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Essays on Paths of Discovery in the Biomedical Sciences
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During a long and productive career, Louis Pasteur established himself as one of the most famous figures in the history of science, one whose researches, cutting across many fields of endeavor, had a profound impact upon our health and understanding of a range of fundamental physicochemical and biological phenomena. Of the many topics which occupied Pasteur's attention during five decades, from the mid-1840's to the late 1880's, he perhaps is best known for his work on the causes and prevention of infectious diseases. In these studies, he succeeded admirably in identifying the microbes responsible for silkworm disease, anthrax, chicken cholera, and swine erysipelas, and in developing means to prevent these and other major agricultural, veterinary, and human diseases. Concomitantly, Pasteur's work on infectious diseases yielded basic techniques for research in microbiology, the establishment of the germ theory of disease, valuable insights into the physiology of microorganisms, and the first workable concepts of virulence and immunity.

An earlier and less familiar period in Pasteur's career, which we will examine in this chapter, was the research on "diseases" of wine and vinegar that occupied his attention from 1855-1865. One familiar result of his work during this time was the invention of "pasteurization," but that was only one of many remarkable accomplishments of this decade of intense work. Pasteur himself saw his fermentation research as the indispensable prelude to his justly famous medical research. But it resulted as well in a revolutionary new theory of fermentation and putrefaction, a solid disproof of spontaneous generation, and a new understanding of the importance and ubiquity of microorganisms in nature.

Our account of Pasteur's 1855-1865 work, however, will deal less with the outcomes of his experiments than with their beginnings. We will consider the debated question of why Pasteur chose this particular line of investigation, given his earlier interests and his ideas about the nature of life. And we will explore how Pasteur's feelings about the "proper conduct" of scientific research, and how tensions about the roles of and relationships between "applied" and "basic" research in the mid-19th century, bore upon Pasteur's own interpretation of his work.

Pasteur's work, as well as analyses of that work by Pasteur and by his chroniclers, epitomize the difficulties that can occur in attempting to unravel the relationships between various lines of research, whether historical or contemporaneous. His many biographers have treated Pasteur as a pure scientist who kept getting "sidetracked" onto applied problems, as a "physician without a degree," as a "free-lance of science," and as an applied scientist who made immensely fruitful fundamental discoveries. These various depictions, however, are no more ambivalent than Pasteur's own views, as reflected in his statements about the importance of his work on industrial problems and disease. At times, he argued that the pursuit of "practical applications of science" could be a snare for the "servant of pure science." Thus, shortly after he had spent a triumphant week at Emperor Napoleon III's palace in 1865, demonstrating his discoveries on the microbial causes of wine and silkworm diseases, Pasteur wrote to the Emperor that the scientist who works on practical problems "clutters up his life and thinking with preoccupations which paralyze his faculty for discovery," and he risks both "his peace of mind and the success of his investigations" (Pasteur, Correspondence II, 19 Dec. 1865, p. 237).

While in charge of the science faculties at Lille and at the École Normale in Paris, Pasteur campaigned in favor of a strong emphasis on pure sciences in the curriculum. The student who mastered the theory, principles, and methods of pure science, he insisted on many occasions, would have no trouble turning his knowledge to applications in France's time of need.(1) Yet, Pasteur himself taught very popular courses in applied chemistry and worked on a long series of practical problems. And, as we read in his letters to Napoleon III, the Emperor's Aide de Camp General Fave, and various ministers of education he often justified his requests for research funds by pointing to the immediate economic or medical significance of his investigations.

Pasteur had a favorite and much-quoted aphorism, that he used to underscore the primacy of pure science, the trees whose fruit were the applications of science.(2)

There does not exist a category of sciences to which we can give the name of 'applied sciences.' There are science and the applications of science. [END OF PAGE 11]

But as we read this aphorism, and other statements by Pasteur about "applied science," it is important to realize that he had a rather different understanding of the term from our own today, an understanding conditioned by the nature of and relationships between technology and science in the mid-19th century.(3) Pasteur considered the phrase "applied science" to be a "shocking" and "false" combination of words. For, as technology and science were viewed at the time, it suggested that the largely empirical discoveries of industry were more than a mere "collection of recipes" and rules-of-thumb; it suggested that they too could claim to rest on the rigorous methods, theories, and experiments that were seen as the foundations of pure science.

Pasteur's formulation about "science and the applications of science" also had the advantage of making his own work on industrial fermentations and the diseases of men, animals, wines, vinegars, and beers appear an indivisible part of his "purely scientific" work on crystals and spontaneous generation. It saved him from feeling defensive about the years he devoted to practical problems when he wished to regard himself as a "servant of pure science."

Pasteur's earliest research, before his work on fermentation, did not require him to cope with questions about the "applied/pure" nature of his work that would trouble him later in his career. As a student at Paris' École Normale Superieur from 1843-1846, he was infected by his professors' enthusiasm for the new science of crystallography, which then offered physicists and chemists one of the few ways to recognize and obtain pure laboratory samples of a substance and to gain knowledge of molecular structures (Burke 1966).(4) Pasteur's entry into the field of crystallography began at the end of 1846, when the chemist Auguste Laurent joined the laboratory where Pasteur was working as an assistant. Laurent asked Pasteur to assist him with some experiments, and Pasteur recalled that "one day it happened that M. Laurent -studying, if I mistake not, some tungstate of soda, perfectly crystallized and prepared from the directions of another chemist, whose results he was verifying - showed me through the microscope that this salt, apparently very pure, was evidently a mixture of three distinct kinds of crystals, easily recognizable with a little experience of crystalline forms. The lessons of our modest and excellent professor of mineralogy, M. Delafosse, had long since made me love crystallography; so. . .I began to carefully study the formations of a very fine series of combinations, all very easily crystallized, tartaric acid and the tartrates." Pasteur continued: "Another motive urged me to prefer the study of those particular forms. la Provostaye had just published an almost complete work concerning them; this allowed me to compare as I went along my own observations with those, always so precise, of that clever scientist" (Merz 1965, pp.. 404-405).

In the course of these researches, Pasteur became fascinated by the problem of explaining the relationship between common tartaric acid and its isomer, racemic acid (also called paratartaric acid), which possessed all the chemical properties of tartaric acid but which exhibited a strikingly different optical behavior in polarized lights.(5) Pasteur examined crystals of racemic and tartaric acid under the microscope with great care and discovered in 1848 that racemic acid was in fact a mixture of two crystals which were mirror-images of one another. Moreover, one of these two crystals was absolutely identical - in its crystalline geometry, its chemical properties, and its response to polarized light - to ordinary tartaric acid. From this discovery came the realization that the left- or right-handedness of a dis-symetrical (to use the word Pasteur coined to describe this special kind of asymmetry) crystal and its underlying molecular structure can affect its physical and chemical properties - the basis of stereochemistry (Alworth 1972).

Both the ordinary right-handed crystals of tartaric acid and the mixture of right-handed and left-handed tartaric acid crystals in racemic acid were produced as a by-product of the alcoholic fermentation of grapes. Tartaric acid was commonly found as crystals on barrels of wine, while racemic acid had only been found occasionally and in small quantities. In 1852 Pasteur spent a busy month visiting industrial refineries of tartaric acid in hopes of discovering the conditions under which the rare little tufts of racemic acid would form in the midst of the large tartaric acid crystals. He was able to establish that only the crude mother-liquors of tartaric acid would produce racemic acid before the industrial processes of refinement took place, but he still could not say why racemic acid arose on the rare occasions that it did. Instead, he went back to his laboratory at Strasbourg, where he was now a professor of chemistry, and there succeeded in turning ordinary tartaric acid crystals into racemic acid by complicated chemical manipulations.

In his work on tartaric acid and many other organic compounds which also showed dissymetry, Pasteur [END OF PAGE 12] observed that only one kind of crystal was normally found when these compounds occurred as natural products of living things. Thus, the right-handed crystal of tartaric acid was commonplace; its left-handed mirror-image - either alone or in the racemic acid - was exceptional. And, the right-handed one reacted differently with other optically active compounds from the left-handed counterpart.

Having demonstrated with chemical reactions that his structural principle of molecular dissymmetry influenced chemical affinities, Pasteur began to speculate about the cause of dissymmetry. Sharing the desire of many 19th century scientists to find universal forces or principles, Pasteur imagined that the dissymmetry of organic compounds reflected a cosmic or universal dissymmetry:

The universe is an asymmetric whole. I am inclined to think that life, as manifested to us, is a function of the asymmetry of the universe and of the consequences it produces. The universe is asymmetrical; for, if the whole of the bodies which compose the solar system moving with their individual movements were placed before a glass, the image in the glass could not be superposed upon the reality. Even the movement of solar light is asymmetrical. A luminous ray never strikes in a straight line upon the leaf where plant life creates organic matter. Terrestrial magnetism, the opposition which exists between the north and south poles in a magnet and between positive and negative electricity, are but resultants of asymmetrical actions and movements . . . Life is dominated by asymmetrical actions. I can even imagine that all living species are primordially, in their structure, in their external forms, functions of cosmic asymmetry" (Quoted in Dubos 1950, p. 111).

Viewing the rotation of the earth and its magnetic polarity as two possible dissymmetric influences on living matter, Pasteur began to devise experiments to see what happened to the dissymmetric chemistry of plants when the earth's magnetic forces were reversed by a solenoid or when the sun's rays appeared to move from west to east. Although his friends and mentors begged him not to waste his time on research that probably would lead nowhere, Pasteur had great hopes. His wife wrote to her father-in-law during this period that "Louis is rather too preoccupied with his experiments. You know that those he is undertaking this year ought to give us - if they succeed - a Newton or Galileo" (Pasteur, Correspondence I, 10 Nov. 1853, p. 324).

The experiments, however, did not go well, and Pasteur abandoned them for the time being. But he never rejected the idea of a universal dissymmetry manifested in the dissymmetry of living matter. Throughout his career he returned to the subject, discussed it in papers and public lectures, and picked up his abandoned experiments once more to distract himself from the bitterness of France's defeat in the Franco-Prussian War. At the end of his life he regretted that he had not pursued the idea further, that he had not explained the ultimate "cause of one of the greatest mysteries of nature" (Pasteur, Correspondence I, 7 Dec. 1853, p. 325; P. Vallery-Radot, 1957b, P. 185).

In September 1854, Pasteur accepted the position of professor of chemistry and dean of the new Faculty of Sciences at Lille. Lille was the industrial center of northern France, and the town itself had underwritten the new science school in hopes of training its young men in the theory and industrial applications of science. The teaching in the school stressed practical matters and thus "appeared to be the public's taste," Pasteur reported to his superior, the rector of the Academie de Douai, in 1855 (Pasteur, Correspondence I, 26 Jan. 1855, P. 359). Pasteur's course in chemistry attracted the largest number of students and auditors -nearly 250, he boasted to a friend. He was particularly pleased at the young men who had already finished their education and started to work in industry, yet came to the school to profit from studying in subjects most closely connected to their future careers. There was, for example, the son of a distillery owner who would take over his father's business in a few years; since he obviously needed to know more chemistry than physics or natural history, he was allowed to take the chemistry course by itself and to pay reduced fees.

Pasteur's mixed feelings about the relative importance of pure science and applied science are revealed in his correspondence and papers during his three years at Lille. In his inaugural address as dean, for instance, he first spoke eloquently to the citizens about the excitement their sons would feel when they were introduced to the daily utility- of science. "Where in your families will you find a young man whose curiosity and interest will not be immediately awakened when you put into his hands a potato, when with that potato he may [END OF PAGE 13] produce sugar, with that alchol ether and vinegar?" (R. Vallery-Rodot 1960, p. 75; Pasteur, "Discours," 7 Dec. 1854, Oeuvres VII, pp. 130131). But, he hastened to add, "God forbid that theory should ever disappear from this teaching. We must not forget that theory is the mother of practice. Without theory, practice is just routine born of habit."

The Minister of Public Instruction, in fact, feared that Pasteur would put too much emphasis on theory at the expense of practical knowledge. Even while he praised Pasteur's teaching, the Minister urged him to keep the industrial needs of the region constantly in mind: "M. Pasteur must always guard against being carried away by his love for science, and he must not forget that the teaching of the Faculties, while keeping up with scientific theories, in order to produce useful results and extend its happy influence, should through the most numerous applications adapt itself to the real needs of the country" (Pasteur, Correspondence I p. 374 n. 1).

Pasteur apparently heeded his superior's advice. His activities at Lille included an analysis of fertilizers at the request of the General Council of the Department du Nord, which saw it as an important piece of work in so rich an agricultural region, and also as an opportunity to popularize and increase the influence of the new Faculty. One Easter vacation was spent in Belgium visiting metallurgical factories "since my position as chemistry professor," he wrote his father, "requires I know a good deal about this" (Pasteur, Correspondence I, 11 Jan. 1856, p. 386; Nov. 1856, p. 406). In 1855 and 1857 he offered a course on "chemistry applied to industries" which was received with great enthusiasm by both his audience and the Minister of Public Instruction. Every lesson was followed by a field trip to a local factory where Pasteur would discuss technical details and clarify the techniques by drawing pictures on the blackboard (Pasteur, "Compte Rendu des travaux de la Faculte des Sciences de Lille pendant I'annee scolaire, 1855-1856," Oeuvres VII, P. 144-145).

Pasteur put a special emphasis on teaching about and helping the sugar-beet industry of northern France. A large part of his course on applied chemistry was devoted to the details of the manufacture and refinement of sugar and alcohol from beet juice. He was impressed by the industry's eagerness to keep up with scientific innovations and to adopt new processes. But, he remarked in 1855, "a prejudice which must be fought is this:. . .they are very disposed to believe that there is an applied science, that the applications form a separate body of doctrines, when really the applications of the sciences are nothing but deductions from purely scientific discoveries" (Pasteur, Correspondence I, 15 Nov. 1855, pp. 382-383). Much of Pasteur's later career confirmed his belief that "applications are nothing but deductions from purely scientific discoveries." Yet, there is irony in the fact that this earliest formulation of his aphorism about applied science should concern the industry whose practical problems were soon to stimulate Pasteur into entering the field of biology and there making fundamental new discoveries.

In 1856 Pasteur's interests in molecular dissymetry and his responsibilities as a teacher of the practical applications of science converged in the study of beet juice fermentations. A student of his, Emile Bigo, had tried to make vinegar from sugarbeet alcohol, but relying only on the standard reference works and his notes on Pasteur's lectures, the young man had little success. Pasteur wrote on his behalf to a friend, a physics professor at Nancy, to enquire about a method of preparing vinegar using beechwood shavings that Pasteur had seen at the friend's brother-in-law's house (Pasteur, Correspondence I, July 1856, p. 394-395). We do not know what became of young Bigo's experiments on vinegar in Pasteur's laboratory, but Pasteur's encouragement and interest in his attempts had important consequences. Bigo's father - the owner of a beet juice distillery in Lille - sought Pasteur's help on a problem he was having in his factory. The sugarbeet juice was not fermenting into alcohol, but into lactic acid.

Pasteur soon was so absorbed with the puzzle brought to him by the elder Bigo that he went to the factory every day; Madame Pasteur complained wryly that he was living "neck-deep in beet juice" (Pasteur, Correspondence I, 10 Dec. 1856, p. 412). Pasteur's early experiences with a microscope now proved its value. He spent long hours comparing samples of beet juice and testing one idea after another. On the first day he began studying the fermenting juice, he observed little globules which grew and budded in the liquid. In the samples of juice that were producing the unwanted lactic acid, he soon noticed another kind of globule, smaller and longer than the globule he found in the healthy vats. Grasping the practical implications of his observations, Pasteur told the Bigos to test the healthiness of the fermentation by watching the shape of the microscopic [END OF PAGE 14] globules; if they were large and round, the fermentation was going well; if they became elongated, lactic acid fermentation was replacing the desired alcoholic fermentation (R. Vallery-Radot 1960, p. 79; P. Vallery-Radot, 1958a, p. 10).(6)

We have little information about this period in Pasteur's career, and it is not clear just when and how he realized that the two kinds of globules he saw in the fermenting beet juice were in fact living organisms and the cause of the fermentations. His reports on his investigation to the Society of Science in Lille only described his chemical analyses of the fermentations, and not his microscopic studies. He told his students "how the ferment looks under the microscope" but did not suggest that the globules were alive and actively making the juice turn to alcohol or lactic acid (P. Vallery-Radot, 1958a, p. 10). Pasteur, however, was predisposed to consider such an explanation, even though it directly opposed the two prevailing theories of fermentation championed by the most influential chemists of the day, Liebig and Berzelius.(7) Berzelius regarded the yeast of alcoholic fermentation as simply a kind of chemical catalyst; Liebig believed that yeast caused fermentation by its disintegration and decomposition, which in turn disturbed the sugar molecules so that they broke down into alcohol. Pasteur, though, had long been convinced that the dissymmetry of organic molecules was somehow directly correlated with the fact that they were produced by living - not disintegrating - entities. In 1855, after giving up his romantic experiments on the ultimate cause of molecular dissymmetry, he had gone back to studying examples of organic compounds which exhibited optical activity. Amyl alcohol was a case which especially aroused his curiosity, because it did not behave according to the rule he had formulated for tartaric acid and similar compounds. Amyl alcohol showed optical activity, rotating polarized light like tartaric acid, but its crystals did not show the dissymmetric structures Pasteur expected.

Lille provided Pasteur with ample opportunity to study amyl alcohol, for it was a common by-product of several industrial fermentations, including the beet juice lactic acid fermentation which was giving M. Bigo such trouble. Pasteur did not take long to decide that Liebig's explanation of amyl alcohol's optical activity was untenable. Liebig argued that optically active sugar molecules, excited by the disintegration of the unstable yeast, broke down into amyl alcohol molecules which preserved the optical activity of the precursor. Pasteur voiced his opposition to Liebig's views in an 1857 "Memoir on Lactic Acid Fermentation," which he presented to the Society of Sciences, Agriculture, and Arts of Lille. In his Memoir, which Bulloch characterizes as epitomizing "the essential points of all Pasteur's work on fermentation, and indeed of bacteriology," Pasteur argued as follows (Bulloch 1938, p. 60).

The molecular constitution of sugars seems to me to be very different from that of amyl alcohol. If this alcohol, when active, originated from sugar, as all chemists agree, its optical activity would derive from that of sugar. I am loath to believe this, considering the present state of our knowledge, for every time that one tries to find the rotatory property of a substance in its derivatives, it promptly disappears. The fundamental molecular group must remain in some measure intact in the derivative if the latter is to continue optically active, a result that can be foreseen from my investigations, since the property of optical activity is entirely due to a dissymmetric arrangement of elementary atoms. But I think that if the molecular group of amyl alcohol does derive from sugar, it is too distantly connected to retain the dissymmetric arrangement of atoms. (Pasteur, "Memoire sur la Fermentation appele lactique," 1857, Oeuvres, II, pp. 3-4; Conant 1952, p. 25)

What then in the beet juice was responsible for altering the arrangement of the sugar molecule?, Pasteur asked.

Pasteur confessed that his preconceived ideas about the role of molecular dissymmetry in the "organization of living organisms" led him to examine the juice under the microscope for living organisms. In the grey nitrogenous scum on the top of the juice, he discerned "little globules or very short segmented filaments, isolated or in clusters," which he admitted would look very like tiny bits of disaggregated protein to anyone who was not forewarned! But he then invented ingenious techniques for isolating and growing these little globules in a pure state, and demonstrated that lactic acid fermentation took place whenever a trace of the living grey deposits was sown in a suitable mixture of alkaline liquid and sugar.

In his first paper on fermentation in 1857, Pasteur told his audience in Lille how his earlier study of amyl alcohol had made him ask about the process of fermen-[END OF PAGE 15]tation that gave rise to alchol, how he was mentally prepared to find living organisms, how he isolated and grew the lactic acid ferment, and how he could always produce lactic fermentation (and no other kind) whenever he put the globules into the proper medium. To the naked eye, he said, this newly discovered ferment resembled in appearance and activity the well-known product of alcoholic fermentation, brewer's yeast. Each of the two ferments, however, was absolutely specific: pure lactic acid ferment never caused alcholic fermentation, and pure brewer's yeast never produced lactic acid. Moreover, the two throve in different conditions: brewer's yeast grew best and turned sugar to ethyl alcohol most efficiently in a neutral medium,while the globules of lactic acid ferment preferred an alkaline environment. Most important, the yeast or ferment had to be alive. The process of fermentation, Pasteur affirmed, was simply a manifestation of the globules' living organization, development, and physiological activity, and not, as Liebig held, a sign of their death and putrefaction.

Not long after presenting this paper on lactic acid fermentation, Pasteur observed something that clearly demonstrated the intimate connection between fermentation and molecular dissymmetry. He noticed that a solution of racemic ammonia tartrate (ammonia paratartrate) lying about in his laboratory had become moldy and begun to ferment. (8 ) Such accidents were common enough, but at this point any kind of fermentat(on would have attracted Pasteur's eager attention. To his great satisfaction, he found that the mold was choosing between the two forms of ammonia tartrate, fermenting the right-handed one and leaving the lefthanded one alone. It was a far easier way to isolate the left-handed isomer than the elaborate chemical techniques Pasteur had worked out a few years before. He was so pleased with this elegant finding that he submitted a paper about it to the illustrious Academy of Sciences to be considered for the Prize in Experimental Physiology. He received the prize early in 1860 for his work on fermentation in general, but this observation won special mention from Claude Bernard and the other judges. When he reviewed his life work many years later, Pasteur ignored his interest in amyl alcohol and M. Bigo's request for help and made it sound as if his discovery of this signal fact was what had led him from crystallography to the study of fermentations (P. ValleryRadot 1958a, p. 12; Pasteur, "La Dissymetrie Moleculaire," 1883, Oeuvres I, p. 376).

Pasteur had no doubt tht every kind of fermentation or putretaction required its own peculiar microorganism. Between 1857 and 1863, he published paper after paper identifying these specific living agents of fermentation and describing the conditions they required for survival. One of these papers, published in 1861 is particularly notable. In the course of systematically studying the products of lactic acid fermentation, Pasteur noticed that the microorganisms associated with the formation of butyric acid from lactic acid behaved differently from the infusoria now familar to him from a variety of fermentations. When he watched the infusoria of the lactic acid ferment move about in a drop of liquid under a coverslip, he could see them cluster about the edges of the coverslip. But the butyric acid infusoria appeared to shun the edges of the coverslip. He followed up this observation with experiments which demonstrated that the butyric acid ferment could live in the absence of free oxygen, and that, in fact, oxygen would kill the tiny microbes. Turning back to consider the oxygen needs of other ferments, Pasteur came to the conclusion that "fermentation was life without air." Some microbes, like the butyric acid ferment, were strictly anaerobic (a word coined by Pasteur): they could live and produce butyric acid only in the absence of oxygen. Most microbes, though, were aerobic: they preferred to live in the presence of oxygen, yet they too could survive without oxygen by fermenting, by breaking down organic compounds in their environment to obtain the energy they needed to live.

Yeast, Pasteur found, can live either aerobically or anaerobically, and in studying the conversion of sugar into alcohol and yeast protoplasm by yeast grown with and without oxygen, he discovered what later was termed the "Pasteur effect": sugar is converted into yeast protoplasm more efficinetly under aerobic conditions than anaerobically, but, for complex reasons, the actual utilization of sugar is lowered.(9) The Pasteur effect subsequently was demonstrated in freshly picked fruit by Pasteur in 1872, and then in frog muscle tissue by Paschutin in 1874. The mechanism of the Pasteur effect continues to intrigue physiologists and biochemists to this day, and it surely counts as one of the most interesting basic discoveries to come out of Pasteur's research on fermentation.

During these years in which Pasteur generalized the phenomenon of fermentation, he also worked hard on two closely related lines of research. In the fall of 1857, [END OF PAGE 16] he was given the important post of director of scientific research studies at his beloved École Normale Supérieure in Paris. His official duties no longer required him to worry about the practical problems of industrial fermentations, but a similar problem of even greater economic importance was soon set before him: what caused the diseases of vinegars and wines?

Pasteur's earliest research on this subject may have been inspired by a kind of local patriotism. For in 1858 he wrote a friend that he was taking a microscope with him on his trip home to Arbois in order to study the grape-must disease, "which requires my presence in Arbois throughout the month of September" (the month of the grape harvest). The first spoiled wines Pasteur looked at were those of his native Jura vineyards, and in them he spied microorgnaisms similar to the lactic acid ferment he had discovered the year before (Pasteur, Correspondence II, 28 August 1858, pp. 35-36; "Introduction," Oeuvres, III, p. V).

He did not, however, spend much time just then on the maladies of wine and vinegar, because the fundamental assumption of his experiments on fermentation was under attack, and Pasteur became embroiled in one of the now classic controversies in the history of science. In maintaining that each kind of fermentation and putrefaction was caused by a specific kind of living microorganism - the germ theory of fermentation Pasteur had implicitly ruled out the possiblility of spontaneous generation of microscopic life. For if microbes could come into life from the random jostling of organic matter in the course of decomposition and fermentation, then there was no sense to the specific actions of the ferments that Pasteur had watched with such care. In 1858, a professor of medicine in Rouen, Felix Pouchet, presented his "proofs" of spontaneous generation before the Academy of Sciences in Paris; a year later he described his experiments and metaphysical ideas about the spontaneous generation of microorganisms in an immense book, Heterogenie. Pasteur's direct involvement in the debate stirred up by Heterogenie began when Pouchet asked him in a private letter whether he thought the lactic acid ferment might not be spontaneously generated. Pasteur replied that there was not as yet enough evidence to say, and that Pouchet might have been too hasty in asserting the reality of spontaneous generation, given the ease with which microbes like the lactic acid ferment could contaminate the air and the broths of organic matter from which the microbes has seemingly been created (Farley and Geison 1974, p. 179).

After this polite response, Pasteur joined the debate in earnest ¯ much against the advice of his friends. In 1860-1861 he published five papers on his spontaneous generation experiments, which have become justly famous for their elegance and meticulous technique. He drew out the necks of glass flasks of boiled broths into long curves which allowed air to flow in easily, but which caught the dust-motes ' germs, and spores in the air on the damp sides of the neck: the broths remained perfectly clear. He carried flasks of sterile broths high into the Alps to prove that, even in the mountain air, germs could contaminate the broths, and also that some samples of mountain air were completely germ-free. (Pasteur, "Memoires sur les corpuscles organisees qui existent dans I'atmosphère," 1861, Oeuvres, II, pp. 210-294; Conant 1953).

Pasteur's carefully designed and executed experiments dealt several damaging blows to the theory of spontaneous generation, and the observations and experiments on which it rested. Pasteur, for example, demonstrated that micororganisms or their germs floated in the air, whereas Pouchet only claimed that the "eggs" or "germs," rather than the adult microbes, came into being spontaneously from decomposing organic matter. He showed too that air alone could not initiate the generation of living things, as Pouchet and others had argued, and that simple measures of heating and air filtration could prevent "organic broths" like those prepared by Pouchet from showing any signs of life.

The question of spontaneous generation was pit before a commission of the Academy of Sciences for a decisive judgment in 1864. The dramatic clarity of Pasteur's experiments, his scornful condemnations of Pouchet's logic and technique, his self-assured explanations of his own results, and finally Pouchet's affronted withdrawal from the official demonstrations of the major experiments, convinced the commission that spontaneous generation did not occur. Another round of the controversy, with the English physician, Henry Charlton Bastian, defending spontaneous generation, took place in the 1870s, but for the time being Pasteur could consider the question settled triumphantly in his favor and he could give more time to his work on the diseases of vinegars and wines (Duclaux 1920, pp. 109-111; Farley and Geison, 1974, p. 161-198).

Pasteur's researches on the diseases of vinegar and wine were a logical but not a necessary sequel to his general studies of fermentation and spontaneous generation. In his Studies on the Mycoderms: The Role of [END OF PAGE 17] These Plants in Acetic Fermentation, delivered at the Academy of Sciences in February 1862, Pasteur explained that he had long suspected that microscopic fungi were involved in the production of vinegar from wine (i.e., acetic acid from alcohol):

In the researches on fermentations which I have pursued for many years now, various indications led me to think that the mycoderms could not be alien to the formation of acetic acid. These indications multiplied and defined themselves more and more; I applied all my efforts to follow them up with direct experiments. (Oeuvres, III, pp. 7-12)

Indeed, he had started noticing these "indications" even before he started his work on alcoholic and lactic fermentation. As we have seen, young Emile Bigo had tried to produce vinegar while working in Pasteur's lab at Lille in 1857, and Pasteur had then sought information from his friends about processes for making vinegar. It is clear from Pasteur's first report on acetic fermentation, to the Chemical Society of Paris on July 26, 1861, that he had fully expected what he found: a microscopic fungus, mycoderma, covered the wine's surface with a delicate transparent film and turned the alcohol into vinegar. The German process in which the wine was poured over beechwood chips entirely depended on the presence of this fungus on the chips. The beechwood chips had no mysterious catalytic property, as Liebig and many other eminent chemists had maintained in their textbooks."(11) Six months after this first report, Pasteur patented a reliable method for sowing the mycoderm into wine and then put the process into the public domain. No longer would the vinegar-makers of Orleans have to wait anxiously for the thin veil of the fungus to establish itself by chance.

Pasteur's long memoir of 1864 on acetic fermentation, vinegar, and the mycoderma simply elaborated the points he had made in the first paper, for by this time his interest had shifted to the maladies of wine. Pasteur's 1866 book, Studies on Wine, Its Diseases, and Causes Which Provoke Them, with new processes for conserving and aging wine, opened with a dedication to Napoleon III:

In the month of July 1863, the Emperor urged Me to turr. my researches toward the understanding of the diseases of wines. Directed by observations of detail which my studies on fermentations had suggested to me, I had already caught sight of the possibility of a worthwhile piece of work on this to which I have dedicated myself ever subject since with the thought of his concern for one of the greatest agricultural products of France and with the desire to respond to the kindness of an August patron. (Pasteur, Études sur le vin, Oeuvres III, pp. 112-113).

Although Occupied With his work on fermentation and his experiments on spontaneous generation, Pasteur had begun thinking about the diseases of wines several years before the Emperor made his suggestion. In 1858. We have noted, he had examined diseased wines from his native countryside, and in 1859 he had justified his fermentation studies to the Minister of Public Instruction by pointing out a practical result of his research: healthy wine contained not only alcohol, but also hitherto unsuspected by-products of fermentation such as glycerine and succinic acid, which helped give wine its "pleasant properties." Then, in 1861, his friend, the chemist Balard, asked Pasteur to look at some diseased wines from the vineyards of Montpellier; Pasteur was pleased to recognize the micro-organisms he had seen in the Jura wines. And, of course, Pasteur's work on acetic fermentation was, in effect, a study of the commonest ailment of wines, their souring and turning to vinegar. But the Emperor's encouragement - and the financial support that it implied - made Pasteur set to work in earnest in 1863.

During the wine harvests of 1863 and 1864, Pasteur and a small band of his favorite former students left Paris for the wine growing regions "to watch the fermentation practices . ., to study diseased wines on the spot, and to collect the observations and views of men competent in these matters" (Pasteur, Correspondence II, 14 July 1863, p. 125). As he had expected, he was soon able to associate every malady and evil taste of wine with its own microorganism. One turned the wine sour, another made it bitter, yet others made it ropy or oily. Given an apparently healthy sample of wine, he could predict from microscopic studies of its alien ferments among the yeast globules just how it would taste in a few days. At the same time, he showed that the only rationale for the traditional fear of air reaching the wine was that the air could carry in the germs of these diseases; otherwise, oxygen actually helped healthy wine to mature in flavor and color. Moreover, just like the yeast, the undesirable ferments were normally present on the grapes themselves. If the diseases were to be [END OF PAGE 18] prevented, the parasitic microorganisms had to be killed or weakened without destroying the wine at the same time.

Pasteur first experimented with tasteless antiseptic agents (inorganic phosphates and sulphates), but with no great success. He then turned to heat, for his experiments on spontaneous generation had proven that heat could kill microbes. Although centuries of tradition forbade heating wine, Pasteur tried the experiment and announced the happy results to the Academy of Sciences in May 1865, less than two years after acting on the Emperor's suggestion. Wine heated to 50-60ºC, well below boiling, did not lose its flavor or color and it did not spoil (Duclaux 1920, pp. 141-144; Pasteur, "Nouvelles observations au sujet de la conservation des vins," 1865, Oeuvres III, pp. 418-422). He patented the technique of heating the wine and put the process in the public domain, as he had done with his vinegar processes. The technique was quickly dubbed "pasteurization" and used for all kinds of perishable foods and liquids. That fall the Emperor invited Pasteur to spend a week at the palace, where the scientist gave himself the pleasure of showing Napoleon III that the microorganisms of wine diseases could be found even in bottles from the Imperial cellars (Pasteur, Correspondence II, November-December 1865, pp. 216-238).

To us, it sounds odd to call an unwanted change in fermentation a "disease," but the usage goes back to antiquity. Indeed, men had often tried to cure diseased wines with the same remedies they used to cure their own ailments (Majno 1975, pp. 221-224). Linked to this was another traditional analogy: the corruptions of contagious disease were like the "metamorphoses of fermentation" and putrefaction. In ancient medicine a whole class of diseases were labeled "putrid diseases," as Pasteur reminded the Academy of Sciences in 1863, and to him these connotations of "disease" and "fermentation" Were tremendously suggestive. As early as 1859, he was arguing to the Minister of Public Instruction and to the Emperor himself that fermentations, putrefactions, and contagious diseases played similar parts in the "unending circle of life and death" and that they owed their existence to similar causes (Pasteur, "Note remise au Ministre de I'Instruction publique et des cultes," 1859, Oeuvres III, 1. 481). This became a constant theme in his progress reports to the Minister and Emperor during the early 1860's.

However, even though Pasteur recognized the "interest and ability" of research on the general problem of infection by microorganisms, he did not entei the field of his own accord. Until 1865, using a strategy common to scientists seeking funds for their work, he was content to appeal to the possible medical applications of his work to justify to his sponsors the costs of his researches on fermentation and spontaneous generation. The year 1865, however, marked an important turning point in Pasteur's career. Until then he could consider himself a chemist who "happened" to work on problems that involved living matter. But, while Pasteur was still engrossed in the details of pasteurization, he was suddenly asked by his beloved teacher, J. B. Dumas, to investigate a disease of higher organisms. Pasteur's student and assistant, Emile Duclaux, vividly recalled the day when his master was asked to find out what was killing silkworms and ruining the economy of southern France.

. . . Pasteur, returning to the laboratory, said to me with some emotion in his voice: "Do you know what M. Dumas has just asked me to do? He ants me to go into the South and study the disease of silkworms." I do not recall my reply; probably it was that which he had made himself to his illustrious master: "is there then a disease of silkworms? And are there countries ruined by it? " (Duclaux 1920, p. 145)

Pasteur protested his complete ignorance of silkworms to Dumas, expressing astonishment, according to one anecdote , at learning that inside every silk cocoon there is a silkworm turning into a moth! Dumas only replied, "So much the better! For ideas you will have only those which shall come to you as the result of your own observations" (Dubos 1950, pp. 213-214).

From then on, Pasteur worked primarily on problems of infectious disease, first dealing with two epidemics which were simultaneously devastating the silkworm industry, then anthrax in cattle, fowl cholera, swine erysipelas, and finally rabies in dogs and people. The twenty years that Pasteur spent on medical research, years in which he contributed signally to the rise of medical bacteriology and the development of immunology, were a splendidly successful elaboration and application of the ideas and techniques he had worked out during the previous ten years of fermentation research.

The year 1865; then, is an appropriate place to close our account of Pasteur's early career, and to turn to a discussion of the pattern of his discoveries during the years of crystallographic and fermentation research. [END OF PAGE 19] Pasteur's published scientific papers and lectures offer us many statements of his views on the subject. To the modern reader, Pasteur's papers - written for oral delivery before scientific societies - seem astonishingly informal and conversational in style, including incidental remarks that no scientist today would be able to publish. The reports of the experiments frequently lack the measurements and details of technique that other researchers would need to duplicate them, Pasteur prefaced many papers with comments about the line of thought or preconceived ideas that had led to the experiments at hand, and ended them with speculations about the ultimate significance of the results. Ren6 Dubos has wittily imagined how an editor of a scientific journal today would react if young Pasteur had sent him that first paper on lactic fermentation:

"Dear Dr. Pasteur," the editor would write, "you have observed a few interesting phenomena, but your account of them is almost useless for lack of precise description and of quantitative data. Furthermore, you would do well to dissociate more clearly than is done in your paper wellestablished facts from your personal opinions concerning the nature of life processes. Allow me to tell you, for your own good, that these romantic opinions are entirely out of place in a dignified scientific paper - enjoyable as they may be when heard over several glasses of beer or wine in the twilight of an evening's conversation." (Dubos 1958, p. 16)

Pasteur, however, used his autobiographical and metaphysical digressions to immense rhetorical effect, for such artless candor about the workings of a scientist's mind could not fail to charm his audiences. It is very easy to see from his papers why his lectures were so popular.

By continually harking back to his earlier work, Pasteur acted as his own historian. He often claimed that his life's work had been guided by the principle of molecular dissymmetry which he had discovered in his early crystallographic studies of racemic acid. In 1883 he wrote in a memorable passage: "Carried on, enchained should I say, by the almost inflexible logic of my studies, I have gone from investigations of crystallography and molecular chemistry to the study of ferments; I have been engrossed with the thought of admitting dissymmetry into chemical phenomena" (Pasteur, "La dissymetrie moleculaire," 1883, Oeuvres I. p. 736).

Similarly, when he jotted down an outline in 1877 for a possible book on "Studies on contagious or transmissible diseases," he reminded himself to include his 1860 memoir on alcoholic fermentation, his reports on anaerobic fermentation, and his studies of the diseases of wines and silkworms (Oeuvres, VI: intro., p. V). Because the germ theory of contagious disease was so clearly implied by these earlier researches, he believed they would make the best, the most logical introduction to the projected book. In his own reconstruction of his .researches, the immediate reason for Pasteur's actually commencing work on infectious disease - Dumas' urgent request that he study the dying silkworms seemed to be beside the point. Sooner or later, he implies, something would have provided a similar occasion for starting research on diseases of animals and men.

Given Pasteur's training and orientation as a nineteenth century French scientist, his Cartesian insistence that "logic" determined the sequence of his work is not surprising, and his retrospective arguments to that effect are very persuasive. His grandson's seven volume edition of Pasteur's collected works was designed to underscore the rational unity that Pasteur saw in his researches; each volume's introduction comments directly on the formidable logical chain that binds all of Pasteur's work together.

René Dubos, however, makes two cogent criticisms of Pasteur's belief that he was pushed by "an almost inflexible logic" to make the discoveries he did. First, Dubos points out, the origins of the ideas owe little to logic but a great deal to intuition, keen observation, and bold guessing. "In the work of Pasteur, logic is evident in the demonstration and exploitation of his discoveries rather than in their genius. It is the phase of his work devoted to the development of his ideas which makes the bulk of his long papers, and which gives the impression of orderly logical progression" (Dubos 1950, p. 362). Second, Dubos observes, the logical chain of ideas was far more flexible than Pasteur granted. "His career might have followed many other courses, each one of them as logical, and as compatible with the science of his time and with potentialities of his genius" (Dubos 1950, p. 377).

Dubos argues that Pasteur may have felt apologetic both to himself and to his contemporaries and posterity because he had failed to follow up his earliest ideas on molecular dissymmetry with the vigor and skill he brought to his other work. Perhaps this is why in the 1880's Pasteur implied so strongly that the chance [END OF PAGE 20] observation of the fermenting tartrate solution, rather than the study of amyl alcohol and M. Bigo's beet juice, had carried him from crystallography to fermentation research. The fermenting tartrate solution was so good an example of the correlation of molecular dissymmetry with the process of life that it should have been the link in the logical chain of discovery. The studies of amyl alcohol, let alone the industrial problems of beet juice fermentation, were less direct, less reasonable, less satisfying intermediate steps and therefore harder to acknowledge.

There is yet another kind of "almost inflexible logic" that governed Pasteur's account of his work. To Pasteur, as we have seen, it was axiomatic that "pure" science preceded its applications. The very word "application" implied the pre-existence of pure science standing ready to be used. Furthermore, within the intellectual and scientific heritage of his time - a heritage that persists today - Pasteur viewed pure science, the establishm nt of theory upon sound experimental studies of natural phenomena, as a superior kind of activity; that was how a scientist ought to spend his limited time and energy. Consequently, Pasteur often ignored in his autobiographical remarks the immediate practical problems or motives that may have provided the occasion for taking up a line of research. If we had to rely entirely on Pasteur's published scientific papers and lectures we would never guess, for example, that the lactic acid ferment research had begun wiih his visits to a beet juice distillery. The logic of the relationship between science and its applications demanded that this commonplace problem could not be the starting point for a major scientific discovery. Instead something else, something that was unquestionably pure science, had to come first. The puzzle of amyl alcohol's peculiar optical activity, even though it meant Pasteur had to admit to working from preconceived ideas, was a more suitable beginning than an industrialist's request for help.

Once Pasteur had established the basic concept of the microbial cause of fermentation, it was easier for him to admit to working on practical questions: he was simply using the theory to explain everyday examples of the general phenomenon. Even so, it is interesting to see that he preferred to give only the most impressive reasons for straying from the road of pure science. He studied the diseases of wine, he says, partly because the Emperor suggested it, partly because France needed it. He apologized for undertaking the investigations on silkworm diseases: he was badly prepared for it, he doubted he could carry it "to a logical conclusion," he regretted abandoning the research on ferments and spontaneous generation so dear to his heart. But, again, it was a patriotic duty, and the Minister of Agriculture (he does not mention J. B. Dumas' request) had himself made the request (Lechevalier and Solotorovsky 1965, pp. 39-40). Nationalistic fervor also inspired his last contribution to the problems of fermentation. He had bitterly watched France's defeat in the Franco-Prussian War of 1870 and resolved to prove to the world that France could surpass Germany even at the thing Germany did best: with processes derived from the fecund principles of his research on wines, vinegars, and silkworm disease, he declared, France could produce a "beer of national revenge" superior to Germany's f i nest brew.(12)

We must, in short, be wary of accepting Pasteur's version of the origins, motivations, and character of his research. His day-to-day correspondence and his laboratory notebooks provide more reliable evidence than his published papers. In his papers he was all too likely to make progress of his research appear to conform to his notions of the way science ought to proceed: always from theory to practice. No wonder his biographers cannot agree whether he was primarily a pure scientist distracted by practical concerns or a brilliant and lucky applied scientist. Pasteur's own historiography makes it difficult now to say just which of his many contributions to biology arid physiology and to medicine and industry were the result of research directed toward a problem of immediate human importance and which were the result of research inspired by scientific curiosity. Both kinds of research certainly fed into his most general scientific accomplishment, the founding of the discipline of microbiology, although his spectacular later achievements (joined to those of Robert Koch) in research on disease gave the new science a decidedly medical bent.

Nevertheless, the careful study of some of Pasteur's discoveries reveal where new insights into life processes flowed from research on a practical problem. His patriotically inspired studies of beer, for instance, although "based on the same principles" as his studies of wine and silkworm diseases, forced Pasteur to work out the biology of yeasts and to formulate his general theory of fermentation as "life without air." One particularly noteworthy result of these studies, given the contemporary debates on spontaneous generation and Darwin's theory of evolution, was the demonstration that one [END OF PAGE 21] kind of microscopic mold could not turn spontaneously into another, as Pasteur and many others had once firmly believed (Duclaux 1920, pp. 193-197). Before then, Pasteur's studies of vinegar manufacture -especially his comparisons between the open barrel system of the Orlean industry and the beechwood chip system of the Germans - had yielded the information he needed to disprove part of Liebig's theory of fermentation.

The most important example, of course, is Pasteur's work on lactic and alcoholic fermentation in M. Bigo's beet juice distillery. His 1857 paper stated several fundamental new ideas in biology explicitly, and hinted at others. He asserted that fermentations are caused by microscopic living organisms; that fermentations are correlated with the development and organization of the tiny creatures, not with their death and decomposition; that each kind of fermentation is due to a specific kind of microorganism; and that each kind of microorganism needs a particular set of environmental conditions for its growth and reproduction. He gave ingenious methods for growing pure cultures of microorganisms, the technical prerequisite for any successful microbiological research. He commented on the specific differences in the microbes' vulnerability to changes in their surroundings - the acidity of the medium or the presence of an antiseptic like the oil of onion juice (and how, one wonders, did Pasteur come to think of trying onion juice?). He described the competition between microorganisms for organic nutrients. And, he implied that spontaneous generation was impossible, that even germs had parents like themselves - a conclusion that modern geneticists see as "the axiomatic foundation of molecular biology" (M. R. Pollock, in Monod and Borek 1971, p. 83; Handler 1970, p. 19). But, above all, Pasteur made it plain that microorganisms, until then little more than a curiosity of science, played a literally vital role in the economy of nature not just in the economy of France. [END OF PAGE 22]

Notes Chapter 2

(1) See, for example, Pasteur's "Note sur I'enseignement professional" (1863) and his "Porquoi la France We pas trouve d'hommes supérieurs; au moment du peril?" (1871), in Oeuvres VII, pp. 187-190, 211-221.

(2) Pasteur's meaning comes through most clearly in his earliest and least epigrammatic expression of these views. in 1855 he wrote a letter about the receptivity of the distilleries of Lille to science, and commented that they were handicapped by their belief that there was applied science, that the applications make up a body of doctrine. In truth, of course, Pasteur continued, the applications of science are only deductions from purely scientific discoveries (Correspondence I, p. 382-383, to the Rector of the Academia de Douai, 15 Nov. 1855). His biographers have relied on his later statements made in hi 1863 note on professional education addressed to the Minister of Public Instruction, Victor Duruy (Oeuvres 1/11, p. 188) and his 1871 article "Pourquoi la France We pas trouve d'hommes supdrieurs au moment du peril?" (Oeuvres V11, p. 215). He used the aphorism once again in a speech on the difference between the taste of the grapes and the wine made from them at the Congres viticole et sericole de Lyon in 1872 (Oeuvres I//, p. 464).

(3) For materials on the status of and relationships between science and technology in the 19th century see Morz 1965, especially Vols. I and 11; Singer at al. 1958; and Taton 1965.

(4) Among the significant early developments in crystallography that formed a background to Pasteur's early researches was Malus' 1808 discovery that all reflected light is polarized: the vibrations of reflected light are not in all directions perpendicular to the light ray, as in ordinary light, but are restricted to one direction. The plane formed by the ray and its perpendicular vibrations was called the plane of polarization. Then ' in 1810, Hauy discovered small facets (or faces) on quartz crystals, facets which could not be predicted from the normal form of the crystal, a regular hexagonal prism bounded by two six-faced pyramids. Hauy hypothesized that crystals are composed of characteristic molecules arrayed in three-dimensional patterns, a conviction shared by Pasteur. To others, the tiny facets in the varied, complex, rough structures of crystals represented random flaws, not characteristic variations of structure.

From observations of polarized light passed through quartz crystals, Argo reached several conclusions in 1811, among them that quartz crystals could split white polarized light into several colored rays, which were deflected at different angles upon leaving the quartz crystal. Then, in 1813 Biot gave lawful form to these and many other physical phenomena of the deviation of polarized light by quartz crystals. One observation, which he studied with precise measurements, was that different quartz crystals deviated polarized light sometimes to the right and sometimes to the left. Finally, and importantly for Pasteur's later work, Blot discovered that certain solutions of organic processes, one such solution being tartaric acid, deviated the plane of polarized light. While inorganic crystals deviated polarized light, inorganic solutions never did. The organic solutions were unique. From these findings Biot concluded, though not stated so precisely, that rotation of the plane of polarization of light depended somehow on the crystal form of quartz, and on the molecular form of organic solutions.

(5) In 1819, Mitscherlich discovered that chemical compounds having the same number of atoms, irrespective of the nature of those atoms, took the same crystal form, a phenomenon termed isomorphism. Its definition was later modified to state that compounds having the same number of atoms took roughly similar crystal forms. Then Liebig, in 1824, was one of several chemists who discovered that compounds having the same elements in the same numerical proportions could have entirely different qualities, a phenomenon named isomerism by Barzelius in 1830.

Tartar was a by-product of the fermentation of grapes. In 1770 Scheele, using the double salt of potassium and sodium tartrate, prepared the first organic acid, tartaric acid, which found wide use in the textile indus" and in medicine. Tartaric acid's remarkably similar cousin, racemic or paratartaric acid, was discovered by Gay-Lussac in 1826, in crystalline form mixed with crystals of ordinary tartaric acid during wine fermentation. The study of isomerism began to preoccupy chemists after Berzelius in 1830 found that the salts of tartaric and racemic acid were chemically identical. He then asked Mitscherlich to study the crystals of these salts in hopes that "should the forms be different, then the awkward difficulty of the dual relationship of bodies with the same composition would be solved in a simple and possibly correct manner" (Bernal 1953, PP. 188-190). Biot communicated Mitscherlich's results to the French Academia in a note in 1844. It was Pasteur's reading of this note in 1846, when he was a student at the Éole Normale, that led him into his later famous studies of tartaric and racernic acid.

(6) It is not clear from published accounts whether Pasteur (or the Bigos) believed that the round yeast-globules changed shape as the fermentation changed from alcoholic to lactic acid, or whether he realized that there were two kinds of globules corresponding to the two kinds of fermentation and that the longer globules were supplanting the round ones. In Pasteur's later work on silkworm diseases, he made recommendations to the silkworm growers long before he understood the nature of the disease. It is not impossible that he gave the Bigos a convenient rule-of-thumb to follow before he knew that the differentshaped globules were different kinds of living organisms.

(7) The controversy over the nature of fermentation that raged during the 19th century, involving such eminent figures as Liebig, Berzolius, and Pasteur, was central to the debates among chemists and biologists about the nature of the differences between inorganic and organic matter, and to the debates between "vitalists" and "reductionists" about the nature of living matter. For accounts of the fermentation controversy see: Bulloch 1938, pp. 41-55; Conant 1952; Merz 1965, 1: pp. 191-218 and II: pp. 106-117, 387-396; Farley and Geison 1974.

(8) The date on which Pasteur observed this is in dispute. Bulloch (1938, p. 60) gives 1858, the year Pasteur published his "Memoire sur ia fermentation do I'acide tartarique," Oeuvres II, p. 24-28. Dubos ~1950) says first 1854 (p. 41) and then 1857 (p. 106) without noticing the contradiction. R. Vallery-Radot (1919) gives no date but suggests by his narrative that the incident occurred in 1854. P. Vallery-Radot (0ouvres II, p. vi) gives 27 August 1857 as the date on which "Pasteur set in motion the experiment which showed that, when ammonia racemate started [END OF PAGE 23] fermenting, the left-handed tartrate appeared and the righthanded tartrate decomposed." However, in his "The Story of Pasteur's Discovery" (1957a), he suggests that Pasteur had made the observation before he published the 1857 lactic acid fermentation paper, but did not Work on it until afterwards. The first mention of the observation in Pasteur's correspondence is in a letter to his mentor, the celebrated old chemist, J. B. Biot, 7 September 1957 (Correspondence 11, pp 427428 and notes), which makes the 27 August 1857 date most plausible.

(9) On the discovery of the "Pasteur effect," see Lechevalier and Solotorovsky 1965, pp. 23-29; Pasteur, "Sur la fermentation visqueuse at la fermentation butVrique," 1861, Oeuvres II, pp. 134-136; and "Faits nouveaux pour servir a la connaissance do la théorie des fermentations proprement dites," 1872, Oeuvres II, pp. 387-394.

[No footnote #10 present within original text]

(10) In this very brief account of the Pasteur-Pouchet debate, wo have had to leave aside several important scientific and political issues. Emile Duclaux (1920, pp. 109-111), Pasteur's student and collaborator, pointed out that, if Pouchet had not withdrawn, Pasteur would have found it hard to explain away Pouchet's experiments With hay broth: the spores of the hay bacillus readily withstood the preliminary boiling of the broth, and the subsequent growth of the bacillus looked very much like spontaneous generation.

Farley and Geison (1974) have shown that the French scientific establishment found Pasteur's disproof of spontaneous generation congenial on religious and political grounds. The commission itself, they note, was strongly biased in Pasteur's favor from the start; two members, for example, were teachers and close friends of Pasteur and one (Balard) had even suggested the use of swan-neck flasks for the experiments in spontaneous generation!

(11) Liebig died in 1873, still believing that fermentation in general was a process of decomposition and that vinegar was produced by a catalysis caused by the beechwood chips.

(12) See Oeuvres V, p. 5, and Geison 1974, p. 354. For a critical evaluation of the practical results of Pasteur's research on beer, see Klöcher 1903, pp. 4-6, 9, 353. [END OF PAGE 24]

Chapter 2

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Vallery-Radot, R. 1960. The Life of Pasteur. Transl. R. L. Devonshire. New York: Dover Publications, Inc. (orig. publ. in 2 vols., 1901 and 1906). [END OF PAGE 25]

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