From math major to transplant pioneer: An interview with William Harmon, MD
William Harmon, MD, a pioneer in pediatric dialysis and kidney transplantation, passed away on May 29, 2016 after 45 years at Boston Children’s Hospital. He was 72 years old. Starting as an intern in 1971, the year the hospital performed its first kidney transplant, he worked his way up to Nephrologist-in-Chief, a position he held for 25 years.
Harmon was passionate about caring for children with end-stage renal disease (ESRD), pioneering techniques and devices to adapt hemodialysis to infants and young children. He helped get NIH support for child-specific transplant research and led multiple clinical trials of treatment protocols to help children not only tolerate their transplants, but thrive. He also worked to ensure that government guidelines and legislation on ESRD and kidney transplant gave priority to children.
Harmon was the first chair of the pediatric committee of the United Network for Organ Sharing (UNOS) and the first pediatrician to chair the New England Organ Bank’s Board of Directors. He was passionate about teaching, training more than 65 pediatric nephrology fellows.
Below are lightly edited excerpts from interviews with Harmon, most recently in 2014.
How did you decide to go into pediatric nephrology?
In college, in the 1960s, it took me eight years to finish three and a half years because I went off and researched. I started as a chemistry major, then rotated into math. Math was the thing I liked the best, but I incorrectly thought that there is no future for somebody majoring in math. I left school, not deciding what I was going to be doing, and got a position in Cleveland, where I lived, in a research laboratory. It was headed by Harry Goldblatt, a pathologist [who] found that the kidney was an essential part of blood pressure management. He restricted blood flow to one of a dog’s kidneys and the dog became hypertensive. Which led to the discovery that kidneys excrete a hormone called renin that causes your blood pressure to go up.
I could see the application of this research to the clinical side. Dr. Goldblatt knew I was interested in medicine, so suggested I talk to a physician at Case Western Reserve — who, as it turned out, was a one-man admissions committee for the medical school. I had not formally applied for anything or taken medical school tests. This person said, “Don’t bother to apply to any schools that you rank below us.” And I said, “Does this mean you have accepted me to medical school even though I haven’t even applied?” He said, “Yes, we will take you.”
Case Western Reserve at the time was a very unusual school. You saw a patient and participated in their care right from the beginning. You would follow a pregnant woman and then follow the baby after that, getting a sense of what a physician should be doing. The curriculum was designed to get people interested in the human side of medicine rather than the textbook side.
People who would do dialysis or transplant in children were looked upon as strange, maybe almost barbaric.When we got to the kidney section, that was interesting because many of the nephrologists had a sense of math, science and physics. The physiology of the kidney has to do with equilibrium, mass transfer, conservation of matter and things that sounded more like chemistry and physics than many of the other [specialties]. I found those courses interesting because of my tendency to like math and science.
The last year and a half of medical school was clinical rotations. When I came [to Boston Children’s] for my residency, I still wasn’t sure what I wanted to do. I was very disinterested in nephrology but kind of curious about transplant, because transplant was starting to catch on. Two surgeons here did their first transplants in adolescent patients in 1971, the year that I was an intern. The initial transplants were actually done at [Brigham and Women’s Hospital].
And then leadership changed in the Nephrology department, just as you were leaving for the National Health Service Corps.
One of the nephrologists from Case Western Reserve, Warren Grupe, was coming to take over the department here. He was one of those people that I found very attractive back in Case. And that’s when I decided I would follow in nephrology. Dialysis was a very quantitative thing, and transplant was a very exciting field in a different way. They were both consolidated in nephrology. And I also saw [a growth] opportunity. [Dr. Grupe] remembered me from medical school and he agreed to take me on as a fellow [in 1976].
In the midst of the fellowship, Dr. Grupe asked me to take over the development of the dialysis unit. We still did not have a dialysis unit here at Children’s. Children were being dialyzed at the Brigham. So I got educated by their nephrologist and we set up the dialysis unit here. When I finished my fellowship, I became the chief.
Tell us about those early days of dialysis.
When I started, it was unthinkable that a child with kidney failure could survive. The idea of dialyzing an infant for a long period of time didn’t exist.
We started off dialyzing adolescents and managed to graduate down to infants.
Hemodialysis was being done in infants maybe in three or four hospitals at the time. We were able to take the principles and make them work for small people and make the hardware work for small people. We made our own catheters because there weren’t commercial options available.
I began to see that transplant was really where we had to go for children with end-stage renal disease. Dialysis is a perfectly adequate treatment to keep people alive. It’s not a very good treatment [long-term], because we are not replacing total kidney function, but it allows us to do the transplant in the best possible conditions. So when I took over the division [in the mid 1980s], I also took on transplant.
[For] many pediatric nephrologists in the world at the time, [the] perspective was, “dialysis and transplant are much too suffering for children. We should just let them die.” People who would do dialysis or transplant in children [were] looked upon as strange, maybe almost barbaric.
Where was the transplant field at that point?
People thought we could never do [transplant research in children] because, ‘how can you risk children, how can you randomize them, how can you put them in trials?’ And the response is simply, ‘how can you not do that?’ There weren’t very many pediatric programs that were much involved in transplant. At the time, the transplant world was not very developed or regulated. There were very few controlled trials of anything in transplantation in the 1970s and 80s and very few things in our literature other than single-center reports. In fact if you read the whole literature about transplantation, there was lots of criticism in early days of transplantation because it failed a lot.
Transplantation was becoming a national issue because kidneys were being allocated from [donors] and there were all these questions on fairness. The National Organ Transplant Act was passed in 1984 and identified that every hospital had to be associated with an organ procurement organization [OPO]. And it was the OPO’s responsibility to recover the organs. The kidneys would then be distributed based on a national algorithm, not on a “my patient needs [it] more than your patient” basis that was like the Wild West.
How has pediatric kidney transplant evolved?
When we started transplant in children, they were the highest-risk recipients. Their outcomes were terrible. Their graft losses were very high. We took the highest risk group and made them into the most successful group.
Unfortunately, we then uncovered we have a new “worst group.” These are the adolescent patients, who frankly don’t take their immunosuppression medicines like they should. So that is our biggest challenge.
You’ve chaired national research to improve adherence and transplant outcomes by changing the immunosuppressive regimens.
We formed a multi-center clinical trials resource, [the Cooperative Clinical Trials in Pediatric Transplantation]. We have a registry that is pediatric-specific, so we’ve been able to learn from each other. People thought we could never do [transplant research in children] because, “how can you risk children, how can you randomize them, how can you put them in trials?” And the response is simply, “how can you not do that?”
So we changed the whole immunosuppression world and the scientific world to look at pediatric-specific issues. We’ve learned a lot from the children and the families who have agreed to participate in these trials. Again it is the collaboration of all the pediatrics programs to do this together that’s been successful.
These trials have enabled children to get down to just two long-term immunosuppressant drugs.
Much of our research has been focused on using the smallest amounts of the least toxic drugs, and we have accomplished that. [In the future] we hope to get to tolerance. Tolerance would be the situation where you don’t have to take medications and you don’t get rejections, and then you don’t get complications because you are not taking medications. If we [got down] to two drugs, maybe we can get to one, and if we get to one drug, you’ve got to believe that we can get patients off all drugs. Your reach has to exceed your grasp.
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