312 THEOBALD SMITH'S PHENOMENON 



amount to produce so great an effect), and kept for a fortnight or 

 more. If then a second injection of a larger amount of the same 

 serum be made (J-y- c.c. or more, the usual testing dose being 5 c.c.), 

 the animal develops a series of remarkable symptoms, the most 

 noteworthy being respiratory failure, paralysis, and clonic spasms. 

 Symptoms usually appear within ten minutes, and death occurs 

 within an hour. Death does not always follow. The less sensitive 

 the animal, the later the development of symptoms (which in 

 highly sensitive animals come on within ten minutes), and the 

 greater the chance of survival. The process evidently affects the 

 nervous system in a very special way, and the heart may continue 

 to beat for an hour after death. In some cases, but not in all, 

 there are definite haemorrhagic lesions present ; they usually occur 

 in the stomach, less frequently in the caecum, lungs, spleen, 

 adrenals, or other parts. 



The phenomena had often been seen in the process of testing 

 diphtheria and other antitoxins for the presence of free toxin, in 

 which several cubic centimetres of the serum are injected intra- 

 peritoneally into guinea-pigs. Animals that have been previously 

 used for the standardization of the antitoxin are often employed, 

 and as these have received minute doses of the latter substance 

 they may be hypersensitive. The phenomenon is a familiar one, 

 but it is only recently that its true method of origin has been 

 apparent. It has no connection with the antitoxin as such, and 

 the same phenomena of hypersensitiveness may be produced by 

 means of egg-albumin. 



The action is to a certain extent a specific one. An animal 

 sensitized with horse serum is less susceptible to the serum of the 

 cow, pig, sheep, etc., than to that of the horse. It may show 

 symptoms after the injection of one of these heterologous sera, 

 but usually recovers. And the same is true for an animal sensi- 

 tized by small doses of another sera. Symptoms are not usually 

 produced by horse serum, and if they are, are not fatal. Animals 

 can be sensitized by feeding with horse serum or with horseflesh. 

 Rosenau and Anderson thought that children might be sensitized 

 in this way, and so develop toxic symptoms after the use of anti- 

 toxin, but abandoned the idea. 



Otto and Rosenau and Anderson thought that small doses were 

 necessary for the production of this form of hypersensitiveness, 

 large ones appearing to bring about immunity ; but Gay and 

 Southard show that large doses simply delay the incubation 



