A tribute to Edmund J Lewis, MD

On November 12, 2023, the world lost an amazingly talented and brilliant individual. I personally lost a mentor, colleague, collaborator, and friend. Edmund Jean Lewis was born on November 10, 1936, into a working-class Jewish family in New York City. His father was a high steel welder, and his mother was an accountant. He had a younger sister who died at the age of 12 from kernicterus, an event that had an effect on him for the rest of his life. Although he made his career as a physician working in hospitals, he absolutely hated being a patient, and I think it was in no small part a result of the experience that he had watching his sister suffer. Ed graduated college cum laude in 1958 with a BS degree from McGill University in Montreal. He was also on the varsity swim team. He attended medical school at the University of British Columbia in Vancouver, was elected into Alpha Omega Alpha, and graduated in 1962. He told me that he trained in Canada because at that time there were limits to admission for Jews in many universities in the United States and it was not uncommon to leave the country to matriculate. He completed his residency in internal medicine at Johns Hopkins Hospital and was a research fellow at the Robert Breck Brigham Hospital, Harvard Medical School in Boston under the guidance of John Merrill, MD. In 1969, he became the Chief of the renal division at the Thorndike Memorial Laboratory of Harvard Medical Unit in Boston City Hospital where his research career really began. Ed's primary research interest was in the immunology of glomerulonephritis. Even at an early stage of his career, it was clear that he was a visionary, publishing an article in the New England Journal of Medicine, which supported the concept that glomerulonephritis could in part be a result of cellular hypersensitivity to glomerular basement membrane antigens.1Rocklin R.E. Lewis E.J. David J.R. In vitro evidence for cellular hypersensitivity to glomerular-basement-membrane antigens in human glomerulonephritis.N Engl J Med. 1970; 283: 497-501Google Scholar This theory came under great criticism at a time when it was felt that glomerular injury was due to autoantibodies and immune complexes. Several decades later, Ed was vindicated when the proof of this mechanism was provided first by his former fellow Kline Bolton at the University of Virginia and later by several other laboratories. Dr. Lewis' work in the area of immunologic mechanisms of renal disease caught the attention of 2 aspiring nephrologists, William (Bill) Couser and Kline Bolton, who were completing their internal medicine residency at the Harvard Medical Unit at the Boston City Hospital. They were so intrigued by Ed's research that they elected to work with him at the Thorndike Medical Laboratory. In 1971, Ed was recruited to be the head of the Section of Nephrology at the University of Chicago, Pritzker School of Medicine, and Bill and Kline followed him as his first nephrology fellows. After completing their fellowship, Dr. Couser, first at Boston University and later as Scribner Professor and Head of the Division of Nephrology at the University of Washington, continued studying immunologic mechanisms of glomerulonephritis, and his first fellow, David Salant, continued research in the field leading to the discovery of the PLA2R antigen in membranous glomerulonephritis. Kline Bolton became Chief of the Nephrology Division at the University of Virginia, where his laboratory was the first to confirm Ed's hypothesis that T cells could mediate several forms of glomerulonephritis. In 1973, Ed was recruited to be Director of the Section of Nephrology at Rush Presbyterian St. Luke's Medical Center (now Rush University Medical Center) by Dr. Robert Kark. Dr. Kark felt that Ed's interest in immunologic mechanisms of renal disease made him a perfect candidate to carry on the legacy that Drs. Kark, Muehrcke, Pollack, and Pirani had established in defining lupus nephritis. Ed became the Muehrcke Family Professor of Nephrology at Rush and held this position for over 40 years. After arriving at Rush, he recruited a young nephropathologist, Dr. Melvin M. Schwartz, whom he had met at Boston City Hospital. In the early days at Rush, Ed and Mel along with their colleagues, Jimmy Roberts and Zev Sharon, continued to pursue basic research in the area of immunologic renal disease. And, as part of the Nephrology Fellowship Training Program, Ed and Mel instituted the renal biopsy conference, which was held every Thursday afternoon and attracted nephrologists from other local institutions. This conference continues to this day but is now live virtually with an international audience. I first met Ed in 1976 as a second-year medical student at Rush when he was leading the renal pathophysiology course. It was the best course I had experienced, consisting of 12 lectures and 8 three-hour workshops that were "case-based." The case-based method may not seem novel today, but it was completely revolutionary at the time. I later met Ed as a second-year resident during my rotation on the nephrology service. I was struck by his charisma and how knowledgeable he was. And, I found him to be an exceptional clinician. At that point, I was hooked on nephrology. Through the years, medical students and residents from outside institutions would rotate on the Nephrology Service at Rush to experience the genius of Ed Lewis. In 1982, when Ed was the attending and I was the fellow, a fourth-year medical student from the University of Illinois, Brad Rovin, made a point to rotate on the nephrology service at Rush in order to be with Ed. Dr. Rovin's subsequent success in the field of glomerulonephritis is well known. In 1979, Ed directed his focus from bench research to conducting clinical trials. He along with Marc Pohl (Cleveland Clinic Foundation), Lee Hebert (Ohio State University), and Larry Hunsicker (University of Iowa) organized the Lupus Nephritis Collaborative Study Group (later to become the Collaborative Study Group CSG). Ed believed that studies should be "investigator-directed," which meant the CSG would exclusively be responsible for developing the protocols, managing the data, and writing the final manuscripts, not "industry." There was no compromise on this, and as the CSG's principal investigator, he subsequently passed up many opportunities for major clinical trials in which he felt that the CSG did not have the ultimate control. The CSG's initial study (National Institutes of Health–funded) sought to address whether the addition of plasmapheresis to standard immunosuppressive therapy would be beneficial in the treatment of severe lupus nephritis. Plasmapheresis was becoming a popular therapy for severe lupus nephritis despite the lack of controlled data to support its use. And while the study, published in the New England Journal of Medicine in 1992,2Lewis E.J. Hunsicker L.G. Lan S.P. et al.A controlled trial of plasmapheresis therapy in severe lupus nephritis. The Lupus Nephritis Collaborative Study Group.N Engl J Med. 1992; 326: 1373-1379Google Scholar reported that plasmapheresis offered no significant advantage in the treatment of severe lupus nephritis, the clinical pathologic information gained from this study was instrumental in the revised lupus nephritis classification published in 2004 by the International Society of Nephrology/Renal Pathology Society. There were at least 20 more publications that arose from the data generated from the "plasmapheresis" trial. In addition, Ed edited a book entitled Lupus Nephritis with editions in 1999 and 2011. The CSG turned their efforts to evaluating the effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on type I and type II diabetic nephropathy, respectively. The results of the industry-sponsored "Captopril Trial"3Lewis E.J. Hunsicker L.G. Bain R.P. Rohde R.D. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group.N Engl J Med. 1993; 329: 1456-1462Google Scholar and the Irbesartan in Diabetes nephropathy trial4Lewis E.J. Hunsicker L.G. Clarke W.R. et al.Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.N Engl J Med. 2001; 345: 851-860Google Scholar took the laboratory work of Barry Brenner of the effect of renin-angiotensin-aldosterone system inhibition on the progression of renal disease in animal models to humans. These were landmark trials that changed the trajectory of progressive kidney disease in patients with diabetic as well as nondiabetic renal disease. It is arguable that fewer things in nephrology have had a larger impact on the lives of patients with kidney disease than renoprotection afforded by renin-angiotensin-aldosterone system inhibition. Over these impactful clinical trials, the CSG grew from investigators at 12 institutions in the United States to over 250 investigators in 25 countries internationally. Ed ran the section of nephrology at Rush for over 40 years and, during that time, fostered the careers of over 100 fellows. Ed loved tradition. Every Friday afternoon in the nephrology conference room, a bottle of wine would be served during the "sign-out" of the clinical service to the attending, fellow, and residents who would be covering for the weekend. At Christmas time, he and the chief research technician, Richard Rohde, would make "renal punch." This was a concoction that consisted of grain alcohol, champagne, and peach brandy, and orange juice was added to give it the appearance of urine. Ed would proudly serve this potent brew up using a urinal. Although these events are clearly a thing of the past, they were legendary during their time. Whenever an attending was promoted or some honor was bestowed to one of the faculty, Ed would take the entire faculty to an exclusive private French restaurant that he was a member at. Ed was truly a renaissance man. He loved the opera and the symphony and had season tickets to both. He was a world traveler, but his favorite destination was Hawaii, where he and his family would go once or twice a year. One of his greatest loves, however, was Asian art. Just as he excelled in medicine, he approached Asian art the same way. He amassed an amazing collection that on 2 occasions was the subject of exhibits at prestigious museums. He wrote numerous academic articles about Asian art and published 2 books. Ed had 2 separate lives, one in the world of art and the other in the world of medicine. I will never forget when he and the love of his life, Julia, were married in 1997; I met a number of his friends from the art world, and all were amazed to find out that Ed was actually a physician. He had never talked about it with them, and thus, they had no idea. I am grateful that I had 40 years with this amazing individual. My experiences and collaboration with him and Mel were truly some of the best times in my life. I cannot imagine my professional trajectory without him. When Ed turned 80, Julie had a birthday party for him at Brown's Hotel in London, which was attended by his family and 40 of his closest friends in the Asian art world and medicine. I was fortunate that at that occasion, I was able to formally tell him how much I appreciated him and how much he had changed my life. About a month before his passing, our colleague and fellowship program director, Roger Rodby, organized a reunion of fellows who had trained at Rush over the past 50 years. Over 70 fellows attended the reunion as did Ed (Figure 1) and Mel Schwartz. One after another of his former trainees used this opportunity to thank him for the role he played in their career. Giants like Edmund Jean Lewis do not leave this earth without a huge impact. The author would like to thank Dr. Roger Rodby for his much-appreciated assistance in editing this tribute. And, I greatly appreciate Drs. William Couser, Kline Bolton, Marc Pohl, and Julia Lewis for their valuable input.