There is an important distinction between the effects of a single excessive dose of alcohol, and those produced by immoderate quantities frequently repeated, even though these quantities may be, and usually are, smaller than the single dose which gives rise to intoxication. From the single excessive dose proceed intoxication-effects which, as will be shown later on, are mainly apparent in disturbance of the functions of the brain; but when the alcohol is eliminated from the system these symptoms disappear, and the subject soon returns to his normal state. It is quite otherwise with chronic alcoholism. In this there are changes of the drinker's tissues which persist long after all the alcohol has been eliminated, and which may be, and often are, permanent in character. Moreover, these changes are not limited to the nervous centres, but in one way or another may affect most of the organs of the body. They are complex changes, only partially the direct effect of alcohol. Largely they are brought about through its detrimental action on the lining membrane of the stomach and bowel, causing chronic catarrh and failure in the action of the digestive secretions, and so promoting the absorption from the alimentary canal of digestive and microbial toxins, which in healthy conditions of the mucous membrane would be formed in lesser amount, or not at all, and in any case would not pass so freely into the system.

It is, indeed, a question whether many of the morbid changes which occur in other organs in the course of chronic alcoholism may not really be secondary to these local disorders in the gastrointestinal tract. In some recent experimental inquiries it has been found that when alcohol was administered to guinea-pigs by inhalation, instead of by the mouth, no visible alterations were produced in the animal's tissues, even when the intoxication was kept up for periods as long as three years.2

There are two essential factors in the causation of chronic

1 Loc. cit., p. 90.

2 Stockard, Amer. Naturalist, 1913, 47; Proc. Soc. Exp. Biol. Med., 1914, 11.

M M alcoholism. First, the drug must be taken in sufficient quantity to exercise an injurious action on the tissues; and secondly, that action must be more or less continuous. Excess of dose alone, without continuity of action, does not give rise to persistent tissue changes: an isolated bout of intoxication does not leave lasting after-effects. On the other hand, chronic poisoning is not induced by even the regular use of alcoholic beverages so long as only moderate quantities are taken. As to how much alcohol there must be in the blood, and how long its action must be kept up, in order to exercise a detrimental effect on the vitality of the tissues, nothing very definite can be said. The available data are insufficient, or are not exact enough, to justify more than the foregoing general statement.

Different individuals show wide variations of susceptibility to the injurious effects of alcohol in chronic alcoholism. Moreover, they differ also very widely as regards the tissues or organs most prone to suffer. In one subject the liver may be specially attacked, in another the nervous system, and so on.