karl

My knees wobbled as I walked down the long second-floor corridor of the Rockefeller Institute for Medical Research 1 in New York that day in 1929. I was a very frightened young medical student. A telephone call had summoned me to the laboratory of one of the great research men of our time-Dr Karl Landsteiner.
At the time there were two main theories on how the various types of blood were inherited. I had written a mathematical analysis of the theories, and for good measure had thrown in the statement that the Chinese had discovered the blood groups in the thirteenth century.
Now I stood before Landsteiner, a six-footer with dark piercing eyes, bushy eyebrows and drooping moustache. The laboratory window was made of frosted glass: Landsteiner wanted no distracting views.
Where, he asked, had I learnt that the Chinese had discovered the blood groups? I cited my source, a mention in a paper I had read. A flicker of a smile

passed over the no-nonsense countenance. "I you will find it better, young man," he said, "always to consult original sources." I would find a book in the library-he gave me the exact reference-that I might read. The interview was over.
The Chinese, of course, hadn't discovered the blood groups: Landsteiner had.
After my initial chastisement we became good friends, and eight years later, working together, we discovered the Rh factor-the basis of the blood incompatibility which had mysteriously caused the death of thousands of infants in the womb or within hours of birth.
Medical Genius. The panorama of accomplishment of this giant of research has few equals in the annals of medicine. He laid the groundwork for research on today's polio-protective vaccines. He delineated the mechanism of skin allergies. His research on Rtckettsia microbes opened the way for vaccines to prevent typhus and Rocky Mountain spotted fever. Almost single-handedly he founded and developed the science of immunochemistry. He made blood typing possible, and so opened the way for the tens of millions of life-saving transfusions to come. Any one of these things would have ranked Landsteiner with the immortals. Yet this is only a partial list of his accomplishments.
Bom in Baden, Austria, in 1868, the son of a journalist, young Landsteiner graduated from medical school and spent four additional years studying chemistry. Then he joined the University of Vienna and began work on his lifelong interest, the mystery of blood.
Since the I600's, venturesome doctors had been trying transfusions- with results so disastrous that France, Italy and England had eventually passed laws prohibiting such experiments. Viennese medical bigwigs had a pat explanation for the difficulty. AH blood, they claimed, was alike; transfusion disaster resulted when the donor's blood was diseased. Landsteiner had the audacity to question these oracles.

Big Step Forward. He collected blood samples, allowed them to clot, then separated clot from straw-coloured serum. Then the mixing began-red cells from one individual, serum from another. Landsteiner peered through his microscope to watch the results and saw a starling drama unfold. Normally, red cells look like evenly distributed grains of sand, but on many of the slides red cells were clumping together- agglutinating-like bunches of grapes!
In precise handwriting Landsteiner recorded his findings, drew up charts, and from them drew momentous conclusions. Bloods were not alike. Some red cells contained a mysterious A substance, some a stuff, some contained neither and were labelled o-nought. Later, people would misread this nought, and it became the letter O for a third great group of bloods.

(Landsteiner missed the fourth class- AB-because none of the volunteers from whom he wheedled blood specimens were in this rare group, but a year later two of his workers, one of them a student, tracked this one down.) The obvious conclusion was: If you transfused A blood into an A person, or B into a B, there should be no difficulty. But never put A into a B.
Successful transfusion was now possible, but medicine wasn't ready to put the revolutionary discovery to work. The world paid not the slightest attention.
Ignored, Landsteiner could go along being what God had made him, a restless malcontent making enormous contributions to human knowledge through an unending stream or research projects. He led a busy life. In ten years, besides lecturing and teaching, he performed 3,639 post-mortems.
Then in 1908, Landsteiner left the university to accept the post of chief pathologist at Wilhelminen Hospital. He had a new project right at hand. Vienna was in the midst of a frightening polio epidemic.
No one knew what caused the disease. Previous attempts to transmit it to animals for study had failed, but now Landsteiner undertook the job. He pulverized the spinal cord of a recently dead victim of this terrible illness, made a suspension of the cells, and injected it into monkeys. Then he waited, apparently in vain. Just when he was ready to abandon the whole business, one monkey developed paralysis of the back legs. It was polio.
After further animal work, getting the disease firmly established so that it could be studied in the laboratory, Landsteiner passed more ground-up cord suspension through a filter fine enough to strain off ordinary bacteria. Would the stuff that went through still produce the disease? Soon, the monkeys that got the filtrate were paralysed. It was the next big step forward: it proved that polio had to be a virus disease.
At this point Landsteiner lost interest. He had done the pioneering, the sort of thing he liked to do. Let others do the detail work that would eventually lead to vaccine.
At this point Landsteiner lost interest. He had done the pioneering, the sort of thing he liked to do. Let others do the detail work that would eventually lead to vaccine.
In 1919, chaos fell on Vienna as the aftermath of defeat in the First World War. The communists threatened to take over. There was shooting in the streets, and wild inflation. Landsteiner brought his meagre salary home in a suitcase-but it was hardly enough to buy a loaf of bread. He had to walk three kilometres for a small pail of goat's milk for his two-year-old son. One night the fence round his tiny cottage disappeared-fuel for someone's stove. Worse, there were no laboratory supplies, no research animals. Work came to a virtual standstill.

body responds by producing specific antibodies to combat them, Thus, if you press a little smallpox vaccine (antigen) into the skin of the arm, the body responds by building smallpox antibodies which will protect against the disease for years to come. Or, if a person who is sensitive to ragweed pollen (antigen) sniffs a bit of it, the result is a runny nose and bleary eyes- for an allergy, too, is simply an antigen-antibody manifestation.
The point that impressed Landsteiner most was that all this was so extraordinarily specific. There seemed to be a separate antibody for every antigen. His work would eventually lead to an explanation for the whole mysterious business of immunity and allergy, and a book, The Specificity of Serological Reactions, that became the bible of the new science of immunochemistry.
Invited to head his own research laboratory at the Rockefeller Institute, Landsteiner sailed for New York in 1922. For him, the Institute was a dream come true: laboratory facilities such as he had never seen; animals; as many assistants as he needed; stimulating minds to confer with. He had all he needed to get back to his original love, blood.
He was sure it contained other things besides his A and B Stuff. Indeed, he felt pretty sure that in time blood would turn out to be almost as individual as fingerprints. With a talented young assistant, Dr Philip Levine, he began looking for new factors. In rapid succession they found three new ones-M, N, P. These weren't all-important in transfusion, as A and B were. They rarely cause reactions. Yet they were important in legal medicine as in identifying blood stains or establishing non-paternity.
Key Factor. In the late I930's, in my laboratory at the Chief Medical Examiner's office, I had been doing some work with blood from monkeys-spider monkeys, woolly monkeys, rhesus monkeys, monkeys, any kind I could find. I asked for Landsteiner's help and we began working together.
In 1937 we began shooting rhesus monkey blood into rabbits, then later drawing off rabbit blood and seeing how the serum reacted with human red cells. Eighty-five percent of the time the serum clumped human red cells! Rhesus monkeys shared a new blood factor with man. We christened it the Rh factor, for rhesus.
Mightn't Rh be just as important in transfusion as factors A and B? Dr Raymond Peters had written to me from Baltimore about severe transfusion reactions he had experienced although bloods matched according to the four original groups. Rh incompatibility? The answer, 1 discovered, was yes.

Shortly afterwards Levine and Dr Lyman Burnham encountered an unusual case in Newark, New Jersey. A woman had delivered a baby dead of a mysterious disease, erythroblastosis. Ill herself, she had then been transfused with her husband's blood-and had nearly died as a result, although the bloods apparently matched.
Was it possible, Levine wondered, that the baby had inherited some blood factor from the father which caused its blood and its mother's blood to war on each other-resulting in the infant's death? Her violent reaction to her husband's blood suggested this. And it turned out to be true. The thing involved here was the Rh factor Landsteiner and I had found in our rhesus monkeys. The way was now open for conquest of this formerly deadly blood incompatibility. Millions of patients and blood donors are now Rh-tested each year.
Everyone recognized Landsteiner as a genius. But his gruff exterior hid a shy man

underneath, a man dedicated to his work. In 1930, the Institute switchboard was flooded with calls from newspapers, after reports that Landsteiner had just won the Nobel Prize for Medicine for his work in blood-typing. He refused to talk and just went on working. When he got home that evening he didn't even mention it to his family. Eventually a cable arrived from Stockholm. "I have just won the Nobel Prize," he said to his wife Helene. Then he went back to his scientific journals.
Nearly always, after a full nine-to-five day in the laboratory, there would be four hours of work after dinner. For ten years I spent Wednesday evenings with him. He would sit at the dining-room table munching apples while we discussed research under way, or worked on papers to be published.
At 75, Landsteiner was still keeping to his rigorous schedule. He was58 at his laboratory bench on the morning of June 24,1943, when he was struck down by a massive heart attack. For two days he lingered in pain, fretting about his book, driving assistants forward with current experiments. Then life passed from him.
Buried as he wished in a little cemetery on Nantucket Island, he lies in an unnoticed grave swept by the sea wind and covered with a thatch of beach grass. It is a quiet resting spot indeed for the most authentic medical research giant of our century-a man whose work has touched and benefited nearly every human being now alive.