The Nobel Prize in Physiology or Medicine 1990
Joseph E. Murray, E. Donnall Thomas
Presentation Speech by Professor Gösta
Gahrton of the Karolinska Institute
Translation from the Swedish text
Your Majesties, Your Royal Highnesses,
Ladies and Gentlemen,
During the 19th century, the association between disease symptoms and organ damage was well understood. Trouble with urine could be caused by damage of the kidney, and if the skin was yellow the cause could be in the liver. Damage to the kidney was most often incurable. Therefore, it was thought very early that perhaps a new undamaged organ from somebody else could cure the disease. Thus, at the turn of the century many heroic attempts were made to transplant kidneys from swine, sheep and goats, however without success. In 1902, attempts were made to transplant a kidney from one human being to another, again with no success. Very soon it was discovered that it was possible to transplant an organ or tissue within an individual without harm, but not between individuals. In 1912, Alexis Carrel received the Nobel Prize among other things for his discoveries concerning transplants of blood vessels and organs. However, this success was limited to transplants within an individual. Carrel concluded that there was a biological force that prevented transplantation between individuals, and he believed that it would never be possible to succeed in having an organ from one individual function in another. He received support for his belief from among others, the 1960 Nobel Prize-Winner, Peter Medawar, who discovered the role of the immune defence system in rejection of a graft and also showed that the biological force defined by Carrel was of an immunological nature.
Joseph Murray was not discouraged by this knowledge. There were reasons to believe that the immunological barrier was lacking between identical twins. Joseph Murray developed a surgical technique for kidney transplantation in dogs and showed that a kidney that was transplanted from one dog to the other could be induced to function. He used the technique in the first successful kidney transplant between identical twins in December 1954. Richard Herrick, who had incurable kidney damage was the first candidate. In order to make sure that he and his brother Ronald were identical twins, Joseph Murray asked the police in Boston to document their fingerprint patterns. During a routine review of police records, journalists found out about the investigation and its confidentiality was breached. However, Richard Herrick appeared to take this leakage to the press calmly. He became the darling of the media. The operation worked out perfectly and the kidney functioned well. Richard Herrick married his recovery-room nurse and became the father of two children. He lived happily for eight years when he died of a heart infarction. Joseph Murray later performed several other transplants between identical twins. However, most patients with incurable kidney damage had no twins, and it was therefore some time before such patients could become transplant candidates.
About two years later Donnall Thomas attempted to use bone marrow transplantation to cure terminal cancer patients, most of them with leukemias or cancers involving the bone marrow. He first treated the patients with bone-marrow-ablative total body irradiation. The goal was to cure the patients from the cancer disorder and to kill the bone marrow cells. Donnall Thomas showed that it was possible to remove about one liter of bone marrow out of the bones of a healthy individual. It was possible to give this marrow to the cancer patient by infusing it into a blood vessel. The bone marrow cells found the right spots in the new body where they could produce new normal and functioning blood cells, which soon appeared in the circulatory system. However, the healthy marrow also contained the defense cells, and these attacked their new host. The result was unfortunately a reversed and deadly rejection reaction called the graft-versus-host-reaction.
During the 1950s and 1960s some discoveries were made that were of the utmost importance for future successes in transplantation research. Jean Dausset discovered human transplantation antigens, a kind of fingerprints of the cells in the body. He was rewarded for this discovery with the Nobel Prize in 1980. About the same time George Hitchings and Gertrud Elion discovered the first cytotoxic drugs for which they were awarded the Nobel Prize in 1988. These cytotoxic drugs could also diminish the rejection reaction. Joseph Murray first used total body irradiation in attempts to prevent this reaction. Later he and others showed that azathioprin, one of the drugs discovered by Hitchings and Elion, was the most effective of these drugs in preventing rejection. This led to the first successful kidney transplantation between relatives that were not identical twins, and also to the first successful transplantation using kidneys from deceased persons. The best results were obtained when donors were selected who matched the patient's transplantation antigens. Kidney and organ transplantation was established as a treatment method. Today about 20,000 kidneys are transplanted every year, and more than 100,000 patients have gained a new and better life after transplantation.
Donnall Thomas managed to diminish the graft-versus-host reaction using the cytotoxic drug methotrexate. He showed very soon that if a donor, usually a sibling, was selected by typing for transplantation antigens, it was possible to cure leukemia, certain inherited disorders of the bone marrow, and the severe blood disorders, aplastic anemia and thalassemia. More than 10,000 patients have been cured, or have been given a normal life, with the help of bone marrow transplantation.
Dr. Joseph Murray and Dr. Donnall
On behalf of the Nobel Assembly of the Karolinska Institute I would like to congratulate you on your outstanding accomplishments and ask you to receive the Nobel Prize in Physiology or Medicine from the hands of His Majesty the King.
From Nobel Lectures, Physiology or Medicine 1981-1990, Editor-in-Charge Tore Frängsmyr, Editor Jan Lindsten, World Scientific Publishing Co., Singapore, 1993
Copyright © The Nobel Foundation 1990
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