World of Microbiology and Immunology on Karl Landsteiner
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.
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