IMMUNITY IN TUBERCULOSIS—FLEXNER. 637 
this distinction, it can be said that while the tuberculous organism 
has acquired a degree of immunity to reinfection, the organism 
merely poisoned with tubercle bacilli has failed to develop this state 
of resistance. 
The experimental results, which I shall relate to you, upon which 
are based our belief in the artificial production of immunity to tuber- 
culosis, were all obtained by the use of living bacilli. It would, there- 
fore, seem as if in the course of their residence and development 
within the body the immunizing organisms behave differently from 
those in artificial cultivations. This difference in behavior could 
be accounted for on the supposition that under conditions of parasitic 
life, surrounded as the bacilli are with complex fluids and more com- 
plex cells, they form, in their growth, products which either are 
distinct from those which are formed by them in cultures, or these 
products, in statu nascendi, are acted upon and modified by the active 
and labile ferments in the fluid and protoplasm of cells, with which 
the growth-products must come into immediate contact. Professor 
Welch, to whom this variation in behavior of bacteria under parasitic 
and saprophytic states of existence was fully apparent, endeavored 
a few years ago in his Huxley lecture to explain the difference in 
activity of bacteria growing within and outside the body by suppos- 
ing that in the body they are induced to secrete substances the stim- 
ulus to the production of which is absent in the culture tube. How- 
ever this may be, it is evident that the only form of immunity in 
tuberculosis which deserves the name has been obtained by the em- 
ployment for inoculation of living cultures of the tubercle bacillus. 
Although the earhest experiments which had for their object the 
production of immunity in small animals by means of previous in- 
oculation of products of the growth and of attenuated cultures of the 
tubercle bacillus were published in 1890 (Martin and Grancher, 
Courmont and Dor), yet, I think, the first really promising, because 
successful, achievements of this end were made by Trudeau in 1902 
and 1903 and by De Schweinitz in 1904, 
Trudeau protected rabbits from virulent tubercle bacilli by first 
injecting them with a culture of bird tubercle bacilli, the subsequent 
injection of virulent mammalian bacilli being made into the anterior 
chamber of the eye. The rabbits to be protected were twice injected 
subcutaneously at intervals of twenty-one days with cultures of the 
avian bacilli. About one in four of the rabbits died within three 
months, profoundly emaciated, but without tubercular lesions. The 
remaining animals recovered and were apparently in good health, 
when, with an equal number of controls, they were inoculated in the 
eye with a culture of mammalian tubercle bacilli. The results are 
instructive: In the controls little or no irritation following the oper- 
ation is observed and the eye remains quiescent or nearly so for about 
