314 THEOBALD SMITH'S PHENOMENON 



appears to be to make the fatty constituents of the cells flow 

 rapidly together. This occurs especially in the endothelium of 

 the capillaries, and leads to haemorrhages. 



This can hardly be regarded as a full explanation, and fails, 

 moreover, to explain a most remarkable fact discovered by 

 Besredka : that sensitized animals do not react to the injection of 

 horse serum if previously anaesthetized with ether. No theory 

 that has yet been suggested will explain all the extraordinary 

 phenomena connected with this subject, and no good purpose 

 would be served by discussing others that have been brought 

 forward. We seem to be on the eve of a series of discoveries 

 that may prove to have as great an effect on our ideas of immunity 

 and cell nutrition as the discovery of the antibodies themselves, 

 and until the facts are better known hypotheses seem out of 

 place. 



We may, however, be permitted to point out that it is quite 

 possible that the tuberculin reaction may be a phenomenon of 

 exactly the same order as the serum anaphylaxis of the guinea-pig. 

 Tuberculin is in itself non-toxic for a normal animal, just as is 

 serum, but we may imagine that the tubercle bacilli in the lesions 

 produce it in small amounts until the animal becomes anaphy- 

 lactized, in which case it will react violently to a small injection. 

 The wasting and fever which accompany the evolution of the 

 disease may be phenomena akin to the phenomenon of Arthus, 

 and simply indicate the reaction of a hypersensitive animal to 

 repeated small doses of a non-toxic substance. If this is the case 

 we may regard tuberculin as being, after all, the true toxin of the 

 disease, though non-toxic to animals unless the processes of tissue 

 nutrition and metabolism have been profoundly modified by the 

 prolonged action of minute amounts of the same substance. That 

 a reaction does not occur in a normal person after two injections 

 of tuberculin does not surprise us, for the active principle is (as 

 shown by the fact that it dialyzes) of small molecule, and may be 

 eliminated more quickly than the large-moleculed toxic ingredient 

 of horse serum, so that for hypersensitiveness to occur it may be 

 necessary to have a continued stream of minute amounts from a 

 lesion in the tissues. It may be pointed out, however, that occa- 

 sionally a local reaction may be seen round the spots at which 

 tuberculin has been previously injected, suggesting that the tissues 

 in this region may be anaphylactic. 



There appears to be no connection between this phenomenon of 



