On Wednesday, February 7, at 5 pm Eastern Time, Fred Appelbaum, M.D., Dartmouth Class of 1968, will be our guest for a Casual Conversation on Zoom. Dr. Appelbaum appears courtesy of the efforts of our classmate Peter Schaeffer, and Dr. Appelbaum is the author of Living Medicine: Don Thomas, Marrow Transplantation, and the Cell Therapy Revolution (Mayo Clinic Press 2023).
Here is Dr. Appelbaum’s narrative write-up as it appears on the website of the Fred Hutch Cancer Center where he is Executive Vice President, in which position he serves as the associate director for clinical research for the Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium: https://www.fredhutch.org/en/about/about-the-hutch/leadership/appelbaum-spotlight.html?&link=sfb . Dr. Applebaum is one of the world’s leading experts on bone marrow transplants and the many ways in which the research has expanded the availability and reduced the costs of treating blood cancers through chemotherapy, total body irradiation, the use of HLA typing to obtain a suitable autologous donor, and amelioration (over many years of research and clinical trials) of the risks of toxicities, graft rejection, disease recurrence, suffering from the possible consequences of the use of immunosuppressants, and of graft-versus-host disease (GVHD). As a result of the work of Dr. Thomas, and, of course, Dr. Appelbaum, as well as many others in this country and around the world, not only leukemias that were once death sentences for children (and adults) have been cured (not in all patients, of course, given the risks that remain), but also lymphomas, and sickle-cell anemia and thalassemia.
As to the two latter diseases, as Dr. Appelbaum writes:
By showing that these disorders can be reversed by replacing a genetically abnormal marrow with a normal one, Thomas was also suggesting that that it should also be possible to treat these diseases by removing a portion of the abnormal marrow, correcting the disease-causing defect, and then conducting an autologous transplant using the gene-corrected marrow. With this approach, no donors are needed and there are no concerns for graft rejection or GVHD.
Just as the costs of bone marrow transplants has decreased dramatically as the use (and success) has increased even more dramatically (an allogenic transplant now costs about $1million and half that for an autologous transplant, with QALY survival gains running, for example, at $18,000 for myeloma and $52,000 for acute myeloid leukemia in first remission). Still expensive, but now well within the federal guidelines.
But what about these gene-correcting therapies which are now “out of reach of most patients in need”? Should we continue or devote resources elsewhere? Dr. Appelbaum stands squarely in favor of continuing development of these therapies: “An initial high cost shouldn’t be used as an argument against developing these therapies. If a treatment really works, science will figure out a way to produce it less expensively.” Dr. Appelbaum cites monoclonal antibodies as an example, which “today . . . make up a large part of our therapeutic armamentarium.” Who would have thought? Actually, reading Living Medicine, I would have, because the entire book is a lesson in the development over decades of life-saving treatments that are now within the reach of thousands of patients, at least in the United States: 15,000 autologous and 10,000 allogenic—each year.
There are those who disagree with Dr. Applebaum. For example, in reviewing in TLS (01/19/2024), Philip Ball’s new book How Life Works: A user’s guide to the new biology, University of Surrey Molecular Genetics Professor Johnjoe McFadden writes: “At the time [of the announcement in 2000 the the completion of the first-draft sequence of the genome of a single human] it was hoped that this would usher in a new era of gene-targeted medicines – magic bullets to shoot down cancer or diabetes. The hope was misplaced. More than two decades later, we are still waiting for these revolutionary therapies. Hundreds of thousands of genomes have now been sequenced, but hardly any medical advances have been developed as a consequence.” Even I can realize that is not true, even as a non-physician and non-geneticist: HLA typing by genes on chromosome 6, is a major advance in marrow transplantation. Different silos? It has been known to happen and is discussed by Dr. Appelbaum as a hurdle to overcome in spreading the good news and saving lives.
Dr. McFadden is not the only dissenter: James Tabery concludes that personalized medicine is unethical (yes: from very much a progressive point of view), as stated in his new book Tyranny of the Gene: personalized medicine and its threat to public health, described in the review in TLS (12/15/2023) by Gregory Radick.
The last word, for now, is from Dr. Applebaum:
One way to make transplantation and related therapies less expensive and more available is to make them better. If toxicities are eliminated, the total cost of therapies drops and they become more portable. As cure rates rise, cost-effectiveness improves. Transplantation totally as an outpatient procedure is within our grasp.
(You will have to go to your local library to read the TLS reviews. Unlike the WSJ, I cannot send them to others. By the way, I recommend subscribing to TLS and to NewScientist, both UK publications and both fairly expensive. Several years ago, TLS celebrated its anniversary as a publication by offering a lifetime subscription for a little over $1,900. After a little back-of-envelope calculating, I concluded that I would come out even if I lived to 80. Still alive and counting. I was the last person to sign up for the offer. And that was before I knew that I would be organizing the Casual Conversation series.)
Come join the discussion, and ask questions. We will be speaking with Dr. Applebaum about science, scientists, and life-saving procedures. Who knows, one of them might one day save the life of a loved one or friend, or your own. Perhaps it already has.
Usual rules. If you want to participate, send me an email at arthur.fergenson@ansalaw.com on or before this Sunday, February 4.
Arthur Fergenson