The following excerpt is from “Living Medicine: Don Thomas, Marrow Transplantation, and the Cell Therapy Revolution,” by Fred Appelbaum, MD, Metcalfe Family Professor at the Fred Hutchison Cancer Center. A conversation and podcast recording with Appelbaum is available on the Cancer History Project.
Late in the summer of 1960, Dr. Clem Finch invited Dr. Don Thomas to Seattle to give a talk about his early experience with transplantation. Clem, who had been Thomas’s hematology fellowship instructor at the Brigham in Boston, had since moved to Seattle to join the faculty of the new University of Washington School of Medicine. During his lecture in Seattle, Thomas acknowledged his frustration that he had yet to show that marrow transplantation could cure anyone—either there had been problems with graft rejection and graft-versus-host disease, or the leukemia recurred.
After the lecture, a young physician came rushing up to the podium. “We have the ideal patient!” Moreno Robins remembered saying more than 50 years later. Robins was a pediatrician completing his internship at the University of Washington and was caring for a six-year-old girl, Nancy Lowry. Nancy had been well until a few months before, when something changed. She became pale, her gums began to bleed, bruises spontaneously formed over her arms and legs, and she developed intermittent fevers. Examination of her blood showed a paucity of white cells, red cells, and platelets, and a bone marrow examination was markedly abnormal, being largely devoid of cells and replaced by fat. Nancy had aplastic anemia. She also had an identical twin.
Aplastic anemia, first described by Paul Ehrlich in 1888, is a terrifying and mysterious disease in which the marrow suddenly stops working. With no red cells, platelets, or white cells being produced, the patient quickly becomes profoundly pale and anemic, susceptible to bleeding, and at risk for the development of overwhelming infections. Even today, aplastic anemia is imperfectly understood. Most scientists think that exposure to a drug or virus can trigger the patient’s immune system to turn temporarily against its own blood-forming cells. Evidence for this is that some patients with aplastic anemia improve if treated with potent immunosuppression. In Nancy’s case no offending agent was identified. And in 1960, there were no treatments for aplastic anemia. As Robins said, “We had a little girl who was going to die of aplastic anemia. Nobody lived with that disease.”
Over the weeks in Robins’s care, Nancy had deteriorated. The bruising had extended, she had hemorrhages in both eyes, and infections leading to the death of tissue had developed at the sites of prior IVs. Her parents were desperate. Treatment with steroids and androgens had failed. So when he heard Thomas’s lecture, Robins approached him and asked whether together they might perform a bone marrow transplant for Nancy. With an identical twin, there should be no risk of graft rejection or graft-versus-host disease, and unlike Thomas’s leukemic cases, there was no malignant disease to eradicate. Thomas agreed.
On August 12, 1960, Thomas joined Robins in the operating room, and after Nancy’s twin sister, Barbara, was placed under general anesthesia, they harvested bone marrow from her hip bones and shins. They stuck Barbara forty-four times with an 18-gauge needle, each time removing a teaspoon or two of marrow, which looks very much like thick blood. They filtered the marrow through a steel mesh to get rid of any bone fragments, placed it into a sterile bag, took the cells to Nancy, and, over the course of about an hour, let the cells flow through an intravenous line into her vein. Then they waited.
For the first week not much happened. Nancy remained dangerously ill, with persistent fever and an expanding local infection around her urethra. Then came a marked change. Around ten days after the marrow infusion, the number of white cells in her blood began to rise, and with the increase in blood counts, her appetite and energy improved. A bone marrow examination performed two weeks after the transplant showed an increase in the overall cellularity of the marrow. Her blood counts continued to climb, and she was discharged from the hospital on October 11, two months after the transplant. Two months later, her blood counts and a bone marrow examination were normal, and she was able to return to school in the same class as her twin sister. Nancy’s recovery was reported in an Associated Press story that ran nationwide. In describing Nancy’s recovery, her mother noted that once again she had to peek at the twins’ shoes to tell one from the other. “Nancy’s shoes are white,” she told the AP. “At least they were when we left home this morning.”
Rarely, aplastic anemia can spontaneously remit, and without a marker to distinguish Nancy’s and Barbara’s cells, it is theoretically possible that this is what happened here. However, in those uncommon cases when a patient spontaneously recovers, the rate of blood count recovery is usually gradual. Given her rapid recovery occurring at exactly the time anticipated with a successful transplant, it is overwhelmingly likely that Nancy Lowry was the first patient on the planet ever cured with a bone marrow transplant.
Fred Appelbaum, M.D., is the Metcalfe Family Professor at the Fred Hutchison Cancer Center. His work has ranged from studying basic molecular abnormalities of cancer to conducting national and international studies of its treatment. This article is excerpted from his forthcoming book, Living Medicine: Don Thomas, Marrow Transplantation, and the Cell Therapy Revolution (Mayo Clinic Press).