George Santos, founder of Johns Hopkins University Bone Marrow Transplantation Program, pioneered many of the innovations used in bone marrow transplantation that are relevant today—but he didn’t get nearly as much credit as others working in the field.
E. Donnall Thomas, another early pioneer of bone marrow transplantation who conducted research out of Fred Hutchinson Cancer Research Center, shared the 1990 Nobel Prize in Medicine with Joseph E. Murray “for their discoveries concerning organ and cell transplantation in the treatment of human disease.”
“Much of what we’re currently doing in bone marrow transplant internationally was developed by George,” Richard J. Jones, professor of oncology and medicine, director of the Bone Marrow Transplantation Program, and co-director, Hematologic Malignancies Program, at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, said on the Cancer History Project podcast.
Previously on the podcast, Fred Appelbaum, executive vice president, professor in the Clinical Research Division, and Metcalfe Family/Frederick Appelbaum Endowed Chair in Cancer Research at Fred Hutchinson Cancer Center, presented an overview of Thomas’s contributions to the field of Bone Marrow Transplantation.
Appelbaum is the author of “Living Medicine: Don Thomas, Marrow Transplantation, and the Cell Therapy Revolution.” After reading The Cancer History Project’s conversation with Appelbaum, Jerome Yates, emeritus professor of oncology at Roswell Park Comprehensive Cancer, wrote a letter to the editor that called attention to Santos’s contributions to the field.
“[Santos] had quite a chip on his shoulder regarding Seattle and Donnall Thomas,” Jones said. “George felt that he was doing a lot of the innovations that were moving the field, like, he in fact did the first conditioned matched sibling allogeneic transplant.”
Santos was responsible for a lot of the firsts in the field of bone marrow transplantation, Jones said.
“Nobody would argue that he did the first studies with cyclophosphamide. Nobody would argue that he did the first studies with busulfan,” he said. “He developed these two drugs, which are now some of the major drugs, if not the major two drugs used in the field. He did the first non-myeloablative transplants.”
In the 1960s, Santos and Albert H. Owens, one of the founders of the field of medical oncology, conducted mouse studies using Cytoxan (cyclophosphamide).
“George and Al actually found out that cyclophosphamide in their hands was the best drug for both getting the transplant in and preventing graft-versus-host disease,” Jones said. “When I started here, cyclophosphamide was the major drug we were using for the transplant and after the transplant to prevent graft-versus-host disease.
“If you now go forward about 55 years or so, cyclophosphamide has now been basically accepted by the community as the best way of preventing graft-versus-host disease,” Jones said.
Researchers at Hopkins continued the work with cyclophosphamide that began with Santos and Owens.
“We figured out how it worked, why it worked, and that you could in fact give it at high doses after the transplant,” he said. “This work started back in the 1960s with George and Al, and continued here at Hopkins over the last half of a century by many people.”
In a recent study published in The New England Journal of Medicine, the use of post-transplant cyclophosphamide, also known as PTcy, proved to be more effective than the standard of care treatment of calcineurin inhibitor plus methotrexate in patients undergoing allogeneic hematopoietic stem-cell transplantation, Jones said.
“The development of post-transplant cyclophosphamide is probably one of the major advances in bone marrow transplant ever. And certainly the clinical use of it in this millennium,” he said. “That work was started by George and Al Owens again in the 1960s here at Hopkins, in animals. And it took over 50 years.”
What did the field of bone marrow transplantation look like back when Santos and Owens conducted their research? At Hopkins, BMT and cancer researchers were driven far away from Hopkins’s main medical campus.
“He and Al Owens were actually farmed out to a city hospital called Baltimore City Hospital that’s about five miles east of the Hopkins main medical campus,” Jones said. “And that’s where they did all the original laboratory research and clinical research.”
Department chairs did not look fondly upon cancer researchers.
“Using radiation and animal models and transplanting cells between human beings was not thought to be hard science,” he said. “In fact, I think it’s fair to say that all cancer research at the time was not thought to be hard science.”
When Hopkins received NCI-designation in 1973, NIH mandated that the cancer center move its cancer research operation back to the main medical campus.
“That was not viewed to be great by the rest of the medical school at the time,” Jones said. “And it became a little bit of a problematic area throughout the cancer center. And in fact, oncology became a department at Hopkins. In most places, it’s a division under a department of medicine, largely because they had to hire people, and other departments wouldn’t let them hire into their departments. So, the dean just made it a full department in Hopkins.”
When Jones began as a fellow at Hopkins in the 1980s, he recalls Santos holding court at a dinner one evening while speaking between cigarettes.
“He was very engaging,” Jones said. “Many people thought he was crazy, and in many ways he was. But he was also very insightful.”
Santos’s passion for his research was apparent in the way that he spoke.
“He was unbelievably committed to this emerging field of transplant,” Jones said. “He would just talk about treating patients with doses of radiation and chemotherapy that would kill them if they didn’t have this transplant. And most people knew about graft-versus-host disease by this time, and scared people, and he was just so committed and sure that this was going to work.”
Santos was also close with his patients—the wall behind his desk was covered in their photos.
“Bone marrow transplants are a little bit different than many other cancer treatments because the patients remain at the transplant center for several months back then, maybe even longer,” he said. “Bone marrow transplant doctors see their patients every day. So, in many ways, the relationships they develop are incredibly close. You get to know them very well. You get to know their families.”
He left behind a book in which he wrote down the name of all of his patients. When he retired in 1994, the number of patients stood at 1,936.
At the time, researchers at major hubs for bone marrow transplant studies like the Hutch, Hopkins, and Memorial Sloan Kettering, worked in their own silos, Jones said.
“It allowed people to innovate, develop different approaches, and figure out the one that worked the best,” he said. “We’ve become much more collaborative in the field over the last 20 years, basically through the development of an NIH-funded grant called the Bone Marrow Transplant Clinical Transplant Network. And I think we’re, as a group, figuring out which of these approaches work the best.”
Thomas and Santos might be considered friendly rivals, Jones said.
“There’s sort of a joke that says if you get 10 bone marrow transplanters in the room and talk about how to treat a patient, you’ll get 10 different ideas of how to move forward,” Jones said. “They were both trying to develop an area and they both were sure it was going to work. I think George and Don had the utmost respect for one another.”
This column features the latest posts to the Cancer History Project by our growing list of contributors.
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