Landsteiner, Karl

(b. Vienna, Austria, or Baden [near Vienna], Austria, 14 June 1868; d. New York, N.Y., 26 June 1943)

medicine, serology, immunology.

Landsteiner, who has been called the father of immunology, was the only son of Leopold Landsteiner, a well—known journalist and newspaper publisher, and Fanny Hess Landsteiner. He began his medical studies in 1885 and received his M.D. in 1891. In 1916 he married Helene Wlasto; their only child, Ernst Karl, was born the following year. Poor working conditions caused him to leave Vienna in 1919; but facilities in The Hague, where he was prosector at the RK Hospital for three years, were no better. He therefore accepted an offer from the Rockfeller Institute in New York, and went to the United States in 1922; he became an Ameridcan citizen in 1929. Landsteiner was a modest, self—critical, rather timid man of science known for his wide reading. He was also an excellent pianist.

Although he had an M.D., Landsteiner’s first scientific work was in chemistry, which he bagan to study in Ludwig’s laboratory in Vienna while still a student. He continued these studies in Germany and Switzerland from 1892 to 1894. Which Emil Fischer he synthesized glycolaldehyde at Würzburg in 1892. At Munich in 1892–1893, he learned the chemistry of benzene derivatives from Bamberger, and in Zurich in 1893–1894 he studied organic chemistry under Hantzsch.

Medicine, however, remained Landsteiner’s chief interest. For a short time after receiving his M.D. he had worked with Kahler at the Second Medical University Clinic in Vienna: and from 1894 to 1895 he served with Eduard Albert at the First Surgical University Clinic. During 1896–1897 Landsteiner was assistant to Gruber in the newly established department of hygiene at the University of Vienna; and there his interest was awakened in serology and immunology.

Landsteiner’s next teacher was Weichselbaum, whose assistant he was from 1897 to 1908. At that time Weichselbaum was director of the Pathological-Anatomical Institute of the University of Vienna. Under his supervision, Landsteiner conducted 3,639 postmortem examinations that gave him a comprehensive view of medicine and extensive experience as a pathological anatomist.

In 1900 Landsteiner published only one paper. But one of its footnotes contained information on one of his most important discoveries, namely, the interagglutination occurring between serum and blood cells of different humans as a physiological phenomenon, which he explained by individual differences. The following year, in the article “Über Agglutinationsercheinungen normalen menschilden Blutes,” Landsteiner described a simple technique of agglutination, whereby he divided human blood into three groups: A, B, and C (later O). Two of his inspired co-workers, the clinicians Decastello and Sturli, examined additional persons and found the fourth blood group, later named AB.

The blood grouping is done by mixing suspensions of red cells with the test sera anti-A and anti-B:

Blood group O is agglutinated by neither of the sera, AB by both, A by abti-A but not by anti-B, and B by anti-B but not by anti-A. The serum of group O has anti-A and anti-B antibodies, that of A has only anti-B, that of B has only anti-A, and that of AB has neither. According to Landsteiner’s rule, serum contains only those antibodies (isoagglutinins) which are not active against their own blood group.

The discovery of blood groups made possible the safe transfusion of blood from one person to another, although several years passed before this knowledge was put to practical use. Richard Lewisohn’s discovery in 1914 that adding citrates to blood prevented it from coagulating was the last prerequisite for the establishment of the modern blood bank, since blood could now be preserved for twoto three-week periods under refrigeration. Operations on the heart, lungs, and circulatory system, previously impracticable because of the magnitude of blood losses involved, were now feasible, as were complete blood exchanges in cases, for example, of intoxication or severe jaundice of the newborn.

Instead of pursuing further developments in blood groups, Landsteiner sought out other differences in human blood. He conceived the idea that the particularity of blood was reflected in antigen differences, and that these differences could be used to distinguish one person from another and to draw a serological “fingerprint.” Today—if hereditary serum groups and enzyme groups are included—millions of combinations are possible; and Landsteiner’s concept of the individuality of human blood, revealed serologically, has practically been realized. At first Landsteiner did not know that blood types were inheritable, for Mendel’s laws of heredity had passed into oblivion. In 1900 the laws were rediscovered by Correns, De Vries, and Tschermak-Seysenegg. Ten years later Emil von Dungern and Hirzfeld postulated the first hypothesis for the inheritance of blood groups; this theory was corrected in 1924 by the mathematician B. A. Bernstein and was finally established. Serological genetics has existed since then and is applied in cases of disputed paternity. Today about 99 percent of paternity questions are settled by serological means.

During this period Landsteiner also worked on characterizing and evaluating the physiological meaning of cold agglutinations in human blood serum. In 1904 he and Donath described a test for the diagnosis of paroxysmal cold hemoglobinuria. In this disease, after the patient is exposed to cold, hemoglobin appears in his urine because some of the red blood cells have been lysed.

Ehrlich had also concerned himself with this problem. He originated a simple clinical diagnostic test, the so-called Ehrlich finger test. A finger to which a rubber tourniquet has been applied is put in ice water. After the dissolution of the congested material, hemoglobinuria occurs. Ehrlich erroneously attributed the phenomenon to a pathological change in the endothelium of the blood vessels. In opposition to Ehrlich, Ladsteiner postulated that the disease-causing agent was found in the blood serum of the patient and that it was an antibody which, when exposed to cold, combines with the red cells and later, under warm conditions, causes their breakdown in the body. He demonstrated this process in a test tube and noted the lysis of the red cells (the Donath-Landsteiner test). Landsteiner also made important contributions to the etiology of meconium ileus in newborn children.

In 1905–1906 Landsteiner and Ernest Finger, then chief of the Dermatological Clinic in Vienna, were successful in infecting monkeys with syphilis. Experimentation with Spirochaeta Pallida, the causal agent of the disease, was thereby made possible. The two investigators determined that infectious spirochetes were present in gummas. With the help of the venereologist Mucha they were able to demonstrate the syphilitic spirochetes in the dark field of the microscope and also describe their typical movements. In collaboration with the neurologist Poetzl and the serologist Mueller, they elucidated the previously unknown mechanism occurring in the wassermann reation. In 1907 Landsteiner also demonstrated that for this test, the extract (antigen) previously exclusively obtained from human organs could be replaced by a readily available extract of bovine hearts. This made possible the widespread use of the Wassermann test.

From 1908 to 1919, while he was prosector at the Royal-Imperial Wilhelminen Hospital in Vienna, Landsteiner concerned himself extensively with poliomyelities. After conducting a postmortem examination of a child who had died of the disease, he injected a homogenate of its brain and spinal cord into the abdominal cavity of various experimental animals, including rhesus monkeys. On the sixth day following the injections, the monkeys showed signs of paralysis similar to those of poliomyelitis patients. The histological appearance of their central nervous systems also was similar to that of humans who had died of the disease. Since he could not prove the presence of bacteria in the spinal cord of the child who had died, Landsteiner postulated the existence of a virus: “The supposition is hence near, that a so-called invisible virus or a virus belonging to the class of protozoa, cause the disease.” Between 1909 and 1912 he and Levaditi of the Pasteur Institute at Paris devised a serum diagnostic procedure for poliomyelitis and a method of preserving the viruses that cause it.

During the 1920’s Landsteiner made further discoveries. In 1921, for instance, utilizing investigations dating as far back as 1904, he demonstrated the existence of the antigens; this discovery was influential in the development of immunology. Landsteiner also differentiated various hemoglobin by means of chemical and serological techniques. In 1926 he and Philip Levine discovered the irregular agglutinins ?₁ and ?₂; the following year they found the blood factors M, N, and P. In 1934, with Strutton and Chase he described a blood factor found only in Negroes, which today is called the Hunter-Henshaw system.

Landsteiner and his co-workers Alexander Wiener and Philip Levine made an important discovery, reported in a paper (1940), describing a new factor in the human blood, the rhesus (Rh) factor. Levine was the first to see the connection between this factor and jaundice occurring in newborn children. A mother who does not have the Rh factor—that is, who is Rh-negative—can be stimulated by an Rh-positive fetus to form antibodies against the Rh factor. The red cells of the fetus are then destroyed by these antibodies, and the product of hemoglobin decomposition forms bilirbin which cause jaundice. Permanent brain damage can result, and the fetus or newborn child may die. By means of serological tests such cases can be recognized in time and saved by means of blood exchange transfusions.

The Rh factor is also of vital importance in blood transfusions, for Th-positive blood must not be transfused into Rh-negative patients. If it is, Rh antibodies will be formed; and further transfusion of Rh-positive blood will leas to severe hemolytic reactions and the patient can die.

In the field of bacteriology, it should be noted that Landsteiner and Nigg were successful in 1930–1932 in culturing Rickettsi prowazekii, the causative agent of typhus, on living media.

Landsteiner’s honors include honorary doctorates from the University of Chicago (1927), Cambridge (1934), the Free University of Brussels (1934), and Harvard (1936); the presidency of the American Association of Immunologists (1929); and the Nobel Prize in physiology or medicine (1930).

BIBLIOGRAPHY

I. Original Works. The Specificity of Serological Reactions (New York, 1962), a trans. of Landsteiner’s major work, Die Spezifitaet der Serolgischen Reaktionen, contains, in additions to a new perface, a bibliography of Landsteiner’s 346 scientific papers compiled by Merrill W. Chase.

II. Secondary Literature. On Landsteiner’s life and work, see H. Chiari, o?sterreichische Naturforscher, AÄrzte und Techniker (Vienna, 1957); H. A. L. Degener, Unsere Zeitgenossen (Leipzig, 1914; Berlin, 1935); I. Fischer, Biographisches Lexikon der hervorragenden A?rzte der letzten 50 Jahre, vol. II (Berlin-Vienna, 1933); J. and R. Gicklhorn, Die österreichische Nobelpreistro¨ger (Vienna, 1958); T. W. MacCallum and S. Taylor, The Nobel Prize Winners and the Nobel Foundation 1901–1937 (Zurich, 1938); F. Oehlecker, Die Bluttransfusion (Berlin-Vienna, 1933); Peyton Rouse, “Karl Landsteiner,” in Obituary Notices of Fellows of the Royal Society of London, 5 (1947), 295–324, with bibliography; L. Schönbauer, Das Medizinische Wien (Berlin-Vienna, 1944; 2nd ed. 1947); M. Schorr, Zur Geschichte der Bluttransfusion im 19. Jahrhundert (Basel-Stuttgart, 1956); G. R. Simms, The Scientific Work of Karl Landsteiner (Zurich, 1963); and P. Speiser, Karl Landsteiner, Entdecker der Blutgruppen. Biographie einers Nobelpreisträgers aus der Wiener Medizinischen Schule (Vienna, 1961), with a complete bibliography of Landsteiner’s works.

A number of obituary notices appeared in a variety of medical journals at the time of his death; see especially Journal of the American Medical Association, 122 (1943), and Wiener medizinische Wochenschrift, 94 (1944).

Paul Speiser