The History of Antibodies
The earliest reference to antibodies came from Emil von Behring and Shibasabura
Kitasato in 18901. In a landmark publication they showed that the transfer of
therapeutic serum from animals immunized against diphtheria to animals suffering
from it could cure the infected animals1,2. The potential for treatment in humans
was immediately apparent and Behring was later awarded the Nobel Prize for this
work in 19013.
In 1900 Paul Ehrlich, proposed the side-chain theory, where he hypothesized that
side chain receptors on cells bind to a given pathogen. He was the first to propose a
model for an antibody molecule in which the antibody was branched and consisted
of multiple sites for binding to foreign material, known as antigen, and for the
activation of the complement pathway. This model agreed with the ‘lock and key’
hypothesis for enzymes proposed by Emil Fischer4,5.
Astrid Fagraeus in 1948 described that plasma B cells are specifically involved in
antibody generation and by 1957 Frank Burnet and David Talmage had developed
the clonal selection theory6. This stated that a lymphocyte makes a single specific
antibody molecule that is determined before it encounters an antigen, which was in
contrast to the instructive theory developed by Linus Pauling in 1940 where the
antigen acted as a template for the antibody7.
By 1959 Gerald Edelman and Rodney Porter independently published the molecular
structure of antibodies8,9, for which they were later jointly awarded the Nobel Prize
in 197210. The first atomic resolution structure of an antibody fragment was
published in 197311 and this was quickly followed by the invention of monoclonal
antibodies12 in 1975 by Georges Köhler and César Milstein signaling the start of the
modern era of antibody research and discovery.
Figure 1: Antibody research has come a long way from its earliest reference by Emil Von Behring in 1890.
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- Behring, E. a. K., S. Ueber das Zustandekommen der Diphtherie-Immunitat und der Tetanus-Immunitat bei thieren. Deutsche medizinsche Wochenschrift 16, 1113-1114 (1890).
- Behring, E. Untersuchungen ueber das Zustandekommen der Diphtherie-Immunitat bei Thieren. Dt. Med. Wochenschr 16, 1145-1148 (1890).
- Nobelprize.org. The Nobel Prize in Physiology or Medicine 1908
- Fischer, E. Einfluss der Configuration auf die Wirkung der Enzyme. Berichte Der Deutschen Chemischen Gesellschaft 27, 2985-2993 (1894).
- Lemieux, R. U., and Spohr, U. . How Emil Fischer was led to the lock and key concept for enzyme specificity. Adv Carbohydr Chem Biochem 50, 1-20 (1994).
- Burnet, F. M. A modification of Jerne's theory of antibody production using the concept of clonal selection. CA Cancer J Clin 26, 119-121 (1976).
- Pauling, L. A Theory of the Structure and Process of Formation of Antibodies. J. Am. Chem. Soc. 62, 2643-2657 (1940).
- Porter, R. R. The hydrolysis of rabbit y-globulin and antibodies with crystalline papain. Biochem J 73, 119-126 (1959).
- Edelman, G. M., Benacerraf, B., Ovary, Z., Poulik, M.D. Structural differences among antibodies of different specificities. Proc Natl Acad Sci USA 47, 1751-1758 (1961).
- Nobelprize.org. The Nobel Prize in Physiology or Medicine 1972
- Inbar, D., Hochman, J., and Givol, D. . Localization of antibody-combining sites within the variable portions of heavy and light chains. Proc. Natl. Acad. Sci. USA 69, 2659-2662 (1972).
- Kohler, G. & Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495-497 (1975).
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