Perspectives in Biology and Medicine

ELMER McCOLLUM AND THE DISAPPEARANCE OF RICKETS GALE W. RAFTER* Butfor rickets vitamin D would not have been discovered. Its discovery was the secret to rickets; its use is essentially the therapy of that disease. When Edwards Park [1] wrote this in 1936, the value of vitamin D for the treatment and prevention of rickets was universally accepted by physicians. Supplementation ofdiets with vitamin D has led to the disappearance of this once-common childhood disease. Vitamin D has a curious history, and in this paper the contributions of Elmer V. McCollum are delineated in the context of how a fundamental biological discovery finds its way to the clinic for the benefit of the patient. Rickets is a systemic, metabolic disease related to blood calcium and phosphorus concentration. When the concentration is low, precipitation of calcium phosphate cannot take place, and defective calcification or mineralization of newly formed bone results. The bones of the rachitic patient lack strength and bend under the weight ofthe body. Because of rickets' obvious skeletal deformities, it was described very early. The first description is usually attributed to Hippocrates. In more recent times, after industrialization of Western Europe in the nineteenth century, its morbidity increased so that it became the major disease of childhood. Two matters that concerned early investigators as well as those who followed were its cause and how to treat it. Environmental conditions were usually cited as its cause by physicians in the nineteenth century, since the disease was common in impoverished populations. A noteworthy exception to this notion was promulgated by an English physician, George Budd [2], who recognized rickets as a nutritional disease. Furthermore , he anticipated the findings of twentieth-century investigators ?Department of Biochemistry, West Virginia University School of Medicine, Morgantown , West Virginia 26506.© 1987 by The University of Chicago. AU rights reserved. 003 1-5982/87/3004-0555$0 1 .00 Perspectives in Biology and Medicine, 30, 4 ¦ Summer 1987 \ 527 that absence of a specific substance in the diet could result in a specific disease. Another perceptive piece of work that came at the end of the nineteenth century and to which more attention was paid than to Budd's ideas was Theobald Palm's [3] study on the epidemiology of rickets. On the basis of its geographic distribution, he recognized the importance of sunlight in its prevention and saw clearly that more was involved in its etiology than economic status. It is not necessary to understand the etiology of a disease to treat it, and indeed, this was the case with rickets. Fish oils, especially cod-liver oil, were used successfully to treat rickets as early as the eighteenth century. Cod-liver oil might have been dismissed as a folk remedy lacking any scientific basis except that its use was legitimized by physicians both in Europe and Great Britain during the nineteenth century through their experience and writing. Nonetheless, use of cod-liver oil to treat rickets declined toward the end of the century and fell into disrepute [4, 5]. Hess [6] in his monograph on rickets has commented on this state of affairs. "It is a sad commentary on the fallibility of clinical medicine that a therapeutic action as well defined as that of cod liver oil could not be conclusively established by means of bedside observation carried out in many countries over a period of one hundred years, but that physicians had to await the proof of its specificity from non-clinical sources." At the beginning of this century, appropriate amounts of carbohydrate , protein, fat, and salts in a diet were thought to supply all that was needed for complete animal or human nutrition. The studies on which thisjudgment was based utilized natural foods. Studies in which animals were fed less complex sources of the major nutrients failed—with the animals either not growing or dying. Elmer McCollum, embarking on his first independent research project at the College of Agriculture of the University of Wisconsin, took note of these studies. His project was to examine the suitability of different foodstuffs of the same chemical composition for cow nutrition. Before coming to the University of Wisconsin in 1907, he had obtained a Ph.D. in...