Louis Pasteur’s risky move to save a boy from almost certain death

Louis Pasteur: The Man Who Saved Billions of Lives
https://www.youtube.com/watch?v=oLKaJtv-QbU

Images
1. Front Marie and Louis Pasteur with their grandchildren Louis and Camille. Rear Pierre Vallery-Radot, René Vallery-Radot and his wife Marie-Louise Pasteur
2. Birth of his son Jean-Baptiste 1851
3. 1853 Birth of his daughter Cécile (died in 1866).
4. Louis Pasteur 'When I approach a child, he inspires in me two sentiments; tenderness for what he is, and respect for what he may become.'

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Abstract
Louis Pasteur long has been heralded as the “father of modern hygiene, public health and much of modern medicine,” despite early controversies regarding his findings and methodology. A recently published biography, however, has shed new light on both Pasteur's scientific acumen and integrity. Reactions to this portrayal have been mixed. This article provides an overview of Pasteur's life and the debate regarding his scientific discoveries and honesty that has ensued for more than 100 years, with insights gained from both supporters and critics of the new biography by Gerald L. Geison. Copyright 2002, Elsevier Science (USA). All rights reserved.

Louis Pasteur long has been heralded as the “father of modern hygiene, public health and much of modern medicine,”1 as well as the father of microbiology and immunology. One of the hallmarks of his research is the extensive breadth of his accomplishments. Pasteur himself believed that his research was “enchained to an inescapable, forward-moving logic, and, certainly, from the distance of time, we see how one discovery, one concept, led almost ‘inescapably’ to another.”2 Until recently, with the 1995 publication of a biography by Gerald L. Geison3 that was the winner of the 1996 William H. Welch Medal of the American Association for the History of Medicine, few people had questioned either Pasteur's personal life or his scientific acumen. Geison sheds new light on both aspects. Reactions to his portrayal have been mixed, ranging from accolades of its being “not just a book but a historical treatise [in which he] paints a detailed picture of Pasteur, illuminating a great yet imperfect man who was both a strong, diligent, and driven researcher and teacher and a sometimes secretive and deceptive brute”4 to calling it a “rather filthy ‘objective’ story [in which] Geison inflates every ‘small hocus-pocus’ out of all proportions.”5 This article does not seek to make an evaluation of either Pasteur's work or Geison's book, but instead provides an overview of Pasteur's life and the debate regarding his scientific acumen and honesty that has ensued for more than 100 years, with insights gained from both Geison's supporters and his critics.


Personal life
Pasteur was born in 1822 in Dole, the only son of a poorly educated tanner, Jean Pasteur, who had served in Napoleon's grande armee.[6], [7] He spent his early childhood in Arbois. Because Pasteur was not particularly interested in scholastic endeavors, his years of elementary education were those of a rather mediocre student, one who preferred to go fishing and to draw various subjects. Geison describes Pasteur's early childhood as being one also with memories of the screams of villagers having their wolf bites cauterized by the local blacksmith's hot iron to prevent rabies, which later greatly influenced his research. Not until he went to college, where his art work, primarily portraits of classmates, continued to show indications of a promising superior portrait artist, did Pasteur's academic acumen become apparent. In 1840, he earned a BA degree from the Royal College in Besancon, and in 1842, he earned a BSc. His father's greatest desire was that his son complete his education and become a professor in the college at Arbois. The headmaster of the college had other goals, however, having recognized Pasteur's potential for far better options, and recommended that Pasteur apply for admission to the Ecole Normale Superieure in Paris to study chemistry. The university had been founded specifically to train outstanding students for university careers in science and letters and was the most prestigious French University. Pasteur spent 3 years of this time tutoring younger students and preparing for the Ecole Normale Superieure.8
Pasteur was accepted by the university and, with his matriculation in 1843, embarked on a long journey into a scientific milieu.[1], [2], [5], [6] In 1845, he became licencie es sciences (the equivalent of a Master of Science), and in 1847 he graduated with a docteur es sciences (doctor of philosophy) in science. The next year (1848), he accepted a position as professor of physics at Dijon Lycee and in 1849 the post of Professor of Chemistry at the University of Strasbourg. On May 29, 1849, he married Marie Laurent, the daughter of the rector of the university. She proved to be a devoted wife and scientific comrade for the remainder of his life. They later had 5 children, only 2 of whom survived.[2], [5], [6]
In 1854, Pasteur was appointed Dean and Professor of Chemistry at the Faculty of Sciences in Lille, France. The industrial city was the home of numerous distilleries and factories, and the Minister of Public Instruction was not completely supportive of “science for science's sake.” The Minister is quoted as reminding the university faculty that “whilst keeping up with scientific theory, you should, in order to produce useful and far reaching results, appropriate to yourselves the special applications suitable to the real wants of the surrounding country.”2 According to certain reports, Pasteur was an ideal candidate for this environment because he enjoyed taking his students on tours of the factories and informed managers at the distilleries that he was available for consultation if they encountered a problem. His offer led to the discovery of alcohol fermentation, as described below.

Early discoveries
By the time he moved to Strasbourg, Pasteur already had gained recognition, at the age of 26, from a paper on the optical activity of stereoisomers presented before the Paris Academy of Sciences.6 The discoveries arose from investigations of tartaric acid he undertook while working on his doctorate in chemistry in the laboratory of Antoine Balard. At the time, crystallography was an emerging branch of chemistry, and Pasteur's project involved crystallizing numerous different compounds. He began working with tartaric acid, the crystals of which are present in large amounts in the sediments of fermenting wine. Crystals of another acid, paratartaric acid or “racemic acid,” often were found in the sediments of wine barrels. Although a few years earlier the chemical compositions of the two acids had been determined to be identical, in solution they displayed striking differences: tartaric acid rotated a beam of polarized light passing through it to the right, whereas paratartaric acid did not rotate the plane of polarized light.[7], [9]
The finding intrigued Pasteur, who refused to accept the notion that the 2 acids had the same chemical composition. Contrary to accepting the prevailing theory, he was convinced that the internal structures of the 2 compounds must be different and that the difference could be demonstrated in the crystal form. Determined to arrive at a reason for the different reactions to the beam of light, he began intensely examining the 2 acids under a microscope. He finally detected the difference: in the pure tartaric acid, every crystal looked like every other one, but the crystals in the paratartrate acid had the distinction of having mirror images. Quite excited at having detected these mirror images, he then performed what has been called “one of the simplest and yet most elegant experiments in the annals of chemistry.”2 Using a specialized microscope, he separated the 2 types (“left-handed” and “right-handed”) of crystals into 2 piles and then demonstrated that in solution, one form rotated light to the left, whereas the other rotated it to the right. The simple experiment showed that organic molecules with the same chemical composition can exist in space in unique stereospecific forms. This discovery of asymmetry of organic molecules provided Pasteur with the logic that then led to his studies on alcoholic fermentation.[2], [7], [8], [10], [11]

Fermentation and pasteurization
Pasteur's willingness to engage in consultations with the managers of the distilleries in the town of Lille led in 1856 to his receiving a request for assistance from M. Bigot, the father of one of his students. Bigot was having difficulties manufacturing alcohol by fermentation of beetroot: instead of alcohol, lactic acid was being produced. At that time, fermentation leading to the production of wine, beer, and vinegar was thought to be a straightforward chemical breakdown of sugar to the desired molecules, due, according to the chemical experts of the day, to the presence of inherent unstabilizing vibrations. The theory was that one could transfer these vibrations from a vat of finished wine to new grape pressings to start a new process of fermentation.[2], [7], [9], [10]
Although yeast cells had been found in the fermenting vats of wine and recognized as being live organisms, researchers thought they were either a product of fermentation or catalytic agents that provided useful ingredients to the fermentation process. The information provided to the distilleries was of little use, and the brewers were facing economic distress related to adverse results of fermentation: yields of alcohol suddenly falling; wine being unexpectedly ropy or sour or, worse, turning to vinegar; and vinegar failing to form when it was needed, with lactic acid occurring instead.[2], [7], [9], [10]
Pasteur's call for assistance brought him into this milieu, where he soon made 3 findings that led to a new awareness of alcohol fermentation. He first noted that alcohol normally produced yeast cells that were plump and budding, but when lactic acid formed instead, small rodlike microbes always were mixed with the yeast cells. Next, his analyses of the batches of alcohol showed that amyl alcohol and other complex organic compounds were being formed during the fermentation process and their formation could not be explained by the simple catalytic breakdown of sugar. He determined that some additional process had to be taking place. The third finding, which probably proved to be the critical clue, was that some of the compounds rotated light, indicating that they were asymmetric. Based on his earlier conclusion that only living cells produce asymmetrical compounds, he now determined and was able to demonstrate that living cells, namely the yeast, were the agents responsible for forming alcohol from sugar and that contaminating microorganisms were the culprits that turned the fermentations sour. During the next few years, Pasteur identified and isolated the specific microorganisms that were responsible for both normal and abnormal fermentations in the production of wine, beer, and vinegar. He also showed that heating these products to moderately high temperatures for a few minutes would kill the living microorganism and, thereby, sterilize (or pasteurize) them and prevent any degradation.[2], [7], [9], [10]

Spontaneous generation
While Pasteur's findings on fermentation were eliciting excitement and speculation from the scientific world, a long-standing debate concerning spontaneous generation was receiving considerable attention. Although his colleagues cautioned Pasteur to avoid entering the fray, he thought that his findings with regard to sources of yeasts and other microorganisms that were found during fermentation and putrefaction perhaps offered a clue. Pasteur performed a series of investigations that basically destroyed every argument given in support of the “spontaneous generation” theory. He first demonstrated that the skin of grapes at the beginning of the grape harvest was the source of the yeast. He did so by drawing grape juice from under the skin with sterile needles and showing that it would not ferment. He then demonstrated how covering the grape arbors with fine cloth or wrapping the grapes with cotton to protect them from contaminating dust yielded grapes that would not produce wine. By allowing air collected at different altitudes to enter sterilized vessels containing fermentable solutions, he showed that dust of the air carried the contaminants and that the higher the altitude, the less dust in the air, and, hence, the fewer contaminants.2
The convincing argument was his experimental design using the swan-neck flask, for which he placed fermentable juice in a flask; heated the neck and drew it out as a thin tube, taking a gentle downward then upward arc that resembled the neck of a swan; and then sealed the end of the neck. As long as the neck remained sealed, the contents did not change; as soon as the flask was opened, air entered but was trapped on the wet walls of the neck, thereby keeping the fluid sterile and showing that air alone could not trigger the fermentation process. Once the flask was tipped to allow the liquid to touch the contaminated walls, growth of microorganisms began immediately. He is quoted as saying in 1864, “Never will the doctrine of spontaneous generation recover from the mortal blow of this simple experiment. There is no known circumstance in which it can be confirmed that microscopic beings came into the world without germs, without parents similar to themselves.[2], [7], [9], [10], [12]

Silk worms
Subsequently, Pasteur was asked by the Department of Agriculture to head a commission to investigate a devastating disease of silkworms that was destroying the French silk industry. Pasteur knew nothing about silkworms, nor did he have any idea that they suffered from diseases, but he accepted the challenge. He first encountered 2 different types of silkworm disease: pebrine, which usually, but not always, causes black spots and corpuscles on the worm, and flacherie, which does not produce spots but causes a lethargy that prevents the worms from spinning cocoons. By selectively breeding eggs of only those worms not demonstrating either disease, he was able to produce healthy worms and to show the silkworm breeders how to identify and eliminate the sick worms from their stock, thereby returning the silk industry in France, Italy, and other European countries to its former status.2
These studies he considered as landmarks in the study of infections and infectious diseases. His expanded research revealed that healthy worms became infected when they were allowed to nest on leaves that had been used by infected worms and that the susceptibility of the worms varied widely, with some worms dying shortly after being infected, some dying weeks later, and some not dying at all. From these observations, he determined that other factors, such as temperature, humidity, ventilation, sanitation, and adequate separation of the brooks of newly hatched worms all played a role in susceptibility to disease. These studies launched the awareness of environmental factors on contagion.2

Germ theory of disease and vaccination
His crowning achievement was providing the germ theory of disease, which also led to discoveries associated with various individual diseases, including anthrax and rabies (addressed later in this article); the development of vaccines; and a controversy regarding his methodology that continues to this day. After Pasteur demonstrated the existence of microbes that affected the juice of grapes, many physicians began to sterilize their instruments and bandages, and by 1875, the recognition that many diseases were accompanied by specific microorganisms was becoming more accepted. Nonetheless, the prevailing consensus was that diseases such as cholera, diphtheria, scarlet fever, and smallpox, among others, could not be caused by such agents. One extreme example was provided by Pasteur's son-in-law, who described the closing of the hospital and the transfer of women from the Paris Maternity Hospital after 64 fatalities caused by childbirth fever occurred in 347 confinements. Sadly, the disease was not eliminated, and almost all of the women died. Pasteur became convinced that the infection was being spread by physicians and hospital attendants, who were taking the disease from sick patients to healthy ones, and urged them to avoid contracting and spreading the microbes.2

Chicken cholera
The development of vaccinations was the direct product of studies he performed on chicken cholera that at the time was a serious problem for farmers. The disease would spread through a barnyard rapidly and was capable of wiping out an entire flock in as few as 3 days. He determined that the disease could be spread by contaminated food or animal excrements, and he was successful in identifying and culturing the cholera bacillus. Chickens injected with the bacillus died within 48 hours.
In the summer of 1881, Pasteur stored his cultures on the shelves of the Arbois and left Paris to escape the heat. When he returned to Paris at the end of the summer, he attempted to inoculate chickens with the stored Cholera bacilli. Instead of becoming ill, the chickens remained healthy. Disappointed with the results, his group then set to work to make new cultures of the bacillus, which they tested on new birds as well as those that had remained healthy after being inoculated with the “old” culture. They were astonished at the results: whereas the new birds all died, the birds inoculated previously continued to remain healthy.
Pasteur recognized that his results were similar to those of Edward Jenner's experiments conducted 80 years earlier, which had conferred on humans immunity to smallpox by vaccinating them with a mild form of cowpox (for biography of Edward Jenner, see Seminars in Pediatric Infectious Disease 12:81-84, 2001).13 This “chance” observation, though now questioned as being so “accidental,” led Pasteur to the idea of attenuation and vaccination, the latter term (meaning artificial induction of protection) being coined by Pasteur in honor of Jenner. Pasteur reproduced attenuated cultures of chicken cholera vaccines, which were used routinely to prevent cholera in chickens. These series of observations in chickens also inaugurated the fields of immunology and vaccinology.[2], [14] However, even this finding is not without its questionable components. Later, in the debate that ensued between Pasteur and Robert Koch, the great German physician and scientist, Koch argued that Pasteur's “chicken-cholera” was of no practical use to the poultry men and that the existence of a specific pathologic microbion of such a disease had yet to be demonstrated.15

Anthrax
At approximately the same time that farmers were having difficulty with their chickens dying, a fatal disease was striking sheep and cattle, crippling the sheep industry and the French economy. Koch had isolated anthrax bacillus, previously identified by the French physician Davain, from the spleens of infected cattle and had shown that under resting conditions the bacillus formed long-lived spores. However, definitive proof that the cultured bacillus itself was causing the disease, rather than another product of Koch's culture medium, was still lacking when Pasteur entered the scene. According to Dubos, Pasteur placed a drop of blood from a sheep dying of anthrax into 50 mL sterile culture, grew the bacterium, and repeated the process 100 times. Although the experiment represented a huge dilution of the original culture, the final culture, which contained not a single molecule of the original culture, was as active as was the first one in producing anthrax. Because only the bacillus itself, by growing each time in the new culture, could escape the dilution, Pasteur's studies proved beyond any doubt that the anthrax bacillus alone could be responsible for the disease. These results confirmed and firmly established Pasteur's germ theory, but the means of spread of the disease remained a mystery.2
According to some accounts, his earlier finding on silkworms provided a clue. While traveling through a field where sheep were grazing, Pasteur noted that the ground in one portion was a different color from the other ground. Upon inquiring, he learned that the farmer had buried some sheep that had died of anthrax and that the color of the soil was caused by earth worm casts. Pasteur then realized that the worms feeding on the carcasses of the sheep were bringing the anthrax spores to the surface, with the result that other sheep were grazing on the contaminated soil. Although one means of containing the disease was to keep the sheep from the contaminated ground, Pasteur realized that more was needed, and he determined to apply what he had learned about vaccination of the chickens to the problem being encountered with anthrax. Various techniques of oxidation and aging were used to create a vaccine that was reported as being successful in preventing anthrax in laboratory trials.2
Despite the excitement generated by the findings, a well-known veterinarian, Rossignol, found the reports unbelievable and challenged Pasteur to conduct a carefully controlled public trial at Pouilly le Fort, a farm in the town of Melun south of Paris. The terms required that 25 sheep be used as controls and another 25 be vaccinated by Pasteur, after which all animals would receive a lethal dose of anthrax. In order for Pasteur's claims to be accepted, all of the control sheep had to die and all of the inoculated sheep had to live. Some of his constituents were concerned about the terms, noting that the vaccines were still in the developmental stage, but Pasteur, a showman as well as a researcher, was happy to accept the challenge. Public interest was intense, with a reporter from the London Times sending back daily dispatches, newspapers in France following the events with daily bulletins, and crowds of onlookers forming a carnival atmosphere. Even Pasteur is reported as being privately concerned that he had acted too soon and impetuously in accepting Rossignol's challenge. The experiment, however, proved to be a complete success: 2 days after the final inoculation was given (May 5, 1882), all 25 control sheep were dead, and all 25 inoculated sheep were still living. News spread throughout France and Europe and beyond, and within 10 years, a total of 3.5 million sheep and one-half million cattle had been vaccinated, with a mortality rate of less than 1 percent. The immediate savings to the French economy were enormous. Pasteur expanded his studies to identify and isolate during the next 2 to 3 years the microbes for many other diseases, including swine erysipelas, childbirth fever, and pneumonia.[2], [7], [9], [10]
Not everyone found Pasteur's experiments as convincing as he claimed them to be, however. In fact, Koch raised numerous objections in an enormous acrimonious dispute that developed between him and Pasteur and became a focus of the International Congress of Hygiene at Geneva, recorded in the Boston Medical and Surgical Journal of January 18, 1883. In addition to bringing numerous charges, described by the Journal as an “arraignment” (Table 1), Koch attacked Pasteur's claim of having discovered and enunciated a general law for the modification of poisons and their protective inoculation of infectious diseases (Table 2); the only exception Koch allowed was the splenic fever (anthrax), for which he noted that even for this one disease the results were “thus limited to sheep, and both the strength of the virus to be used for the first and second inoculations and the length and degree of protection secured are still very uncertain, much more uncertain than Pasteur has acknowledged.”15Koch also acknowledged that Pasteur's modification of the virus was much better than Toussaint's (who first inoculated the modified virus; see below), but he challenged Pasteur's “interpretation of the process by which the modification is brought about” as being incorrect, for “it is not, as his own experiments show, the direct action of oxygen which produces the modification, but the presence of products evolved by the microbions themsleves, an evolution favored by oxygen, by elevation of temperature, and replaced by the presence of carbolic compounds.”15
Table 1. Summary of some Koch's basic charges against Pasteur as presented in the Boston Medical and Surgical Journal editorial
• Pasteur goes much too fast and too far in proclaiming the discovery and development of a general method of protective inoculation against infectious disease.
• Two latest examples cited by Pasteur in favor of such a position are not merely absolutely valueless in that respect but admirably exhibit Pasteur's false methods of investigation.
• Pasteur's methods led to false conclusions.
• Pasteur's methods depart from the rules Koch considers necessary for proper research (see Table 2).

• Pasteur's methods and results are unreliable because of the absence of proper microscopical research, the inoculation of mixed substances, and selection of unsuitable animals for the experiments.
Table 2. Summary of Koch's requirements for proper scientific investigations of infectious diseases15
• Proof that an infectious disease is caused by parasitic microorganisms must be found in each separate case of the parasitic nature of the disease.
• The first step of such proof involves careful examination of all parts of the body affected by the disease for the presence of parasites, a knowledge of their relative frequency in the affected organs, and knowledge of their relation to the tissues.
• All the aids that the microscopical technique of the present day offer are to be brought to bear upon such an examination.
• Microorganisms thought to be of a pathological nature and the specific cause of the disease in question must be propagated in unmixed cultures and then inoculated in the same species of animal as that originally attacked, or at least upon such animals as are well known by unmistakable symptoms to be subject to the disease in question.
More recently, Geison, in his biography of Pasteur,1 not only reveals the initial defects of the much-publicized anthrax vaccine, but demonstrates that Pasteur secretly incorporated his rival's (Toussaint's) findings to make his version of the vaccine work. Using Pasteur's original notebooks, Geison portrays the race to develop the anthrax vaccine among numerous instances of Pasteur's success depending not solely on his scientific talents, but also on his rhetorical skills and his willingness to conceal any inconvenient details of his research.16 Basically, this newer biography elaborates the issue with regard to the vaccine first developed by veterinarian Toussaint, arguing that Pasteur took the vaccine and presented it as his own at Pouilly-le-Fort. Another reviewer seems surprised that Geison's portrayal is presented as original, stating that an earlier biography by Vallery-Raddot17 had already admitted both Toussaint's priority in developing an anthrax vaccine and the fact that Pasteur simply followed and repeated his experiments. Although admitting that the “obvious distortion” of facts in Raddot's account “leaves many questions about Toussaint-Pasteur relations and does not look absolutely honest,” the review goes on to charge Geison with “producing a cheap sensation rather than historical treatise out of this intriguing episode. In fact, Geison retails [sic] the official version of relations between Toussaint and Pasteur as his own iconoclastic discovery, which gives him a logical pretext to make a decisive claim that vaccine made by Tussaint [sic] was identical to that used by Pasteur at Pouilly-le-Fort.” However, even the charge that Geison was remiss in not knowing that “the name of Tussaint was not Geison's discovery” apparently overlooks the early reference by Koch noted above. These instances all demonstrate that the controversy and often heated debates about Pasteur's work that began with Koch continue to this day.
Rabies
The most famous, and perhaps the most controversial, aspect of Pasteur's research was the development of a vaccine against rabies, or hydrophobia. Because of the horrific visions often evoked of “raging victims, bound and howling, or asphyxiated between two mattresses,”2 the disease had long been a source of public concern and fear. Reports of methods used to treat victims, such as cauterizing the bite wounds with red-hot pokers, elicited as much fear as did the disease itself. Although few persons died in any year from the disease and often symptoms did not present for weeks to months, if at all, Pasteur and his young colleague Emile Roux (later Director of the Pasteur Institute in Paris from 1904 to 1933) recognized the public acclaim that would be theirs if rabies could be conquered.2 Pasteur recently had been elected a member of the Academie Francaise in April 27, 1882, and he realized the advantages such publicity would have for both his own research and the academy.
In their initial experiments, Pasteur and Roux attempted to transfer infection by injecting healthy dogs with saliva from rabid animals, but the results varied and were unpredictable. Once they determined that the active agent was in the spinal cord and brain, they applied the extracts of rabid spinal cord directly to the brains of dogs, which produced rabies in the test animals in the course of a few days. Their goal then became to develop a vaccine that would protect the subject before the rabic agent moved from the site of the bite to the spinal cord and the brain. This protection was accomplished by injecting into test animals suspensions of spinal cord of rabid rabbits that were attenuated in strength by air-drying for a 12-day period in what is now called the Roux Bottle. They suspended a strip of spinal cord from a hanger in the center of a bottle containing a hole at the top of the bottle and one on the lower side. Air entering from the bottom opening passed over a drying agent and exited from the top. The longer the cord was dried, the less potent was the tissue in producing rabies.2
The treatment plan for developing immunity involved injecting under the skin of a dog the least potent preparation of minced spinal cord, followed by injecting stronger and stronger extracts on subsequent days, “separated by an interval of two days, until one [reached] the most virulent spinal tissue, that was placed for only a day or two in the flask. In this manner [was] the dog rendered immune to rabies.”18 By the end of the course, the dog supposedly was completely resistant to bites of rabid dogs and failed to develop rabies even when the most potent extracts were applied to their brains. Pasteur claimed to have used the method on 50 dogs of all ages and breeds refractory to rabies, without a single failure.18 The reports of their success were published, and as they had expected, Pasteur and Roux received wide acclaim and much favorable publicity, which led to pressure to reproduce the results in humans. Initially, Pasteur hesitated, partly for fear of consequences if something went wrong and partly because he was unable to isolate the rabic substance.[2], [7], [9], [10], [18], [19]
However, a specific incident, with a later tragic and poignant ending, launched Pasteur into the limelight again. According to Pasteur, on July 6, 1886, 3 persons appeared at his laboratory: Theodore Vone, a grocer from Meissengst and a mother accompanied by her 9-year-old son, Joseph Meister. Both the grocer and the child had been bitten by the same dog, which proved several days later to be rabid. Because the grocer's arm had been covered and the sleeve had not been pierced, Pasteur saw no potential danger and sent him home. However, the child had been bitten repeatedly (Pasteur recounts 14 times) and was so badly mauled that he could hardly walk. The mother begged Pasteur, who supposedly had treated approximately 50 dogs, most of which had resisted the disease, to treat her son.18 According to one version of the event, Pasteur consulted with physician colleagues (Pasteur was not a medical doctor) and, having overcome his own trepidation, agreed to treat the child.[2], [18] Despite Pasteur's supposed concerns, Meister made a complete recovery and remained in good health for the remainder of his life. Later, Meister came to the Pasteur Institute (which had been inaugurated 2 years after his own incident with rabies) as an employee and served for many years as gatekeeper. When, many years later in 1940, German troops ordered him to open Pasteur's crypt, Meister committed suicide rather than comply.
A few months after Pasteur successfully treated Meister, another young victim, a shepherd who had been bitten by a “mad dog,” appeared. After successfully treating him as well, Pasteur became widely known, and reports of these successes brought victims of dog and wolf bites from France, Russia, and the United States pouring into his laboratory for treatment. Pasteur became a national hero and a legend, and, with funding from public and governmental subscriptions, was able to build the Pasteur Institute in Paris. It initially was designed to treat victims of rabies; later, other Pasteur Institutes, including 3 in the United States, were built to treat human rabies and other diseases.2
More recently, the account has been described in less laudatory terms with regard to Pasteur. According to Geison, when Meister appeared, Pasteur had been reporting animal experiments using “attenuated” rabies vaccine produced by repeated passage of infectious nervous tissue through dogs or monkeys. His college, Roux, considered an able physician, had been working with a killed vaccine produced by desiccating the spinal cords of infected rabbits. Pasteur used Roux's idea and this vaccine on the young Meister. Several ethical issues are raised in this account: one, that Roux apparently decided the risk of causing rabies by possible inadequate inactivation of the infectious spinal cord tissue was too high, but Pasteur decided otherwise and used a vaccine he had tested in only 11 dogs (he stated 50 in his paper), and the other being that Pasteur concealed the process he used to make the vaccine, allowing the scientific community to believe that the vaccine injected into Meister was an “attenuated” one. Both charges are based on his laboratory notes, which, according to Geison, reveal that Pasteur used Roux's desiccated spinal cord process. Furthermore, although the vaccine apparently was Roux's, not Pasteur's, no credit was given to Roux until the notebooks were reviewed a century later.[1], [20]
Another report, one that purports to defend Pasteur, admits that, with regard to successfully preventing rabies in dogs if vaccinations have been started 6 to 8 days after infection develops, “alas, Pasteur lied. And formally this is the most serious type of deception that can follow from [sic] experimental scientist-reporting success instead of reporting failure. Later independent research failed to confirm this claim and showed that therapeutic vaccination practically does not work in dogs.” Demonstrating the extent and nature of the emotion that enters the debate about Pasteur is this same author's response to what he himself has termed a “lie” and “the most serious type of deception”: “it appears that Pasteur's ability to make seriously fraudulent claims was an open secret to professional scientists” and “though Pasteur's wrongdoings were sometimes formally serious, they always can be easily justified.”5
With his health failing and paralysis of his left side from a serious stroke hampering his activities, Pasteur spent his last days in the laboratory, but working became increasingly difficult. In 1888, The Pasteur Institute had been inaugurated in Paris, with its main purposes being to undertake fundamental research on the prevention and treatment of rabies. Although he was in failing health, Louis Pasteur headed the Institute until his death, which occurred on September 28, 1895, after he suffered additional strokes. His body was buried by the French Government at the Cathedral of Notre Dame; the remains later were transferred to a permanent crypt in the Pasteur Institute, Paris.
Today's controversy
The debate that began with Koch's charges in 1885 continues today, even with regard to the validity of charges made in Geison's book. The Boston Medical and Surgical Journal reported the conclusions of reviews of both Koch's comments (published in January 1883) and Pasteur's responses (published in March 1883): “To Pasteur we must, probably, accord the full credit of solving the riddle of the nature of the ferment in what were formerly known as zymotic diseases, and of teaching the possibility and developing a method-if not the best method-of the attenuation and inoculation of the virus. [Koch] now confesses that Pasteur must be credited with working out the attenuation of the active principle of disease ferments. In these respects at least Pasteur is a genuine ‘path-breaker,’ and has enabled Koch to make his own brilliant discovery of the bacillus tuberculosis.”15
Subsequently, researchers have revealed a darker side, one of deception and manipulation.21 Geison's book has caused its own debate by revealing a questionable side of Pasteur's scientific acumen and credibility, while also showing him to be a “consummate publicist and showmanthe perfect anti-hero for our anti-heroic age.”22 The reactions to his book have evoked both emotional and unemotional responses, such as “Geison uses [Pasteur's private laboratory] notebooks, correspondence, and other unpublished material to reconstruct the actual process of Pasteur's research-full of false starts and intellectual twists and turns, in contrast to the clean, coherent, and rational versions presented in public and published in contemporary scientific journals.”16 In a more emotional vein, the charge has been issued that “modern science still does not know what is important and what is unimportant in the process of developing effective vaccineWhat's really bad is that this pornogrpahy was mistaken forscientific biography at its best' and even for ‘tour-de-force’ by scientific mediaand I am glad to mention that it supports my old sneaking suspicions that vaccinology is governed by idiots.” The author of the latter comments adds that he did not hope to get the note published, and, although he sent it to major science tabloids and Mr Geison himself, he “received not a single response!”5
Perhaps the best summation of both the book and the history is offered by Elizabeth Fee, PhD, of Johns Hopkins University School of Hygiene and Public Heath: Geison's controversial but stunning biography raises many important questions about the nature of science, past and present. Representing some of the newer interpretive trends in the history of science and medicine, it requires us to reevaluate our heroes and consider the complexities of science as it is actually created instead of merely clinging to comforting and heroic myths.16
References
References
[1] MF Perutz The pioneer defended. New York Review of Books
http://www.nybooks.com/articles/article-preview?article_id=1688 (February 28, 2002)
Available at Accessed
[2] DV Cohn The life and times of Louis Pasteur
A lecture at the School of Dentistry, University of Louisville
(February 11, 1996)
[3] GI Geison The private science of Louis Pasteur
Princeton University Press (1995)
[4] DP Francis, Book review: The private science of Louis Pasteur, http://www.thebody.com/iapac/pasteur.html (Available at Accessed February 28, 2002).
[5] DK Yuryev Falsified “new” discoveries in L. Pasteur's biography
http://www.ore.ru/~yur77/geison.htm (December 19, 2001)
Available at Accessed
[6] B Gardner Louis Pasteur
http://web.ukonline.co.uk/b.gardner/pasteur.htm (December 19, 2001)
Available at Accessed
[7] M Schwartz The life and works of Louis Pasteur
J Appl Microbiol, 91 (2001), pp. 597-601
[8] E Klein, Louis Pasteur, http://www.physics.ucla.edu/class/85HC_Gruner/bios/pasteur.html (Available at).
[9] LF Haas Louis Pasteur (1822-1895) J Neurol Neurosurg Psychiatry, 64 (1998), p. 330
[10] KL Manchester Louis Pasteur (l822-1895)-chance and the prepared mind
Trends Biotechnol, 13 (1995), pp. 511-515
[11] SY Rhee Louis Pasteur (1822-1895) Genetech Inc
http://www.acessexcellence.org/AB/BC/Louis_Pasteur.html (December 19, 2001)
Available at Accessed
[12] R Dubos Louis Pasteur: free lance of science
Da Capo Press Inc (1960)
[13] J McNally A brief life of Edward Jenner
Sem Ped Infect Dis, 12 (2001), pp. 81-84
[14] SA Plotkin A hundred years of vaccination: the legacy of Louis Pasteur
Pediatr Infect Dis J, 15 (1996), pp. 391-394
[15] DP Cohn Pasteur Koch controversy
http://pws.prserv.net/foundersofscience/past_koc.htm (December 19, 2001)
(Posting of the editorial of the Boston Medical and Surgical Journal, January 18, 1883, Vol CVIII, No. 3 entitled Dr. Robert Koch's latest estimate of Pasteur's methods and discoveries, and of the present position of the general inoculation problem.)
[16] FEE F Book review: The private science of Louis Pasteur
N Engl J Med, 333 (1995), pp. 884-885
(author, Geison FL)
[17] R Vallery-RadotLa vie de Pasteur
http://www.orc.ru/~yur77/geison.htm (October 10, 1999)
(Russian translation: Izd-vo inostr.lit. Moakva, 1950). Available at Accessed
[18] L Pasteur, Original report to the French Academy of Sciences given on October 26, 1885, http://psw.prserv.net/foundersofscience/Rabies.htm (translated by DV and ET Cohn from the original paper read by Pasteur. Complete paper available in French: Bulletin de l'Academie de medecine, seance du 23 ser Available at).
[19] G PortmannLouis Pasteur (1822 to 1895)
Arch Otolaryngol, 90 (1969), pp. 800-812
[20] DP Francis, Book review: The private science of Louis Pasteur by Geison GL, http://www.thebody.com/iapac/pasteur.html (Available at Accessed February 28, 2002).
[21] C Anderson Pasteur notebooks reveal deception
Science, 259 (1993), p. 1117
[22] WF Bynum Nature
http://pup.princeton.edu/titles/5670.html (February 28, 2002)
cited by Princeton University Press. Available at Accessed
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Louis Pasteur's early days and his contributions to science are dramatically presented. The challenges Pasteur faced from longtime members of the Academy of Medicine in Paris, as he made discoveries they were not progressive and enlightened enough to accept, are tersely enumerated. The case of Joseph Meister, a boy attacked by a rabid dog and treated with a Pasteur vaccine never before tried, is re-enacted. Meister was inoculated over a period of 14 days in 1885 and survived, after which the world paid tribute to Pasteur's "mad science." Toward the end of his life, Pasteur is celebrated and honored by European scientists and the French state. Film skips about one minute in, and it is unclear how much footage is missing.
https://www.youtube.com/watch?v=OFWIGBnmSP8

Images:
1.1886 print of Louis Pasteur pursuing a rabies vaccine in this etching by young Finnish artist, Léopold Flameng.
2. Louis Pasteur as a young adult
3. Louis Pasteur 'Never will the doctrine of spontaneous generation recover from the mortal blow struck by this simple experiment.'
4. 1849 Louis Pasteur married Marie Laurent, daughter of the rector of Strasbourg University

[https://www.sciencehistory.org/historical-profile/louis-pasteur]
Louis Pasteur
During the mid- to late 19th century Pasteur demonstrated that microorganisms cause disease and discovered how to make vaccines from weakened, or attenuated, microbes. He developed the earliest vaccines against fowl cholera, anthrax, and rabies.
Louis Pasteur (1822–1895) is revered by his successors in the life sciences as well as by the general public. In fact, his name provided the basis for a household word—pasteurized.
His research, which showed that microorganisms cause both fermentation and disease, supported the germ theory of disease at a time when its validity was still being questioned. In his ongoing quest for disease treatments he created the first vaccines for fowl cholera; anthrax, a major livestock disease that in recent times has been used against humans in germ warfare; and the dreaded rabies.

Early Life and Education
Pasteur was born in Dole, France, the middle child of five in a family that had for generations been leather tanners. Young Pasteur’s gifts seemed to be more artistic than academic until near the end of his years in secondary school. Spurred by his mentors’ encouragement, he undertook rigorous studies to compensate for his academic shortcomings in order to prepare for the École Normale Supérieure, the famous teachers’ college in Paris. He earned his master’s degree there in 1845 and his doctorate in 1847.

Study of Optical Activity
While waiting for an appropriate appointment Pasteur continued to work as a laboratory assistant at the École Normale. There he made further progress on the research he had begun for his doctoral dissertation—investigating the ability of certain crystals or solutions to rotate plane-polarized light clockwise or counterclockwise, that is, to exhibit “optical activity.” He was able to show that in many cases this activity related to the shape of the crystals of a compound. He also reasoned that there was some special internal arrangement to the molecules of such a compound that twisted the light—an “asymmetric” arrangement. This hypothesis holds an important place in the early history of structural chemistry—the field of chemistry that studies the three-dimensional characteristics of molecules.

Louis Pasteur in his laboratory, holding a jar containing the spinal cord of a rabbit infected with rabies, which he used to develop a vaccine against the disease.

Louis Pasteur pursuing a rabies vaccine in this etching by Léopold Flameng.

Science History Institute/Gregory Tobias
Fermentation and Pasteurization
Pasteur secured his academic credentials with scientific papers on this and related research and was then appointed in 1848 to the faculty of sciences in Strasbourg and in 1854 to the faculty in Lille. There he launched his studies on fermentation. Pasteur sided with the minority view among his contemporaries that each type of fermentation is carried out by a living microorganism. At the time the majority believed that fermentation was spontaneously generated by a series of chemical reactions in which enzymes—themselves not yet securely identified with life—played a critical role.
In 1857 Pasteur returned to the École Normale as director of scientific studies. In the modest laboratory that he was permitted to establish there, he continued his study of fermentation and fought long, hard battles against the theory of spontaneous generation. Figuring prominently in early rounds of these debates were various applications of his pasteurization process, which he originally invented and patented (in 1865) to fight the “diseases” of wine. He realized that these were caused by unwanted microorganisms that could be destroyed by heating wine to a temperature between 60° and 100°C. The process was later extended to all sorts of other spoilable substances, such as milk.

Germ Theory
At the same time Pasteur began his fermentation studies, he adopted a related view on the cause of diseases. He and a minority of other scientists believed that diseases arose from the activities of microorganisms—germ theory. Opponents believed that diseases, particularly major killer diseases, arose in the first instance from a weakness or imbalance in the internal state and quality of the afflicted individual. In an early foray into the causes of particular diseases, in the 1860s, Pasteur was able to determine the cause of the devastating blight that had befallen the silkworms that were the basis for France’s then-important silk industry. Surprisingly, he found that the guilty parties were two microorganisms rather than one.

A New Laboratory
Pasteur did not, however, fully engage in studies of disease until the late 1870s, after several cataclysmic changes had rocked his life and that of the French nation. In 1868, in the middle of his silkworm studies, he suffered a stroke that partially paralyzed his left side. Soon thereafter, in 1870, France suffered a humiliating defeat at the hands of the Prussians, and Emperor Louis-Napoléon was overthrown. Nevertheless, Pasteur successfully concluded with the new government negotiations he had begun with the emperor. The government agreed to build a new laboratory for him, to relieve him of administrative and teaching duties, and to grant him a pension and a special recompense in order to free his energies for studies of diseases.

Attenuating Microbes for Vaccines: Fowl Cholera and Anthrax
In his research campaign against disease Pasteur first worked on expanding what was known about anthrax, but his attention was quickly drawn to fowl cholera. This investigation led to his discovery of how to make vaccines by attenuating, or weakening, the microbe involved. Pasteur usually “refreshed” the laboratory cultures he was studying—in this case, fowl cholera—every few days; that is, he returned them to virulence by reintroducing them into laboratory chickens with the resulting onslaught of disease and the birds’ death. Months into the experiments, Pasteur let cultures of fowl cholera stand idle while he went on vacation. When he returned and the same procedure was attempted, the chickens did not become diseased as before. Pasteur could easily have deduced that the culture was dead and could not be revived, but instead he was inspired to inoculate the experimental chickens with a virulent culture. Amazingly, the chickens survived and did not become diseased; they were protected by a microbe attenuated over time.
Realizing he had discovered a technique that could be extended to other diseases, Pasteur returned to his study of anthrax. Pasteur produced vaccines from weakened anthrax bacilli that could indeed protect sheep and other animals. In public demonstrations at Pouilly-le-Fort before crowds of observers, twenty-four sheep, one goat, and six cows were subjected to a two-part course of inoculations with the new vaccine, on May 5, 1881, and again on May 17. Meanwhile a control group of twenty-four sheep, one goat, and four cows remained unvaccinated. On May 31 all the animals were inoculated with virulent anthrax bacilli, and two days later, on June 2, the crowd reassembled. Pasteur and his collaborators arrived to great applause. The effects of the vaccine were undeniable: the vaccinated animals were all alive. Of the control animals all the sheep were dead except three wobbly individuals who died by the end of the day, and the four unprotected cows were swollen and feverish. The single goat had expired too.

Rabies and the Beginnings of the Institut Pasteur
Pasteur then wanted to move into the more difficult area of human disease, in which ethical concerns weighed more heavily. He looked for a disease that afflicts both animals and humans so that most of his experiments could be done on animals, although here too he had strong reservations. Rabies, the disease he chose, had long terrified the populace, even though it was in fact quite rare in humans. Up to the time of Pasteur’s vaccine, a common treatment for a bite by a rabid animal had been cauterization with a red-hot iron in hopes of destroying the unknown cause of the disease, which almost always developed anyway after a typically long incubation period.
Rabies presented new obstacles to the development of a successful vaccine, primarily because the microorganism causing the disease could not be specifically identified; nor could it be cultured in vitro (in the laboratory and not in an animal). As with other infectious diseases, rabies could be injected into other species and attenuated. Attenuation of rabies was first achieved in monkeys and later in rabbits. Meeting with success in protecting dogs, even those already bitten by a rabid animal, on July 6, 1885, Pasteur agreed with some reluctance to treat his first human patient, Joseph Meister, a nine-year-old who was otherwise doomed to a near-certain death. Success in this case and thousands of others convinced a grateful public throughout the world to make contributions to the Institut Pasteur. It was officially opened in 1888 and continues as one of the premier institutions of biomedical research in the world. Its tradition of discovering and producing vaccines is carried on today by the pharmaceutical company Sanofi Pasteur.
Bert Hansen: How the Public Became Interested in Medical Science
Historian Bert Hansen discusses his book, Picturing Medical Progress from Pasteur to Polio.
A Great Experimenter and Innovative Theorist
Pasteur’s career shows him to have been a great experimenter, far less concerned with the theory of disease and immune response than with dealing directly with diseases by creating new vaccines. Still it is possible to discern his notions on the more abstract topics. Early on he linked the immune response to the biological, especially nutritional, requirements of the microorganisms involved; that is, the microbe or the attenuated microbe in the vaccine depleted its food source during its first invasion, making the next onslaught difficult for the microbe. Later he speculated that microbes could produce chemical substances toxic to themselves that circulated throughout the body, thus pointing to the use of toxins and antitoxins in vaccines. He lent support to another view by welcoming to the Institut Pasteur Élie Metchnikoff and his theory that “phagocytes” in the blood—white corpuscles—clear the body of foreign matter and are the prime agents of immunity.
The information contained in this biography was last updated on December 14, 2017.

The Artist in the Laboratory
Albert Edelfelt broke the rules when he painted his friend Louis Pasteur in the scientist’s natural element.

By Bert Hansen | June 7, 2015
Louis Pasteur holds a drying bottle, contemplating a piece of nerve tissue from a rabid rabbit. He’s using the bottle to attenuate the deadly hydrophobia virus, the key to his lifesaving rabies shots. In this brilliant portrait there is no sign of friendship, but it was fundamental to the painting’s creation. In fact, the history of this print reveals two friendships.

Pasteur began his career in physical chemistry but went on to revolutionize biology and medicine. By age 63 he had made discoveries in stereochemistry, fermentation, the preservation of wine, and diseases of silkworms. He had abolished the notion that simple creatures can be generated spontaneously from organic compounds without any parent organisms. He had established evidence for the germ theory of disease and produced a vaccine for anthrax.

In spring 1885 Pasteur invited a young Finnish artist, Albert Edelfelt, to paint a large formal portrait. They had become close friends a few years earlier through Pasteur’s son, Jean-Baptiste, a part-time journalist who often wrote about art.

Edelfelt was responsible for the unprecedented scene in the painting. Portraits of eminent people made at this time rarely included a naturalistic setting and almost never a realistic workplace. The artist recorded his ambitions in a letter home. “Monday, I will again go to see the old fellow Pasteur to see if there is a possibility to make something of him in the laboratory because it is only there, in that environment, that I want to paint him. The old fellow Pasteur in tails and high collar is something ridiculous. No—he has to be in his own element.”

Not only did Pasteur consent to the painter’s presence in the crowded laboratory over several weeks, but he also worked with Edelfelt on the composition. “He has gone through all the accoutrements I placed around him, asking me to take away some of them, ‘the objects that are useless from the scientific point of view,’ and to replace them with other objects.”

The portrait’s huge success at the Paris Salon in the spring of 1886 created a market for prints. Lithographs, etchings, and engravings were used since photographs could not yet capture the tonal range of a canvas over five feet high. Such a handmade reduction required special skill, and Edelfelt was thrilled when he learned that a dealer had commissioned Léopold Flameng to make an etching, pronouncing him “France’s best.” The subtleties of the large painting are preserved exceptionally well even in this modestly sized print (21¼ × 17½ inches).

The copy in CHF’s collection—an original artist’s proof—reveals a second friendship. Printmakers do their own imprints to check the state of the finished metal plate. Flameng liked this particular impression so well that he kept it and personally inscribed it later “to my dear friend,” for Paul Raymond-Signouret, a writer known for art-exhibition catalogues and French translations of plays, including Shakespeare’s Macbeth.

Bert Hansen has recently published three articles about Louis Pasteur’s friendships with artists in the Bulletin of the History of Medicine and the Journal of Medical Biography. He discusses how the public first became interested in medical science at distillations.org/video."

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