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Landsteiner, Karl

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Summary Article: Karl Landsteiner from Encyclopedia of Life Sciences
Abstract

(1868-1943) Austrian-American pathologist and immunologist who discovered the human blood groups.

keywords

ABO blood groups

hapten

azoprotein

conjugated antigen

immunochemical specificity

Landsteiner was born in Vienna in 1868. The son of a journalist, he attended the University of Vienna from 1885 to 1891, graduating MD. After 5 years of training in organic chemistry under the tutelage of Emil Fischer, Eugen von Bamberger and Arthur Hatzsch, Landsteiner began his work on the specificity of serological reactions using chemically modified antigens. In 1896, he became Assistant at the Institute of Hygiene directed by Max von Gruber. Here he was introduced to immunology and serology, which occupied his research interests for the remainder of his career. After Gruber's departure for Munich, he became Assistant to Anton Weichselbaum, also of the Vienna Faculty of Medicine in 1897. See also Fischer, Emil Hermann

He co-authored nine papers with Julius Donath including a report on paroxysmal haemoglobinuria. Landsteiner was appointed Research Assistant at the Vienna Pathological Institute in 1898 where he remained until 1908. He then became Chief of Pathology at the Royal Imperial Wilhelminen Hospital and adjunct professor in the Medical Faculty of the University of Vienna.

Landsteiner discovered the human blood groups in 1900 when he found that the blood serum of some individuals could cause the agglutination of red cells from others. This led him to characterize red blood cells according to their antigens, leading subsequently to a description of the ABO blood groups. He took samples of his own blood, and from his colleagues Adriano Sturli and Jakob Erdhein, Dr Pletschnig and his assistant Zaritsch. In 1902, Sturli and Alfred Descastello, under Landsteiner's direction, designated one more group, which was actually not named 'AB' until 10 years later when Emil F. von Dungern and Ludwik Hirszfeld, studying the genetic inheritance of blood types, designated the fourth type and gave Landsteiner's 'C' group the designation. It was for this discovery, rather than his elegant studies on immunochemical specificity, that he won the Nobel Prize in Medicine 30 years later. The development of citrates as anticoagulants in 1914 by Richard Lewisohn, together with Landsteiner's blood grouping, led to the widespread practice of blood transfusion. See also Blood Group Genetics, Blood Group Incompatibility, Blood Groups and Transfusion Science; Anticoagulant Drugs

Landsteiner investigated poliomyelitis between 1908 and 1922. He discovered that a rhesus monkey became paralysed following the injection of brain and spinal cord from a polio victim. After finding no bacteria in the monkey's nervous system, Landsteiner concluded that a virus must be the causative agent. He perfected a technique to diagnose poliomyelitis. Landsteiner discovered that an extract of ox heart could replace the antigen derived from livers of babies with congenital syphilis for use in the Wassermann test for syphilis. See also Poliovirus; Syphilis

In 1918, Landsteiner coupled organic radicals to proteins. The ability of a particular chemical to act as a determinant of specificity was tested by coupling it to an aromatic amine such as aniline. The product of this reaction was diazotized and coupled to a protein to form a conjugated antigen or azoprotein. From these studies, which dominated Landsteiner's research activities until his death in 1943, the chemical basis for serological specificity- was proved. Not only the nature of radicals coupled to proteins but the position of the attachment site on the ring (ortho, meta or para) was shown to be of critical importance with respect to specificity. This represented the 'golden age of immunochemistry', when the views of chemists prevailed over those of biologists. Paul Ehrlich had attempted to develop a selective theory of antibody formation with his side-chain concept, which required that every cell involved in antibody production be capable of reacting against every known antigen in nature. However, it was precisely this weakness in the hypothesis which allowed Landsteiner to deal it a death blow by raising antibodies against haptens (partial antigens) which he had manufactured in the chemical laboratory and which had never appeared before in nature. He pointed out that it was inconceivable that nature would provide receptors for antigens which the animal body would never see. See also Ehrlich, Paul, Haptens, Antigen Processing; Affinity of Antigen-Antibody Interactions

Landsteiner's years in Vienna were among his most fruitful, with more than 170 papers published. Following World War I, the newly formed Republic of Austria was chaotic and experienced inflation, fuel and food shortages. Fleeing disruptive working conditions, Landsteiner left for The Hague in the Netherlands in 1919 where he accepted a position in the Catholic Hospital. In 1923, Simon Flexner invited him to join the Rockefeller Institute for Medical Research in New York City where he was made a full member and given a modest laboratory. He continued there for the rest of his life, completing 346 papers during his enormously productive career. Several of the investigators who trained under his direction, including Philip Levine and Merrill W. Chase, gained scientific acclaim in their own right in subsequent years. See also Flexner, Simon

Among those who worked with him in the field of immunohaematology were Phillip Levine and Alexander Wiener. In 1927, Landsteiner and Levine discovered the M and N blood group antigens by injecting human erythrocytes into rabbits. They are not of significance in transfusion since human blood serum does not contain isoagglutinins (antibodies) against them, differentiating MN from the ABO groups.

In 1940, Landsteiner, Levine and Wiener discovered the Rh blood group system. They found that antibodies raised in rabbits and guinea-pigs immunized with blood from a rhesus monkey were able to agglutinate the red blood cells of many humans who were termed Rh positive, whereas those not possessing the Rh factor were termed Rh negative. This factor was shown to be important in haemolytic disease of the newborn. See also Rhesus Haemolytic Disease of the Newborn

In the early 1940s, Landsteiner, Chase and Battisto performed extensive investigations into delayed-type hypersensitivity reactions to simple chemical haptens and described the successful transfer of reactivity to previously nonreactive animals by suspensions of lymphoid cells. See also Hypersensitivity: Immunological

With his excellent background in chemistry, medicine and pathology, Landsteiner continued his serology and immunology work at the Rockefeller Institute. He examined the effect of position on attached radicals. He discovered that immunochemical specificity was altered by the ortho, meta or para position on aromatic rings of stereoisomers. He found that position was more important than the nature of the radical. Landsteiner further showed that partial antigens termed haptens were unable to elicit antibody formation but could react with those formed in response to a complete antigen comprising a hapten bound to a carrier molecule. He demonstrated carrier-specific and hapten-specific antibodies. His extensive investigations on immunochemical specificity were first summarized in his book entitled Die Specifizität der Serologischen Reactionen, published in 1933. The English translation was published in 1936 and a revised edition appeared in 1945 following his death. He found that haptens could combine with preexisting antibodies to produce allergic desensitization. See also Allergy

Landsteiner became an American citizen in 1929 and died in New York City on 26 June 1943. His work laid the foundation for much of modern immunology including the construction of synthetic vaccines as a representative application of his research.

Further Reading
  • Landsteiner, K (1901) Ueber Agglutinationserscheinungen normalen menschlichen Blutes. Wiener Klinische Wochenschrift 14: 1132-1134.
  • Landsteiner, K (1945) The Specificity of Serological Reactions, revised edn. Cambridge, NA: Harvard University Press.(Reprinted Dover Publications, 1982.).
  • Corner, GW (1964) A History of the Rockefeller Institute 1901-1953. Origins and Growth. New York: Rockefeller Institute Press.
  • Farr, AD (1979) Blood group serology - the first four decades (1900-1939). Medical History 23: 215-226.
  • Heidelberger, M (1969) Landsteiner June 14, 1868-June 26, 1943. National Academy of Sciences Biographical Memoirs 40: 177-210.
  • Mazumdar, PMH (1975) The purpose of immunity: Landsteiner's interpretation of the human isoantibodies. Journal of the History of Biology 8: 115-133.
  • Speiser, P and Smekal, FG (1975) Karl Landsteiner, Rickett, R (transl.). Vienna: Verlag Brüder Hollinek.
  • JM Cruse
    University of Mississippi Medical CenterJackson, Mississippi, USA
    RE Lewis
    University of Mississippi Medical CenterJackson, Mississippi, USA

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