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Contribution of physiologists to the identification
of the humoral component of immunity in the
19th century
Yves-Marie Lahaie & Hervé Watier
To cite this article: Yves-Marie Lahaie & Hervé Watier (2017) Contribution of physiologists to the
identification of the humoral component of immunity in the 19th century, mAbs, 9:5, 774-780, DOI:
10.1080/19420862.2017.1325051
To link to this article: https://doi.org/10.1080/19420862.2017.1325051
© 2017 The Author(s). Published with
license by Taylor & Francis Group, LLC©
Yves-Marie Lahaie and Hervé Watier
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PERSPECTIVE
Contribution of physiologists to the identification of the humoral component
of immunity in the 19th century
Yves-Marie Lahaie
a
and Herv
e Watier
a
,
b
,
c
a
Universit
e Fran¸cois-Rabelais de Tours, Laboratoire d’Immunologie, Tours, France;
b
CNRS, UMR 7292, Tours, France;
c
CHRU de Tours, Service
d’immunologie, Tours, France
ARTICLE HISTORY
Received 9 January 2017
Revised 19 April 2017
Accepted 26 April 2017
ABSTRACT
The history of antimicrobial humoral immunity usually focuses on the works of the German school at the
end of the 19th century, born in the tradition of chemistry and disinfection. Starting from an old quarrel of
priority about serotherapy between Emil von Behring (1854–1917) and the French physiologists Charles
Richet (1850–1935) and Jules H
ericourt (1850–1938), we first confirm that the latter stated the principle of
serotherapy in 1888 and put it into practice before the seminal Behring’s article in 1890, observing several
adverse effects of this new immunotherapy. We also find that researchers who can be considered heirs of
the French school of Physiology founded by Claude Bernard (1813–1878) also investigated the field of
humoral immunity in the 1870–1880s. Maurice Raynaud (1834–1881), Auguste Chauveau (1827–1917),
and eventually Charles Richet applied the experimental method of Claude Bernard to the young field of
microbiology, illustrating a movement called by Jacques L
eonard “physiologization of the pasteurism.”
However, the contribution of physiologists in this field started before Louis Pasteur, leading to the
conclusion that physiologists and chemists synergistically contributed to the birth of bacteriology and
immunology.
KEYWORDS
Charles Richet (1850–1935);
Emil von Behring (1854–
1917); French school of
physiology; immunology
history; Jules H
ericourt
(1850–1938); serotherapy
history; 19th century
Introduction
Several historians have shown that the concept of humoral
immunity was born at the very end of the 19th century within
the German School, around George Nuttall (1862–1937), Emil
von Behring (1854–1917) and Paul Ehrlich (1854–1915).
1,2,3
The invention of serotherapy in 1890 by Behring and his asso-
ciate Shibasaburo Kitasato (1852–1931)
4,5
therefore appears to
originate from this movement. However, as recently shown by
Jonathan Simon, this discovery needs instead to be placed in
the tradition of disinfection: as his colleagues at the Koch’s
Institute, who were especially interested in disinfectants and
had a chemical view of immunity, Behring conceived serother-
apy in terms of disinfection.
6
Rewarded in 1901 with the first
Nobel Prize for Medicine, Behring is of course widely recog-
nized as “the pioneer”of serotherapy,
7,8,9,10
according to the
words pronounced by Professor K.A.H. M€
orner, Rector of the
Royal Caroline Institute, during the Nobel Prize ceremony.
11
Another historian, Stewart Wolf, in his Charles Richet’s biog-
raphy published in 1993, relates an old quarrel of anteriority
about the discovery of serotherapy. This quarrel opposed Behr-
ing to the French physiologist Charles Richet (1850–1935), both
of them claiming to be the first inventor of serotherapy. Charles
Richet indeed described “h
ematoth
erapie”with his associate
Jules H
ericourt (1850–1938) as early as 1888.
12
Their contribu-
tion to the discovery of serotherapy has never been studied in
detail, neither has the context in which this took place. Whereas
almost nothing has been published concerning Jules H
ericourt,
Charles Richet is well known because of his discovery of anaphy-
laxis, awarded a Nobel Prize in 1913, and because of his many
other contributions, notably in the field of neurosciences.
12,13
Charles Richet was the heir of Claude Bernard (1813–1878) and
of the French School of Physiology, so could have performed his
research with a totally different mindset than that of Behring.
Richet and possibly H
ericourt can be seen as actors of what the
French historian of medicine Jacques L
eonard called, using a
neologism, a movement of “physiologization of pasteurism,”
14,15
when physiologists moved into the field of bacteriology in the
1880s, which led to the birth of Immunology. When describing
this movement, L
eonard both referred to cellular and humoral
immunity. However, the fame of Elie Metchnikoff’s (1845–
1916) discoveries about phagocytosis
1
somehow masked the
humoral side of the “physiologization of pasteurism”movement,
which remains to be described.
To address this question, we first analyze whether physiolo-
gists, after Claude Bernard, investigated the concept of immunity
and its physiologic substratum. We then explore the works of
Richet and H
ericourt, whether they depart from that of the other
physiologists, and whether they are truly –or not –the first
enunciation of the serotherapy principle. We also analyze the later
contribution to serotherapy of Richet and H
ericourt, i.e.,anti-
cancer serotherapy, which has already been explored with the per-
spective of more general attempts to fight cancer,
16,17
and has also
been evoked by several authors
12,13,18,19,20
but still needs to be ana-
lyzed in the context of serotherapy and immunity.
CONTACT Herv
e Watier watier@med.univ-tours.fr Laboratoire d’Immunologie, Facult
edeM
edecine, 10 Boulevard Tonnell
e, 37044 Tours, France.
Published with license by Taylor & Francis Group, LLC © Yves-Marie Lahaie and Herv
e Watier
This is an Open Access article distributed under the terms of the Creative Commons Attribut ion-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/),
which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
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Input of physiologists in the field of immunity
Maurice Raynaud (1834–1881), who described Raynaud’s dis-
ease (recurrent vasospasm of the fingers and toes occurring in
response to cold exposure) and discussed the neuronal regula-
tion of the vascular tonus in reference to the works of Claude
Bernard and that of Etienne-Jules Marey (1830–1904), was
probably also the first physiologist to investigate the concept of
immunity. In the late 1870s, he questioned the mechanisms of
induction of immunity during the process of Jennerian vaccina-
tion. According to him, only one of the 3 general systems, i.e.,
blood circulation, lymphatic circulation or nervous system,
could convert the local and transient vaccinia pustule into the
long-lasting and general phenomenon called immunity. After
having analyzed each of these systems, he concluded that the
vaccinia virus was converted inside the lymph nodes into an
“elaborated lymph,”which was then transmitted through blood
to the whole body, conferring immunity. Raynaud therefore
anticipated the discovery of cell-mediated mechanisms of spe-
cific immunity, and appears to have been the first to have con-
sidered immunity from the perspective of the host, as
immunologists do.
21,22
Above all, he was the first who explicitly
associated blood and immunity, even though he never tried to
do any transfer of immunity.
21,22
The French veterinarian Auguste Chauveau (1827–1917),
from Lyon, was a great anatomist and physiologist, and consid-
ered himself to be an heir of the physiologist Claude Bernard
although he never attended his teaching. Chauveau also early
devoted himself to microbiology and, in our opinion, he should
be considered the real founder of this science, years before
Louis Pasteur (1822–1895). Going deeper than Casimir
Davaine (1812–1882) (who proved in 1863 the microbial
nature of anthrax
23,24
), Chauveau showed in 1868 the corpus-
cular nature of the factors responsible of glanders, cowpox and
variola, i.e., one bacterial and 2 viral diseases,
25,26,27
and then
developed a theory, which synthesized 2 fundamental epidemi-
ologic concepts, considered to be opposite, contagion and
infection (the concept of infection was used to explain the
appearance of an epidemic disease without any contagion
mechanism). This “th
eorie de la contagion m
ediate ou miasma-
tique”(theory of mediate or miasmatic contagion) redefined
infection as a mediate contagion, that is to say a contagion
through environment.
28,29,30,31
Thus, Chauveau built the foun-
dations of microbiology: microbes, depicted as factors of dis-
eases, are involved in contagion as well as in infection.
Chauveau was also the author, in the 1880s, of an immunity
theory that conflicted with Pasteur’s view. Whereas Louis Pas-
teur thought that immunity was due to an exhaustion of the
nutrients that were necessary for microorganisms,
32
Chauveau
maintained that microorganisms produced, within their host’s
blood, some substances, which were harmful to themselves.
33,34
Consequently, although he conceived it exactly in the reverse
manner, Chauveau perceived the existence of a humoral immu-
nity. This is an illustration of the main role of the French school
of Physiology, to which Richet also belonged, in formulating
the basic concepts of immunity.
35
To verify his immunity the-
ory, Chauveau tried to transmit immunity against anthrax to
sheep, transfusing them with large volumes of anthrax-infected
blood whose microorganisms had been previously killed by
heating.
36
As the experiment failed, Chauveau abandoned and
did not generalize the concept.
Works of Richet and H
eRicourt before the ones
of Behring and Kitasato
Charles Richet and Jules H
ericourt
Born in Paris in 1850, son of Prof. Alfred Richet (1816–1891), a
famous surgeon who was a friend of Claude Bernard, Charles
Richet (Fig. 1A) became professor of Physiology at the Faculty
of Medicine of Paris in 1887. During his lifetime, he studied
many fields of physiology, such as gastric juice, thermoregula-
tory mechanisms, dive reflex and psychology. He also discov-
ered anaphylaxis, for which he was awarded the Nobel Prize in
1913. Very cultured and curious, he also devoted himself to lit-
erature, theater, and aviation.
12,37
Much less known than Richet, Jules H
ericourt (Fig. 1B)is
however an interesting character. Also born in Paris in 1850,
but in a popular milieu, he became friend with Richet while
studying together in secondary school, then spent several years
as a medical officer in the French Army, where he manifested a
deep interest in microbiology. In 1887 he joined Charles Richet
at his Physiology laboratory and during 15 y he performed
many studies with Richet, particularly in the field of serother-
apy. Moreover, H
ericourt was a committed physician: at the
time of the Dreyfus Affair, he was one of the first “Dreyfusard”
intellectuals, and testified in favor of Dreyfus at the Zola trial in
1898. He also co-founded the “Ligue des Droits de l’Homme”
(Human Rights League) and was one of its Deputy-Presidents.
Deeply concerned about social issues, he later dedicated himself
to poor people, mainly as director of an anti-tuberculosis dis-
pensary from 1904 to 1934.
38
Both Richet and H
ericourt were great admirers of Louis Pasteur.
As soon as 1883, Richet published a series a scientificpapersonfish
bacteria with Louis Olivier (1854–1910), a Louis Pasteur’s
pupil.
39,40,41,42
He also published a very surprising bacteriology-fic-
tion short story under his writer pseudonym Charles Epheyre in
1890.
43
Later in 1914, he anonymously won the competition
launched by the French Acad
emie des Sciences with the best poem
on the glory of Louis Pasteur.
12
On his side, H
ericourt published a
Figure 1. Charles Richet (1850–1935) (left) and Jules H
ericourt (1850–1938) (right).
(Fonds Watier, Rabelais Fundation; University Library of Medicine, Universit
e Fran¸c ois-
Rabelais de Tours).
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first scientific review on the pathogenic role of microbes in 1884,
44
popularizing the theories of Louis Pasteur, while devoting himself
to agents of cholera,
45,46,47,48,49,50,51
and tuberculosis.
52,53
It is also
established that H
ericourt had personal contacts with Louis Pas-
teur
54
(Fig. 2).
Formulation of the principle of serotherapy
In 1888, Richet and H
ericourt isolated by chance a bacterium
they called Staphylococcus pyosepticus, probably a strain of S.
aureus. After a few experiments, they noticed that dogs were
naturally resistant to this bacterium, whereas rabbits were sus-
ceptible and died.
55,56
They also showed that it was possible to
induce an acquired immunity against S. pyosepticus by vacci-
nating rabbits in accordance with Pasteurian procedures: “les
effets virulents du St. pyosepticus comportent une vaccination”
(“the virulent effects of St. pyosepticus carry a vaccination”).
57
Influenced by Chauveau’s works, and using like him the experi-
mental approaches recalling the ones of Claude Bernard’sschool,
they hypothesized that immunity could be transmitted from dogs
to rabbits through blood. But there was a fundamental difference
with Chauveau’s experiments: in contrast to him, Richet and
H
ericourt decided not to use infected blood, but blood from
healthy dogs. Their experiments were described in an announce-
ment read on the 5
th
of November 1888 at the Acad
emie des Scien-
ces by Aristide Verneuil (1823–1895), of whom Charles Richet was
a pupil. After having transfused rabbits with dogs’blood, they
inoculated them 36 hours later with S. pyosepticus and made 2
observations: canine blood transfusion appeared to confer
immunity against S. pyosepticus, and this immunity was stronger
if the donor animal had been –accidentally –inoculated by S. pyo-
septicus a few months before. They attached great importance to
this second point: “Il nous semble donc assez probable que le sang
deschiensinocul
es pr
ec
edemment avec le Staph. pyosepticus, puis
absolument gu
eris, conf
ere une immunit
epluscompl
ete que le sang
deschiensintacts”(“it seems to us quite likely that the blood of dogs
that have been previously inoculated by Staph. pyosepticus, then
that have absolutely recovered, gives a greater immunity than intact
dogs’blood”). In other words, the blood of vaccinated dogs conveys
an acquired immunity, which can be transmitted. Eventually,
Richet and H
ericourt did not hesitate to generalize their discovery:
“cette influence du sang de chien […]s’
etend peut-^
etre
ad’autres
microrganismes (le charbon, la tuberculose)”(“this influence of
dog’s blood […] maybe applies to other microorganisms (anthrax,
tuberculosis)”).
58
The 2 scientists had thus discovered a new immunization
method against infectious diseases, based on a transfer of
humoral immunity from a resistant animal to a sensitive ani-
mal. At this time, H
ericourt and Richet believed it was possible
to transfer what is now called innate immunity as well as
acquired immunity. Nevertheless, it appears undeniable that
the general principle of serotherapy, even taken in a restrictive
sense of acquired immunity, is settled in this paper published
in November 1888.
Application of this new method by Richet and H
ericourt
Fully aware of the great importance of their discovery, in spite
of their colleagues’indifference,
59
Richet and H
ericourt quickly
decided to apply it to human diseases. After having hesitated
between diphtheria, anthrax and tuberculosis, they chose the
latter since “white plague”was a huge problem of public health.
In hindsight, it is obvious that this was the worst choice: immu-
nity against tuberculosis is now known to be cell-mediated and
not antibody-mediated but, more importantly, they had no
possibility to induce an acquired immunity, even in animals.
Their first experiments (1889–1990) were therefore focused on
blood transfer of innate immunity. Considering that dogs were
said to be resistant to tuberculosis, Richet and H
ericourt first
tried to transmit their innate immunity to rabbits, using dogs
that had never been exposed to Koch’s bacillus. They found
that dog’s blood transfusion seemed to slow the progression of
tuberculosis.
60,61,62,63,64
Shortly after, other French researchers
performed similar experiments, attempting in 1890 blood
transfers of innate immunity from goats to humans (Fig. 3).
Richet and H
ericourt’s area of concern, however, was to find
a way to obtain an acquired immunity that could be trans-
ferred; in other ways, they had to find a mean to vaccinate
against tuberculosis. They first tried to administer into rabbits
avian mycobacteria (given by Andr
e Chantemesse (1851–
1919)), which were killed by heating, in a typical Pasteurian
frame of mind.
65
Then in September 1890, Richet and
H
ericourt reported having inoculated a dog with virulent
bacilli; after a few days, the dog’s blood, supposed to carry an
acquired immunity, was injected to rabbits, which seemed to
have become more resistant to tuberculosis.
66
Consequently, at the end of November 1890, Richet and
H
ericourt had already applied their method to 2 microorganisms,
Figure 2. Dedication of Louis Pasteur to Jules H
ericourt, at the front of his
emblematic book Etudes sur la maladie des vers
a soie (Fonds Watier, Rabelais Fun-
dation; University Library of Medicine, Universit
e Fran¸cois-Rabelais de Tours).
776 Y.-M. LAHAIE AND H. WATIER
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S. pyosepticus and Koch’sbacillus.Theirinterpretationofthetrans-
fer of immunity is quite interesting. Using reasoning similar to that
of German scientists, they put forward a “humoralist”hypothesis:
“le sang de chien contient des substances qui passent dans les tissus
du lapin et qui, par leur action chimique propre, s’opposent au
d
eveloppement du microorganisme”(“dog’s blood contains some
substances which pass into the rabbit’s tissues, and which by their
own chemical action oppose to the development of the microorgan-
ism”).
67
However, it is of note that all their experiments were per-
formed with whole blood; Richet and H
ericourt reported to have
used blood serum instead of whole blood only on December 6,
1890,
68
which was two days after Behring’s seminal publication of
serotherapy.
4
The use of serum was obvious for the German school,
since Emil von Behring had shown in 1888 that blood bactericidal
activity is borne by the serum.
69
However, the first researchers who
used serum in the context of immunity transfer seem to be Ogata
and Jasuhara, from Tokyo, in June 1890 (cited in ref. 70).
Richet and H
ericourt’s anticancer serotherapy
In 1895, while Behring’s serum against diphtheria was highly
successful, Richet and H
ericourt, discouraged by their failure in
tuberculosis, tried to develop a serum against cancer, thought
to be an infectious disease.
71
As was mentioned, this episode
has already been described by several historians, but it is impor-
tant to report it here again, not only because it constitutes an
original work from Richet and H
ericourt, but because it offers
the opportunity to make new relevant observations and to for-
mulate bold scientific hypotheses, shedding light on the original
scientific approach they adopted.
After having immunized a donkey and 2 dogs with extracts
of an osteosarcoma, Richet and H
ericourt collected the sera
and injected them into 2 patients, one having a cancer of the
thoracic wall and the other having a tumor of the upper abdo-
men. After a few weeks of daily injections, both patients
showed a considerable decrease of their tumor’s volume and an
improvement of their general condition.
72
These results were
reported to the Acad
emie des Sciences in April 1895 and
received a warm welcome. Many physicians, in particular Ren
e
Boureau (1854–1936) from Tours, tried to reproduce Richet
and H
ericourt’s experiments.
73
Anticancer serum was shown to
improve patients’conditions and sometimes to temporarily
reduce the volume of the tumors (facts that were observed by
many investigators, rather surprisingly), but not to stop disease
progression.
74,75
Richet and H
ericourt eventually abandoned the field of sero-
therapy to dedicate themselves to other studies (Fig. 4). It is,
however, interesting to point out that Richet and H
ericourt’s
anticancer serum, based on a wrong hypothesis and a lot of
naivety regarding such a complex disease, really anticipated the
current fantastic successes of monoclonal antibodies in cancer.
Very intriguingly, H
ericourt’s understanding about the way
their anticancer serum could be efficient, stated in 1899 and
probably inspired by other authors’thoughts (in particular
Charles Bouchard (1837–1915),
76
Elie Metchnikoff (1845–
1916) and Emile Roux (1853–1933)
77
), is somewhat visionary:
“ce secours dont l’organisme a besoin [pour triompher de la
Figure 3. Transfusion of blood from a goat to a consumptive (tuberculous) woman
by Samuel Bernheim (1855–1915) (L’Illustration. 1891 Mar 7;2506:213. Fonds Watier,
Rabelais Fundation; University Library of Medicine, Universit
e Fran¸cois-Rabelais de
Tours). Samuel Bernheim, transfusing goat’s blood directly to humans, tried a vari-
ant of the method of 2 researchers from Nantes (France), Georges Bertin (1833–
1916) and Jules Picq.
89
Bertin and Picq worked on blood transfusion against tuber-
culosis from 1890.
90
Like Richet and H
ericourt, they focused on this dreadful illness,
but contrarily to them, they only tried a transfer of innate (natural) immunity, con-
sidering goats as naturally resistant against tuberculosis. Bertin and Picq are the
inventors of the word “h
ematoth
erapie,”which was widely used in France at that
time.
91
They were also the first to perform a blood injection (subcutaneously) to a
human being with tuberculosis, on the 3rd of December 1890.
92
This operation
caused a sensation worldwide, as witnessed by a New York Times article in January
1891.
93
Figure 4. Caricature of Jules H
ericourt published in the issue #75 of Chanteclair in
1911 (Fonds Watier, Rabelais Fundation; University Library of Medicine, Universit
e
Fran¸cois-Rabelais de Tours). Just after their works on serotherapy, Richet and
H
ericourt set up a raw meat juice-based therapy against tuberculosis, which they
called “zomoth
erapie.”This picture shows H
ericourt squeezing out raw meat juice
with a printing press. In the background, some various sera phials remind his con-
tributions to serotherapy (tuberculosis, cancer, syphilis). A cartridge pouch on the
wall (pink-colored because of the “Revue rose,”nickname of the “Revue scientifi-
que”for which H
ericourt was successively secretary, chief editor and manager,
from 1887 to 1903) evokes the military past of H
ericourt.
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maladie], le s
erum le lui apporte; et les phagocytes y trouvent le
stimulant n
ecessaire
a leur insuffisante activit
e. C’est l’appoint
qui d
ecide la victoire en leur faveur”(“the serum provides the
organism with the assistance he needs [to beat the disease]; and
the phagocytes find there the necessary stimulus to their insuffi-
cient activity. This contribution determines the victory in their
favor”).
78
Indeed, the current use of antibodies targeting cancer
cells and recruiting immune effector cells to favor cancer cell
killing,
79,80
or that of immune checkpoint inhibitors waking up
these effector cells,
81
are really modern transpositions of
H
ericourt conceptions.
Anticancer serotherapy also gave Richet and H
ericourt the
opportunity to describe some adverse reactions of serotherapy.
They had first mentioned one case of pain and “two or three”
cases of pruritus after serum injection in 1891,
82
being probably
the first to do so. Their description with the anticancer serum
in 1895 is more precise: “Ces injections de s
erum […] produi-
sent vers la troisi
eme ou quatri
eme injection, rarement plus t^
ot,
quelquefois plus tard, une
eruption urticaire,
eryth
emateuse,
comme en produisent d’ailleurs tous les s
erums […].”(“These
serum injections […] induce around the third or the fourth
injection, rarely earlier, sometimes later, an urticarial, erythem-
atous rash, as anyway all serums do […].”)
83
Richet and
H
ericourt therefore described typical cases of what will be
called later “serum sickness.”Type 3 hypersensitivity reactions
related to serum were mentioned by several authors as early as
the mid-1890s,
84
but they were clearly characterized in 1905 by
Clemens von Pirquet (1874–1929) and B
ela Schick (1877–
1967) as serum sickness.
85
H
ericourt and Richet also noted:
“Dans quatre cas, l’injection a provoqu
e des accidents syncopaux
(rapidement dissip
es) dont la cause nous est encore inconnue”
(“In 4 cases the injection induced syncopal accidents (quickly dis-
appeared), the origin of which remains unknown to us”).
83
The
nature of these syncopal accidents remains more uncertain:
anaphylactic shocks or, in this context of anticancer serum,
“cytokine-release syndromes”(CRS)? In 1899, H
ericourt better
developed the clinical symptoms: the dry cough followed by
dyspnoea and face cyanosis he described
78
would rather evoke
the laryngeal edema that characterizes CRS.
86
Discussion
The 2 French physiologists always claimed priority for the dis-
covery of serotherapy, but Behring never acknowledged it and,
in a quite discourteous way, quoted their works only to dis-
credit them.
87
At that time, many scientists agreed that Richet
and H
ericourt were right, even in Germany, as witnessed by an
article written in 1893 by another pupil of Koch, Carl Fraenkel
(1861–1915), where he supported H
ericourt and Richet’s claim
for priority.
88
Of course we cannot rule out the possibility of a
rivalry between Fraenkel and Behring, whose successes trig-
gered many jealousies, the most famous being the one from
Koch himself. But Fraenkel was right, anyway, as clearly shown
in the preceding paragraphs. In Behring’s defense, it is conceiv-
able that he never heard of Richet and H
ericourt’s works before
1890, considering that he reached the discovery of serotherapy
with a totally different turn of mind than theirs. Besides, it is
undisputable that the first proved clinical success of serother-
apy must be attributed to Emil von Behring, and these successes
fully justify his Nobel Prize. He also revolutionized the immu-
nization concept, using toxins instead of microbes, a rupture
from the Pastorian mindset, which allowed Paul Ehrlich to
develop his famous side-chain theory.
3
Nevertheless, Behring
did not deserve this award as “the pioneer”of serotherapy,
according to the imprecise words of Prof. M€
orner pronounced
at the Nobel Prize ceremony,
11
and therefore unfortunately
engraved in marble.
Beyond this question of priority, we have shown the role of
the French School of Physiology in formulating the early con-
cepts of immunity, particularly humoral immunity, a role that
was neglected due to the radiance of the Institut Pasteur on the
one hand, and to the triumph of the German School on the
other. The trajectory followed by H
ericourt and Richet is
indeed probably the best illustration of the “physiologization of
pasteurism”theory: they were great admirers of Louis Pasteur
and had already some experience in bacteriology when they
started addressing questions of antimicrobial immunity with
experimental approaches typical of those of the French school
of Physiology. In this way, we can consider that their works,
and that this movement, led to the birth of a new discipline,
Immunology, comprising clinical Immunology with the first
descriptions of adverse effects (hypersensitivity reactions) of
serotherapy and later of course, for Charles Richet, the discov-
ery of anaphylaxis. They were, however, unlucky in their
attempts to translate this knowledge into medical applications,
neither with tuberculosis nor cancer, but they already sensed
the potential of their discovery in Immunotherapy.
Our study also led to a rather unexpected finding, i.e., that
some French physiologists like Maurice Raynaud addressed the
question of immunity just a few months after Louis Pasteur for-
mulated his germ theory. Moreover, the physiologist Auguste
Chauveau discovered the pathogenic role of microbes before
Louis Pasteur, in total conflict with the “physiologization of the
pasteurism”theory formulated by Jacques L
eonard.
14,15
It
rather appears that Bacteriology like Immunology arose at the
interface between Chemistry (Louis Pasteur; German School)
and Physiology, and that both probably brought their own
specificities.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Acknowledgments
We thank Claire Marchand for her preliminary works on Jules H
ericourt
and Marie Watier for the careful reading of the manuscript.
Funding
This work was supported by the French Higher Education and Research
Ministry under the program “Investissements d’Avenir”grant agreement:
LabEx MAbImprove ANR-10-LABX-53–01.
ORCID
Herv
e Watier http://orcid.org/0000-0002-2139-4171
778 Y.-M. LAHAIE AND H. WATIER
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