Dr. E. Donnall Thomas, who showed that it was possible to transplant bone marrow to save the lives of patients dying from blood cancer and other blood disorders, a discovery that earned him a Nobel Prize, died on Saturday in Seattle. He was 92.
His death was announced by the Fred Hutchinson Cancer Research Center in Seattle, where he had long been on the faculty.
When Dr. Thomas began his research in the late 1950s, bone marrow transplants were seen as a frightening last resort. Patients suffered dangerous complications from the procedure, and survival rates were grim. The patient’s immune system would either destroy the transplanted marrow as foreign, or the transplanted marrow, which contains immune system cells, would destroy the patient’s lungs, kidneys and other organs.
The only successes were in identical twins because their tissue types matched.
Many physicians abandoned the approach, believing that bone marrow transplantation would never be safe enough to be practical. Dr. Thomas persevered, despite numerous failures and the criticism that he was exposing his patients to undue risks. He learned to match tissue types between recipients and donors, and to use drugs to tamp down the immune system.
His team carried out its first transplant using a matched sibling donor for a patient with leukemia in 1969. Eight years later, the team performed the first matched transplant from an unrelated donor, a success that led to the formation of a national registry that now includes more than 11 million marrow donors.
Dr. Thomas received the 1990 Nobel Prize in Physiology or Medicine with Dr. Joseph E. Murray, who performed the first successful kidney transplant. In announcing the prize, the Karolinska Institute said discoveries by both men were “crucial for those tens of thousands of severely ill patients who either can be cured or given a decent life when other treatment methods are without success.”
Today, bone marrow transplants are an accepted treatment for leukemia and other blood cancers, and can cure some inherited forms of anemia, like sickle cell disease.
Edward Donnall Thomas was born on March 15, 1920, in Mart, Texas, a rural town about 100 miles south of Dallas. He was the only child of Dr. Edward E. Thomas, a general practitioner, and Angie Hill Donnall, a teacher. He learned to hunt and fish, and as an adult, he would unwind after a hard day by filling shells with gunpowder.
He studied chemistry at the University of Texas at Austin, receiving his bachelor’s degree in 1941 and his master’s degree in 1943.
To pay for his education, he worked odd jobs around campus. After a shift waiting tables at a women’s dormitory, he got into a snowball fight with a journalism student, Dorothy Martin. The couple married in 1942, and soon afterward, his wife shifted her career ambitions to become his laboratory technician and lifelong collaborator.
Dr. Thomas went on to Harvard Medical School, where he became interested in leukemia and bone marrow. He received his medical degree in 1946, spent two years in the Army, then returned to Boston to complete his residency and conduct research. In 1955, he was appointed physician in chief at the Mary Imogene Bassett Hospital, now Bassett Medical Center, in Cooperstown, N.Y., an affiliate of Columbia University.
As soon as he arrived, Dr. Thomas started experimenting with bone marrow transplants in dogs, to work out the technical problems, and in people dying of leukemia. He reasoned that replacing a patient’s diseased marrow with that from a healthy donor could cure leukemia. By 1957, his team had performed marrow transplants on six patients, after first destroying the patients’ own marrow with radiation. The results were dismal. None of the patients survived beyond 100 days.
“Most people left the field,” Dr. Thomas told an interviewer. “They felt that this couldn’t ever be done.” Some physicians felt strongly that the transplants “shouldn’t go on as an experimental thing,” he said.
Dr. Thomas found that dogs given whole-body radiation and marrow from their litter mates had the same problems that humans did with infection, rejection and graft-versus-host disease, in which immune cells in the graft attack the patient’s organs as foreign. But occasionally, a dog survived the procedure and remained healthy. Dr. Thomas surmised that matching donors to patients was crucial.
In 1963, he moved to the University of Washington and developed a system for matching the tissue types of dogs. By the mid-1960s, he showed that most irradiated dogs that received marrow from matched donors survived long-term. Around the same time, researchers elsewhere had worked out methods for matching human tissue types. In 1969, Dr. Thomas began transplanting marrow from matched siblings to patients with very advanced leukemia.
Patients were irradiated in an underground bunker at a former military facility, the only place in the Seattle area with the required radiation sources, then rushed by ambulance to a sterile hospital ward. “We went back and forth like Ping-Pong balls,” Dr. Thomas said.
He would inoculate horses to obtain a serum to treat graft-versus-host disease, sometimes getting kicked in the process. Because patients were highly susceptible to infection until the transplanted marrow took hold, Dr. Thomas had their food sterilized in an autoclave normally used for germ-proofing surgical tools. Most of his initial 54 patients died of transplant complications or leukemia despite the precautions, but six experienced complete remissions.
These small successes led him to conduct transplants in patients with less advanced leukemia. In 1979, he reported curing half the leukemia patients who underwent transplantation when their disease was in chemotherapy-induced remission. Bone marrow transplants now can cure 70 to 80 percent of the healthiest children and teenagers with leukemia.
Dr. Thomas joined the Fred Hutchinson Cancer Research Center in 1974, serving as its first director of medical oncology and later as director of the clinical research division. The center has become a world leader in bone marrow transplantation.
Dr. Thomas was named professor emeritus of medicine at the University of Washington in 1990. He became a member of the National Academy of Sciences in 1982 and received the National Medal of Science in 1990.
Besides his wife, his survivors include two sons, E. Donnall Jr. and Jeffrey, and one daughter, Elaine Thomas.