The following is an excerpt from the Mayo Clinic Press book Living Medicine by Fred Appelbaum, M.D.
I first heard of Dr. E. Donnall Thomas in 1970 when I was a second-year medical student in Boston learning to do a physical exam. My clinical mentor, Dr. Jane Desforges, was taking four of us around the ward to see patients with various physical signs of disease. Half proud and half embarrassed in our new short white coats, we gathered around Desforges before entering each room to hear her describe the patient who had generously agreed to be poked and prodded. That day’s group included a barrel-chested man with emphysema; an older chronic alcoholic with yellow, jaundiced eyes; and a young woman with the fluid-filled belly of ovarian cancer. Then we came to the room of a middle-aged man with acute leukemia who, according to Desforges, had only a few months to live. The patient, obviously a Red Sox fan based on the pennants thumbtacked over his bed, joked with us as Desforges demonstrated the proper way to examine an abdomen. As we took turns trying to palpate the man’s swollen spleen, Desforges happened to mention a strange new therapy she had just read about, one that someday might help patients like ours.
Curious, that afternoon I went to the medical school library and found the article she had mentioned. It was a description from Thomas’s group of a radical new treatment, bone marrow transplantation. As a second-year medical student, I knew that bone marrow was the fatty, gelatinous material inside bones responsible for producing blood and immune cells, and that acute leukemia was a frightening cancer of the marrow that was almost always rapidly fatal. What Thomas described in that article seemed astounding. He had purposely exposed a forty-eight-year-old man suffering from leukemia to what was surely a lethal dose of radiation. Thomas was trying to wipe out the leukemia even if it meant destroying the patient’s normal bone marrow. To reverse the lethal effects of the radiation, he stuck needles into the hip bone of the patient’s sister, sucked up some of her marrow cells, and injected them into the patient’s vein. The idea was that his sister’s marrow cells would somehow find their way to the patient’s marrow space, engraft, and rebuild a normal functioning marrow in his body. Remarkably, that’s what appeared to happen. Before the procedure, the patient’s blood was filled with leukemia; following radiation, the leukemic cells vanished; several weeks after the transplant, his blood was repopulated with new normal cells produced by his sister’s transplanted marrow. The patient died of a complication of the procedure two months later, but the leukemia had temporarily disappeared, and the graft had taken. Reading that article was like having my brain tattooed. I thought about the patient whose spleen I had been feeling just a few hours before, and I thought about what Thomas was trying to do. After that, I couldn’t get the idea of marrow transplantation out of my head.
While I first learned of Thomas in 1970, I didn’t meet him until 1975. My fascination with marrow transplantation continued through medical school, internship, and residency. I’m not sure why. Undoubtedly, part of it was its potential impact; if successful, marrow transplantation offered a possible cure for every blood- and immune-based disease known to humankind, everything from sickle cell anemia and leukemia to multiple sclerosis. Part of it was the drama; transplantation meant dealing with critically ill patients in a life-threatening setting. And part of it was the mystery; there was so little known about transplantation and participating in the discovery process appealed to me. Impact, drama, mystery—whatever it was, I continued to read what I could about transplantation, and when it came time to pick a subspecialty, I chose hematology-oncology and went to the National Cancer Institute (NCI) in Bethesda, Maryland, for training. My first year was devoted to clinical work, and then I joined a laboratory focused on transplantation biology. During our lab year, we could attend one national meeting, and I picked the American Association for Cancer Research convention in San Diego.
On the flight there, I scanned the meeting agenda and circled sessions of interest. At the top of my list was a morning devoted to the science of blood formation that included a talk by Thomas. The session was in a small auditorium that held maybe a hundred attendees. I sat near the back and listened as each speaker gave their fifteen-minute presentation followed by a short question-and-answer period. Some of the talks were fascinating, others not so much.
When it was Thomas’s turn to speak, I watched as he walked unhurriedly to the podium, a slender middle-aged man, about six feet tall, balding with a close-cropped graying beard, wearing an ill-fitting, unfashionable black suit. When others presented, there was usually some background noise as attendees checked their programs or whispered to their neighbors, commenting on the data or making dinner plans. During Thomas’s talk, the audience grew silent. He was presenting results suggesting that bone marrow transplantation might be able to cure an occasional patient of otherwise incurable leukemia. Most of his patients died, often directly from his therapy, but a handful were now approaching the magical five-year mark after treatment, alive without any evidence of leukemia—the functional definition of cure. Thomas commanded the room. He spoke softly, slowly, using few, simple words. When he finished, there was a moment of silence as people digested what they’d heard. He answered a few benign questions and then it was time for a coffee break.
Thomas’s talk impressed me, but as I overheard snippets of conversation during the break, I realized not everyone agreed: “I can’t believe how many patients he killed.” “That approach is barbaric!” Two of the most common sayings in medicine stand in direct opposition. Hippocrates warned, “Primum non nocere—First, do no harm.” Shakespeare observed, “Diseases desperate grown, by desperate appliance are relieved. Or not at all” (Hamlet, Act 4). Thomas appeared to favor Shakespeare.Three years later, I was in Seattle, working as a member of his team.
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