12 
of various agents currently supposed to influence physiological oxida- 
tions. One of the first substances studied in this connection was 
alcohol. Although familiar with the view that alcohol dirninishes 
oxidation, I was led to the hypothesis that oxidation in this case would 
be increased. This reasoning was based on a consideration of the 
probable cause of tolerance for alcohol. It is rather striking that so 
little attention has been paid to this factor in alcoholism. Although 
tolerance is one of the most familiar facts m connection with alcohol, 
I could find no reference to it m a bibliography on alcohol covering 
several hundred pages. One of the few drugs studied from the stand- 
point of tolerance is morphine. Faust “ found that the establishment 
of tolerance for morpliine was accompanied b}^ an increased power on 
the part of the organism to destroy (oxidize) morphine, and he attrib- 
uted the tolerance to this power It seemed reasonable to suppose 
that the tolerance for alcohol is accompanied by a similar increased 
power on the part of the body to oxidize alcohol and it was but a fur- 
ther step to suppose that, if the body became increasingly capable of 
oxidizing alcohol, it would also oxidize alkyl groups in general, such 
as the methyl group, more readily. If this should occur with the 
methyl group of acetonitrile, then animals accustomed to alcohol 
should be especially susceptible to this nitrile. Such was found to 
be the case. Animals which had received for a few weeks or months 
small amounts of alcohol — amounts far too small to ever cause any 
indications of intoxication — succumbed to doses of acetonitrile which 
produced no symptoms in the controls which had received no alcohol. 
These seem to be the first experiments in which marked functional 
disturbances have been found in animals which may be compared to 
strictly moderate drinkers. The first series of these experiments 
were performed upon mice. 
EXPERIMENTS ON MICE. 
As w^as pointed out in a recent paper‘d the susceptibility of mice 
to acetonitrile varies very considerably; the age of the animal, the 
character of the food, the temperature and season, all seem to have 
an influence. Hence in order to obtain satisfactory results it is neces- 
sary to have many controls. In the following experiments great care 
was taken to keep the conditions as uniform as possible, and a num- 
ber of controls were made in every experiment. 
The alcohol was administered by soaking the food (usually oats) in 
it. There was probably some loss by evaporation; but this was les- 
sened by having the feeding cups narrow and deep. The strength of 
Arch, f. exper. Path. ii. PharmakoL, v. 44, p. 216; 1900. 
&Hausmann (Pfltiger’s Archiv*, 113, p. 337; 1906) has recently suggested that pos- 
sibly the form in which the morphine is excreted changes as the tolerance is established, 
so that the drug can no longer be detected by the usual methods. 
cHuntj Journ. Biol. Chem., vol. 1, p. 33; 1905. 
