TORIma Academy Logo TORIma Academy
Louis Pasteur
Science

Louis Pasteur

TORIma Academy — Microbiologist / Chemist

Louis Pasteur

Louis Pasteur

Louis Pasteur ( , French: [lwi pastœʁ] ; 27 December 1822 – 28 September 1895) was a French chemist, pharmacist, and microbiologist renowned for his…

Louis Pasteur (, French: [lwi pastœʁ] ; 27 December 1822 – 28 September 1895) was a French chemist, pharmacist, and microbiologist recognized for his groundbreaking discoveries, including the principles of vaccination, microbial fermentation, and pasteurization, a process subsequently named in his honor. His chemical investigations yielded significant advancements in comprehending disease etiology and prevention, thereby establishing fundamental principles for hygiene, public health, and a substantial portion of contemporary medicine. Pasteur's contributions are widely credited with preserving millions of lives through the creation of vaccines for rabies and anthrax. He is considered a foundational figure in modern bacteriology and has been posthumously recognized as the "father of bacteriology" and the "father of microbiology," a title he shares with Robert Koch, while the latter designation is also ascribed to Antonie van Leeuwenhoek.

Louis Pasteur (, French: [lwipastœʁ] ; 27 December 1822 – 28 September 1895) was a French chemist, pharmacist, and microbiologist renowned for his discoveries of the principles of vaccination, microbial fermentation, and pasteurization, the last of which was named after him. His research in chemistry led to remarkable breakthroughs in the understanding of the causes and preventions of diseases, which laid down the foundations of hygiene, public health and much of modern medicine. Pasteur's works are credited with saving millions of lives through the developments of vaccines for rabies and anthrax. He is regarded as one of the founders of modern bacteriology and has been honored as the "father of bacteriology" and the "father of microbiology" (together with Robert Koch; the latter epithet also attributed to Antonie van Leeuwenhoek).

Pasteur definitively refuted the doctrine of spontaneous generation. His pivotal experiment, conducted under the patronage of the French Academy of Sciences, conclusively demonstrated that no life developed in sterilized and hermetically sealed flasks, whereas microorganisms proliferated in sterilized but open flasks. In recognition of this experiment, the academy bestowed upon him the Alhumbert Prize, valued at 2,500 francs, in 1862.

Pasteur is additionally recognized as a progenitor of the germ theory of diseases, a concept that held limited medical prominence during his era. His extensive experimental work demonstrated that disease transmission could be averted by eliminating or inhibiting microbial agents, thus providing direct empirical support for the germ theory and its subsequent application in clinical practice. To the broader public, he is most renowned for developing the technique of heat-treating milk and wine to prevent bacterial spoilage, a process universally known today as pasteurization. Furthermore, Pasteur made substantial contributions to chemistry, particularly concerning the molecular basis of asymmetry in specific crystals and the phenomenon of racemization. An early career investigation into sodium ammonium tartrate pioneered the field of optical isomerism. This research significantly influenced structural chemistry, with far-reaching implications across numerous disciplines, including medicinal chemistry.

He served as the director of the Pasteur Institute, founded in 1887, until his demise, and his remains were interred in a crypt beneath the institution. Despite Pasteur's pioneering experimental work, his legacy has been linked to several controversies. A historical reevaluation of his laboratory notebooks indicated instances of deceptive practices employed to gain advantage over his scientific competitors.

Early life and education

Louis Pasteur was born on December 27, 1822, in Dole, Jura, France, into a Catholic family of modest means, headed by a tanner. He was the third offspring of Jean-Joseph Pasteur and Jeanne-Etiennette Roqui. The family relocated to Marnoz in 1826, subsequently moving to Arbois in 1827. Pasteur commenced his primary education in 1831. He exhibited characteristics of dyslexia and dysgraphia.

During his formative years, he was an unremarkable student, displaying limited academic inclination, with his primary interests centered on fishing and sketching. He produced numerous pastels and portraits depicting his parents, friends, and neighbors. Pasteur pursued his secondary education at the Collège d'Arbois. In October 1838, he departed for Paris to matriculate at a boarding school; however, he experienced homesickness and returned the following November.

In 1839, he enrolled at the Collège Royal in Besançon to pursue philosophical studies, obtaining his Bachelor of Letters degree in 1840. He subsequently received an appointment as a tutor at the Besançon college, concurrently pursuing a science degree program with a specialization in mathematics. He was unsuccessful in his initial examination in 1841. He successfully passed the baccalauréat scientifique (general science) examination from Dijon, where he was awarded his Bachelor of Science in Mathematics degree (Bachelier ès Sciences Mathématiques) in 1842, albeit with an unremarkable performance in chemistry.

In late 1842, Pasteur undertook the entrance examination for the École Normale Supérieure. During this assessment, he contended with exhaustion and found proficiency primarily in physics and mathematics. Although he successfully completed the initial examination phase, his low ranking prompted Pasteur to defer his admission and reapply the following year. He returned to the Parisian boarding school to intensify his preparation, concurrently attending courses at the Lycée Saint-Louis and lectures delivered by Jean-Baptiste Dumas at the Sorbonne. By 1843, he successfully passed the examination with a superior ranking, securing his entry into the École Normale Supérieure. Subsequently, he studied under Jean-Baptiste Boussingault at the Conservatoire national des arts et métiers. In 1845, he was awarded the licencié ès sciences  degree. The following year, 1846, saw his appointment as a professor of physics at the Collège de Tournon in Ardèche. However, chemist Antoine Jérôme Balard sought his return to the École Normale Supérieure as a graduate laboratory assistant (agrégé préparateur). Pasteur accepted Balard's invitation, concurrently commencing his crystallographic research. In 1847, he submitted two theses: one in chemistry, titled "Research on the Saturation Capacity of Arsenious Acid. Studies of Potassium, Sodium, and Ammonium Arsenites," and another in physics, titled "1. Studies of Phenomena Related to the Rotatory Polarization of Liquids. 2. Application of the Rotatory Polarization of Liquids to the Solution of Various Chemical Questions."

Following a brief tenure as a professor of physics at the Dijon Lycée in 1848, Pasteur assumed the role of professor of chemistry at the University of Strasbourg. It was there, in 1849, that he encountered and courted Marie Laurent, the daughter of the university's rector. Their marriage took place on May 29, 1849. The couple had five children, though only two reached adulthood, with the remaining three succumbing to typhoid fever.

Career Overview

Pasteur received an appointment as professor of chemistry at the University of Strasbourg in 1848, subsequently ascending to the chair of chemistry in 1852.

In February 1854, Pasteur secured a three-month paid leave, facilitated by a medical certificate, to dedicate time to research that could qualify him for the title of correspondent of the Institute. He subsequently extended this leave until August 1st, coinciding with the commencement of examinations. Regarding this extension, he stated, "I inform the Minister that I will attend to the examinations so as not to exacerbate service difficulties. Furthermore, it is to avoid relinquishing a sum of 6 or 700 francs to another."

During the same year, 1854, Pasteur was appointed dean of the newly established faculty of sciences at the University of Lille, a position where he initiated his seminal investigations into fermentation. It was in this context that Pasteur articulated his frequently cited observation: "dans les champs de l'observation, le hasard ne favorise que les esprits préparés" ("In the field of observation, chance favors only the prepared mind").

In 1857, Pasteur relocated to Paris to assume the directorship of scientific studies at the École Normale Supérieure, a role he held from 1858 to 1867. During his tenure, he implemented a series of reforms designed to elevate the quality of scientific endeavors. These reforms included making examinations more stringent, which consequently yielded improved academic outcomes, heightened competition, and enhanced institutional prestige. Nevertheless, many of his directives were perceived as inflexible and authoritarian, precipitating two significant student uprisings. Notably, during "the bean revolt," he mandated that a mutton stew, previously rejected by students, be served and consumed every Monday. On a separate occasion, his threat to expel any student found smoking resulted in the resignation of 73 out of the 80 enrolled students.

In 1863, Pasteur was appointed professor of geology, physics, and chemistry at the École nationale supérieure des Beaux-Arts, a position he maintained until his resignation in 1867. That same year, 1867, he assumed the chair of organic chemistry at the Sorbonne, though he later relinquished this role due to declining health. Also in 1867, the École Normale's laboratory of physiological chemistry was established at Pasteur's behest, and he directed this laboratory from 1867 to 1888. In Paris, he founded the Pasteur Institute in 1887, serving as its director for the remainder of his life.

Research Focus

Molecular Asymmetry

During his initial scientific endeavors as a chemist, commencing at the École Normale Supérieure and subsequently at Strasbourg and Lille, Pasteur meticulously investigated the chemical, optical, and crystallographic characteristics of a class of compounds referred to as tartrates.

In 1848, he resolved a problem concerning the fundamental nature of tartaric acid. Solutions of this compound, when derived from biological sources, exhibited the property of rotating the plane of polarized light. Conversely, tartaric acid produced through chemical synthesis lacked this optical activity, despite possessing identical chemical reactivity and elemental composition.

Pasteur observed that tartrate crystals exhibited minute facets. Subsequently, he noted that racemic mixtures of tartrates comprised an equal proportion of right-handed and left-handed crystals. When dissolved, the right-handed enantiomer demonstrated dextrorotation, while its left-handed counterpart exhibited levorotation. Pasteur concluded that optical activity was intrinsically linked to crystal morphology and that an inherent asymmetric molecular arrangement within the compound accounted for the observed rotation of light. Specifically, the (2R,3R)- and (2S,3S)- tartrates were identified as isometric, non-superimposable mirror images. This groundbreaking work marked the inaugural demonstration of molecular chirality and provided the initial elucidation of isomerism.

Certain historians regard Pasteur's investigations in this domain as his "most profound and most original contributions to science," alongside his "greatest scientific discovery."

Fermentation and the Germ Theory of Disease

While employed in Lille, Pasteur became motivated to investigate the process of fermentation. In 1856, M. Bigot, a local wine producer whose son was one of Pasteur's students, solicited his expertise regarding challenges in beetroot alcohol production and spoilage. Pasteur initiated his research by replicating and validating the earlier findings of Theodor Schwann, who had demonstrated a decade prior that yeast constituted living organisms.

As documented by his son-in-law, René Vallery-Radot, Pasteur submitted a paper on lactic acid fermentation to the Société des Sciences de Lille in August 1857; however, its presentation occurred three months subsequent to its submission. A comprehensive memoir was subsequently published on November 30, 1857. Within this memoir, he articulated his hypothesis, asserting: "I intend to establish that, just as there is an alcoholic ferment, the yeast of beer, which is found everywhere that sugar is decomposed into alcohol and carbonic acid, so also there is a particular ferment, a lactic yeast, always present when sugar becomes lactic acid."

The complete version of this memoir, focusing on alcoholic fermentation, was published in 1858. Previously, Jöns Jacob Berzelius and Justus von Liebig had advanced a theory positing that fermentation resulted from decomposition. Pasteur's research disproved this theory, establishing that yeast was the causative agent for the fermentation of sugar into alcohol. Furthermore, he showed that contamination of wine by alternative microorganisms led to the production of lactic acid, thereby causing the wine to sour. In 1861, Pasteur noted a reduced rate of sugar fermentation per unit of yeast when the yeast was exposed to atmospheric air. This phenomenon of diminished aerobic fermentation subsequently became recognized as the Pasteur effect.

Pasteur's investigations additionally revealed that microbial proliferation was responsible for the spoilage of various beverages, including beer, wine, and milk. Building upon this understanding, he devised a process involving the heating of liquids, such as milk, to temperatures ranging from 60 to 100 °C. This thermal treatment effectively eliminated the majority of bacteria and molds present in these substances. On April 20, 1862, Pasteur, in collaboration with Claude Bernard, concluded experiments on blood and urine. In 1865, Pasteur patented this process, specifically aimed at combating the "diseases" affecting wine. The technique, subsequently termed pasteurization, was rapidly adopted for the preservation of beer and milk.

The insights gained from beverage contamination prompted Pasteur to hypothesize that microorganisms were causative agents of diseases in both animals and humans. His proposition for preventing microbial ingress into the human body subsequently inspired Joseph Lister to formulate antiseptic surgical techniques.

In 1866, Pasteur authored Études sur le Vin, a treatise on the pathologies of wine, followed by Études sur la Bière in 1876, which addressed the diseases affecting beer.

During the early 19th century, Agostino Bassi had demonstrated that muscardine, a disease affecting silkworms, was caused by a fungal infection. From 1853 onward, two distinct diseases, designated pébrine and flacherie, had severely impacted silkworm populations across southern France, resulting in substantial economic losses for farmers by 1865. In 1865, Pasteur relocated to Alès, where he conducted research for a five-year period, concluding in 1870.

Silkworms afflicted with pébrine exhibited corpuscles on their bodies. Initially, for three years, Pasteur hypothesized that these corpuscles represented a symptom rather than the etiology of the disease. By 1870, he revised his conclusion, asserting that the corpuscles were, in fact, the causative agents of pébrine, a condition now understood to be caused by a microsporidian. Furthermore, Pasteur demonstrated the hereditary nature of the disease. To counteract pébrine, Pasteur devised a preventative system: after female moths deposited their eggs, the moths themselves were macerated into a pulp. This pulp was then microscopically examined; the presence of corpuscles mandated the destruction of the corresponding eggs. Regarding flacherie, Pasteur posited a bacterial etiology. However, contemporary understanding attributes the primary cause of flacherie to viruses. Flacherie's transmission could occur either accidentally or through hereditary mechanisms. Accidental flacherie could be mitigated through rigorous hygiene practices. To prevent hereditary flacherie, only moths free of the causative microorganisms in their digestive tracts were selected for egg-laying.

Spontaneous Generation

Subsequent to his fermentation research, Pasteur established that grape skins served as the natural reservoir for yeasts, and that both sterilized grapes and grape juice failed to ferment. He extracted grape juice from beneath the skin using sterilized needles and also enveloped grapes in sterilized cloth. Neither experimental approach resulted in wine production within sterilized containers.

Pasteur's discoveries and hypotheses directly challenged the then-dominant concept of spontaneous generation. Félix Archimède Pouchet, director of the Rouen Museum of Natural History, notably issued a severe critique of Pasteur's work. To resolve this scientific dispute between the prominent researchers, the French Academy of Sciences instituted the Alhumbert Prize, offering 2,500 francs to any individual who could experimentally substantiate or refute the doctrine.

Pouchet contended that ubiquitous atmospheric air possessed the capacity to induce the spontaneous generation of living organisms within liquids. During the late 1850s, he conducted experiments which he asserted provided evidence for spontaneous generation. Earlier, in the 17th and 18th centuries, Francesco Redi and Lazzaro Spallanzani, respectively, had presented evidence challenging the concept of spontaneous generation. Spallanzani's 1765 experiments indicated that atmospheric air was a source of bacterial contamination in broths. In the 1860s, Pasteur replicated Spallanzani's experimental design; however, Pouchet reported divergent outcomes when employing a distinct broth.

Pasteur conducted a series of experiments specifically designed to refute the theory of spontaneous generation. He introduced boiled liquid into a flask, subsequently allowing hot air to enter. Upon sealing the flask, no microbial growth was observed. In a subsequent experiment, opening flasks containing boiled liquid permitted the ingress of dust, leading to microbial proliferation in a subset of these flasks. The incidence of microbial growth was inversely correlated with altitude, indicating that air at higher elevations contained reduced quantities of dust and microorganisms. Pasteur also utilized "swan neck" flasks, which contained a fermentable liquid. Air was permitted to enter these flasks through an elongated, curving tube designed to trap dust particles. No growth occurred in the broths unless the flasks were tilted, thereby allowing the liquid to contact the contaminated interior surfaces of the neck. This conclusively demonstrated that the living organisms observed in these broths originated externally, carried by dust, rather than spontaneously arising within the liquid or being generated by pure air.

These experiments represent some of the most pivotal contributions to the refutation of the theory of spontaneous generation. In 1881, Pasteur delivered a series of five presentations detailing his findings to the French Academy of Sciences, subsequently published in 1882 under the title Mémoire Sur les corpuscules organisés qui existent dans l'atmosphère: Examen de la doctrine des générations spontanées (Account of Organized Corpuscles Existing in the Atmosphere: Examining the Doctrine of Spontaneous Generation). Pasteur was awarded the Alhumbert Prize in 1862. His definitive conclusion was:

The doctrine of spontaneous generation will never recuperate from the decisive impact of this straightforward experiment. No known circumstances exist under which it can be substantiated that microscopic organisms originate without antecedent germs or without progenitors akin to themselves.

Silkworm Diseases

In 1865, Jean-Baptiste Dumas, a chemist, senator, and former Minister of Agriculture and Commerce, requested that Pasteur investigate a novel disease, pébrine, which was devastating silkworm farms across southern France and Europe. This disease was macroscopically identifiable by black spots and microscopically by "Cornalia corpuscles." Pasteur agreed, undertaking five extended visits to Alès between June 7, 1865, and 1869.

Early Misconceptions

Upon his arrival in Alès, Pasteur began to study pébrine, alongside flacherie, also known as dead-flat disease, which was a previously identified silkworm ailment. Unlike Quatrefages, who introduced the term pébrine, Pasteur initially erred by assuming that these two diseases, and indeed most known silkworm diseases, were identical to pébrine. He first differentiated between pébrine and flacherie in correspondence with Dumas on April 30 and May 21, 1867.

Pasteur committed a further error by initially refuting the "parasitic" (microbial) etiology of pébrine, a concept that several researchers, particularly Antoine Béchamp, considered firmly established. A publication by Balbiani on August 27, 1866, which Pasteur initially appeared to receive positively, had no immediate impact on his views. It was noted that "Pasteur is mistaken. He would only change his mind in the course of 1867."

Eradication of Pébrine

Before fully comprehending the etiology of pébrine, Pasteur disseminated an effective method for preventing infections: a selection of chrysalises was crushed, and the resulting material was examined for corpuscles. If the proportion of corpuscular pupae in the sample was minimal, the breeding chamber was deemed suitable for reproduction. This "seed" (egg) sorting technique resembled a method proposed by Osimo several years prior, though Osimo's trials had not yielded conclusive results. Through this process, Pasteur successfully mitigated pébrine, thereby preserving a significant portion of the Cévennes silk industry.

Flacherie's Persistence

During the Congrès international séricicole in 1878, Pasteur acknowledged that "if pébrine is overcome, flacherie still exerts its ravages." He posited that flacherie's continued prevalence was due to farmers' non-adherence to his recommendations.

By 1884, Balbiani, despite his skepticism regarding the theoretical underpinnings of Pasteur's research on silkworm diseases, conceded that Pasteur's practical methodology had effectively mitigated the devastation caused by pébrine. However, Balbiani also noted that this positive outcome was often offset by the proliferation of flacherie, a disease less understood and more challenging to control.

Despite Pasteur's successful intervention against pébrine, French sericulture ultimately did not avoid significant damage.

Immunology and Vaccine Development

Avian Cholera

Pasteur's initial investigations into vaccine development focused on avian cholera. He obtained bacterial samples, subsequently named Pasteurella multocida in his honor, from Henry Toussaint. Due to a stroke in 1868 that prevented him from conducting experiments personally, Pasteur extensively relied on his assistants, Emile Roux and Charles Chamberland. Research into avian cholera commenced in 1877, and by the following year, Roux successfully maintained a stable bacterial culture using broths. As Pasteur later documented in his notebook in March 1880, in October 1879, a delay in his return to the laboratory, occasioned by his daughter's wedding and his own ill health, led him to instruct Roux to initiate a new chicken cholera culture using bacteria from a culture that had been dormant since July. The two chickens inoculated with this novel culture exhibited some signs of infection; however, rather than succumbing to the typically fatal disease, they made a full recovery. Following an additional eight days of culture incubation, Roux re-inoculated the same two chickens. As also recorded by Pasteur in his March 1880 notebook, and contrary to certain narratives, these chickens subsequently died. Consequently, while the attenuated bacteria did not confer immunity in this instance, these experiments yielded crucial insights into the artificial attenuation of bacteria in a laboratory setting. Upon Pasteur's return, the research trajectory shifted towards developing a vaccine through attenuation.

In February 1880, Pasteur articulated his findings to the French Academy of Sciences under the title "Sur les maladies virulentes et en particulier sur la maladie appelée vulgairement choléra des poules (On virulent diseases, and in particular on the disease commonly called chicken cholera)," subsequently publishing them in the academy's official journal (Comptes-Rendus hebdomadaires des séances de l'Académie des Sciences). He postulated that bacterial virulence was diminished through contact with oxygen. He elucidated that bacteria maintained in sealed containers retained their full virulence, whereas only those subjected to aerobic conditions within culture media proved suitable for vaccine development. Pasteur coined the term "attenuation" to describe this reduction in virulence, stating before the academy:

The virulence of microorganisms can be attenuated through modifications in their cultivation methods. This principle constitutes the pivotal aspect of my current research. I respectfully request that the Academy refrain, for the present, from scrutinizing the certainty of my experimental protocols, which enable the determination of microbial attenuation, thereby safeguarding the autonomy of my investigations and ensuring their continued advancement... In conclusion, I wish to highlight two significant implications arising from the presented findings: the prospect of cultivating all microbes and the potential to develop vaccines for all infectious diseases that have persistently afflicted humanity, imposing substantial burdens on agriculture and animal husbandry.

In practice, Pasteur's vaccine developed for chicken cholera failed to consistently elicit robust immunity and was subsequently demonstrated to be inefficacious.

Anthrax

Subsequent to his findings concerning chicken cholera, Pasteur adapted the immunization methodology established for that disease to formulate a vaccine against anthrax, a significant affliction of cattle. Preceding this, in 1877, Pasteur had instructed his laboratory to cultivate the causative bacteria from the blood of infected animals, building upon Robert Koch's initial discovery of the bacterium.

The infection of animals with the bacterium invariably resulted in anthrax, thereby substantiating its etiological role in the disease. A high mortality rate among cattle due to anthrax was observed in areas colloquially termed "cursed fields." Pasteur learned that sheep succumbing to anthrax had been interred in these fields. He hypothesized that earthworms could facilitate the translocation of the bacteria to the surface. His subsequent discovery of anthrax bacteria in earthworm excrement corroborated this hypothesis. Consequently, he advised farmers against burying deceased animals within agricultural lands.

Pasteur's commitment to developing an anthrax vaccine was significantly invigorated on 12 July 1880, when Henri Bouley presented a report by Henry Toussaint, a veterinary surgeon not affiliated with the academy, before the French Academy of Sciences. Toussaint had devised an anthrax vaccine by inactivating the bacilli through heat treatment at 55 °C for 10 minutes. His vaccine was evaluated on eight dogs and eleven sheep, with half of the inoculated animals succumbing to the disease, indicating limited efficacy. Upon learning of these findings, Pasteur promptly communicated to the academy his skepticism regarding the viability of a killed vaccine, asserting that Toussaint's proposition "overturns all the ideas I had on viruses, vaccines, etc." Subsequent to Pasteur's critique, Toussaint modified his approach, employing carbolic acid (phenol) to inactivate anthrax bacilli, and tested this revised vaccine on sheep in August 1880. Pasteur maintained that such a killed vaccine would be ineffective, based on his conviction that attenuated bacteria consumed nutrients essential for bacterial proliferation. He posited that prolonged exposure of bacteria to oxygen in culture broth diminished their virulence.

Pasteur's laboratory, however, discovered that anthrax bacillus was not readily attenuated by air culturing due to its spore-forming capability, a characteristic absent in chicken cholera bacillus. In early 1881, his team identified that cultivating anthrax bacilli at approximately 42 °C rendered them incapable of producing spores, a method he formally presented in a speech to the French Academy of Sciences on February 28. Despite initial inconsistent outcomes, Pasteur announced the successful vaccination of sheep on March 21. Responding to this news, veterinarian Hippolyte Rossignol proposed that the Société d'agriculture de Melun organize a public experiment to validate Pasteur's vaccine. Pasteur formally accepted this challenge by signing an agreement on April 28. Pasteur's assistants, Roux and Chamberland, who were assigned to conduct the trial, expressed reservations about the attenuated vaccine's reliability. Consequently, Chamberland secretly prepared an alternative vaccine utilizing chemical inactivation. Without disclosing their vaccine preparation method to anyone except Pasteur, Roux and Chamberland proceeded with the public experiment in May at Pouilly-le-Fort. The trial involved 58 sheep, 2 goats, and 10 cattle; half of these animals received the vaccine on May 5 and 17, while the other half remained untreated. On May 31, Roux and Chamberland subsequently injected all animals with a fresh, virulent culture of anthrax bacillus. The official results were observed and analyzed on June 2, in the presence of over 200 spectators, including Pasteur himself. The outcomes aligned with Pasteur's confident prediction: "I hypothesized that the six vaccinated cows would not become very ill, while the four unvaccinated cows would perish or at least become very ill." Indeed, all vaccinated sheep and goats survived, whereas the unvaccinated animals had either succumbed or were in the process of dying before the assembled audience. His report to the French Academy of Sciences on June 13 concluded:

From a scientific perspective, the development of a vaccination against anthrax constituted a significant advancement beyond Jenner's initial vaccine, as the latter had never been experimentally derived.

Pasteur did not explicitly disclose the preparation methods for the vaccines utilized at Pouilly-le-Fort. Although his report characterized it as a "live vaccine," his laboratory notebooks subsequently revealed that he had, in fact, employed a potassium dichromate-killed vaccine, a technique developed by Chamberland and notably similar to Toussaint's method.

The principle that an attenuated form of a disease could confer immunity against its virulent counterpart was not novel, having been recognized for smallpox for an extended period. Inoculation with smallpox, known as variolation, was understood to induce a significantly milder illness and substantially reduce mortality rates compared to naturally acquired infection. Edward Jenner had also investigated vaccination using cowpox (vaccinia) to establish cross-immunity to smallpox in the late 1790s, leading to the widespread adoption of vaccination across most of Europe by the early 1800s.

The fundamental distinction between smallpox vaccination and the vaccinations for anthrax or chicken cholera lay in the origin of the attenuated pathogens: the latter two disease organisms were artificially weakened, thereby eliminating the necessity of identifying a naturally occurring mild form. Pasteur's pioneering work in developing artificially attenuated pathogens fundamentally transformed research in infectious diseases. In homage to Jenner's discovery, he subsequently applied the generic term "vaccines" to these artificially weakened disease agents.

In 1876, Robert Koch definitively demonstrated that Bacillus anthracis was the causative agent of anthrax. However, in his publications between 1878 and 1880, Pasteur referenced Koch's contributions only in a footnote. The two scientists met at the Seventh International Medical Congress in 1881. Several months thereafter, Koch published criticisms alleging that Pasteur had employed impure cultures and committed methodological errors. Pasteur addressed these accusations in a speech in 1882, which prompted an aggressive rejoinder from Koch. Koch asserted that Pasteur had tested his vaccine on inappropriate animal models and that his research lacked proper scientific rigor. In his 1882 treatise, "On the Anthrax Inoculation," Koch systematically refuted several of Pasteur's conclusions regarding anthrax, further criticizing Pasteur for maintaining secrecy about his methods, drawing premature conclusions, and exhibiting imprecision. In 1883, Pasteur countered by stating that his cultures were prepared using methods analogous to his successful fermentation experiments and accused Koch of misinterpreting statistical data and disregarding Pasteur's earlier work on silkworms.

Swine erysipelas

In 1882, Louis Pasteur dispatched his assistant Louis Thuillier to southern France due to an epizootic of swine erysipelas. Thuillier successfully identified the causative bacillus in March 1883. Pasteur and Thuillier subsequently enhanced the bacillus's virulence through serial passage in pigeons. They then attenuated the bacillus by passing it through rabbits, thereby developing a vaccine. Pasteur and Thuillier erroneously characterized the bacterium as having a figure-eight morphology, whereas Roux accurately described it as rod-shaped in 1884.

Rabies

Pasteur's laboratory developed the first vaccine for rabies, employing a method devised by his assistant Roux. This technique involved cultivating the virus in rabbits and subsequently attenuating it by drying the infected nerve tissue. Emile Roux, a French physician and Pasteur's colleague, initially created the rabies vaccine using this method, which produced a killed vaccine. Prior to its first human application, the vaccine underwent testing in 50 dogs. On July 6, 1885, the vaccine was administered to nine-year-old Joseph Meister, who had been severely bitten by a rabid dog. This intervention carried personal risk for Pasteur, as he was not a licensed physician and faced potential prosecution for treating a patient. Following consultation with medical professionals, he proceeded with the treatment. Over an eleven-day period, Meister received thirteen inoculations, each containing viruses attenuated for progressively shorter durations. Three months subsequent to the treatment, Meister was examined and found to be in good health. Pasteur was celebrated as a hero, and the legal implications were not pursued. Subsequent analysis of Pasteur's laboratory notebooks revealed that he had treated two individuals prior to Meister's vaccination. One patient survived but may not have contracted rabies, while the other succumbed to the disease. On October 20, 1885, Pasteur initiated successful treatment for Jean-Baptiste Jupille. Later in 1885, individuals, including four children from the United States, sought inoculation at Pasteur's laboratory. By 1886, he had treated 350 individuals, with only one subsequently developing rabies. The success of this treatment established a precedent for the development and production of numerous other vaccines. This achievement also led to the establishment of the first Pasteur Institute.

In The Story of San Michele, Axel Munthe recounts some of the risks Pasteur assumed during his rabies vaccine research:

Pasteur himself was absolutely fearless. Anxious to secure a sample of saliva straight from the jaws of a rabid dog, I once saw him with the glass tube held between his lips draw a few drops of the deadly saliva from the mouth of a rabid bull-dog, held on the table by two assistants, their hands protected by leather gloves.

Stemming from his germ theory research, Pasteur advocated for medical practitioners to sterilize their hands and surgical instruments prior to operations. Previously, such aseptic practices were rarely adopted by physicians or their assistants. Notably, Ignaz Semmelweis and Joseph Lister had previously implemented hand sanitization in medical settings during the 1860s.

Controversies

In 1878, at the age of 55 and already a French national hero, Pasteur discreetly instructed his family to withhold his laboratory notebooks from public access. His family complied, maintaining and inheriting all his documents in strict secrecy. Given Pasteur's policy of not permitting other laboratory members to maintain notebooks, this secrecy rendered numerous aspects of his research unknown until recent times. Ultimately, in 1964, Pasteur's grandson and last surviving male descendant, Pasteur Vallery-Radot, bequeathed the papers to the French National Library. However, access to these papers for historical study remained restricted until Vallery-Radot's death in 1971. A catalogue number was not assigned to the documents until 1985.

In 1995, coinciding with the centennial of Louis Pasteur's death, science historian Gerald L. Geison published an analysis of Pasteur's private notebooks in his work, The Private Science of Louis Pasteur. Geison asserted that Pasteur had presented several misleading accounts and engaged in deceptions concerning his most significant discoveries. Max Perutz subsequently published a defense of Pasteur in The New York Review of Books. Further examinations of Pasteur's documents led French immunologist Patrice Debré to conclude in his 1998 book, Louis Pasteur, that despite his genius, Pasteur possessed certain flaws. According to a book review, Debré characterized Pasteur as "sometimes unfair, combative, arrogant, unattractive in attitude, inflexible and even dogmatic".

Fermentation

Prior to Pasteur's investigations, fermentation had been a subject of scientific inquiry. During the 1830s, researchers Charles Cagniard-Latour, Friedrich Traugott Kützing, and Theodor Schwann utilized microscopy to examine yeasts, concluding that these were living organisms. However, in 1839, Justus von Liebig, Friedrich Wöhler, and Jöns Jacob Berzelius posited an alternative view, asserting that yeast was not an organism but rather a product formed through the interaction of air with plant sap.

In 1855, Antoine Béchamp, a Professor of Chemistry at the University of Montpellier, conducted experiments involving sucrose solutions, initially concluding that water was the critical factor in fermentation. By 1858, he revised his findings, asserting that fermentation was directly linked to the proliferation of molds, which necessitated air for their development. Béchamp considered himself the pioneer in demonstrating the involvement of microorganisms in the fermentation process.

Pasteur commenced his experimental work in 1857, publishing his results in the April 1858 issue of Comptes Rendus Chimie, whereas Béchamp's relevant paper was published in January of the same year. Béchamp observed that Pasteur's contributions did not introduce any novel concepts or experimental methodologies. Conversely, Béchamp was likely cognizant of Pasteur's preliminary investigations from 1857. This concurrent claim of priority regarding the discovery led to a protracted dispute between the two scientists, encompassing various scientific domains and persisting throughout their careers.

Ultimately, Béchamp's claims did not prevail, as evidenced by a BMJ obituary that noted his name was "associated with bygone controversies as to priority which it would be unprofitable to recall." Béchamp had advanced the erroneous theory of microzymes. K. L. Manchester further indicates that anti-vivisectionists and advocates of alternative medicine promoted Béchamp's work and the concept of microzymes, making unsubstantiated accusations of plagiarism against Pasteur.

Pasteur initially hypothesized that succinic acid was responsible for the inversion of sucrose. However, in 1860, Marcellin Berthelot isolated invertase, demonstrating that succinic acid did not, in fact, invert sucrose. Pasteur maintained the belief that fermentation was exclusively attributable to living cells. This stance led to a prolonged debate with Berthelot concerning vitalism, a concept Berthelot vehemently rejected. Subsequently, Hans Buchner identified zymase (a complex mixture of enzymes, rather than a single enzyme), establishing that fermentation is catalyzed by intracellular enzymes. Eduard Buchner further revealed that fermentation processes could occur independently of living cells.

Anthrax Vaccine Development

In 1881, Pasteur publicly asserted his achievement in developing the anthrax vaccine. However, the initial development of this vaccine is attributed to Henry Toussaint, who transitioned from an admirer to a rival of Pasteur. Toussaint had isolated the bacterium responsible for chicken cholera in 1879 (later designated Pasteurella in Pasteur's honor) and provided samples to Pasteur for his research. On July 12, 1880, Toussaint presented his successful findings to the French Academy of Sciences, detailing the use of an attenuated anthrax vaccine in dogs and sheep. Driven by professional rivalry, Pasteur challenged this discovery by publicly demonstrating his own vaccination method at Pouilly-le-Fort on May 5, 1881. Subsequently, Pasteur provided an inaccurate description of the anthrax vaccine's preparation used in his experiment. He claimed to have created a "live vaccine," yet he employed potassium dichromate to inactivate anthrax spores, a technique analogous to Toussaint's. This highly publicized experiment proved successful, contributing to the commercialization of Pasteur's products and securing him significant acclaim and recognition.

Ethical Considerations in Experimentation

Pasteur's experimental practices, particularly his vaccination of Joseph Meister, are frequently cited as contravening medical ethics. Notably, Pasteur lacked both experience in medical practice and a medical license, a fact often highlighted as a significant challenge to his professional and personal standing. His close collaborator, Émile Roux, who possessed medical qualifications, declined to participate in the clinical trial, presumably due to ethical concerns. Nevertheless, Pasteur proceeded with the boy's vaccination under the direct observation of practicing physicians Jacques-Joseph Grancher, who headed the pediatric clinic at the Paris Children's Hospital, and Alfred Vulpian, a member of the Commission on Rabies. Although Pasteur supervised the inoculations, he was not permitted to administer the syringe. Grancher assumed responsibility for the injections and subsequently defended Pasteur's actions before the French National Academy of Medicine regarding this matter.

Criticism has been leveled against Pasteur for maintaining secrecy regarding his procedures and for failing to conduct adequate preclinical trials on animals. Pasteur asserted that the confidentiality of his method was necessary for quality control, though he subsequently revealed his procedures to a select group of scientists. While Pasteur documented having successfully vaccinated 50 rabid dogs prior to administering the treatment to Meister, Geison's analysis of Pasteur's laboratory notebooks indicates that only 11 dogs had been vaccinated.

Awards and Honors

In 1853, the Pharmaceutical Society recognized Pasteur with 1,500 francs for his synthesis of racemic acid. The Royal Society of London bestowed upon him the Rumford Medal in 1856 for his elucidation of racemic acid's nature and its relationship to polarized light, followed by the Copley Medal in 1874 for his contributions to fermentation research. He was subsequently elected as a Foreign Member of the Royal Society (ForMemRS) in 1869.

The French Academy of Sciences conferred several accolades upon Pasteur, including the 1859 Montyon Prize for experimental physiology in 1860, and both the Jecker Prize in 1861 and the Alhumbert Prize in 1862 for his empirical disproof of spontaneous generation. Despite unsuccessful bids for membership in 1857 and 1861, he secured election to the mineralogy section of the French Academy of Sciences in 1862. He later served as permanent secretary of the academy's physical science section from 1887 to 1889. Concurrently, in 1866, he was granted honorary membership in the Manchester Literary and Philosophical Society.

Pasteur's distinguished career continued with his election to the Académie Nationale de Médecine in 1873, the same year he was appointed commander in the Brazilian Order of the Rose. In 1881, he gained a seat at the Académie française, succeeding Émile Littré. The Royal Society of Arts presented him with the Albert Medal in 1882. His international recognition expanded in 1883 with his election as a foreign member of the Royal Netherlands Academy of Arts and Sciences, followed by membership in the American Philosophical Society in 1885. On June 8, 1886, Ottoman Sultan Abdul Hamid II conferred upon Pasteur the Order of the Medjidie (I Class) and a monetary award of 10,000 Ottoman liras. He received the Cameron Prize for Therapeutics from the University of Edinburgh in 1889. In 1895, the Royal Netherlands Academy of Arts and Sciences awarded Pasteur the Leeuwenhoek Medal for his significant contributions to microbiology.

Pasteur's progression within the Legion of Honour began with his appointment as a Chevalier in 1853. He was subsequently promoted to Officer in 1863, Commander in 1868, Grand Officer in 1878, and ultimately attained the rank of Grand Cross in 1881.

Legacy

Numerous streets globally bear Pasteur's name as a tribute. Examples include locations in the United States (Palo Alto and Irvine, California; Boston and Polk, Florida, adjacent to the University of Texas Health Science Center at San Antonio); Jonquière, Québec, Canada; San Salvador de Jujuy and Buenos Aires, Argentina; Great Yarmouth, Norfolk, United Kingdom; Jericho and Wulguru, Queensland, Australia; Phnom Penh, Cambodia; Ho Chi Minh City and Da Nang, Vietnam; Batna, Algeria; Bandung, Indonesia; Tehran, Iran; Warsaw, Poland (near the central campus of Warsaw University); Odesa, Ukraine (adjacent to the Odesa State Medical University); Milan, Italy; and Bucharest, Cluj-Napoca, and Timișoara, Romania. Notably, Avenue Pasteur in Saigon, Vietnam, is among the few streets in that city to retain its original French designation. In Boston's Longwood Medical and Academic Area, Avenue Louis Pasteur was named in his honor, adhering to the French convention of placing "Avenue" before the dedicatee's name.

Both the Institut Pasteur and Université Louis Pasteur bear his name. Educational institutions named in his honor include Lycée Pasteur in Neuilly-sur-Seine, France, and Lycée Louis Pasteur in Calgary, Alberta, Canada. Healthcare facilities also commemorate Pasteur, such as the Louis Pasteur Private Hospital in Pretoria and Life Louis Pasteur Private Hospital in Bloemfontein, South Africa, as well as the Louis Pasteur University Hospital in Košice, Slovakia.

A statue commemorating Pasteur stands at San Rafael High School in San Rafael, California. Additionally, a bronze bust of Pasteur is located on the French Campus of Kaiser Permanente's San Francisco Medical Center. This sculpture, designed by Harriet G. Moore, was cast in 1984 by Artworks Foundry.

The UNESCO/Institut Pasteur Medal, established on the centenary of Pasteur's death, is awarded biennially in his honor. This prestigious recognition acknowledges exceptional research that significantly benefits human health.

French Academician Henri Mondor remarked, "Louis Pasteur was neither a physician nor a surgeon, yet his contributions to medicine and surgery are unparalleled."

Pasteur Institute

Following the development of the rabies vaccine, Pasteur advocated for the establishment of a dedicated institute. In 1887, a fundraising campaign for the Pasteur Institute commenced, attracting international donations. The institute's official charter, registered in 1887, outlined its dual objectives: "the treatment of rabies according to the method developed by M. Pasteur" and "the study of virulent and contagious diseases." The institution was formally inaugurated on November 14, 1888, bringing together a diverse group of scientists. Its initial five departments were led by two graduates of the École Normale Supérieure—Émile Duclaux (general microbiology research) and Charles Chamberland (microbe research applied to hygiene)—alongside biologist Élie Metchnikoff (morphological microbe research) and physicians Jacques-Joseph Grancher (rabies) and Émile Roux (technical microbe research). A year after the institute's opening, Roux initiated the world's first microbiology course, then known as Cours de Microbie Technique (Course of microbe research techniques). Since 1891, the Pasteur Institute has expanded globally, now encompassing 32 institutes across 29 countries worldwide.

Personal Life

In 1849, Pasteur married Marie Pasteur (née Laurent), the daughter of the University of Strasbourg's rector, who also served as his scientific assistant. The couple had five children, three of whom tragically died during childhood. Their eldest daughter, Jeanne, born in 1850, succumbed to typhoid fever at the age of nine in 1859 while attending boarding school in Arbois. In 1865, their two-year-old son, Camille, died from a liver tumor. Shortly thereafter, they brought Cécile home from boarding school, but she also died of typhoid fever on May 23, 1866, at the age of twelve. Only Jean Baptiste (born 1851) and Marie Louise (born 1858) lived to adulthood. Jean Baptiste later served as a soldier in the Franco-Prussian War.

Faith and Spirituality

Louis Pasteur Vallery-Radot, Pasteur's grandson, documented that Pasteur retained only a spiritual outlook from his Catholic upbringing, devoid of religious practice. Conversely, Catholic commentators frequently asserted that Pasteur maintained fervent Christian beliefs throughout his life. His son-in-law, in a biographical account, noted:

Absolute faith in God and in Eternity, coupled with a conviction that the capacity for good bestowed upon humanity in this world would persist beyond it, permeated his entire existence. The virtues of the gospel consistently guided him. Demonstrating profound respect for the religious traditions of his ancestors, he naturally sought spiritual solace in them during the final weeks of his life.

An October 18, 1902, entry in The Literary Digest quotes Pasteur stating that he prayed during his work:

Future generations will undoubtedly deride the folly of contemporary materialistic philosophers. The deeper my study of nature, the greater my astonishment at the Creator's work. I engage in prayer while conducting my laboratory research.

Maurice Vallery-Radot, an outspoken Catholic and grandson of Pasteur's son-in-law's brother, similarly contended that Pasteur remained fundamentally Catholic. Both Pasteur Vallery-Radot and Maurice Vallery-Radot assert that the widely circulated quotation attributed to Pasteur—"The more I know, the more nearly is my faith that of the Breton peasant. Could I but know all I would have the faith of a Breton peasant's wife"—is apocryphal. Maurice Vallery-Radot indicated that this spurious quotation first emerged shortly after Pasteur's death. Nevertheless, despite his belief in God, Pasteur's perspectives have been characterized as those of a freethinker rather than a strict Catholic, emphasizing spirituality over formal religion. He also opposed the conflation of scientific inquiry with religious doctrine.

Death

Louis Pasteur experienced a debilitating stroke in 1868, which resulted in left-sided paralysis, though he subsequently recovered. However, his health significantly deteriorated in 1894 due to another stroke or uremia. Unable to achieve a full recovery, he passed away on September 28, 1895, in the vicinity of Paris. Following a state funeral and initial interment at the Cathedral of Notre Dame, his remains were later reinterred within the Pasteur Institute in Paris, resting in a vault adorned with Byzantine mosaics illustrating his scientific achievements.

Publications

The primary published works by Pasteur include:

Infection Control

References