LAUSR

Maurice Benjamin “Moe” Burg, who revolutionized our understanding of kidney physiology through his invention and exploitation of a technique for microdissection and study of isolated nephron segments, died on April 24, 2022, at the age of 91. The knowledge gained from his isolated perfused tubule studies forms the basis of what every medical student is taught today about nephron function. Moe was an inspiration to generations of kidney researchers who built on his seminal findings about kidney transport. The kidney research community has lost an inspiring leader and a wonderful friend. Moe received his Bachelor of Arts from Harvard College in 1952 and his Doctor of Medicine from Harvard Medical School in 1955. He arrived at the NIH to join the National Heart Institute as a postdoctoral fellow in 1957 under Jack Orloff. Moe became an Investigator in the Laboratory of Kidney and Electrolyte Metabolism in 1960 and Laboratory Chief in 1975. He held this post until 2009, when he became Senior Investigator in the Systems Biology Center of the National Heart, Lung and Blood Institute. Prior to Moe’s seminal work on kidney function, knowledge about transport of water and solutes in the kidney was derived from two main techniques, renal clearance studies that investigated the input-output function of the whole intact kidney, and micropuncture, which involved insertion of sharpened tiny pipettes into the lumina of renal tubules accessible at the surfaces of rat or dog kidneys. Conclusions were confined to so-called “proximal” and “distal” tubules. Beginning in the 1960s, Moe recognized the limitations of these methods; structures internal to the kidney could not be studied. Moe credited Ivar Sperber for the idea that the internal structures (nephrons and collecting ducts) could be microdissected from the kidney (1). Sperber, as a graduate student in Stockholm during World War II, carried out extensive structural studies of the kidneys of a large number of mammalian species by microdissecting the kidneys after HCl maceration (2). Sperber’s work made it clear that renal tubules making up the substance of mammalian kidneys consisted of more than just proximal and distal tubules, but also included several other morphologically distinct segments whose functions were unknown. Sperber’s microdissected tubules were dead, but Moe wondered if live tubules could be obtained using gentler dissection methods. He discovered indeed that tiny, intact tubule segments, made up of 200 to 1,000 cells, could be manually microdissected from pathogen-free rabbits. To study transport, he invented a system of tiny, concentric glass pipettes that allowed him to perfuse the tubules from one end and collect the fluid exiting from the other end. Transport rates could be calculated from the measured difference in composition between the perfusate and collected fluid, and the flow rate. Transport mechanisms were inferred from the transport rates and simultaneously measured transepithelial electrochemical driving forces. With the new technique (3) came a flurry of studies conducted in Moe’s laboratory, identifying transport processes and their mechanisms in previously inaccessible parts of the kidney. Examples include transport processes that subsequently became targets of drugs commonly used today in patient care, such as coupled sodium/potassium/chloride cotransport in the thick ascending limb of Henle’s loop (diuretics: furosemide, bumetanide), sodium-coupled glucose transport in the early proximal tubule (antidiabetic drugs: canagliflozin, dapagliflozin, empagliflozin), and vasopressinregulated osmotic water transport in the collecting duct (vasopressin receptor antagonist tolvaptan). Much of present day canonical knowledge about kidney physiology is derived from the studies done by Moe and his trainees using the Burg renal tubule microperfusion technique. Later in Moe’s career, he shifted his focus to a new area of research: osmotic regulation in the kidney (4). The urinary Maurice B. Burg at the dissection microscope. Image credit: Mark Knepper (National Heart, Lung, and Blood Institute).