Sidney Martin has recently[78] elaborated the views announced by him in 1892, and it is right that reference should be made to his new classification of bacterial poisons. This may be represented as follows:—
1. The poisons secreted by the bacterium itself = (ferment? toxin?) |  | = Extracellular bacterial poisons. |
2. Products of digestive action of bacterium = albumoses: | ||
3. Final non-proteid products = animal alkaloid; | ||
4. Poisons present in the bodies of the bacillus | = Intracellular bacterial poisons. | |
The poisons of bacteria are, according to Sidney Martin, of a kind which cannot be fully expressed chemically, but only pathologically. They may be of a ferment nature in diphtheria and tetanus. The arguments in support of that view are—(1) that they act in infinitesimal doses, (2) that they may act slowly and produce death after many days by profoundly affecting the general nutrition, and (3) that they are sensitive to the action of heat in a way that no chemical poisons are known to be. If they are considered as ferments, they must be substances which have a peculiar affinity for certain tissues of the body on which they produce their special toxic effect. As for the products of digestion, they are formed either by the bacillus ingesting the proteid and discharging it as albumose, or the digestion occurs by means of a ferment secreted by the bacillus in the body of an individual or animal suffering from the disease.
Sidney Martin suggests that anthrax produces albumoses and an alkaloidal substance, the former producing fever, the latter stupor. In tetanus the bacillus produces a secretion of the bacillus which causes the convulsions. The albumoses present in this disease are probably due to the secretory toxin. In diphtheria, too, we have a secretory poison in the membrane and in the tissues, and an albumose which is possibly the result of the secretion. It will be seen that these views differ in some particulars from those to which we have already referred.
However the details of the modus operandi of the formation of toxins are finally settled, we know that there comes a time when the disease symptoms vanish, the disease declines, and the patient recovers. Many of the older schools of medicine explained this satisfactory phenomenon by saying that this disease exhausted itself after having "gone through" the body. In a sense that idea is probably true; but recently a large number of investigators have applied themselves to this problem, and with some promising results.
Various protective inoculations against anthrax were practised as early as 1881, and the protected animals remained healthy. In 1887 Wooldridge succeeded in protecting rabbits from anthrax by a new method, by which he showed that the growth of the anthrax bacillus in special culture fluids gave rise to a substance which, when inoculated, conferred immunity. In 1889 and 1890 Hankin and Ogata worked at the subject, and announced the discovery in the blood of animals which had died of anthrax of some substances which appeared to have an antagonistic and neutralising effect upon the toxins of anthrax and upon the anthrax bacilli themselves. These substances, they afterwards found, were products of the anthrax bacillus. Behring and Kitasato arrived at much the same results for tetanus and diphtheria. The next step was to isolate these substances, and, separating them from the blood, investigate still further their constitution. A number of workers were soon occupied at this task, and since 1891 Buchner, Hankin, the Klemperers, Roux, Sidney Martin, and others have added to our knowledge respecting these toxin-opposing bodies known as antitoxins. In diphtheria, as we have seen, the toxins turned out to be soluble bodies allied to the proteids, albumoses, and an organic acid. Then arose the question of the source of antitoxins. Some believed they were a kind of ultratoxin—bodies of which an early form was a toxin; others held that, as the toxins were products of the bacteria invading the tissues, the antitoxins were of the nature of ferments produced by the resisting tissues. Finally, they came to be looked upon as protective substances produced in the body cells as a result of toxin action, and held in solution in the blood, and there and elsewhere exerting their influence in opposition to the toxins.[79] The progress of disease is therefore a struggle between the toxins and the antitoxins: when the toxins are in the ascendency we get an increase of the disease; when the antitoxins are in the ascendency we get a diminution of disease. If the toxins triumph, the result is death; if the antitoxins and resistance of the tissues triumph, the result is recovery.
We may now consider shortly how these new facts were received and what theories of explanation were put forward to explain continued insusceptibility to disease. It had of course been known for a long time past that one attack of small-pox, for example, in some degree protected the individual from a subsequent attack of the same disease. To that experience it was now necessary to add a large mass of experimental evidence with regard to toxins and antitoxins. The theories of immunity were as follows:
1. The Exhaustion Theory. The supporters of this idea argued that bacteria of disease circulating in the body exhausted the body of the supply of some substance or condition necessary for the growth and development of their own species.
2. The Retention Theory. It was surmised that there were certain products of micro-organisms of disease retained in the body after an attack which acted antagonistically to the further growth in the body of that same species.
3. The Acquired Tolerance Theory. Some have advanced the theory that, after a certain time, the human tissues acquired such a degree of tolerance to the specific bacteria or their specific products that no result followed their action in the body. The tissues become acclimatised to the disease.