Louis Pasteur: The Chemist Who Saw the Invisible

Few scientists in modern history have transformed the texture of everyday life as completely as Louis Pasteur. The food in our refrigerators, the wine and beer in our cellars, the safety of our hospitals, the survival of children once doomed by epidemic disease, the very practice of clinical medicine and the design of laboratories around the world — all of these bear the marks of his work. When this provincial French chemist died in the autumn of 1895 at the age of seventy-two, he was the most celebrated scientist in the world, a national hero of the Third Republic, an honorary member of academies on every continent, and the founder of an institute that has since carried his name and methods to more than a hundred countries. Within his lifetime he had founded the science of stereochemistry, dismantled the ancient doctrine of spontaneous generation, established the germ theory of disease on a secure experimental foundation, invented the procedure that bears his name for preserving milk and wine, rescued the French silk industry from collapse, and produced effective vaccines against anthrax and rabies. The pace and breadth of his achievement were so extraordinary that contemporaries struggled to find a category large enough to contain him: he was, by training, a chemist; by inclination, an experimentalist; by accomplishment, a microbiologist and immunologist before either of those disciplines had names; by public reputation, a savior of humanity. The Catholic Church considered canonizing him; the Republic gave him a state funeral; the world's working physicians, brewers, surgeons, and farmers absorbed his methods so thoroughly that they ceased to recognize them as his.

Yet Pasteur is among the most contested figures in the history of science. He was a man of fierce ambition who fought hard for credit and recognition, sometimes generously and sometimes ungenerously to his rivals. He kept meticulous laboratory notebooks that, when at last opened to scholarly examination a century after his death, revealed shortcuts and inconsistencies that complicate the polished public account he gave of his most famous experiments. He combined a scientific genius of the first rank with a showman's instinct for the dramatic public demonstration, and he was willing — as a kind of necessary instrument of progress — to risk reputations, including his own, on experiments whose outcomes he could not be certain of in advance. He fought the medical establishment of his day, the philosophical establishment, the rival schools of microbiology in Germany; he was patriotic to the point of intolerance toward the Germans after the disastrous war of 1870, and he returned an honorary degree to the University of Bonn in protest of the bombardment of French cities. He believed devoutly that science and religion were compatible and that the laws of nature, as the experimentalist discovered them, were the laws of God; he raised his children in the Catholic faith of his upbringing and saw nothing inconsistent in this with his rigorous empiricism in the laboratory. To grasp the man requires holding together these incongruities: the methodical experimentalist and the visionary public actor, the cautious chemist and the bold inoculator, the loyal son of Catholic France and the citizen of an emerging international scientific republic, the conservative bourgeois of provincial Arbois and the revolutionary thinker who replaced ancient doctrines of disease with a new theory of microbial agents.

Birth and Family in the Franche-Comté

Louis Pasteur was born on 27 December 1822 in the small market town of Dole, in the department of the Jura in eastern France. The Jura is a region of low mountains and wooded valleys lying along the eastern frontier of France between Burgundy and Switzerland, a country of vineyards, dairy farms, ancient salt works, and modest provincial towns whose stone houses with their red-tiled roofs cluster around squat romanesque churches. Dole, the principal town of the lower Jura, had once been the capital of the Free County of Burgundy and the seat of a famous university; in the early nineteenth century it was a quiet sous-préfecture of perhaps eight thousand inhabitants, set on a ridge above the Doubs River, with the canal of the Rhône-au-Rhin running below the old town walls and the great Gothic collegiate church of Notre-Dame dominating the skyline.

The Pasteur family had lived in this region for generations as small tradesmen and tanners. Louis's grandfather Claude-Étienne Pasteur, a tanner born in 1769, had been a serf of the Abbey of Saint-Claude before the Revolution emancipated him and gave him the rights of a French citizen. The grandfather's redemption from servitude was an event the family preserved in its memory, and Louis would later allude to it with pride: his very existence as a citizen-scientist of the Republic was rooted in the revolution that had ended the ancien régime. Claude-Étienne's son Jean-Joseph Pasteur, Louis's father, was born in 1791 in the village of Salins-les-Bains, learned the tanner's trade in his father's workshop, and was conscripted in 1811 into the Grand Army of Napoleon. He served in the Spanish campaign, was promoted to sergeant for bravery, was decorated with the Cross of the Legion of Honor for his conduct at the battle of Bayonne, and was discharged after the Restoration with the modest pension of a non-commissioned officer.

Jean-Joseph Pasteur returned to his trade at Salins-les-Bains, married Jeanne-Étiennette Roqui in 1816, and moved with his bride first to Dole and then back to the nearby town of Arbois, where Louis would spend most of his childhood. The Pasteurs were respectable working people of the artisanal middle class — neither poor nor prosperous, but solid, hard-working, and ambitious for their children. Jean-Joseph could read and write, kept his accounts carefully, was a regular communicant at the parish church, and held strong republican and Bonapartist political opinions that he had absorbed during his army service. The Cross of the Legion of Honor that he wore on Sundays was the family's most precious possession, and the photograph of the old sergeant in his veteran's uniform would hang in Louis's laboratory at the École Normale and later at the Pasteur Institute for the rest of his life.

Jeanne-Étiennette Roqui Pasteur, Louis's mother, was a gardener's daughter of Salins-les-Bains, a woman of warm temperament and quick intelligence. She bore her husband four children: Jeanne, the eldest, born in 1816; Louis, the only son, born in 1822; Joséphine, born in 1825; and Émilie, born in 1826. The family was close-knit and the parents were unusually concerned with their children's education. Both Jeanne-Étiennette and Jean-Joseph had limited formal schooling themselves, but they believed firmly in the new opportunities that public education was opening to the children of the working classes in post-Revolutionary France, and they pushed all four of their children — daughters as well as sons — to learn what they could.

The Arbois of Louis's childhood was a town of perhaps four thousand inhabitants set in the heart of the Jura wine country. The narrow streets climbed the slope of the Cuisance River, the vineyards rose in terraces above the town, and the air in autumn was filled with the smell of fermenting grapes and the sweet rankness of the tanneries down by the river. The Pasteur tannery, the family's home and workshop, was a tall stone building on the rue de la Tannerie just below the church of Saint-Just, with the great vats of bark and lime in the cellars, the drying lofts on the upper floors, and the cramped family quarters on the second floor above the workshop. Louis grew up amid the smells and rhythms of leather-making — the scraping of hides, the pounding of bark, the slow cyclical labor of soaking and tanning that gave the family its bread — and these early sensory impressions, of organic substances slowly transformed by patient craft, may have left some unconscious mark on the chemist who would later spend his life examining the slow transformations of fermentation.

Early Education at Arbois

The first formal schooling of Louis Pasteur took place at the École primaire of Arbois, where he enrolled at the age of nine in 1831. He was, by all accounts, an unremarkable pupil in his early years — diligent and obedient but slow, more interested in drawing than in arithmetic, given to long quiet periods of observation rather than the quick verbal display that schoolmasters then prized. His father, watching the boy with the careful attention of a man who wanted more for his son than the trades of Arbois, was patient with the slow start; he believed, correctly, that Louis's apparent slowness was actually a kind of deliberateness, a refusal to give an answer before he was sure of it.

Louis's chief talent in those early school years was for drawing. He produced, between his thirteenth and sixteenth years, a series of remarkable pastel portraits of his parents, his sisters, his neighbors, and the curé of Arbois — works of such skill that some have been preserved in the museum of the Pasteur Institute and continue to surprise modern viewers by their accomplishment. The pastels show a steady eye, a careful hand, and a sympathetic insight into character that suggests the kind of patient attention that would later be turned upon the contents of his microscope. Several of his teachers urged him to pursue the visual arts as a career, and his mother (who had a particular love for these drawings) was at one point inclined to support that course. But Louis himself, by the time he was fifteen, had decided that science was his vocation, and the pastels were set aside in favor of textbooks.

The headmaster of the Arbois school, Captain Roussot, took a particular interest in the young Pasteur and arranged for him to receive supplementary instruction in mathematics and the sciences beyond what the ordinary curriculum offered. In 1837, Roussot wrote to a colleague in Paris recommending the boy as a candidate for the École Normale Supérieure — the great training school for teachers and academics that had been founded in 1794 and that had become, by the 1830s, one of the most prestigious institutions of higher education in France. The path from Arbois to the École Normale ran through the Royal College of Besançon, where Louis would spend the years of his lycée education preparing for the entrance examination.

But Louis was not yet ready for that step. In late 1838, his father (who had been reluctant to send him away from home) agreed to enroll him in the pension Barbet in Paris, a preparatory boarding school catering to provincial boys aspiring to enter the great Parisian institutions. Louis traveled to Paris by stagecoach in the autumn of 1838, accompanied by a slightly older friend from Arbois named Jules Vercel; he was fifteen years old, had never been more than thirty kilometers from his birthplace, and felt the displacement intensely. Within a few weeks of his arrival at the pension Barbet, he was so overcome with homesickness that he asked his father to bring him home. Jean-Joseph, who had himself been a soldier in foreign countries at a younger age, recognized that his son was simply not yet prepared for the trial of separation from his family. He came to Paris, collected the boy, and brought him back to Arbois without reproach. Louis resumed his studies at the Arbois school and then transferred to the Royal College of Besançon in the autumn of 1839, when he was nearly seventeen.

The Royal College of Besançon

Besançon, the principal city of the Doubs department and historic capital of the Franche-Comté, lay some forty kilometers north of Arbois — close enough that Louis could return home for the long vacations, but far enough that the displacement that had defeated him in Paris would now be manageable. The Royal College (later renamed the Lycée Victor Hugo, after its most famous alumnus) was an old institution, well-staffed, with a strong reputation for the sciences. Louis lodged in a pension within walking distance of the college and embarked on the rigorous classical and scientific curriculum that prepared boys for the entrance examinations of the grandes écoles.

His teachers at Besançon found him a serious and methodical worker, less brilliant than persistent, with a particular gift for the patient solution of mathematical problems and an emerging talent for chemistry. He completed his baccalauréat ès lettres in August 1840 with a respectable but not distinguished record; his record in mathematics and physics was somewhat better. In the same month he was appointed preparator (préparateur) of mathematics at the college, a post that paid a modest stipend and required him to assist the regular instructor in the teaching of mathematics to the younger pupils. The combination of his own studies for the second baccalauréat in mathematics and his teaching duties consumed the years 1840 and 1841. He passed the baccalauréat ès sciences in August 1842, with a mention médiocre in chemistry — a discouraging beginning for a man who would become the most celebrated chemist of the nineteenth century.

The medocre chemistry mark seems to have stung Louis particularly because he had already begun, even at Besançon, to feel that his vocation lay in that science. He resolved to repeat the examination, took an additional year to prepare, and passed the entrance examination for the École Normale Supérieure in 1843. He was admitted with a respectable ranking — fourteenth in his cohort, not at the top of the list but solidly in the middle — and he traveled to Paris in October 1843 to begin the three years of study that would qualify him for a career in higher education.

The École Normale Supérieure

The École Normale Supérieure of the 1840s occupied a venerable building on the rue d'Ulm in the fifth arrondissement of Paris, just behind the Panthéon. The institution had been founded in the heroic period of the Revolution to train teachers for the new republican schools, suppressed under the Restoration, refounded under Louis-Philippe; by the time Pasteur arrived in 1843 it had established itself as the most rigorous training ground for the future professors of the French university system. The student body of perhaps fifty per year was selected by competitive examination from the entire country and lived in close monastic conditions within the rue d'Ulm building, with shared dormitories, common dining halls, a chapel, libraries, and a small but adequate scientific laboratory.

The faculty under whom Pasteur studied included some of the great names of French science. Jean-Baptiste Dumas, the senior professor of chemistry, was one of the most distinguished chemists in Europe, the author of major works on organic chemistry and the founder of an important school of theoretical thinking about the constitution of compounds. Antoine-Jérôme Balard, the discoverer of bromine, was a more modest but equally exacting teacher who would become Pasteur's principal mentor during his years at the École Normale. Joseph-Louis Gay-Lussac, the great physicist and chemist of the previous generation, was still active at the Sorbonne and at the École Polytechnique; Pasteur would attend his lectures and absorb the rigorous experimental tradition that Gay-Lussac had inherited from his own master Berthollet.

The young Pasteur threw himself into his studies with the intensity that would mark all his subsequent work. He spent long hours in the laboratory, often returning after the evening meal to continue experiments by the light of oil lamps. His correspondence with his family at Arbois — which has survived in considerable bulk and constitutes one of the most extensive collections of letters from a nineteenth-century scientist — shows him torn between homesickness, intellectual ambition, and a stubborn determination to make himself worthy of his father's confidence. The letters to Jean-Joseph are remarkable for their tone of filial affection and respect; Louis writes as a son who knows that his every accomplishment is a vindication of his father's sacrifices, and he reports his progress in mathematics, in chemistry, in mineralogy with the careful attention of a man giving an account of his stewardship.

During the École Normale years, Pasteur attended also the lectures of Auguste Laurent and the courses on crystallography of Gabriel Delafosse at the Faculty of Sciences. Laurent's work on the relationship between chemical constitution and crystalline form would prove decisive for Pasteur's later researches; Delafosse, a former student of the great crystallographer René-Just Haüy, transmitted to his students the French school's tradition of mathematically rigorous crystallographic analysis. The combination of training in organic chemistry under Dumas, in mineralogy and crystallography under Delafosse, and in the broader theoretical questions of chemistry under Laurent, gave Pasteur a unique preparation for the work he would soon undertake: he was, perhaps uniquely among his contemporaries, equipped to think simultaneously in chemical, crystallographic, and three-dimensional geometrical terms about the same molecules.

He passed the agrégation des sciences physiques — the qualifying examination for university teaching — in August 1846, ranking third in his cohort, and was immediately assigned as preparator in chemistry to Balard at the École Normale itself. The position was junior and not well-paid, but it gave him access to the laboratory and to Balard's continuing supervision, and it allowed him to begin work on the doctoral thesis that would launch his independent scientific career.

The Doctoral Thesis and the Birth of Stereochemistry

The problem that Pasteur chose for his doctoral research was a particular peculiarity of the tartrate salts — substances that occur naturally as a byproduct of wine fermentation and that had been the subject of considerable chemical investigation in the early nineteenth century. The German chemist Eilhard Mitscherlich had pointed out, in a memoir of 1844, that two salts of tartaric acid (the ordinary tartrate, on the one hand, and the so-called "racemic" or paratartrate, on the other) appeared to have identical chemical composition, identical crystallographic forms, identical physical properties — except for one: the ordinary tartrate, when dissolved in water, rotated the plane of polarized light to the right, while the racemic tartrate had no effect on polarized light at all. The puzzle was acute. If the two substances were truly identical in all chemical and physical respects, what could account for the difference in their optical behavior?

Pasteur attacked this problem with the careful patience that would mark all his subsequent work. He prepared, by methods that he refined progressively, large and well-formed crystals of both the ordinary and the racemic tartrates, and he examined them under his microscope with the techniques of crystallographic measurement that he had learned from Delafosse. What he discovered, in the course of patient examination during the autumn and winter of 1847–48, was that the crystals of the racemic salt were not in fact identical to those of the ordinary salt. The racemic crystals existed in two distinct forms: some were the mirror images of the ordinary tartrate crystals, while others were the mirror images of the first. In every other respect the two kinds of racemic crystal were identical, but they were related to each other as the right hand is related to the left hand — they were enantiomorphs, to use the term that would later be coined for the phenomenon.

The decisive moment came in the laboratory of Balard one morning in the spring of 1848. Pasteur, working with a quantity of racemic sodium ammonium tartrate that had been crystallized at room temperature, had carefully separated the two kinds of crystal under his microscope, using a fine pair of forceps to pick out one form and then the other. He dissolved equal quantities of each form in water and tested the solutions in a polarimeter. The first solution rotated the plane of polarized light to the right, with exactly the same magnitude as the ordinary tartrate; the second rotated it to the left, with exactly the same magnitude as the first but in the opposite direction; the racemic salt was, therefore, not optically inactive in any fundamental sense but rather a mixture of equal quantities of two optically active forms, whose opposing rotations canceled out to give the appearance of inactivity.

The implications of this discovery were profound. Pasteur had shown that molecules, like the crystals they form, could exist in two distinct forms related to each other as mirror images. The chemical formula could not capture this difference; the chemical reactions of the two forms, with ordinary reagents, would be identical; only the interaction with polarized light or with other asymmetric molecules could distinguish them. The phenomenon — which Pasteur called "molecular dissymmetry" (later renamed "chirality" by William Thomson, Lord Kelvin) — opened a new dimension in the understanding of chemical structure. It was the foundation of what would later be called stereochemistry, and it was the first experimental demonstration that chemistry was, in a fundamental sense, three-dimensional.

Pasteur, in the excitement of his discovery, rushed from the laboratory to the corridor outside, embraced the first person he met (who happened to be the laboratory steward), and exclaimed that he had made a great discovery. He immediately wrote to Biot, the venerable physicist who had pioneered the study of optical rotation in liquids and crystals, and asked for the opportunity to demonstrate the experiment in Biot's presence. Biot, a man of seventy-five who had little patience for excited young chemists, was initially skeptical, but he invited Pasteur to bring his apparatus to the Collège de France and repeat the separation under his own eyes. Pasteur did so. He crystallized the racemic salt in Biot's laboratory, with Biot watching every step; he separated the right- and left-handed crystals; he dissolved them in water; he placed the solutions in Biot's own polarimeter; and Biot, observing the rotations himself, declared that the demonstration was perfect. "My dear son," he is reported to have said, taking the young Pasteur's hand, "I have loved science so much in my life that this discovery has affected me to the heart." It was the kind of generous senior endorsement that any twenty-five-year-old researcher dreams of receiving, and it established Pasteur's reputation in the senior ranks of French science.

The doctoral thesis was submitted and defended in August 1847, with secondary memoirs on the molecular asymmetry of the tartrates following in 1848 and the years immediately after. Pasteur returned to the topic repeatedly through the 1850s, extending and refining his analysis of how the symmetry properties of molecules related to the chemistry of life, and the cumulative body of his work on molecular asymmetry would, in retrospect, be seen as the founding work of stereochemistry as an independent science. He had, before his twenty-sixth birthday, opened a new chapter in the history of chemistry; the achievements that would make him famous to the general public lay yet ahead, but the scientific community had already taken his measure.

Dijon, Strasbourg, and Marriage

The success of the doctoral work brought Pasteur into the network of French academic appointments. He was appointed in 1848 to a position as professor of physics at the lycée of Dijon — a respectable provincial post but one that Pasteur regarded as inadequate to his ambitions, since it required him to teach the elementary physics of the secondary school rather than continuing his research in chemistry. He held the position for only three months before securing, through the intervention of Balard and Dumas, an appointment as suppléant (acting professor) in chemistry at the Faculty of Sciences of Strasbourg, beginning in January 1849.

Strasbourg was a substantial city, the principal town of the German-speaking Alsace region, with a respectable university and a vigorous intellectual life. Pasteur threw himself into his teaching duties and continued his crystallographic researches in the modest laboratory of the Faculty of Sciences. Within a few weeks of his arrival, he had paid a courtesy call on the rector of the Academy of Strasbourg, Charles Laurent — a man of substantial standing in the local establishment, with a large house and a large family. The Laurents had three daughters of marriageable age. The eldest, Marie, was twenty-three years old, attractive, intelligent, and well-educated; Pasteur, observing her for a few weeks across the dinner table at the rector's house, fell into one of his characteristic rapid and complete enthusiasms. On 10 February 1849, less than two weeks after first meeting her, he wrote a formal proposal of marriage to her father in which he described his prospects, his ancestry, and his expectations with a frankness that combined provincial earnestness with academic precision.

Charles Laurent and his daughter discussed the proposal for some weeks before accepting; Marie herself, who had had little chance to know the awkward young chemist beyond what she had observed at her parents' table, found him serious to the point of solemnity but evidently devoted, sincere, and not without his own gentle humor. They were married on 29 May 1849 in the Catholic ceremony at the rector's parish church, and the couple set up housekeeping in a modest apartment near the Faculty of Sciences. The marriage would last for forty-six years, until Pasteur's death; Marie would be, by every account, the great steadying presence of his adult life, the manager of his household, the protector of his quiet time for work, the confidante of his hopes and disappointments, the patient and uncomplaining nurse of his various illnesses, and the secretary who in his later years took dictation of his correspondence and many of his manuscripts.

The marriage produced five children — three daughters and two sons — of whom only two would survive to adulthood. The eldest daughter, Jeanne, born in 1850, died of typhoid fever in 1859 at the age of nine; this was the first of several family tragedies that would shape Pasteur's mature concern with infectious disease. The eldest son, Jean-Baptiste, born in 1851, would survive to adulthood and follow a diplomatic career; the second daughter, Cécile, would die in 1866 at the age of twelve, also of typhoid fever; the third daughter, Marie-Louise, born in 1858, would survive to adulthood and marry René Vallery-Radot, who would later become Pasteur's principal biographer and the editor of his collected works; the second son, Camille, born in 1863, would die of a tumor in 1865 at the age of two. Of the five children, then, only two would live to see their parents grow old. The deaths of Jeanne, Cécile, and Camille in the family's middle years marked Pasteur with a settled grief that he carried for the rest of his life and that gave a personal urgency to his later work on infectious disease.

Lille and the Turn to Fermentation

In September 1854, after five years at Strasbourg during which his reputation had steadily grown, Pasteur was appointed professor of chemistry and the first dean of the newly created Faculty of Sciences at the University of Lille, in the industrial north of France. The Lille faculty had been established as part of a deliberate policy of the Second Empire to bring scientific education and research into the industrial regions of the country, where the application of science to manufacturing was understood to be the key to French economic competitiveness. The university authorities, in choosing Pasteur to lead the new faculty, were betting on a young chemist whose work on crystallography had brought him academic renown but who had not yet shown any particular concern with the practical problems of industry. They could not have known how completely Pasteur would embrace the new role.

Lille in the 1850s was a city in industrial transformation. The textile mills had been mechanized; the surrounding country produced sugar beets in great quantity, and the distilling of alcohol from beet juice had become a substantial local industry; the breweries of the Nord were among the most productive in France. Pasteur, mindful of his charge to make the new Faculty of Sciences relevant to the region, organized regular factory visits for his students and made himself personally available to local manufacturers who had scientific questions about their processes. It was through one such consultation, in the summer of 1856, that he was led into the line of work that would dominate the next twenty years of his life.

Monsieur Bigo, a beet-sugar distiller of Esquermes, a suburb of Lille, came to Pasteur to ask for help with a recurring problem. The fermentation of his beet juice, which ordinarily yielded alcohol with reliable efficiency, had repeatedly failed in recent months; instead of producing alcohol, his vats had produced quantities of a sour-smelling liquid that ruined the entire batch. Bigo had no idea why the failures were occurring and wanted to know whether Pasteur could identify the trouble and suggest a remedy. Pasteur, taking samples of both the successful and the failed fermentations, examined them under his microscope and was surprised by what he saw. The successful fermentations were dominated by small spherical or oval bodies — the yeast cells of the brewer's craft, well-known to microscopists since Schwann and Cagniard de Latour had described them in the 1830s. The failed fermentations contained scarcely any yeast at all but were teeming with much smaller, rod-shaped microorganisms that Pasteur did not recognize.

This simple observation — that two different chemical outcomes (alcoholic fermentation versus what would prove to be the lactic acid fermentation) were associated with two different kinds of microscopic organisms — set Pasteur on the track he would pursue for the rest of his career. The dominant view of fermentation in the 1850s, defended by such chemical authorities as Justus von Liebig in Germany and Marcellin Berthelot in France, was that fermentation was a purely chemical process — a kind of catalysis or decomposition driven by unstable albuminous substances that needed only to begin breaking down in the presence of the sugar to set in motion the production of alcohol or other fermentation products. On this view, the yeast cells that Schwann and Cagniard de Latour had described were merely accidental by-products or scaffolding of the chemical process, not its cause. Pasteur, examining Bigo's samples and many others over the following months, became convinced that this view was wrong. Fermentation, he came to believe, was the work of living microorganisms — yeasts produced alcoholic fermentation, certain bacteria produced lactic acid fermentation, other bacteria produced butyric acid fermentation, and so on — and the chemical outcome depended on which microorganism was active in the substrate.

He published his first results on lactic acid fermentation in 1857, in a paper that has rightly been called the founding document of microbiology. The paper described the small rod-shaped organisms responsible for the lactic fermentation, demonstrated that they could be transferred from one batch of beet juice to another and would reliably produce the same fermentation in the new substrate, and argued that the chemical change of fermentation was a necessary consequence of the metabolic activity of the living organism. Over the following years he extended the analysis to the alcoholic fermentation (1860), the butyric fermentation (1861), the fermentation of urine (1862), and the acetic fermentation that produced vinegar (1862), in each case demonstrating that a specific microorganism was responsible for a specific chemical transformation.

The work on butyric fermentation produced a particularly striking discovery: the microorganisms responsible for the butyric fermentation, Pasteur observed, lived and multiplied in the absence of free oxygen. They were what he called "anaerobes" — organisms that did not require atmospheric oxygen for their metabolism, and that were in fact poisoned by oxygen. The discovery of anaerobic life was, in its own right, a fundamental contribution to biology; it overturned the assumption that all living organisms required atmospheric oxygen and opened the way for the later investigation of the anaerobic pathogens (such as the tetanus and botulism bacilli) that would become so important to medical microbiology.

By the early 1860s, Pasteur's name was associated, at least in the French scientific community, with a comprehensive new theory of fermentation. It was a theory that had powerful implications. If fermentations were the work of specific microorganisms, then the practical control of fermentation — in distilling, in brewing, in winemaking, in vinegar production, in any of the host of industries that depended on these processes — required the control of the microorganisms involved. Spoilage and unwanted fermentations were the result of contamination by foreign microorganisms; the prevention of spoilage required the exclusion or destruction of these contaminants. The principles that Pasteur was working out in the abstract terms of his fermentation researches were going to revolutionize a half-dozen industries within a generation.

The Battle over Spontaneous Generation

The fermentation work raised, almost inevitably, the ancient question of the origin of microorganisms. If fermentation was the work of living organisms, where did those organisms come from? They were not introduced by the experimenter; they appeared, apparently, of their own accord in any suitable substrate left exposed to the air. The traditional explanation, traceable to Aristotle and refined by generations of natural philosophers, was that they were produced by spontaneous generation — the appearance of living forms from non-living matter under suitable conditions. The seventeenth-century work of Francesco Redi had cast doubt on the spontaneous generation of larger organisms (Redi had shown that maggots did not appear in meat protected from flies), but for microscopic organisms the question remained open. In the late eighteenth century, the Italian abbot Lazzaro Spallanzani and the English clergyman John Needham had conducted experiments whose interpretations conflicted, with Needham claiming to have observed the spontaneous appearance of microscopic life in sealed and heated infusions and Spallanzani claiming, on the contrary, that sufficiently rigorous heating would prevent any appearance of microorganisms.

By the mid-nineteenth century the question had been reopened by the French naturalist Félix-Archimède Pouchet, the director of the Natural History Museum at Rouen. Pouchet, a man of considerable learning and considerable conviction, published in 1859 a substantial monograph, Hétérogénie, in which he argued from extensive experimental work that spontaneous generation of microscopic organisms was an undeniable fact. He had performed careful experiments in which sealed flasks of organic infusion, heated to temperatures sufficient to kill any pre-existing organisms, when opened in the presence of pure oxygen and pure heated mercury, still produced microorganisms after a few days. The conclusion seemed inescapable: living microscopic organisms could arise from non-living organic matter under the right conditions.

Pasteur was drawn into the controversy by his fermentation work. If microorganisms could arise spontaneously, then the contamination of fermentation by foreign organisms was not a question of external introduction but of intrinsic appearance, and the practical control of fermentation would be much more difficult than his theory implied. More fundamentally, the spontaneous generation thesis was incompatible with the general framework he was developing, in which living organisms reproduced from pre-existing organisms of their own kind. He undertook, between 1860 and 1864, a series of experiments designed to refute the Pouchet thesis decisively.

The experiments were ingenious and beautiful. In the first series, Pasteur prepared infusions of organic material (yeast extract, sugar solution, urine), boiled them in a flask, and then sealed the flask while still hot. The sealed flasks, he showed, remained free of microorganisms indefinitely — for weeks, for months, for years. Only when the flasks were opened to the air did microorganisms appear. The air, then, contained something that produced the microbial contamination; the infusion itself did not generate organisms spontaneously.

The next question was: what was the active principle in the air? Pasteur designed an experiment to filter air through cotton wool, then dissolve the cotton wool in a mixture of alcohol and ether (which would dissolve away the cotton fibers but leave any insoluble particles intact), and examine the residue under the microscope. He found in the residue, exactly as he had predicted, dust particles of various kinds, including unmistakable shapes that he identified as the spores and cells of fungi and bacteria. The air, then, contained suspended particles, some of them living microorganisms; it was these microorganisms (or their spores) that, falling into a suitable substrate, initiated the appearance of microscopic life in flasks that had been opened to the air.

The most famous of all Pasteur's experiments on this question was the demonstration with the "swan-necked" flasks. He prepared infusion-filled flasks whose necks had been drawn out into long curving S-shaped tubes; the flasks were boiled to sterilize the contents, and then left open. Air could pass freely through the open tube, but the curve of the neck trapped suspended particles by gravity, so that no microorganisms could fall into the contents. These flasks, Pasteur showed, remained free of microbial contamination indefinitely — and the contents could be drunk from them years later with no contamination, as he demonstrated to his lecture audiences. The infusion was not chemically protected; it was as accessible to the air as it could possibly be; only the dust-bearing particles were excluded. If spontaneous generation were possible, the contents should have begun teeming with microorganisms within days. They did not. The conclusion was unambiguous: microorganisms came from other microorganisms, never from non-living matter.

The dispute with Pouchet was not, however, settled by the experimental work alone. Pouchet repeated his own experiments with various refinements and continued to obtain results that he believed supported spontaneous generation. Both sides accused the other of methodological errors. The French Academy of Sciences appointed in 1862 a commission to evaluate the question, with both Pasteur and Pouchet invited to demonstrate their experiments before the commission. Pasteur attended; Pouchet, at the last moment, withdrew, declining to expose his work to what he considered a rigged proceeding. The commission ruled for Pasteur, and the question, in the French scientific community, was settled — although the controversy continued to be debated abroad, particularly in England, where Henry Charlton Bastian continued to defend a modified spontaneous generation thesis well into the 1870s.

The victory over Pouchet established Pasteur as a defender of the principle "omne vivum ex vivo" — all life from life. The principle was conservative in the sense that it preserved the traditional Christian framework of the unique creative act of God as the source of all life. Pasteur himself, though he generally avoided overtly theological argument in his scientific writings, was clearly aware of the implications and considered them congenial; he was content to leave to nature the principle that creation occurred only at the origin and was not continuous, with all subsequent life proceeding by reproduction from prior life. The position was simultaneously a triumph of experimental rigor and a vindication of a particular metaphysical view — and these two dimensions of the victory were not, for Pasteur, in conflict with each other.

Wine, Beer, and the Birth of Pasteurization

The fermentation researches had practical implications, and Pasteur was not the man to neglect them. Through the late 1850s and 1860s he extended his work to the practical problems of winemaking, brewing, and the production of vinegar, and from this practical work emerged the procedure that would carry his name into every household in the developed world.

The problem of wine spoilage had concerned French winemakers for centuries. Wine that had been successfully produced and barreled could nonetheless turn — could become sour, or thick, or develop off-flavors — during storage and transportation, with substantial losses to the producers and to the export trade. Pasteur, called upon by the Minister of Agriculture in 1863 to investigate the problem, established that the various forms of wine sickness were the work of various microorganisms — different from the yeast that had produced the original alcoholic fermentation but introduced from the air or from inadequately cleaned vessels, and proliferating in the wine to produce the chemical changes that constituted spoilage. The remedy he proposed, after extensive experimental trials, was elegantly simple: brief heating of the bottled wine to a temperature sufficient to kill the spoilage organisms but not so high as to damage the flavor of the wine. He determined experimentally that heating to between 55 and 60 degrees Celsius for a few minutes was sufficient; the wine, after this treatment, would keep indefinitely.

The procedure was published in 1866 in his Études sur le vin, a substantial volume that became a standard reference for the French wine industry. Within a few years it had been adopted by the major producers; the export of French wine, particularly to England and the Americas, became commercially viable on a scale that had been impossible while spoilage in transit remained a routine hazard. A few years later, in his Études sur la bière (1876), Pasteur extended the analysis to beer, demonstrating that the same principles applied — the bacterial contaminants of beer could be killed by brief moderate heating without damaging the product. The German brewing industry, which dominated world beer production, was slow to adopt the French procedure, in part for nationalist reasons (the war of 1870 had soured Franco-German relations) and in part because the German brewers thought their own traditional methods of cold storage and careful sanitation were sufficient. But by the 1880s the Pasteurian heating procedure had been adopted widely in both wine and beer production, and the name "pasteurization" had entered the technical vocabulary of food processing.

The extension of pasteurization to milk came somewhat later, and the credit for its development as a public health measure must be shared among several figures. The German chemist Franz von Soxhlet proposed in 1886 that milk should be pasteurized for infant feeding to reduce the high rates of infant mortality from gastrointestinal infections; the American department store magnate Nathan Straus organized in the 1890s a campaign of milk pasteurization for the slum districts of New York City; the formal regulatory requirement that commercial milk be pasteurized was adopted progressively, city by city and country by country, through the first decades of the twentieth century. By the time of the Second World War, pasteurized milk was the universal standard in most of the developed world, and the routine pasteurization of milk had become one of the great quiet contributions to the reduction of infant mortality and the improvement of public health that the nineteenth century bequeathed to the twentieth. The procedure that Pasteur had developed for the preservation of wine had been transformed into one of the foundations of modern food safety.

The Silkworm Disease: a National Disaster

In June 1865, Pasteur was called upon to undertake a task of national economic importance: the investigation of the silkworm diseases that were devastating the French sericultural industry. Silk had been one of the great export products of southern France since the Middle Ages, with the mulberry orchards and silkworm-raising establishments of the Cévennes and the Rhône Valley supporting tens of thousands of families and contributing substantially to the trade balance of the country. Beginning in the 1840s, a mysterious disease had begun to attack the silkworms; the disease, called pébrine ("pepper disease," from the black spots that appeared on the bodies of affected larvae), had spread progressively through the silk-producing departments, and by the early 1860s the French silk production had fallen to a fraction of its earlier levels. The losses were enormous — tens of millions of francs annually, with the ruin of many families and the collapse of an entire regional economy. The disease had spread also to the silkworms of Italy and Spain, threatening the European silk industry as a whole.

The appointment of Pasteur to the investigation was made by the chemist and senator Jean-Baptiste Dumas, his old teacher, who had himself been born in the silk-producing region of Alès (Alais) and felt a personal as well as a professional concern with the disaster. Pasteur, who had no prior experience with sericulture and had never even seen a silkworm at close range, accepted the commission with characteristic confidence; he established his investigative headquarters at Alès in the Gard department, in the heart of the affected region, and spent the next five years dividing his time between Paris and the south.

The work was difficult and emotionally taxing. The first summer at Alès, Pasteur observed the silkworms with care, examined the affected and unaffected animals under his microscope, and identified the corpuscles — small ovoid bodies — that were present in all silkworms suffering from pébrine but absent from healthy ones. The corpuscles, he proposed, were the agent of the disease (we now know them to be the spores of a microsporidian parasite, Nosema bombycis). He established that the disease was transmitted hereditarily through the eggs of infected females, that it could be transmitted also by contact among the larvae, and that systematic microscopic examination of the female moths after they had laid their eggs would permit the identification and rejection of infected eggs, allowing the next generation to be reared from clean stock. The procedure — examination of every female moth's body for the characteristic corpuscles, with the destruction of the eggs from any infected mother — was laborious but effective, and within a few years it had brought the pébrine epidemic under control.

The work on pébrine was complicated, however, by the simultaneous presence of a second silkworm disease — flacherie, in which the larvae weakened and died without showing the characteristic pébrine corpuscles. Pasteur worked out the etiology of flacherie as well, identifying it as a bacterial infection of the silkworm intestine and developing methods of hygiene that limited its spread. By 1870, after five years of work, he had reduced both diseases to manageable levels and the French silk industry had begun a slow recovery — never to its pre-pébrine peak, but to a substantial fraction of it.

The pébrine work was important not only for what it did for the silk industry but for what it taught Pasteur. He had now made an exhaustive study of an infectious disease — not in humans or in domesticated mammals, but in invertebrates of relatively simple physiology where the etiology could be worked out without the complications of more advanced immune systems. He had identified specific microorganisms as the causes of specific diseases. He had developed methods of microscopic diagnosis and of preventive hygiene. He had, in short, developed and tested in miniature the principles that he would later apply to the great problem of infectious disease in humans. By the time he turned to the larger question, he had a tested experimental framework and a confident sense of how to proceed.

Personal Tragedy and the First Stroke

The years of the silkworm work were also years of intense personal sorrow for the Pasteur family. The death of the eldest daughter Jeanne from typhoid fever in 1859, before the pébrine work began, had been an early blow. The death of the second daughter Cécile from typhoid fever in 1866, in the middle of the silkworm work, was even more devastating; Cécile was twelve years old, intelligent and warm-hearted, and her death after a brief illness in Marseille (where the family was en route from Alès to a summer vacation) left her parents inconsolable for many months. The youngest son Camille had died the previous year, in 1865, at the age of two, of a tumor of the liver; Pasteur, working at Alès on the silkworms, had received the news by telegram and had returned to Paris in time only for the burial. The accumulated weight of these family losses pressed heavily on Pasteur through the late 1860s, and his correspondence shows a man who was working harder than ever, partly as a refuge from grief and partly out of a settled conviction that the work he was doing was important — that the conquest of infectious disease was the only consolation he could offer to the memory of his lost children.

The conditions of the silkworm work, with its constant travel between Paris and the south, its irregular hours, its emotional and physical strain, exacted their toll. On 19 October 1868, at the age of forty-five, Pasteur suffered a stroke — a cerebral hemorrhage in the right hemisphere of his brain that left his left side partially paralyzed and threatened, for some weeks, to be fatal. He recovered slowly through the autumn and winter; his speech was unaffected, his mental faculties were intact, but his left arm and leg were permanently weakened, and he would walk with a limp for the rest of his life. The stroke might have ended a less determined man's career; Pasteur, after some months of forced rest, resumed his work with all the energy he had ever shown, with his wife Marie taking on a larger role as his constant nurse and amanuensis. The remaining twenty-seven years of his life would be lived under the shadow of this physical disability, but it would not in any way diminish the productivity or the public impact of his work.

The War of 1870 and the Break with Germany

The Franco-Prussian War of 1870–71 was a national catastrophe for France — the defeat at Sedan in September 1870, the capture of Napoleon III, the proclamation of the Republic, the siege of Paris, the surrender of January 1871, the Commune of the spring, the harsh peace terms that included the loss of Alsace and most of Lorraine to the new German Empire, and the indemnity of five billion francs that the defeated French nation undertook to pay. For Pasteur, who was a fervent French patriot and who had a special attachment to Strasbourg (the city where he had courted and married Marie), the war and its aftermath were occasions of deep emotional crisis.

Pasteur had received an honorary doctorate from the University of Bonn in 1868, in recognition of his scientific work. In January 1871, after the German bombardment of Paris and at the height of his anti-German feeling, he wrote a formal letter to the rector of Bonn returning the diploma — declaring that "the sight of this parchment is odious to me, and I feel offended at seeing my name, with the qualification that you have given it, placed under a name which is, henceforth, an object of execration to my country." The letter, by the standards of the international scientific community, was a serious breach of academic etiquette; it caused some criticism even among Pasteur's French colleagues, who felt that the proper response to military and political catastrophe was not the breaking of scientific ties. But the gesture was characteristic of Pasteur's intensity and of the depth of his patriotic feeling, and he never regretted it.

The war and the loss of Alsace left Pasteur with a lifelong antipathy toward Germany and a particular rivalry with the great school of German microbiology that emerged in the 1870s and 1880s under the leadership of Robert Koch. The rivalry was personal as well as scientific; Pasteur and Koch were both founders of medical microbiology, both ambitious for the recognition of their respective schools and countries, and the priority disputes between them — over the etiology of anthrax, over the technique of pure culture, over the method of producing attenuated strains — were sharpened by the wider Franco-German antagonism that lay behind them. The disputes would damage the personal relations between the two schools but would not, in the end, prevent the steady accumulation of microbiological knowledge that both sides contributed.

Anthrax and the Turn to Disease

By the early 1870s, Pasteur was the most famous chemist in France and the recognized authority on industrial fermentation. He was a member of the Academy of Sciences (elected in 1862), a professor at the École Normale (since 1857 he had been director of scientific studies there), and the recipient of numerous medals and prizes. The natural next step in his career — and the one that he had been preparing himself for, in some sense, throughout his fermentation work — was the systematic extension of his methods to the diseases of higher animals and ultimately of human beings.

Anthrax, the disease that Pasteur chose for his first major attack on this problem, was a serious affliction of livestock — particularly of sheep and cattle — that periodically devastated entire regions of the French countryside. The disease was characterized by sudden death; whole flocks of sheep could die in a few days, the soil of the affected pastures could become permanently infectious (the so-called "cursed fields" of rural French folklore), and the disease was occasionally communicated also to human beings, particularly to butchers, tanners, and shepherds who handled the carcasses of infected animals. The agent of the disease had been identified in 1850 by the French veterinarian Casimir Davaine, who had observed rod-shaped bodies in the blood of infected animals — the same bacterium (now known as Bacillus anthracis) that the German country doctor Robert Koch would later study in his pioneering investigations of the late 1870s.

The priority for the identification of the anthrax bacillus belongs primarily to Davaine and to Koch. Koch's contribution, made in his country medical practice at Wollstein in 1876, was particularly important: he had developed methods of pure cultivation that allowed him to grow the bacillus in nutrient liquids outside the animal body, to follow its complete life cycle including the formation of the long-lived spores that explained the persistence of infectivity in the soil, and to demonstrate by experimental inoculation that pure cultures of the bacillus, introduced into healthy animals, produced the characteristic disease. Koch's anthrax work, published in 1876, was one of the founding documents of bacteriology and a model of rigorous experimental investigation.

Pasteur, who had been working in parallel on the same problem, was not the first to identify the bacillus or to demonstrate its causal role. His contribution to the anthrax work was somewhat different and would ultimately be more important: the development of a vaccine that could prevent the disease in living animals. The development of that vaccine, however, depended on a prior discovery that had been made in another disease entirely.

Chicken Cholera and the Principle of Attenuation

In 1879, Pasteur had been working on chicken cholera — a deadly disease of poultry that ruined many French farms — and had isolated the responsible microorganism (now known as Pasteurella multocida). In the course of the work, an accident occurred that would change the history of medicine. A culture of the chicken cholera microbe, having been prepared for inoculation experiments, was inadvertently left on Pasteur's laboratory bench during the summer vacation of 1879. When Pasteur and his assistant Charles Chamberland returned in the autumn, they used the old culture (along with fresh ones) to inoculate test chickens. The fresh cultures killed their birds in the usual way; the old culture, surprisingly, failed to kill its birds — the inoculated chickens showed only mild symptoms and then recovered. Most strikingly, when these recovered birds were subsequently challenged with fresh, fully virulent cultures of the chicken cholera microbe, they did not become ill — they had been rendered immune by their prior exposure to the weakened culture.

This was the first observation of what would come to be called "attenuation" — the deliberate weakening of a pathogenic microorganism so that it could produce immunity without producing serious disease. The principle had been known in a single special case since Edward Jenner's work on smallpox vaccination in the 1790s, but Jenner had used cowpox virus — a naturally occurring related virus that produced mild disease in humans and immunity to smallpox — and the principle of his method (the use of a closely related but less virulent agent) had seemed peculiar to smallpox and not generalizable to other diseases. Pasteur's chicken cholera observation suggested for the first time that attenuation might be a general phenomenon: that virulent organisms could be deliberately weakened in the laboratory by environmental manipulation, and that the weakened organisms could be used as vaccines against the full-virulence disease.

Pasteur grasped immediately the importance of the observation and set himself to develop systematic methods of attenuation. The chicken cholera attenuation, he established, was the result of prolonged exposure of the culture to atmospheric oxygen; he could reliably produce attenuated cultures by suitable exposure. He developed similar techniques for other organisms, including the anthrax bacillus, and by early 1881 he was ready to undertake a public demonstration of vaccination against anthrax in livestock — the dramatic event that would establish his international reputation as the founder of practical immunology.

Pouilly-Le-Fort: the Great Public Demonstration

The site of the great anthrax vaccination experiment was a farm at Pouilly-le-Fort, near Melun, southeast of Paris, in the spring of 1881. The arrangements were elaborate and public. The Agricultural Society of Melun, in conjunction with the veterinary press and with extensive coverage by the Paris newspapers, organized a comparative trial in which Pasteur would vaccinate one group of sheep with his attenuated anthrax culture, leaving a second group unvaccinated as controls; both groups would then be inoculated with the full-virulence anthrax bacillus, and the survival or death of the animals would constitute the test of the vaccine.

The trial began on 5 May 1881. Twenty-four sheep, one goat, and six cows received the first dose of vaccine; twenty-four sheep, one goat, and four cows in the control group received no vaccine. On 17 May the vaccinated animals received a second, stronger dose. On 31 May all the animals — vaccinated and controls — received an inoculation of the virulent anthrax bacillus. Pasteur and his collaborators returned to Paris to await the results.

The challenge inoculation took its course over the following two days. On 2 June, when the assembled audience of veterinarians, agricultural officials, and journalists returned to Pouilly-le-Fort to inspect the animals, the result was as dramatic as any experimentalist could have wished. All twenty-four vaccinated sheep were alive and healthy; twenty-one of the twenty-four control sheep were dead, with the remaining three dying within hours of the inspection. The goats showed the same pattern: the vaccinated goat was healthy, the control goat was dead. The cows had not died — anthrax is less reliably lethal in cattle than in sheep — but the vaccinated cows showed no symptoms while the unvaccinated cows showed clear signs of the disease.

The success was overwhelming. The newspaper coverage was triumphant; Pasteur was hailed in the French press and abroad as having achieved a definitive demonstration of the efficacy of vaccination. The principle of attenuated vaccines was established; the practical application to livestock disease followed quickly, with vaccination programs against anthrax saving the lives of millions of sheep and cattle in France and abroad over the following decades.

The history of the Pouilly-le-Fort experiment was, however, more complicated than the polished public account suggested. Pasteur had not, in fact, used the heat-attenuated vaccine that he had been developing in his own laboratory; he had used, instead, a vaccine prepared by his collaborator Charles Chamberland by a different method — chemical attenuation with potassium dichromate — that had been developed in parallel by the veterinarian Jean-Joseph-Henri Toussaint of Toulouse. Pasteur, anxious to ensure the success of the public demonstration, had taken the safer course of using a vaccine whose efficacy was already proven, rather than the technically purer vaccine of his own preferred method. He had not, in his public statements, acknowledged this substitution or given Toussaint the credit due to him for the chemical attenuation method. The omission would not be discovered for a hundred years — it emerged from the laboratory notebooks that were finally opened to scholarly examination by Gerald Geison in the 1990s — and it would tarnish, retrospectively, the simplicity of the heroic public account of Pouilly-le-Fort. But the general principle that the experiment was designed to demonstrate — that attenuation could produce effective vaccines, that the principle could be applied beyond smallpox to a wide range of diseases — was real, and the practical impact of the demonstration on the subsequent development of vaccination was enormous.

Rabies: the Great Terror

If anthrax was the work that established Pasteur's principle of attenuation, it was rabies — the most dreaded of the infectious diseases of the nineteenth century — that fixed his name in the popular imagination as the savior of human lives. Rabies was a disease of legendary horror: transmitted by the bite of a mad dog or other infected animal, the disease incubated invisibly for periods of weeks or months and then erupted into a fatal illness whose terminal stages included the famous hydrophobia, the convulsive horror of water that gave the disease its alternative name. There was no treatment; once the symptoms appeared, death was certain, and the death itself was protracted, painful, and accompanied by torments of thirst and terror. Although the absolute number of rabies deaths in France was small (a few dozen per year), the disease occupied a disproportionate place in the public imagination because of its peculiar horror and because of the helpless terror that gripped any victim of a dog bite who could not know, during the long incubation, whether he or she was condemned.

Pasteur, like every French child of his generation, had grown up with the folklore of rabies. He had been particularly affected, as a boy of eight in Arbois, by an incident in which a wolf rabid with the disease had attacked several villagers; one of the bitten men, the local blacksmith Nicole, had been brought to the forge to have his wounds cauterized with red-hot iron (the only treatment then known, and applied immediately after a bite in the desperate hope of preventing the infection from taking hold). The young Louis had witnessed the cauterization through the open door of the forge, and the screams of the blacksmith — and the man's subsequent death weeks later from the disease — had left a permanent impression. When he turned, in 1880, to the systematic investigation of rabies, the memory of Nicole was, by his own account, one of the motivations behind the work.

The rabies investigation was, in some ways, the most challenging Pasteur ever undertook. Unlike the chicken cholera or anthrax bacilli, the rabies agent (which we now know to be a virus, but which Pasteur could not see with his microscope) could not be cultured in laboratory media. Pasteur could only work with the agent as it occurred in living animals — in the saliva of infected dogs, in the brain and spinal cord tissue, in the nerve fibers along which the agent traveled to reach the central nervous system. The disease was difficult to transmit experimentally; bite inoculations were unreliable, with many of the inoculated animals failing to develop the disease. Pasteur's collaborators Émile Roux and Pierre-Paul-Émile Roux solved this problem by developing the technique of direct intracranial inoculation: a quantity of infected nervous tissue, injected directly into the brain of a healthy animal through a small trephine hole in the skull, reliably produced rabies in the inoculated animal after a short and predictable incubation period.

The intracranial inoculation technique made systematic experimental work possible. Pasteur and his collaborators could now follow the disease through serial passage from one rabbit to another, observing the evolution of the agent as it adapted to its new host. They discovered, through this work, that prolonged passage in rabbits progressively shortened the incubation period of the disease and increased the consistency of its lethality — the agent, passed many times through rabbits, became a "fixed virus" of standardized virulence, very different from the variable "street virus" obtained from naturally infected dogs.

The crucial step in the development of a vaccine was the discovery of a method of attenuation. The chicken cholera attenuation had used exposure to atmospheric oxygen; the anthrax attenuation had used elevated temperature and exposure to oxygen. For rabies, Pasteur and his collaborators developed an entirely new method: the spinal cords of infected rabbits were removed at death, suspended in dry sterile air in special flasks, and allowed to desiccate over a period of one to fourteen days. The desiccating cords, examined daily, were found to lose their virulence progressively; a cord that had been desiccated for fourteen days was almost completely attenuated, while a cord desiccated for only one or two days retained nearly full virulence.

Using this graduated series of attenuated preparations, Pasteur developed a vaccination protocol. A dog bitten by a rabid animal would be given a series of inoculations beginning with the most attenuated preparation (the fourteen-day desiccated cord) and progressing daily through preparations of increasing virulence, ending with cord material only a day or two old. The progressive series of inoculations, Pasteur reasoned, would stimulate the dog's immunity in such a way that by the time the active disease (incubating from the bite) attempted to take hold, the immune system would have been primed to suppress it. The relatively long incubation of rabies — typically two to four weeks, sometimes much longer — provided the time window in which post-exposure vaccination could be effective; this was a fundamental departure from the prior practice of vaccination, in which immunity was developed before exposure rather than after.

The method was tested extensively in dogs over the course of 1884 and early 1885, with results that confirmed its efficacy: dogs that had been bitten by rabid animals and then immediately put through the vaccination course did not develop rabies, while control dogs that had been bitten and not vaccinated developed the disease with the usual fatal outcome. Pasteur was preparing to publish the results of the canine trials and to recommend the establishment of veterinary vaccination centers when an event occurred that overtook his deliberate schedule.

Joseph Meister: the First Human Trial

On 6 July 1885, a nine-year-old Alsatian boy named Joseph Meister was brought to Pasteur's laboratory by his mother and a neighbor. The boy had been attacked two days earlier on a country road by a dog that had been clearly mad; he had been bitten fourteen times in various places on his body and was, by the prevailing medical opinion of the day, certain to develop rabies. The dog had been killed; its stomach, opened at autopsy, contained hay, straw, and pieces of wood, confirming the diagnosis of rabies (a rabid animal eats whatever is in front of it, including indigestible matter). The boy's local physician, a young Alsatian named Dr. Weber, had cleaned and cauterized the wounds and had then advised the family to go to Paris to seek Pasteur's help — the rumor of Pasteur's canine vaccine had spread through the medical community, and Weber knew that the boy's only chance of survival lay in trying the experimental treatment.

Pasteur was confronted with one of the most agonizing decisions of his scientific life. The vaccine had been tested in dogs but never in humans; he could not be certain that it would not itself produce rabies in a human subject; the principle of attenuated vaccines was new and the rabies vaccine in particular consisted of inocula that, at the strongest end of the series, were essentially undamaged samples of infected nervous tissue. To inoculate a child with such material was to take a risk of unknown magnitude. On the other hand, the boy without treatment was, in the considered opinion of the medical authorities of Paris, certain to die a horrible death within weeks. Pasteur consulted with two physicians of his acquaintance — Alfred Vulpian and Joseph Grancher — both of whom examined the boy, reviewed the bite history, and confirmed the diagnosis and the certainty of the prognosis without intervention. They advised Pasteur to proceed with the vaccination. On the evening of 6 July 1885, in the laboratory of the École Normale on the rue d'Ulm, Joseph Meister received the first of thirteen inoculations of the Pasteurian rabies vaccine, beginning with material from a cord desiccated for fourteen days and progressing over the following ten days through preparations of increasing virulence.

The boy tolerated the inoculations well. He showed no signs of disease through the period of the vaccination course; he continued to play in the courtyard of the École Normale where the Pasteur family lived; he showed no signs of disease in the weeks following the completion of the vaccinations; he did not develop rabies. By the end of August 1885, when he returned to his family in Alsace, it was clear that the vaccination had succeeded.

Pasteur announced the success of the Meister vaccination to the Academy of Sciences on 26 October 1885, in a memoir that became one of the most famous communications in the history of medicine. The announcement was cautious — Pasteur emphasized that one case was not yet a demonstration of the general efficacy of the method, that further cases would be needed, that the technique remained experimental. But the news spread immediately around the world; within weeks, dog-bite victims from across France and from abroad were arriving at the rue d'Ulm to seek treatment. A second case — a fifteen-year-old shepherd, Jean-Baptiste Jupille, who had been bitten while trying to protect younger children from a rabid dog — was treated successfully in October 1885 and became the subject of a famous statue that stands today in the courtyard of the Pasteur Institute. By the end of 1886, more than two thousand patients had been treated at the rue d'Ulm laboratory; the mortality rate among those treated within a few days of exposure was less than one percent — an extraordinary result, given that without treatment the mortality among confirmed rabid-dog bites would have been perhaps fifteen to twenty percent (most bites of rabid animals do not actually transmit the disease, but the mortality among those that do is essentially one hundred percent).

The Founding of the Pasteur Institute

The success of the rabies vaccination created a practical problem that the existing facilities at the École Normale could not handle. The laboratory was small; the patients were many; the daily inoculations required organized clinical management; the production of the vaccine required a substantial rabbit colony and dedicated technical staff. Pasteur appealed to the French government and to private subscribers for the construction of a new institute that would combine clinical treatment, vaccine production, and ongoing scientific research in microbiology and immunology.

The response was overwhelming. A national subscription, organized by the Academy of Sciences and given strong support by the press, raised more than two million francs from private donors in France and abroad; the French government contributed substantial additional funds; the Tsar of Russia, the Emperor of Brazil, and the Sultan of the Ottoman Empire all made substantial personal contributions in recognition of the international importance of the work. A site was acquired in the Vaugirard district of Paris, on the rue Dutot (now the rue du Docteur Roux), and construction of the new Pasteur Institute began in 1887. The building — a substantial three-story structure with laboratories, lecture halls, a clinical inoculation service, vaccine production facilities, and a residential apartment for Pasteur and his family — was completed in 1888 and inaugurated on 14 November 1888 in the presence of the President of the Republic, Sadi Carnot.

The Pasteur Institute was, from its founding, a new kind of scientific institution. Unlike the older academic institutes that combined teaching with research, the Pasteur Institute was dedicated primarily to research, with a secondary clinical mission (the rabies treatment service) and a financial structure that combined government grants, private donations, and revenue from the sale of biologicals to support its work. The model proved enormously successful and would be widely imitated; institutes on the Pasteur model would be established in cities throughout France and around the world over the following decades, including the great medical research institutes that would carry the Pasteurian methods to North Africa, Indochina, South America, and beyond.

The intellectual genealogy of the Institute was also extraordinary. The first generation of Pasteur's collaborators — Émile Roux, Charles Chamberland, Élie Metchnikoff, Edmond Nocard, Pierre-Paul-Émile Duclaux — became the founders of multiple new disciplines and the teachers of subsequent generations of microbiologists, immunologists, virologists, and parasitologists. Roux would develop the serum therapy for diphtheria in the 1890s (one of the great immediate triumphs of the Pasteur Institute); Chamberland would develop the bacterial filter that bears his name and that would lead, in the hands of Dmitri Ivanovsky and Martinus Beijerinck, to the discovery of viruses; Metchnikoff would develop the cellular theory of immunity (the role of phagocytic cells in defending the body against infection) for which he would share the Nobel Prize in 1908. The Pasteur Institute became, within a decade of its founding, the most productive center of microbiological research in the world, and it remained the institutional home of French biomedical research throughout the twentieth century.

The Last Years

The years following the founding of the Institute were the years of Pasteur's greatest public fame and of his progressive physical decline. The stroke of 1868 had left him permanently weakened; subsequent smaller strokes through the 1880s further diminished his capacity, though they did not affect his mental faculties. By the early 1890s he could no longer work in the laboratory and could walk only with assistance; he spent most of his days in the apartment at the Institute, receiving visitors, dictating correspondence to his wife and to his son-in-law René Vallery-Radot, following the progress of his collaborators' researches through their daily reports.

The honors of his later years were extraordinary. He had been elected to the French Academy (the Académie Française, the literary academy as distinct from the Academy of Sciences) in 1881 — an unusual honor for a scientist and one that reflected his command of French prose. He had been made a Grand Officer of the Legion of Honor in 1881 and a Grand Cross in 1881 (the highest grade); the Republic awarded him a national pension by special legislation in 1874 and increased it after the rabies success. Foreign honors were innumerable: honorary doctorates from universities in every country of Europe and in the United States, foreign membership in the Royal Society of London (1869), the Academy of Sciences of St. Petersburg, the Berlin Academy of Sciences (despite the Bonn affair), and dozens of other learned bodies. The Copley Medal of the Royal Society, the highest honor that scientific society could confer, was awarded to him in 1874; the Albert Medal of the Society of Arts followed in 1882; the Order of the Pour le Mérite of the German Empire was offered to him in 1889 (he declined to accept it, the wound of 1871 still being too fresh).

The seventieth birthday in December 1892 was the occasion of a great national celebration. A jubilee ceremony was held at the Sorbonne; the President of the Republic, Sadi Carnot, presided; the Minister of Public Instruction delivered an oration; foreign delegations attended from a score of countries; Joseph Lister, the British surgeon whose application of Pasteurian principles to surgery had transformed the practice of medicine, embraced Pasteur in the presence of the assembled dignitaries — a symbolic embrace of two of the great medical innovators of the century. Pasteur himself, too weakened to deliver an extended response, allowed his son Jean-Baptiste to read for him a short speech in which he expressed gratitude to the gathering and exhorted the young men present to "live in the serene peace of laboratories and libraries" and never to despair of the eventual triumph of patient scientific work.

The last three years of his life, from 1892 to 1895, were lived in the increasing seclusion of the Institute. He continued to follow the work of his pupils — the development of the diphtheria antitoxin by Roux and his collaborators (a triumph of the new serum therapy), the work on plague by Yersin in Hong Kong, the work on tuberculosis by Calmette and Guérin — but he no longer participated personally in the research. His mental faculties remained intact, his interest in his subject never flagged, but his physical capacity gradually declined. In the summer of 1895, the family moved him to a small house on the property of his son-in-law's estate at Villeneuve-l'Étang, near Garches, just west of Paris; the air was cleaner than in the city, and the family hoped that the country setting would extend his life.

It was at Villeneuve-l'Étang, on the afternoon of 28 September 1895, that Louis Pasteur died, at the age of seventy-two. The cause of death was a series of strokes, the cumulative effect of the cerebral disease that had begun with the first stroke of 1868. He died in the presence of his wife Marie, his daughter Marie-Louise, his son-in-law René Vallery-Radot, and his grandchildren; a crucifix was in one of his hands, and his last words, according to his family, were "I cannot."

The funeral was an event of national mourning. The body was returned to Paris on a special train; it lay in state for a day at the Pasteur Institute; on 5 October 1895 a state funeral was conducted at the Cathedral of Notre-Dame, presided over by the Cardinal Archbishop of Paris and attended by the President of the Republic, the diplomatic corps of all the major powers, delegations from foreign academies and universities, and an immense crowd of ordinary Parisians who filled the surrounding streets for hours before and after the ceremony. The body was initially interred in a temporary tomb at Notre-Dame; some months later, when the Pasteur Institute had constructed an elaborate underground crypt, it was transferred to its permanent resting place. The crypt, decorated in a Byzantine style with mosaics depicting the events of Pasteur's career — the silkworms, the sheep, the dog bites, the vines — became, and remains, one of the great pilgrimage sites of modern science.

Personal Character and Daily Habits

The man who was thus honored by his country and his world was, to those who knew him in private, a figure of mingled affection and difficulty. The image of Pasteur that emerges from the letters of his family and the memoirs of his collaborators is of a man of intense loyalties, narrow but deep affections, immense capacity for work, and considerable difficulty in personal relations outside his immediate family.

His daily life, throughout his active career, was organized around the laboratory with a discipline that bordered on the monastic. He rose early, took a light breakfast with his wife, and was at his work table by eight in the morning. He worked through the morning until lunch, returned to the laboratory after lunch, worked through the afternoon, ate dinner with his family, and then often returned for a few more hours of work in the evening. He took no formal vacations during the active years of his research, though he sometimes traveled in connection with his work (to the silk-producing regions, to the agricultural societies of various provinces). He neither smoked nor drank wine in significant quantity (a notable abstinence, for a man whose work touched so much on the fermentation industries); he ate sparingly and without much attention to what was set before him; his only recreations were music (he loved the chamber works of Beethoven and Schubert), occasional games of dominoes with family and friends, and the long Sunday walks with Marie that were a feature of his Paris years.

His relations with his collaborators were complicated. He was a generous teacher to the young men who worked under him — Roux, Chamberland, Metchnikoff, Nocard, Duclaux, and many others — and he gave them, in the work of the Pasteur Institute, opportunities and resources that they could not have found elsewhere. But he was also imperious in his control of the work, jealous of his own priority, sometimes slow to acknowledge the specific contributions of his subordinates. The Pouilly-le-Fort affair, in which he had used Toussaint's chemical attenuation method without acknowledging the source, was characteristic. So was his treatment of Émile Roux during the development of the diphtheria antitoxin in 1894: Roux's contribution was the central one, but Pasteur was credited (perhaps unfairly) with the broader honor for the work of the Institute. The collaborators accepted these patterns of the patron's relationships with his disciples; the disciples themselves usually went on to substantial independent careers in which they could establish their own priority.

His marriage to Marie Pasteur was, by every external measure, an unusually successful one. The forty-six years of their union — from the marriage in May 1849 to Pasteur's death in September 1895 — were marked by mutual devotion, by the shared sorrow of the deaths of three of their children, by Marie's increasing role as her husband's manager and amanuensis as his health declined. The correspondence between them during their occasional separations is filled with the language of affection, with the day-to-day reports of family and work, with the small mutual references that have meaning only to husbands and wives of long standing. Marie outlived him by fifteen years, dying in 1910 at the age of eighty-four; she was buried in the crypt at the Pasteur Institute beside her husband, where their tomb is one of the most visited shrines of the institution.

His relations with his children were close and demanding. Of the five children born to the marriage, only two survived to adulthood: Jean-Baptiste, the elder son, who became a French diplomat and consul; and Marie-Louise, the younger daughter, who married René Vallery-Radot and became the mother of Pasteur's grandchildren. Pasteur was deeply devoted to both surviving children and to the grandchildren who appeared in his later years; the photographs of him as a grandfather, holding his grandchildren on his lap in the apartment at the Pasteur Institute, are some of the most affecting images of his old age. The deaths of the three children who died young — Jeanne, Cécile, and Camille — left wounds in the parents' lives that never healed; Pasteur was known to mention them rarely but with such evident pain that those who heard him did not press the subject.

Religious Beliefs and the Question of Science and Faith

Pasteur was, throughout his life, a practicing Catholic of the French provincial bourgeois tradition in which he had been raised. He attended Mass on Sundays, observed the principal feasts of the church calendar, was married in a Catholic ceremony, baptized his children in the Catholic faith, and received the last sacraments before his death. His Catholicism was not particularly demonstrative or theological; he did not, like some Catholic intellectuals of his day, engage in extensive public arguments about the doctrines of the church; he did not write apologetic works defending the compatibility of Catholicism with science; he did not, on the other hand, ever hide his religious commitments or pretend (as some of his scientific colleagues did) to a secular indifference that he did not in fact feel.

The relation between his religious commitments and his scientific work was, in his own understanding, simple. The laws of nature, as they were progressively discovered by the experimentalist, were the laws established by God in the act of creation; the work of the scientist was to illuminate those laws and to apply them for the benefit of humanity; nothing in the experimental method or its results was, in principle, in conflict with the basic truths of Christian faith. He stated this view publicly on a number of occasions — most famously in his acceptance speech at the Académie Française in 1882, where he declared that "the more I contemplate the mysteries of nature, the more my faith becomes that of a Breton peasant; if I could know all things, I might have the faith of a Breton peasant's wife." The remark was characteristic in its slight self-mockery (the simple faith of provincial Catholics was a familiar trope of French Catholic apologetics) and in its placement of the contemplation of nature at the center of religious experience.

The relation was not, however, a simple matter of separation. Pasteur was clearly aware that some of his scientific positions had religious implications — that the refutation of spontaneous generation, in particular, was congenial to a Christian framework in which life was the result of a unique creative act rather than a continuous spontaneous process. He did not press these implications in his scientific writings, but he was aware of them, and they doubtless gave him an additional reason for the energy with which he attacked the Pouchet thesis. On the larger question of evolutionary biology — the great theoretical project of his generation, advanced most prominently by Charles Darwin — Pasteur was characteristically cautious. He neither embraced nor publicly opposed the Darwinian theory; he limited himself, as a working scientist, to the questions that fell within the range of his experimental investigation, and left the broader theoretical disputes to others.

The French anticlerical movement of the Third Republic — which was at its height during the last fifteen years of Pasteur's life and which produced, among other measures, the secularization of public education in 1881–82 and the eventual separation of church and state in 1905 — placed Pasteur in an awkward position. He was personally a believing Catholic; he was also a hero of the Republic and a beneficiary of the republican system of state-supported scientific institutions. He navigated the tension with characteristic discretion: he supported the public funding of science and the institutional autonomy of scientific bodies; he opposed the more aggressive forms of anticlericalism that would have removed religious instruction from schools entirely; he remained a personal friend of clerical figures (he was close to the Cardinal Archbishop of Paris in his later years) while continuing to participate fully in the republican scientific establishment. His position satisfied no one entirely, but it was characteristic of the man and of the broader strategy by which French Catholic intellectuals of his generation attempted to find a place within the secular institutions of the Third Republic.

The Laboratory Notebooks and the Geison Controversy

For more than a century after Pasteur's death, the documentary record of his scientific work was known primarily through his published papers and through the official biography written by his son-in-law René Vallery-Radot (La Vie de Pasteur, published in 1900). The laboratory notebooks that Pasteur had kept throughout his career were preserved by the family but were not made available for scholarly examination; the family's policy, established by Vallery-Radot, was that the notebooks were a family possession and would be released only when no living person whose reputation might be affected by their contents remained. The last of Pasteur's direct heirs, his grandson Louis Pasteur Vallery-Radot, died in 1971, and the notebooks were then deposited with the Bibliothèque Nationale in Paris and opened to scholarly examination.

The notebooks were used in the following decades by a small group of historians of science, most prominently the American historian Gerald L. Geison of Princeton University, whose book The Private Science of Louis Pasteur (1995) constituted the most extensive analysis of the notebook material yet undertaken. Geison's book — published in the centenary year of Pasteur's death — was controversial because it documented, with the precision that the notebooks allowed, a number of discrepancies between the polished public accounts that Pasteur had given of his major experiments and the actual experimental record. The most important of these discrepancies were in the Pouilly-le-Fort anthrax demonstration (where, as already noted, the vaccine actually used was prepared by Chamberland on a method borrowed from Toussaint, not the heat-attenuated vaccine that Pasteur publicly attributed to himself) and in the early human trials of the rabies vaccine (where, before the Meister case, Pasteur had apparently treated at least one other patient — Joseph Mester or another — with a method that he did not publicly disclose and that may have been less successful than the polished account suggested).

The Geison book provoked substantial controversy in the French scientific community and among historians of medicine. Some critics argued that Geison had overstated the discrepancies, had not adequately credited the genuine genius of Pasteur's work, and had relied too heavily on his own interpretation of ambiguous notebook entries. Others argued that the book performed a necessary service in correcting the heroic mythology that had grown up around Pasteur and in placing his work in a more realistic historical context. The general scholarly consensus, in the decades since Geison's book, has been that the documentation of methodological compromises in some of Pasteur's most famous experiments is real and significant, but that the larger framework of his scientific contribution — the establishment of microbial etiology of disease, the development of the principle of attenuated vaccines, the founding of practical microbiology and immunology — is not in any way diminished by the discovery that some of the particular experiments were less unequivocal than their public presentations suggested.

The controversy has had the additional effect of placing Pasteur in a broader historiographical debate about the role of public demonstration and rhetorical presentation in scientific work. Pasteur was unusually adept at the dramatic public demonstration — Pouilly-le-Fort was perhaps the most striking example, but he employed similar techniques throughout his career — and the question of whether such demonstrations are essentially honest presentations of scientific results, or essentially theatrical productions in which the science is dressed up for public consumption, has been raised with respect to many other scientific figures. The Pasteur case has become, in this sense, an important reference point in the historiography of scientific publication and display.

Pasteurization in Modern Life

The technique that bears Pasteur's name — pasteurization, the brief heat treatment of foods and beverages to destroy harmful microorganisms — has, in the century and a quarter since his death, become one of the most widely applied technologies of modern public health. The treatment was first developed by Pasteur for the preservation of wine and beer; it was later extended, by Soxhlet, Straus, and many others, to milk; it was applied in the twentieth century to a great range of additional foods and beverages, including fruit juices, eggs, ice cream, and many ready-to-eat foods.

The public health impact of the routine pasteurization of milk has been particularly enormous. Before pasteurization, milk was a major vehicle for the transmission of bovine tuberculosis (which causes serious disease in humans, particularly children), brucellosis (undulant fever), Q fever, diphtheria, typhoid fever, and a host of other infections. The infant mortality rates of cities with substantial dairy populations were significantly elevated by milk-borne disease, and the introduction of compulsory pasteurization of commercial milk supplies — adopted progressively in cities across the developed world during the first half of the twentieth century — was one of the central public health measures that brought infant mortality rates down to modern levels. The benefits were quiet and statistical rather than dramatic and individual, but they were enormous in aggregate.

In modern developed countries, the pasteurization of commercial milk is essentially universal, and the elimination of milk-borne disease as a public health problem is essentially complete. The continued production of unpasteurized "raw" milk for connoisseur consumption has been the subject of considerable regulatory debate; the consumption of raw milk continues to produce small numbers of disease outbreaks each year, and public health authorities generally advise against its use except in carefully managed circumstances. The basic Pasteurian framework — that brief moderate heating can destroy pathogenic microorganisms without significantly damaging the nutritional or sensory qualities of the food — has been refined and extended (ultra-high-temperature processing, flash pasteurization, and many specialized techniques have been developed) but the basic principle remains as Pasteur established it in the 1860s.

The Germ Theory and Modern Medicine

The larger framework of Pasteur's work — the establishment of the germ theory of infectious disease, the demonstration that specific microorganisms cause specific diseases, the development of attenuated vaccines, the principles of antiseptic and aseptic practice that followed from these discoveries — transformed the practice of medicine and surgery in the decades after his death. The transformation was, in many ways, more important than any specific therapy that Pasteur himself developed; it provided the framework within which subsequent generations of physicians and microbiologists could work out the etiology of disease after disease and develop treatments and preventions for them.

The application of Pasteurian principles to surgery was pioneered by the British surgeon Joseph Lister of Edinburgh (later of London), who had read Pasteur's papers on fermentation and the airborne origin of microorganisms in the early 1860s and had immediately grasped their relevance to the problem of surgical sepsis. Surgery before Lister was an exceedingly dangerous practice; even minor wounds, including the wounds produced by surgery itself, became infected with such regularity that the mortality from amputations, for example, was commonly above thirty or forty percent. Lister, applying Pasteurian principles, developed a system of antiseptic surgery in which the surgeon's hands, the patient's wound, and the surgical instruments were all treated with carbolic acid to kill the microorganisms that might cause infection; the carbolic acid spray was applied also to the operating room air during the procedure to reduce airborne contamination. The results were dramatic: surgical mortality fell, in Lister's wards, from above forty percent to below ten percent within a few years, and Lister's antiseptic system spread (more slowly than it should have) through the surgical practice of the world. By the end of the nineteenth century, antiseptic surgery had evolved into aseptic surgery (in which the goal was the complete exclusion of microorganisms from the operating field rather than their destruction by chemical agents), and the modern practice of surgery had been established on the foundations that Lister had built on Pasteur's principles.

The application to obstetrics had an equally important precursor in the work of the Hungarian physician Ignaz Semmelweis, who in the 1840s — before Pasteur's fermentation work and before any clear theoretical understanding of the etiology of disease — had recognized empirically that childbed fever (puerperal sepsis) was being transmitted from patient to patient by the physicians' unwashed hands and had instituted in his Vienna obstetric ward a regime of hand-washing with chlorinated water that had dramatically reduced the mortality. Semmelweis's reform had been rejected by his medical colleagues during his lifetime and had been forgotten in the years after his death in 1865. The Pasteurian and Listerian framework provided, in retrospect, the theoretical explanation for what Semmelweis had observed, and the reintroduction of systematic asepsis into obstetric practice in the 1870s and 1880s (now justified by germ theory) finally accomplished what Semmelweis had attempted to bring about a generation earlier.

The systematic identification of the bacterial causes of major infectious diseases, in the decades following Pasteur's work, was largely accomplished by the German school under Robert Koch and his collaborators. The anthrax bacillus (Koch, 1876), the tubercle bacillus (Koch, 1882), the cholera vibrio (Koch, 1883), the diphtheria bacillus (Klebs and Löffler, 1883–84), the typhoid bacillus (Eberth, 1880), the plague bacillus (Yersin and Kitasato, 1894), and many others were identified during this remarkable period. The Pasteurian framework provided the theoretical justification for these searches; Koch's methods of pure cultivation, microscopic examination with new staining techniques, and experimental inoculation provided the technical means; the new disciplines of bacteriology and pathological microbiology, which had no existence before Pasteur's work in the 1860s, were firmly established by the 1890s and would dominate medical research for the following half-century.

The Pasteur Institute Network Abroad

The international expansion of the Pasteurian project began in Pasteur's own lifetime and continued, with extraordinary rapidity, in the decades after his death. The first Pasteur Institute outside Paris was established in Saigon, in French Indochina, in 1891, under the direction of Albert Calmette — a young naval doctor who had been trained at the rue d'Ulm laboratory and who would become one of the great pioneers of tropical microbiology. Other early establishments followed: Tunis (1893), Algiers (1894), Brazzaville (1908), Tananarive (1898), Athens (1919), Tehran (1921), Shanghai (1937), Phnom Penh (1953). By the early twentieth century there were more than twenty Pasteur institutes around the world, all sharing the Parisian model of combined clinical service, vaccine production, and research, and all serving as foci for the training of local microbiologists and for the implementation of public health programs based on Pasteurian principles.

The scientific contributions of the international Pasteur network through the twentieth century were considerable. The development of the BCG vaccine against tuberculosis by Calmette and his collaborator Camille Guérin (the work was begun at Lille in 1900 and brought to fruition at the Pasteur Institute of Paris between 1908 and 1921) was perhaps the most important; the BCG vaccine has been administered to more than four billion people worldwide since its introduction in 1921 and remains a central instrument in the control of tuberculosis in many countries. The work of Yersin in Hong Kong on the plague bacillus in 1894, the work of Laveran on the malaria parasite, the work of Nicolle on epidemic typhus (for which he received the Nobel Prize in 1928), the work of Bordet on whooping cough (for which Bordet received the Nobel Prize in 1919) — all of this was Pasteur Institute work, conducted in the network of institutions that Pasteur had established or whose founding had been inspired by his example. The Institut Pasteur of Paris would receive ten Nobel Prizes in Physiology or Medicine over the course of the twentieth century; its alumni and associates would receive many more.

In the late twentieth century the Pasteur Institute network was at the forefront of the new discipline of molecular biology and of the response to the HIV/AIDS epidemic. Luc Montagnier and Françoise Barré-Sinoussi, working at the Institut Pasteur in 1983, identified the human immunodeficiency virus as the causative agent of AIDS — the first of the great viral diseases of the late twentieth century to be characterized at the molecular level. They would receive the Nobel Prize in 2008 for this work, in a recognition that was both a tribute to their specific contribution and a continuing acknowledgment of the central role that the Pasteur Institute has played in microbiological research for more than a century.

In the twenty-first century the Pasteur network — now formally organized as the Institut Pasteur International Network, with member institutes in more than twenty-five countries — continues to play a central role in the international response to infectious disease. Pasteur Institute scientists were central to the international response to the SARS outbreak of 2003, the H1N1 influenza pandemic of 2009, the Ebola outbreaks in West Africa beginning in 2014, the Zika outbreak of 2015–16, and the COVID-19 pandemic that began in late 2019. The institutional model that Pasteur established in the rue Dutot in the 1880s has proved itself, across more than a century, to be remarkably well-adapted to the demands of an integrated international response to infectious disease.

Pasteur and the Language of Microbiology

The vocabulary of modern microbiology, like the vocabulary of modern chemistry that we noted earlier, owes a considerable debt to Pasteur's specific terminology. The terms "anaerobic" and "aerobic" (for organisms that do or do not require oxygen) were coined by Pasteur in his butyric fermentation paper of 1861. The term "attenuated" (for weakened vaccine strains) became established through his work on chicken cholera and anthrax. The term "vaccine" itself, originally limited (after Jenner) to the cowpox preparation used against smallpox, was generalized by Pasteur to apply to any attenuated preparation used to confer immunity against an infectious disease; the term "vaccination" likewise became a general term covering any inoculation with an attenuated agent. The procedure that bears his name — "pasteurization," in French as in English — was first applied (the word coined in the early 1870s) to the heat treatment of wine and beer and was then extended to milk and other beverages.

The institutional vocabulary of microbiology also bears his mark. The "institut" model of dedicated research and clinical centers, supported by a combination of public funding, private philanthropy, and commercial revenue, was largely his creation. The model of the senior research scientist surrounded by a stable of younger collaborators in dedicated laboratories, with formal training programs for foreign visitors and a publication apparatus for the dissemination of results — this was the model of the Pasteur Institute, and it has been the model of biomedical research institutes around the world ever since.

The rhetorical conventions of microbiological publication owe a particular debt to Pasteur. His characteristic style — combining a clear narrative account of the experimental work with explicit statements of the theoretical principles, supported by careful presentation of the numerical data and the visible results — established a model that has been widely followed in the subsequent literature of microbiology. The publication of microbial cultures, with their characteristic colony morphologies and their characteristic biochemical signatures; the publication of vaccination trials, with their formal comparison of treated and control groups; the publication of epidemiological investigations, with their careful tracing of the chain of transmission — all of these forms of microbiological publication trace back, in important respects, to the precedents set by Pasteur in the 1860s and 1870s.

Honors and Memorials

The honors paid to Pasteur after his death have been commensurate with the scale of his contributions. The Pasteur Institute itself, with the crypt in which he is buried beneath the founding building, has been since 1895 the principal monument to his memory. Statues of Pasteur have been erected in Paris (in front of the Sorbonne and at the Pasteur Institute), in his native town of Dole (where the family home is now a museum), in Arbois (where he spent his childhood and where another family house is preserved as a museum), in the silk-producing town of Alès (where the silkworm work was conducted), and in dozens of other cities around the world. The street outside the Institut Pasteur in Paris was renamed the rue du Docteur Roux in honor of Pasteur's principal collaborator; many of the streets, squares, and public buildings of France bear Pasteur's name.

The hundredth anniversary of his birth in 1922 and the hundredth anniversary of his death in 1995 were observed as occasions of national celebration in France and as occasions of international scientific commemoration. The 1922 celebration produced the official biography by his grandson Louis Pasteur Vallery-Radot, a substantial multi-volume work that compiled and re-edited the documentary material on Pasteur's life and work. The 1995 commemoration produced, among many other publications, the controversial Geison book that we have discussed, and a major exhibition at the Institut Pasteur that drew visitors from around the world.

His name has been given to many things: an asteroid (4804 Pasteur), a lunar crater, a Mars crater, a class of streetcars in San Francisco that ran through the Mission District, an esteemed Quebec university (the Université Laval has a Pasteur building), a chain of hospitals in France (the Hôpital Pasteur of Nice), countless schools, laboratories, and research institutes around the world, the official mascot of the French scientific community for many decades, and (more frivolously) the title character of several films and television series of varying historical accuracy. His face has appeared on French currency (the five-franc note of the 1960s) and on French postage stamps of many denominations.

The Pasteur five-franc note circulated through the years of the late Third Republic, the Vichy regime, the Fourth Republic, and the early Fifth Republic, with his familiar features (the brushed-back gray hair, the trim beard, the sober expression) becoming as familiar to French citizens as those of Napoleon or Marianne. The note was withdrawn from circulation only in the 1960s when the new franc was introduced; the older notes, now collector's items, remain in many French households as small mementos of a national hero who was perhaps the most beloved scientific figure in the history of the Republic.

Historiographical Reception

The way that historians have understood Pasteur has, like the way they have understood any major historical figure, undergone significant evolution over the century and more since his death. The first phase, lasting roughly from his death in 1895 through the 1950s, was dominated by the hagiographic tradition that his son-in-law René Vallery-Radot had established with the official biography of 1900. In this tradition, Pasteur appeared as a heroic figure of essentially unmixed virtue: a brilliant scientist, a devoted family man, a patriotic Frenchman, a sincere Catholic, a man whose principles and methods were as exemplary as his discoveries. The tradition was maintained by his grandson Louis Pasteur Vallery-Radot, who controlled the family papers through the middle decades of the twentieth century and who produced a number of additional biographical and scholarly works on his grandfather's life and work.

The second phase, beginning in the 1970s with the opening of the notebooks to scholarly examination, has produced a more complex and contextualized account of Pasteur. The work of the French historian of science Antonio Cadeddu, the British historian Bruno Latour (whose Pasteurization of France, 1984, is a sociological analysis of how the Pasteurian program acquired political support in late-nineteenth-century France), the American historian Gerald Geison (whose Private Science of Louis Pasteur we have already discussed), and the French biographer Patrice Debré (whose Louis Pasteur of 1994 is the most extensive recent treatment) has produced a Pasteur who is more historically situated, less mythologically heroic, and more interestingly human than the hagiographic tradition had allowed.

Latour's contribution, in particular, has been to place Pasteur in the context of the broader social and political transformations of late-nineteenth-century France. Pasteur did not simply discover germs and vaccines and impose them on a passive society; he had to enlist allies — the hygienist movement, the agricultural societies, the veterinary profession, the army (which had a strong interest in any sanitary measures that might reduce the mortality of recruits), the school medical service, the public health authorities of cities and departments — in a long process of negotiation through which the Pasteurian program acquired the political and institutional support that allowed it to be implemented at scale. Latour's analysis, although sometimes accused of overemphasizing the political dimension at the expense of the scientific, has been valuable in showing that the success of the Pasteurian program was not simply a question of correct science triumphing over error but also a question of skillful institutional politics conducted over decades.

The recent historiography has also given more attention to Pasteur's rivalries and conflicts with other scientific figures of his generation — with Pouchet over spontaneous generation, with Liebig over fermentation, with Koch over the etiology of anthrax and tuberculosis, with Toussaint over chemical attenuation, with the medical establishment of his day over many particular questions. These rivalries have been treated, in the older literature, as essentially personal matters or as cases in which Pasteur was straightforwardly right and his opponents straightforwardly wrong; the recent literature has been more inclined to see them as legitimate scientific disagreements in which Pasteur's position was usually but not always the more sustainable one and in which the personal dynamics of the scientific community played a real role.

The cumulative effect of this historiographical work has been, as in the parallel case of Copernicus that we have already discussed, to humanize and contextualize a historical figure who had been excessively mythologized in earlier accounts. The Pasteur of contemporary historiography is a more complicated and more interesting man than the Pasteur of the official biographies — a man of real genius and real flaws, a participant in a complex scientific and political world, a figure whose accomplishments must be measured both by what he did and by what he failed to do or did imperfectly. The complications do not diminish the magnitude of his achievement; they place it more securely in the historical record from which it had been previously somewhat detached.

Conclusion: the Meaning of Pasteur

What, in the end, is the meaning of Louis Pasteur for the history of science and for the broader culture of the modern world? Several elements of his significance can be distinguished.

In the first place, he was the founder, more than any other single individual, of the science of microbiology. The recognition that microscopic organisms constitute a vast and significant kingdom of life, with its own metabolic processes, its own ecological relationships with the larger organisms in which it sometimes lives, its own potential to cause and to prevent disease — this is the framework that Pasteur established and that has dominated biological and medical research for more than a century. The subsequent development of bacteriology, virology, mycology, parasitology, and molecular microbiology has built on the framework that he provided; the specific discoveries within those fields have refined his conclusions and extended them, but the framework itself has remained essentially as he left it.

In the second place, he was the founder of practical immunology, the discipline that studies and applies the body's defenses against infectious disease. The principle of attenuated vaccines, established by the chicken cholera observation and developed in the anthrax and rabies work, has remained the central principle of vaccine development to the present day; the live attenuated vaccines against measles, mumps, rubella, yellow fever, polio (the Sabin vaccine), and many other diseases are direct descendants of Pasteur's methods. The newer techniques of subunit vaccines, conjugate vaccines, and mRNA vaccines (developed in the early twenty-first century in response to the COVID-19 pandemic) have built on the Pasteurian framework even as they have moved beyond his specific techniques; the basic idea of stimulating the immune system to produce a protective response against a pathogen, without the dangers of the actual disease, is his idea.

In the third place, he was the founder of the modern principles of food safety and public hygiene. The procedure of pasteurization, the principle of antiseptic and aseptic surgical practice, the systematic application of microbiological principles to the inspection and regulation of food production, the campaigns of vaccination against major epidemic diseases of livestock — all of these descend directly from his work. The decline in infant mortality, the conquest of many infectious diseases, the safety of modern food and water supplies — these enormous public health achievements of the twentieth century rested on the foundations that Pasteur laid in the 1860s and 1870s.

In the fourth place, he was the founder of a new institutional model of biomedical research. The Pasteur Institute and its international network demonstrated that scientific research, clinical service, vaccine production, and the training of future researchers could be combined in a single institution; that the funding for such an institution could be drawn from a combination of public grants, private donations, and commercial revenue; that an institution thus established could be the center of an international community of researchers conducting work of broad importance. The model has been imitated around the world; the great biomedical research institutes of the twentieth century — the Rockefeller Institute in New York, the Lister Institute in London, the Robert Koch Institute in Berlin, the National Institutes of Health in the United States, the Wellcome Trust laboratories in Britain — all owe something to the Pasteurian precedent.

In the fifth place, he was a model of the integrated scientific career — a model in which fundamental research, practical application, public education, and institutional leadership were combined in a single individual's work over a lifetime. Pasteur moved freely throughout his career between fundamental questions (the nature of fermentation, the existence of spontaneous generation) and practical applications (the preservation of wine, the rescue of the silk industry, the vaccination of dogs and human beings against rabies); between laboratory experiments and public demonstrations; between teaching, research, and public advocacy. The model of the scientist as a public figure of national importance, engaged simultaneously in fundamental research and in addressing the practical concerns of the society at large, was largely his creation and has been one of the central images of the modern scientist ever since.

The personal characteristics that made all this possible — the immense capacity for work, the patience, the methodical attention to detail, the willingness to follow a problem wherever it led, the rhetorical skill in presenting results to specialist and lay audiences, the strategic intelligence in mobilizing political and institutional support — were unusual but not unique; other scientists of his generation possessed some of these qualities to comparable degrees. What was unusual about Pasteur was the combination of all of them in a single individual, sustained over a working lifetime of nearly fifty years, and applied to a sequence of problems each of which was of fundamental importance.

The flaws that the recent historiography has documented — the occasional shortcut in experimental method, the occasional ungenerosity to rivals and subordinates, the occasional dramatization of scientific results for public effect — were real and they should not be erased. But they do not diminish the magnitude of what he accomplished, and they do not change the basic verdict of the history of science: Louis Pasteur was one of the half-dozen most important experimental scientists who have ever lived, and the changes that his work brought about in the practice of medicine, in the safety of the food supply, in the framework of biological understanding, are among the largest contributions that any single individual has made to the improvement of human life. The man who lies in the Byzantine crypt beneath the Pasteur Institute in Paris is the founder of practices and institutions that have, in the century and a quarter since his death, saved tens of millions of lives and made the modern world possible in ways that almost no one now living can recognize as his work. The success of his project has been so complete that the very methods he established have become the invisible substrate of modern existence: we drink pasteurized milk without thinking of him, we receive childhood vaccinations without thinking of him, we are operated on under aseptic conditions without thinking of him. The chemist who saw the invisible has, by the very success of his project, become invisible himself — present everywhere in the institutions and practices of modern medicine, recognized by name only in the special contexts of historical commemoration. It is, perhaps, the kind of legacy that he would have wished for himself: not a personal monument towering over the landscape of subsequent science, but a quiet pervasive transformation of human life that draws no attention to its origins because it has so completely become the way that things are.

Pasteur and the Culture of the Third Republic

A final word on the cultural context of Pasteur's life may help to set his achievement in its historical place. The France in which Pasteur conducted his work was undergoing a profound political and social transformation. The Second Empire of Napoleon III, under which Pasteur had begun his scientific career, was a regime of conservative authoritarianism in which the imperial court patronized the sciences as part of its broader strategy of modernization. The defeat of 1870, the proclamation of the Republic, the bloody suppression of the Paris Commune in 1871, and the gradual consolidation of the parliamentary Third Republic over the following decade produced a new political framework in which scientific research and education would be redefined as essential responsibilities of the secular republican state.

The Republic that Pasteur served through the last two decades of his life was a self-consciously modernizing regime that placed great emphasis on the cultivation of science, the secularization of public education, and the cultural prestige of the savant. The reforms of the public education system carried out by Jules Ferry in the early 1880s — the establishment of free, compulsory, and secular primary education, the modernization of secondary education, the expansion of state-supported scientific institutions — created the framework within which French science would operate for the rest of the century. The Pasteurian project benefited enormously from this republican commitment to science; the funding for the Pasteur Institute, the official honors that were lavished on Pasteur himself, the popular celebration of his achievements as triumphs of French national genius, were all expressions of the republican cultural program that placed the scientist at the center of national life.

Pasteur was not, however, a republican of the militantly anticlerical type; his personal piety and his conservative cultural attitudes placed him outside the most active currents of republican reform. He occupied, instead, a kind of middle ground — supporting the republican project of public science while preserving his personal Catholicism and his loyalty to a more traditional vision of French culture. The position satisfied no faction completely but was characteristic of a substantial part of the French bourgeoisie of his generation, who supported the institutions of the Republic without embracing all of its ideological commitments. The Pasteur who appears in the official iconography of the Third Republic — the grave bearded scientist, the patriotic Frenchman, the savior of children from terrible disease — was constructed in part by his admirers and was a figure that all political tendencies in the Republic could embrace.

The international position of France in the late nineteenth century was also relevant to the cultural reception of Pasteur. The defeat of 1870 had been a shattering blow to French national self-confidence; the loss of Alsace and Lorraine, the burden of the German indemnity, the rapid industrial and military growth of the new German Empire, all combined to produce in France a sense of national diminishment that the cultural achievements of the country could compensate for only imperfectly. Pasteur's emergence in the 1880s as the most celebrated scientist in the world was, in this context, a matter of national consolation: France had been defeated militarily and had lost its position as the dominant power in continental Europe, but France had also produced Louis Pasteur, whose discoveries were transforming the practice of medicine throughout the world and whose name was honored from Buenos Aires to St. Petersburg. The Pasteur Institute, with its international reach, was a French cultural institution of global importance in an age when the political and military instruments of French power had been substantially diminished.

The Dreyfus affair, which divided French society in the 1890s and after, occurred in the last years of Pasteur's life and after his death. He did not live to see the great crisis of the affair (1898–1906); his political views on the question of Alfred Dreyfus's guilt or innocence would have been, at most, those of a man approaching seventy who took little active part in current political controversies. But the Pasteurian institutional network was very much part of the divided France that the Dreyfus affair revealed: some Pasteur Institute scientists (most prominently Émile Duclaux, who succeeded Pasteur as director) were public Dreyfusards, while others remained more sympathetic to the anti-Dreyfusard cause. The institutions that Pasteur had built outlived him into a France that was very different from the country of his youth, and the institutional culture of the Pasteur Institute would adapt to and survive the great political upheavals of the twentieth century with remarkable resilience.

The Final Assessment

To stand today in the courtyard of the Institut Pasteur on the rue du Docteur Roux is to feel something of the continuing vitality of the project that Louis Pasteur began. The original building of 1888, now a museum displaying his apartment and the relics of his life and work, stands at one end of the courtyard; around it, in buildings constructed over the following century and a quarter, the Institute's three thousand scientists, technicians, and support staff continue the work of fundamental research and applied microbiology that he established. The crypt where Pasteur lies, with the mosaics depicting the silkworms and the vines and the sheep and the dogs of his investigations, is a small chapel of secular pilgrimage that visitors continue to seek out in considerable numbers. The clinical service that he created for the treatment of rabies bite victims still functions in modified form; the vaccine production facilities of the original Institute have been transferred to commercial subsidiaries that distribute Pasteur Institute vaccines around the world; the research laboratories continue to produce work of fundamental importance, with the Institute's recent contributions to the molecular biology of HIV, the genetics of malaria, the biology of prions, and the immunology of emerging viral diseases continuing the Pasteurian tradition of combining fundamental science with practical application.

The man whose life and work we have been examining was, on a personal level, an ordinary French bourgeois of the nineteenth century — a man of provincial origin and provincial values, a faithful husband, a devoted father, a sincere Catholic, a patriotic Frenchman of his time. He was not particularly imposing in appearance; he was not particularly gifted in conversation; he was not particularly cultivated in the broader sense of the term (he read little outside his scientific specialty, took no interest in the philosophical or literary debates of his time, traveled little except in connection with his work). His personal qualities were those of the disciplined working man rather than of the brilliant intellectual or the charismatic public figure: persistence, accuracy, careful attention to detail, the patience to follow a problem for years without losing interest, the modesty (in his private life if not always in his professional rhetoric) to accept setbacks and to begin again.

What he had, and what allowed all the rest, was the rarest of intellectual qualities: the capacity to see, in the ordinary phenomena of the laboratory or the workshop, the fundamental questions whose answers would transform a whole field of inquiry. The crystals on the wine cask, the spoiled beet juice in Bigo's distillery, the dying silkworms of the Cévennes, the dead sheep of the cursed fields, the bitten child from the Alsatian countryside — these were the materials of his work, and from each of them, by patient experimental investigation, he extracted insights that have shaped the modern world. The chemist who saw the invisible saw, perhaps more clearly than any other scientist of his century, that the smallest organisms could have the largest consequences, that the patient laboratory work of one man and his collaborators could, over the course of a lifetime, alter the conditions of human life on a scale that whole governments and armies might envy.

Nicolaus Copernicus had set the Earth in motion among the planets; Charles Darwin had placed the human species in continuity with the rest of the living world; Louis Pasteur, somewhere between these two in scale of conceptual revolution but quite possibly their superior in immediate practical impact, had reduced the great kingdom of infectious disease — which from time immemorial had been the principal cause of human death and suffering — to a problem of identifiable agents and developable preventions. The conquest is not yet complete; many infectious diseases remain incurable or unprevented, and new ones emerge with disconcerting regularity; the antibiotic resistance crisis of the early twenty-first century is a reminder that the battle is unending. But the framework within which the battle is fought, the methods by which new pathogens are identified and characterized, the institutions through which the response to outbreaks is organized — all of these are Pasteurian. The astronomer who moved the Earth has been at rest for nearly five centuries; the chemist who saw the invisible has been at rest for nearly a century and a third; the revolutions they began continue.