Karl Landsteiner and the Blood Classification System

Karl Landsteiner (1868-1943)

Karl Landsteiner (1868-1943)

On June 14, 1868, Austrian biologist, physician, and immunologist Karl Landsteiner was born. Landsteiner distinguished the main blood groups in 1900, having developed the modern system of classification of blood groups from his identification of the presence of agglutinins in the blood, and identified, with Alexander S. Wiener, the Rhesus factor, in 1937, thus enabling physicians to transfuse blood without endangering the patient’s life.

“A single kind of red cell is supposed to have an enormous number of different substances on it, and in the same way there are substances in the serum to react with many different animal cells. In addition, the substances which match each kind of cell are different in each kind of serum. The number of hypothetical different substances postulated makes this conception so uneconomical that the question must be asked whether it is the only one possible. … We ourselves hold that another, simpler, explanation is possible.”
— Karl Landsteiner, [8] (1902)

Karl Landsteiner – Youth and Education

Karl Landsteiner was born in Baden, near Vienna, Austria. His father Leopold, a well-known journalist and first editor-in-chief of the newspaper Die Presse, died at the age of 58 when Karl was six years old. This gave him a very close relationship with his mother Fanny, née Heß. Her death mask hung in his bedroom until his death. Landsteiner studied medicine at the University of Vienna from 1885, after passing his school-leaving examination at today’s Gymnasium Wasagasse in Vienna with distinction, and received his doctorate there in 1891. During his studies he already published a paper on the influence of diets on the composition of the blood.

Medical Research and Further Studies

After his studies Landsteiner spent five years abroad in laboratories in Zurich with Arthur Hantzsch, in Würzburg with the famous German chemist Emil Fischer and in Munich with Eugen Bamberger. In 1896 he returned to Vienna and initially became a surgical trainee at the 1st Surgical Clinic under Theodor Billroth. After completing this practical training, he devoted himself again to theory and became an assistant at the Institute of Hygiene headed by Max von Gruber. There he conducted studies on the mechanism of immunity and the nature of antibodies. Between 1898 and 1908 Landsteiner was an assistant at the Pathological Anatomy of the University of Vienna, then until 1919 he was prosector at the Wilhelminenspital in Vienna.

University Career and Polio

In 1903 he habilitated in pathology under Anton Weichselbaum and in 1911 Landsteiner was appointed associate professor of pathology. During this time he published many medical papers, among others on the transmission of polio. Landsteiner’s achievement – together with Erwin Popper – was the definitive proof that polio is an infectious disease, proven by injecting spinal fluid from a child who died of the disease into monkeys and subsequently transmitting it from one animal to another.

The Human Blood Group System

Landsteiner noticed in 1900 that blood of two people often clumped together when mixed. The significance of this observation was not yet clear to him when writing the manuscript, as he only describes the process of haemagglutination in a footnote. He reported that this effect also occurred through contact of blood with blood serum. In his work “On Agglutination Phenomena of Normal Human Blood“, he demanded for the first time, again in a footnote, that there must be three blood groups. He succeeded in identifying the blood group characteristics A, B and 0 (the latter referred to as C). The blood group trait AB (which Emil von Dungern and Ludwik Hirszfeld only designated as such in 1910) was discovered in 1902 by two of Landsteiner’s colleagues, the Viennese internist Alfred von Decastello-Rechtwehr and his colleague Adriano Sturli. The AB0 nomenclature proposed by Dungern and Hirszfeld in 1910 was not adopted internationally until 1928.

Blood Transfusions

It was also Landsteiner who recognized that blood transfusion between persons of the same group did not lead to the destruction of blood cells, but rather between persons of different blood groups, so that in 1907 the first successful blood transfusion based on his work was performed at Mount Sinai Hospital in New York by Reuben Ottenberg. Today we know that people with blood group AB accept erythrocytes of all other blood groups (universal recipient), erythrocytes of blood group 0 can be received by all groups (universal donor). This is because people with blood group AB do not produce antibodies against blood group A or B. Blood group 0, on the other hand, has neither characteristic A nor characteristic B, so no antibodies against it can be formed in the recipient after the transfer. Nowadays, blood transfusions only transfer erythrocyte concentrates without blood serum containing antibodies. This knowledge is particularly important for blood transfusions and operations. Landsteiner was awarded the Nobel Prize for Medicine in 1930 for his discovery of blood groups.

The Rh Blood Group System

In 1937 Landsteiner discovered the rhesus factor (later Rh Blood Group System) together with Alexander Solomon Wiener, who named it after a similar factor found in rhesus monkey blood. The significance of the discovery was not immediately apparent and was only realized in 1940, after subsequent findings by Philip Levine and Rufus Stetson. The serum that led to the discovery was produced by immunizing rabbits with red blood cells from a rhesus macaque. The antigen that induced this immunization was designated by them as Rh factor to indicate that rhesus blood had been used for the production of the serum.

Further Research

After the end of the First World War, economic hardship in Austria was great and the prospects for an orderly academic career in Vienna seemed extremely uncertain. Landsteiner therefore accepted job offers from abroad. In 1919 he went to The Hague, where he managed the prosection of a small Catholic hospital. He remained scientifically active and treated various serological problems in a total of twelve publications. In 1921, for example, he reported on low-molecular “specific substances” which require binding to a protein in order to become a so-called full antigen, and for which he proposed the name haptene. In 1922 Landsteiner accepted a position at the Rockefeller Institute in New York, where in 1940, together with his students Philip Levine and Alexander Solomon Wiener, he described the rhesus factor that he had discovered in the blood of rhesus monkeys. Besides working on the blood groups, he dealt with questions concerning the development of paroxysmal cold hemoglobinuria, which led to the development of the Donath-Landsteiner reaction as a test for the confirmation of a diagnosis

Later Years

In 1932 Landsteiner was elected to the National Academy of Sciences . For his groundbreaking findings, which are considered the foundation of polio control, he was posthumously inducted into the Polio Hall of Fame in Warm Springs, Georgia, inaugurated in January 1958. In his last years he worked on oncological issues, as his wife had a malignant tumour of the thyroid gland. Karl Lanfsteiner died on 26 June 1943 in New York City at age 75. For his pioneering work, he is recognized as the father of transfusion medicine.

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