Originally published in Volume 35 Issue 3 of Artificial Organs, 15 March 2011
Writing this “editorial” has been delayed for 2 months of introspection, during which I attempted to analyze why the term “pioneer” might be applied to me. What follows is more a story of intoxicating personal fulfillment than that of planned scientific exploration.
When Belding H. Scribner, in 1960, demonstrated that lost kidney function could be repeatedly replaced by Willem J. Kolff’s life-sustaining artificial kidney, the disciplines of Nephrology and Artificial Organs were born. While it would make a better tale to recount how after thoughtful study, I sought nephrology training at the institution that established America’s first acute renal failure hemodialysis unit and gained Nobel Prize recognition for successful kidney transplants in identical twins, my arrival after graduation from the State University of New York’s Downstate Medical Center in 1957 at Boston’s Peter Bent Brigham Hospital resulted from my medical chief’s (General Perrin H. Long) telephone call to Brigham Medicine Chief George W. Thorn suggesting consideration of his aggressive student who might benefit from Brigham seasoning. Lacking knowledge of dialysis, transplants, or the concept of training at a Harvard institution, it had been my intent to pursue residency training as an internist at a local hospital.
My first Brigham internship rotation was through its brand new artificial kidney service—a unique medicine training component then or now. After 2 weeks of daily duty, I was “hooked” by the combination of science fiction, futuristic medicine, and mystery. John P. Merrill, who returned from World War 2 duty as an Air Force Flight Surgeon to the Enola Gay—the Hiroshima B29 Bomber—directed what was termed the Cardiorenal Service and became my mentor. During my internship, Merrill filed my American Heart Association fellowship application, outlining testing of animal and human leukocyte antigenicity about which I knew less than nothing. Although I botched the fellowship interview, revealing my absolute ignorance of immunology, the fix was in and I got the award. To my surprise, the Brigham moved me from internship to fellowship without an intervening residency. Thereafter, it was a downhill roller coaster ride careening from transplants after total body radiation, thoracic duct leukocyte depletion, and application of chemotherapy to immunosuppression to blunt transplant rejection. I conversed daily with Joseph E. Murray (Nobel 1960) and was able to question Robert Schwartz about his use of 6-mercaptopurine to curb antibody synthesis in rabbits given bovine serum albumin while learning from Roy Y. Calne how BW 57-322 (azathioprine) permitted dogs to maintain renal allografts.
During my first year of fellowship, Merrill’s lab was visited by future Nobelists Medawar, Burnet, and Dausset, as well as multiple extraordinary founders of nephrology including Hamburger, Brun, Kincaid-Smith, Alwall, Relman, Richet, Schreiner, Seldin, Thurau, Kurokawa, and Barsoum. Without exaggeration, the intoxicating atmosphere of being where a disease (uremia) was being conquered was so seductive that I devoted nearly my total existence to immersion in Merrill’s forward progress. Indeed, I was totally consumed by what is now called nephrology and never had the time to think of doing anything else. My late wife Mildred “Barry” (who subsequently developed renal failure due to diabetes and gained 17 years of life from her sister’s transplanted kidney) understood that she was competing with an obsession proffering a lure greater than infidelity, gambling, or substance abuse. Nephrology was exciting, fulfilling, and made getting up each morning an adventure waiting to happen.
One seemingly ordinary morning, I was paged over the hospital’s speaker system to report immediately to Dr. Merrill’s office. In Merrill’s office, I was introduced to a Canadian multimillionaire toy manufacturer, whose son, Lionel, had been referred to our care for advanced renal failure. Lionel’s two older brothers died from hereditary nephritis (Alport’s Syndrome). His industrialist father had read newspaper accounts of Vladimir P. Demikhov’s Two-Headed Dog experiments and was convinced that the Russian team “solved” the problem of transplant rejection. Because Merrill had extensive university obligations, he was unable to honor the request that he immediately fly to Moscow to investigate a possible “cure” for Lionel. Instead, with no prior notice, I was instructed to fly to Russia that evening, given a fistful of $100 bills, along with instructions and introductory letters to meet with three future Noble Laureates in England and France.
The 1960 Cold War U-2 incident highlighted by an American Spy Plane being shot down was only 2 weeks old when I departed in mid-May. Mention of the U-2 is included to convey the permeating atmosphere of extraordinary competition and Soviet–American brinkmanship during the era of Nephrology’s birth. Although I returned bearing no evidence-based solution to transplant rejection, I was convinced that extraordinary people were leading the quest.
A productive second year of fellowship using rabbit and human skin grafting established that human leukocyte antigens were present in both peripheral white blood cells and skin documenting their potential function as transplant antigens. Merrill sent me to present at national medical meetings and publication in journals I respected forged an irrevocable bond to academic medicine.
After four Brigham years, I was recruited as an Epidemic Intelligence Officer to the then named Communicable Disease Center of the US Public Health Service and returned to my Brooklyn alma mater as an assistant professor in 1963. Once again, my plans were altered by “happenstance” when I was asked to establish the first federally funded hemodialysis unit at Kings County Hospital (KCH), our teaching facility. My selection was based, I later learned, on my training in kidney failure without any affiliation with Scribner that might bias my interpretation of whether the “Seattle Story” of long duration life extension by repetitive hemodialysis treatments was true.
Reluctantly, at first, responding to pressure from our Dean to accept the offered federal grant, I agreed to supervise fresh construction of a Hemodialysis Unit that within 90 days began accepting previously doomed patients with what was subsequently to be termed end stage kidney disease. It was a fascinating interval as KCH had only direct current while available dialysate pumps used alternating current. My department chair, Ludwig W. Eichna, and first fellow, Gerald E. Thomson, enthusiastically gave daily support to a project that all on our growing renal team realized was to change medical practice.
An unimagined ethical challenge arose as our freshly hired corps of dialysis nurses and technicians, along with medical house staff and attending physicians, struggled to define who should or should not be offered the opportunity to initiate a life permitted by “chronic dialysis.” At first, Downstate copied the “Seattle Criteria” for selecting dialysis patients excluding those older than 45 or having diabetes or an unstable home circumstance. Within 3 months, our treatment capacity was reached forcing either extension into home treatments or acceptance of candidate patient deaths. Unwilling to accept the upper age restriction, by our second year we began dialyzing progressively older patients as well as the first Black, Hispanic, and Orthodox Jewish patients ever treated by dialysis.
Together with patients at the University of California at Los Angeles, Downstate dialysis patients formed the National Association of Patients on Hemodialysis (NAPH) with a mimeographed newsletter printed six times a year and a membership fee of $1.00 a year. NAPH members actively lobbied for inclusion of dialysis costs under National Health Insurance. On November 4, 1971, NAPH Vice President Shep Glazer testified before the House Ways and Means Committee while attached to a fully functioning artificial kidney machine leading to Committee Chairman Wilbur D. Mills’ introduction of H.R. 12043 to add dialysis therapy to Social Security Disability Benefits. At the urging of Downstate’s newly appointed Department of Surgery Chair, Samuel L. Kountz, in 1972, an established transplant surgeon, the patient organization name was changed to the National Association of Patients on Hemodialysis and Transplantation reflecting the growing success and application of kidney transplants. Because the addition of a second “p” in recognition of increasing numbers of patients undergoing peritoneal dialysis made its name unpronounceable, the patient organization adopted its current name as the American Association of Kidney Patients (AAKP). From its inception, my service as medical advisor to AAKP has been one of my treasured achievements.
Laboratory investigation coupled with applied epidemiology has continuously fascinated me. Early in our dialysis program, when travel of patients “on dialysis” was restricted to very limited locations that might accept visiting patients, I designed and used a “Suitcase Artificial Kidney,” a concept still attractive in various formats, especially as a Wearable Artificial Kidney still being improved. For over a decade, I have attempted to substitute bowel extraction of nitrogenous wastes for dialysis sessions by oral administration of enzymes, sorbents, and now probiotic bacteria. A trial of specially cultivated bacteria in patients undergoing hemodialysis was initiated early this year.
My devotion to nephrology continues though Kolff, Scribner, Merrill, and other true pioneers are now gone. For no other major organ system collapse has replacement therapy become universally available as have dialysis and/or kidney transplantation for everyone in the USA. True, rehabilitation on dialysis is far from perfect and patients given a deceased donor renal transplant may anticipate a mean functional graft 5-year survival of only 50%. Nevertheless, no other branch of organ replacement medicine presently offers as great a chance of accomplishment, involvement, and inner satisfaction as nephrology.
For fresh medical school graduates, exposure during training to a transplant rotation or an elective in nephrology will make evident that in 2011, there is more to being a kidney doctor than determining the dose of heparin or antihypertensive drug for the nth dialysis. Exactly which component of the “nephrology virus” needs to be inoculated to transfer the contagion is a reasonable subject for inquiries though the joyful chase and heady infatuation strongly persists.
Eli A. Friedman, MD, a Brooklyn native, is a Distinguished Teaching Professor of Medicine at the State University of New York’s Downstate Medical Center, Brooklyn, New York. In 1963, Dr Friedman established the first federally funded hemodialysis center linked to an organ (kidney) transplant facility in the United States. His hemodialysis patients at Kings County Hospital formed the American Association of Kidney Patients for whom he until this year served as Medical Advisory Board Chair. He has been president of the American and International Societies for Artificial Organs, and received honorary memberships from many kidney societies. In 2003, Dr Friedman was elected President of the International Society for Geriatric Nephrology and Urology. Author of 510 scientific publications including 10 books, Dr Friedman’s investigations identified human transplantation antigens in leukocytes and found synergism in application of immunosuppressive drugs employed for transplants. Current studies explore: (i) Potential utility of orally administered probiotic bacteria to recycle nitrogenous wastes as an alternative to dialytic therapy. (ii) Possible prevention of diabetic complications by blocking synthesis of advanced glycation end-products.