We
need no reminder that the foundations of our knowledge of health and disease
were constructed by scientific giants who worked decades, even centuries,
ago. It is with tributes such as the one today to Louis Pasteur that
we pay homage to these great minds -- to acknowledge their achievements and
our indebtedness to them which we can never repay.
With certainty, one hallmark of Pasteur's research was not only the
importance of his individual discoveries, but the overwhelming breadth of
his accomplishment. Pasteur's long time collaborator, Emile
Duclaux, wrote, "A mind ... of a scientific man is a bird on the wing;
we see it only when it alights or when it takes flight. ... We may by
watching closely keep it in view, and point out just where it touches the
earth. But why does it alight here and not there? Why has it taken this
direction and not that in its flight toward new discoveries?"
Pasteur, himself, provided us with an answer: He believed that his research
was "enchained" to an inescapable, forward moving logic. As we
review today Pasteur's scientific discoveries we shall see the truth of this
statement: how one discovery, one concept, led almost
"inescapably" to another.
Education and Growing Up
Pasteur was born in Dole and grew up in the nearby town of Arbois, the only
son of a poorly educated tanner, Jean Pasteur. Louis was not an outstanding
student during his years of elementary education, preferring fishing and
drawing to other subjects (Fig.1) In fact, young Louis drawings suggested
that he could easily have become a superior portrait Artist. His later
drawings of friends done at college were so professional that Pasteur was
listed in at least two compendia of XIX C. artists.

Fig.
1. Portrait of Pasteur's father by
young Louis.
The
Senior Pasteur, however, did not see his son ending up as an Artist, and
Louis, himself, was showing increasing interest in chemistry and other
scientific subjects. The highest wish Father Pasteur had for his son was
that he complete his education in the local schools and become a professor
in the college at Arbois. However the headmaster of the college
recognized that Louis could do much better and convinced father and son that
Louis should try for the Ecole Normale Superieure in Paris. This most
prestigious French University was founded specifically to train outstanding
students for University careers in science and letters. And it was here that
Pasteur entered and began his long journey of scientific discovery.
Crystallography
It may surprise some to learn that Pasteur, the father of microbiology and
immunology, was a chemist who launched his memorable scientific career by
studying the shapes of organic crystals. Pasteur was 26 years old, working
for his doctorate in chemistry in the laboratory of Antoine Balard.
Crystallography was just emerging as a branch of chemistry. His project was
to crystallize a number of different compounds. Happily he started working
with tartaric acid. Crystals of this organic acid are present in large
amounts in the sediments of fermenting wine. Often one also found in the
sediments in the wine barrels crystals of a second acid called paratartaric
acid or "racemic acid". A few years earlier, the chemical
compositions of these two acids, tartaric and paratartaric, had been
determined. They were identical. But in solution there was a striking
difference. Whereas tartaric acid rotated a beam of polarized light passing
through it to the right, paratartaric acid did not rotate the light (Fig.
2). This puzzled the young Pasteur. How could this be?

Fig. 2.
Paratartrate does not rotate polarized light
while tartrate does.
Pasteur refused to accept the notion that two
compounds that had the same chemical composition yet acted so differently in
respect to rotation of light could be identical. He was convinced that the
internal structure of the two compounds must be different and this
difference would show itself in the crystal form. The experts in this field
had looked examined tartrate and paratartrate crystals but never saw a
difference, perhaps because, as Duclaux thought, they believed that no
difference could exist. Pasteur believed that there were differences and
indeed found them!
Upon intense examination beneath his microscope, he saw that every crystal
of pure tartaric acid looked like every other one. When he examined the
paratartrate crystals, on the other hand, he saw two types of crystals,
nearly identical but not quite! One type was the mirror image the other --
the way the right hand mirrors the left hand. This was the difference he was
looking for!
Pasteur then performed one of the simplest and yet most elegant experiments
in the annals of chemistry. With a dissecting needle and his microscope, he
separated the left and right crystal shapes from each other to form two
piles of crystals (Fig. 3). He then showed that in solution one form rotated
light to the left, the other to the right. This simple experiment proved
that the organic molecules with the same chemical composition can exist in
space in unique stereospecific forms. And with this work did Pasteur launch
the new science of stereochemistry.

Fig 3. Dextro- and
levorotary forms of tartrate. An equal mixture of the two forms cancels each
other's rotation. Hence, the mixture does not rotate polarized light.
To Pasteur this discovery had a deeper meaning. He proposed that
asymmetrical molecules were indicative of living processes. In the broadest
sense, he was correct. We know today that all of the proteins of higher
animals are made up of only those amino acids that exist in the left-hand
form. The mirror image right-hand amino acids are not used by human or
animal cells. Likewise, our cells burn only the right-handed form of sugar,
not the left-handed form that can be made in the test tube. It was the
discovery of asymmetry of organic molecules that provided Pasteur with the
"inescapable forward moving logic" that enchained him as he began
his studies on alcoholic fermentation.
(For more details on Pasteur's crystallographic research, click
on Rumford
Medal)
Alcoholic Fermentation
Pasteur served on the faculty of science of Dijon for a brief period and
then was transferred to Strasbourg University where he continued his studies
on molecular asymmetry. In Strasbourg, Pasteur had the immense good fortune
to meet and marry the University Rector's daughter Marie Laurent, who was to
be his devoted wife, mother and scientific helpmate through the remainder of
his life.
In 1854 Pasteur was appointed Dean and professor of chemistry at the Faculty
of Sciences in Lille, France. Lille was an industrial town with a number of
distilleries and factories. The Minister of Public Instruction was not
completely sold on "science for science's sake". He reminded
university faculty that (and here I quote the Minister's words) "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."
Pasteur, in contrast to other faculty, needed no prodding. He enjoyed taking
his students on tours of the factories and was quick to advise the managers
that he was available to help solve their problems. In the summer of 1856,
M. Bigot, father of one of his students in chemistry, called upon Pasteur to
help him overcome difficulties he was having manufacturing alcohol by
fermentation of beetroot. Often, instead of alcohol, Bigot's fermentations
yielded lactic acid.
To better appreciate the discoveries to follow, we should understand what
was believed at that time about alcoholic fermentation. Chemistry was
emerging as a true science, freed from the pseudoscience of the alchemist.
The mysterious chemical processes of living animals were slowly being
unraveled in strictly chemical terms. Lavoisier had shown that chemical
combustion in living animals was quantitatively identical to that occurring
in a furnace. Lavoisier also showed that sugar, the starting product of
fermentation, could be broken down to alcohol, CO2 and H2O by simply
dropping a sugar solution on heated platinum. Woehler startled the
scientific world by synthesizing the organic compound urea, showing for the
first time that organic compounds, believed up to then as capable of
synthesis only by living animals could be made in a test tube. And due, in
no small part to Pasteur's work on crystals, internal structure and analysis
of complex organic compounds was becoming routine.
In this light, fermentation leading to production of wine, beer and vinegar
was believed to be a straightforward chemical breakdown of sugar to the
desired molecules. The chemical experts of the day proclaimed that the
breakdown of sugar into alcohol during fermentation of sugar to wine and
beer was due to the presence of inherent unstabilizing vibrations. One could
transfer these unstabilizing vibrations from a vat of finished wine to new
grape pressings to start fermentation anew.
Yeast cells were found in the fermenting vats of wine, and were recognized
as being live organisms, but they were believed simply to be either a
product of fermentation or catalytic agents that provided useful ingredients
for fermentation to proceed. Those few biologists who earlier concluded that
yeast was the cause of, and not the product of, fermentation were ridiculed
by the scientific experts: The deep conviction of the scientific
establishment was that chemistry had come too far to allow a vitalistic life
force theory to challenge pure chemical explanations of molecular reaction.
To attribute such chemical changes to mysterious life forces would represent
a major backward step in science!.
Unfortunately, the "scientific establishment" was not providing
much help to the brewers of wine, beer and vinegar. These manufacturers were
plagued by serious economic problems related to their fermentations. Yields
of alcohol might suddenly fall off; wine might unexpectedly grow ropy or
sour or turn to vinegar; vinegar, when desired, might not be formed and
lactic acid might appear in its place; the quality and taste of beer might
unexpectedly change making quality control a nightmare! All too often the
producers would be forced to throw out the resultant batches, start anew,
and sadly have no better luck!
Into M. Bigot's factory, microscope in hand, came Pasteur. He quickly found
three clues that allowed him to solve the puzzle of alcoholic fermentation.
First, when alcohol was produced normally, the yeast cells were plump and
budding. But when lactic acid would form instead of alcohol, small rod like
microbes were always mixed with the yeast cells. Second, analysis of the
batches of alcohol showed that amyl alcohol and other complex organic
compounds were being formed during the fermentation. This could not be
explained by the simple catalytic breakdown of sugar shown by Lavoisier.
Some additional processes must be involved. Third, and this may have been
the critical clue to Pasteur, some of these compounds rotated light, that is
they were asymmetric. As we said earlier, Pasteur suspected that only living
cells produced asymmetrical compounds. He concluded and was able to prove
that living cells, the yeast, were responsible for forming alcohol from
sugar, and that contaminating microorganisms turned the fermentations sour!
Over the next several years Pasteur identified and isolated the specific
microorganisms responsible for normal and abnormal fermentations in
production of wine, beer, vinegar. He showed that if he heated wine, beer,
milk to moderately high temperatures for a few minutes, he could kill living
microorganism and thereby sterilize (pasteurize), the batches and prevent
their degradation. If pure cultures of microbes and yeasts were added to
sterile mashes uniform, predictable fermentations would follow.
Spontaneous Generation
In the midst of the great excitement and controversy created by Pasteur's
research on fermentation, a debate was ongoing in the scientific world on
the theory of "spontaneous generation". The idea that beetles,
eels, maggots and now microbes could arise spontaneously' from putrefying
matter was speculated on from Greek and Roman times. And in the 1860's
spontaneous generation was still a subject of debate in the exalted French
Academy of Sciences. Against the advice of his colleagues, who saw dabbling
in this field as thankless and unrewarding, Pasteur entered the fray. Based
on his work on fermentation it seemed obvious to him that the sources of
yeasts and other microorganisms that were found during fermentation and
putrefaction entered from the outside, for example, on the dust of the air.
Pasteur conducted a series of ingenious experiments that destroyed every
argument supporting "spontaneous generation". He showed that the
skin of grapes towards the beginning of grape harvest was the source of the
yeast. Drawing grape juice from under the skin with sterile needles gave
juice that would not ferment. Covering the grape arbors with fine cloth or
wrapping the grapes with cotton to keep off contaminating dust, gave grapes
that would not produce wine. In order to show that dust of the air was the
carrier of contamination, he allowed air collected at different altitudes,
from sea level to mountain tops, to enter sterilized vessels containing
fermentable solutions. The higher the altitude the less the dust in the air
and the fewer flasks showed growth.
The experimental design that clinched the argument was the use of the
swan-neck flask. In this experiment, fermentable juice was placed in a flask
and after sterilization the neck was heated and drawn out as a thin tube
taking a gentle downward then upward arc -- resembling the neck of a swan
(Fig 4). The end of neck was then sealed. As long as it was sealed, the
contents remained unchanged. If the flask was opened by nipping off the end
of the neck, air entered but dust was trapped on the wet walls of the neck.
Under this condition, the fluid would remain forever sterile, showing that
air alone could not trigger growth of microorganisms. If, however, the flask
was tipped to allow the sterile liquid to touch the contaminated walls and
this liquid was then returned to the broth, growth of microorganisms
immediately began.

Fig
4. Swan flask. The long "swan-like" neck
is open to air, but dust and air-borne microbes cannot reach the liquid.
Some of Pasteur's preparations are at the Pasteur Institute, Paris where
they continue to remain sterile for more than 100 years.
In the words of Pasteur "Never will the doctrine of spontaneous
generation recover from the mortal blow of this simple experiment. No, there
is now no circumstance known in which it can be affirmed that microscopic
beings came into the world without germs, without parents similar to
themselves."
Diseases of Silkworms
As if Pasteur was not busy enough with his studies on
fermentation and spontaneous generation, he was asked by the Department of
Agriculture to head a commission to see what could be learned about a
devastating disease of silkworms that was destroying the French silk
industry (Fig. 5). Even though Pasteur knew nothing of silkworms and had no
idea that they suffered from disease, his research on silkworms forged
another link in his "inevitable" chain of discovery.

Fig. 5.
Healthy silkworms
Now
there were at least two different types of silkworm diseases that Pasteur
came to grips with: Pebrine, in which black spots and corpuscles are
generally, but not always, present on the worm. In such cases the worms
often die within the cocoons. In the second type of disease, flacherie,
the worms exhibit no corpuscles or spots but fail to spin cocoons. Pasteur
suspected, but was not sure, that pebrine corpuscles were associated with
the failure of the worms. Nonetheless, by examining the worms under the
microscope he was able to identify those free of pebrine and used only their
eggs for breeding. Next he excluded from breeding eggs from worms with
flacherie whom he identified by their sluggish behavior in climbing leaves
when about to construct cocoons. He instructed the silkworm farmers on these
methods of selection and how to use the microscope to detect sickness in the
worms. Soon the silk industry in France, Italy and other European countries
returned to health.
Pasteur
considered these studies important landmarks in his investigations on
infection and infectious disease. As he expanded his research, he found that
healthy worms became infected when allowed to nest on leaves used by
infected worms. He also noted that the susceptibility of the worms varied
widely, some worms dying shortly after infection, some weeks later, some not
at all. He determined that temperature, humidity, ventilation, quality of
the food, sanitation and adequate separation of the broods of newly hatched
worms each played a role in susceptibility to the disease. So here from
Pasteur's research we see the emergence of his future concepts of the
influence of environment on contagion.
Germ Theory of Disease
The crowning achievements of Pasteur's career were development of the germ
theory of disease and the use of vaccines to prevent these diseases.
Pasteur's studies on contamination of wine and beer by airborne yeast
clearly stimulated certain investigators to recognize that these
"diseases" were due to entry of foreign microorganisms. Lister in
England was so impressed by Pasteur's work that he began to systematically
sterilize his instruments, bandages and sprayed phenol solutions in his
operatories thus reducing infections following surgery to incredibly low
numbers.
By 1875 many physicians recognized that some diseases were accompanied by
specific microorganisms, but the body of medical opinion was unwilling to
concede that important diseases --cholera, diphtheria, scarlet fever,
childbirth fever, syphilis, smallpox - could ever be caused by these agents.
To give you an idea of the magnitude of the problem, according to Pasteur's
biographer son-in-law Vallery-Radot between April 1 and May 10, 1856, in the
Paris Maternity Hospital there were 64 fatalities due to childbirth fever
out of 347 confinements. The hospital was closed and the patients were
transferred to a different hospital. Sadly, the contagion followed these
women and nearly all of them died!
As Pasteur wandered through hospital wards he became increasingly aware that
infection was spread by physicians and hospital attendants from sick to
healthy patients. Pasteur impressed on his physician colleagues that
avoidance of microbes meant avoidance of infection. In a famous speech
before the august Academy of Medicine in Paris he stated, "This water,
this sponge, this lint with which you wash or cover a wound, may deposit
germs which have the power of multiplying rapidly within the tissue....If I
had the honor of being a surgeon....not only would I use none but perfectly
clean instruments, but I would clean my hands with the greatest care...I
would us only lint, bandages and sponges previously exposed to a temperature
of 1300 to 1500 degrees. Slowly, but surely, through the preachings of
Pasteur, Lister and other physicians antiseptic medicine and surgery became
the rule.
Anthrax
At this time, anthrax, a fatal disease of sheep and cattle, was decimating
the sheep industry and the economy of France. Important strides in
identifying the causative agent of anthrax had been made by the time Pasteur
entered the arena. The great German physician/scientist Robert Koch,
isolated the anthrax bacillus, previously identified by the French physician
Davain, from infected spleens and showed that under resting conditions the
bacillus formed long-lived spores.
Definitive proof was still lacking that the cultured bacillus, itself, and
not something carried along in Koch's culture medium was responsible to
giving injected animals anthrax. Pasteur provided this proof. As described
by Dubos, Pasteur placed one drop of blood from a sheep dying of anthrax
into 50 ml of sterile culture, grew up the bacterium, and then repeated this
process 100 times. This represented a huge dilution of the original culture
so that not a single molecule of the original culture remained in the final
culture. Yet, the last culture was as active as the first in producing
anthrax. As only the bacillus, itself, by growing up each time in the new
culture, could escape dilution, it proved beyond all doubt that the anthrax
bacillus and nothing else could be responsible for the disease. Thus was the
germ theory of disease firmly established!
But how did the disease spread? Why was one field deadly to sheep, another
harmless? Here Pasteur's studies on silkworm contagion provided the clue.
During one of Pasteur's excursions to a field where sheep were grazing he
noted that the ground in one part of the field was differently colored than
the rest. There it was that the farmer had buried some sheep dead of
anthrax. The color of the soil was due to earth worm casts. He realized that
earth worms were feeding on the carcasses of the buried sheep and bringing
the anthrax spores to the surface where other sheep could graze on the
contaminated soil. Although containment of the animals on uncontaminated
fields would help control the spread of anthrax, more was needed.
Interestingly, Pasteur's studies on chicken cholera going on at this time
provided the breakthrough that led to development of specific vaccines to
fight disease. Cholera was a serious problem for farmers. Chicken cholera
would spread through a barnyard rapidly and wipe out the entire flock in as
little as 3 days. Spread could be by contaminated food or animal excrements.
Pasteur had identified the cholera bacillus and was growing it in pure
culture. When injected, chicken invariably died in 48 hours.
Then luck intervened. During the heat of the summer, Pasteur returned to
Paris leaving the cholera cultures used for infection stored on the shelves
of the Arbois laboratory. Upon return, Pasteur's collaborators were
disappointed to find that these stored cultures no longer killed injected
chickens, nor even made them sick. The group set to work to make new
cultures of the bacillus and tested these batches on new birds and those
healthy previously treated birds. The results were astonishing: The
previously injected birds were unaffected by the bacillus, while the new
birds all died. When Pasteur saw these results he immediately realized that
in a sense he was repeating the studies of Jenner 80 years earlier who had
conferred on humans immunity to smallpox by vaccinating individuals with a
mild form of cowpox. Pasteur then reproducibly manufactured attenuated
cultures of chicken cholera vaccines by growing the cholera bacillus at 42 -
43 degrees C. at which temperature the bacillus is non-infectious. These
attenuated bacterial cultures could routinely prevent cholera in the
vaccinated chickens.
If attenuated cholera bacillus could render chickens resistant to the
disease, would not an attenuated anthrax bacillus render sheep immune to
anthrax? By various techniques involving oxidation and aging, anthrax
vaccines indeed prevented anthrax in laboratory trials. Pasteur's reports on
preventing sheep anthrax were so exciting to some and unbelievable to many,
that he was challenged by the well-known veterinarian Rossignol to conduct a
carefully controlled public test of his anthrax vaccine. This was to take
place at Pouilly le Fort, a farm in the town of Melun south of Paris (Fig.
6). Twenty-five sheep were to be controls, the other twenty-five were to be
vaccinated by Pasteur and then all animals would receive a lethal dose of
anthrax. All of the control sheep must die and the vaccinated sheep must
live. When Pasteur's colleagues learned that he had agreed to the test they
were concerned. The challenge was severe and there was no room for error.
The vaccines were still in the developmental stage. "What succeeded
with 14 sheep in our laboratory will succeed with 50 at Melun", said
Pasteur.

Fig. 6. Vaccinating
sheep at Pouilly-le-fort.
The
publicity was intense. A reporter from the London Times sent back daily
dispatches. Newspapers in France followed the events with daily bulletins.
There were crowds of onlookers, farmers, engineers, veterinarians,
physicians, scientists and a carnival atmosphere. Would Pasteur's claims of
vaccination hold up? Even Pasteur was privately concerned that he had acted
impetuously in accepting the challenge. Happily, the trial was a complete
success -- indeed, a triumph! Two days after final inoculation (May 5,
1882), every one of 25 control sheep was dead and every one of the 25
vaccinated sheep was alive and healthy. The fame of Pasteur and these
experiments spread throughout France, Europe and beyond. It was, says
Duclaux, "the anthrax vaccine that spread through the public mind faith
in the science of microbes". Within 10 years a total of 3.5 M sheep and
a half M cattle had been vaccinated with a mortality of less than 1%. The
immediate savings to the French economy were enormous, at least 7 M francs,
estimated to be enough to cover the reparations that France was required to
pay to Prussia for the loss of the Franco-Prussian War in 1880.
Supported by the successes with anthrax and fowl cholera diseases, Pasteur
identified and isolated over the next 2-3 years the microbes for many other
diseases including swine erysipelas, childbirth fever and pneumonia.
(Robert Koch sharply criticized Pasteur's scientific methodology
and conclusions in the area of Anthrax Vaccination leading to a bitter
dialog between these two scientists. To learn more about this
controversy, click
here.)
Rabies
The final and certainly most famous success of Pasteur's research was the
development of a vaccine against rabies or hydrophobia as it is also known.
The disease has always had a hold on the public imagination and has been
looked upon with horror. It evokes visions of "raging victims, bound
and howling, or asphyxiated between two mattresses" (Duclaux). The
treatments applied to victims were as horrible as the supposed symptoms:
this included cauterizing the bite wounds with a red-hot poker. Actually
very few persons die in any year from being bitten by a rabid dog or wolf.
The symptoms of the disease are variable: onset may take weeks to months to
develop if they develop at all. Nonetheless, Pasteur and his colleague Roux
realized that conquest of rabies would be recognized as a great achievement
to the world of science and to the public at large.
Pasteur and Roux initially attempted to transfer infection by injecting
healthy dogs with saliva from rabid animals. The results were variable and
unpredictable. Later, recognizing that the active agent was in the spinal
cord and brain, and because they were unable to detect a specific rabic
microorganism, Pasteur and Roux applied extracts of rabid spinal cord
directly to the brain of dogs. With this technique they could reproducibly
produce rabies in the test animals in a few days.
The goal was next to develop a vaccine that would provide protection to the
subject before the rabic agent moved from the bite site to the spinal cord
to the brain. This was achieved by injecting into test animals suspensions
of spinal cord of rabid rabbits that were attenuated in strength by air
drying over a 12-day period in the now-famous Roux Bottle (Fig. 7). A
strip of spinal cord was suspended from a hanger in the center of the bottle
containing a hole at the top of the bottle and one on the lower side. Air
entered 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.

Fig.
7. Roux bottle. The strip of spinal cord hangs from the top of
the flask; the drying agent rests on the bottom. Sterility is preserved by
the cotton plugs that allow air but not microbes to enter.
The
treatment plan used to develop immunity to rabies was to inject under skin
of a dog the least potent preparation of minced spinal cord, followed every
day for the next 12 days with a stronger and stronger extract. At the end of
this time, the animal was completely resistant to bites of rabid dogs and
failed to develop rabies if the most potent extracts were applied directly
to the brain. Forty dogs were successfully treated in this
manner.
Following confirmation of his reports in 1885 that he had made dogs
refractory to rabies by vaccination, Pasteur received wide acclaim and much
favorable publicity. But why not use the vaccine on humans? Frankly, Pasteur
was terribly afraid of things going wrong and he was particularly uneasy
about being unable to isolate the rabic substance. And so he continued to
insist that many years of additional research was necessary before the
treatment could be tried on humans.

Fig.
8. Pasteur examining a spinal cord specimen in a
Roux bottle.
But
the press of events made him act sooner. Two initial trials in humans
conducted with the help of his physician colleagues were indecisive: one
patient was discharged from the hospital by the administration after one
injection and what became of him was not known; the second patient was
a young girl suffering from an advanced stage of rabies such that she died
shortly after the procedure had commenced. A full trial of the
anti-rabies vaccine was yet to be made. On July 6, 1885, 9 year old
Joseph Meister and his mother appeared at Pasteur's laboratory. Two days
earlier the young boy had been bitten repeatedly by a rabid dog. He was so
badly mauled that he could hardly walk. His mother appealed to Pasteur to
treat her son as this youth faced certain death. Pasteur, with much
trepidation, treated the youth. Despite Pasteur's fears, Meister made
a perfect recovery and remained in fine health for the remainder of his
life.
A few months later another victim turned up. He was a young shepherd also
bitten by a mad dog. Following reports of his successful treatments, the
wild acclaim for Pasteur knew no bounds! Victims of dog and wolf bites from
France, Russia, the United States poured into his laboratory for treatment.
The newspapers and public followed these treatments and cures with intense
interest. Pasteur became a hero and a legend. The Pasteur Institute funded
by public and governmental subscriptions was built in Paris initially to
treat victims of rabies who were coming to Pasteur's laboratory in
increasing numbers. Later, Pasteur Institutes were built, including 3 in the
United States, to deal with human rabies and other diseases.
(A
translation of the original paper by Pasteur presented before the French
Academy of Science in 1885 describing his treatment for rabies is available:
Click
here)
Rabies was the last major research of the master scientist. His health was
failing and a paralysis of his left side from a serious stroke he suffered
in his 46th year made his working in the laboratory increasingly difficult.
Pasteur died in 1895 after suffering additional strokes. He was buried, a
national hero, by the French Government. His funeral was attended by
thousands of people (Fig. 9).

Fig. 9.
Pasteur funeral cortege
His
remains, initially interred in the Cathedral of Notre Dame, was transferred
to a permanent crypt in the Pasteur Institute, Paris (Fig 10).

Fig. 10. The
marble and mosaic crypt in the lower level of the Pasteur Institute, Paris.
In
a tragic footnote to history, Joseph Meister, the first person publicly to
receive the rabies vaccine, returned to the Pasteur Institute as an employee
where he served for many years as Gatekeeper. In 1940, 45 years after his
treatment for rabies that made medical history, he was ordered by the German
occupiers of Paris to open Pasteur's crypt. Rather than comply, Joseph
Meister committed suicide!