Innovators & Pioneers
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, he and [Alexander Wiener] discovered the Rh factor, which helped save the lives of many fetuses with mismatched Rh factor from their mothers. For his work identifying the human blood groups, he was awarded the Nobel Prize for medicine in 1930.
Born June 14, 1868, Landsteiner was the only child of Dr. Leopold Landsteiner, a famous Viennese journalist, and Fanny Hess Landsteiner. Leopold Landsteiner was the Paris correspondent for several German newspapers and the founder of the daily PRESSE, an influential liberal newspaper. The family lived in Baden bei Wien, an upper-middle-class suburb of Vienna. Karl was six years old when his father suffered a massive heart attack and died. Karl was placed under the guardianship of a family friend, but remained extremely close to his mother.
In 1885, when he was seventeen, Landsteiner passed the entrance examination for medical school at the University of Vienna, where early in his training he expressed enthusiasm for the study of chemistry. 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. Landsteiner 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 celebrated 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. He had found a subject that was to occupy his entire scientific career.
Discovers Blood Types
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 a 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 fifty-two papers on serological immunity, thirty-three on bacteriology and six on pathological anatomy. He was among the first to dissociate antigens, which 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.
Works Toward Polio Vaccine
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.
It had generally been 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 said that the development of a vaccine against poliomyelitis might prove difficult but was certainly possible. The first successful intravenous polio vaccine, developed by Jonas Salk, wasn't administered until 1955.
Landsteiner kept a grueling work schedule that 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. Helene bore a son christened Ernst Karl on April 8, 1917. After the war, Landsteiner's Austria was in chaos, with extreme shortages of food and fuel. He accepted a position as chief dissector in a small Catholic hospital in The Hague, Netherlands. There, from 1919 to 1922, he performed routine laboratory tests on urine and blood. Nevertheless, he managed to publish twelve papers on different aspects of immunology . It was during this time that 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." 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.
Post-War Europe Prompts Move to United States
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.
The Landsteiner family spent their summers in an isolated house on Nantucket that reminded Landsteiner of his Scheveningen home in the Netherlands. Landsteiner developed a profound dislike for his growing celebrity as the world's foremost authority on the mechanisms of immunity. He never got used to the noise and crowds of New York City, confessing to friends that he wished he could lock his family away when he was not home. Despite these problems, he became a United States citizen in 1929. Always shunning publicity, even avoiding offers to give public seminars, Landsteiner was stunned when he was besieged by reporters in 1930, upon the news that he had won the Nobel Prize.
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 SPEZIFITAT DER SEROLOGISCHEN REAKTIONEN, which was later revised and published in English, under the title THE SPECIFICITY OF SEROLOGICAL REACTIONS.
Landsteiner officially retired in 1939, at the age of seventy-one, but went on working. With [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 dreaded infant disease, erythroblastosis fetalis, which occurs when mother and fetus have incompatible blood types and the fetus is injured by the mother's antibodies. During his later years, Landsteiner formed a friendship with Linus Pauling, the American biochemist who won the Nobel Prize in chemistry in 1954. Their discussions led Pauling to apply his knowledge to immunology and to contribute a chapter to the revised edition of Landsteiner's book, THE SPECIFICITY OF SEROLOGICAL REACTIONS.
Landsteiner was said to worry incessantly and was overcome toward the end of his life with fear that the Nazis would take over the civilized world. He began to fear for his family's lives. Something of a scandal developed when he tried to prevent publication of his Jewish descent. Later his fear of fascism was surpassed by the discovery that Helene had a malignant thyroid tumor. On June 14, 1943, Landsteiner celebrated his seventy-fifth birthday with his wife, Helene, and his son, who had completed medical school and was a practicing physician. On June 24, Landsteiner had just sent off the final revision of the manuscript for his book, when he was seized by a coronary obstruction. He died two days later on Saturday, June 26, 1943. Helene died the same year on Christmas day. 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.
Source: From NOTABLE TWENTIETH-CENTURY SCIENTISTS. Gale Research, 1995. Reprinted by permission of The Gale Group.
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