The idea of intoxication by these products has now replaced the idea of the direct action of the microbe on the elements or the liquids of the organism.
The occurrence that takes place in diphtheria and tetanus is one of the best examples to cite in support of this view.
Here, in fact, the pathogenic microbe is found only in a very limited area in the organism attacked—the false membrane, in the case of diphtheria, or frequently only a slight wound in the case of tetanus, and the microbe becomes localized there only. Now, in both cases, there are general phenomena of toxic effects. There must hence be a diffusion of toxic substances which, distributed by the blood, affect the different systems and exert a toxic action on the entire organism.
It must be observed that the toxins act as toxic agents only when in a condition to be introduced into the circulation subcutaneously. The cause of this innocuousness of the toxins when given per os has frequently been studied. It appears to be quite probable that the cause of the attenuation of the morbid properties is due to the intervention of the digestive microbes. Such is the opinion of Levaditi and Charrin[22]; it is also the conclusion that is to be drawn from the experiments of Mme. Metchnikoff and of Calmette[23] on the modifications undergone by a vegetable toxalbumin, abrin, and by serpent venoms, when these toxalbumins are inoculated with the bacillus subtilis chromogenus. Moreover, Charrin and Lefèvre,[24] on the one hand, and Nencki, Sieber and Somanowsky,[25] and Carrière,[26] on the other hand, have discovered that the digestive ferments, particularly trypsin, destroy, even though but little, the toxins secreted by the Loeffler and Nicolaier bacilli. This is practically contrary to the opinion of Behring and of Rauson,[27] according to which the innocuousness of the microbial poisons when administered per os is due exclusively to the lack of absorption.
Nature of the Toxins.—The molecules of the toxins are very nearly like those of the diastases. Like these, the toxins appear to have a very complex, and very unstable, internal structure. Their mode of action frequently depends, as in the case of the diastases, upon the medium in which they occur. Again, like the diastases, they are generally destroyed by the action of sufficiently prolonged heat, but less easily, for there are certain toxins that resist a temperature of 100° C. for an indefinite period. They are, like the diastatic albuminoids, insoluble in strong alcohol, and are precipitated from their solutions on the addition of this reagent. They easily adhere to precipitates that form in liquids in which they occur in solution, and possess the remarkable property of diastases in that imponderable masses produce considerable results.[28]
Although closely allied to certain alkaloidal bases, the toxins are sharply distinguished by the remarkable fact that their action is never immediate, but is always preceded by a period of incubation, which may be quite long.
Like the alkaloidal bases, they appear to result from the hydrolyzing breaking down of albuminoids and nucleo-albumins, and they appear to be intermediary, from a chemical point of view, between these bodies, the general characters of which they retain, and the alkaloids proper, or ptomaines, to which we have called attention, and the principal chemical and physiological properties of which they possess.
No absolutely precise knowledge is had regarding the chemical nature and constitution of these remarkable substances. A number of analyses of these substances have been published which, in general, permit no definite conclusion to be drawn.[29] I have, however, elaborated several speculative ideas regarding this subject.[30]
We must here call particular attention to the ideas of Ehrlich regarding the constitution of the toxins. According to this scientist, their molecules contain two functional groups; the one, to which he has given the name "haptophore," is that which enables the toxin to attach itself to any cellular element whatever, and which it then renders non-toxic by means of the other, or "toxophore," group. We will particularize farther on regarding this very important conception.
Origin of the Toxins.—These toxic bodies result either as the products of the secretion of microbial life, or as the result of the normal functionation of cellular life in the higher vegetable or animal organisms.