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Landsteiner, Karl

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:

 0ABAB
Serum Anti-A-+-+
Serum Anti-B--++
+ Agglutination    
- No Agglutination    

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 α1 and α2; 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, ŏsterreichische Naturforscher, AÄrzte und Techniker (Vienna, 1957); H. A. L. Degener, Unsere Zeitgenossen (Leipzig, 1914; Berlin, 1935); I. Fischer, Biographisches Lexikon der hervorragenden Ärzte 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

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Landsteiner, Karl (1868-1943)

Landsteiner, Karl (1868-1943)

American immunologist

Karl Landsteiner was one of the first scientists to study the physical processes of immunity . He is best known for his identification and characterization of the human blood groups, A, B, and O, but his contributions spanned many areas of immunology , bacteriology, and pathology over a prolific forty-year career. Landsteiner identified the agents responsible for immune reactions, examined the interaction of antigens and antibodies, and studied allergic reactions in experimental animals. He determined the viral cause of poliomyelitis with research that laid the foundation for the eventual development of a polio vaccine . He also discovered that some simple chemicals, when linked to proteins, produced an immune response. Near the end of his career in 1940, Landsteiner and immunologist Philip Levine discovered the Rh factor that helped save the lives of many unborn babies whose Rh factor did not match their mothers. For his work identifying the human blood groups, Landsteiner was awarded the Nobel Prize for medicine in 1930.

Karl Landsteiner was born on in Vienna, Austria. In 1885, at the age of 17, Landsteiner passed the entrance examination for medical school at the University of Vienna. He graduated from medical school at the age of 23 and immediately began advanced studies in the field of organic chemistry, working in the research laboratory of his mentor, Ernst Ludwig. In Ludwig's laboratory Landsteiner's interest in chemistry blossomed into a passion for approaching medical problems through a chemist's eye.

For the next ten years, Landsteiner worked in a number of laboratories in Europe, studying under some of the most celebrated chemists of the day: Emil Fischer, a protein chemist who subsequently won the Nobel Prize for chemistry in 1902, in Wurzburg; Eugen von Bamberger in Munich; and Arthur Hantzsch and Roland Scholl in Zurich. Landsteiner published many journal articles with these famous scientists. The knowledge he gained about organic chemistry during these formative years guided him throughout his career. The nature of antibodies began to interest him while he was serving as an assistant to Max von Gruber in the Department of Hygiene at the University of Vienna from 1896 to 1897. During this time Landsteiner published his first article on the subject of bacteriology and serology , the study of blood.

Landsteiner moved to Vienna's Institute of Pathology in 1897, where he was hired to perform autopsies. He continued to study immunology and the mysteries of blood on his own time. In 1900, Landsteiner wrote a paper in which he described the agglutination of blood that occurs when one person's blood is brought into contact with that of another. He suggested that the phenomenon was not due to pathology, as was the prevalent thought at the time, but was due to the unique nature of the individual's blood. In 1901, Landsteiner demonstrated that the blood serum of some people could clump the blood of others. From his observations he devised the idea of mutually incompatible blood groups. He placed blood types into three groups: A, B, and C (later referred to as O). Two of his colleagues subsequently added a fourth group, AB.

In 1907, the first successful transfusions were achieved by Dr. Reuben Ottenberg of Mt. Sinai Hospital, New York, guided by Landsteiner's work. Landsteiner's accomplishment saved many lives on the battlefields of World War I, where transfusion of compatible blood was first performed on a large scale. In 1902, Landsteiner was appointed as a full member of the Imperial Society of Physicians in Vienna. That same year he presented a lecture, together with Max Richter of the Vienna University Institute of Forensic Medicine, in which the two reported a new method of typing dried blood stains to help solve crimes in which blood stains are left at the scene.

In 1908, Landsteiner took charge of the department of pathology at the Wilhelmina Hospital in Vienna. His tenure at the hospital lasted twelve years, until March of 1920. During this time, Landsteiner was at the height of his career and produced 52 papers on serological immunity, 33 on bacteriology and six on pathological anatomy. He was among the first to dissociate antigens that stimulate the production of immune responses known as antibodies, from the antibodies themselves. Landsteiner was also among the first to purify antibodies, and his purification techniques are still used today for some applications in immunology.

Landsteiner also collaborated with Ernest Finger, the head of Vienna's Clinic for Venereal Diseases and Dermatology. In 1905, Landsteiner and Finger successfully transferred the venereal disease syphilis from humans to apes. The result was that researchers had an animal model in which to study the disease. In 1906, Landsteiner and Viktor Mucha, a scientist from the Chemical Institute at Finger's clinic, developed the technique of dark-field microscopy to identify and study the microorganisms that cause syphilis.

One day in 1908, the body of a young polio victim was brought in for autopsy. Landsteiner took a portion of the boy's spinal column and injected it into the spinal canal of several species of experimental animals, including rabbits, guinea pigs, mice, and monkeys. Only the monkeys contracted the disease. Landsteiner reported the results of the experiment, conducted with Erwin Popper, an assistant at the Wilhelmina Hospital.

Scientists had accepted that polio was caused by a microorganism, but previous experiments by other researchers had failed to isolate a causative agent, which was presumed to be a bacterium. Because monkeys were hard to come by in Vienna, Landsteiner went to Paris to collaborate with a Romanian bacteriologist, Constantin Levaditi of the Pasteur Institute. Working together, the two were able to trace poliomyelitis to a virus, describe the manner of its transmission, time its incubation phase, and show how it could be neutralized in the laboratory when mixed with the serum of a convalescing patient. In 1912, Landsteiner proposed that the development of a vaccine against poliomyelitis might prove difficult but was certainly possible. The first successful polio vaccine, developed by Jonas Salk , wasn't administered until 1955.

Landsteiner accepted a position as chief dissector in a small Catholic hospital in The Hague, Netherlands where he performed routine laboratory tests on urine and blood from 1919 to 1922. During this time he began working on the concept of haptens, small molecular weight chemicals such as fats or sugars that determine the specificity of antigen-antibody reactions when combined with a protein carrier. He combined haptens of known structure with well-characterized proteins such as albumin, and showed that small changes in the hapten could affect antibody production. He developed methods to show that it is possible to sensitize animals to chemicals that cause contact dermatitis (inflammation of the skin) in humans, demonstrating that contact dermatitis is caused by an antigen-antibody reaction. This work launched Landsteiner into a study of the phenomenon of allergic reactions.

In 1922, Landsteiner accepted a position at the Rockefeller Institute in New York. Throughout the 1920s Landsteiner worked on the problems of immunity and allergy. He discovered new blood groups: M, N, and P, refining the work he had begun 20 years before. Soon after Landsteiner and his collaborator, Philip Levine, published the work in 1927, the types began to be used in paternity suits.

In 1929, Landsteiner became a United States citizen. He won the Nobel Prize for medicine in 1930 for identifying the human blood types. In his Nobel lecture, Landsteiner gave an account of his work on individual differences in human blood, describing the differences in blood between different species and among individuals of the same species. This theory is accepted as fact today but was at odds with prevailing thought when Landsteiner began his work. In 1936, Landsteiner summed up his life's work in what was to become a medical classic: Die Spezifität der serologischen Reaktionen, which was later revised and published in English, under the title The Specificity of Serological Reactions.

Landsteiner retired in 1939, at the age of seventy-one, but continued working in immunology. With Levine and Alexander Wiener he discovered another blood factor, labeled the Rh factor, for Rhesus monkeys, in which the factor was first discovered. The Rh factor was shown to be responsible for the infant disease, erythroblastosis fetalis that occurs when mother and fetus have incompatible blood types and the fetus is injured by the mother's antibodies. Landsteiner died in 1943, at the age of 75.

See also Antibody and antigen; Antibody-antigen, biochemical and molecular reactions; Blood agar, hemolysis, and hemolytic reactions; History of immunology; Rh and Rh incompatibility

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Landsteiner, Karl

Landsteiner, Karl

6/14/18686/26/1943
AUSTRIAN
IMMUNOLOGIST

Karl Landsteiner was one of the first scientists to study the physical processes of immunity. In the field of forensic science , he is best known for his identification and characterization of the human blood groups, A, B, and O, but his contributions spanned many areas of immunology, bacteriology, and pathology over a prolific 40-year career. He helped establish the science of immunochemistry.

Karl Landsteiner was born in Vienna on June 14, 1868. In 1891, he was awarded a medical degree by the University of Vienna. For the following five years he studied physiological chemistry in laboratories in Germany and Switzerland.

Landsteiner moved to Vienna's Institute of Pathology in 1897, where he was hired to perform autopsies. He continued to study immunology and the mysteries of blood on his own time. In 1900, Landsteiner wrote a paper in which he described the agglutination of blood that occurs when one person's blood is brought into contact with that of another. He suggested that the phenomenon was not due to pathology, as was the prevalent thought at the time, but was due to the unique nature of the individual's blood. In 1901, Landsteiner demonstrated that the blood serum of some people could clump the blood of others. From his observations he devised the idea of mutually incompatible blood groups. He placed blood types into three groups: A, B, and C (later referred to as O). Two of his colleagues subsequently added a fourth group, AB. In 1930 he received the Nobel Prize for medicine for his discovery.

In 1907, the first successful transfusions were achieved by Dr. Reuben Ottenberg of Mt. Sinai Hospital, New York, guided by Landsteiner's work. Landsteiner's accomplishment saved many lives on the battlefields of World War I, where transfusion of compatible blood was first performed on a large scale. In 1902, Landsteiner was appointed as a full member of the Imperial Society of Physicians in Vienna. That same year he presented a lecture, together with Max Richter of the Vienna University Institute of Forensic Medicine, in which the two reported a new method of typing dried blood stains to help solve crimes in which bloodstains are left at the scene.

In 1906, Landsteiner and Victor Mucha introduced the use of the dark-field method of diagnosis for the presence of the spirochete of syphilis. Landsteiner also determined the viral cause of poliomyelitis with research that laid the foundation for the eventual development of a polio vaccine. In 1908, Landsteiner reported the transmittal of poliomyelitis to monkeys from human material, thus substantiating the theory that the cause of the disease was a virus. In 1919, he went from his work as professor of pathologic anatomy at the University of Vienna to The Hague in the Netherlands as pathologist at the R. K. Ziekenhuis. In 1922, he went to New York City's Rockefeller Institute and continued at the institute until his death. In 1929, he became a citizen of the United States.

In 1927, Landsteiner and Philip Levine announced the discovery of the M and N agglutinogens, and in 1940, Landsteiner and a colleague discovered still another group of agglutinogens called the Rh factors. Of fundamental importance to the rise of immunochemistry was Landsteiner's demonstration that serological specificity is based on the chemical structure of antigens. Although he officially retired in 1939, Landsteiner continued his work in immunology until two days before his death in 1943, at the age of 75.

see also Antigen; Blood; Bloodstain evidence; Immune system.

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Karl Landsteiner

Karl Landsteiner

Karl Landsteiner (1868-1943), the Austrian-born American immunologist and Nobel Prize winner, discovered blood groups and helped establish the science of immunochemistry.

Karl Landsteiner was born in Vienna on June 14, 1868. In 1891 he was awarded a medical degree by the University of Vienna. For the following 5 years he studied physiological chemistry in laboratories in Germany and Switzerland. In 1898 he moved to the Pathological Anatomical Institute in Vienna, where he carried on work that led to the discovery of blood groups.

It was known that blood transfusion often resulted in dangerous or fatal clumping of the red blood corpuscles. After a series of tests performed in his laboratory, Landsteiner postulated the existence in the corpuscles of agglutinogens (antigens) called A and B and in blood serum of agglutinins (antibodies) called anti-a and anti-b. Reaction to transfused blood (clumping) depended on whether the agglutinogens A, or B, or A and B, or neither were present in the red blood corpuscles. Where the agglutinogen A was present, serum containing the agglutinin anti-a could not be used, and so forth. Landsteiner's discovery was first announced in a footnote to a paper appearing in 1900. In 1909 he devised the familiar classification scheme for blood groups: A, B, AB, O. In 1930 he received the Nobel Prize for his discovery.

In 1906 Landsteiner and Victor Mucha introduced the use of the dark-field method of diagnosis for the presence of the spirochete of syphilis. In 1908 Landsteiner reported the transmittal of poliomyelitis to monkeys from human material, thus substantiating the theory that the cause of the disease was a virus. In 1919 he went from his work as professor of pathologic anatomy at the University of Vienna to The Hague in the Netherlands as pathologist at the R. K. Ziekenhuis. In 1922 he went to New York City's Rockefeller Institute. He became a citizen of the United States and continued at the institute until his death.

In 1927 Landsteiner and Philip Levine announced the discovery of the M and N agglutinogens, and in 1940 Landsteiner and a colleague discovered still another group of agglutinogens called the Rh factors. Both discoveries were announced in the Proceedings of the Society for Experimental Biology. Of fundamental importance to the rise of immunochemistry was Landsteiner's demonstration that serological specificity is based on the chemical structure of antigens. His findings were summarized in Specificity of Serological Reactions (1936). Landsteiner continued to work until 2 days before his death on June 26, 1943.

Further Reading

A sketch and a list of Landsteiner's more than 350 publications is in Obituary Notices of the Fellows of the Royal Society, vol. 5 (1945). Another short sketch is in Theodore L. Sourkes, Nobel Prize Winners in Medicine and Physiology (1953; rev. ed. 1966). Nobel Foundation, Nobel Lectures in Physiology or Medicine, 1922-1941, vol. 2 (1965), provides biographical data and information on the events leading to Landsteiner's discovery and its significance. □

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Landsteiner, Karl

Karl Landsteiner (kärl länt´shtīnər), 1868–1943, American medical research worker, b. Vienna, M.D. Univ. of Vienna, 1891. In 1922 he came to the United States to join the staff of the Rockefeller Institute (now Rockefeller Univ.). He later became a U.S. citizen. For his discovery of human blood groups he won the 1930 Nobel Prize in Physiology or Medicine. As a result of his research in immunology and the chemistry of antigens and serological reactions, he made valuable contributions in hemolysis and in methods of studying poliomyelitis. In 1940 he identified, in collaboration with A. S. Wiener, the Rh factor.

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Landsteiner, Karl

Landsteiner, Karl (1868–1943) US pathologist, b. Austria. Landsteiner discovered the four different blood groups (A, B, AB, and O) and demonstrated that certain blood groups are incompatible with others. He received the 1930 Nobel Prize in physiology or medicine. In 1940, with A. S. Wiener, he identified the rhesus (Rh) factor in blood.

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Karl Landsteiner

Karl Landsteiner

1868-1943

Austrian-American Immunologist and Pathologist

Karl Landsteiner is recognized for his pioneering research into the workings of the human immune system. He was awarded the 1930 Nobel Prize for Physiology or Medicine for his discovery of human blood groups, which he classified in the ABO blood type system. He also discovered the polio virus and developed a test for syphilis.

Born in Vienna on June 14, 1868, Landsteiner was the only child of Dr. Leopold Landsteiner, a noted journalist. His father was the Paris correspondent for several German newspapers and later founded his own newspaper, Presse. When Karl was six, his father died of a massive heart attack, and he was placed under the guardianship of a family friend.

At age 17, Landsteiner entered the medical school at the University of Vienna, where he developed an interest in organic chemistry. He remained close to his mother, and in 1889 they both converted from Judaism to Catholicism. He graduated from medical school at the age of 23 and immediately went into a research laboratory, where he applied his passion for organic chemistry to the field of medicine.

While at the Vienna Pathological Institute (1898-1908), he became interested in the problem of why some people could get blood from others but some died. While doing autopsies at the institute, he noted that some blood would clump or agglutinate when mixed with other blood. He proposed there were factors in the blood that were compatible and others that were not. He called these A, B, and C (C was later renamed O). Two other researchers added AB. He showed that a kind of sugar-containing substance, called an antigen, was attached to the plasma membrane of the red blood cells that determined these factors. Further investigation showed that A would always clump with type B. Type O was a universal donor and did not clump with either. The rare form AB was identified as the universal recipient.

Testing the research of Landsteiner in 1907, Dr. Reuben Ottenberg of Mt. Sinai Hospital, New York, performed the first successful blood transfusion. The discovery saved many lives during World War I, the first time that transfusions were performed on a large scale.

Using the information on blood types, Landsteiner and a colleague, Max Richter of the Institute of Forensic Medicine, also devised a plan to use dried blood left at crime scenes to help investigators solve the crime.

From 1908-1920 Landsteiner was head of the pathology department at the Vienna Wilhemina Hospital. There, he wrote numerous papers on bacteriology and immunology and made several important discoveries, including how antigens and antibodies are related. He also developed methods for purifying antibodies and laboratory techniques related to immunology. Although refined, many of the techniques are still used today.

Landsteiner was one of the first to use animal models to study disease. He successfully transferred the sexually transmitted disease syphilis from humans to apes. Later, he worked to develop a technique called dark-field illumination to identify the bacteria that cause syphilis.

While at the institute, a young boy who had died of polio was brought in for autopsy. Using part of the spinal cord from the boy, Landsteiner injected it into rabbits, guinea pigs, mice, and monkeys. He was puzzled that only the monkeys developed the disease. It was thought that the condition was caused by a bacterium, and Landsteiner went to Paris to collaborate with Romanian scientist Constantin Lefaditis of the Pasteur Institute. The two realized that polio was not caused by a bacterium, but a virus. They traced how it was transmitted, how long the exposure must be, and how the serum of another patient could neutralize the virus in the laboratory. In 1912 they predicted that a vaccine against this virus could be developed, however, this did not occur until 1955, when Jonas Salk developed the first successful polio vaccine.

Dedicated completely to his work, Landsteiner did not marry until age 48, when he met his wife, Helene, at a war hospital. They married in 1916 and had one son, Ernst Karl, in 1917. Postwar Austria was very chaotic, with shortages of food and supplies. Fortunately, Landsteiner was able to get a job at a small Catholic hospital in the Netherlands. Although he was assigned to do routine blood and urine work, he made a major discovery with haptens, small organic molecules that determine antigen-antibody reactions in the presence of a protein. He showed that certain inflammations of the skin caused contact dermatitis and launched into the study of allergic reactions.

Landsteiner was fortunate to be offered a position at the Rockefeller Institute in New York. Refining his previous work, he found new blood groups M, N, and P. He and Philip Levine published a work in 1927 that described the use of blood groups in paternity suits.

In 1929 Landsteiner became a United States citizen, but did not like the crowds of New York and did not care to be a celebrity. When he won the Nobel Prize in 1930, he shunned publicity. His Nobel lecture, describing differences in blood between individuals, as well as species, was at odds with the medical community of the day, although it is well accepted now.

He officially retired in 1939, but continued to work on another blood factor called Rh, because it was first discovered in rhesus monkeys. The incompatible blood factor is responsible for a condition that occurs when a mother without the blood factor carries a fetus with the factor. The infant may have a deadly condition known as erythroblastosis fetalis.

Toward the end of his life, Landsteiner became increasingly worried that the Nazis would take over the world. He died in 1943, at age 75, of a massive heart attack just after completing the manuscript of a new book and seeing his son finish medical school. Tributes were paid to Landsteiner, but there was no mention of his death in Germany or Austria, his home, until 1947, after the Nazis had been defeated.

EVELYN B. KELLY

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Landsteiner, Karl

LANDSTEINER, KARL

LANDSTEINER, KARL (1868–1943), scientist and Nobel Prize laureate, discoverer of the basic human blood groups and of the Rhesus blood factor. Landsteiner was born in Vienna; from 1898 to 1908 he worked at the Pathology Institute of Vienna University and from 1909 to 1919 taught pathology at the University's Wilhelminenspital. After three years in Holland he went to New York in 1922 to become a member of the Rockefeller Institute for Medical Research, and worked there for the rest of his life. He died a Roman Catholic.

In 1927, together with Philip *Levine, Landsteiner described the m, n, and p factors in human blood. These hereditary factors came to be used to decide cases of doubtful paternity. In 1930 he was awarded the Nobel Prize for physiology and medicine, for his discovery of four different groups of human blood, a, b, ab, and o, distinguished by their clotting factors. This became the basis for matching donor and recipient in blood transfusions.

In 1940 Landsteiner and Alexander S. Wiener completed the research leading to their discovery of the Rhesus or Rh factor which was to become of lifesaving importance in obstetrics and clinical medicine. Landsteiner also made other major contributions to medical science: he introduced dark-field illumination for demonstrating spirochetes in syphilitic lesions and discovered that the rhesus monkey could be infected by the poliomyelitis virus – a finding which was the basis, decades later, for the development of the *Salk vaccine. His The Specificity of Serological Reactions (1936) has become a classic.

bibliography:

T.N. Levitan, Laureates: Jewish Winners of the Nobel Prize (1960), 128, 137–40; Heidelberger, in: Science, 98 (1943), 233f.; P. Speiser, Karl Landsteiner (Ger., 1914), including list of his publications.

[Samuel Aaron Miller]

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