VACCINE THERAPY IN THEORY AND PRACTICE 607 



is, if a normal index really exists. Bulloch accordingly investi- 

 gated the opsonic index of sixty-six healthy persons, regarding 

 himself as normal ; he found an average of '95, the variations 

 ranging from '8 to i'2, and concluded that the sera of normal 

 individuals are almost identical. 1 Very numerous observations 

 on the tuberculo-opsonic index followed these researches ; and 

 a fact which was soon elicited was that, while patients with 

 strictly localised tuberculosis have consistently low indices, 

 those who suffer from constitutional disturbance have variable 

 indices, which may be either above or below normal, and it was 

 concluded that such patients live in a constant succession of 

 negative and positive phases, due to the entrance of bacilli into 

 their blood from the focus of infection, and consequent " auto- 

 inoculation." At this time a case of cystitis was examined which 

 presented the appearance of tuberculosis ; the indices yielded 

 were consistently normal, and no tubercle bacilli were ever 

 found. The case was declared not to be tubercular, and was 

 ultimately cured by the use of a vaccine made from another 

 organism isolated from the urine. 2 



The possibilities and limitations of vaccine therapy were 

 recognised by Wright from the first, and he very early drew 

 attention to the negative phase and the possibility of increasing 

 it. A correct inoculation leads to a short negative phase, a 

 steep rise, and a gradual fall to a level higher than that at which 

 inoculation was begun ; this is described as the " Law of ebb, 

 and flow, and reflow, and maintained high-tide of immunity." 3 



In early experiments in immunisation, without access to any 

 delicate means of recording the results of inoculation, it was 

 considered necessary to produce some degree of constitutional 

 disturbance to ensure the formation of anti-bodies. One of the 

 early results of observations on the opsonic index was to show 

 that this is unnecessary, and that a satisfactory immunising 

 response can be excited without discomfort. 4 Dosage was 

 accordingly reduced. In the earliest cases published by Wright 

 the doses varied from ^Truv to T jt mg. of T.R., but in 1906 he 

 recommended the use of doses between -oVo and ^oW nig., and 

 at the present time doses as small as o^oo m g. ai *e in frequent 



1 Bulloch, Trans. Path. Soc Lond., vol. Ivi. 



2 Wright and Reid, Proc. Roy. Soc, vol. lxxvii. 



3 Wright, Clinical Journal, Nov. 9, 1904. 



4 Wright, Trans, Roy. Med. Chi, Soc, 1906. 



