This section is from the book "The Newer Knowledge Of Nutrition", by Elmer Verner McCollum. Also available from Amazon: The Newer Knowledge of Nutrition: The Use of Food for the Preservation of Vitality and Health.
Simple as the discussion of the adequate diet appears to be in the present state of our knowledge, it was a most difficult task to bring order and understanding into the field of nutrition. In experiments with the rat using simplified and purified food substances such as were necessary for solving the problems of what constitutes the simplest adequate diet, the difficulty in succeeding was much greater than one would at first thought suppose. The small prospect of success will be better appreciated when it is realized that there were, for the nutrition of the rat, two indispensable dietary factors whose existence were hardly more than suspected by students before that time. These were the anti-ophthalmic and anti-neuritic substances, fat-soluble A and water-soluble B, respectively. In addition there were three variable factors whose importance was appreciated in a general way, but for which no satisfactory standards had been established. These related especially to the quality of the protein, the concentration of the several mineral elements essential to normal nutrition, especially calcium and phosphorus, but also in an important degree to the content of sodium and chlorin in the diets. Any one or more of these factors might easily be so constituted as to determine the failure or success of an experiment. If the purified protein happened to be of relatively poor quality, the amount of it included in the diet might easily be too scanty to support growth, yet it would be impossible except through the conduct of a considerable number of experiments, to gain a satisfactory insight into this matter. If, in deciding on the amount of calcium to introduce into an experimental diet, it was assumed that a cereal, such as wheat, probably contained a proper amount to meet the nutritive needs of an animal, this error would have foredoomed the resulting growth experiment to failure, even if an abundance of protein of good quality, and vitamins in liberal amounts were supplied, and satisfactory adjustment of every other constituent of the food was by good fortune realized. A similar statement may also be made regarding phosphorus, but the shortage of this element is not so serious in most vegetable or animal foods, and if the investigator was guided by the content of phosphorus in ordinary cereals in arriving at a decision as to how much of this element to include, a less serious error was likely to be made. Even the failure to add a sufficient amount of common salt would have been disastrous to such experiments as we are discussing, the object of which was to find just what elements and complexes are indispensable in a diet, and to prepare the simplest possible food mixture which could support growth and normal well-being. Such studies required much time and labor in the preparation of carefully purified substances, and failure in a considerable number of attempts would be expected to lead to discouragement and cessation of effort to solve such a problem since the chances of success would seem so remote.
When it is appreciated that there was no other possible method of attacking the solution of this problem than the conduct of a series of feeding experiments with simplified diets, and the interpretation of the results on the basis of whether the animals in numerous groups grew or failed to grow, it will be conceded that the prospects of succeeding in arriving at an understanding of the essentials and non-essentials of an adequate diet were very remote. By good fortune, however, this problem was successfully solved in its broad outlines, and further detailed researches can now be undertaken with definite aims and the guidance of an adequate theory.
 
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