646 



SCIENCE 



[N. S. Vol. XXVII. No. 695 



"When a foreign proteid is injected into 

 an animal and a certain interval of time 

 is allowed to elapse, a second injection of 

 the same proteid is likely to cause the 

 development of untoward symptoms and 

 possibly death in a short time. These 

 symptoms are exactly those which I have 

 described as being due to the free poison, 

 and I can see no reason for doubting that 

 they are due to the same poison which is 

 set free in the animal body by a cleavage 

 process giving analogous but much more 

 perfect results than those obtained by the 

 action of alkali and alcohol in the retort. 

 With some proteids, the first or sensitizing 

 dose need not be the unbroken proteid, but 

 its non-poisonous or haptophoi-e group. 

 For instance, the haptophore group of the 

 egg-white molecule sensitizes to unbroken 

 egg-white quite as well as the unbroken 

 molecule itself does. If the proteid of the 

 colon or typhoid bacilli be split into hapto- 

 phore and toxophore groups and animals 

 be sensitized with the former, such animals 

 wiU bear several times the ordinarily fatal 

 dose of the homologous living bacillus. An 

 animal sensitized with the haptophore 

 group of a dead proteid dies on the subse- 

 quent injection of the same proteid in un- 

 broken form, provided that the time in- 

 terval between these injections has been a 

 certain minimum or greater, this minimum 

 varying with different proteids. An ani- 

 mal sensitized with the haptophore group 

 of the colon or typhoid bacillus survives a 

 subsequent inoculation with the living 

 homologous bacillus. These results have 

 struck observers as being antipodal and so 

 they may seem, when in one instance death 

 results in an animal apparently perfectly 

 normal and, in the other, an animal treated 

 with a fatal dose of toxicogenic bacterium 

 remains unaffected. The animal that has 

 been previously treated with the egg-white 

 haptophore is said to be in a state of hyper- 

 susceptibility or in an anaphylactic state 



(without protection), while the one that 

 has received the bacterial haptophore is 

 said to be immune. Tet, a close study of 

 these two sets of phenomena will, I think, 

 convince any one that the apparently antip- 

 odal are in reality identical. In both the 

 process is certainly identical and consists 

 in the cleavage of the molecule of the for- 

 eign proteid and the liberation of the toxo- 

 phore group. How has the one animal been 

 sensitized or brought into this state of hy- 

 persusceptibility and how has the other 

 been immunized ? Both of these conditions 

 have been brought about in the same man- 

 ner ; indeed the processes are identical. In 

 both there has been developed in certain 

 cells in the animal body a specific zymogen, 

 which on the second treatment is converted 

 into a proteolytic ferment, and this splits 

 up the proteid into its poisonous and non- 

 poisonous groups. The animal treated with 

 the second injection of egg white is not 

 killed unless the proteid given is sufficient 

 in quantity to yield a fatal dose of the 

 toxophore when it is split up, and the ani- 

 mal immunized to the typhoid bacillus is 

 certainly killed if the inoculated bacilli be 

 sufficiently numerous to yield a fatal quan- 

 tity of the toxophore when their proteid 

 substance is split up. Ordinarily more 

 than a fatal dose of the dead proteid is 

 administered at the second treatment and 

 the animal promptly dies. What we call 

 the minimum fatal dose of a bacterial cul- 

 ture does not contain enough toxophore to 

 kill the animal, even without any acquired 

 immunity, but it develops that amount 

 during what we call the period of incuba- 

 tion, which in guinea-pigs inoculated with 

 colon or typhoid bacilli means generally 

 from ten to twelve hours. Now, it must 

 be evident that if the proteid substance of 

 the injected bacilli be split up before the 

 living organisms have time to develop a 

 fatal amount of the toxophore, the animal 

 does not succumb to the inoculation and 



