52 EVOLUTION OF THE INFECTIOUS DISEASES 



tuberculous antigen, tuberculin, exerts apparently no direct 

 pathogenic action on organs or normal tissues. But we know 

 that a dose of tuberculin known to be harmless for the normal 

 organism, or even a much smaller dose, will provoke in a tuber- 

 culous patient a general reaction more or less severe when 

 injected under the skin or into the blood and a local reaction 

 when a drop of it is placed on a break in the skin (cuti- 

 reaction) or on the cornea (oculoreactiori) . We also know 

 by the reaction of complement fixation that this general and 

 local hypersensitiveness coincides with the existence of a 

 specific antibody in the blood. 



But this antibody does not neutralize tuberculin in vitro. 

 A mixture of it with tuberculin will cause a general and local 

 reaction identical to those provoked by tuberculin alone. 

 We have a total of facts which seem contradictory. The prob- 

 lem of the evolution of tuberculosis is much more compli- 

 cated than that of diphtheria. To solve it, it is necessary 

 to analyze carefully each of the elements which compose it. 

 Before beginning this study it is necessary to explain the 

 exact meaning of the terms which will be employed in what 

 follows. 



We will define : 



1. Artificial tuberculin as the total of the secretions of the 

 tubercle bacillus obtained in vitro, whatever may be the 

 culture medium and the method employed in its preparation. 



2. Natural tuberculin, as the total of the products secreted 

 by the bacilli in vivo during infection. 



3. Normal antibody, as the intracellular substance which 

 possesses a specific affinity for tuberculin and which combines 

 with it in the interior of cells; and 



4. Antibody in excess, or antituberculin as the same sub- 

 stance as the normal antibody but multiplied and existing 

 in excess in the tissues and in the blood of the diseased. 



After reviewing the total of experimental work and clinical 

 observations published on tuberculosis and tuberculin since 

 Koch's discovery of the germ and the facts well established 

 and verified by numerous experiments; we know that artificial 

 tuberculin does not act on normal tissues and that repeated 

 injections of this product do not provoke the formation of an 



