Neal S. Bricker, MD
April 18, 1927 - May 4, 2015
Neal S. Bricker, MD, an internationally renowned physician, devoted husband and father, and lifetime humanitarian, died of natural causes on May 4th, 2015. Dr. Bricker was a pioneer in the field of renal pathophysiology, and was nominated for the Nobel Prize in 1974. He also was among the founding members of the American Society of Nephrology (ASN), where he became the organization's first president from 1966-1967
Dr. Bricker grew up in Denver, Colorado, and attended the University of Colorado Medical School. He became a physician at the age of 22, and was awarded the “Gold-Headed Cane” for being at the top of his graduating class. Dr. Bricker completed his residency at Bellevue Hospital in New York, and worked for Homer Smith, a pioneer in the field of nephrology. He later served as Chief of Renal Physiology at Fitzsimons Army Hospital, where he began to conduct research on polycystic renal disease in soldiers. In all, he served in three branches of the military service – the Army, Navy, and U.S. Coast Guard. Additionally, he was a senior assistant resident at Peter Bent Brigham Hospital, where he served as a Howard Hughes Investigator. During that time, he measured the post-transplantation renal function of identical twins.
Dr. Bricker taught at Harvard University and was later recruited to work at Washington University Barnes Hospital in the mid-1950s. During this time, Dr. Bricker proposed the “Intact Nephron Hypothesis” based on a series of experiments he devised in dogs and rats that looked at the function of the diseased kidney in a normal environment and then in a uremic environment. Prior to his experiments, the prevailing theory was that the diseased kidney was made up of a mass of disparate nephrons and no nephron functioned like any other. Dr. Bricker proposed that, on the contrary, each nephron functioned as an intact nephron and was subject to the same control systems. This was a very exciting time in the nephrology unit at Washington University.
Three basic models were used. In the dog, he deployed the split bladder technique which allowed him to study each kidney separately before disease was induced. Then unilateral pyelonephritis or glomerulonephritis was produced in one kidney. Both kidneys were studied in a normal environment. The normal kidney was then removed and the diseased kidney was studied in a uremic environment. The second model was the development of chronic pyelonephritis in the rat. The third model was the production of the remnant kidney model in the rat. Branches of the renal artery to one kidney were progressively ligated until 80-85% of the kidney was infarcted, leaving 10-20% of normal non-diseased nephrons. Surprisingly, the remnant kidney functioned in an identical fashion to the chronically diseased kidney, both in a normal environment and in uremia.
When the tubular functions were factored by the glomerular functions in all 3 stages, normal, diseased kidney or remnant kidney in a normal environment and a diseased or remnant kidney in a uremic environment, all functions were virtually identical for the handling of NH3, PO4, urate, titratable acid, glucose, PAH and effective renal plasma flow.
It took the nephrology world many years to accept the “Intact Nephron Hypothesis” but it is now acknowledged as the basis of all renal pathophysiology. The following is a quote from Dr. Barry Brenner in the 9th Edition of Brenner & Rectors “The Kidney”:
“The kidney's primary function of maintaining constancy of the extracellular fluid (ECF) volume and composition is remarkably well preserved until late in the course of chronic renal disease (CRD). When nephrons are lost through disease or surgical ablation, the least affected or remaining nephrons undergo remarkable adaptive physiologic responses resulting in nephron hypertrophy and hyperfunction that combine to compensate for the acquired loss of renal function. Appropriate kidney function requires close integration of glomerular and tubular functions. Indeed, the preservation of glomerulotubular balance seen until the terminal stages of chronic renal failure (CRF) is fundamental to the intact nephron hypothesis of Bricker which essentially states that as CRF advances, kidney function is supported by a diminishing pool of functioning (or hyperfunctioning) nephrons, rather than relatively constant numbers of nephrons, each with diminishing function. This concept has important implications for the mechanisms of disease progression in CRF.”
From these studies, Dr. Bricker also proposed the “Tradeoff Hypothesis” and the “Magnification Phenomenon” which are widely accepted as to how the body deals with advancing renal disease.
Along with his studies on chronic renal disease in the mid 60's, Dr. Bricker became intensely interested in how the kidney controlled sodium and many other electrolytes. Once again he looked at sodium handling in the diseased kidney. He became convinced that there must be some final modulator, or fine tuner, that directed the kidney to excrete every 24 hours what was ingested. This is true even when 98% of the nephrons are destroyed. After a 40-year search he isolated, synthesized, and produced xanthurenic acid 8-O-β-D-glucoside, a potent natriuretic substance.
From 1971-1981 Dr. Bricker was named chairman of multiple committees on space flight by the National Academy of Sciences. He, along with others, studied various metabolic changes in astronauts during prolonged periods of weightlessness. From these studies, Dr. Bricker edited a pamphlet on “The Sea Within Us: A Clinical Guide to Fluid and Electrolyte Balance,” by New York: Science and Medical Publishing Company, Inc. 1975. Contributors included Drs. Seldin, Goldberg, Welt, Giebisch, Schrier and Maxwell. He also edited a monograph for the National Academy of Sciences entitled “Life Beyond Earth's Environment. The Biology of Living Organisms in Space.”
In addition, he led an investigative team which qualified for one of the longest living program project grants in the history of the National Institutes of Health (NIH). During a year-long sabbatical from Barnes Hospital, he worked at the Institution of Biological Chemistry in Denmark, Copenhagen with Dr. H.H. Ussing. He also spent numerous summers working in Mt. Desert Biological Laboratory, located in Bangor, Maine. As an established investigator for the American Heart Association, he conducted research at the Marine Biology Institute on the transport of sodium by red blood cells from the dogfish shark.
At Washington University, Dr. Bricker helped to set up and secure funding for that institution's first dialysis unit, for dialyzing chronic patients. During this time, he was active in many organziations. He not only served as ASN's first president, but he was also president of the American Society for Clinical Investigation (ASI); often referred to as “Young Turks.” He was a founding member and vice president of the International Society of Nephrology, 1966-1969 and was treasurer from 1969-1981. He was a member of the Institute of Medicine from 1975-2015 and served on the board of directors of the American Board of Internal Medicine from 1970-1978, as well as many other prestigious organizations.
Following his resignation from Washington University, Dr. Bricker was appointed to the position of Chair of Medicine at Albert Einstein College of Medicine. Later, he was invited to join the University of California, Los Angeles (UCLA) as head of the Program in Kidney Disease. Dr. Bricker's research has been published in medical and scientific journals, including Nature, The New England Journal of Medicine, the American Journal of Physiology, Journal of Clinical Investigation, Proceedings of the National Academy of Sciences, Kidney International, etc. At the age of 87, he published his most recent paper in Frontiers of Medicine, on the natriuretic hormone, a naturally occurring molecule he identified and patented. The identification of this chemical substance led to the development of a company called Naturon.
Dr. Bricker retired in 2010 after serving as Professor of Medicine at the University of California, Riverside for 12 years. He later divided his time between writing and collaborating on research projects.
Dr. Bricker will be remembered as a scientist who forged new ground, who challenged the status quo and who then set out to prove his hypotheses. He was a man of many interests, but above and beyond all of this, he was a compassionate, very kind friend and colleague, father and grandfather.
Bricker is survived by his wife Ruth T. Bricker, his daughters, Dusty (Dale) Bricker, Cary Alison Bricker, and Suzane Lynn Bricker; his son, Dann Baker, his son-in-law, Jay Leach, and his grandson, Max Michael Bricker. His first wife, Miriam T. Bricker, died of cancer at the age of 44.
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