A hundred years after the publication of his first work on the human blood groups, we celebrate Karl Landsteiner (Fig. 1), recognizing his role as father of the science of blood transfusion (1,2), and one of the fathers of the population genetics (3), the tissue transplantation (4), and immunology (5). He was a man who, without funds or assistance, developed a deep understanding of the individual differences in human blood.
Landsteiner was so averse to praise, so honest and so good, that he never achieved complete happiness in his personal life, finding his greatest satisfaction in his solitary scientific work. Indeed, he was so sad and melancholy that Hans Zinsser, a famous colleague in immunology who taught at the Harvard Medical School, told him repeatedly: “Karl, you are always crabby, always complaining.”
Karl Landsteiner was born on 14 June 1868, son of the enterprising reporter Leopold Landsteiner, from whom he inherited great self-control, a notable fondness for logical thought, and a strong tenacity. Karl Landsteiner, however, maintained that his father’s seriousness and methodical habits were irritating. However, Landsteiner inherited from his mother, Fanny Hess, great modesty and reserve, attributes that ought to distinguish all great and famous men. Although it is usually recorded that Karl Landsteiner was born in the city of Vienna, he was actually born in the Jewish quarter, referred to as Baden bei Wien. His Jewish origin caused many difficulties for him during his scientific career.
He was a precocious and model student. After completing primary school and the first 4 years of secondary school, in 1880 he attended the Staatsgymnasium in Linz as an “honours student”. During these studies he developed a great interest in the natural sciences and mathematics. Landsteiner entered the University of Vienna in 1885 and studied under the most famous scientists of the day: Langer, with whom he studied anatomy; Claus, who specialized in zoology; and Schenk, from whom he learned histology. He also studied hematological chemistry and the metabolism of the blood with Mauthner and Ernst von Fleishl. However, organic chemistry remained his first love, and his experimental work was conducted in the footsteps of Professor Ernst Ludwig. All his publications in this field anticipated his subsequent serological studies.
On February 21, 1891, Landsteiner took a degree in medicine. He then began work in the laboratory of the medical clinic directed by Otto Kahler, who discovered and described the Kahler syndrome, today called “multiple myeloma.” From 1891 to 1893 Landsteiner completed his apprenticeship under two experts in the field of organic chemistry. First, in Würzberg, he studied under Emil Hermann Fischer (6), who was awarded the Nobel Prize in 1902 for his works about the organic synthetic approaches to glucose, oligopeptides, and caffeine. Later, in Munich, Landsteiner worked with Eugen von Bamberger in the laboratory of the Academy of Sciences and published jointly with him a treatise on the reaction of diazobenzol to calium permanganate. It was during this period that Karl Landsteiner based his immunological studies on the Fischer concept: “an antibody fits an antigen as a key fits a lock.” This concept remains fundamental to an understanding of the mechanisms of serological, immunological, and enzymatic reactions. These two teachers, Fischer and von Bamberger, who belonged to the Justus von Liebig school of research, attested their approval and recognition of their gifted and aspiring pupil.
From January 1, 1896 to December 31, 1897, while working as voluntary assistant to Max von Gruber, the famous Professor of Hygiene, at the University of Vienna, Landsteiner began his real study of, and developed his keen interest in, serology. When Landsteiner and von Gruber were investigating the Gruber-Widal test for typhoid they discovered the law of specific bacteriological agglutination. Moreover, it was here that Landsteiner studied tuberculosis with Jacob Erdheien, Julius Bartel, and Anton Ghon. With Ghon, he isolated the Ghon-Sachs-Clostridium septic Bacillus. From this period to 1907, Landsteiner worked in the discipline of pathological anatomy, publishing 75 manuscripts: 52 of these addressed serological issues, 12 concerned bacteriology and virology, and 11 referred to pathological anatomy. Included in these publications was the work demonstrating the discovery of the different blood types for which he was awarded the Nobel Prize (Fig. 2). This work, “Zur Kenntnis der antifermentativen, lytischen und agglutinierenden Wirkungen des Blutserums und der Lymphe”(7) (Figs. 3 and 4), was the 30th of his 52 serological publications. These years were scientifically fruitful for Karl Landsteiner, who also became an important member of the Imperial Society of Physicians of Vienna. Despite his success, Landsteiner always remained modest and avoided all publicity, although he again worked with famous colleagues, including Richard Paltauf, discoverer of Hodgkin’s lymphoma or Paltauf-Sternberg syndrome, and Konstantin von Economo, who first described Economo lethargic encephalitis.
From January 1, 1908 to March 31, 1920, Landsteiner worked as associate to Professor Wiesner in pathological anatomy at the Wilhelmina Hospital in Vienna. In the years of the First World War, after the death of his father, Landsteiner underwent a period of grief and solitude, which was followed by the death of his mother. During this time he married, but always shielded his wife and his son, Karl Ernst, from any publicity. In the Wilhelmina Hospital, Landsteiner prepared 52 immunological publications, 33 papers concerned bacteriological issues and 6 were on pathological anatomy, and played a prominent role in the study of the cytokines and the hemagglutinins. Landsteiner’s research was interrupted by a severe financial crisis, and he worked until 1923 in a small hospital in the Hague in Holland.
The real turning point in Landsteiner’s career came in the spring of 1923, when Simon Flexner, Director of the Rockefeller Institute of Medical Research in New York, invited him to work in the field of immunology. In this Institute, where Landsteiner worked until his death, he studied the azoproteins (8,9), and together with Van der Scheer, those regarding the antigenic differences between serum proteins in different species (10–16); the Rhesus factor and the difference regarding the blood systems in the humans with Philip Levine (17–25); the role played by Rickettsia during typhus fever with Clara Nigg (26,27); and the study about the allergy and passive transfer of tuberculin sensitivity with lymphocytes with Merril Chase (28–30). Furthermore, with Wiener (31–33) and Levine he made a definitive study of the A, B, and 0 blood groups, and discovered the M and N groups.
On November 8, 1930, Karl Landsteiner was awarded the Noble Prize. Although highly prestigious, the award did not change his character. With typical modesty and generosity, he suggested that Thomas Hunt Morgan might be a more suitable recipient. (Morgan was awarded the Noble Prize in 1933 for his discovery of chromosomal crossing-over and his study of sex-linked inheritance.) The lecture given by Landsteiner at the conferment of his Noble Prize was based on the “differences in the blood of human individuals.” He said an own theory about the finding of several blood group systems in different humans and the species specificity of serum proteins underling the proof of the difference not only among different species, but also within the same species. This theory was very important to Landsteiner, who confided to his most beloved pupil, Philip Levine, a desire to be remembered and celebrated for his work “Die Spezifität der serologischen Reaktionen”(34). Today, a hundred years later, this theory about the isoantigens is an accepted and fundamental part of the theoretical bases of immunology, tissue transplantation, forensic medicine, and population genetics.
From the end of 1939 Landsteiner ceased to work as an active researcher at the Rockefeller Institute, but continued to teach and study as Professor Emeritus. He confessed to Philip Levine his wish to die after his wife (who was suffering from a thyroid tumor), but in fact he died of a heart attack on June 25, 1943 while working in his laboratory, 6 months before his wife, who died on 25 December 1934 (35).
We wish to emphasize the wonderful personality of Karl Landsteiner, the “melancholy genius”(36) as he was known by his colleagues, by presenting an extract of an interview given to an American reporter of The Times, after the conferment of his Noble Prize (35).
Interviewer offers praise to Landsteiner as showing personal charme and modesty, a personality concentrated exclusively on his work and includes a quote Please I have not done anything. I am just working and that is all.
Interviewer asks what led to the discovery and is given a standard answer with the ending but this will not interest the layman or others.
Interviewer asks whether he expected to be honoured with the Noble Prize. Landsteiner gives the straightforward answer that he was told by a journalist.
Interviewer asks whether Landsteiner would like to tell out readers something about the Vienna Medical School. Landsteiner replies No, for God’s sake, no. . .whatever I would say about it would sound like boasting. . .
1. Bird GW. Landsteiner Award. Some aspects of serological specificity. Transfusion 1990; 30: 390.
2. Widman FK. Early observations about the AB0 blood groups. Transfusion 1997; 37: 665.
3. Mourant AE, Kopéc AC, Domaniewska-Sobczak K. The distribution of the human blood groups and other polymorphysm. London: Oxford University Press, 1976.
4. Samuelsson B. From Karl Landsteiner to human xenotransplantation. Vox-Sang 1998; 74: 65.
5. Silverstein AM. The dynamics of conceptual change in twentieth century immunology. Cell Immunol 1991; 132: 515.
6. Fischer E, Landsteiner K. Über den Glycolaldehyd. Ber Deut Chem Gesell 1892; 25: 2549.
7. Landsteiner K. Zur Kenntnis der antifermentativen, lytischen und agglutinierenden Wirkungen des Blutserums und der Lymphe. Centr Bakt Orig 1900; 27: 357.
8. Landsteiner K. Experiments on anaphylaxis with azoproteins. Proc K Akad Wetenschappen Section of sciences. 1923; 25: 34.
9. Landsteiner K. Experiments on anaphylaxis to azoproteins. J Exp Med 1924; 39: 361.
10. Landsteiner K, Van der Scheer J. Serological examination of a species-hybrid. I. On the inheritance of species-specific qualities. J Immunol 1924; 9: 213.
11. Landsteiner K, Van der Scheer J. Serological examination of a species-hybrid. II. Tests with normal agglutinins. J Immunol 1924; 9: 221.
12. Landsteiner K, Van der Scheer J. On the specificity of agglutinins and precipitins. J Exp Med 1924; 40: 91.
13. Landsteiner K, Van der Scheer J. On the antigens of red blood corpuscles. Proc Soc Exp Biol Med 1924/25; 22: 98.
14. Landsteiner K, Van der Scheer J. Flocculation reactions with hemolytic immune sera. Proc Soc Exp Biol Med 1924/25; 22: 170.
15. Landsteiner K, Van der Scheer J, With DH. Group specific flocculation reactions with alcoholic extracts of human blood. Proc Soc Exp Biol Med 1924/25; 22: 289.
16. Landsteiner K, Van der Scheer J. On the antigens of red blood corpuscles. The question of lipoid antigens. J Exp Med 1925; 41: 427.
17. Landsteiner K, Levine P. A new agglutinable factor differentiating individual human blood. Proc Soc Exp Biol Med 1926/27; 24: 600.
18. Landsteiner K, Levine P. Further observations on individual differences of human blood. Proc Soc Exp Biol Med 1926/27; 24: 941.
19. Landsteiner K, Levine P. On individual differences in human blood. J Exp Med 1928; 47: 757.
20. Landsteiner K, Levine P. On the racial distribution of some agglutinable structures of human blood. J Immunol 1929; 16: 123.
21. Landsteiner K, Levine P. On isoagglutinin reactions of human blood other than those defining the blood groups. J Immunol 1929; 17: 1.
22. Landsteiner K, Levine P. On the racial distribution of certain agglutinable structures in human blood. Profilakticheskala Medizina; Supplément, Rec. Dédié Prof. S. I. Zlatogoroff en l’honneur du XXX-éme ann. De son travail, sci. Med Et péd. 1897–1927, Kharkov, 1929, 63.
23. Landsteiner K, Levine P. On the inheritance and racial distribution of agglutinable properties of human blood. J Immunol 1930; 18: 87.
24. Landsteiner K, Levine P. Note on individual differences in human blood. Proc Soc Exp Biol Med 1930/31; 28: 309.
25. Landsteiner K, Levine P. The differentiation of a type of human blood by means of normal serum. J Immunol 1931; 20: 179.
26. Nigg C, Landsteiner K. Studies on the cultivation of the typhus fever Rickettsia
in the presence of liver tissue. J Exp Med 1932; 55: 563.
27. Nigg C, Landsteiner K. Note on the cultivation of the typhus fever Rickettsia
. Proc Soc Exp Biol Med 1931/32; 29: 1291.
28. Landsteiner K, Chase MW. Studies on the sensitization of animals with simple chemical compounds. VII. Skin sensitization by intraperitoneal injections. J Exp Med 1940; 71: 237.
29. Landsteiner K, Chase MW. Skin sensitization to a simple compound by injections of conjugates. Proc Soc Exp Biol Med 1940; 44: 559.
30. Landsteiner K, Chase MW. Studies on the sensitization of animals with simple chemical compounds. IX. Skin sensitization induced by injection of conjugates. J Exp Med 1941; 73: 431.
31. Landsteiner K, Wiener AS, Matson GA. Distribution of the Rh factor in American Indians. J Exp Med 1942; 76: 73.
32. Landsteiner K, Wiener AS. Tests for the Rh factor with guinea pig immune sera. Proc Soc Exp Biol Med 1942; 51: 313.
33. Wiener AS, Landsteiner K. Heredity of variants of the Rh type. Proc Soc Exp Biol Med 1943; 53: 167.
34. Landsteiner K. Die Spezifität der serologischen reaktionen. Berlin: Springer, 1933.
35. Speiser P, Smekal FG. Karl Landsteiner. Entdecker der Blutgruppen un Pionier der Immunologie; Biographie eines Nobelpreistraegers aus der Wiener Medizinischen Schule. Wissenschaft, Berlin: Blackwell Ueberrenter, 1990.
36. Gottlieb AM. Karl Landsteiner, the melancholy genius: his time and his colleagues, 1868–1943. Transf Med Rev 1998; 12: 18.