Karl Landsteiner brought chemistry into immunology

Person: Karl Landsteiner
Lived: 1868–1943
Field: Pathology
From: Austrian-American

The story

Besides blood groups, Karl Landsteiner made deep contributions to understanding how the immune system recognises substances. After qualifying in medicine at the University of Vienna in 1891, he spent several years in the chemistry laboratories of Arthur Hantzsch in Zurich, Emil Fischer in Würzburg and Eugen Bamberger in Munich. That unusual training gave him a chemist's way of thinking that he carried into medicine.

Back in Vienna he became an assistant to Max von Gruber at the Hygiene Institute, where he concentrated on the mechanism of immunity and the nature of antibodies. Over the following two decades, while working in pathology, he studied the immunology of syphilis and the Wassermann test used to diagnose it.

In this work he discovered immunological factors that he named haptens, from a Greek word meaning to fasten. A hapten is a small molecule that cannot trigger an immune response on its own but can do so when attached to a larger carrier such as a protein. The discovery also clarified the Wassermann reaction: the active substances in the organ extracts used in the test turned out to be haptens.

When conditions in post-war Vienna made laboratory work very difficult, Landsteiner moved to a small hospital in The Hague. There, between 1919 and 1922, he published twelve papers on new haptens, on protein conjugates that could induce severe allergic reactions, and on how the haemoglobins of different animal species could be told apart by their immune reactions. He continued this research after moving to the Rockefeller Institute in New York in 1923.

The Nobel Foundation's biography says one of his great merits was that he introduced chemistry into the service of serology, the study of blood serum and antibodies, and he investigated the chemistry of antigens and antibodies to the end of his life. His collaborator Alexander Wiener later called him the father of both blood grouping and immunochemistry.

The hapten idea remains central to medicine. It helps explain contact allergies such as nickel allergy, in which metal ions bind to skin proteins, and some drug reactions, including certain reactions to penicillin. Hapten–carrier compounds are also used to produce antibodies and build sensitive laboratory tests.