SUBSTRATES OF GROWTH 489 



Internal Secretions are synthesized are dietary constituents of this 

 essential type, for example the Iminazolyl-grouping, which in all 

 probability forms an essential constituent of the active principles of 

 both lobes of the pituitary body, the Catechol-grouping which is an 

 essential complement of the molecule of Adrenalin, and the Indole 

 radical which, from the observations of Kendall, would appear to be a 

 component of the active principle of the thyroid, are examples which 

 will serve to illustrate the essential importance of specific molecular 

 groupings or arrangements of atoms, which, if not synthesizable by 

 animal tissues, must necessarily form a part of the diet in order to 

 maintain bodily equilibrium; and to a still greater extent, of course, in 

 order to render normal growth a possibility. 



The Vitamines, which appear to be nitrogenous substances closely 

 related to the Purines, are dietary constituents of this type. They are 

 essential for growth, and even for the maintenance of bodily equi- 

 librium, yet the amount required to maintain the weight of the body 

 or to permit satisfactory growth is extremely minute. They evidently 

 represent a group of non-synthesizable essential constituents of living 

 matter which would appear not to be excessively complicated in struc- 

 ture since they are usually obtainable in crystalline form and their 

 relationship to the pyrimidines and the purines has frequently been 

 established. 



Then, again, there are fatty constituents or substances soluble in 

 Fats which are probably of a more complex character and which 

 are equally essential elements of a complex dietary. According to the 

 older view of metabolism, fats and carbohydrates were considered to be 

 mutually replaceable in the dietary in isodynamic, i. e., equicalorific 

 proportions. Provided the fats in the dietary be not too greatly dimin- 

 ished this is still recognized to be true, but it has now been repeatedly 

 shown that development and maintenance upon an absolutely fat-free 

 diet is impossible, no matter what excess of carbohydrate may be 

 furnished and, furthermore, that Vegetable Oils do not supply this 

 deficiency. According to McCollum the essential constituents of the 

 diet, in addition to the requisite mineral salts, amino-acids and calorific 

 value in the form of fats or carbohydrates, fall into two groups, of which 

 one is soluble in water, while the other is insoluble in water and is 

 soluble in fats and in fat-solvents such as ether. It is immaterial from 

 what source these constituents may be derived; provided merely that 

 they are both present and the diet conforms to the other requirements 

 outlined it will suffice to maintain life and permit growth. These 

 substances have been provisionally designated by McCollum "Fat- 

 soluble A" and "Water-soluble B"; we are as yet ignorant of their 

 structure or affinities. But from their essentiality for growth, and 

 even maintenance for any prolonged period, we may infer that they are 

 Substrates or raw materials which are required in the manufacture of 

 living tissue and cannot be synthesized by the tissues themselves. 



The clearest indication of the dependence of tissue-synthesis upon the 



