taking the least amount which will stop the heart which will usually 
occur anywhere between thirty-five and one hundred minutes (Zie- 
genbein says within two hours), while the latter takes as his end 
reaction the stoppage in from fifty to seventy minutes. Focke, 
therefore, prefers his method because it is more convenient, taking 
less time and because it is more exact, showing according to him only 
8 per cent of error. 
After Focke developed this method he considered a number of 
factors which influence the results of standardization and the varia- 
bility of digitalis preparations. In order to determine the effect of 
season upon the frog’s susceptibility, he examined leaves which had 
been very carefully dried and which would retain the same value at 
the various times of the year. He found that in the spring they 
gave an average value of 2.66; from the end of June to October, 4.36; 
and in October, 5. At this time he considered these variations due 
to differences in the nutrition of the frogs, but later researches® 
seemed to indicate that the temperature factor might also play 
some part in changing the V obtained. 
Thus frogs operated on at a temperature of 17.5° to 18.5° in De- 
cember showed a V of 5.5. At the same temperature the same drug 
had a Y of only 4.7 the last of February, but at 19° to 21° gave 
nearly the original value. In June, to obtain this value, it was nec- 
essary to increase the temperature to from 22° to 23°, at 18.5°, the 
original December temperature, the value being only 3.8. At the 
same temperatures there seemed to be no difference in the reaction 
of frogs which had been captured recently and those kept in captivity 
for several months. 
Physiological standardization may be carried out according to 
Focke, therefore, at any time during the year, but it is first neces- 
sary to standardize the animal against digitalis leaves of known 
value by regulating the temperature and then by cooling or heating 
the operating room to carry out the assay at the temperature found 
to show the standard value as arbitrarily adopted. 
It has been recognized that wild plants are more toxic than cul- 
tivated, and in confirmation of this view Focke found the former to 
give a Y of from 5 to 6, while the latter gave as Ys 2.6 and 3. The 
yearly variation in plants from the same district he found to be 
quite marked, the weakest giving a value of 4.3, while the strongest 
had a Y of 8.5. It has been universally recognized also that the 
second-year plants just before flowering are more active than the 
first year. In agreement with this view Focke found that the second- 
year leaves collected in June have a toxic value 15 to 20 per cent 
higher than first-year leaves collected from plants grown in the 
same locality. Plants flowering in July seed in August, and at this 
a Focke, Arch. d. Pharm., 1907, CCXLV, 646. 
