Further study showed that the various bacterial toxins produce not only a fatal intoxication, but that each has its distinctive effect, as shown by symptoms or anatomical lesion, when injected into animals, thus demonstrating that the poison of each bacterium possessed a specific action. This led not only to a better understanding of the pathology of such diseases as diphtheria and tetanus, but eventually, and of far greater importance, to the discovery of curative and prophylactic sera, or as they are generally known, antitoxic sera. The first step in this direction was taken when Behring and Kitasato (1890) showed that animals could be immunized against weakened diphtheria toxin and that the serum of such animals is capable of protecting other animals against its intoxication, and, moreover, demonstrated that such a serum can be used to cure the toxic symptoms produced by the diphtheria bacillus. This curative power, furthermore, was found to be due not to an action on the bacteria, but to a neutralization of the toxin which the bacteria produced; also the serum was strictly specific, that is, the serum of an animal immunized against diphtheria toxin protects only against diphtheria; that prepared by the use of tetanus bacilli, only against tetanus. This led directly to the production by Behring and Knorr of diphtheria antitoxin for therapeutic purposes (1894) on a large scale and to a general awakening as to the possibilities of serum therapy. The great benefits of diphtheria antitoxin as a curative and prophylactic serum are known to all; since its general use, in 1896, a reduction of the death rate in diphtheria from 45 per cent, to 10 per cent, marks this therapeutic measure as one of the most brilliant discoveries of medicine and of the brilliant century in which this discovery occurred.
The success with diphtheria antitoxin aroused the hope that a general principle—that of the formation of antibodies for the toxins of all bacteria—had been established on the basis of which it would be possible to develop curative sera for all infections. This expectation—on account of the simple fact that most bacteria do not produce soluble poisons—has not been fulfilled; but the impetus which the principle of serum-therapy gave to investigation has led to activity of great and permanent value, and to the development of a new science, immunology or serology, as it is variously called, which attempts to establish laws for the conditions which determine natural resistance to infectious diseases and the factors which increase or diminish this resistance. I approach this subject with hesitation, for the many difficulties it offers can not readily be overcome in a short presentation such as this must be. A few brief statements, stripped of the less familiar terms may, however, serve to elucidate the main lines of investigation.
All immunological studies are based on the known fact of the reinforcement of natural resistance to disease, as illustrated by serum