E. (Edward) Donnall Thomas, MD, the Nobel laureate whose single-mindedness and perseverance established bone marrow transplantation (BMT) as an effective and life-saving therapy for hematologic cancers, died on October 20, in Seattle, at age 92 from cardiovascular disease.
Regarded as the "father of bone marrow transplantation," he was also considered a father figure to his Fred Hutchinson Cancer Research Center family.
He performed the first successful BMT to treat leukemia in 1956 when he was at Mary Imogene Bassett Hospital, now Bassett Medical Center, in Cooperstown, NY, an affiliate of Columbia University. Both the patient and donor were identical twins, but subsequent transplants between siblings who were not identical twins proved unsuccessful.
He published his findings in 1957 in the New England Journal of Medicine, but most medical professionals abandoned the procedure, which was considered extremely risky, with poor outcomes and generally believed to be impractical.
For 10 years Thomas went back to working with animal models, using beagles who were littermates, and continued his work when he moved to the University of Washington in 1963, where he became the first head of the Oncology Division. In 1974 he joined the newly created Fred Hutchinson Cancer Research Center as its first Director of Medical Oncology, where he remained until retiring in 2002.
Over the years he was named Associate Director and then Director of the Center's Clinical Research Division, stepping down from that post in 1990, just before receiving his Nobel Prize in Physiology or Medicine for discoveries "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 BMT, and its related blood stem cell transplantation, has proven successful for treating leukemia, lymphoma, and other blood disorders, and both have increased survival rates from about zero to nearly 90 percent for some blood cancers.
Thomas persisted experimenting with bone marrow transplants in dogs to figure out the technical problems, believing that replacing a leukemia patient's marrow with marrow from a healthy donor could produce a cure.
Most of the dogs receiving whole-body radiation and marrow from littermates suffered from infection, rejection, and graft-versus-host disease, but from the few that survived he reasoned it was crucial to match donors to patients and developed a system for matching dogs' tissue types.
By the mid-1960s Thomas showed that most irradiated dogs receiving marrow from matched donors were able to survive long-term, and other researchers began developing techniques for matching human tissue types, which allowed Thomas to begin transplanting marrow from matched siblings to patients with advanced leukemia in 1969.
Although many of his initial 54 patients died from leukemia or complications from the transplant, six had complete remissions, leading Thomas to transplant patients who had less advanced disease; and by 1979 he successfully treated half his transplanted leukemia patients when they were in remission from chemotherapy.
Fred Appelbaum
Fred Appelbaum, MD, Director of Hutchinson's Clinical Research Division, the post formerly held by Thomas, said his career path was influenced by Thomas' work, and he received a job offer from Thomas after Appelbaum and colleagues at the NIH published an article in Blood in 1977 about the first autologous transplant they had accomplished.
Appelbaum arrived in 1978 and began working in the laboratory of Rainer F. Storb, MD. In 2004 Appelbaum would edit the third edition of Thomas' Hematopoietic Cell Transplantation, which followed the 1994 and 1999 editions of the seminal bone marrow transplantation reference book, Hematopoietic Cell Transplantation, edited by Thomas.
"Don really pushed the field, especially after so many difficult years," Appelbaum said. "He truly believed, was very stubborn, and very focused. He received some criticism for not developing other [solid tumor] medical oncology programs [here] because he was totally in support of the transplant program in hematologic malignancies."
Noting that Thomas could be a stern and demanding taskmaster, he added, "Don was a wonderful man-by far the most influential person in my life except for my father. He was a true hero, and helped create a real personality for the cancer center."
Rainer Storb
One member of the Hutchinson BMT team who often found himself in lively public discussions with Thomas was Rainer Storb, a longtime Member of the Clinical Research Division, Head of its Transplantation Biology Program, and Professor of Medical Oncology at the University of Washington.
Storb was working in a basic science laboratory in Paris in 1965 when he decided to do something more patient oriented, he explained. He wrote to researchers in Seattle and Boston and at the NIH, and chose to work with Thomas because he found bone marrow transplants more challenging and interesting.
"Don and I would oftentimes have very hefty discussions in public, but the following day we usually got together and put it to rest," Storb said.
"We were constantly finding new problems with the transplantation and finding solutions, but Don was a visionary. He let us do whatever we wanted to do, and then we presented our plans to him and he would criticize them. That was his role, and we would defend it and then do the experiments and come back again."
Storb said that Thomas was someone you could bounce ideas off, and that he was an incredibly charismatic leader who was adored by all, even though he didn't say much, could seem cold, and never gave the impression of being your friend.
"Don's commanding presence would make you want to do something, and want to do your best. He could even get prima donnas to work together collegially as a team."
Don and Dottie: 73-Year Romance
Dottie Thomas, his wife and research partner, said she first met Don at the University of Texas at Austin when she was a 17-year-old freshman and her future husband was a junior working as a waiter in the dining hall.
The two somehow got involved in a snowball fight, and Dottie, who said it was the first time she had ever experienced snow, hit Don squarely in the face, and that was the beginning of a romance that lasted some 73 years.
They married after Dottie graduated, and they eventually moved to Boston when Don was admitted to Harvard Medical School.
Dottie said that she had always been interested in science and since she would never see Don while he was in medical school, which was an accelerated three-year program, she enrolled in a two-year medical technician course.
"It gave me an opportunity to spend more time with him, but it also gave me a better grasp of what he was doing, and over the years I moved from laboratory to administration and grant writing, and earned my PhD in nagging."
She noted that Don always said he was tenacious and kept on going because he believed there was always something more that could be changed. He would change chemotherapy doses and tap all resources until he got it right.
"He was a wonderful husband, wonderful father, and wonderful doctor. He really cared about his patients."
In addition to Dottie, Thomas' survivors include two sons, E. Donnall Jr. and Jeffrey, and one daughter, Elaine Thomas.
Donations in Thomas' memory can be made to Hutchinson's Clinical Research Division at http://getinvolved.fhcrc.org/thomas.
Online Extra
A more extensive version of this article, with additional remembrances, is available on another part of the http://oncology-times.com website: http://bit.ly/OT-DonnallThomas