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Biographical Article

William J. Darby, 1913–2001¹

Harold H. Sandstead^* and Conrad Wagner²

^* Department of Preventative Medicine and Community Health, University of Texas Medical Branch, Galveston, TX 77555; and the Departments of Biochemistry and Veterans Affairs Medical Center, Nashville, TN 37212

²To whom correspondence should be addressed. E-mail: conrad.wagner{at}vanderbilt.edu.

	INTRODUCTION

TOP INTRODUCTION LITERATURE CITED

 
William J. Darby, affectionately known as Bill or WJD, was born November 6, 1913 in Galloway, AR. He married Elva Louise Mayo on June 12, 1935. They had three boys, William, James and Douglas, four grandchildren, and four great-grand children. Bill died at age 87 on Wednesday June 6, 2001 in Nashville, TN. Elva and their progeny survive him.

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Dr. Day encouraged Bill to enroll part-time in college as a premedicine student and then to matriculate in the Medical School. Bill graduated with a BS in 1936 and with an MD in 1937. During that time he courted Elva whom he first met in the high school orchestra while playing clarinet. She played violin.

After graduation, Bill and Elva moved to Ann Arbor where Bill was a student of Professor H. B. Lewis in the Department of Biological Chemistry at the University of Michigan. Bill recounted (1 ) that Dr. Lewis’ "superb lectures and graduate seminars" were "punctuated" with "assigned reading of landmark reports of nutrition research" that supplemented by personal anecdotes pertaining to investigators, provided "appreciation of our rich scientific heritage and sharpened" his "insight into the scientific method." Bill completed the MS in Biological Chemistry in 1941, then after 1 year as a National Research Council Fellow in Medical Sciences in the Department of Biochemistry at Columbia University College of Physicians and Surgeons, received the PhD from the University of Michigan in 1942.

In 1942 Bill and Elva moved to Nashville where Bill was Special Fellow in Nutrition, International Health Division, Rockefeller Foundation in the Department of Medicine, Vanderbilt University School of Medicine. His chief was John B. Youmans, MD, "one of the remarkable men who enormously influenced" his "career and became my warm friend and demanding mentor" (1 ). Bill first learned of Dr. Youmans as a 3rd-year medical student from the Professor of Surgery at Arkansas, George V. Lewis, MD. As Bill recalled (1 ), one day on rounds, Dr. Lewis "abruptly asked, ‘Darby, you are in biochemistry. Now tell me about protein deficiency.’ After I stuttered out in response a standard explanation of protein-deficiency hypoalbuminemia he commented abruptly, ‘don’t you ever read the JAMA? You had better read the paper by Dr. Youmans." Bill read the paper, "Endemic Edema," and learned "a great deal about clinical protein deficiency and was introduced to the concept of chronic moderate deficiency syndromes (so-called subclinical)." At Vanderbilt Bill learned about clinical nutrition, nutrition survey techniques and other aspects of clinical medicine from Dr. Youmans. Other mentors and lifelong friends in the Department of Medicine included the Chairman Hugh Morgan, MD, and Professors Rudolph Kampmier, MD and Edgar Jones, MD. Bill saw patients on ward rounds and in the clinic, participated in research, and taught in the Nutrition course that "was initiated in the 1920s" by Dr. Youmans and Charles S. Robinson, PhD, Professor of Biochemistry.

Bill and Elva moved to Chapel Hill, NC in 1943 where he was Instructor in Preventive Medicine and Director of Medical Nutrition, North Carolina State Board of Health at Duke University School of Medicine, and Assistant Research Professor in Nutrition at the University of North Carolina School of Public Health. Lessons learned at Vanderbilt helped prepare him for this job. In collaboration with D. F. Milam of the Rockefeller Foundation, he reported (1945) his first nutrition survey in which he described essential components of the assessment of nutrition in a community.

In 1945 Bill was appointed Assistant Professor in Biochemistry and Medicine at Vanderbilt; in 1946 he was appointed Associate Professor of Biochemistry; and in 1948 he was appointed Professor of Biochemistry. He succeeded Charles S. Robinson as Chairman of Biochemistry (1949–1971). Other positions at Vanderbilt included Director, Division of Nutrition (1948–1971), Professor of Nutrition (1964–1979) and Professor of Medicine in Nutrition (1965–1979). He was appointed Professor Emeritus of Biochemistry (Nutrition) in 1979. Although Bill is principally known for his contributions to nutrition, it is not generally appreciated that as Chairman of Biochemistry, he presided over the modernization of the Department by recruiting a number of outstanding biochemists to the faculty. This included Frank Blood, PhD, William Pearson, PhD, John Coniglio, PhD, Oscar Touster, PhD, Leon Cunningham, PhD, Jack Hayes, PhD, Ben Wilson, PhD, Robert Neal, PhD, Harry P. Broquist, PhD, Conrad Wagner, PhD, Jan Van Eys, PhD, MD, Laken Warnock, PhD and Stanley Cohen, PhD who won the Nobel Prize in 1985. His faculty referred to him as the "perfect Chairman. He supports you when you have a problem, but otherwise he leaves you alone." Bill also served as mentor to a number of graduate students including Glenn H. Booth, JR., MD, PhD, Rodolfo Florentino, PhD, Kristen Wallwork McNutt, PhD, Manuel P. Macapinlac, PhD, Gabriella I. Molnar, PhD, Boriboon Phornphiboul, PhD, Raymond E. Poore, PhD, Jan Van Eys, MD, PhD and Chung S. Song, MS. He also established the Divisions of Nutrition and Toxicology based within the Department. His service to Vanderbilt was characterized by his intense loyalty to the University.

Bill’s highly successful leadership resulted from his warm personality, emotional steadiness, optimism, thoughtfulness, patience, integrity, high intelligence and ability to do prodigious amounts of work. He was accessible and collegial with faculty and students, gave minimal direction, provided opportunities, assumed others would do well and acknowledged their successes. He and Elva were sincerely interested in the lives and families of all members of the Department, from Janitor to Professor. He appeared to never forget a name, or the previous times he had spent with a person. He kept disappointments private.

Elva’s support was important for Bill’s success. She was his faithful companion and the loved one to whom he returned from his many travels. Her calmness was a counterpoint to his energetic, and sometimes, frenetic pace. She provided continuity. The high regard her peers and others at Vanderbilt have for her attests to her success as a helpmate and member of the community.

Bill was a staunch advocate of the scientific method and the experimental approach for solving problems. He had little patience with those who confuse statistical significance for physiological importance. Poor science was anathema. He believed epidemiological associations should be tested by experiment. He did not hesitate to question popular paradigms. He fulfilled his duty as a physician through research and service. His research was notable for its many facets. His ability to evaluate problems creatively and to stimulate others to do so is evident in the results of work he did with many colleagues.

Bill’s earliest research experience occurred in the laboratory of Dr. Day, where his duties included the care and feeding of the laboratory animals (rats and monkeys). Dr. Day included Bill as a "coinvestigator" in his research on riboflavin. The work included the induction of cataracts in M. mulatta by riboflavin deficiency. An unintended consequence was the discovery of a lethal "fulminating blood disease, characterized by marked anemia, leukopenia, gingivitis, and diarrhea," that in some instances resulted in "noma" (personal communication, WJD, 1998). The condition occurred before development of advanced cataract and was prevented by dried brewers yeast. Bill coauthored two reports (2 ,3 ) describing the nonefficacy of niacin, and the discovery that the condition was caused by a previously unrecognized nutritional factor (vitamin M). Later, in 1945 Day showed that purified L. casei factor (folic acid) also cured the anemia and leukopenia and, therefore, was the same substance as vitamin M. From Bill’s perspective (personal communication, WJD, 1998), these findings and those of Wills in 1929 on "tropical macrocytic anemia" set the stage for the clinical demonstration by Bill, Edgar E. Jones, MD and others during 1945–1949 that L. casei factor (vitamin M, folic acid) was efficacious for the macrocytic anemia and aspects of nontropical sprue. Bill’s interest in folate continued throughout his career. In 1948 with Calvin Woodruff, MD and others he measured relationships between folate and ascorbic acid nutriture, in 1950 with R. Furman, MD, Edgar Jones, MD, and others he showed the nonefficacy of vitamin B-12 for "pernicious anemia of pregnancy" and its successful treatment with folic acid, and also in 1950 with J. Dawson, JR. and Calvin Woodruff, MD and with Sam Clark, JR., MD and Charles Dodgen in 1953 described renal toxicity of pteroylglutamic acid. Also with Calvin Woodruff, MD and J. Peterson, MD in 1951 he showed the efficacy of folate for megaloblastic anemia in infants, with Willard Faulkner, PhD in 1958 the effects of folate on myoglobin, with William N Pearson, PhD and others in 1959 developed an ultramicro-assay for pteroylglutamic acid, and in 1961with A. Mangay-Chung and others estimated the human dietary intakes of folate, pyridoxine, pantothenic acid, and vitamin B-12. Later in 1972 with C. I. Waslien, PhD at Naval Medical Research Unit 3 (NAMRU-3) and K. Kamel, MD and R. Asfour, MD in 1977 and others at NAMRU-3 and the American University in Beirut, he measured the folate requirements of infants and children.

Bill’s interest in micronutrients and their interactions in metabolism led to research on other vitamins including tocopherol, retinol, niacin, pyridoxine and vitamin B-12. Relevant to his interest in the macrocytic anemias, he with Richard C. Bozian, MD in 1963 and Robert M. Heyssel, MD in 1966, and others measured vitamin B-12 requirements and metabolism in adults. In 1963 he also collaborated with James S. Dinning, PhD, Amin Majaj, MD and others in studies of vitamin E and coenzyme Q₄ chromanol responsive megaloblastic anemia in infants with severe protein-energy malnutrition. Although a similar anemia had been described in M. mulatta, the condition had not been recognized in humans.

Bill’s interest in essential minerals prompted his collaboration with George R. Meneely, MD and others in 1953 in pioneering work that showed excess sodium fed to rats causes renal vascular injury and hypertension, and in 1961 showed that potassium is protective. These findings provided a basis for others to determine the roles of sodium, potassium and other minerals in human hypertension and for dietary recommendations.

Bill’s interest in minerals encompassed trace elements. His early work with Paul F. Hahn, MD (Department of Biochemistry at Vanderbilt) and others in 1947 concerned iron deficiency anemia in a rural community in North Carolina. Later, in 1947, with Paul F. Hahn, MD and others he measured iron absorption of children and in 1951 the iron metabolism of pregnant women.

The wide prevalence of protein-energy malnutrition, iron deficiency and other micronutrient deficiencies motivated Bill in 1960 to establish the Vanderbilt University Nutrition Research Group at NAMRU-3 in Cairo, Egypt. Bill had been a Consultant for the World Health Organization on pellagra in 1949. This activity took him to Egypt and led to his acquaintance with scientists at NAMRU-3. Later collaboration between the Interdepartmental Committee on Nutrition for National Defense (Development) (ICNND) and NAMRU-3 for accomplishment of the nutrition survey of Ethiopia (below) led to friendship with Captain John Seale, MD, Commanding Officer, NAMRU-3. Captain Seal suggested collaboration between NAMRU-3 and Vanderbilt University "to enhance the capabilities of NAMRU-3 for addressing malnutrition, a major problem in the region" (1 ). This nearly 25-y research program provided Bill the opportunity to mentor many younger scientists including Ananda S. Prasad, MD, PhD, Harold H. Sandstead, MD, James P. Carter, MD, James T. Davis, PhD, Yank D. Coble, MD, L Kristen Wallwork, PhD, Carol I. Waslien, PhD, and Charles H. Halsted, MD, who he recruited to the research team that also included Arthur R. Schulert, PhD and Vinayak N. Patwardhan, PhD. At the very beginning, Bill set the course of the research program to one of discovery and personal satisfaction for all participants. Bill helped plan and facilitated research that tested Ananda S. Prasad’s (1961) hypothesis that the syndrome of dwarfism, hypogonadism, anemia and hepatosplenomegaly among low-income farmers was caused by zinc deficiency. Shortly after developing his theory, Prasad had moved from Shiraz, Iran to Cairo, Egypt to join Bill’s research team. Soon after arriving, Ananda showed Bill Egyptian farmers with the same physical appearance as his Iranian subjects. Bill indicated the condition was new to him and agreed the condition should be studied. Bill’s reasoned approach to research and skill at obtaining support made confirmation of Prasad’s hypothesis possible. At times it was an uphill battle against the prevailing paradigm that human zinc deficiency was very unlikely. The support of Arnold E. Schaeffer, PhD of the ICNND and of several Commanding Officers of NAMRU-3, and the work of many collaborators resulted in the first elucidation of human zinc deficiency (4 ). The great importance of this discovery has become evident over the past 40 y. Bill greatly enjoyed the evolution of knowledge concerning zinc and its role in human health and function.

The Vanderbilt Nutrition Research Group at NAMRU-3 studied many aspects of nutrition including nutrition in ancient Egypt. This activity involved two key collaborators, Louis Grivetti, MS, an aspiring nutritional anthropologist, now a PhD and Professor of Nutrition and of Cultural Geography at the University of California at Davis, and the endocrinologist Paul Ghalioungui, MD, an authority on Pharonic medicine. Their collaboration resulted in the definitive monograph, Food: the Gift of Osiris (5 ). The "15 years during which these volumes were being assembled permanently fixed (Bill’s) long existing interest in history of food, food science, and nutrition that had been initiated by teachings of Paul Day, PhD and Howard B. Lewis, PhD. During these years (Bill) became an avid bibliophile" (1 ).

A special research interest of Bill’s concerned nutrition of pregnant women and their infants. Initial work in 1948 included measurements of nutrition status and iron metabolism in 1951. This was followed by a comprehensive study that involved many colleagues during the period from 1953 through 1958. This study provided a basis for research by others and the contemporaneous Recommended Dietary Allowances.

Bill’s clinical interests prompted his work on assessment of nutritional conditions of populations. John B. Youmans, MD, was his mentor. Bill’s early published work in 1945 reported findings from rural North Carolina. It was followed in 1950 by a study with Grace A. Goldsmith, MD and others of the nutrition status of the population of Norris Point, Newfoundland, and nutrition surveys of school children for the Tennessee Department of Health (with William J. McGanity, MD and others). Subsequently, Bill and colleagues in 1955 did the first comprehensive nutrition study of Navajo Indians. His principal colleagues were William J. McGanity, MD, Harold R. Sandstead, MD and Edwin Bridgeforth, all of whom contributed to work of the ICNND.

For nearly two decades Bill was a consultant to the ICNND. Bill described the work as "personally rewarding, uniquely scientifically productive, and of remarkable humanitarian benefit" (1 ). "The ICNND, organized in 1955, had as its primary objective assisting developing countries to assess their nutritional status, defining problems of malnutrition, and identifying means for solving these problems by taking advantage of the countries own resources." As a member of the editorial board of the Manual for Nutrition Surveys (6 ), Bill had a major influence on its content and organization. Utilization of the methodology resulted in comprehensive descriptions of the nutrition status of the populations of 32 nations. Bill directed six of the surveys (Philippines, Ethiopia, Ecuador, Lebanon, Jordan and Nigeria).

Another outlet for Bill’s energy was his service on many committees and review boards. Examples include the Council on Foods and Nutrition of the American Medical Association (1948–1962, 1965–1973, chairman 1960–1962 and 1967–1970), the Food and Nutrition Board, National Research Council, National Academy of Sciences (1949–1971, steering committee 1955–1971, vice chairman 1960–1962), the Committee on Food Protection (FPC), National Academy of Sciences (1950–1971, chairman 1954–1971), the Expert Advisory Panel on Nutrition, World Health Organization (1950–1982), the Food and Agricultural Organization/World Health Organization Joint Expert Committee on Nutrition (1954, 1957, 1961, 1966, chairman 1957), the Panel on Nutrition of the Space Science Board, National Academy of Sciences (1962–1972), and many committees of the National Institutes of Health (Study Section on Biochemistry and Nutrition, 1948–1951; Chairman Metabolism and Nutrition Study Section, 1951–1953; Consultant on Nutrition, USPHS, 1950–1953; Consultant Interdepartmental Committee on Nutrition for National Defense, 1955–1966; Chairman General Medicine Study Section, 1956–1959; Board of Scientific Counselors, National Institute of Arthritis and Metabolic Diseases, 1957–1959; Chairman Nutrition Study Section, 1959–1961; Committee on International Centers for Medical Research and Training, 1961–1965; Advisory Committee, Diet, Nutrition and Cancer Program of the NCI, 1975–1977) and Public Trustee of The Nutrition Foundation (President 1972–1982).

One of Bill’s more important contributions was his 17-y leadership of the FPC of the National Academy of Sciences. "The reports of the FPC were evolved by critical study of all available scientific evidence, objectively assessing it, then following with recommendations of general or specific nature; the sole objective was to attain maximal public benefit with minimal risks. The Committee early recognized the principle that the concept of absolute safety is invalid and set down guiding principles concerning the use or exclusion of food ingredients of additives." "In the early 1950s there existed no complete list of substances employed as food additives. Compilation and publication of such a list was promptly undertaken by the FPC." Over three decades the FPC served the United States and others by "elaborating general principles, responding to needs to evaluate the safety of specific categories of substances such as surfactants and sweeteners, publishing two classical monographs on naturally occurring toxic material inextricably present in food stuffs, and producing the Food Chemical Codex, which not only is the first official codex of food chemicals in the United States but has been adopted by many of the major countries of the world. This codex is as basic to the field of foods as are pharmacopoeias to medicine." Health of people throughout the world is better because of the work of the FPC.

Late in his career Bill was President of the Nutrition Foundation. During his tenure the Foundation sponsored meetings on contemporaneous nutrition issues including nutrition education in medical schools, and published 16 monographs and Nutrition Reviews. These activities were an extension of Bill’s experience as a writer of 48 reviews on various nutrition topics. Bill’s reviews and those of the scientists who prepared Nutrition Foundation monographs and wrote for Nutrition Reviews continue to enhance knowledge of nutrition scientists.

One of Bill’s later activities was serving as Honorary Curator for the History of Medicine/Nutrition Collection in the Eskind Biomedical Library at Vanderbilt University Medical Center. This collection of rare books numbered 3500 volumes when Bill began as Honorary Curator and grew to over 12,000 volumes. Bill’s enthusiasm for antique books related to nutrition and metabolism was contagious. He influenced many individuals to become collectors and several made generous financial contributions to the library’s rare book collection. Bill also worked with the architects to help design a new home for the rare book collection. Bill gave his collection of rare books on nutrition to the Library. It is planned that his unique collection will be made available to the scientific community on the Library’s web site.

Bill’s peers recognized his contributions through many awards. Although these recognitions gave Bill pleasure, he always acknowledged that success was in part due to the hard work of those with whom he was associated and that Elva’s support was essential. Among his awards was election to the U. S. National Academy of Sciences in 1972.

The preceding is a far from adequate description of this multifaceted man. He is deeply missed by his colleagues and loved ones.

	FOOTNOTES

 
¹ A complete bibliography of Dr. William Darby’s publications is included as supplemental data in the on-line posting of this article at www.nutrition.org.

Manuscript received 30 January 2002. Revision accepted 25 February 2002.

	LITERATURE CITED

TOP INTRODUCTION LITERATURE CITED

 

1. Darby, W. J. (1985) Some personal reflections on a half-century of nutrition science: 1930s–1980s. Ann. Rev. Nutr. 5:1-24.[Medline]

2. Day, P., Langston, W. & Darby, W. (1938) Failure of nicotinic acid to prevent nutritional cytopenia in the monkey. Proc. Soc. Exp. Biol. Med. 38:860-863.

3. Langston, W., Darby, W., Shukers, C. & Day, P. (1938) Nutritional cytopenia (vitamin M deficiency) in the monkey. J. Exp. Med. 68:923-940.[Abstract/Free Full Text]

4. Sandstead, H. H. (2001) Importance of the report: syndrome of iron deficiency anemia hepatosplenomegaly, hypogonadism, dwarfism and geophagia. J. Trace Elements Exp. Med. 14:145-155.

5. Darby, W., Ghalioungui, P. & Grivetti, L. (1997) Food: The Gift of Osiris 1st ed. 1997 Academic Press London, UK. .

6. Interdepartmental Committee on Nutrition for National Development (1963) Manual for Nutrition Surveys 1st and 2nd eds. 1963 U. S. Government Printing Office Washington, DC. .

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