IMMUNITY IN TUBERCULOSIS 239
body the immunizing organisms behave differently from those in arti- ficial 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 complex 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 nas- cendi, 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 supposing that in the body they are induced to secrete substances the stimulus to the production of which is absent in the culture tube. However this may be, it is evident that the only form of immunity in tuberculosis which deserves the name has been obtained by the employment for inoculation of living cultures of the tubercle bacillus.
Although the earliest experiments which had for their object the production of immunity in small animals by means of previous inocula- tion 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, achieve- ments 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 21 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 con- trols little or no irritation following the operation is observed and the eye remains quiescent or nearly so for about two weeks, when the changes described in the early parts of this address manifest them- selves. After a few weeks general inflammation of the structures of the eye develops, the inoculation wound becomes cheesy and the eye is more or less completely destroyed. The disease, however, remains usually localized in the eye for many months, and may remain there permanently, depending upon the virulence and number of bacilli injected.