1915] on Anti-Typhoid Inoculation 431 



only anti-toxins, injection of their serum cannot kill the enteric 

 bacilli, although some enteric toxins may be neutralized. 



2. In the case of B. typhosus the toxins are endo-toxins — i.e. so 

 intimately associated with the bodies of the organisms that they 

 cannot by filtration be obtained free from the organisms. This made 

 it necessary that the bodies of the organisms should themselves be 

 injected as the stimulating antigen to promote formation of anti- 

 bodies, and thus confer active immunity to enteric fever. 



Auto-inoculation. This brings us to the point at which Sir 

 Almroth Wright, in 1896, found progress barred along all other 

 roads than that of auto-inoculation. It is W'ith justifiable pride in 

 our profession that we study the history of the advance along that 

 perilous solitary road, and it is with a special pride in my corps that 

 I recall the devotion to duty which led officers of the R.A.M.C. to 

 offer themselves for this purpose. Without the possibility of a pre- 

 liminary comparable test on animals, it became necessary for the 

 officers experimented on to receive massive injections of dead enteric 

 organisms, the effect of which could only be surmised by analogy. 



As one can sympathize with the tension of this step in the dark- 

 ness, so one can appreciate the satisfaction with which these officers 

 found, in the subsequent development of protective substances in 

 their blood, the promise of a brilliant outcome to their devotion and 

 courage. It is interesting to note that they received in a single 

 injection three times the number of enteric organisms which are now 

 given as a dose. 



The Methods noiv in Use. 



1. The Emulsion. As the term "serum" is wholly inaccurate, 

 and "' vaccine " is often regarded as a term to be applied to a growth 

 of living organisms, the fluid which is injected in this method is 

 styled the anti-enteric (or anti-typhoid) emulsion. 



The strain of organism used is one of very low virulence — as has 

 been proved on two occasions when accidents with rubber connections 

 have resulted in the laboratory personnel getting- considerable intra- 

 oral doses of the living culture. 



The culture is a forty-eight hour broth-culture at blood-heat, and 

 generally gives a concentration of about 3,000 million organisms 

 per c.c. 



The dose is 500 million dead organisms in the first and 1,000 

 million in the second injection. The reasons for this division of the 

 dose are given later. 



The standardization is obviously a matter of great importance in 

 relation to the dosage. Various methods of determining the number 

 ■of organisms per c.c. have been tried and successively abandoned for 

 improved means. 



{a) Weighing was regarded hopefully until it was found that 



2 F 2 



