Several distinguished authorities 17 have favored the hypothesis that rickets arises from deficiency of fat in the diet,17a a view which received support from the often-quoted work of Bland-Sutton on lion cubs in the zoological gardens,18 in which the addition of cod-liver oil, milk, and crushed bones to the ordinary diet of lean meat was found to protect the animals against rickets, and also from the well-recognized beneficial effect of cod-liver oil in the treatment of rickets.19 That the fat in itself is not the fundamental factor is clearly proved by the work of Mellanby,20 who has shown that different fats have very different values in this respect; of Osborne and Mendel21 and von Grocr,22 who have shown, that normal nutrition can be secured for a considerable time, at least, on diets almost devoid of fat; of Mackay and Tozer 22a who have studied the effect on kittens of a diet deficient in fats, and found no evidence of rickets, although the kittens became emaciated, ceased growing, and suffered from diarrhoea and abdominal distension; and of Shipley, Park, McCollum, Simmonds, and Parsons," who have demonstrated that cod-liver oil contains some substance or substances which cause the deposition of calcium in the bones in the same way in which it occurs in spontaneous healing of rachitis in man.

However this is disputed by Telfer (see reference on p. 177).

17 Holt, Dis. of Inf. and Child. 1907; Cheadle, Artific. Feeding and Food Disorders of Infants, 1906.

17a As a result of feeding experiments and clinical reports, it has been accepted that vitamin A is highly important for man, and that the lack of it leads to nutritional disorder in children. To study this question, five infants, ranging in age from 5 to 12 months, were given a diet complete except for a very small amount of vitamin A. It consisted of 180 g. daily of skimmed milk (0.2% fat), 90 g. cane sugar, 15 to 30 g. autolised yeast, 15 c. c. orange juice, 30 g. cottonseed oil, and cereal for the older infants. On this diet no detrimental effect was observed over a period of 8 to 9 months. These results suggest that either a very small amount of this vitamin suffices to supply the needs of human nutrition, or that this deficiency has to be maintained for a period of years to bring about harmful result. Infants fed on this diet did not develop signs of rickets. The disorder developed however in infants receiving large quantities of milk containing ample vitamin A. Hess and Unger,17b therefore, do not believe that rickets is brought about by the lack of this principle.

Golding, Drummond and Howard (Biochem, J. 15, 427, 1921) carried out experiments on rationing pigs with extracted dried milk, cream, purified caseino-gen and salt mixture. At the same time, feeding tests of a like nature were carried out except that autoclaved olive oil was substituted for cream. The results obtained do not offer any definite information on the relationship of fat-soluble A to the etiology of rickets.

17b Proc. Soc. Exptl. Biol. Med. 17, 49, 1919.

18 Quoted by Cheadle and Paynton, Allbut's Syst. of Med. 3, 85.

19 Hess and Unger, J. Am. Med. Assn. 1917, 1583. 20 Mcllanby, Lane. 1919, i, 407.

21 Osborne and Mendel, J. Biol. Chem. 45, 145, 1920.

22 Von Grocr, Bioch. Z. 97. 311, 1919.

22a Mackay and Tozer, Biochem. J. 25, 19, 28, 1921.

Defective hygienic conditions of various sorts, bad ventilation,24 insufficient lighting,25 and lack of exercise 26 have all been represented as responsible, and Hansemann27 has classed together all the unwholesome features of civilization under the comprehensive term " domestication " and regards the disease as the product of the combination. In this connection the observation of Hess and Unger27a that exposure to sunlight had a marked and curative effect on rickety children, is of interest.

Ferguson's statistical study of the social and economic factors in the causation of rickets28 indicates inadequate air and exercise as potent factors in determining the onset of rickets, and minimises the effect of diet. In this study the average number of persons per room was found to be almost one person greater in the rachitic than in the non-rachitic families, the cubic space per person was 32 per cent' less in families with cases of marked rickets than in families who were free from the disease, and the cleanliness of the house was distinctly better in the non-rachitic than in the rachitic family. Commenting on this investigation, Mellanby 29 says:

In the study of rickets in Glasgow made by Ferguson, analysis of the average diets of rachitic and non-rachitic families studied shows that in practically every case the diet of the rachitic families contained more of substances allowing rickets such as flour, potatoes, sugar, oatmeal, and less of antirachitic foods, such as milk, meat, fat, fish, eggs, and cheese. While the differences are not large, they probably indicate a very decided dietetic disadvantage to the children of the rachitic families.

23 Shipley, Park, McCollum, Simmonds and Parsons, J. Biol. Chem. 46, 343,1020.

24 Dudgeon, Rep. of the Soc. for Study of Dis. in Child, Vol. VIII, p. 56; Clement Lucas, Brit. Journ. of Child. Dis., Feb. 1908; Baser, Munch. Med. Woch. 818, 1907; Kaasowitx, Die Pathogenese der Rachitis. Wien. 1885.

25 Dieting, Deutsch. Med. Wochschr. 39, 552.

26 Findlay, Brit. Med. J. 1908, ii. 13; Paton, Findlay, and Watson, 76. 1918, ii. 625.

27 Hansemann, Berl. klin. Woch. 1906, Nos. 20 and 21.

27a Hess and Unger, J. Am. Med. Assoc. 77, 39, 1921.

28 Med. Res. Com. Spec. Rep. 20.

29 Mellanby, Lane. 1920, i. 856.

While admitting that poor surroundings and lack of exercise may be powerful predisposing factors, Mellanby refuses to consider these as direct causes. He points out that the diets used by Findlay (1. c.) were such as will eventually produce rickets regardless of other conditions.

The beneficial effect of freedom, he states, is what might be expected, as constant movement must raise the whole metabolic changes in the body and in the first place prevent or delay deposition of fat with its accessory A, and secondly bring into activity any antirachitic factor normally stored away and ineffective. Exercise therefore gives greater opportunity for any antirachitic factor in food or tissues of animals to play its part in the animal economy.

In a very extensive investigation involving the use of over 200 puppies30 Mellanby believes he has obtained conclusive evidence that rickets is caused by the lack of a specific antirachitic factor which is either identical with or similar to the vitamin A. In his experimental work he made use of four types of rachitic diets.

I. Whole milk, 175 cc, oatmeal, rice; salt, 1-2 g. II. " " " " bread, ad lib. III. Separator milk, 175 cc.; bread (70 per cent wheat) ad lib; linseed oil, 10 cc; yeast, 10 g.; salt, 1-2 g. IV. Separator milk, 250 to 350 cc.; bread (70 per cent wheat), ad lib.; linseed oil, 5 to 15 cc.; yeast, 5 to 10 g.; orange juice, 3 cc.; salt, 1-2 g.

Using diet I, he found that increasing the whole milk from 175 to 600 cc. per day prevents the development of rickets.

On diet II, meat, and also watery and alcoholic (80 per cent) extract of meat, had an inhibiting effect. On the other hand, the protein residue after loss of the extractives allows rickets to develop. Yeast extract or yeast had no protective influence. Malt extract had some inhibiting action and delayed the onset of rickets when added to diet II.