ashamed to reply. In the intervening months, Wyart told Mauskopf, he had located the notebooks and would have them copied onto microfiche—flat pieces of film containing tiny photographs of the notebooks’ pages. He also told Mauskopf he would then deposit the notebooks in BnF.

In the 1980s, Mauskopf copied the microfiche (there are five of them) for Gerald L. Geison, a science historian at Princeton University who wrote a biography of Pasteur. Geison told Mauskopf that he had visited BnF only to find that the 1847 and 1848 notebooks were not there. Geison deposited his microfiche in Princeton’s library in 1987 with a note that the current whereabouts of the notebooks were unclear.

This was all the information Girolami and Gal had about the notebooks when they began their gumshoe work last year. They presumed the notebooks were lost. In the meantime, they had the 1972 microfiche and were using them to study early drafts of Pasteur’s 1848 presentation to the French Academy of Sciences. But the microfiche aren’t a perfect facsimile of the notebooks: They’re missing page numbers.

Why there are no page numbers in the microfiche is a mystery and also a complication. Scholars have long known that the microfiche are not in chronological order, but that could be explained if Pasteur kept different notebook sections for different projects. Still, Girolami and Gal think there’s good evidence that the microfiche pages are misordered compared with the notebook. Girolami points to a distinctive ink stain on one page of a microfiche. The page that has the mirror image stain, presumably the neighboring page in the notebook, appears on a completely different microfiche.

So Gal and Girolami desperately wanted to find the original notebooks. Several months into their recent search, they got a lead: The duo came across “Pasteur: Cahiers d’un savant,” a 1995 book by Prévost and Françoise Balibar, a science historian at Paris Diderot University. The book contained color photographs of pages from both notebooks.

It turns out that Wyart did donate the notebooks to BnF, but not until 1990. “They were acquired by the BnF without fanfare,” Girolami said, “and except for people inside the BnF, nobody knew they were there.” The notebooks are cataloged separately from all of Pasteur’s other notebooks. And unlike Pasteur’s other notebooks, no copies exist in Gallica, BnF’s free, searchable digital library.

According to Guillaume Fau, the chief conservator at BnF, the notebooks are indeed there. They are separate from the general Pasteur donation, he says, because the library’s classification system is by provenance. “They have not been digitized yet,” Fau adds, “because the amount of collections to digitize is enormous at the BnF, and we do this little by little.”

Gal hopes to make a trip to Paris to see the notebooks soon. And Girolami and Gal plan to publish the partial drafts of Pasteur’s first 1848 paper that appear in the 1848 notebook as well as their analysis of how those drafts differ from the final publication.

Mauskopf says there’s no question that studying original notebooks is preferable to studying the microfiche, in particular to address “questions regarding whether all pages of the manuscript have been included and in the correct order in the microfiche.”

Another mystery they’d like to solve? Many of the pages of the original notebooks, including those with Pasteur’s key discovery about chirality, are torn and put back together with clear adhesive tape. Such tape wasn’t invented until 1930, and it’s unknown when and how the books were torn.

“Apart from Balibar and Prévost,” Girolami pointed out, “I don’t know that any scholar has studied the original notebooks since Bernal did in 1946.”