BACTERIAL CELLULAR SUBSTANCE 51 



" (g) The immune serum of the rabbit exerts no protec- 

 tive action for the guinea-pig against the germ substance. 



"3. The immunity obtained by treating animals with 

 the germ substance is apparently of short duration, and 

 if the interval between the administration of doses be 

 prolonged, death is likely to follow even when there is no 

 increase in the dose. It will thus be seen that the attempt 

 to immunize animals to the germ substance of the colon 

 bacillus is beset with difficulties. If the intervals be too 

 short, and the animal has not fully recovered, death is 

 likely to result, and the same will also probably happen 

 when the interval is unduly long. Even after a marked 

 degree of immunity has been obtained, this is apparently 

 lost within a few weeks, and a repetition of a dose of the 

 same size causes death. The following table, showing next 

 to the last, and the last injections given to certain animals, 

 will illustrate our meaning: 



January 19, 1902, rabbit No. 17, 1780 grams, had 372.3 mg. (1 to 4780), 

 and recovered. 



March 29, 1902, rabbit No. 17, 1880 grams, had 273.5 mg. (1 to 5048), 

 and died March 31. 



January 18, 1902, rabbit No. 29, 2000 grams, had 293.3 mg. (1 to 6819), 

 and recovered. 



March 29, 1902, rabbit No. 29, 1880 grams, had 293.3 mg. (1 to 6409), 

 and died March 31. 



January 6, 1902, pig No. 93, 485 grams, had 28 mg. (1 to 17,329), and 

 recovered. 



March 29, 1902, pig No. 93, 645 grams, had 28 mg. (1 to 19,464), and 

 died March 31." 



Later these experiments were repeated and extended to 

 goats by V. C. Vaughan, Jr., and Gumming, with prac- 

 tically the same results. We concluded that the capability of 

 the animal to bear increased doses of the cellular substance 

 was not sufficiently marked to be designated by the term 

 immunity, and it was decided to recognize it as increased 

 tolerance. This opinion we still hold. 1 



1 It will be seen from this work as here recorded that we met with the 

 phenomena of protein sensitization or so-called anaphylaxis as early as 

 1902 in our studies on the bacterial cellular substances, but that we failed 

 to follow it up and indeed did not attach much importance to it. 



