Gamble and Darrow: pathfinders in body fluid physiology and fluid therapy for children, 1914-1964

The development of body fluid physiology and fluid therapy in pediatrics has special importance in the history of medicine because this development introduced physiology into clinical practice. James Gamble and Dan Darrow were leaders in this enterprise. Gamble was part of the group John Howland attracted to Johns Hopkins to establish the first organized program for clinical investigators in pediatrics. This group initiated fluid therapy as effective treatment for diarrheal dehydration and, led by Gamble, developed the discipline of body fluid physiology. Gamble was the first to describe the nature of extracellular fluid (ECF) to clinicians, using the new terminology for characterizing electrolytes in solution. In doing so, he became the teacher of body fluid physiology to a generation of medical students. Inexplicably, in his later years he failed to adopt yet newer terminology defining cations, anions, and acid-base status. This failure compromised his legacy. Dan Darrow extended our understanding of how body fluids react to hyper- and hyponatremia and to potassium deficiency. He was the first to add potassium to parenteral fluid therapy. In doing so, he broadened clinicians' understanding of body fluids but changed the emphasis of fluid therapy from rapid ECF restoration to replacement of estimated deficits. Unfortunately, this change in concept, taught by his successors as deficit therapy, slowed the adoption of oral rehydration therapy for treating diarrheal dehydration. The lapses noted for each of these men, now seen in hindsight, pale in comparison to their contributions. Pediatrics, medicine, and surgery are all indebted to the research of each, which emphasized the value of basic physiology in clinical practice.