THERAPEUTIC APPLICATIONS OF TUBERCULINS 301 



It is possible that in many cases this is due to wide variations 

 in individual susceptibility and to differences in susceptibility 

 at different age periods. Thus on the whole the most acute 

 cases of tuberculosis are found in childhood. In view of the 

 widespread opportunities for infection which occur, especially 

 in city life, it is probable that the great mass of the adult 

 population is on the border line between complete resistance and 

 a susceptibility of varying degree. On the other hand, there is 

 some evidence that variations exist in the virulence of different 

 strains of the tubercle bacilli. As has been pointed out, it is 

 probable that the bovine variety is less pathogenic for man than 

 the human, but it is probable that even amongst human strains 

 variations in virulence occur, as has recently been insisted upon 

 by Burnet. It has been supposed by many that a cause of insus- 

 ceptibility in the adult is found in the fact that infection has 

 previously occurred in childhood whereby an immunity is 

 established. The evidence for this at present is rather of an 

 academic nature, and it is certainly extremely difficult to 

 immunise animals against infection with virulent bacilli. It 

 may be said that the relation of the phenomena of supersensitive- 

 ness to those of the development of immunity is at present 

 very obscure. 



Therapeutic Applications of the Tuberculins. As has been 

 indicated, the injection of tuberculins into an infected subject 

 may cause necrosis in a focus of infection, and it was originally 

 supposed by Koch (1890-91) that the origination of such a 

 necrosis might free the body of the invading bacilli. It was 

 soon shown, however, that many single bacilli penetrating the 

 tissues around the focus were left unaffected, and this method of 

 treatment was therefore abandoned. 



Tuberculin-R was introduced by Koch in 1897 as a toxin 

 having a minimum of necrotic effect, and the object of its use 

 was to increase the natural powers of resistance of the tubercular 

 subject. Doses commencing with T J^ to -5 J^ mgrm., gradually 

 increased, were given every second day, the rule laid down for 

 the regulation of the dosage being that no amount should be 

 administered which raised the patient's temperature more than 

 5 F. In such doses profound local and general effects were, 

 however, still produced and these were sometimes of a harmful 

 character. The difficulty of controlling the effects militated 

 against the general use of this tuberculin as a curative agent, and 

 it was thus not until Wright investigated the effects of extremely 

 minute doses of the agent that it again came into prominence for 

 therapeutic purposes. At the present time the tendency is to 



