Side-chain theory

The side-chain theory (German, Seitenkettentheorie) is a theory proposed by Paul Ehrlich (1854–1915) to explain the immune response in living cells. Ehrlich theorized from very early in his career that chemical structure could be used to explain why the immune response occurred in reaction to infection. He believed that toxins and antitoxins were chemical substances at a time when very little was known about their nature. The theory explains the interaction of antibodies and antigens in the blood, and how antibodies are produced.

In 1891, Paul Ehrlich joined the newly established Robert Koch Institute in Berlin upon the invitation of Robert Koch himself. By 1896 a new branch, the Institute for Serum Research and Testing (Institut für Serumforschung und Serumprüfung), was established in Frankfurt with Ehrlich as its founding director. He worked on antitoxins for diphtheria and their binding to antibodies in the blood. He hypothesised that antibodies bind to antitoxins through special chemical structures that he called "side chains" (which he later named "receptors"). Borrowing a concept used by Emil Fischer in 1894 to explain the interaction between an enzyme and its substrate, Ehrlich proposed that binding of the receptor to an infectious agent was like the fit between a lock and key. He published the first part of his side-chain theory in 1897, and its full form in 1900 in a lecture he delivered to the Royal Society in London.

Ehrlich's theory can be summarised with the following tenets:

Ehrlich supposed that living cells have side-chains in the same way dyes have side-chains which are related to their coloring properties. These side chains can link with a particular toxin (or any antigen), just as Emil Fischer said enzymes must bind to their receptors "as lock and key."

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