The Accomplished Life of William G. Couser, MD

A few weeks ago, at the age of 85, Bill Couser passed away leaving only sterling memories of a distinguished American physician and one of the great academic nephrologists of the modern era.

A native of Lebanon, New Hampshire, Couser attended Harvard College and Harvard Medical School. He did house officer training at the University of California, San Francisco, and after 2 years in Vietnam as a Captain in the Army Medical Corps, returned to finish his training on the Harvard Medical Service at Boston City Hospital. His first laboratory experiences centered around GN guided by Edmund Lewis at the Thorndike Memorial Laboratories at Boston City Hospital. As a result, he became hooked on performing medical research to help improve the human condition beyond the individual patient.

After a few years on faculty with Lewis at the University of Chicago and later returning to the Boston University School of Medicine, Couser moved west to became Head of the Division of Nephrology at the University of Washington and the Belding Scribner Professor of Medicine for some 20 years of productive academic work, training his most important legacy, the next generation of superb nephrologists. Of his some 30 research trainees and 60 clinical trainees in nephrology, ten became Chiefs of Nephrology somewhere in the world, four Deans of medical schools, and four Presidents of various nephrology societies. His Division of Nephrology also received one of the first George M. O'Brien Kidney Center grant from the National Institutes of Health.

What do you say about a complex but self-assured man; outwardly shy but uniquely charismatic with a sardonic sense of humor, academically agile, gifted as a scientist and clever teacher, loved by two sons and his lovely wife, Adrienne, and one of the kindest people one could sit with to sort out the many twists and turns of academic life. To know him, droll colleagues might have thought Couser was born an adult, but he actually had great impish humor among his friends. He lived by an inspiring notion that integrity had no need of rules; to Bill, principles only meant something if you stuck by them when it was inconvenient. One also remembers his authentic sense of moral dignity, his charity toward the unevenness of the human condition, his brilliance at problem solving, and of course, his remarkable sense of fairness.

It is not an overstatement to say that Couser was a major force in bringing research on immunologic kidney diseases into the forefront of our discipline. By the late 1970s, Frank Dixon at Scripps and others had identified two major types of GN: one due to circulating immune complexes that would deposit passively in the glomerulus and the second being an autoimmune disease in which antibody was directed to an antigen within the glomerular basement membrane causing antiglomerular basement membrane disease.^1,2 There also was an idiopathic nephrotic syndrome not mediated by humoral immunity and was believed to be some type of T-cell disorder.³

Couser's first major discovery was the observation that discontinuous, granular staining could represent the binding of an antibody to an antigen within the capillary wall, whether it be an endogenous autoantigen or an exogenous antigen that had localized (“planted antigen”) to the capillary wall. One of his key studies was in a model of membranous nephropathy known as the Heymann nephritis induced by actively or passively immunizing rats with a portion of proximal tubule brush border.⁴ It was widely thought the formed immune complexes that resulted were being passively trapped in the subepithelial space of the glomerular capillary wall. However, Couser demonstrated that antibodies to these tubular lysates formed subepithelial deposits in the glomerular capillary wall by binding in situ to an intrinsic glomerular antigen, later shown by Farquhar et al. to be megalin, coexpressed on rat podocytes as well as in the tubular brush border.⁵ This led to the insight that membranous nephropathy might not be a disease from circulating immune complexes but rather from an autoimmune reaction to antigens on the podocyte. These findings set the stage for subsequent clinical studies identifying podocyte antigens in human membranous nephropathy, including neutral endopeptidase as the alloimmune target in neonatal membranous nephropathy,⁶ the phospholipase A2 receptor, as the major antigen in primary membranous nephropathy (Beck et al.⁷), and a plethora of other antigens in primary and secondary forms of membranous nephropathy (see review by Sethi and Fervenza⁸).

A second major discovery came from work in the Couser laboratory. Another classic viewpoint was the role of complement in immune kidney disease that was primarily due to the release of chemotactic factors (such as C5a) after complement activation that would subsequently recruit inflammatory cells such as neutrophils and macrophages to the glomerulus where they could cause local injury. Diseases such as membranous nephropathy, which did not have inflammatory infiltrates, were believed to have complement activation that was innocent, as any C5a released would be on the outer side of the glomerular basement membrane and would be washed away by tubular fluid. A landmark study by Salant et al. found that complement depletion could prevent proteinuria in the passive Heymann model. This led to a large number of studies in the Couser and Salant laboratories that identified C5b-9 (the terminal portion of activated complement) as the mediator acting directly on the podocyte.⁹ These key studies fundamentally broadened our views of complement in glomerular disease that paved the way to new treatments aimed at blocking the complement system.

A third major discovery related to the identification of a type of crescentic, rapidly progressive GN in which there were no immune deposits. When the first reports came out, it was widely believed that the lack of immune deposits was a methodologic error. However, Couser showed definitively that this was a separate type of GN, now called pauci-immune, that later became recognized as ANCA-associated rapidly progressive GN.¹⁰ Indeed, Couser was one of the first to show that high-dose “pulse” steroids could have a dramatic effect on disease outcomes.¹¹

His list of discoveries could also be extended to studies on the podocyte (largely with Stuart Shankland), the mesangial cell (largely with Rick Johnson), and on many animal models of glomerular disease (largely with Charlie Alpers), but there were two additional major contributions worth mentioning. First, Couser being one of the world leaders in immune kidney disease helped reorganize that nomenclature and types of glomerular disease that are still used today. Second, he championed immune kidney disease as a key subspecialty of kidney disease that helped bring this field alongside longstanding interests in renal physiology and tubular transport.

As a result of his landmark research contributions to the field of nephrology, Couser coedited a textbook on the Immunology of Renal Disease (with Eric G. Neilson) for two editions until the field got too expansive to keep up in that format; rose to become President of the American Society of Nephrology, the Council of American Kidney Societies, and the International Society of Nephrology; and became the Editor-in-Chief of JASN. He was also the recipient of the David M. Humes Award from the National Kidney Foundation for high ideals of scholarship and humanitarianism; the Joel D. Kopple Award from the International Federation of Kidney Foundations for outstanding performance in kidney disease detection, prevention, treatment and care; and the John. P. Peters Award from the American Society of Nephrology for individuals who made substantial contributions to the discipline of nephrology and have sustained achievements in one or more domains of academic medicine including clinical care, education, and leadership.

In his later years, as Head of the Division of Nephrology, Couser was caught up in a national Medicare kerfuffle regarding the billing of dialysis patients. In a plea deal to end a difficult moment for his university that for all intents and purposes ended his academic career, the prosecutors recommended it was in the best interest of the national and international medical community, and population of patients with kidney disease, that he be permitted to continue his research and writing regarding kidney function and disease. As usual, he handled this denouement to his remarkable career with great dignity while grieving in a silence you would expect from a private man of resolute character.

In contemplating so many more cheerful memories of Bill, we are reminded of an old proverb that goes something like this: If you wish to be happy for 3 hours, eat at La Tour d’Argent in Paris. If you wish to be happy for 3 days, get married. If you wish to be happy for 3 weeks, play golf. And if you wish to be happy forever, have Bill Couser as your friend. May you rest in peace, dear friend.

Supplementary Material

jasn-36-991-s001.pdf ^{(1.3MB, pdf)}

Disclosures

Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/JSN/F113.

Funding

None.

Author Contributions

Writing – original draft: Richard Johnson, Eric G. Neilson.

Writing – review & editing: Richard Johnson, Eric G. Neilson.