- Donath-Landsteiner antibodies
- Donath-Landsteiner phenomenon
- Donath-Landsteiner syndrome
- Donath-Landsteiner test
- Landsteiner's classification
- Landsteiner-Fanconi-Andersen syndrome (Dorothy Hansine Andersen)
Biography of Karl Landsteiner
Karl Landsteiner was one of the first scientists to study the physical processes of immunity and is reckoned as the founder of serology. He discovered that there are several types of human blood and established the ABO-system based on haemagglutination. This blood typing made blood transfusion routine medical practice. In 1930 he was awarded the Nobel prize in physiology or medicine "for his discovery of human blood groups".
The blood-typist as a young man
Landsteiner was the only child of Dr. Leopold Landsteiner, a famous journalist and the founder of the Vienna daily PRESSE, and Fanny Hess Landsteiner. The family lived in Baden bei Wien, an upper-middle-class suburb of Vienna. Karl was four years old when his father suffered a massive heart attack and died. Karl was placed under the guardianship of a family friend, but remained close to his mother.
In 1885, when he was seventeen, Landsteiner passed the entrance examination for medical school at the University of Vienna. He took a year off from school at the age of twenty for his obligatory military service. When he was twenty-one, Landsteiner and his mother converted from Judaism to Catholicism and Karl was christened Karl Otto Landsteiner.
Besides the medical curriculum Landsteiner had a thorough grounding in the basic sciences, particularly chemistry. His first scientific work was in chemistry, which he began to study in Ernst Ludwig’s (1842-1915) laboratory in Vienna while still a student. He also attended lectures by Ludwig Mauthner (1840-1894).
He received his medical degree from the University of Vienna in 1891, aged 23. For the next three years he continued his chemical studies in Germany and Switzerland. In 1892 he synthesized glycolaldehyde at Würzburg with Emil Fischer (1852-1919), later to become the winner of the Nobel prize in Chemistry for 1902. During 1892-1893 he learned the chemistry of benzene derivatives from Eugen von Bamberger (1858-1921) in Munich, and in Zurich in 1893-1894 he studied organic chemistry under Arthur Rudolf Hantzsch (1857-1935) and Roland Scholl (1865-1945). With these famous scientists he published many journal articles
Medicine, however, remained Landsteiner’s chief interest. For a short time after receiving his M. D. he had worked with Otto Kahler (1849-1893) at the Second Medical University Clinic in Vienna; and from 1894 to 1895 he served with Eduard Albert (1841-1900) at the First Surgical University Clinic. During 1896-1897 Landsteiner was an assistant to Max von Gruber (1853-1927) in the newly established Institute of Hygiene at the University of Vienna. At this Institute, then intensely interested in experimenting on bacterial agglutination, his interest was awakened in serology and immunology and the nature of antibodies, and he now published his first papers on agglutination and immunology.
In 1897 Landsteiner moved to Vienna's Institute of Pathology in 1897, where he was hired to perform autopsies. Here his new teacher was Anton Weichselbaum (1845-1920) whose assistant he was from 1897 to 1908. Under Weichselbaum's supervision, Landsteiner conducted 3,639 post-mortem examinations and also began his work on serology.
And then there was blood
In a footnote to his only paper published in 1900, Landsteiner reported his perhaps most important discovery, the interagglutination occurring between serum and blood cells of different humans. He suggested that the phenomenon was not pathology, as was the prevalent thought at the time, but was a physiological phenomenon due to the unique nature of the individual's blood.
In an article the following year he described a simple technique of agglutination and was able to show that there were at least three major types of human blood that vary according to the kinds of sugar-containing substances, known as antigens, attached to the plasma membrane of the red blood cells. Based on this he divided human blood into three groups: A, B, and C (later 0).
Two of his co-workers, the clinicians Alfred von Decastello (Decastello-Rechtwehr, born 1872) and Adriano Sturli (1873-1964), examined additional persons and in 1902 found the fourth blood group, later named AB.
For his experiments, Landsteiner drew blood from himself and collected blood samples from his colleagues, doctors Jakob Erdheim (1874-1937), Pletschnig, Oskar Stoerk (1870-1926) and Adriano Sturli.
In 1903 Landsteiner became a Privatdozent at the University of Vienna.
Transfusion made possible
The discovery of blood groups made possible the safe transfusion of blood from one person to another. The first successful transfusions were achieved in 1907 by Dr. Reuben Ottenberg (1882-1959) of Mt. Sinai Hospital, New York. In 1913, Richard Lewisohn (1875-1961), a surgeon at the Mount Sinai Hospital, discovered that adding citrates to blood prevented it from coagulating. This was the basis for his introduction of the modern technique of blood transfusion, and the last prerequisite for the establishment of the modern blood bank, since blood could now be preserved for two- to three-week periods under refrigeration. The first transfusion on a human using Lewisohn's citrate method was performed by Dr. Howard Lilienthal (1860-1946). His comment:
The ease and simplicity of this transfusion was most amazing to me, who had so often suffered more than the patient in performing this life-saving operation.
During World War I, transfusion of compatible blood was first performed on a large scale and saved many lives. Operations on the heart, lungs, and circulatory system, previously impracticable because of the magnitude of the blood loss involved, were now feasible, as were complete blood exchanges in cases, for example, of intoxication or severe jaundice of the newborn.
Landsteiner's work added an important chapter to the development of legal medicine, providing admissible evidence in paternity suits and murder trials. In 1902 Landsteiner presented a lecture, together with Max Richter (1867-1932) 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.
At first Landsteiner did not know that blood types were inheritable, for Mendel’s (Johann Gregor Mendel, 1822-1884) laws of heredity, first presented in 1865, had passed into oblivion. In 1900 the laws were rediscovered by the German botanist and geneticist Carl Erich Correns (1863-1933), the Austrian botanist Erich Tschermak von Seysenegg (1871-1962), and the Dutch botanist and geneticist Hugo de Vries (1848-1935). Ten years later Emil Freiherr von Dungern (born 1867) and Ludwig Hirschfeld (born 1884) postulated the first hypothesis for the inheritance of blood groups. This theory was corrected in 1924 by the German mathematician Felix Bernstein (1878-1956) and was finally established. Since then, denying paternity has never been the same.
Testing, testing . . .
During this period Landsteiner also worked on characterizing and evaluating the physiological meaning of cold agglutinations in human blood serum. In 1904 he and the Austrian internist Julius Donath (1870-1950) described a test for the diagnosis of paroxysmal cold haemoglobinuria. This test is now known as Donath-Landsteiner phenomenon or test.
In 1905-1906 Landsteiner and Ernest Finger (1856-1939), then chief of the Clinic for Venereal Diseases and Dermatology in Vienna, were successful in infecting monkeys with syphilis, making possible experimentation with Spirochaeta pallida, the causal agent of the disease. In collaboration with the neurologist Otto Pötzl (1877-1962) and the serologist Rudolf Müller (1877-1934), they elucidated the previously unknown mechanism occurring in the Wassermann reaction (August Paul von Wassermann, German bacteriologist, 1866-1925). 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.
In 1908 he left the Pathology Institute to accept a position as director of the laboratories of the Royal-Imperial Wilhelmina Hospital in Vienna. This position afforded him the opportunity to become his own chief, thus allowing him to delegate the routine pathological work to an assistant and continue his personal research along the lines of his own choosing.
Landsteiner now concerned himself extensively with poliomyelitis. One day in 1908 the body of a young polio victim was brought in for autopsy. After the autopsy, Landsteiner injected a homogenate of its brain and spinal cord into the abdominal cavity of two rabbits, two guinea pigs, two mice and two monkeys (Cynocephalus hamadryas and Macacus rhesus). The rabbits, guinea pigs and mice remained well, but on the sixth day following the injections the Cynocephalus became sick and showed signs of paralysis similar to those in poliomyelitis patients. Two days later he died.
The histological appearance of the central nervous system of the monkeys 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 causes the disease. »
The disease could then be transmitted from monkey to monkey and eventually it was possible to transfer a strain of the virus to the rat and to the mouse, which could be used in sufficient numbers to establish the existence and virulence of the polio virus. The experiment was conducted with his assistant Erwin Popper. In volume 2, 1909 of the Zeitschrift für Immunitätsforschung, they reported that they might have found an `invisible virus' that had caused the polio epidemics. Today the World Health Organisation (WHO) still credits Landsteiner and Popper as having found the poliovirus with this experiment.
Landsteiner spent the years 1909-1912 in Paris collaborating with the Romanian bacteriologist, Constantin Levaditi (1874-1953) 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 1911 Landsteiner was promoted to Professor Extraordinarius.
War, marriage and chaos
Landsteiner's work schedule allowed little time for social activity. He was serving at a war hospital in 1916 when, at the age of 48, he married Leopoldine Helene Wlasto. Their only child, a son, was born the following year and was christened Ernst Karl on April 8, 1917.
After the war, Austria was in chaos, with hyperinflation and extreme shortages of food and fuel. conditions similar to those experienced by Germany a few years later. Landsteiner accepted a position as chief dissector in a small Catholic hospital, R. K. Ziekenhuis, in The Hague, Holland. There, from 1919 to 1922, he performed routine laboratory tests on urine and blood. It wasn't much more than a technician's job, but it protected him and his family at least against hunger and cold.
In 1921, utilising investigations dating as far back as 1904, Landsteiner 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." This discovery was influential in the development of immunology and launched Landsteiner into a study of the phenomenon of allergic reactions.
However, the working conditions in The Hague were no better than in Vienna. He therefore accepted an offer from the Board of Directors of the Rockefeller Institute in New York, and went to the United States in 1922. Throughout the 1920s Landsteiner worked on the problems of immunity and allergy. In 1927 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 and, in 1927, the types began to be used in paternity suits.
Karl Landsteiner became a United States citizen in 1929.
In the field of bacteriology, it should be noted that Landsteiner and Clara Nigg were successful in 1930-1932 in culturing Rickettsia prowazekii, the causative agent of typhus, on living media.
In 1934, with W. Strutton and Merril W. Chase (born 1905) he described a blood factor found only in Negroes, which today is called the Hunter-Henshaw system.
The Rh factor
Landsteiner officially retired in 1939, at the age of seventy-one, but went on working. Already in 1940 he and his co-workers Alexander Wiener (1907-1976) and Philip Levine (1900-1987) made an important discovery. In a paper published that year, they described a new factor in the human blood, the Rh factor, for Rhesus monkeys, in which the factor was first discovered. Levine was the first to see the connection between this factor and jaundice occurring in newborn children.
Before the introduction of the Euro, Landsteiner was the last to have his portrait on a one thousand shilling banknote, sharing such honour with Erwin Schrödinger (1887-1961).
Landsteiner was described as a modest, self critical, rather timid man known for his wide reading He was also an excellent pianist. Over the years he became ever more committed to his work, and in his later years he had little time for friendships.
Upon his death, tributes were published around the world, but no mention of his death was published in his native Austria or Germany until 1947, after the war and the defeat of Nazism.
Awards and honours:
1926: Hans Aronson Foundation Prize.
1929: President of the American Association of Immunologists
1930: Nobel Prize for Physiology or Medicine
Paul Ehrlich Medal for chemistry.
Chevalier of the French Legion of Honour
Dutch Red Cross Medal
Honorary doctorates from the University of Chicago (1927), Cambridge (1934), Université Libre de Bruxelles (1934), and Harvard (1936).
- "Time is so short and there is so much to do. We must hurry."
George MacKenzie: unfinished manuscript on the life of Karl Landsteiner.
"He was an extraordinarily persistent, industrious and brilliant experimenter. When fascinated by a problem he could work day and night".
Robert Doerr, cited in:
George MacKenzie: unfinished manuscript on the life of Karl Landsteiner.