In 1901, Austrian physician Karl Landsteiner solved a centuries-old medical mystery when he discovered the existence of blood groups. His work, which led to his receiving the 1930 Nobel Prize in Physiology or Medicine, helped usher medicine into the 20th century, with the first successful blood transfusion performed in 1907, the first blood-typing tests used in 1910 and the first blood banks established in the 1930s. Within a few more years, blood transfusion was a regular surgical practice, and while it saved countless thousands of lives each year, a second, less apparent mystery soon became evident: A small but noticeable percentage of patients was still presenting with hemolytic reactions to transfusions of their own ABO blood type. Dr. Landsteiner’s identification of the Rh factor in 1937 resolved this problem and garnered him a share of the 1946 Albert Lasker Clinical Medical Research Award.
In 1922 Dr. Landsteiner moved from Vienna to the United States, where he continued his research into blood antigens as a member of The Rockefeller Institute of Medical Research. By examining the cross reactions of blood types in different animals, he had by the 1930s determined that blood-type similarities had been evolutionarily conserved across mammalian species, and that blood antigens have a mosaic-like structure, added to and altered little by little through the evolution of multiple allelic genes. Since the stronger, more ubiquitous blood types of the ABO system are shared by other animals, he reasoned, the same should also be true for rarer, less visible antigens. Injecting the blood of various animals into rabbits, he created antisera for numerous different antigens. By pairing his antisera with samples of human red blood cells, he was then able to draw a number of previously unidentified human antigens out of hiding.
While most of these new antigens proved clinically insignificant — because their antibodies occur rarely in human blood and then only in very weak concentrations — there was one that Dr. Landsteiner thought merited further investigation. Antiserum obtained by injecting the blood of rhesus macaque monkeys into rabbits turned out to be reactive against the blood of about 85 percent of Caucasian humans, in a manner entirely unrelated to the ABO blood types. Case studies he examined over the next several years confirmed Dr. Landsteiner’s initial findings and led him and his colleagues to the conclusion that the huge majority of ABO-compatible transfusion reactions were caused by this antigen. He named it the Rh factor, after the rhesus macaque.
The mosaic structure of the Rh factor was subsequently shown to be far more complex than that of its ABO counterparts. Further investigations by Dr. Landsteiner’s group revealed no less than eight different types of anti-Rh antibody, accounting for the frequent variation of severity that had been observed in Rh-incompatible transfusion reactions. More types were subsequently identified, including some that react to both Rh-positive and Rh-negative blood, most common in African populations. His studies of the wide spectrum of antibodies elicited by single antigens led Dr. Landsteiner to suggest a now-common key-and-lock analogy, with isoantibodies acting like exact keys that fit with only very particular antigens and others that are like skeleton keys and can fit general classes of antigen.
The medical implications of Dr. Landsteiner’s discovery were immediate, as it effectively removed the last major risk of blood transfusion. Concurrent with his work, Philip Levine — earlier a Rockefeller colleague of Dr. Landsteiner — identified the Rh factor as the cause of a common disease of childbirth that has now been all but eradicated in developed nations. The Rh factor has also proved a useful tool in other fields, including anthropology. While no blood antigen is unique to any one ethnic group, the incidence ratios of different blood groups are different among ethnicities — most remarkably so with the Rh factor. Rates of Rh-positivity vary from 99 percent, in Asians, to 65 percent among Europeans from the Basque region. Dr. Landsteiner shared the 1946 Lasker Award with Dr. Levine as well as John Mahoney of the United States Marine Hospital and Alexander Wiener of the New York Medical Examiner’s Office.
Dr. Landsteiner was born in Vienna in 1868. Following his medical degree from the University of Vienna in 1891, he continued his studies in biochemistry at the Universities of Zurich, Wurzburg and Munich. Returning to Vienna, he became a research assistant to Max von Gruber at Vienna’s Hygiene Institute in 1896. From 1898 to 1908, he was an assistant in the department of pathological anatomy at the University of Vienna. From 1908 to 1919 he was prosector at the Wilhelmina Hospital, and in 1911 he also became professor of pathological anatomy at the University of Vienna. With the difficulties faced by researchers in Austria following World War I, Dr. Landsteiner moved to The Hague, where he served as prosector in a small Roman Catholic Hospital until 1922, when he accepted a post at The Rockefeller Institute. He retired in 1939 but continued his research, and in 1943 died in his laboratory. In addition to the Lasker Award, Dr. Landsteiner received the 1930 Nobel Prize in Physiology or Medicine.