568 THE BIOLOGICAL BASIS OF INDIVIDUALITY 



the aromatic group in the protein molecule is of great importance in fixing 

 the species-specific nature of the latter, still it is apparently not the only 

 determining factor. 



On the foundation laid by Obermayer and Pick, Landsteiner and his asso- 

 ciates built further and they established, among others, the following im- 

 portant facts: 



(1) Xanthoprotein and diazotized protein show a close serological rela- 

 tionship ; similarly, there is a strong cross-reaction between iodo- and bromo- 

 protein ; but there is a sharp serological distinction between the nitrated and 

 diazotized protein on the one hand, and the halogenated protein on the other. 

 These differences may depend not only on the nature and the number of the 

 substituting groups, but also on the place of substitution, and there is an 

 indication of gradations in these reactions. While in this way a new specificity 

 can be produced, a remnant of the old organismal specificity may still be 

 left, and although chemically altered horse serum calls forth the production 

 of antibodies, which react also with other protein compounds which have 

 been coupled with similar radicles, still the reaction may remain most 

 intense with the substituted compounds of horse serum. Antiserum against 

 diazobenzene serum protein from cattle, precipitates diazobenzene protein 

 from cattle serum, but not that from human, horse or rabbit serum; nor is 

 there a reaction with the native, unchanged serum from cattle. Thus it 

 becomes conceivable that diseased or functionally changed tissues may give 

 off proteins, which may act as antigens in other individuals of the same 

 species. We have here to deal with the combination of a species and a struc- 

 tural specificity of certain substances, which recalls the complex specificity 

 due to the combination of organ and organismal specificities previously dis- 

 cussed. However, the chemical alteration of a protein must be fargoing if 

 the immune serum is to react with antigens derived from a different, non- 

 related species into which the same group has been introduced. 



(2) Introduction of complex organic groups, together with the diazo and 

 certain other radicles, increases the specificity of the reaction to the new 

 substance. Of special importance in determining the specificity of the azo- 

 protein are acid groups which are introduced into the benzene ring, while 

 the introduction of methyl, methoxyl, halogen and nitro groups is less effec- 

 tive in changing the specific character of the antigenic substance. 



(3) Likewise, the position of certain groups introduced into the protein 

 molecule helps to determine the specificity of the latter. Hence the same 

 group, if introduced into the ortho, meta or para position, calls forth in each 

 case the production of specific antibodies, although weaker cross-reactions 

 may occur also with other than the homologous antibodies. The specificity of 

 these substances is therefore not absolute, but relative and graded, and 

 there are, moreover, certain preparations which elicit reactions that do not 

 conform to the expected specificity. In addition to the ortho, meta and para 

 positions, also differences in the stereoisomeric constitution of certain sub- 

 stances may yield specific antibodies. 



(4) Perhaps the most important finding of Landsteiner, however, con- 



