Editor’s Note: With this article, we introduce a new feature to The Hematologist: “One on One.” This interview series will shine a spotlight on professionals of varying experience and backgrounds, whether they are just starting out in their hematology careers or are longtime and celebrated leaders, such as our first interview subject, Fred Appelbaum, MD.
Title: Professor of hematology and oncology at the University of Washington; Metcalfe Family/Frederick Appelbaum Endowed Chair in Cancer Research at the Fred Hutch Cancer Center in Seattle
Notable: Author of Living Medicine: Don Thomas, Marrow Transplantation, and the Cell Therapy Revolution
Several months ago, I picked up the book Living Medicine, an homage to the field of marrow transplantation and to transplant’s founding father, E. Donnall Thomas, written by Fred Appelbaum, MD. As a hematologist who has practiced and studied blood and marrow transplantation for the last decade, I was captivated immediately by Dr. Appelbaum’s vivid telling of the early trials and tribulations of transplantation.
Living Medicine is part history, part biography, and, at its core, an authentic and loving tribute to the people who had the foresight, creativity, and wherewithal to transform a kernel of an idea into a lifesaving therapy and medical discipline.
I spoke recently to Dr. Appelbaum about the process of writing Living Medicine, Dr. Thomas’ legacy, and the enduring magic of marrow transplantation. An edited excerpt of our conversation follows. The audio version of our full conversation is available as an episode of The Hematologist podcast at www.thehematologist/podcasts.
What led you to write Living Medicine?
I had been thinking about it for a while. Don’s story was so extraordinary, and I felt that it would be such a tragedy if it were lost for future generations.
Tell me more about the process
Around four years ago, I began reading about the early history of hematology research and combing through Don’s records, which were comprehensively archived at the Hutch. As part of my research, I traveled to Cooperstown, where Don’s original work was conducted, and to Chicago, to see sites of early experiments detailed in the book. I interviewed numerous people along the way — 70 or so — and then spent a year writing the book. The publication process was very different than getting a paper published in Blood. I was lucky to find a literary agent rather quickly, followed by a publisher, and a good editor, who requested that I shorten the manuscript. That was probably the hardest thing because I didn’t want to dumb it down and cheat the science. As you know, it’s hard to briefly explain, for example, histocompatibility.
Let’s turn to the star of the book. Can you share Dr. Thomas’ role in the history of marrow transplantation?
Don was born in 1920 and had an opportunity to attend Harvard Medical School because of the shortage of doctors during World War II. While at Harvard, he learned of Leon Jacobson’s spleen-shielding experiment demonstrating that mice with lead-shielded spleens could survive high-dose radiation, even following subsequent splenectomy, while non-shielded mice would die of bleeding and infection. While Jacobson believed that a noncellular humoral factor was responsible for cellular repair and survival in spleen-shielded mice, it was later recognized that hematopoietic progenitors migrating from the shielded spleen to the marrow were responsible for blood count recovery.
Don had the idea that if you could destroy a normal bone marrow and replace it as Jacobson and Egon Lorenz had subsequently done in mice, maybe you could destroy an abnormal bone marrow and replace it to get rid of leukemia and lymphoma. And so, he started working on this concept well before there was any idea of histocompatibility, and in 1957 published an article on the first six attempts to transplant patients, all of whom failed to engraft. He then began working out the details of histocompatibility in a canine model, and when he could finally, repetitively, achieve engraftment through [dog leukocyte antigen (DLA)] matching, he once again began pursuing human marrow transplantation. Don successfully completed the first successful transplants for leukemia and built the transplant program in Seattle at the Fred Hutch. In 1990, he was awarded the Nobel Prize for his contributions to the development of hematopoietic cell transplantation.
What was it like to work with Dr. Thomas?
Don was old-school in the best way. He was very polite. He wore a tie to work every day. I never heard him swear. He didn’t say a lot, but whatever he said was very thoughtful. His most unique characteristics were that he was incredibly focused on transplantation, and he was persistent. He was not embarrassed to admit what he didn’t know, he loved to learn, and he displayed a certain humility. Don just had this aura — he was a very special person.
You arrived in Seattle in 1978. What were the early days of transplantation like?
I mean, it’s kind of mind-blowing even to read about it. We had no antiemetics. The poor patients, we would essentially give them sedatives that made them virtually comatose during the preparative regimen because the vomiting from cyclophosphamide and [total body irradiation (TBI)] was so extreme. We were giving TBI as a single fraction over four hours. Patients would stay in isolated laminar flow rooms for 50 days without ever getting out. Most of us knew our own [human leukocyte antigen (HLA)] types because we were donating platelets for our patients. It was really incredible.
What lessons have you learned from writing Living Medicine?
There are a couple of lessons that I hope will come through. The first is that you don’t have to understand every bit of the biology behind something to make clinical progress if you are willing to do stepwise appropriate studies. To do that, it takes persistence and focus. The second is that if you make a scientific advance, it can have huge implications in many other fields. Don’s discoveries in marrow transplantation taught us about gene therapy, about adoptive immunotherapy, about tolerance. I think that’s a very important lesson that Don taught us.
I would like to use the opening line of your book to end this interview: “Even though I’ve been doing it for decades, every time I perform a bone marrow transplant it seems like magic.”
It is amazing to me that we can do transplants, that the hematopoietic system can reform itself, that you can get tolerance and see a patient who you transplanted 20 years ago, and they look and act and feel totally normal, and yet 15% of their cells are someone else’s and it all just works. I still feel it.
Competing Interests
Dr. Muffly indicated no relevant conflicts of interest.
