In 1911 Osborne and Mendel1 published the first results of a prolonged series of valuable contributions to the knowledge of growth. These authors found that if a single protein, like casein, were added to a diet made up of starch, lard, agar, and "protein-free milk," such a diet became adequate for the growth of rats during the first two months of their lives. This is because it contains "water-soluble" vitamins. The "protein-free milk" contains 0.7 per cent, of nitrogen, 80 per cent, of lactose, and 15 per cent, of inorganic salts, and Osborne and Mendel2 estimate that 2.2 per cent, of milk protein is present. This makes 0.6 per cent, of the weight of the whole diet, or 3 per cent, of the total quantity of protein ingested when an isolated protein, like casein, is added to the food in such measure as to make the diet contain 18 per cent, of casein. In later work Osborne and Mendel state that the "protein-free milk" introduces protein only to the extent of 0.13 per cent, of the food given.

Hopkins8 showed that a synthetic food, consisting of protein, carbohydrate, lard, and the proper salts, became an entirely satisfactory diet for growing rats if only 2 c.c. of milk were given also. The milk was administered before the rest of the diet in order to prove that it was not a lack of palatability in the synthetic food which was the cause of the failure of the rats to grow. Hopkins also made the very significant discovery that an alcoholic extract of milk solids or of yeast, when added to the synthetic diet "in astonishingly small amounts," caused normal growth. Though the synthetic diet contained plenty of calories (see p. 414) growth took place only when the accessory substances were administered.

1Osborne and Mendel: "Feeding Experiments with Isolated Food-substances, Parts I and II," Carnegie Institution, 1911, Publication 156.

2 Osborne and Mendel: "Zeitschrift fur physiologische Chemie," 1912, lxxx, 316.

3 Hopkins, F. G.: "Journal of Physiology," 1912, xliv, 425.

McCollum and Davis1 reported that, although young rats grew for sixty or ninety days on such diets as have been described, yet after this time growth suddenly stopped. It could be re-established if butter fat or the ether extract of egg-yolk was added to the diet. Apparently, the organism runs out of some organic complex which is indispensible to normal growth and without which maintenance in good condition is impossible.

Osborne and Mendel2 independently reached the same results. There was a primary growth when a synthetic diet which included lard and "protein-free milk" was given, followed by failure to grow. If the lard were replaced by butter or egg-yolk or cod-liver oil, growth was resumed, but almond oil was inefficient in this regard. In connection with the high efficacy of cod-liver oil in promoting growth, Osborne and Mendel refer to its "popular yet inexplicable reputation for unique nutritive potency." Beef fat was found to be more valuable than lard.

McCollum and Davis3 show that olive oil and cotton-seed oil, like almond oil and lard, cannot be used to foster growth, whereas the fat of cod testicle and pig's kidney are very efficient. Curiously enough, the fat of the pig's heart is not of value in producing growth. Animal fats and especially milk fats have, therefore, nutrient virtues not expressed in calories.

1 McCollum and Davis: "Journal of Biological Chemistry," 1913, xv, 167. 2 Osborne and Mendel: Loc. cit., 1913, xv, 311; xvi, 423; 1914, xvii, 401. 3 McCollum and Davis: Loc. cit., 1914, xix, 245; 1915, xx, 641; xxi, 179.

McCollum and Davis1 have given to rats a standard diet without any fat in it and have brought them after twenty to twenty-five weeks to the threshold of death. Then on giving the standard diet with an equal quantity of different grains the following results were observed:

The authors remark that such results illustrate the paucity of our knowledge regarding the special nutritive value of the common cereals.

Finally McCollum and Davis2 describe how, if casein be dialyzed against water and acetic acid so that all the salts are washed out, this product when given with butter, dextrin, and salts causes no growth in rats.

For a more complete discussion the reader is referred to other sources.3 One may, however, summarize the work upon the influence which the ingestion of purified food-stuffs has upon growth, as follows:

* Water or alcohol extract of peas, rice polishings, wheat, yeast, or "protein-free milk," which are able to cure polyneuritis in a pigeon in a few hours.

1 McCollum and Davis: "Journal of Biological Chemistry," 1915, xxi, 179. 2 McCollum and Davis: Ibid., 1915, xxiii, 231.

3Mendel: "Journal of the American Medical Association," 1915, lxiv, 1539; McCollum: "New York Medical Journal," 1916, ciii, 838.

The value of the water-soluble and the fat-soluble vitamins is apparent.

Since the purified protein may be given free from phosphorus without prejudice to the capacity to grow, it is evident that an animal, when fed with a diet of pure protein, carbohydrate, fat, and simple inorganic salts, may produce synthetically lecithin, phosphatids, nuclear material (purins, etc.), hemoglobin, and bone-tissue. McCollum states that he has never seen growth enhanced by the addition of organic phosphorus to a diet. Certain amino-acids, however, must be furnished preformed. Mendel and Osborne and McCollum and Davis are in essential accord with regard to these underlying principles, and science owes them much for their laborious and painstaking contributions to this long obscure chapter of dietetics.