Development of the Complement-Fixation Test: Jules Bordet
By Janet Lee
Jules Bordet was born in 1870 and was raised in Brussels, Belgium as the
second son of Charles Bordet, a primary school teacher.
Bordet became interested in chemistry and eventually enrolled in the
medical program at the Universite Libre de Bruxelles at the age of sixteen.
Six years later, Bordet graduated medical school, during which he
performed research on adaptation of viruses to vaccinated organisms in the
Annales de l’Institute Pasteur.
For his work, Bordet received a grant from the Belgium government in 1894
to join the Pasteur Institute under the mentorship of Elie Metchnikoff, the
Ukrainian zoologist who was a leading pioneer in cellular immunology.
Upon arriving in Paris, Bordet set to work on in vitro experiments to
test a previous observation, or the “Pfeiffer phenomenon”.
This observation showed that bacteriolysis would result when serum taken
from an immune animal was introduced into a non-immune animal.
Bordet saw that Pfeiffer’s phenomenon applied in vitro, when serum from
an immunized animal was microbicidal against a cholera suspension.
However, microbicidal activity was eliminated when the serum was heated
to fifty-five degrees centrigrade, although agglutination remained unaffected.
Furthermore, the heated serum regained its killing ability when fresh
serum from non-immune animals was added.
From these experiments, Bordet concluded that there were two factors
responsible for the bacteria killing—a heat-stable sensitizing factor or
antibody, and a heat-sensitive non-specific substance that acted only on a
sensitized target. This non-specific
substance was later named “complement” by German bacteriologist Paul Ehrlich.
Bordet’s experiments set the basis for humoral immunity: a highly ironic
outcome viewed from the perspective as Metchnikoff’s protégé.
Bordet astutely recognized a parallel between his experiments involving
bacteriolysis and previous hemolysin experiments involving the agglutination of
erythrocytes. In 1898, Bordet
demonstrated the universality of Pfieiffer’s phenomenon by discovering that red
blood cells added to blood serum resulted in hemolysis of the red blood cells if
complement was present in the serum. However, if the red blood cells were added
after bacteriolysis, hemolysis did not occur since the free complement was
already bound to antigen-antibody complexes.
Bordet developed complement fixation tests as a serodiagnostic tool for
detection of antibodies to determine if a person was exposed to a particular
agent. This became valuable for
pathogens which not easily culture from clinical specimens.
August von Wassermann adopted the complement-fixation test for the
diagnosis of syphilis (the Wasserman test).
Additional complement-fixation tests were developed for typhoid fever and