Today’s most groundbreaking experiments in medicine — gene editing to correct inherited disorders, immunotherapies to cure cancer, molecularly engineered organs for human transplantation — stem from the strides of one visionary: Dr. E. Donnall Thomas.
Frederick Appelbaum, M.D., a member of Dr. Thomas’ research team, details Dr. Thomas’ story in the new Mayo Clinic Press book “Living Medicine: Don Thomas, Marrow Transplantation, and the Cell Therapy Revolution.”
Dr. Appelbaum is the Metcalfe Family Professor at the Fred Hutchinson Cancer Center and has authored or co-authored over 800 peer-reviewed scientific papers, and hundreds of chapters, invited reviews and editorials.
Mayo Clinic Press asked Dr. Appelbaum some questions about his book, his writing process and the future of medicine.
Q: Your book is somewhat unusual in that its subject, Dr. Thomas, the father of bone marrow transplantation, is someone you knew and worked alongside for decades in the lab. Did being this close to your subject make it more difficult or easier to write his story?
A: Not having tried the alternative, more difficult or easier is impossible for me to say, but if I hadn’t worked with him, the book would surely have been different. Don was a reserved, quiet man, but as his colleague, I got to know him well and had firsthand knowledge of many of the key events, providing insights probably inaccessible to an outsider. But being his colleague also threatened my objectivity, and it was a challenge to try and remain unbiased. I didn’t want the book to turn into a hagiography.
Q: What are your hopes for the future of this technology and procedure, and where do you see its biggest challenges?
A: Medical researchers often draw fire for overpromising and underdelivering, but as I explain in Chapter 24, the future potential of marrow transplantation and the therapies that derive from it is extraordinary.
The experience with marrow transplantation taught us many things, but three principles stand out. First, the procedure can cure virtually every marrow-based disease, including sickle cell anemia, leukemia, lymphoma and hundreds of others. Second, part of the way transplantation cures leukemia is that the transplanted immune system sees the leukemia as foreign and rejects it. And third, lifelong immunosuppression is not required after marrow transplantation, and once a patient has a marrow graft, they will accept any other organ from that donor.
These three principles will shape the future. For inherited marrow-based diseases like sickle cell anemia, instead of relying on a donor’s marrow, we will be removing a portion of the patient’s own genetically abnormal marrow, correcting it, and transplanting that repaired product back to the patient to cure their disease. This approach is already approved by the Food and Drug Administration (FDA).
For the treatment of leukemia, lymphoma and certain other malignancies, we can isolate immune cells from the donor or the patient and genetically engineer those immune cells to specifically attack the patient’s tumor, thereby curing otherwise incurable cancers. Finally, transplanting marrow simultaneously with solid organs, like kidneys, hearts and lungs, may provide a means to allow organ transplantation without the need for lifelong continued immunosuppression.
None of these therapies are perfect, and we need to make them safer, more effective and more widely accessible. We are making remarkable progress on all these fronts, but the biggest challenge is simply the complexity of the biology of humans and their diseases — really the biology of all living things. Every week, I open my issues of Nature, Science, and the New England Journal of Medicine and read in amazement about the new discoveries, which lead to the next unanswered questions. It’s like peeling back the layers of an infinitely large onion (without the tears).
Q: What would be the one thing you’d hope a reader takes away from reading your book?
A: It’s the obverse of the last answer. Despite the incredible complexity of human biology and disease, with persistence and teamwork, extraordinary advances in the care of patients can be achieved. Don Thomas had the idea of curing leukemia with marrow transplantation. He didn’t know all the barriers he would face or how to overcome them when he started, but by relying on the principles of medical research, after several decades he and his team achieved the feat. I like the quote attributed to E.L. Doctorow when describing writing, “It’s like driving a car at night in the fog. You never see further than your headlights, but you can make the whole trip that way.”
Q: What’s a myth or misunderstanding many people have about this topic?
A: When asked about marrow transplantation, many — I suspect most — people think of it like kidney or liver transplantation, where there is a surgical procedure and aside from the operation itself, the biggest challenge is to prevent the patient from rejecting the graft. In fact, with marrow transplantation no real surgery is required. The marrow stem cells can be harvested from the marrow space using specialized needles or from the blood and transplanted by a simple intravenous transfusion. And instead of just worrying about the patient rejecting the graft, the challenge is both to prevent graft rejection, but more importantly, to prevent the graft from rejecting the patient. Thus, the immunologic barriers to successful marrow transplantation exist in both directions making the procedure doubly complex.
Q: What was the hardest topic or section in the book to get right? Did your research uncover facts or ideas that surprised you?
A: The hardest part of writing the book, and I make no claims to getting it right, was selecting which specific scientific insights (and the responsible scientists) to include and which to edit out. So many wonderful scientists made incredibly important contributions to the field that could easily have been included. On the one hand, I didn’t want to artificially simplify the story, and on the other, I wanted to keep the narrative moving. This dilemma was particularly difficult in writing Chapter 21, where I explain how the results of allogeneic marrow transplantation for leukemia fueled the recent development of cell-based immunotherapies for cancer.
The most enjoyable part of writing this book was doing the research — interviewing the scientists and patients and doing the background reading. I started my own career in marrow transplantation almost 50 years ago (1974). I thought I had a pretty good understanding of the history, having written textbooks on the topic and living through much of it. Boy (or girl), was I surprised! When I went back and read the original papers, I discovered that some researchers whose experiments I frequently cited (like Leon Jacobson), completely misinterpreted their results. In other cases, with only primitive methods and limited results, scientists like Peter Medawar predicted with amazing accuracy what future experiences would reveal. Deciding to write this book, and therefore doing the background research, was one of the best decisions I ever made.
Relevant reading
Living Medicine
A sweeping biography of the visionary behind bone marrow transplantation and the story of the diseases cured by Don Thomas’s discovery.
Shop Now
