Part III* 
THE TOXIC ACTION BEARS NO RELATION TO DIPHTHERIA. 
THE POISON IS NOT TOXONE. 
It occurred to us that possibly diphtheria antitoxic serum may con- 
tain free toxone which, when injected into a “used” or “treated” 
guinea pig, might produce acute effects upon the nervous system of 
such a pig, which, on account of the previous effects of diphtheria 
toxine, had been rendered peculiarly susceptible. It is well known 
that the toxone does not cause the acute death of a guinea pig, but 
only produces a local edema and late paralysis. This fact, first dem- 
onstrated by Ehrlich, may readily be demonstrated by inoculating 
guinea pigs with toxine and antitoxin mixed in such proportions so 
that the toxine is but partly neutralized. We were further led to 
believe that the poisonous effects of horse serum upon a treated guinea 
pig might be a manifestation of the toxones because the symptoms so 
plainly point to the nervous system. The pigs almost invariably 
show* paresis or paralysis. 
The fact that neither toxone nor any other constituent in the toxine 
plays any role in the poisonous action of horse serum is demonstrated 
in the following experiment : 
G. P. No. 4161. 0.1 c. c. toxine No. 15 (MLD = .01) was injected into the peritoneal cavity. 
No symptoms. Completely paralyzed at the time, resulting from previous treatment. 
[Previous treatment: 31 days previously inoculated subcutaneously with 0.22 c. c. 
toxine No. T+o-jq c. c. diphtheria antitoxic serum (Mulford’s No. 942).] 
One hour 50 min. later this same pig was inoculated with 6 c. c. diphtheria antitoxic 
serum (P. D. & Co. No. 08022) into the peritoneal cavity. Death in 10 minutes. 
It is well known that overpowering doses of toxine injected either 
subcutaneous!}^ or into the peritoneal cavity of a guinea pig require 
about twenty hours to kill the animal. These large doses of toxine 
do not cause immediate symptoms. 
It occurred to us, however, that while toxine alone may not have 
this power, nevertheless when it is mixed with antitoxic horse serum 
and when large doses of the mixture are injected into a guinea pig 
there may be a sufficient liberation of toxone or other poisonous 
substances capable of producing symptoms and sudden death. 
28337— No. 29—06 2 (17) 
