Thomas Willis (1621-1675): First Steps into Renal Physiology

Background: The 17th century marks a pivotal transition of traditional medical dogmatism to a modern experimental investigative discipline founded on the basic sciences established by the natural philosophers of the period. Thomas Willis (1621-1675), a celebrated clinical investigator of the times, is famous for his neuroanatomical discoveries. Unfortunately, his significant contributions to renal physiology have gone unnoticed and neglected. This study examines the evolution of Willis's concepts of kidney function during this critical era. Methods: We analyzed the pivotal but underrecognized contributions of Thomas Willis (1621-1675) to the foundations of renal physiology by comparing his early work De Urinis (1659), which mainly interpreted urinary diagnosis through humoral traditions; with his subsequent section on “Of the Diuresis or Evacuation by Urine” in his Pharmaceutice Rationalis (1674-75), which delves into renal function, specifically renal blood flow, urine formation, tubular function, and diabetes mellitus. Results: Building on the 1628 cardiac pump and blood circulation model of William Harvey and the 1662 tubular structure of the kidney of Lorenzo Bellini, Willis rejected the Galenic physiology that the kidney attracted blood because it was in its nature to do so in favor of a mechanical model of "straining or percolation" driven by the force of circulating arterial blood, with the resultant “watery serum” then entering the tubules which are “impervious to blood”, while the blood is received by the veins to return to the circulation. He further proposed that the salt residue of urine is regulated by the tubules. Willis also considered diabetes a blood disorder rather than a kidney disease, noting that, unlike imbibed fluids, diabetic urine tastes sweet “as if it were imbued with Honey or Sugar". Documented by subsequent observations, Willis' work proposed three critical principles: the blood-clearing function of the kidney depends on circulatory dynamics, tubules modify urine composition, and urinary changes reflect systemic physiology rather than just renal pathology. Conclusion: Willis’ renal model, though incomplete, clearly marks the initial but fundamental first steps in the evolution of our current understanding of renal physiology. It provided the first systematic framework for kidney function that would be documented in subsequent centuries.