THE HISTORY OF PROTEIN THERAPY 7 



action that followed the injections, noted in particular the typical 

 effect on the leukocytic picture. 



We have then a whole list of agents and methods that have been 

 employed, some empirically, others with a definite immunological 

 theory underlying their use, but all, whether bacteriological product, 

 or enzyme, or chemical, producing a more or less marked constitutional 

 reaction on the part of the patient. It is curious that this common 

 feature was not emphasized or even recognized as a possible part of 

 the therapeutic mechanism. 



Throughout the period under discussion, when these various meth- 

 ods and substances were being introduced, vaccinotherapy as ad- 

 vocated by Wright was being tried out in practically every form of 

 infection; not always with success but with sufficient result to keep 

 the method in use in medical practice. 



When failure resulted there were, as a rule, extenuating circum- 

 stances upon which to throw the blame. At first it had been the 

 practice to use as a vaccine an organism of the type known to cause the 

 particular infection with which we were dealing. Then when results 

 were not forthcoming, effort was made to isolate the particular organ- 

 ism causing the infection in order to produce an autogenous vac- 

 cine. This failing, we had the consolation that we probably had not 

 succeeded in isolating the particular strain that had caused the in- 

 fection. 



On the basis of his opsonic work Wright had differentiated a 

 negative and a positive phase of resistance following the vaccine in- 

 jection. The dread of the negative phase was sufficiently impressed 

 on every immunologist to prevent the use of large doses of vaccine 

 or such that would lead to a general reaction on the part of the pa- 

 tient. Indeed, ever since the time of Koch's work with tuberculin, 

 when overzealous workers using large doses of tuberculin had often 

 done irreparable damage by breaking down the normal connective 

 tissue defense of the patient, immunologists had used great care 

 in avoiding general systemic reactions. 



When vaccines were carefully used there was no doubt that the 

 patient gave evidence of increased antibody production, measured 

 both by the opsonic index, the agglutinin titer and the method of 

 complement deviation, but here again the therapeutic result did not 

 measure up to the expectation. Immune bodies might be stimulated 

 to a sufficient degree but the patient was not cured. 



The modern conception of protein therapy and nonspecific re- 

 sistance was a direct development, however, of this work with vac- 

 cines. In typhoid fever the therapeutic use of vaccines, either made 

 up of killed but otherwise unaltered organisms, or of bacteria altered 

 in a number of ways, had been given rather extended use and with 

 fair clinical results. In the decade following the year 1906, the bacteri- 

 otherapy of typhoid began to be a recognized procedure. The dura- 



