THE CHEMICAL NATURE OF DIFFERENTIALS 567 



therefore began to study the chemical factors underlying the species specificity 

 of the precipitinogens. Their principal finding was as follows: The species 

 specificity of cattle serum was not greatly altered by heat, nor by such 

 substances as alkali, toluol and chloroform, but it was fundamentally changed 

 by introducing the iodine of Lugol's solution into the protein molecules, by 

 diazotizing the protein, or by producing xanthoproteins by means of nitric 

 acid. The species specificity was destroyed by the latter processes and new 

 specificities were created instead. The antibodies which originated through 

 immunization with these new antigens, reacted specifically also with other 

 proteins into which similar chemical radicles had been introduced, but no 

 longer or very little with the unaltered proteins of the original serum. Fur- 

 thermore, they made it probable that it was an aromatic constituent of the 

 protein, tyrosin, to which the new group was anchored. They concluded, 

 therefore, that the aromatic constituents of proteins were mainly responsible 

 for the antigen specificity. 



These observations led Obermayer and Pick to distinguish between the 

 constitutional and the original structure of a protein ; by the latter was meant 

 its species characteristics. A first type of substances, such as acid, alkali, 

 toluol, as well as application of heat, leave the latter intact but change the 

 former, while introduction of a second group of radicles, such at N-N, N0 2 , 

 or J, Br, changes the species specificity. However, the distinction between 

 these two types of specificity no longer seems to be as sharp as Obermayer 

 and Pick assumed. A part of the species-specificity of the serum may still 

 be left even after introduction of a new group of the second type of substances, 

 especially after diazotation; on the other hand, specificities may be modified 

 also by alkali and by heating. Furthermore, even the introduction of the 

 methyl and acetyl group, or of other groups which do not combine with the 

 aromatic constituent of the protein molecule, may likewise modify the species- 

 specificity. Thus, as Landsteiner has shown, esterification with acid alcohol, 

 acetylation and methylation may cause loss of specificity of a protein, although 

 these groups do not directly affect the aromatic nucleus of the protein. But 

 essentially, Obermayer and Pick have established some of the basic facts 

 concerning the constitution of antigens and their species-specificity. These 

 investigators also made the important observation that a number of partial 

 precipitins may develop through immunization with a protein, the constitu- 

 tion of which has been altered experimentally; and some evidence has been 

 found by subsequent investigators which confirms the conclusion that the aro- 

 matic protein group is of great importance for the specificity of the antigen. 

 Thus, Wells pointed out that gelatin, which lacks the aromatic group, also 

 lacks antigenic powers, and still later it was shown that the introduction of 

 the metanilic acid radicle into gelatin changes the latter into a potential 

 antigen, which reacts also with an antiserum against the combination of 

 another protein with metanilic acid. Furthermore, Wormall found that iodine, 

 in altering the specificity of the protein, combines with the tyrosin radicle. 

 However, while all these data point to the conclusion that the character of 



