Derek Ashworth Denton (27 May 1924 – 18 November 2022) was an Australian scientist who elucidated the regulation of electrolytes in extracellular fluid, the hormones controlling this regulation, particularly aldosterone, and the instinctive behaviours controlling intake of water and salts. He was cited in 1995 at election to the U.S. National Academy of Sciences as the world’s leading authority on the regulation of salt and water metabolism and relevant endocrine control mechanisms. He was one of Australia’s most eminent scientists.
Career
Denton was the founding Director and Emeritus Director of the Howard Florey Institute, Honorary Professor at the University of Melbourne and a consultant at the Baker Research Institute. Denton's last book is The Primordial Emotions: The Dawning of Consciousness.
Research
Three months after medical graduation in 1947, he made a basic discovery on kidney function at the Royal Melbourne Hospital. In the face of profuse alkaline drainage (Na+ in excess of Cl- relative to extracellular proportions) from a pancreatic fistula (2-3 litres/day) the patient’s kidneys primarily regulated the ionic pattern of the extra cellular fluid – not plasma concentration or the load of ions to the kidney tubules. As the fistula drained, blood pressure declined, respiration increased, and Cl- excretion in urine increased despite decline in plasma Cl- level below the so called “renal threshold “. Adequate intravenous infusion of sodium lactate, or oral sodium bicarbonate reduced or stopped the urinary Cl- excretion. In this era, urinary Cl- was measured at the bedside (Fantus test) to assess whether salt content of the body was adequate or whether salt administration was needed urgently. This was recommended by Marriott in his Croonian Lecture and was the practice of the British Army in India. The proposal was physiologically unsound in specific circumstances of loss of Na in excess of Cl, and Marriott altered his recommendations. It was the wrong approach in diseases such as e.g. dysentery, cholera and paralytic ileus. No rapid estimation of urinary sodium by flame photometry had yet emerged.
Denton recognised also a crucial biological fact that no biologically relatively inactive cation had evolved in Metazoan organisms to play a role analogous to that which increase of bicarbonate plays on the anion side of the pattern during vomiting and excess Cl- loss. In this latter case no large urinary Na excretion was obligatory to keep acid-base balance compatible with life. The initial finding with pancreatic fistula was published by Nature (London, 1948). In 1949, he, and Dr Victor Wynn who had joined him in study of a second case, were supported by Professor R. D. Wright and Sir MacFarlane Burnet to set up the Ionic Research Unit of the NHMRC in the Physiology Department at Melbourne University. The Ionic Research Unit originated flame photometry in clinical medical practice internationally – a Wynn initiated step. Rapid measurement of sodium and potassium in blood and urine helped originate intensive care, and they published a monograph in Acta Medica Scandinavica. Denton and Wynn’s approach, particularly flame photometry with rapid assessment of biochemical disorder, eventually resulted in saving of tens of thousands of lives in Australia as well as in other countries by chemically accurate intervention. In 1952 Wynn went to London, where Professors Pickering and Robb at St Mary’s Hospital established a metabolic intensive care unit which Wynn directed. Some years later he was visited by Professor Francis Moore of Harvard who incorporated the Melbourne classification of distortion of body fluid status viz subtraction acidemia e.g. pancreatic fistula; addition acidemia e.g. diabetic coma; subtraction alkalemia e.g. vomiting gastric juice; and addition alkalemia (excess alkali ingestion) into his textbook ‘Metabolic Aspects of Surgery”
Denton, in Melbourne, directed his efforts to basic physiological processes involved in regulation of body fluids.