McCollum27 regards xerophthalmia as a true deficiency disease specifically due to a lack of A. His view is confirmed by Bmmett28 who reports that out of 122 rats in a group fed on a diet in which A was lacking, 120 (98.3 per cent) showed positive signs of xerophthalmia sooner or later, and when A was present, with or without B, none of the 319 rats under observation showed evidence of this trouble. All the rats were fed individually in practically every case. They were kept in metal cages without any bedding, provided with a special removable wire screen floor. The cages and the food and water cups were always disinfected once or twice a week. The conditions were precisely the same for all the rats and the possibilities of infection were uniform.

Osborne and Mendel29 have reviewed the statistics on 1000 rats from their own stock to which no animals have been admitted from extraneous sources for several years.

All of these animals have been under study for at least a year. They are kept in the same laboratory under conditions which are identical except as to diet. Their cages are sterilized twice a week, but the rats are regularly weighed in a common container, and it is stated that the proximity of the open-mesh wire cages to one another offered sufficient opportunity for dissemination of contagion. Nevertheless, in observations on several thousands of rats they have never observed the distinctive symptoms of eye disease in any animals except those suffering from deficiency of A. The results for the particular group under consideration are summed up as follows:

In only a few cases did administration of A fail to effect a cure. In a number of cases a dosage of 100 mg. of butter-fat per day effected a cure within a week, and in others 42 mg. of grass oil per day relieved the symptoms within 10 days, 70 mg. of alfalfa oil within seven days, and 66 rag. of spinach oil within 21 days. They point out that the xerophthalmia is rare in more mature animals even on diets free from A. Freiae, Goldschinidt and Frank (1. c.) could not observe it in rats which weighed more than 130 g. when the experiments started. Osborne and Mendel, however, have occasionally observed it even in large animals.

27 McCollum and Simmonds, J. Biol. Chem. 32, 182, 1917; McCollum, Simmonds, and Parsons, 76. 38, 124, 1919. 28 Bmmett, Sci. 52, 157, 1920. 29 Osborne and Mendel, J. Am. Med. Ass. 76, 905, 1921.

McColIum30 emphasizes one point which may help to explain some of the apparently contradictory results of different observers; namely, that an amount of A which is amply sufficient when the diet is otherwise well constituted will prove inadequate in other cases where the quality of one or another factor is of a low order. In the case of animals on a diet consisting principally of seed products it has been found that xerophthalmia develops unless additional A is supplied. If, however, the seed ration is supplemented by additional protein and inorganic salts, in both of which seeds are deficient, the animals may withstand the onset of xerophthalmia for a long time, even though no supplementary A is given, whereas if the deficiency is made up in respect to one factor only, for instance inorganic salts, the combined effects of lack of two factors simultaneously (in this case protein and A) will hasten the onset of xerophthalmia.

Fig. 20. - This child was fed on skimmed milk and as a result an ulcer developed on one eyeball. The remedy is the use of plenty of cream, butter or cod liver oil.

Courtesy of the Connecticut Agrciultural Experiment Station (Bulletin 215, Photograph from Bloch).

30 McColIum, "Newer Knowledge of Nutrition," p. 87; McColIum and Simmonda, J. Biol. Chem. 32, 347, 1917.

When judging the effects of the diet on an animal, McCollum advocates the precaution to take into account the fact that the diet is a complex thing, and that if it is properly constituted with respect to all factors but one an animal may tolerate it without apparent injury whether the fault lies in one or another of the essential components. Hence the value of one component may fall well below that which will lead to serious malnutrition, when a second dietary factor is likewise inadequate.

The suggestion has been made occasionally that "night blindness " is a deficiency disease occurring in adults but related to the xerophthalmia of children and animals on a diet deficient in A. The observation that mature animals are very little susceptible to eye trouble as a result of such deficiency would cast some doubt on this theory. More convincing, however, are the observations made by Appleton in the course of a study of the diet in Labrador,31 from which the conclusion is reached that night blindness is a negative after-image following long exposure to the dazzling glare of sun on snow. A poor diet may increase the probability of seeing after-images just as fatigue does. The disease occurs almost exclusively among men in Labrador, and yields readily to any treatment. Only two cases could be found to have occurred among women.

31 Appleton, J. Home Ec. 13, 199, 1921.