July 28, 1916] 



SCIENCE 



121 



bacilli go on increasing in numbers, and 

 although the animal may live for a consid- 

 erable period, the typhoid organisms per- 

 sist in his blood; he has become, in other 

 words, a permanent carrier. In perfectly 

 protected rabbits the bacilli disappear from 

 the circulation within a few hours. It in- 

 terested us to trace the method by which 

 the bacteria disappear in the protected 

 animals, and we found that coincidentally 

 with the disappearance of the infecting 

 bacteria there occurs a sharp rise in the 

 number of white blood cells in the periph- 

 eral circulation. These white cells, leuco- 

 cytes, or phagocytes, as they are called, are 

 known through the work of Metchnikoff and 

 others to be associated with defense of the 

 body against invading bacteria. This leuco- 

 cytic crisis, then, would seem reasonably to 

 be associated with protection in these immu- 

 nized animals. A moderate grade of leuco- 

 cytosis occurs in the normal unprotected 

 animal, but is apparently insufficient for the 

 purpose. In tracing further the cause of 

 the extreme grade of leucocytosis in the 

 immunized animal, we found it to occur 

 only under specific conditions, that is, only 

 when typhoid bacilli are injected in typhoid 

 immune animals, and not when typhoid 

 bacilli are introduced in normal animals, 

 or other bacteria in our immunized animals. 

 It seemed reasonable, then, to think it might 

 be due to the action of the specific immune 

 bodies which circulate in immune animals 

 and are known to increase phagocytosis by 

 their action on the bacteria with which they 

 unite and which they render more attrac- 

 tive to the leucocytes. This hypothesis we 

 were able to verify by injecting bacteria 

 that had been previously treated with 

 typhoid-immune serum into the circulation 

 of normal animals. The same phenomenon 

 of specific hyper leucocytosis also occurred 

 under these conditions. 



Since this hyperleucocytosis is coincident 



with, and apparently the cause of, the 

 body's ridding itself of bacteria, it seemed 

 possible that the artificial production of it 

 in typhoid fever might cure or beneficially 

 affect this condition, which is so character- 

 istically accompanied by a proliferation of 

 bacteria in the blood stream. "We tried out 

 this possibility in our carrier rabbits, those 

 animals in which we had produced a septi- 

 cemia by injecting living typhoid bacilli. 

 In some cases we cured these animals of 

 their septicemia, and then after testing the 

 harmlessness of large doses of our sensitized 

 vaccine in rabbits and monkeys, even when 

 injected directly into the blood stream, 

 looked forward to a cautious adaptation of 

 our results in cases of human typhoid fever. 

 It was nearly a year before we had an 

 opportunity to try this method on human 

 beings. In the meantime the results of 

 other writers in essentially the same direc- 

 tion came to our attention, and further en- 

 couraged our hope in the proposed method. 

 It will be necessary at this point to go back 

 a step and consider preceding work that had 

 been done in attempts at a specific cure in 

 typhoid fever, that is to say, a cure at- 

 tempted in full recognition of the cause of 

 this disease, namely, the typhoid bacillus. 

 Striking success in combating bacterial in- 

 fections has been met with in certain cases 

 by the application of one or more of three 

 pretty definite methods. Some bacteria, 

 like the diphtheria bacillus, produce their 

 harmful effect in the body by the liberation 

 of poisonous substances known as toxins. 

 In the case mentioned, the disease, when 

 taken in time, can be cured in a really 

 miraculous manner by injecting diphtheria 

 antitoxin, which is simply the serum of 

 horses that have been treated with repeated 

 doses of diphtheria toxin and thereby made 

 to produce antitoxins that neutralize the 

 toxin. Other diseases produce their harm- 

 ful results largely by multiplication of the 



