AUGUSTUS WADS WORTH 835 



ity may be quite complex and only in varying degree specific. The presence of non- 

 specific and specific activity is taken to indicate complex reactions, as, for example, 

 antigens which fix with the serum of normal or healthy individuals and also with the 

 serum of specifically infected or immunized individuals. In some instances, it is pos- 

 sible to differentiate these reactions, owing to their difference in intensity, by dilution 

 of the antigen and standardization of the test. Striking evidence of how definitely 

 these antigenic reactions differ is to be found in the antigenic activity of antigens pre- 

 pared from the Treponema pallidum when tested with the serum of syphilitic indi- 

 viduals and the serum of infected and of immunized animals. 



Noguchi' early noted the differences in the reaction of the Wassermann antigen as 

 compared with the antigens prepared from spirochetes ground in medium and sus- 

 pended in salt solution. Recently, Klopstock^ has studied the activity of alcoholic 

 extracts of the spirochete, recording much more specific reactions with this antigen 

 than have been obtained by other observers.^ Although we have also obtained similar 

 results in our work now in progress and not yet reported, the reactions of the syphilitic 

 serum with such spirochetal antigens are variable and do not parallel those secured 

 with the antigens prepared from heart muscle, sometimes quite the contrary. The 

 presence of agar carried over from the culture medium into the antigen may be a 

 disturbing factor, and one must always bear in mind the fact that many substances — 

 as, for example, animal charcoal, and the like^ — will absorb or inhibit complement. 

 Not only may the culture material act antigenically in the reaction but, apparently, 

 in one experiment the culture fluid, free from spirochetes, fixed complement with the 

 heart-muscle antigen in the Wassermann test when substituted for patients' serum. 

 The uninoculated serum broth failed to react. 



All of this research work indicates that it has been practically impossible to 

 standardize the preparation of bacterial antigens. Some of the crude extracts react 

 as well as the purified extracts. In general, the aqueous extracts are perhaps most 

 satisfactory but there is no scientific basis for their standardization as yet, unless it 

 is done with immune sera which may differ quite materially from the serum of an 

 infected individual. Despite all the extensive methods of chemical analysis that have 

 been used, the elements essential to antigenic activity have not been separated from 

 the bacterial culture, nor have the physico-chemical relations in which they must exist 

 to possess an optimum activity been determined. Further progress thus depends 

 upon the results of future study with more precise methods of distinguishing and 

 separating the different substances that possess antigenic activity. 



Bacterial antigens have been so variable that even the attempts to standardize 

 them for the practical diagnosis of infection have not been encouraging. The data 

 available consist of desultory reports in the literature, as above noted. Moreover, al- 

 though the standardization of the Wassermann antigens has been developed as a 



' Noguchi, H.: Laboratory Diagnosis of Syphilis, chap. xiii. New York: Paul B. Hoeber, 1923. 



=" Klopstock, F.: Deutsche med. Wchnsclir., 52, 226. 1926. 



3 Craig, C. F., and Nichols, H. J.: J. Exper. Med., 16, 336. 1912; Kolmer, J. A., Williams, 

 \V. W., and Laubaugh, E. E.: J. Med. Research, 28, 345. 1913. 



■* Practically all the experiments with the injection of such substances — so-called blocking experi- 

 ments — lack adequate control to warrant the definite conclusions that have been drawn. 



