Features
Pasteur: High Priest of
Microbiology
Wherever he turned, Pasteur brought great insight
to benefit humanity
R OBERT
This year marks the centennial of Louis Pasteur’s
death, occasioning a series of events organized by
UNESCO and the Pasteur Institute to celebrate his
many contributions.
When one thinks of the famous names associated
with the history of medical science, certainly Pasteur
ranks among the greatest. Trained as a chemist, Pasteur’s phenomenal success in diverse fields of research
is remarkable. In his 73-year life span, Pasteur distinguished himself as a teacher, patriot, scientist, and
family man. His studies on crystallography, fermentation, diseases of wine and beer, spontaneous generation, silkworm disease, cholera, and anthrax were no
less significant than was his work on rabies.
However, the rabies work was Pasteur’s crowning
glory and established his reputation. Pasteur was 63
when he first treated a patient for rabies, and he was in
poor health from overwork and the effects of a stroke
suffered at age 46. But Pasteur was already a hero in
France and beyond.
Pasteur Heralded in Many Venues
In 1950, Selman A. Waksman wrote, “Pasteur was
not only the great scientist who was largely responsible
for the creation of the science of microbiology, he was
its high priest, preaching and fighting for the recognition of its importance in health and in human welfare.”
Numerous books have been written about Pasteur;
towns, buildings, avenues, boulevards, streets, and
statues bear his name. Further, many texts in microbiology and immunology as well as books in general
biology refer to and contain illustrations about PasRobert I. Krasner is a professor of biology at Providence College in Providence, R.I.
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teur. Even Hollywood got into the act in 1930 with the
feature film Life of Pasteur, starring Paul Muni. The
Society of Illinois Bacteriologists established the Pasteur Award in 1948, which each year recognizes an
individual who has made an outstanding contribution
to microbiology.
Who Was Louis Pasteur?
Pasteur’s early years in school were not particularly
remarkable. He was an average student with a fondness and a talent for painting; he did not display
brilliance. Sent at 16 to Paris to prepare for college, he
quickly became homesick and returned home. Eventually, he studied chemistry and graduated but without
distinction. However, this mediocrity soon gave way to
academic success at the Sorbonne in 1842-1843. He
wrote in a letter, “Once you have got into the way of
working you cannot live without it. Besides everything
in this world depends on it.” This strong work ethic
remained with Pasteur throughout his lifetime and,
undoubtedly, contributed to his success.
Over the next 25 years, Pasteur’s studies moved
from chemistry to fermentation, to diseases of wine and
beer, to spontaneous generation, and to silkworm disease, after which in the early 1870s he focused on
diseases of higher animals and humans. His academic
positions during these years were numerous and varied and included an appointment at the University of
Strasburg in 1848, during which time he met and
married Marie-Laurent, daughter of the head of the
Academy. His scientific accomplishments earned him
the Legion of Honor at the age of 31, for his contributions to chemistry, and election to the Academy of .
Sciences at the age of 40.
Pasteur’s first scientific paper, on crystallography,
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was published by the French Academy of Sciences in
1848. He next turned to fermentation, demonstrating
conclusively that it results from microbial action and
thus establishing the “germ theory” of fermentation. In
a paper published in 1861 he wrote: “It is, I believe, the
first known example of animal ferments, and also of
animals living without requiring ‘oxygen gas’.” He had
also discovered anaerobic bacteria.
Between 1860 and 1864, Pasteur delivered the final
blow to the concept of spontaneous generation. Biology
students perhaps associate Pasteur more with disproving spontaneous generation than they do with his
research on rabies; illustrations of Pasteur’s swan-neck
flasks are found in most biology texts. On 7 ‘April 1864
at the Sorbonne, Pasteur concluded, “Never will the
doctrine of spontaneous generation recover from the
mortal blow of these simple experiments.”
In 1863, at the command of Emperor Napoleon III,
Pasteur undertook studies of “diseases” of, wine and
showed them to be caused by microbial activity. His
cure was simple-“ heat to 50°-60”C”-a process now
called pasteurization and applied to many foods, particularly milk.
In 1865, at the request of the French Government,
Pasteur began studying the diseases of silkworms, a
problem that threatened to destroy the European silk
industry. Within five years Pasteur not only solved the
problem but established preventive measures. Despite
these professional successes, these years were difficult
personally for Pasteur, with the deaths of his father
and of two of his daughters, Camille at the age of 2 and
Cecile at 12, due to typhoid fever. His own health was
not good, and he was worn by the ongoing controversy
over spontaneous generation and his compulsion to
work under primitive conditions.
A New Lab and New Ambitions
During this period, Pasteur wrote to Emperor Napoleon III requesting financial support for a new laboratory: “I wish to have a much larger laboratory to
which would be attached a wing where experiments on
putrid and infectious diseases could be carried out
without endangering the public health.” Pasteur’s request for a larger laboratory for experiments on infectious diseases represents a turning point to interest in
human diseases.
In 1863, Pasteur advised the emperor of his great
ambition to learn the causes of putrid and contagious
diseases. Early in his career he was impressed with
the relationships between fermentation, putrefaction,
spontaneous generation, and infectious diseases. He
reasoned that if microbes could cause such damage in
wine, in beer, and in other foods, why not in the human
body? Some years earlier, Robert Boyle, a distinguished British scientist, had stated that “he who could
discover the nature of ferments and fermentation,
would be more capable than anyone else of explaining
the nature of certain diseases.”
In 1874, Lord Lister paid tribute to Pasteur. In a
letter Lister wrote:
VOL. 61, NO. 11, 1995
I do not know whether the records of British surgery
ever meet your eye. If so, you will have seen from time
to time notices of the antiseptic system of treatment,
which I have been labouring for the last nine years to
bring to perfection. Allow me to take this opportunity
to tender you my most cordial thanks for having, by
your brilliant researches, demonstrated to me the
truth of the germ theory of putrefaction, and thus
furnished me with the principle upon which alone the
antiseptic system can be carried out.
In the early 1870s Pasteur was well renowned and
respected in France and beyond by the scientific community but was regarded as a “mere chemist” by the
medical establishment, which had difficulty accepting
the germ theory of disease. Nevertheless, in 8 years,
Pasteur developed immunizations against fowl cholera, anthrax, swine erysipelas, and rabies, all of which
helped to promote the germ theory of disease.
The anthrax work began in 1887; anthrax killed
from 25 to 30% of sheep in France and in some parts of
Europe had been epidemic, attacking humans as well.
Koch had isolated the bacillus in pure culture. Pasteur
confirmed Koch’s work and in the spring of 1881 at a
farm in Pouilly-le-Fort, Pasteur dramatically demonstrated the effectiveness of his anthrax vaccination,
when the vaccinated flock remained well while the
unvaccinated animals died.
Work on Rabies Lionized Pasteur
The anthrax studies followed on the heels of Pasteur’s paper on the immunization of fowl against cholera. Jenner established immunization against smallpox.
Almost 90 years after Jenner established immunization
against smallpox, the first human immunization against
rabies took place, and this treatment established Pasteur as a popular hero. Which specific event led Pas-
Features
teur to study rabies is not known. One story describes
how, as a young boy, Pasteur had witnessed the agonies of a victim bitten by a rabid wolf; the victim was
undergoing cauterization of wounds with a red-hot
iron.
Rabies is considered one of the most dread diseases,
and stories of this terrifying disease trace to antiquity.
One of Homer’s warriors called Hector a “mad dog.”
Another ancient, Celsus, described the horror of this
disease in vivid terms: “The patient is tortured at the
same time by thirst and by a revulsion toward water.”
By Pasteur’s time, cauterization was the common and
equally terrifying treatment; long, heated needles were
inserted deeply into bite wounds, even those on the
face. Another practice was to sprinkle gunpowder over
the wound and set a match to it.
Pasteur developed a method to cultivate the rabies
virus in the medulla of rabbits and attenuate it by
drying fragments of medulla in sterilized vials. After
Pasteur showed that such material protected dogs, he
was pressured to use the rabies treatment on humans.
Early treatments for rabies
were nearly as terrifying as the
disease: hot needles were
inserted into wounds, or they
were sprinkled with
gunpowder and lit with
matches.
Pasteur considered testing it on himself, as indicated
in a letter from March 1885: “I haven’t dared to treat
humans after bites, but this moment is not too far off,
and I should start with myself.”
Pierre Victor Galtier, a professor at a veterinarian
school in Lyon, preceded Pasteur in vaccinating sheep
against rabies by using saliva from rabid dogs. Galtier’s studies served as the groundwork for Pasteur’s
work. Galtier received many honors for his work and
was nominated for a Nobel Prize in 1908, but he died a
few months before the Nobel Commission decision.
Tested on Desperate Humans, Rabies Vaccine
Proves Effective
6 July 1885 proved a momentous day for Pasteur
and medicine. On that day, Joseph Meister, a g-yearold Alsatian boy, was brought to Pasteur’s laboratory
following a savage attack two days earlier by a mad
dog. He suffered 14 wounds, some very deep, which had
been treated with carbolic acid. The boy’s doctor, recognizing his patient’s peril, urged the boy’s mother to
plead with Pasteur in Paris that her son might be given
the vaccine. Pasteur consulted with colleagues at a
meeting of the Academy of Sciences. “The death of this
child appearing to be inevitable, I decided, not without. . .anxiety. . .to try upon Joseph Meister the method
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which I had found constantly successful with dogs,”
Pasteur noted in a later article. Meister received 13
inoculations of Pasteur’s vaccine over the next 10 days
and survived.
During the treatment, Pasteur was prey to anxiety.
Mme. Pasteur wrote: “My dear children, your father
has had another bad night; he is dreading the last
inoculations on the child. And yet there can be no
drawing back now. The boy continues in perfect
health.” Pasteur kept in touch with the boy through the
years; it appears that he was like a second father to
Meister. Meister later worked at the Pasteur Institute;
in 1940, 55 years after the accident that gave him a
lasting place in medical history, he purportedly committed suicide rather than open up Pasteur’s burial
crypt to German invaders.
Jean Baptiste Jupille, age 15, was the second human rabies case treated by Pasteur. The shepherd boy
was brought to Paris 6 days after being bitten by a
rabid dog, which he heroically subdued to protect his
five companions. Despite this delay before treatment,
he survived. His act of bravery is commemorated with
a statue (see cover) now standing at the Pasteur
Institute.
By October 1886, 15 months after Joseph Meister
was first treated, 1,490 individuals had received the
rabies vaccine. Patients from all over the world flocked
to Paris, including four boys from Newark, N.J., who
had been bitten by a mad dog. These boys, from poor
families, were sent to Paris by means of a public
subscription organized by the New York HeraZd. Other
accounts from that period indicate Pasteur’s laboratory
was crowded with rabies victims who came for lifesaving inoculations from Europe, Russia, the Middle
East, and elsewhere.
In response to a request from Odessa, Russia,
Pasteur sent two rabid rabbits for use in establishing a
rabies vaccine laboratory; on 1 June 1886, Pasteur’s
antirabies treatment was administered by a Russian
on Russian soil for the first time, after which thousands
flocked to Odessa from Siberia, Turkey, and other
countries.
Pasteur Becomes a Celebrity
The name Pasteur became increasingly familiar.
Caricatures of him appeared frequently in newspapers,
sometimes with political overtones. The French Academy of Sciences supported a move to establish the
Pasteur Institute in Paris. About 2 years later, on 16
November 1888, the institute was opened with considerable fanfare. But its director was ill and weary. He
spent much of his time with his wife and supervised the
Hydrophobia Clinic as much as his strength would
allow.
Pasteur’s 70th birthday was celebrated on 27 December 1892 in the great theatre of the Sorbonne amid
other celebrities, including the president of the republic, delegates from French and foreign learned societies, professors, colleagues, and other distinguished
scientists such as Roux, Duclaux, Chamberland, and
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Metchnikoff. Tributes to Pasteur flowed. Lister, representing the Royal Society of London and Edinburgh,
said to Pasteur, “You have raised the veil which for
centuries had covered infectious diseases; you have
discovered and demonstrated their microbian nature.”
Pasteur rose and embraced Lister.
The dean of the Paris Faculty of Medicine declared,
“More fortunate than Harvey or Jenner, you have been
able to see the triumph of your doctrine, and what a
triumph!” The president of the student association
said to Pasteur: “You have been very great and very
good; you have given a beautiful example to students.”
Pasteur, overcome by emotion, asked his son to read his
remarks.
Over the next few years, Pasteur saw several of
these students continue with success in microbiology.
Roux and Yersin studied diphtheria; Yersin later studied plague in China, and Metchnikoff described phagocytosis. However, Pasteur’s own health continued to
fail; his paralysis worsened and his speech was difficult. He died on 28 September 1895. The world mourned
him and continues to honor his name.
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