A Legacy in 20th-Century Medicine: Robert Allan Phillips and the Taming of Cholera

0 Robert Allan Phillips was born in Clear Lake, Iowa , on 16 July 1906. His father and uncle were partners in one of the few medical practices in the area, operating a clinic and small hospital that adjoined Phillips' boy- hood home. During World War I, Phillips' father vol- unteered for duty in Europe as an Army Medical Corps officer. He later served for years as the mayor of Clear Lake. A studious youngster, Phillips received his bach- elor of science degree from the State University of Iowa ( Iowa City) in 1927 , before graduating from the Wash- ington University School of Medicine (St. Louis , MO) in 1929 . During the 3 years that Phillips spent in St. Louis, which included a 1-year surgical internship at Barnes Hospital, he published his first scientific paper on the effect of ergosterol on blood coagulation [1]. Phillips was awarded a National Research Council Fellowship at Harvard Medical School ( Boston , MA) in 1930 . He joined the Physiology Department , which 1 Received 28 December 2001; revised 2 April 2002; electronically published 23 August 2002. The opinions expressed in this paper are those of the author and do not reflect the official policy of the Department of Navy, Department of Defense , or the US Government. Reprints or correpondence: Dr. Stephen J. Savarino, Naval Medical Research Center , 503 Robert Grant Ave., Silver Spring, MD 20910-7500 2 Stephen J. Savarino United States Naval Medical Research Center , Silver Spring, Maryland The legacy of Captain Robert Allan Phillips (1906-1976) was to establish effective, evidence-based rehydration methods for the treatment of cholera. As a Navy Lieutenant at the Rockefeller Institute for Medical Research (New York, New York) during World War II, Phillips developed a field method for the rapid assessment of fluid loss in wounded servicemen. After the war, he championed the establishment of United States Naval Medical Research Unit (NAMRU)-3 (Cairo; 1946) and NAMRU-2 (Taipei; 1955), serving at the helm of both units. Phillips embarked on cholera studies during the 1947 Egyptian cholera epidemic and brought them to maturity at NAMRU-2 (1958-1965), elucidating the pathophysiologic derangements induced by cholera and developing highly efficacious methods of intravenous rehydration. His conception of a simpler cholera treatment was realized in the late 1960s with the development of glucose-based oral rehydration therapy, a monumental breakthrough to which many other investigators made vital contributions. Today, these simple advances have been integrated into everyday medical practice across the globe, saving millions of lives annually. - A persons true wealth is the good he or she does in the world. Muhammad It is a curious commentary on human nature that the ravages of war often foster major advances in medical science and practice. The tumult of World War II set the stage for a major achievement of 20th-century medicine: the development of intravenous and oral rehydration therapy for cholera and related diarrheal illnesses. Captain Robert Allan Phillips, through brilliance, preparedness, and serendipity, became a central figure in this public-health triumph. was directed by the eminent chairman Walter B. Cannon, and engaged in studies of the autonomic nervous system, intestinal and renal physiology, and carbohydrate metabolism. He received further surgical training at Yale University School of Medicine (New Haven, CT) before becoming an instructor in physiology at Stanford University (Stanford, CA). From 1936 to 1940, Phillips served as Assistant Professor in Physiology at Cornell Medical College (New York, NY). Working at these institutions, and influenced by leading physiologists of his day, Phillips developed a reputation as a careful, innovative experimentalist. WORLD WAR II SERVICE As the United States prepared for World War II, Dr. Phillips was commissioned a lieutenant in the US Naval Reserve in August 1940. In December 1940, he was assigned to the Rockefeller Institute for Medical Research (New York, NY), where he joined the laboratory of Donald D. Van Slyke, a renowned leader in clinical chemistry whose laboratory would perform war-related research on shock and blood substitutes. Van Slyke assigned Phillips to develop a deployable method of measuring the specific gravity of blood and plasma, because established methods were impracticable for use in the field [2]. Phillips discovered that copper sulfate solutions worked quite well for this application, and he developed methods to calculate various blood indices and to estimate intravascular fluid deficits on the basis of changes in the specific gravity of blood [3, 4]. The copper sulfate method (figure 1), also known as the PhillipsVan Slyke test, was adopted by the US and British armed services and proved invaluable in the field management of hemorrhage, burns, and shock during the war [2, 5, 6]. The test was later adapted by the Red Cross and, for many years, served as the method of choice for screening the hemoglobin levels of prospective blood donors [7]. In 1944, Phillips was detailed to the Cairo, Egypt, unit of the United States of America (USA) Typhus Commission, the mission of which was to perform research and develop control measures against typhus fever, a serious hazard for Allied forces in North Africa [8]. In Cairo, Phillips upgraded clinical chemistry capabilities at the Commission laboratory and conducted biochemical and physiological studies of patients with typhus on the units research ward at the Abbassia Fever Hospital (Cairo). In May 1945, Phillips was temporarily assigned to the newly liberated concentration camp at Dachau, Germany, where horrid conditions had promoted the spread of typhus fever. He established a laboratory at Dachau to support the clinical care of persons with typhus [9]. Phillips was profoundly affected by these overseas-duty assignments. From a military standpoint, he recognized the importance of such opportunities for the study of diseases in situ Figure 1. The copper sulfate test kit shown here was packaged for use in the field during World War II (adapted from [4]). The test was widely adopted by the US and British armed services for assessment of intravascular fluid deficits in wounded combatants during the war, and it was later used by Robert Allan Phillips in his studies of cholera. Blood (or plasma) specific gravity is determined by releasing drops of fluid into a graded series of copper sulfate solutions covering a defined range of specific gravities. Specific gravity of the body fluid is equivalent to that of the solution in which the drop neither rises nor falls (interpolated in the figure as 1.026). that may threaten combatants. Moreover, he acutely realized the broader value of international scientific cooperation. ESTABLISHMENT OF NAVAL MEDICAL RESEARCH UNIT (NAMRU)3 AND THE FIRST ENCOUNTER WITH CHOLERA As the war in Europe ended in May 1945, the USA Typhus Commission planned to dissolve (...truncated)