1908.] © Diphtheria Antitoxin. 411 
_ (a) From a study of the lesions produced by diphtheria toxin, it is clear 
that the main tissues attacked by this poison are the heart and nervous 
system. Therefore, on Ehrlich’s theory, these tissues are mainly concerned 
in the production of antitoxin. From a general consideration of the metabolism 
of an animal it is improbable that two master tissues as the heart and nervous 
system are responsible for the protection of it. A horse had been immunised 
against diphtheria toxin for five years. At the end of this time it was killed, 
although it was suffering from no obvious disease. During its antitoxic life 
it had produced about 200 litres of antitoxic serum, containing, on an average, 
500 units of antitoxin in each cubic centimetre, and had been injected with 
an appropriate amount of diphtheria toxin. A detailed post-mortem examina- 
tion of the various organs was made. There were no marked pathological 
changes to be noted—the heart showed a little brown atrophy, but no changes 
were found in the nervous system. It is inconceivable that the heart. and 
nervous system could have been attacked by such enormous quantities of 
toxin and have produced such a large amount of antitoxin without being 
more seriously affected. 
A consideration of the amount of antitoxin produced by a horse after the 
injection of a definite quantity of diphtheria toxin is of interest. During a 
period of four weeks 800 priifungs doses of toxin were subcutaneously injected 
into ahorse. At the end of that time the blood contained 400 units of anti- 
toxin per cubic centimetre. Suppose the horse contained 50 litres of blood. 
At the end of four weeks the blood of the animal contained 1000 x 400 x 50 
= 2,000,000 units of antitoxin, or 800 priifungs doses of toxin produced 
2,000,000 units of antitoxin; or each prtifungs dose of toxin produced 
25,000 units of antitoxin. 
If this be interpreted in terms of Ehrlich’s hypothesis, it means that when 
the side chain of a cell is attacked by a molecule of toxin it manufactures 
more than 25,000 new side chains to protect itself. And if Ehrlich’s hypo- 
thesis be correct, the cells which are concerned in this extraordinary 
production are contained in those tissues which perform the main functions 
of the body—namely, in the heart and nervous system. 
(6) The production of antitoxin in a tissue remote from the site of injection 
of the toxin demands the assumption of other specialised mechanisms. 
Let us consider the case of a horse towards the end of its immunisation 
period. At the last injection, probably, an amount of toxin containing 
200 priifungs doses is injected, and at this stage the blood of the animal 
contains 400 units of antitoxin in each cubic centimetre. This toxin, before 
it can produce any effect, must travel in the lymph stream to the thoracic 
duct, and so wd the jugular vein into the general circulation. When once in 
VOL. LXXX.—B. 2K 
