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Articles

Virgil P. Sydenstricker (1889–1964)

Department of Medicine, The Medical College of Georgia, Augusta, GA 30912

	INTRODUCTION

TOP INTRODUCTION Family and education Career overview Research and scientific... Wartime efforts Awards and honors Medical education activities Studies in niacin deficiency... Nutrition in wartime Clinical medicine and nutrition LITERATURE CITED

 
Virgil Preston Sydenstricker (1889–1964 ) was the epitome of the physician nutrition specialist, clinical investigator and medical academician. He performed outstandingly in research, education and service, the three areas in which medical faculty are evaluated for promotion and tenure. For more than 30 years, his career focused on nutrition; he was a pioneer in the area of nutritional deficiency disease. While based at the Georgia state medical school in Augusta, his activities and influence extended nationally and in Europe, as a civilian and in the military.

View larger version (124K): [in this window] [in a new window]   Figure 1. Virgil P. Sydenstricker

	Family and education

TOP INTRODUCTION Family and education Career overview Research and scientific... Wartime efforts Awards and honors Medical education activities Studies in niacin deficiency... Nutrition in wartime Clinical medicine and nutrition LITERATURE CITED

Sydenstricker’s humanitarian and scientific interest in malnutrition was part of a remarkable American family that included the Nobel and Pulitzer prize-winning author Pearl S. (Sydenstricker) Buck and the eminent epidemiologist Edgar Sydenstricker (1) . Virgil Sydenstricker received B.A. and M.A. degrees from Washington and Lee University in 1910 and 1911, and an M.D. degree from the Johns Hopkins University School of Medicine in 1915. He was an intern and assistant resident at the Johns Hopkins University Hospital from 1915 to 1917 and a resident at the University Hospital, the teaching hospital of the Medical Division of the University of Georgia in Augusta, GA from 1919 to 1920. He was licensed to practice medicine in Maryland (1915) and Georgia (1919). He served in World War I with the Johns Hopkins Military Medicine Unit in France, achieving the rank of Captain.

	Career overview

TOP INTRODUCTION Family and education Career overview Research and scientific... Wartime efforts Awards and honors Medical education activities Studies in niacin deficiency... Nutrition in wartime Clinical medicine and nutrition LITERATURE CITED

 
He was appointed an instructor in medicine at the School of Medicine of the University of Georgia (now the Medical College of Georgia, MCG) in 1920 and started a private practice of medicine in Augusta. He became Professor of Medicine in 1922 and was Chairman of the Department of Medicine from 1922 until his mandatory retirement in 1957. He then became Professor Emeritus of Medicine and Chief of Medicine at the VA Hospital in Augusta until his death.

Sydenstricker achieved national and international recognition in the fields of hematology and nutrition. He published 113 scientific articles and abstracts and biographical sketches in journals that included Science, Nature, The Journal of Biological Chemistry, The American Journal of Physiology, The Proceedings of the Society for Experimental Biology and Medicine, The Journal of Nutrition, The Journal of the American Medical Association and six chapters in textbooks of medicine and pathology. His initial research in hematology dealt with innovative methods of blood transfusion and descriptions of sickle cell anemia. In the 1930s, he began research in nutrition addressing problems of vitamin deficiency diseases and malnutrition. He reported experiments in rats in nine articles covering nutritional factors that influenced the eye and a similar number of articles on amino acid deficiencies with special attention to threonine. He published nine articles on niacin and pellagra, six articles on riboflavin deficiency and five on wartime nutrition.

	Research and scientific accomplishments

TOP INTRODUCTION Family and education Career overview Research and scientific... Wartime efforts Awards and honors Medical education activities Studies in niacin deficiency... Nutrition in wartime Clinical medicine and nutrition LITERATURE CITED

 
His first research, as a medical student, resulted in an article co-authored with Nobel Prize winner, G. H. Whipple. As an intern he developed a system of blood transfusion with stored citrated blood (2) that enabled blood to be "banked"; this is the basis for modem blood banking and blood transfusion practices. This method replaced direct transfusion from the donor to the recipient. In 1923, he published the first case report of sickle cell anemia with autopsy findings (3) . His further work and life-long interest in that disease led to national recognition for his contributions; near the end of his career, he described abnormal hemoglobins (4) .

Sydenstricker demonstrated the efficacy of nicotinic acid (niacin) in the prevention and cure of pellagra (5 ,6) . His work was an important clinical follow-up to the earlier studies of Goldberger in Georgia and South Carolina mental institutions that demonstrated that pellagra resulted from a diet deficient in niacin. Pellagra was a prevalent and puzzling disease, particularly widespread in the Southeast (see below).

His nutrition research interest then turned to riboflavin deficiency, especially the ocular manifestations (7) . He described the syndromes of multiple B vitamin deficiencies (6) and reported the effects of B vitamin therapy in patients with psychosis and encephalopathy (8) . He and associates also contributed to the characterization of the syndrome of human biotin deficiency.

	Wartime efforts

TOP INTRODUCTION Family and education Career overview Research and scientific... Wartime efforts Awards and honors Medical education activities Studies in niacin deficiency... Nutrition in wartime Clinical medicine and nutrition LITERATURE CITED

 
From 1940 to 1944, Sydenstricker served on the Food and Nutrition Board of the NRC in developing nutritionally sound combat rations for the army. In 1942, he was sent to England by the Nutritional Health Division of the Rockefeller Foundation to work with the British Ministry of Health (Nutritional Section) to determine the adequacy of the war rations allotted to the British people. In 1944, he was called to active duty as Colonel in the U.S. Army. In 1944–1945, he was Medical Director of the Nutritional Section, U.S. Public Health Service, detailed to the United Nations Relief and Rehabilitation Administration. He was in charge of the medical and nutritional care of 60,000 prisoners released from German prison camps, primarily the camp at Belsen. He was stationed in London, proceeding to Brussels with the Supreme Headquarters Allied Expeditionary Forces. He was assigned to Eindhoven, Holland, where he cared for the released prisoners and conducted nutritional studies of the Dutch civilians. He assisted in the nutritional assessment and care of malnourished people in the geographic area occupied by the Germans where the population had suffered from severe famine. He was honored for these services by the British, Dutch and American governments with awards from King George of His Majesty’s medal for service in the cause of freedom (1946). His work in Europe prevented his accepting an assignment from the State Department to serve as nutrition specialist to assist the Chinese National Health Administration. Sydenstricker was a Consultant to the Surgeon General, U.S. Army.

He compiled a scrapbook with numerous snapshots of his war experience, captioned in Sydenstricker’s handwriting. The original document is on exhibit in the Special Collections Room of the Greenblatt Memorial Library of MCG. The scrapbook graphically depicts the horrors of the dead, dying and malnourished captives in the concentration camp, and their brutal SS guards.

His earlier wartime experiences included his work with Ancel Keys and others in developing the K ration. He summarized his experiences in Britain in the Harvey Lecture in 1943 at the New York Academy of Medicine (9) and in other publications. He was a consultant to Keys in the landmark "Minnesota experiment" that chronicled the effects of semistarvation for 9 mo and subsequent refeeding in conscientious objectors. In 1950, he returned to England with the WHO to evaluate the postwar nutrition of the British people.

Sydenstricker’s research then turned to studies in a rat model of the effects of various essential amino acids (lysine, methionine, phenylalanine, histidine, threonine and tyrosine), especially in the eye, with several "eye" papers published in The Journal of Nutrition. He and collaborators studied the corneal changes and cataract induction from a variety of nutritional deficiencies, including those of pantothenic acid and pyridoxine.

	Awards and honors

TOP INTRODUCTION Family and education Career overview Research and scientific... Wartime efforts Awards and honors Medical education activities Studies in niacin deficiency... Nutrition in wartime Clinical medicine and nutrition LITERATURE CITED

 
Sydenstricker was the recipient of numerous prestigious awards, including the Goldberger Award in Clinical Nutrition from the American Medical Association, presented to him by the Nutrition Foundation in 1958. Invited lectureships included the Thayer Lecturer (Johns Hopkins Medical School), Wyckoff Lecturer (New York University School of Medicine), Campbell Lecturer (Queens University, Belfast, Ireland) and the Lind Bicentennial Lecturer (Edinburgh, Scotland). In 1979, the new wing of the MCG Hospital was named for Dr. Sydenstricker.

He was elected to Phi Beta Kappa and Alpha Omega Alpha honor societies and to membership in numerous scientific societies including the American College of Physicians (Fellow, 1927, Master, 1949), the American Institute of Nutrition (1944), and the Society for Experimental Biology and Medicine. He was awarded Board Certificate #225 from the American Board of Internal Medicine (ABIM) in 1936. He served on the ABIM as an examiner from 1946 to 1952.

	Medical education activities

TOP INTRODUCTION Family and education Career overview Research and scientific... Wartime efforts Awards and honors Medical education activities Studies in niacin deficiency... Nutrition in wartime Clinical medicine and nutrition LITERATURE CITED

 
His other interests that are relevant to contemporary medicine included nutrition education of medical students and the provision of medical care to indigents. He discussed the teaching of nutrition in American medical schools and schools of nursing at the 18th Conference of the Milbank Memorial Fund in 1941. In 1950, the School of Medicine was separated from the University of Georgia and reverted to its status as an independent institution, MCG. Sydenstricker’s multiple honors there included the Student’s Award for Excellence in Teaching at MCG in 1952. He spent his life in a continuing effort to bring knowledge and ability to the future physicians of Georgia. He was a role model who provided compassionate and excellent care to his patients. While his contributions as a scientist had national and international recognition, his chief importance in the state of Georgia was probably his influence as a physician and educator. In 1958, approximately two of every five physicians in practice in Georgia had received their training at the Augusta medical school during Sydenstricker’s 35 years as Professor of Medicine. Curtis Carter, a student, fellow faculty member in the department of medicine and later the Dean of the School of Medicine, summed up his achievements in a tribute at Sydenstricker’s retirement: "He is known among his confreres as the ‘doctor’s doctor’ and among patients he is looked on as the appeal of last resort." Physicians currently practicing in Augusta who were medical students in Sydenstricker’s day recall vividly his brilliance as a diagnostician, his wit and his extensive knowledge, and consider themselves fortunate to have had such an outstanding mentor and role model.

His famous collaborators included Keys, William Sebrell and Hugh Sinclair. At the symposium at MCG celebrating the centenary of Sydenstricker’s birth, Sebrell gave a fascinating account of traveling by train to Augusta and Milledgeville, GA to study pellagra, and working in a "hidden" laboratory at the Augusta medical school. Sinclair described Sydenstricker’s wartime activities with him at Oxford University and elsewhere in England, Holland and at Belsen. Sinclair stated that Sydenstricker had displayed anger that was unusual for him at a driver who had motored with them through a heavily mined area in Holland in May 1945. They had traveled with two mobile laboratories to survey and evaluate the nutritional status of the Dutch who had undergone severe famine for 7 mo, and were planning the refeeding after their liberation. Dr. Frederick Stare headed another similar team of nutritionists in Holland. Sinclair described the repulsive protein hydrolysates that were presumed to be tolerated well by starved individuals. Some 10,000 persons were presumed to have died from starvation in the acute famine in the Netherlands. Liberated Dutch scientists joined Sinclair and Sydenstricker and their team. They examined 3500 persons in Leiden, chosen at random, and performed 25,000 biochemical tests in a few weeks. One problem of interest was the prevalent famine edema.

A photograph in the Sydenstricker collection in the Library at MCG depicts the group studying nutrition and army rations at Camp Carson, CO during World War II; included in the group is Dr. Albert Mendeloff, former editor of The American Journal of Clinical Nutrition. Medical students of Sydenstricker who went on to nationally recognized careers related to nutrition included William Kannel (Framingham Heart Study) and Curtis Hames (Evans County Study, MacArthur Fellow). Their remarks about their medical school days at the 1989 centenary symposium are archived in videotape in Dr. William Darby’s historic collection at Vanderbilt University.

	Studies in niacin deficiency and pellagra

TOP INTRODUCTION Family and education Career overview Research and scientific... Wartime efforts Awards and honors Medical education activities Studies in niacin deficiency... Nutrition in wartime Clinical medicine and nutrition LITERATURE CITED

 
Sydenstricker first published on niacin deficiency and pellagra in 1936, followed by a review of 444 cases of pellagra seen over a 15-y period published in 1937. Subsequent articles reported on niacin in the prevention and treatment of pellagra, culminating in a study of nicotinic acid restriction in humans that was published in The Journal of Nutrition in 1945. His studies with the Augusta biochemist Sam Singal (later Dean of the Graduate School) detailed the intricate relationship of tryptophan, pyridoxine and riboflavin in nicotinic acid metabolism. He also described multiple nutritional deficiencies and mental manifestations that occurred in patients with pellagra. Of related interest is a publication with Hervey Cleckley, the psychiatrist for the patient with multiple personalities disorder who was portrayed in "The Three Faces of Eve." They described the ineffective use of nicotinic acid in the treatment of psychosis that was not part of the pellagra syndrome. Sydenstricker and Cleckley also investigated the use of nicotinic acid in the treatment of various psychiatric disorders (8) .

His investigations of riboflavin deficiency in humans, 1939–1941, included several publications on ocular manifestations (two with Sebrell as co-author), and combined deficiencies of riboflavin and niacin. Two papers on biotin deficiency induction with egg white and cure with biotin (1942) were collaborations with Singal and Harris Isbell.

	Nutrition in wartime

TOP INTRODUCTION Family and education Career overview Research and scientific... Wartime efforts Awards and honors Medical education activities Studies in niacin deficiency... Nutrition in wartime Clinical medicine and nutrition LITERATURE CITED

 
His reports of wartime nutrition, 1943 and 1944, included nutrition in wartime conditions, effects of rationing on nutrition in Great Britain, the role of vitamin supplements, and neurological manifestations of malnutrition (9) . The Harvey Lecture dealt mainly with the implementation and details of food rationing in Britain and the effects on the population. After describing as background the life of the people in wartime (blackouts, serving in the Home Guard), Sydenstricker gave details of how the Ministry of Food and Ministry of Agriculture regulated production of foods and their distribution and pricing. For example, the amount of land under cultivation was increased, and food production focused primarily on carbohydrate foods and green vegetables as well as milk. Other sources of protein and fat could not be increased and were imported. Cheese production was curtailed in favor of whole milk, and fish was scarce because fishing boats could not operate. Distribution of meat was strictly controlled. Potatoes were the most important food crop, the great source of cheap energy, and even more essential than bread. Bread and potatoes were the most important sources of B vitamins, and potatoes (and cabbage) were the main source of ascorbic acid, except for younger children. Tomatoes were cultivated in hothouses for a mandatory 6 mo/y, and sale of apples and plums was controlled. Oranges were distributed only to children <6 y of age. Meat, rationed by price, amounted to 1 lb/wk for adults and half that for children, who were given priority for milk and eggs. Communal feeding was established in restaurants, schools and works canteens. The primary drawback of the program was the monotony of the diet, whether at home or in the feeding program. The rationing leveled the diet—the rich ate less well and lost weight, and the poor ate more of the foods essential for good nutrition and benefited from rationing. It was estimated that the intake of iron, calcium, vitamin A and ascorbic acid was low for adults. The general health of the population improved during the 3.5 y of war up to that time, and the clinical nutritional health of the British people remained good.

	Clinical medicine and nutrition

TOP INTRODUCTION Family and education Career overview Research and scientific... Wartime efforts Awards and honors Medical education activities Studies in niacin deficiency... Nutrition in wartime Clinical medicine and nutrition LITERATURE CITED

 
Sydenstricker’s views on medical education expressed in 1926 (10) would be readily acceptable today. He advocated teaching and training medical students in the outpatient department where patients present with ordinary ailments and disorders at an earlier stage than in the hospital and thus are more representative of the patients he/she will see as a primary care practitioner.

In the second Sydney Watson Smith Lecture of the Royal Society of Medicine, Edinburgh in 1953 (6) , Sydenstricker briefly surveyed the history of vitamin deficiency diseases moving from Chinese observations of night blindness and food intake 3000 years ago to the explosion of knowledge of vitamins that had occurred during the 40 years preceding his lecture. This beautifully written historical account and synthesis of the investigations is pertinent today and provides an easily read summary of the exciting discoveries and their application in the prevention and treatment of vitamin deficiency diseases. He cites 80 seminal references. He concluded that the concept of accessory food factors in the diet, other than energy and macronutrients, that had been proposed by Hopkins in 1906 stimulated investigations by Funk, McCollum, Osborne, Mendel and others that formulated the hypothesis of deficiency diseases (beriberi, scurvy, pellagra, rickets) and specific essential growth factors later termed "vitamines," and finally vitamins. The research involved every branch of medical science, i.e., biochemistry, physiology, pharmacology, pathology, bacteriology and clinical and veterinary medicine; despite skepticism and persistent suspicion of an infectious or toxic etiology for these diseases, the research was met with more enthusiasm than the discovery of bacteria and infectious diseases. He reviewed the work on all of the individual vitamins except vitamin E. He questioned the lack of explanation for why and how the nicotinamide coenzymes involved in carbohydrate metabolism produce the anatomical lesions of pellagra (which was still the case almost 50 years later), "considering the great number of potent enzymes in which riboflavin is active, it is surprising that the manifestations of deficiency in the human subject are not more striking." Sydenstricker’s cogent remarks on vitamin therapy that are still applicable today include administering vitamins in therapeutic amounts to treat deficiency diseases until patients can consume an adequate diet. If this is not possible, or if conditions exist that interfere with intake, absorption or assimilation, then vitamin supplementation should be continued indefinitely. Vitamins must be added to deliberately inadequate therapeutic diets used to treat diseases such as obesity. Patients with massive intestinal resections should be prescribed large doses of supplements, and some may need protein hydrolysates (or, today, amino acids). Preparation for surgery in chronically ill patients with peptic ulcer disease, carcinomas of the stomach or colon, and hyperthyroidism involves the use of vitamins. On the other hand, healthy people eating a normal diet do not need added vitamins. "Vitamins will not cure the ailments of the psychoneurotic or the inertia and insomnia of the depressed. Neither are vitamins a pick-me-up for the tired and hungry. Pills in no way can replace food."

Pellagra played a pivotal role in the development of the modern concept of nutritional deficiency disease and the recognition of neurological disorders of malnutrition. As late as 1912–1916, the Thompson-McFadden Pellagra Commission, after an extensive review, declared that pellagra must be an infectious disease (bacteria, protozoa). Through the work of Goldberger and others, the nutritional etiology was finally accepted. In 1937, Elvehjem discovered that nicotinic acid was the critical nutrient in therapeutic liver extracts. Working in the southeastern United States, Sydenstricker had witnessed the epidemic explosion of endemic pellagra during the Depression. His research helped demonstrate the factors involved in the etiology of pellagra. He described the coexistence of niacin and riboflavin deficiency, and was instrumental in establishing the efficacy of niacin therapy. He and Cleckley first described the syndrome of niacin deficiency encephalopathy without the gastrointestinal and dermatological findings of classic pellagra (1) .

They described a typical patient as follows: "Profound stupor or stupor alternating with delirium and variable reflex changes are the presenting phenomena. Quite regularly there is evidence of underfeeding, though definite signs of avitaminosis are rare and confined to occasional instances of glossitis ... Treatment of this high mortality group of patients with nicotinic acid was at first quite empirical and begun because one such person had a red atrophic tongue. In this condition, as in the acute psychoses already described, the results of the administration of nicotinic acid have been quite remarkably good." In several instances, the encephalopathy was treated first with thiamine with no response, but showed prompt and often impressive improvement with niacin therapy.

Sydenstricker’s group described a variety of neurological and psychiatric symptoms associated with niacin deficiency. Although these symptoms have been related to central chromatolysis of neurons in various areas, the exact contribution of niacin deficiency is unclear because of the coexistence of multiple nutritional deficiencies. As Sydenstricker noted, "more than one factor might be concerned in the production of a typical deficiency syndrome, since the production of a specific deficiency syndrome is quite difficult with the deprivation of a single vitamin in normal human beings."

The work of Sydenstricker and Cleckley has been interpreted as advocating uncontrolled administration of niacin to patients with a variety of psychiatric disorders. Their studies in malnutrition have been cited to justify megavitamin therapy for schizophrenia, a treatment without validated efficacy. Sydenstricker practiced in an environment with an extremely high incidence of pellagra, a disease that was rampant in mental institutions. He specifically asserted that it would be "ridiculous" to infer that all stuporous or psychiatric conditions are manifestations of pellagra; and further, when definite niacin deficiency existed, replacement therapy might fail because of neuronal destruction. From their experience with psychotic, delirious and stuporous patients, they concluded that a trial of nicotinic acid might be worthwhile. These investigations were confounded by the vasodilatation effects of nicotinic acid that may improve mental symptoms such as delirium or dementia resulting from arteriosclerosis. Sydenstricker, however, understood the complexity of niacin metabolism and its synergism with other vitamins, tryptophan, protein intake and general nutritional status.

In his lecture to the Nutrition Foundation in 1958, following his Goldberger award, Sydenstricker reviewed the history of pellagra (5) . He also included the work that he and Sebrell had performed studying riboflavin deficiency, and the occurrence of corneal vascularization as the earliest manifestation of ariboflavinosis. In his 1939 article in The Journal of the American Medical Association (7) as a follow-up to Sebrell and Butler’s description of experimental riboflavin deficiency, Sydenstricker described five patients with active or prior pellagra whose cheilitis, scaly dermatitis and conjunctivitis cleared with large doses of riboflavin (20–60 mg oral or 3, 10, 20 or 50 mg parenteral/d) while consuming an experimental diet deficient in nicotinic acid (pellagra-producing).

In this modern age of communication, I strongly recommend that Sydenstricker’s publications be read by current medical and graduate students, trainees, investigators, educators and practitioners for their timeless science, style, humor and readability. Reading them conveys the excitement and importance of nutrition in science and medicine.

	ACKNOWLEDGMENTS

 
V. P. Sydenstricker’s complete biography, compiled by Dorothy Mims, Research Librarian (retired) at MCG can be read in the Special Collection Room where his wartime scrapbook, awards and medals are displayed. Joseph P. Bailey, M.D., Professor Emeritus of Medicine, and Kimford Meador, M.D., Professor of Neurology, MCG, provided materials for this article.

	LITERATURE CITED

TOP INTRODUCTION Family and education Career overview Research and scientific... Wartime efforts Awards and honors Medical education activities Studies in niacin deficiency... Nutrition in wartime Clinical medicine and nutrition LITERATURE CITED

 

1. Meador K. J., Loring D. W., Nichols F. T., Adams R. J. & Feldman E. B. (1988) Virgil Sydenstricker: special reference to niacin deficiency encephalopathy. South. Med. J. 81:1042-1044.[Medline]

2. Sydenstricker V. P., Mason V. P. & Rivers T. M. (1917) Transfusion of blood by the citrate method. J. Am. Med. Assoc. 68:1678-1680.

3. Sydenstricker V. P., Mulherin W. A. & Howseal R. W. (1923) Sickle cell anemia, report of two cases in children, with necropsy in one case. Am. J. Dis. Child. 26:132-154.

4. Huisman T. H. & Sydenstricker V. P. (1962) Differences in gross structure of two electrophoretically identical ‘minor’ hemoglobin components. Nature (Lond.) 193:489-491.

5. Sydenstricker V. P. (1958) The history of pellagra, its recognition as a disorder of nutrition and its conquest. Am. J. Clin. Nutr. 6:409-414.[Medline]

6. Sydenstricker V. P. (1953) The impact of vitamin research upon medical practice. Proc. Nutr. Soc. 12:256-269.

7. Sydenstricker V. P., Geeslin L. E., Templeton C. M. & Weaver J. W. (1939) Riboflavin deficiency in human subjects. J. Am. Med. Assoc. 113:1697-1700.

8. Sydenstricker V. P. & Cleckley H. M. (1941) The effect of nicotinic acid in stupor, lethargy and various other psychiatric disorders. Am. J. Psychiatry 98:83-91.[Abstract/Free Full Text]

9. Sydenstricker V. P. (1943) Nutrition under wartime conditions 1943 Harvey Lecture May 20, 1943. Bull. N.Y. Acad. Med. 19 749–765. .

10. Goodrich W. H. & Sydenstricker V. P. (1927) Attendance on the city’s sick poor as part of clinical instruction at the medical department, University of Georgia. Methods and Problems of Medical Education 6th series:247-249 The Rockefeller Foundation New York, NY .

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