Elmer Verner McCollum and his collaborators established the existence of vitamin D, named it, and contributed to its use in the eradication of rickets.
Rickets (or rachitis) is a disease that causes abnormal bone formation, particularly in the long bones and the ribs. First described in the second century
Rickets, which usually begins before age three, is caused by the improper and incomplete uptake of calcium into the fast-growing bones of children. The resultant insufficient calcification of these bones prevents them from hardening properly. Therefore, the bones of a rachitic child are so soft that they bend and twist into abnormal shapes. Furthermore, they will fracture easily. Fortunately, as afflicted children grow up, their bones harden, but the abnormal shapes are retained. Rickets is rarely fatal, but it produces several cosmetically unappealing conditions, including curvature of the spine, bow legs, knock-knee, and chicken breast. Rickets sufferers are also unusually susceptible to the common cold, to bronchitis, and to pneumonia.
As may be expected, vitamin D is utilized in preventive chemotherapy, not in the correction of rickets. The two most common forms of the vitamin used in humans are calciferol (vitamin D2) and cholecalciferol (vitamin D3). These fatlike substances are derived from the steroids ergosterol and 7-dehydrocholesterol (7-DC), respectively. The human body converts 7-DC to cholecalciferol at the surface of the skin in a process that is energized by ultraviolet light from the Sun. Exposure of adults to normal amounts of sunlight causes enough vitamin D3 production in the skin to make it unnecessary to add any vitamin D to their diet.
Children, however, require about 0.02 milligram of vitamin D per day in the diet if rickets is to be avoided. One way to administer the vitamin is as the cholecalciferol in cod-liver oil, a rich natural source of the vitamin. Fortification of milk with vitamin D2 is more widespread today. It is important to note, however, that excess dietary vitamin D should be avoided. The Food and Nutrition Board of the Institute of Medicine has set the tolerable upper intake level for vitamin D at 25 micrograms (1,000 international units) for those up to 12 months old and 50 micrograms (2,000 international units) for children, adults, and pregnant or lactating women.
McCollum, who first identified vitamin D and named it, carried out many of the early important studies on this vitamin. McCollum’s interest in biochemistry and vitamins began when he worked at the Connecticut Agricultural Experiment Station under Thomas Burr Osborne. This employment occurred during McCollum’s doctoral training in organic chemistry at Yale University, and ended when he was awarded the Ph.D. in 1906. In 1907, McCollum was employed by the Wisconsin College of Agriculture, where he was assigned to investigate the chemical makeup of the food and excrement of dairy cattle. There he developed the first white rat colony in the United States devoted to use in the study of nutrition. Utilization of rats as experimental subjects allowed McCollum and his coworkers the opportunity to circumvent the complicated and tedious methodology that was required to study cattle and other large animals. This revolutionary concept of nutritional research was so successful that other scientists all over the world soon began to emulate McCollum’s efforts. In six years, McCollum passed through the academic ranks from instructor to full professor.
In 1913, McCollum reported that rats fed “certain fat-deficient” diets exhibited a growth retardation that was reversed by feeding rats with “either extract of egg or of butter.” By 1915, McCollum’s research group had demonstrated that several trace substances, which McCollum called vitamins A and B, were necessary for normal health and growth in rats. Thus McCollum helped to initiate the alphabetical names used in vitamin nomenclature. In 1917, McCollum became the chair of the department of chemistry and professor of biochemistry at the School of Hygiene and Public Health of The Johns Hopkins University in Baltimore. He continued his efforts to understand the vitamins and pioneered the study of vitamin D, for which he is best known, again using rats for his experiments.
McCollum’s pioneering identification of the existence of vitamin D in 1922 was accompanied by development of the line test
In 1922, rickets was a worldwide disorder that affected many children. Today, it has essentially been eradicated in developed nations despite fluctuations in its incidence. The successful treatment of the disease began when McCollum and coworkers produced evidence in 1922 that cod-liver oil contained a specific antirachitic chemical (vitamin D). As McCollum stated in From Kansas Farm Boy to Scientist (1964): “The demonstration of the existence of a vitamin which exerts a profound influence in directing the growth of bones proved to be of great public-health value.”
McCollum’s research findings stimulated great interest among many investigators. Furthermore, the discovery, coupled with the participation of prominent pediatricians in the effort, such as John Howland at The Johns Hopkins Hospital, led to rapid general acceptance by physicians of the efficacy of using cod-liver oil to prevent rickets. From that time on, the medical profession passed from haphazard use of the oil—in a skeptical fashion—to its routine use. As a result, rickets soon became rare.
Actualization of the existence of the antirachitic substance quickly led to isolation and characterization of vitamins D2 and D3. Subsequently, in the hands of other researchers, study of the pure vitamin began to show promise. First, it became possible to add vitamin D2 to milk to ensure almost universal dissemination of the vitamin among the population of the industrialized countries. Next, it was shown that vitamin D2 (or D3) functioned after conversion as another chemical that was actually a hormone
The form of hormone D made by the body from vitamin D3 is called 1,25-dihydroxycholecalciferol. Hormone D acts by stimulating rapid intestinal reabsorption of calcium via a protein. This calcium resorption minimizes calcium loss in the feces and prevents the bone decalcification that results in rickets.
Additional examination of the action of vitamin D has led to better understanding of the processes of bone deposition and resorption as well as to explanation of the interrelationships between hormone D and other calcium-controlling substances (such as calcitonin and parathyroid hormone) made by the body. Such investigations have also led to the realization that bone is not simply a “dead,” body-support matrix. Rather, bone is a vital, live tissue that can produce dissolved calcium in the blood to serve many purposes.
This realization has had further ramifications, and it is clear that calcium serves as a biological signal in life processes that include control of the blood pressure, blood clotting, nerve impulse transmission, and muscle contraction. Therefore, the acorn of McCollum’s efforts had produced a mighty oak tree of intertwined information about life. This information now promises eventual answers to many elusive but fundamental problems of life science that are clearly associated with calcium.
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Carpenter, Kenneth J. “A Short History of Nutritional Science: Part 3 (1912-1944).” Journal of Nutrition 133 (October, 2003): 3023-3032. Third part of a four-part series includes discussion of McCollum’s research on vitamin D. Places McCollum’s work in the context of the history of nutritional science in general. -
Feldman, David, J. Wesley Pike, and Francis H. Glorieux, eds. Vitamin D. 2d ed. 2 vols. New York: Academic Press, 2004. Comprehensive reference set geared toward professionals working in endocrinology, osteology, cancer research, and related fields. First chapter provides a historical overview. Includes illustrations and index. -
Funk, Casimir. The Vitamines. Baltimore: Williams & Wilkins, 1922. Covers many aspects of vitamin research of the time. A source of extensive developmental information on nutrition, containing about sixteen hundred references on basic research on the vitamins and vitamin deficiency diseases. The many references to McCollum’s research indicate McCollum’s influence and research versatility in nutrition. -
McCollum, Elmer V. From Kansas Farm Boy to Scientist. Lawrence: University of Kansas Press, 1964. A charming autobiography that describes McCollum’s life and his research efforts in the study of vitamins, trace minerals, and other aspects of nutrition. Reveals the inner thoughts of a brilliant, sensitive man who was a great scientist. -
_______. A History of Nutrition. Boston: Houghton Mifflin, 1957. An interesting book on the development of nutrition science covering the period from the mid-eighteenth century to 1940. Especially valuable for readers who wish to trace the evolution of the science and those who are interested in details on the development of the understanding of the nature and roles of vitamins. -
_______. The Newer Knowledge of Nutrition. 2d ed. New York: Macmillan, 1922. Covers many aspects of nutrition around 1920. Discusses vitamins, foods, appropriate diets, analysis of foods, vitamin deficiency diseases, and many other topics. Contains many references to the contributions of McCollum’s group, but also provides full, fair coverage of the efforts of others. -
Smith, Emil L., et al. Principles of Biochemistry. 7th ed. New York: McGraw-Hill, 1983. Excellent biochemistry textbook includes details on many aspects of the roles of calcium, vitamin D, and other calcium-regulating substances on biological processes. Provides many references for those who wish more technical information.
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