Download Pasteur Exhibit Text Louis Pasteur was born on December 27, 1822

Pasteur Exhibit Text
Louis Pasteur was born on December 27, 1822 in Dôle, a small village in Eastern France.
The family name was probably derived from the French pâturage, i.e. pasturage, since they
raised and pastured animals for a living. Louis Pasteur was descended from a modest family of
tanners who lived and worked for most of Pasteur’s early years in nearby Arbois.3 His father
Jean Joseph Pasteur and his mother Jeanne Etiennette Roqui, a native of Mamoz, France, were
married in 1816. Louis greatly admired his parents who doted on him. He was particularly proud
of his father Jean Joseph Pasteur who served under Napoleon in the Peninsular War in Spain
from 1812 through 1813. For his bravery, Jean Joseph Pasteur was awarded France’s highest
military honor, Chevalier de la Legion d’honneur (Knight of the Legion of Honor). The honor
given to Louis’s father imbued in Louis a life-long patriotism that most likely led to his zeal to
contribute to French science.
Although Louis Pasteur’s parents were of modest means and not well educated, they and
Louis’s school headmaster of l'Université d'Arbois, Monsieur Romanet, recognized that Louis
was exceptionally intelligent and therefore encouraged him to seek a higher education. But in
childhood, Pasteur displayed little interest to science or in other fields except portrait painting.3
In that respect, the existing portraits of his parents attest to his keen understanding of light and
perspective. But his parents advised a more secure profession, which would require a higher
education. However, as much as they desired the opportunity for their son, his parents could not
afford to send Louis to an institution of higher learning.
Captain Barbier in the Parisian municipal guard, who served with Louis Pasteur’s father in the
Peninsular War learned about Louis’s need and therefore funded his admission to the Almanach
du Commerce in Paris. The Franks were found, and Louis began his education. However, he
floundered in his studies until his late teens, when he seemingly suddenly awakened to an
interest in the physical sciences. That appeared to be due to a great extent to some of the famous
scientists who he encountered during his education. They included the chemist – crystallographer
Auguste Laurent (1808-1853)6 who discovered anthracene and phthalic acid, characterized
carbolic acid, and helped to lay the foundation of organic chemistry; Jean-Baptiste Dumas
(1800-1884), who studied organic synthesis and atomic weights; and the celebrated French
physicist - mathematician - astronomer Jean-Baptiste Biot (1774-1862) who studied the
polarization of light, magnetism, astronomy, and the extraterrestrial origin of meteorites. JeanBaptiste Biot was particularly important to Pasteur because he inspired him and provided the
basis for Pasteur’s early studies on the chiral structures of certain organic crystals. Given that
array of luminaries, it was not surprising that Louis decided to be a chemist. There is no evidence
that he was interested in biology at that point.
At l’Ecole Normale, Louis Pasteur became an assistant to the famous chemist Antoine Louis
Jérôme Ballard. It was in Balard's laboratory that Pasteur discovered the difference between
"right-handed" and "left-handed" crystals while he was working with tartaric acid. That
discovery concerning crystal structures of tartaric acid became the basis for his later
investigations in that field.
Louis Pasteur’s studies in l’Ecole Normale Supérieur en Paris culminated in a Docteur-èsSciences in 1847. Louis Pasteur decided upon an academic career. He quickly became
successful. Two years after obtaining his doctorate degree, Pasteur became Professeur de Chimie
ã Strasbourg in Alsace in Eastern France. Five years later (1854), he moved to Lille in Northern
France (French Flanders) where he became Professor et Doyen de la Faculté de la Science
ã Lille. Pasteur’s stay there was short for he moved in 1865 to l’Ecole Normale Supérieur en
Paris where he had previously studied and became Professeur de Chimie ã l’Sorbonne and
Directeur du Laboratoire de la Physico-chimie. He remained there for the next twenty-two
years. Then in 1887 he became the director of a new scientific institution that still bears his
name, l’Institut Pasteur.3
Louis Pasteur’s first independent research was at the Université à Strasbourg and concerned
the discrepancy between the ability of naturally occurring and synthetic tartaric acid to rotate a
beam of light that passed through them. He was fortunate to investigate appropriate molecules, to
have the correct temperatures in his laboratory for the experiments concerning tartaric acid to
succeed, and to have the patience and skill to identify the different populations of crystals by
microscopy.3 He discovered during his investigations mirror-image populations of several
organic crystals. First, he separated racemic mixtures of tartaric acid crystals by hand into righthanded and left-handed populations. The re-solubilized crystals rotated polarized light to the
right or left depending upon their orientation. Thus, he ascertained by chemistry and physics that
optical refractions of the organic molecules tartaric acid, quinine and aspartic acid were due to
their molecular asymmetries.3,8, 25-27 How these asymmetries developed was unknown but
Pasteur suggested that they were primordial events.3,8 Pasteur was thus one of the first to forge a
link between the physical and biological sciences. His findings spurred investigations by others
that provided insights into the chiral (from the Greek, xeivr or hand) nature (not superimposable
on its mirror image) of many carbon compounds.
Because of his success in understanding the chiral structures of certain organic compounds,
Louis Pasteur was asked by the French Government to examine the cause of wine spoilage
that endangered a major industry in France. He used microscopy to discover that
fermentation that was spoiling wine was due to microorganisms that were destroyed by
controlled heating.28 He concluded that fermentation was due to living microorganisms rather
than chemical processes. In that regard, he was opposed to the views of the famous chemist
Justus von Liebig (1803-1873).29 A few years after Louis Pasteur’s death, the difference in the
interpretations was resolved when fermentative enzymes were found in live microorganisms or
released from dead ones.
Related to the above was Pasteur’s discovery of anaerobiosis, whereby some
microorganisms survive and multiply without oxygen. It was later discovered that was due to
either fermentation or anaerobic respiration.
After his work on fermentation, an old friend of Pasteur, Professor Jean Batiste Andre
Dumas at the Université de Paris turned again to Pasteur to solve another important commercial
problem, the cause of the decline in the silk worms (the larval form of the domesticated
silkworm (Bombyx moriI) that was wrecking the silk industry in the south of France. Louis
Pasteur and four of his best students went to Alais in southern France to investigate the problem.
After a long, trying period that involved tedious microscopic observations and manipulations, he
and his students found that the silkworm disease was due to two separate kinds of infectious.30
Much later, a number of other infectious agents were found to be at fault. In retrospect the
findings were not only important for the beginnings of microbiology, but also because the
findings indicated that different pathogens might cause similar pathogenic events.
Building upon the 1768 observations by the famous Italian biologist Lazzaro Spallanzani
concerning microbes in the air and Charles Cagniard de la Tour and Theodor Schwann
findings, in the early1860s Louis Pasteur delivered the final blow to spontaneous generation in
his experiments in which swan-necked vessels (Figure 3) were used to exclude ‘dust’-borne
microorganisms from growth media in the flask. Pasteur make also have been spurred to do the
experiments after reading Charles Darwin’s 1859 seminal work On the Origin of Species by
Means of Natural selection or The Preservation of Favoured Races in the Struggle for Life.
After preparing a series of flasks, Pasteur drew their necks out into very narrow extensions,
curved in various ways and exposed to the air by an opening one to two millimeters in diameter.
Without sealing these flasks, he boiled the liquid in some of them for several minutes and left
other ones unboiled to serve as controls. When all of the flasks were placed in calm air, the
unboiled liquids became covered with various molds in twenty-four to forty-eight hours, while
the boiled flasks remained unaltered indefinitely. Moreover, if one of the curved necks were
detached from a hitherto sterile flask and placed upright in it, vegetative growths appeared in a
few days. Louis Pasteur concluded that the “sinuosities and inclinations” of his swan-necked
flasks protected the liquids from growths by capturing the dusts that entered with the air. In fact,
Pasteur insisted, nothing in the air—whether gases, fluids, electricity, magnetism, ozone, or some
unknown or occult agent—were a precursor of microbial life except the germs carried by
atmospheric dusts.
Thus Louis Pasteur proved that some infectious agents were airborne.33 These experimental
findings strongly suggested that epidemic diseases were caused not by spontaneous creation of
microbial life but by microbes transmitted by air or other routes. Thus the science of
microbiology began.
Louis Pasteur was then encouraged to investigate infections in certain vertebrates. As with
his earlier research concerning the spoilage of wine and silkworm larva infections, he was
concerned with preventing infections that were of major public concern. His investigations of
chicken cholera,34 anthrax in sheep,35,36 and human rabies36 were important milestones in
the history of microbiology and immunology.
To begin with, Pasteur turned an inadvertent experimental error into the production of a
vaccine against chicken cholera.9 His research associate Charles Chamberlain (1851-1908)
mistakenly left a culture of the cholera pathogen out of the incubator for some days before
injecting it into uninfected chickens.8,34 The injected infected animals survived without apparent
ill effects. Pasteur reasoned correctly that the pathogen was attenuated and could be a vaccine to
prevent the disease. This was confirmed in subsequent experiments.
Next Louis Pasteur extended earlier observations by the veterinarian Casimir-Joseph
Davaine (1812-1882)37 concerning the morphology of anthrax bacilli and the experimental
transmission of anthrax to rabbits. Pasteur discovered that anthrax bacilli lost their virulence but
retained their immunogenicity after heating at 42° to 43° C for eight days while the culture
preparations were infused with oxygen. However, in the famous public trials of the anthrax
vaccine that he and his associates carried out in Pouilly-le-Fort in 1881,36 a variation in a method
developed earlier by Jean-Joseph Henri Toussant (1847-1890)38 was used.
The results of Louis Pasteur’s anthrax experiments were challenged for good reasons by
Pasteur’s major rival, Robert Koch, who was famous for his postulates concerning the criteria
that a microorganism caused a particular disease the isolation of Bacillus anthracis in 1877, and
his discovery of the cause of human tuberculosis (Mycobacterium tuberculosis) in 1882. It was
of interest that these two founders of microbiology were at odds about the efficacy of the
vaccine, since Koch was the first to isolate the pathogen. Eventually the results of Louis
Pasteur’s anthrax vaccine experiments were vindicated. But the basis of Koch’s question came to
light many years later when it was found that Pasteur’s colleagues Roux and Chamberlain
modified the vaccine by treating anthrax bacilli with the oxidizing agent potassium bichromate.8
That change in the vaccine preparation became known only after Pasteur’s laboratory notebooks
housed in l’Bibliotheque Nationale en Paris were opened for study in the 1970s against Pasteur’s
explicit instructions.8
Louis Pasteur’s last scientific contribution was the accidental discovery in 1885 with Emile
Roux of the rabies vaccine. When rabies-infected spinal cords were inadvertently air-dried, they
were found to be non-pathogenic in experimental animals. That laboratory altered tissue
preparation became the basis for a vaccine against that infection.8,39 It was disconcerting to learn
several decades later that Pasteur first used the vaccine in an adult who may not have had rabies
and in a rabid adult who died before the vaccine was tested in experimental animals.8 Moreover,
when Pasteur’s research assistant, Jacque-Joseph Grancher (1843-1907), accidently injected
himself with rabies virus, Pasteur convinced him to receive the vaccine. The injector (Pasteur’s
nephew, Adrien Loir) and Grancher received the vaccine without untoward effects.40 Neither
Loir nor Grancher developed rabies. The famous treatment of the nine-year child Joseph
Meister, who was exposed to rabies,3,8,39 came afterwards but before animal experiments
with the vaccine derived from rabbits were completed.8
Long afterwards Louis Pasteur was criticized severely for prematurely injecting the rabies
vaccine into a human. However, it should be understood that Pasteur did not seek out the child
who was bitten by a rabid dog. Indeed, the mother of the child upon learning that Pasteur was
working on a vaccine to prevent rabies, pleaded with him to save her child. Pasteur, who was not
a physician, at first, resisted her pleas. He nevertheless knew that rabies was inevitably fatal.
Furthermore, his preliminary studies suggested that the vaccine was at least harmless and
possibly protective if used soon enough after exposure to the virus. Of course, current stringent
guidelines concerning human research would have precluded the use of such an experimental
vaccine in humans, but happily the first experimental vaccine used in humans proved to be
successful in that as he related in 1886 to the Académie des Sciences française all but one of 350
patients bitten by a rabid animal were saved by the immunization.
Fortune favored Louis Pasteur in his rabies studies because there is a considerable latent
period between the bite from a rabid animal and the invasion of the brain by the virus. In that
respect the rabies virus undergoes a number of elaborate steps before infecting the brain. First the
virus must enter the host and then replicate in a muscle or peripheral nerve cell by binding the
acetylcholine receptor in those tissues. Pinocytosis (formation of small vesicles that contain the
virus) then occurs and the virus subsequently enters an endosome of the cell. Consequently, the
five proteins (nucleoprotein, phosphoprotein, matrix protein, glycoprotein, and the viral RNA
polymerase) and single strand RNA of the virus are released into the cytoplasm. The viral RNA
polymerase then transcribes 5 mRNA strands and a positive strand of RNA all from the original
negative strand RNA by using free nucleotides in the cytoplasm. These 5 mRNA strands are then
translated into their corresponding proteins at free ribosomes in the cytoplasm of the cells of the
host. The newly propagated viruses are released and when they infect peripheral nerves they are
retrogradely transported to the brain where an extensive fatal encephalitis develops.
An active immunization requires about ten to fourteen days to produce sufficient quantities
of circulating antibodies to nullify the rabies virus infection. Thus, if the immunization is given
quickly enough, the rabies-infected patient is saved. Although the more modern human diploid
cell rabies vaccine is safer and more efficacious, the principles concerning the current rabies
vaccine emanate from Pasteur’s original studies.
Although current commentators have criticized Pasteur for his somewhat premature use of
the rabies vaccine in human volunteers and individuals who had probably contracted rabies
before the experimental animal studies were completed, it should be recalled that rabies was a
fearsome, uniformly fatal, agonizing disease. Undoubtedly Pasteur was torn between inaction
and the possibility that his as yet incompletely tested vaccine might work. Furthermore, he was
handicapped in that there was no way to ascertain whether a bitten individual had rabies until the
individual became symptomatic. We now know that if he waited that long in the case of the
famous child who was infected with the rabies virus, the vaccine would have been ineffective
and the patient would have died. Finally, it is easy but perhaps not always fair to apply current
standards to problems in medical research that occurred well over a century ago.
However, even Pasteur’s critics will agree that few devoted themselves more to science and
applied lessons learned from one experimental field to another than Louis Pasteur. In that
respect, despite little initial training in biology or medicine and a stroke at age 46 that left him
partially paralyzed in his left arm and leg, Louis Pasteur made remarkable discoveries in
bacteriology, fermentation, infectious disease, and immunology.3 In that respect, Pasteur
commented three years before his discovery of mirror-image populations of organic crystals that
‘in the fields of observation, chance favors only the prepared mind.’8 The three mythical princes
of Serendip (hence, serendipity) and the Talmudic Rabbi Yochanan, as related by Rava, would
have heartedly agreed (Hebraic Literature: Translations from the Talmud, Midrashim, and
Kabbala, chapter II.). The vaccines that Pasteur developed by serendipitous means became the
basis for the developments of many other vaccines that would be developed for humans and
other animals.
There is considerable evidence that Louis Pasteur was a complex individual - very intelligent,
highly imaginative, versatile, exceptionally persistent in his research, tenacious, dedicated to the
control of serious diseases, and very active in the last decades of his life in developing some of
his close associates such as Emile Roux who became le Directeur de l'Institut Pasteur en Paris
in 1904 and the world famous, Russian born biologist Ilya Ilich Metchnikoff who almost singlehanded discovered the essential role of phagocytic cells in host defense against infectious agents
and the role of those cells in inflammation. As a result of his very important discoveries,
Metchnikoff founded the field of cellular immunology. He in turn provided the opportunity
for the most famous Belgian immunologist, Jules Bordet to discover complement and their
binding to antigen-antibody complexes, the complement fixation test, anaphylatoxin,
conglutinin, lysozyme in human milk, the formation of thrombin, the participation of
platelets in coagulation, and the pathogen that caused whooping cough. It is to Pasteur’s
credit that Metchnikoff and Bordet were later honored by the Nobel Prize in Physiology or
Medicine.
But on the other hand, at times Pasteur dealt harshly with some of his associates, pointedly
did not share his laboratory notebooks with his colleagues, manipulated some research findings
to suit his purpose, and displayed considerable anger toward some of his scientific rivals such as
Robert Koch when they raised legitimate questions about his research. Thus, Louis Pasteur
emerges as one of the most intriguing individuals in the history of science. Given his complex
life, perhaps the intrigue concerning his library that we discovered should have been expected.
Beginning in 1868, Pasteur suffered a series of strokes that gradually incapacitated him. The
final, fatal stroke occurred on September 28, 1895. Following his death at age 73, Louis Pasteur
was mourned throughout France and in many other countries.11 Indeed, admiration for his
scientific achievements continues to the present day. His tomb in l’Institut Pasteur en Paris
remains one of the most frequently visited memorials in France.