IMMUNITY IN TUBERCULOSIS—FLEXNER. 635 
a diagnostic agent of high value, and its action upon the tuberculosis 
organism 1s so specific and remarkable that it has proved itself of the 
greatest importance and aid in the effort to unravel the complicated 
series of biological phenomena which constitute the tubercular state. 
It is possible to increase somewhat the resistance of animals to 
tubercular infection by previous treatment of tuberculin; but this 
increase is not remarkable. It is possible to bring about arrest of the 
tubercular process in the infected organism by means of tuberculin; 
and in some instances this arrest leads, through the changes induced 
in the tuberculous tissue by means of the tuberculin injections, directly 
to cure, or indirectly, through an increased power of resistance and 
attack on the part of the forces of the organism, to eventual cure. 
But a high and lasting degree of immunity has never been secured by 
the use of tuberculin. This fact, disappointing as it was_at first, is 
now easily explicable. Tuberculin does not represent the entire series 
of forces contained in the bacilli which the body has to resist in pre- 
serving itself from infection with tubercular poison. The peculiar 
principles contained in tuberculin are, indeed, not highly toxic for the 
normal individual; and our experience in securing immunity to micro- 
parasites and their products has taught us that where no reaction or 
response to the introduction of the foreign poison is called forth, no 
degree of protection to larger doses or more virulent poisons of the 
same nature is to be expected. Toxic as is tuberculin to the tuber- 
culous organism, it is almost innocuous to the tubercle-free body. It 
has been found, in keeping with this distinction, that the normal 
animal shows after tuberculin treatment evidence of the minimal 
production of the neutralizing or antibody for the tuberculin, which, 
were tuberculin a direct poison for the tissues, would probably be 
produced in larger amounts. On account of this absence of action on 
the normal organism it has been thought that the active principle in 
tuberculin does not exist in a free state, but occurs in some combina- 
tion, from which the tuberculous, but not the nontuberculous, organ- 
ism can free it, and that the separation takes place in the tubercular 
foci upon which the specific action of the poison is directly exerted. 
If this view is correct then the failure of tuberculin to exercise any 
profound action on the healthy organism is easily grasped. 
Increased knowledge of bacterial infection and immunity has 
taught us that in case of bacteria which invade the depth of the body 
and produce their peculiar effects by reason of their immediate pres- 
ence, we can not expect to achieve marked immunity through the use 
of the soluble gross products of the parasites. The reaction of the 
body to the invasion depends not upon the presence in the invader of 
one set of toxic principles, but of many, some of which are contained 
in the solid substance of the micro-parasite and do not go over into 
the fluids in which they multiply. Thus it has been found, in case of 
