《有机化学》课程教学资源（文献资料）When did Louis Pasteur present his memoir on the discovery of molecular chirality to the Académie des sciences Analysis of a discrepancy.pdf

Review Article When Did Louis Pasteur Present His Memoir on the Discovery of Molecular Chirality to the Academie Des Sciences ? Analysis of a Discrepancy JOSEPH GAL* Division of Clinical Pharmacology and Toxicology, University of Colorado School of Medicine, Denver, Colorado Dedicated to the 160th Anniversary of Louis Pasteur’s Discovery ABSTRACT Louis Pasteur presented his historic memoir on the discovery of molecular chirality to the Acade´mie des sciences in Paris on May 22nd, 1848. The literature, however, nearly completely ignores this date, widely claiming instead May 15th, 1848, which first surfaced in 1922 in Pasteur’s collected works edited by his grandson Louis Pasteur Vallery-Radot. On May 21st, 1848, i.e., one day before Pasteur’s presentation in Paris, his mother died in Arbois, eastern France. Informed at an unknown point in time that she was ‘‘very ill,’’ Pasteur left for Arbois only after his presentation. Biographies of Pasteur by his son-in-law Rene´ Vallery-Radot or the grandson, and Pasteur’s collected correspondence edited by the grandson are incomprehensibly laconic or silent about the historic presentation. While no definite conclusions are possible, the evidence strongly suggests a deliberate alteration of the record by the biographer relatives, presumably for fear of adverse public judgment of Pasteur for a real or perceived insensitivity to a grave family medical emergency. Such fear would have been in accord with their hagiographic portrayal of Pasteur, and the findings raise questions concerning the extent of their zeal in protecting his ‘‘demigod’’ image. Universal recognition of the true date of Pasteur’s announcement of molecular chirality is long overdue. Chirality 20:1072–1084, 2008. VC 2008 Wiley-Liss, Inc. KEY WORDS: discovery of molecular chirality; enantiomorphism; falsification of history; hagiography; stereochemistry; history of chemistry; Pasteur; biography INTRODUCTION Louis Pasteur (1822–1895), a chemist by training, discovered molecular chirality in 1848, and thereby made a fundamentally important contribution to chemistry and several other fields, e.g., crystallography, biochemistry, pharmacology, clinical therapeutics, etc. He presented his revolutionary discovery to the Acade´mie des sciences (Academy of Sciences, Acade´mie henceforth) in Paris in May of the same year, but the correct date of his presentation has been nearly completely ignored and instead an incorrect date has widely persisted in the literature to the present day. In this report the circumstances, causes and implications of the emergence and widespread acceptance of the wrong date are analyzed. THE DISCOVERY OF MOLECULAR CHIRALITY Background Optical rotation was discovered by the French physicist Franc¸ois Arago (1786–1853) when he found, in 1811, that crystalline quartz slices rotated the plane of ‘‘plane-polarized’’ (i.e., circularly polarized) light.1 Subsequently, JeanBaptiste Biot (1774–1862) found,1 beginning in 1815, that some substances rotate polarized light in the noncrystalline state, e.g., in the liquid or gas phase or in solution, and by the mid-1840s a variety of compounds, all natural products (e.g., tartaric acid, oil of turpentine, camphor, quinine, morphine, brucine, various sugars, albumin, etc.), were known to rotate polarized light in the noncrystalline state.2 Biot understood that optical rotation by substances in the noncrystalline state required that some aspect of the structure of the molecules themselves was responsible for the rotation, and he referred3 to such compounds as ‘‘substances mole´culairement actives’’ (molecularly active substances; translations are by the present author unless otherwise indicated), but an explanation of the phenomenon was not available. It was Louis Pasteur who made the connection between optical rotation and molecular structure when he discovered molecular chirality. 4 *Correspondence to: Joseph Gal, Division of Clinical Pharmacology C 237, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262. E-mail: joe.gal@uchsc.edu Received for publication 1 October 2007; Accepted 29 November 2007 DOI: 10.1002/chir.20532 Published online 17 March 2008 in Wiley InterScience (www.interscience.wiley.com). CHIRALITY 20:1072–1084 (2008) VC 2008 Wiley-Liss, Inc

Pasteur Discovers Molecular Chirality Pasteur obtained his doctorate from the University of Paris in August 1847 with two theses, one in chemistry5 and another in physics.6 At the time of his discovery of molecular chirality, in the spring of 1848, he was an assistant to Antoine-Jeˆrome Balard (1802–1876), a professor of chemistry at the E´ cole normale supe´rieure, a prestigious university-level institution in Paris.7 In a letter to his friend Charles Chappuis dated January 20th, 1848, Pasteur mentioned that he had undertaken new studies and hoped to present the results to the Acade´mie sometime later that year.8 These were the studies of the tartrate crystals that led to the discovery of molecular chirality.9 Pasteur’s key finding was that the sodium ammonium salt of paratartaric acid (racemic tartaric acid or (6)-tartaric acid by today’s nomenclature) crystallized under the conditions of his experiments as a conglomerate, i.e., as a mechanical mixture of two crystal types. One of the crystal types contained one of the enantiomers, while the other enclosed only molecules of the other enantiomer. He was led to this finding by his recognition—based on careful observation that identified opposing hemihedral facets on the two crystal types—that the two crystal types were chiral and enantiomorphous, meaning that they resembled each other as the right and left hands, i.e., as a ‘‘handed’’ object and its nonsuperposable mirror image. Pasteur manually separated the two types of crystals and showed that in solution the two tartrate salts (dissolved separately) had equal optical rotation in absolute value (within experimental error) but opposite in direction, and the same was true for the crystal hemihedrism and optical rotation in solution of the corresponding tartaric acids liberated from the salts.10 As Kauffman and Myers pointed out, the experiments required considerable laboratory skills and powers of observation.11 Pasteur’s key experiments were carried out in the spring12 of 1848, and he read his memoir on the discovery at a session of the Acade´mie in May, 1848. The memoir was published in the proceedings of the Acade´mie, the Comptes rendus des se´ances de l’Acade´mie des sciences (Comptes rendus hereafter) with the following title: ‘‘Memoir on the relation that may exist between crystal form and chemical composition and on the cause of rotatory polarization.’’4 Pasteur understood that the cause of optical rotation in the noncrystalline state was the inherent chirality of the molecules of dextro- and levo-tartaric acids, and he expressed this crucial point in his historic memoir to the Acade´mie in the following manner: ‘‘Is it not evident by now that the property of certain molecules of rotating the plane of polarization has as its cause, or at least is linked in a most intimate manner to, the dissymmetry of these molecules?’’4 By dissymmetry, Pasteur meant chirality. 13 Pasteur’s discovery was received by the Parisian scientific establishment with a great deal of interest. For example, Biot insisted on verifying the discovery by having Pasteur repeat the experiment in his presence and using reagents provided by Biot,14 and in October, 1848, a commission appointed by the Acade´mie and consisting of distinguished scientists—including Biot and the celebrated chemist Jean-Baptiste Dumas (1800–1884)—produced a highly favorable report on Pasteur’s chirality work.15 Pasteur had indeed caught the attention of the scientific establishment, and was appointed professeur supple´ant (substituting or acting professor) in chemistry at the University of Strasbourg in late 1848, followed a few years later by appointment as professeur titulaire (tenured professor).16 Pasteur’s discovery, i.e., that some molecules are chiral, was the first clear experimental indication of the importance of the three-dimensional nature of molecules, and is rightly considered the beginning of stereochemistry.17 His discovery of molecular chirality is all the more remarkable, as it was made at a time when little was known about chemical structure and atomic bonding. For example, the quadrivalency of carbon was first proposed18 only in 1858, and the earliest speculations on the tetrahedral nature of saturated carbon only appeared in the 1860s.19 Despite this highly limited state of understanding of molecular structure at the time, Pasteur strongly suspected that molecular chirality would be shown to have important implications for chemistry and biology,20,21 and his intuition in this regard has been amply confirmed. He even proposed that a tetrahedral or a helical arrangement of the atoms within the molecules could be the source of molecular chirality.22 As we know today, he was correct with both suggestions. By the early part of the 20th century, Pasteur’s discovery of molecular chirality was recognized as fundamentally important for the development of stereochemistry.23 DISCREPANCY IN THE DATE OF PASTEUR’S PRESENTATION TO THE ACADEMIE Pasteur’s memoir to the Acade´mie on the discovery of molecular chirality published in the Comptes rendus4 was reprinted in Volume 1 of Œuvres de Pasteur (Pasteur’s collected works, Œuvres hereafter) published in 1922, i.e., 74 yr after Pasteur’s presentation and 27 yr after his death.24 The Œuvres were collected and edited by Pasteur’s grandson, Louis Pasteur Vallery-Radot (1886–1970, LPVR henceforth, see Fig. 1), who devoted a great deal of effort to the preservation and dissemination of the record of Pasteur’s life and scientific work. An editorial footnote accompanying the reprinted memoir in the Œuvres gives the correct reference (source, year, volume, and pages) to the original memoir in the Comptes rendus, and indicates that the presentation of the memoir took place at the May 15th, 1848, session of the Acade´mie25 (see Fig. 2). However, an examination of the volume of the Comptes rendus containing Pasteur’s memoir4 reveals unequivocally that Pasteur in fact presented the memoir during the session of Monday, May 22nd, 1848, i.e., 1 wk later than the date given in the Œuvres. 25 Determination of the date of the session of any presentation before the Acade´mie is trivially simple. The presentations and other material from each session of the Acade´mie were collected in an individual issue (called Compte rendu des se´ances de l’Acade´mie des science, Compte rendu, PASTEUR’S ANNOUNCEMENT OF MOLECULAR CHIRALITY: A DISCREPANCY 1073 Chirality DOI 10.1002/chir

in the singular, henceforth), and the issues were collected in the various volumes of the journal (Comptes rendus, in the plural), each issue appearing as an individual subdivision in a given volume. The first page of each issue clearly indicates the date of the session. Thus, we see in Figure 3(a) ‘‘SE´ ANCE DU LUNDI 22 MAI 1848,’’ i.e, ‘‘Session of Monday, May 22nd, 1848.’’ In addition, at the bottom of the page we see ‘‘C. R., 1848, 1er Semestre, (T. XXVI, No 21)’’. ‘‘C. R.’’ stands for Comptes rendus, ‘‘1er Semestre’’ for 1st semester, ‘‘T. XXVI’’ for Volume XXVI (T. ¼ tome, i.e., volume), ‘‘No 21’’ is the issue number, i.e., the number of the individual Compte rendu within the volume. The image in Figure 3(a) is the first page of the issue for the session at which Pasteur presented his memoir (the page number was not printed on the first page of the issues; for the page shown in Figure 3(a) the page number is 529). Therefore, the date can be readily determined for any presentation by simply turning to the first page of the issue in which the presentation appears. Pasteur’s memoir began on page 535 (Fig. 3b), and turning back to page 529 in the same issue we find (Fig. 3a) the date of the presentation, ‘‘22 Mai 1848.’’ Moreover, there are two other pieces of information in the memoir that formally link it to the date of the session (May 22nd) and rule out May 15th as the session of the presentation. Thus, each issue (i.e., each Compte rendu) is identified with an issue number (‘‘No ’’) which was given at the bottom of the first page of the issue, together with the other information listed above. As mentioned earlier and seen on Figure 3(a), the issue number for the May 22nd, 1848, session at which Pasteur presented his memoir was 21, shown as ‘‘No 21’’ at the bottom of the first page of the issue. The issue number also appeared, sporadically, on a few additional pages of every issue. Thus, ‘‘No 21’’ did appear (together with the year, volume, etc.) on page 537 of Pasteur’s memoir (Fig. 3c). For comparison, Figure 3(d) shows the first page of the issue for the May 15th, 1848, session, i.e., that of the wrong date. The issue number, ‘‘No 20,’’ appears at the bottom. Secondly, and obviously, the page numbers of Pasteur’s memoir (535–538) also rule out the May 15th session, inasmuch as the last page of the Compte rendu for that session is 528. All of the above, then, readily, unequivocally, and clearly links Pasteur’s memoir with the May 22nd, 1848, session of the Acade´mie. All in all, therefore, it is clear that Pasteur’s memoir was presented during the May 22nd session and not on May 15th as claimed in the Œuvres. The first appearance of the erroneous date, May 15th, seems to have been in Volume 1 of the Œuvres in 1922,25 and a search of the literature failed to identify an earlier instance. However, since its first appearance the incorrect date has spread widely, at the expense of the correct date, which is nearly completely absent from the literature. In fact, efforts to locate references to the correct date identi- fied only two independent sources: Jacques Nicolle’s 1953 volume on Pasteur contains the correct date26 (in several subsequent works on Pasteur Nicolle repeated the correct date), and Mislow has it in a recent article.27 The correct Fig. 1. Louis Pasteur Vallery-Radot. (Reprinted from the page on Louis Pasteur Vallery-Radot on the official website of the Acade´mie Franc¸aise (http://academie-francaise.fr/immortels/index.html). Fig. 2. First page of Pasteur’s memoir on the discovery of molecular chirality in Volume 1 of the Œuvres (p 61). Note ‘‘se´ance du 15 Mai 1848’’ (i.e., session of May 15th, 1848) in the footnote. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley. com.] 1074 GAL Chirality DOI 10.1002/chir

date also appears in the Encyclopedia Britannica, but the article was authored by Nicolle.28 Finally, McManus29 and Buckingham30 also provide the correct date in their recent respective volumes but both cite Nicolle as their source. The scarcity of the correct date in the public record is in sharp contrast to the abundance of May 15th, 1848, the incorrect date, in the literature. Since its first appearance in the Œuvres in 1922, it has appeared regularly in a variety of publications (many of them important analyses of Pasteur’s life or work), e.g., Lowry’s milestone volume31 on optical rotation and chirality which appeared more than 70 yr ago, 13 yr after Volume 1 of the Œuvres; an in-depth critique (which appeared 20 yr ago) by Geison and Secord of Pasteur’s own account of his discovery of molecular chirality32; a detailed review and seminal analysis of Pasteur’s discovery by Mauskopf from 197633; the 1994 biography34 of Pasteur by Maurice Vallery Radot (MVR); Debre´ ’s 1994 biography of Pasteur (Debre´ is also mistaken in claiming that Pasteur’s memoir was presented by Balard)35; Geison’s 1995 volume36 on Pasteur’s ethics in science; an article by Kauffman et al.,37 and other publications.38–40 In addition, several websites give May 15th, 1848, as the date of the presentation, including, surprisingly, the website of the Pasteur Institute in Paris.41 Admittedly, it has not been possible in this survey to examine every publication or document in the massive literature on Pasteur, but the relative proportions found clearly indicate the scarcity of the correct date in comparison to the abundance of the erroneous date. THE EVENTS OF THE EPISODE: WHAT DO WE KNOW? As discussed earlier, Pasteur read his memoir to the Acade´mie in Paris on Monday, May 22nd, 1848. His parents lived in the small town of Arbois, in the de´partement (administrative district) of Jura, in the FrancheComte´ region of eastern France. On Sunday, May 21st, 1848—i.e., one day before Pasteur presented his memoir to the Acade´mie in Paris—his mother, Jeanne E´ tiennette Pasteur (ne´ e Roqui, 1793–1848, see Fig. 4), died in Arbois.42–44 In view of the one-day separation between the death of Pasteur’s mother in Arbois and his presentation at the Acade´mie in Paris, the mysterious appearance of the incorrect date for the presentation inevitably attracts the attention. On May 27th Pasteur wrote to Dumas from Arbois: ‘‘I have just returned to my family, called by a letter informing me that my mother was very ill. By the time I arrived she had died.’’ [my emphasis]. This letter appears45 in the Correspondance de Pasteur (Pasteur’s published correspondence, Correspondance hereafter), which was also collected and edited by Pasteur’s grandson. On the same day, May 27th, 1848, Pasteur also wrote46 to Paul-Franc¸ois Dubois, director of the E´ cole normale: ‘‘By the time I arrived my mother had died. She succumbed in a few hours to an attack of apoplexy.’’ On the following day, May 28th, Pasteur, still in Arbois, wrote to Chappuis in a similar vein, indicating that his mother had died within a few hours.47 In these letters no date or time is given for the mother’s death, nor are the dates of Pasteur’s departure from Paris and arrival in Arbois provided. MVR, grand-nephew of Pasteur’s son-in-law Rene´ Vallery-Radot (1853–1933, RVR henceforth, see Fig. 5), writes in his 1994 biography of Pasteur that his mother died suddenly while preparing to attend mass on Sunday, May 21st, 1848, but he does not identify the source of this information nor does he provide any additional details on the events.48 We do not know when Pasteur received the letter alerting him to his mother’s illness, and no information appears to have been published on the method by which the letter was transported from Arbois to him in Paris. Pasteur used the word lettre (i.e., letter) to refer to the communication which informed him of his mother’s illness.45 According to the Muse´e de la Poste (the museum of the French postal services in Paris), it was only in 1851 that electric telegraph service became available to the public in France49 (in 1853, Pasteur marveled at the newly available telegraph system and used it to send a message—he used the term de´peˆche te´le´graphique, i.e., telegram—to Biot).50 As for letters sent via the postal service, according to the Muse´e de la poste a letter sent from Arbois in 1848 would have taken at least 3 days to reach Paris (personal communication obtained at the museum in May 2006). Thus, a letter mailed from Arbois by post a few hours Fig. 4. Pasteur’s mother, Jeanne-E´ tiennette Pasteur; pastel by Louis Pasteur, 1836. (Reprinted from ‘‘IMAGES DE LA VIE ET DE LŒUVRE DE PASTEUR,’’ by L. Pasteur Vallery-Radot, Flammarion, 1956). 1076 GAL Chirality DOI 10.1002/chir