17 
to determine whether the immunity was transmitted to the second 
generation (grandchildren). The results are given below: 
Guinea pig Xo. 6ac. Given 0.22 c. c. toxine Xo. 7 — 1 immunity unit Ehrlich. 
15. VI .06. Died in 3 days 14 hours. Control died in 3 days 17 hours. 
Guinea pig Xo. 6hc. Given 0.22 c. c. toxine Xo. 7 — 1 immunity unit Ehrlich 
15. VI .06. Died in 3 days 20 hours. Control died in 3 days 14 hours. 
Guinea pig Xo. 6ae. Given 0.22 c. c. toxine Xo. 7 + 1 immunity unit Ehrlich 
15. VI. 06. Died in 4 days 4 hours. Control died in 3 days 17 hours. 
Guinea pig Xo. 6be. Given 0.22 c. c. toxine Xo. 7 + 1 immunity unit Ehrlich 
15. VI .06. Died in 3 days 17 hours. Control died in 3 days 14 dours. 
From the above it seems plain that the resistance to diphtheria toxine 
is not transmitted to the second generation. 
THE CUMULATIVE EFFECT OF DIPHTHERIA TOXIXE. 
An attempt was made to immunize female guinea pigs by repeated 
small injections of diphtheria toxine. Doses considerably less than 
the AILD and not sufficient to cause a perceptible reaction were given 
at intervals of about 7 days. Before an amount equal to an AILD 
had been given the animal in each case died. These results are in 
exact accord with the work of Behring and Kitashima,® who found 
that guinea pigs, when given daily injections of diphtheria toxine 
and when the total amount injected was only 4 ^ of an AILD, after a 
time died with the post-mortem lesions of poisoning from diphtheria 
toxine. Instead of being able to produce an immunity to the toxine a 
hypersusceptibility was produced. 
A study of Tables 1 and 2 will show that in no case in which the 
preliminary treatment of the mother was of toxine alone was there 'an 
immunity transmitted by the mother to her young. This at first 
seemed to me a remarkable fact. I conceive the reason of the failure 
far this immunity to be transmitted by pigs whose preliminary treat- 
ment was toxine alone to be due to the fact that the mother pig was 
not immunized by a single dose of toxine, and that it is difficult to 
produce an active immunity in guinea pigs by the repeated injections 
of toxine, for before this result is obtained the cumulative efi'ect of the 
toxine kills the animal. 
It seems to me that instead of calling it a hypersusceptibility to the 
poison, as did Behring and Kitashima, it would be more proper to con- 
sider this action due to the cumulative effect of repeated small doses 
of the toxine. 
It is well known among clinicians that one attack of diphtheria, 
rheumatism, or pneumonia predisposes to a subsequent one. This 
may more properly be considered due to an induced hypersuscepti- 
bility, whereas the repeated injections of toxine, as in the case of the 
guinea pigs, is a cumulative action. 
« Von Behring and Kitashima: Eber Verminderung und Steigerung der ererbten 
Gift empfindlichkeit. Berl: klin. Woch., 1901, p. 157. 
