Bone Marrow Grafting: "A Story of Man and Dog"

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It was in the summer of 1955 that E. Donnall Thomas and a colleague began to discuss the possibility of bone marrow grafting in patients. The setting was Cooperstown, N.Y., site of the Mary Imogene Bassett Hospital where Thomas worked. Their conversations took place sometimes in the lab, sometimes while riding horses around the hills of Cooperstown.footnote 1 These conversations were the beginning of a career that would lead him to the UW School of Medicine and would culminate in his receiving the Nobel Prize in 1990 for developing bone marrow grafting techniques that today have saved thousands of lives.

In that summer of '55, it seemed to Thomas that marrow transplantation might successfully be performed in human patients who had malignant disease, especially leukemia--patients whose immune systems were depressed because of the disease and the effects of radiation treatment.

Thomas and colleagues decided to proceed cautiously with clinical experiments while also initiating animal studies. In a paper published in 1957, Thomas reported that fairly large amounts of specially prepared marrow could be given intravenously without ill effect to the patient. In that paper the team envisioned potential applications of marrow grafts for treating not only bone marrow diseases, but also victims of radiation accidents, a chilling premonition of the tragic events of the Chernobyl accident in the former Soviet Union:

In an atomic age, with reactor accidents not to mention stupidities with bombs, somebody is going to get more radiation than is good for him. If infusion of marrow can induce recovery in a mouse or monkey after lethal radiation, one had best be prepared with this form of treatment in man. The leukemic patient who needs radiation and bone marrow and the uremic patient who needs a spare kidney are people who deserve immediate consideration. From helping them one will be preparing for the atomic disaster of tomorrow and it is high time one did.footnote 2

The reference to a spare kidney relates to the notion that a marrow graft might be necessary to facilitate acceptance of a donated kidney; immunosuppressive drugs for use with organ transplantation were unknown at that time.

In 1959, Thomas and colleagues reported the first marrow transplants in a pair of identical twins with advanced acute lymphocytic leukemia. The patients were exposed to radiation and then given grafts, which succeeded in restoring marrow function--but only for a few months. Soon the leukemia returned in both patients. It didn't take the researchers long to realize that grafts in human patients would be more difficult than they first thought.

Canine studies showed that dogs could routinely survive a dose of radiation three to four times that which ordinarily would kill them, providing that afterwards they were given a graft of their own marrow, removed previously and preserved for the purpose. But many patients receiving allogeneic grafts--from donors who were genetically different from the patient--died from graft failure or from complicating infections. The fact that a few survived led the researchers on a hunt to identify which factors were critical to the success of the procedure.

Meanwhile, Thomas found himself attracted to the developing scientific environment at the burgeoning UW School of Medicine, to the prospect of joining colleagues, in particular, Clement Finch, former head of hematology, and Robert Williams, then chair of medicine--and, Thomas admits, to enjoying the natural amenities of the beautiful Pacific Northwest. In the summer of 1963 he and his family packed up and moved west.

After joining the UW faculty in 1963, Thomas set up the division of medical oncology in 1967, a unit he ran for 18 years. Thomas considers his efforts to establish and build up that division to be one of his two greatest contributions at the UW, the other of course being the development of transplantation techniques. He continued on as a full professor until 1990, when he retired.

In his work over the years at the UW, Thomas pioneered techniques to do tissue typing in dogs in order to find matched donor-recipient pairs. The work paved the way for carrying out transplants between carefully matched human siblings. A first attempt in 1965 failed. The patient, who was a child with end-stage leukemia, died on the 12th day after the procedure due to an infection from a bacterium found to be growing in a bedside water-pitcher. The take-home lesson: a specially designed facility was absolutely essential in carrying out these procedures for patients with such compromised immune systems.

In 1975, Thomas moved the operation to the newly constructed Fred Hutchinson Cancer Research Center where he had begun to work in 1974 and where there were 20 beds and a new, cobalt-60 radiation facility; and in 1985, Swedish Hospital Medical Center made 40 more beds available.

The 1970s and 80s saw the number of long-term survivors--and the number of diseases that could be treated in this way--increase, as the number of marrow transplant centers proliferated. New improvements in the technique continue to be made. Looking back, Thomas reflects:

There was and is an atmosphere on the transplant team for challenging biologic 'truths,' for opening new pathways, and a willingness to take risks when necessary. We learned the need for a dedicated team of workers which extended far beyond the physicians themselves. Nurses, technicians, animal care personnel, and support staff were all importantMoreover, we were inspired by those courageous patients who were willing to take some risks to try for a new approach...footnote 1

  1. "Allogeneic Marrow GraftingA Story of Man and Dog," E. Donnall Thomas, in History of Transplantation: 35 Recollections, Ed. by Paul I. Terasaki, pp. 379-393, The UCLA Tissue Typing Laboratory, 1000 Veteran Ave., Los Angeles, CA 90095.
  2. From "Bone Marrow TransplantationPast, Present and Future," E.Donnall Thomas, Nobel Lecture, Dec. 8, 1990, reprinted from Les Prix Nobel 1990, The Nobel Foundation, 1991, Stockholm.
  3. See also "Bone Marrow Transplantation: 30 Years of Progress," E. Donnall Thomas, The 1990 Noram Prize Lecture, Hong Kong, Nov. 15, 1990.

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