CHIRALITY201072-10842008 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 the16Amniversary of Louis Pasteur's Discovery ABSTRACT sented his histo in ra ectedw 15h,1848 vorks edited by his grandsor Paris,his mother died in Arbois,e tern franc e.Informed at an unknown point in time dere inco tion of the record by the biographer relatives.pre hisnd the 10710.20 KEY WORDS:di INTRODUCTION some substances ered and of compounds,all natura nine pha d his ugnt in ry to the Acad emy of Sci in the noncryst alline state required that some aspe the e for the rotation.and he referred to such compounds stances mo 1 and of the e of the otherwise indicate but an explana on of the phenon een ontical tation and THE DISCOVERY OF MOLECULAR CHIRALITY structure when he discovered molecular chirality RraOoialoaio lices rota of "plane-pola d 29 N mber 20 /chi Baptiste Biot (177416)found.beginning in 1815.that 2008 Wiley-Liss.Inc
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
PASTEURS ANNOUNCEMENT OF MOLECULAR CHIRALITY:A DISCREPANCY 1073 Pasteur Discovers Molecular Chirality -including Biot and the celebrated Pasteur obtained his doct Paris in August from the Uni of with t es,one in emist l caught the the of 1848.he was an assis 876)a pro racting pro r)in chemistry at the University of Stra to his frien cules are chiral tance of the thre ensional nature of moleculesn d th s it s known mic tartaric acid or made at a time when i are)cry only in 1858 mechanical mixture of two crystal types.On e cr this highly limited d sta of unde of the inding by his recognitio areful ob 02 rtant implic the two that the stal r tha a tetrahedral or a he the obiect and its know todav.he with both no the tw type of mole lar id as had equal optical rotation in absolute value undamentally important for the development of stereo nental error)bu the nding tartaric acids liberated fron skills ers of ob asteurs memoir to the Academie on the disc d in dep eur's col a s e me r his de (Com rend es we ected and edite ur's grand oir on the relation that may exist between crystal form and forth.se Fig.D).who devoted a at deal of effo Ro的 ion and diss e record of Pasteur' anrndtoeodte ofropticalnroationn arie acids memoir in the Comptes and indicat that the his hi moir t e May 1 18A he foll w tha ertain molecules ation of the volume of the C ontaini ng Pa in a most intim nate manner to the dissymme of Monday.Ma 1 ted the memoi ing the se pasteur's ed y the Parisian scien 184.ie.wk ater than the date given ia the of the date teur repeat them in his and using ons and other material from ch session the Ac Chirality DOI 10.1002/chin
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
1074 GAL 、or comparison,Figure348 session.ie.that of由e The issue number 21e session,inasmuch as the last page of the Compte rendu for The first appearance of theeron date.May 15th is to h of the failed to identif first appear which is near fied only ts to nde volume on Pasteur contains the (in severa date).and Mislow has it in recent article.he correct he plura),each ssue ring as an individual wm2 Monday.May 221 at the "T.XXV 于wt6 he he er. of the for the se the on page 535 (Fig.3b),and turning back to page 529 in the of in of the h 1. each issu lors qu'il et imp ible de domt which was giv the or e f the ssue,【og her with the other for of the issue.The r also volume,ete.)on page 537 of Pasteur's memoir Fig.3c). com l 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
PASTEURS ANNOUNCEMENT OF MOLECULAR CHIRALITY:A DISCREPANCY 1075 COMPTE RENDU DES SEANCES DE LACADEMIE DES SCIENCES. (a) COMPTE RENDU DES SEANCES DE L'ACADEMIE DES SCIENCES eudy for t pe of th Chirality DOI 10.1002/chin
Fig. 3. (a) The first page of the Compte rendu for the session of May 22nd, 1848, of the Acade´mie. (b) The first page of Pasteur’s memoir on the discovery of molecular chirality, from the Compte rendu of (a). (c) Page 537 from Pasteur’s memoir showing the issue number, 21, in the footnote. (d) The first page of the Compte rendu of the session of May 15th, 1848, of the Acade´mie. Note the issue number, 20, in the footnote. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.] PASTEUR’S ANNOUNCEMENT OF MOLECULAR CHIRALITY: A DISCREPANCY 1075 Chirality DOI 10.1002/chir
1076 GAL ect date in ther but both cite sham contrast to the abundance of May 15th I8 in the res in 1922it has ared 2 da o)by Geison and disco Debre's19 biog 1005 as pre othe 1848.as the date of the pr tati including not beer to examine e erroneou 益产意碳 THE EVENTS OF THE EPISODE WHAT DO WE KNOW? ssed earlier,Pasteur read his Paris on Monday 22nd ioufnandammlnAtasmpdc Rene Val en (administrative district)of Jura.in the Fran Fig to the Acc anne on nor of the one earance of the the nevitably attracts the to h On May 27th Pasteur wrote to Dum as I rom Arbois:" r)to refer that my mother was By the time i ed she the Musee de la Poste (the muse 5 ter ap the Co blished c in Paris),it in tele hereafter). hich also col (n 1853.Pasteur marveled at the egraph iay, eur also wrote o PaulFrancois the or le sent v the to an atta plexy." On the follow g day would hav e taken lays to reach .pe2006 vein.indicating that his mother had died within a few 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
PASTEURS ANNOUNCEMENT OF MOLECULAR CHIRALITY:A DISCREPANCY 1077 there was no train service between Arbois and Diion at the Taking int s.etc..it does not appear at e the preas adimie in Pa to Chapp 丹hgw时mPoA08 that it had taker ts in que the kely,but,tech h的 Arbois,he arrived in time to see his 's death on the 21st and hi at the e on th d,if F 品是宽0恩PAE女 ed bois to appea before on May ore his pre on is i the abo letter of May 27th from Arbois that I have just returne to my family .. ble,ho Saie Fig.6),and even hows the service as it existed in 1850.and it is not certain Ieny-n r.The near (anonymously).while Pa and is Nevers ould ha 1 n pd on Pas r's scientific work.with ch)o me (he of his of the it too rea dista ance ro tioned by date and discussed.Afew nples:his 1877.on the tation of Feb Arbois toN onnerre (if in s such a 28t nthrax vaccine. etc.It that Pasteur's father indicated in 1845 that it took 3 h to major discovery,molecular chirality.before theAcd Chirality DOI 10.1002/chi
before the death of Pasteur’s mother on May 21st would have reached him well after his presentation at the Acade´mie on the 22nd. It is also possible, however, that the letter was carried from Arbois to Pasteur in Paris by a courier. In 1848 there was no rail link to Arbois (see Fig. 6), and even today, there is no railway service to Arbois. The map in Figure 6 shows the service as it existed in 1850, and it is not certain that every railway line on the map was also functioning in 1848; thus, the map is a best-case scenario of the service that may have been available 2 yr earlier. The nearest train stops to Arbois with service to Paris were in Tonnerre and Nevers (see Fig. 6). Thus, a courier would have had to take a diligence (stagecoach) from Arbois at least to one of these towns and then take a train from there to Paris. In 1848 (the year of the events in question) it took ‘‘une journe´ e,’’ i.e., at the minimum the daylight hours of a day, to travel by train from Paris to Le Havre,51 a distance roughly equal to the train trajectory from Nevers to Paris. As for the time it would have taken a stagecoach to travel from Arbois to Nevers or Tonnerre (if indeed there was such a service), it is difficult to estimate it, but it is instructive that Pasteur’s father indicated in 1845 that it took 3 h to travel from Arbois to Dijon (a town considerably closer to Arbois than are Tonnerre and Nevers, see Fig. 6).52 Since there was no train service between Arbois and Dijon at the time, Pasteur’s father was presumably referring to travel by stagecoach or to a combination of stagecoach to Chalon and from there by train to Dijon (see Fig. 6). Taking into account the likely limitations of stagecoach and train schedules, connections, delays, etc., it does not appear at all certain that a courier leaving Arbois Sunday morning, at the earliest, would have been able to reach Pasteur with the letter before the presentation at the Acade´mie in Paris the following day. It is also instructive in this regard that in 1844 Pasteur complained53 to Chappuis that it had taken him 3 days to travel from Paris to Arbois. While Pasteur indicated that on that occasion the service was particularly slow, and it took place 4 yr earlier than the events in question, the three-day trip nevertheless gives an indication of the time-scale of travel between Paris and Arbois in the mid-1840s. Thus, overall, delivery of the letter to Pasteur in Paris before the presentation appears to have been unlikely, but, technically, without more definitive information, it cannot be ruled out with certainty. Two points need to be emphasized here. (1) If it is true that Pasteur’s mother fell ill on Sunday, the 21st of May and died within a few hours, and if he did receive the letter informing him of her illness before the presentation at the Acade´mie on the 22nd and had immediately departed for Arbois, he would not have arrived in time to see his mother alive. (2) Given the short time frame between his mother’s death on the 21st and his presentation at the Acade´mie on the 22nd, if Pasteur did leave for Arbois before his presentation, he could not have returned to Paris in time to appear before the Acade´mie on the 22nd. It is therefore an inescapable conclusion that Pasteur must have left for Arbois after his presentation at the Acade´mie on May 22nd, even if he received the letter before his presentation. This conclusion is in accord with his statement in the above-cited45 letter of May 27th from Arbois that ‘‘I have just returned to my family ....’’ TREATMENT OF THE EPISODE IN THE LITERATURE ON PASTEUR The Works of Rene´ Vallery-Radot Pasteur’s first biographer was his son-in law, RVR (LPVR’s father). His first biography54 of Pasteur appeared (anonymously) in 1883, while Pasteur was still alive, and is known to have been produced under Pasteur’s control.55,56 The biography focused on Pasteur’s scientific work, with few personal details of his adult life mentioned. Pasteur’s presentation of his discovery of molecular chirality to the Acade´mie is not mentioned in this biography, while many other of Pasteur’s presentations to the Acade´mie are mentioned by date and discussed. A few examples: his presentation in 1857 of lactic fermentation57; the presentation of April 30th, 1877, on anthrax58; the presentation of February 28th, 1881, on the anthrax vaccine,59 etc. It is simply incomprehensible that Pasteur’s presentation of his first major discovery, molecular chirality, before the Acade´mie was not even mentioned in RVR’s scientific biography of Pasteur. This was the discovery that catapulted the Fig. 5. Rene´ Vallery-Radot. (Reprinted from ‘‘IMAGES DE LA VIE ET DE LŒUVRE DE PASTEUR,’’ by L. Pasteur Vallery-Radot, Flammarion, 1956). PASTEUR’S ANNOUNCEMENT OF MOLECULAR CHIRALITY: A DISCREPANCY 1077 Chirality DOI 10.1002/chir
1078 GA 1850 the aow.added by the present author.(Reprinted from rdiednl85,ndh19ooRvRpubsheda made and the ion fro of its of Pasteur),a celebrate ann e author mentions by date and dis es n while events of tery of m the of d tha mnlrchayng the as min Chirality DOI 10.1002/chir
unknown 25-yr-old new doctor of science from obscurity to the forefront of French science, brought him recognition and admiration from the French scientific establishment,15 and launched his stellar career. Pasteur died in 1895, and in 1900 RVR published La Vie de Pasteur (The Life of Pasteur), a celebrated biography which went through numerous subsequent editions. In this work RVR mentions60 the death of Pasteur’s mother but does not give a date, and quotes from Pasteur’s May 28th letter47 to Chappuis (see above). Moreover, while RVR outlines the main events of the discovery of molecular chirality, Pasteur’s presentation of the discovery to the Acade´mie is not mentioned.61 This treatment by RVR of two major events in Pasteur’s life in the detailed and thendefinitive biography of Pasteur is, again, difficult to comprehend. The absence of a reference to the presentation of molecular chirality to the Acade´mie is particularly unexpected, since the great importance of the discovery was well-known to RVR in 1900, more than 50 yr after it was made, and the omission from La Vie de Pasteur of its announcement by Pasteur to the Acade´mie is all the more puzzling, since as in the earlier biography by RVR (see above), the author mentions by date and discusses many other of Pasteur’s presentations to the Acade´mie. A few examples: the presentation of March 20th, 1848,62 which took place 2 mo before that on molecular chirality and dealt with a study of dimorphism, an investigation whose significance can only be described, at best, as minor when compared with the discovery of molecular chirality; the presentation of September 30th, 185063; the presentation Fig. 6. Map of the railway network in France in 1850. Arbois is located at the tip of the arrow, added by the present author. (Reprinted from ‘‘GE´ OGRAPHIE DES CHEMINS DE FER FRANC¸ AIS’’, by Henri Lartilleux, Chaix, 1962). 1078 GAL Chirality DOI 10.1002/chir
PASTEURS ANNOUNCEMENT OF MOLECULAR CHIRALITY:A DISCREPANCY 1079 of May 30th,1881,on rabies4;etc.To summarize,the pre- entations by Pasteur to the Acadmie.For example.in Mo n (see above) tation of the molecular chirality. junction with her death. The Works of LPVR The (Euvres. Other works by lPVr.In addition to the Eyures and date of the h eu rand write minin the article ned h the atisfaction with which before,pres shed writ and membe at the phasis) Thus,here too,LPVR places the my mie fran ever. he gives no date or the entlyfrom his handlingof othe er presentations by Pas detailed chrond gical table of Pasteur's wo an exten. to have 1.the ror t here that Jacqu vo ement to the Acad ate Jacques (1901 Works by Other Authors of Pasteur. and his cle 192 tions. bgpiyubishedn196O,IpRde cribes his adm s of the c documentary recordo number o ocuments (pu on arge ortionsof h th prepa sobogapay Aside from the abo he cte sources cited many of th ion on her illne or deat on hi fo L the presentation e evce.The lett corr ection of the erro us date has und in the lit her's il ng that in the Correspondance we find no ater ery of n olecuar chiral- claim:the Comptes s clearly and unequivocally indi Chirality DOI 10.1002/chin
of May 30th, 1881, on rabies64; etc. To summarize, the presentation by Pasteur of the discovery of molecular chirality to the Acade´mie is conspicuously and inexplicably absent from RVR’s biographies of Pasteur. Moreover, no information is provided by RVR on the circumstances of the death of Pasteur’s mother or on Pasteur’s trip to Arbois in conjunction with her death. The Works of LPVR The Œuvres. The editorial inclusion of the incorrect date, May 15, 1848, in the Œuvres for Pasteur’s presentation to the Acade´mie25 is puzzling because the date of the session for any presentation appearing in the Comptes rendus is immediately obvious upon examining the article in the particular volume it appears in, as discussed earlier. LPVR was a distinguished professor of medicine, a noted medical researcher, accomplished writer, and member of the Acade´mie de Me´decine (Academy of Medicine) and the prestigious Acade´mie franc¸aise (French Academy [of letters]).65,66 It is difficult indeed to understand that he could have failed to extract the correct date from the Comptes rendus. The Œuvres were published during the period of 1922–1939. The final volume, 7, dated 1939, contains a detailed chronological table of Pasteur’s work, an extensive index, and other material. In the chronological table, Pasteur’s presentation to the Acade´mie of the discovery of molecular chirality is still shown67 to have taken place on May 15th 1848. Thus, after its first appearance in Volume 1 in 1922, the error was repeated 17 yr later in Volume 7. It is also relevant here that Jacques Nicolle’s 1953 volume on Pasteur gives the correct date of Pasteur’s presentation,26 as mentioned above. Jacques Nicolle (1901– 1971)68 was a French physicist, director of the Laboratory of Biochemistry of Isomers of the E´ cole pratique des hautes e´tudes, Paris. His father, Maurice Nicolle69 (1862– 1932), was a collaborator of Pasteur, and his uncle, Charles Nicolle (1866–1936), also a disciple of Pasteur, was a Nobel laureate (1928) bacteriologist.70 In his autobiography (published in 1966), LPVR describes his admiration for and close friendship with Charles Nicolle,71 and also indicates that he knew Maurice Nicolle.72 In light of the above and considering LPVR’s exhaustive work on Pasteur, it would be difficult to believe that LPVR was not aware of Jacques Nicolle’s publications on Pasteur, and the true date of the presentation therein. LPVR does not mention Jacques Nicolle (who was his contemporary) in his autobiography. The Correspondance. Aside from the above-cited letters by Pasteur from Arbois concerning his mother’s death no other information on her illness or death or on his return to Arbois in connection with these events is found in the letters included in the Correspondance. The letter Pasteur refers to which informed him of his mother’s illness does not appear in the Correspondance. It is also troubling that in the Correspondance we find no letter by or to Pasteur about his momentous announcement to the Acade´mie of the discovery of molecular chirality. This lack is most puzzling in view of the presence in the Correspondance of many letters referring to other presentations by Pasteur to the Acade´mie. For example, in a letter73 to Chappuis dated May 5, 1848, Pasteur expressed satisfaction over the favorable reception (‘‘tre` s bien accueilli’’) of the memoir on dimorphism (see above) which he had read to the Acade´mie ca. 2 mo before the presentation of the memoir on molecular chirality. Another example is that of the presentation of January 3rd, 1853,74 etc. Other works by LPVR. In addition to the Œuvres and the Correspondance, LPVR produced several other volumes about Pasteur, including a short biography in which he gives the date of the death of Pasteur’s mother and writes that ‘‘she died suddenly.’’ He then adds that ‘‘Pasteur’s grief was hardly lessened by the satisfaction with which he had, a few days before, presented at the Academy of Sciences’’ his memoir on molecular dissymmetry75 [my emphasis]. Thus, here too, LPVR places the presentation before the death of Pasteur’s mother on May 21st; however, here he gives no date for the presentation. In addition to placing the presentation before May 21st, LPVR treats Pasteur’s historic announcement very differently from his handling of other presentations by Pasteur to the Acade´mie, several of which are given by date in the biography.76–78 Moreover, on October 26, 1868, shortly after Pasteur suffered a stroke, Dumas read a note by Pasteur to the Acade´mie, and this too is mentioned79 by date in the biography by LPVR. The contrast is striking and it is, again, difficult to comprehend why Pasteur’s historic announcement to the Acade´mie of his first major discovery is almost entirely ignored by LPVR. LPVR died in 1970, and a search of the literature failed to identify a correction by him of the erroneous date. Works by Other Authors Since his death more than a century ago, Pasteur’s life and work has been the subject of numerous other publications. In recent years, several authors have studied extensive portions of the considerable documentary record of Pasteur’s life and work. Geison, for example, examined a large number of archival sources and documents (published and unpublished) in France and elsewhere for his volume, and the French writers Debre´ and MVR also drew on large portions of the documentary record in the preparation of their biographies. Nevertheless, all three authors cite the wrong date for Pasteur’s presentation to the Acade´mie. 34–36 For the purposes of this article, in addition to the sources cited earlier, many other publications80–94 on Pasteur were examined but none of these mention a specific date for the presentation in May 1848. Moreover, no discussion of the discrepancy in the date of the presentation or any correction of the erroneous date has been found in the literature. However, in one of their articles, Kauffman and Myers state95 that Pasteur’s presentation took place on May 15th, 1848, and the memoir published a week later, i.e., on the 22nd. There is, however, no basis for their claim: the Comptes rendus clearly and unequivocally indicates the session in which a memoir was presented, as discussed above. To further illustrate, on the 12th of August, PASTEUR’S ANNOUNCEMENT OF MOLECULAR CHIRALITY: A DISCREPANCY 1079 Chirality DOI 10.1002/chir
1080 GAL Thad the hon or to p sion of Marc sults of a of the the Comptes rendus for thes ion of March THE ESSENTIAL QUESTIONS aric acid. Overall.then.we are left with a striking paucity of facts that the later.on May 2nd.1 is contradicted by the evidence. The events in the literature conclusions ie in the cor he events of May rs prompts the ing ques ions s the true and hid the?That 9f thev therl f RVR m his moth LPVR. d dificult to image of the national hero.regardless of the ent his first maior er should be nearly com red by his date of Pasteur' THE HAGIOGRAPHY As i t he his in the e fields was and of o efore the to dela man health and the of med r the pres tatior eral factors, e.g the exact contents of the letter pre nents As we have s .it is no received before sk ruled out.As seen,how given the lim idu.o 1 ities and imperfectio ns y RVR is als tortion of Pa uch as it lifeti in his ow pat the de Pa More 2a金 the ques of p in Past fath e rfo raphic portray of Pas The RyR on her (Mare's)35th wedding anniversar Chirality DOI 10.1002/chir
1858, Pasteur wrote96 to the members of the Commission on the Experimental Physiology Prize of the Acade´mie: ‘‘I had the honor to present to the Acade´mie during its session of March 29th, 1858, some results of a study of the fermentation of tartaric acid and its isomers.’’ The issue of the Comptes rendus for the session of March 29th, 1858, in fact contains Pasteur’s memoir on the fermentation of tartaric acid.97 In summary, then, the claim by Kauffman and Myers that Pasteur presented his memoir on May 15th, 1848, and that the memoir was then published a week later, on May 22nd, 1848, is contradicted by the evidence. The Events in the Literature: Conclusions As we have seen above, overall, the literature is of little help in our attempt to determine the details and implications of the relevant events of May 1848. Little information is available on the circumstances of the death of Pasteur’s mother, and most publications that give a date for Pasteur’s presentation cite the wrong date. Moreover, the con- flict in the dates is not discussed in the literature. Of considerable significance is the unmistakably terse treatment of the events of the episode in the works of RVR and LPVR. It is indeed difficult to comprehend that Pasteur’s prestigious appearance, at age 25, before the Acade´mie to present his first major discovery should be nearly completely ignored by his biographer relatives in their works, which otherwise can only be described as hagiographic portrayals of the public scientist and the private man. THE HAGIOGRAPHY Pasteur worked on chirality for ca. 10 yr,98 and by the late 1850s had moved on to microbiology, followed later by his celebrated work on infectious diseases. As is wellknown, his work in these fields was revolutionary and of great benefit to human health and the practice of medicine, veterinary medicine, agriculture, etc. His discoveries reveal a scientist with superior scientific intuition, an exceptional observer, and an outstanding experimentalist. However, these qualities and achievements of Pasteur do not suffice in the reconstruction of the totality of the individual. Pasteur was, to be sure, one of the most accomplished scientists the world has known, but he was also a complex individual with both admirable qualities and human failings.99–102 Moreover, it is now recognized that a great deal of the published writings on Pasteur’s life and work engaged in hagiography and often presented a lessthan-accurate image of the scientist and the man, an image closer to a demigod than to a human being with complexities and imperfections.99,102–105 The hagiographic distortion of Pasteur began in his own lifetime, with his first biography, by RVR,54 and continued soon after his death with RVR’s La Vie de Pasteur. Moreover, La Vie de Pasteur considerably influenced103 a great deal of the subsequent works on Pasteur. In this regard, a reading of LPVR’s biography106 of Pasteur clearly shows that LPVR relied heavily on his father’s La Vie de Pasteur, and continued the hagiographic portrayal of Pasteur. The hagiographic image of Pasteur has persisted in the literature for much of the 20th century, and its deconstruction began only relatively recently, but a more accurate depiction of Pasteur and his place in 19th century science, culture, society, and politics remains to be published.102 THE ESSENTIAL QUESTIONS Overall, then, we are left with a striking paucity of facts concerning this important episode in Pasteur’s life. The available information is limited to a puzzling, terse, and incomplete recounting of the events in the biographies by RVR and LPVR, the absence of the presentation at the Acade´mie in the Correspondance, and a bizarre incorrect date in the Œuvres. In light of the pervasive hagiographic approach to Pasteur by his biographer relatives, this state of affairs prompts the following questions: was the true date of the presentation deliberately altered in the Œuvres and did the two family biographers manipulate and hide the facts surrounding the events in their works on Pasteur? That is, was Pasteur’s famous presentation in Paris one day after his mother’s death in Arbois viewed by LPVR and RVR as potentially intolerably damaging to their faultless image of the national hero, regardless of the precise reasons for his absence from Arbois at the time of her death? According to this hypothesis, it is also logical to assume that in addition to altering the date of Pasteur’s presentation, minimizing the discussion of the events would have seemed necessary to RVR and LPVR to avoid potentially causing the emergence of some inconvenient details. This, then, would explain the laconic or silent treatment of Pasteur’s first great discovery and his mother’s death by the two biographers. Another question of interest is whether Pasteur—if he received the letter alerting him to his mother’s illness before the presentation at the Acade´mie—decided to delay his departure to Arbois until after the presentation. Such a decision would presumably have been influenced by several factors, e.g., the exact contents of the letter, the precise time of its receipt, and by train and stagecoach schedules, etc. As we have seen, it is not very likely that Pasteur received notification of his mother’s illness before his appearance at the Acade´mie, but technically it cannot be ruled out. As we have also seen, however, given the limited amount of time available and the travel conditions in the 1840s, in any case, Pasteur could not have arrived in time to see his mother alive. Furthermore, it is also clear that he left for Arbois only after his presentation at the Acade´mie. The silence about Pasteur’s presentation of May, 1848, in the 1883 biography by RVR is also relevant in this context, inasmuch as it is clear that the biography was written under close supervision by Pasteur (see earlier), raising the question of Pasteur’s role in the affair. In considering these matters, we must also bear in mind Pasteur’s renowned unrelenting work habits,107,108 ambition,109 and pursuit of glory,110 which are known to have interfered, at times drastically, with his family life. A portion of a letter Pasteur’s wife Marie (ne´ e Laurent, 1826– 1910, see Fig. 7) wrote to her daughter Marie-Louise and son-in-law RVR on her (Marie’s) 35th wedding anniversary 1080 GAL Chirality DOI 10.1002/chir
PASTEURS ANNOUNCEMENT OF MOLECULAR CHIRALITY:A DISCREPANCY 1081 been ap a po eur's ab day 0 that rance before the Academie in Pa on the follow is CONCLUSIONS ee od atcnonhc ond ent o the nts of Ma .1848.i diefnn ab eir works on Pa o the d ab sumably for fear of an rave family medical eme Rency.Suc creatorsand fervent pro ctors of the hagiographic imag cle raise 轻荒音正盘院成细 is illustrative this context "Your father al he paucity of nformation entury of hagiograph d inte ble in Pasteur has damp for the continuing re the date in today, the 1848 issues of the Cmp teur remains in maythink that he most impo in science matt ha includin witl unts ofits noun nfide e have n getting the concepts right?Mo ce cal ns uracy,but a use such investigations can p justify himself in reaction to his own feelings of remo and their chroniclers In this case,for exam Chirality DOI 10.1002/chin
is illustrative in this context: ‘‘Your father, always very busy, speaks little to me, sleeps little, and gets up at dawn; in a word, he continues the life I started with him 35 yr ago today.’’111 Also relevant in this context is the death of Ce´cile, one of the Pasteurs’ four daughters. In May, 1866, at age 12, she is stricken with typhoid fever in Chambe´ ry. Pasteur is in Ale` s, engaged in studies on diseases of silkworms, studies which he had been asked to undertake by Dumas, and which were eventually credited with saving the French silk industry. Despite the alarming news about Ce´cile, Pasteur remains in Ale` s. His wife Marie writes him pressing letters urging him to join her at Ce´cile’s bedside, and he finally leaves for Chambe´ ry. He finds his daughter feeling somewhat better and remains with her only 3 days, returning thereafter to Ale` s, apparently not trusting his collaborators’ work in his absence. Ce´cile dies on May 23rd without having seen her father again.112 Jeanne, another of Pasteur’s daughters, died at age 9 in Arbois 7 yr earlier, in September, 1859, also of typhoid fever; Pasteur arrived from Paris too late to see her alive.113 Debre´, a biographer of Pasteur highly sympathetic to his subject, writes that after the death of his father in 1865 Pasteur often sought to justify himself in reaction to his own feelings of remorse about putting his passion for science ahead of love for his family.114 Given all of the above, then, it does not appear unreasonable to suggest that RVR and LPVR may have been apprehensive of a potentially negative judgment that would be created by Pasteur’s absence from Arbois on the day of his mother’s death, when that absence is coupled with his appearance before the Acade´mie in Paris on the following day. Does this mean that they did falsify the record? We can only conjecture, but the evidence, in its totality, is strongly suggestive of an affirmative answer to the question. CONCLUSIONS RVR’s and LPVR’s hagiographic treatment of Pasteur’s life and work is a matter of public record, and an inexplicably terse or silent treatment of the events of May, 1848, is also unmistakable in their works on Pasteur. Nonetheless, definite answers to the questions raised above cannot be given in the absence of additional, specific, information. Yet the available evidence strongly suggests an alteration and manipulation of the record, presumably for fear of an adverse public judgment of Pasteur for a real or perceived insensitivity at a time of a grave family medical emergency. Such concerns for Pasteur’s reputation would have been expected from RVR and LPVR, who were the early creators and fervent protectors of the hagiographic image of Pasteur as a ‘‘demigod.’’ Thus, the findings of this article raise new questions concerning the state of mind of Pasteur’s closest biographers and the extent and limit of their zeal in protecting the exalted image they constructed of him. Why has the discrepancy in the date of Pasteur’s historic presentation escaped attention until now? A part of the answer is undoubtedly the paucity of information on the facts of the case. In addition, one wonders whether a century of hagiography on Pasteur has dampened interest in potentially unfavorable information about the ‘‘lay saint.’’ As for the continuing recurrence of the erroneous date in the literature today, the explanation may lie in the considerably greater worldwide availability of the Œuvres than the 1848 issues of the Comptes rendus (personal communication from Clark Driese of Denison Memorial Library, University of Colorado Health Sciences Center). In chronicling the history of science, it is obviously essential to be accurate about the chronology. Some, however, may think that a (‘‘small’’) 1-wk error perpetuated in the literature concerning the date of the announcement of one of the most important discoveries in science matters little. This author (probably as many others) believes, on the other hand, that accuracy in science, including in accounts of its history, is of paramount importance. If we cannot get a simple date right, how much confidence can we have in getting the concepts right? Moreover, researching the origins and causes of errors in historical accounts and correcting them is essential not only for historical accuracy, but also because such investigations can produce additional insights into the history of science, scientists, and their chroniclers. In this case, for example, tracking down the conflict in the dates has revealed that Pasteur’s closest biographers most likely falsified the date and disFig. 7. Marie Pasteur, 8 yr after marrying Pasteur. (Reprinted from ‘‘IMAGES DE LA VIE ET DE LŒUVRE DE PASTEUR,’’ by L. Pasteur Vallery-Radot, Flammarion, 1956). PASTEUR’S ANNOUNCEMENT OF MOLECULAR CHIRALITY: A DISCREPANCY 1081 Chirality DOI 10.1002/chir