all the actions of the body, of whatever sort, are ultimately resolvable into cellular actions. We are therefore to regard the body as in itself a state, or union of states, in which there are myriads of separate individuals, bound together in one confederacy, but bearing various relations to the whole. It is into this great commonwealth of living units that the microbes intrude themselves, and we may well suppose that the cells are not indifferent to the invasion.

In the further study of this matter, it is necessary to separate carefully in our minds these two-the microbes on the one hand, and the toxines, which are their products, on the other.

Taking first the poisonous products of the microbes, it may be said that the symptoms of the various diseases concerned are the results of the action of the toxines on the living cells of the tissues. They may be produced artificially by the toxine without the microbes being present in the body at all, or they may be produced by the toxine acting on one part of the body, while the microbes are situated at a different and perhaps a distant part, as in the case of tetanus, already mentioned.

On the other hand, in regard to the microbes, it is to be said that those concerned in the production of disease are only a small contingent of the great class to which they belong. In regard to all microbes, there is an opposition on the part of the living tissues to their intrusion, and it is only those which successfully overcome this resistance that become the causes of infective diseases. The great bulk of the microbes prey on dead matter alone, and are entirely barred from any invasion of the bodies of living animals. Those which are capable of obtaining a footing may owe this power to different circumstances. In some instances it seems as if they owed their ability in this direction to their own inherent vitality, whereby they are able to resist the control of the living tissues. In the majority of cases, however, it seems more probable that it is due to the influence of their poisonous products that they obtain a footing in the body; that is to say, when a few microbes are introduced, as must usually be the case in the beginning of most cases, they, by means of their toxines, paralyse the opposition of the cells, and so secure their position for further growth. This is well illustrated in the case of the tetanus microbe. If the spores of the microbe, carefully freed (by washing or otherwise) from the toxine, be introduced into the tissues in quantities which are not too great, then tetanus is not

produced. In order to obtain a footing, they require to be accompanied either by their toxine or by some agent which will damage the tissues whilst they slowly multiply. It is found

that various matters, including the products of other microbes and substances of various sorts, are able to give, as it were, the start to the tetanus microbe, and that even a direct injury to the tissue may do so. It is obvious that, in what may be called the natural mode of acquiring the disease, dirt containing microbes of various kinds is introduced, and the tissues are injured, so that the necessary conditions for the growth of the microbe are furnished.

Such being, in the briefest possible sketch, the general facts in regard to the parasitic organisms which produce infective diseases, and the bodies of living animals, which are the seat of their energies, let us now turn to the subject which is more specially before us. From what has been said as to the relation of the living microbes on the one hand, and the living cells on the other, it may readily be inferred that there are differences amongst animals in regard to the various reactions of cells and microbes. Although the living structures of animals are all ultimately composed of cells, yet these cells have, in different animals, and in different parts of the same animal, variations in structure and endowment, and we are not surprised that these differences manifest themselves in this matter of susceptibility. Let me in a few words mention, in regard to tetanus, some of the facts ascertained as to the susceptibility of different species of animals to this form of infection. The horse is known to be singularly susceptible; so also is the guinea-pig; and, to a somewhat less degree, the mouse. The rabbit is still less susceptible, and the rat less than the rabbit. The sheep, the dog, and the pigeon are very slightly susceptible, and the domestic fowl is insusceptible to ordinary inoculation with the microbe. Each species of animal, with its inherited and inherent constitution, has its own specific relations to the parasitic organisms, which are the agents of infective diseases. The same applies in a less degree to the races and varieties of the different species, and in a still less degree to the individuals of each race. A striking difference in susceptibility as affected by race is exemplified in man in the case of yellow fever. The negro race is almost immune to this disease, which is so virulent in persons of the white races. It is also known that in the case of diphtheria, scarlet fever, typhoid fever, &c., there are striking family and personal peculiarities in susceptibility, and, conversely,

in degrees of immunity. It is in this sense that we speak of Natural Immunity, which is part of the constitutional endowment of the animal, and depends, like the other items of his constitution, on inheritance.

If we inquire as to the exact significance of Natural Immunity, we are on more difficult ground. When microbes find their way into the body of an animal which is naturally immune, what is the precise method by which they are disposed of, so that the disease does not develop? It may be stated, at the outset, that it is not because the toxines are not poisonous to the animal. An animal which is immune to the disease as introduced by the microbes is quite susceptible to the poison introduced, with or without the microbes, as when the toxines are used. There is, of course, no proper infection; the disease is not established. It is simply a case of intoxication or poisoning; the symptoms depend on the dose of the poison, and disappear when the poison is exhausted. Natural immunity is a matter of the microbes in relation to the living structures of the body. The fact may perhaps be stated with sufficient accuracy by saying that, in the case of an animal possessing natural immunity to a particular disease, the microbes concerned in that disease are simply relegated to the same category as the great majority of microbes, which, as we have seen, are barred in their attempts to obtain a footing in the body. The modes in which the former are disposed of are, presumably, not different from those applicable to the latter. The manner in which the entrance of microbes is barred, and in which they are dealt with if they obtain entrance, is not fully understood. Probably there are many ways in which these objects are effected, and here, as in all the vital actions of the body, we must look to the active units of the body, the cells, for the explanation.

Some of the possible modes may here be mentioned. For one thing, the various surfaces of the body are covered with a close phalanx of cells, generally in several layers, and these, whilst effectively preventing the entrance of ordinary microbes in all animals, may in the case of immune animals prevent the entrance or lodgment of infective microbes. They may do so by the power which a living body has of preventing the entrance into its substance of foreign bodies, unless it takes them into itself for the purposes of nutrition.

Again, if the microbes get beyond this external boundary, the living cells may deal with them by taking them into their

substance, nullifying them, and ultimately digesting them. This mode of disposal has been worked out with great industry and ingenuity by M. Metchnikoff, who has devised the name "Phagocytosis" for the faculty which many cells have of taking up and digesting particles of matter capable of being assimilated. The observations of Metchnikoff show that in the case of some of the best-known infective microbes, such as those of anthrax and of tuberculosis, when these are introduced into immune or partially immune animals, the living cells of the tissues take them into their substance, and dispose of them. The microbes undergo certain alterations in form and reaction to staining agents, and finally become assimilated by the cells.

Besides these modes, it is not improbable that the living cells may, in the presence of microbes, emit some substance which is capable of paralysing the microbes, and that, when thus weakened or killed, they may be taken up by the cells and digested. This has been asserted more especially in regard to the free wandering cells, which form an important constituent of the blood.

Again, it is not unlikely that in some cases the blood of an animal may be uncongenial by reason of some peculiarity in its chemical constitution to particular microbes. It is an ascertained fact that the blood-serum of some animals is unsuitable for the cultivation of certain microbes, although generally blood is a suitable medium. But this is not to be regarded as at all a general explanation of immunity, as the blood-serum of immune animals has in certain cases been found quite adapted to the culture of the microbes to which the animal itself is immune.

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Another possible view is that in certain animals the cells may be less sensitive to the toxine, and the microbes are thus deprived in some degree of their aid in overcoming the resistance of the tissues. may here recall what was said in regard to tetanus, in which we saw that the toxine, or some agent which acts on the tissues, is necessary, as well as the microbes, in order that the latter may obtain a footing. It is consistent with this that in animals which present immunity only in minor degrees, a larger dose of the agent will sometimes suffice to produce infection.

We may now leave the subject of natural immunity, with the remark that in it we are concerned directly with resistance to the entrance and propagation of the microbes, which are the infective agents, and that in this contest the active cells are, in some form

or other, by their inherited endowments, the opponents of the intruding agents.

It is in the domain of Acquired or Induced Immunity that we have had of late the principal advances in our knowledge. It must have been early a matter of observation that, in the case of such diseases as smallpox, measles, and scarlet fever, a single attack conferred a high degree of immunity against further attacks. There is thus an acquired immunity. It was the knowledge of these facts that begot the idea of producing immunity to smallpox by actual inoculation with the virus of the disease. This was the first attempt at procuring what we may call induced immunity, which is obviously of the same nature as acquired immunity. This method of preventive treatment against smallpox is stated to have been of considerable antiquity. The modern knowledge of it dates from about the year 1715, and, curiously enough, it comes from the Turks at Constantinople. In that year, Dr. Kennedy, a Scotsman, wrote about inoculation for smallpox as practised in Constantinople. Its introduction to this country was, however, essentially due to Lady Mary Wortley Montagu, whose husband was ambassador at the Ottoman Court. She not only wrote to a friend in England describing the method, but, in the year 1717, she had her son inoculated, being the first British subject on whom the operation was performed. The matter taken from a smallpox patient was inoculated in one arm by Dr. Maitland, surgeon to the embassy, and in the other by an old Greek woman, who had been many years in the habit of inoculating. The disease ensued in due course, and there were about 100 pustules. Here was the induction of an actual disease (which generally occurred in a mild form, but was not without its fatal cases), in order to bring about immunity to the more virulent or fatal forms of the disease.

The introduction of vaccination by Jenner, in the year 1798, is the first instance of the production of immunity by the induction of a condition different from the disease against which protection is sought.

I suppose it is scarcely yet decided whether cowpox is a separate disease, or merely a modification of the deadly smallpox; but, whatever be its exact nature, there is no doubt that it confers an immunity which is probably less complete and less enduring than that conferred by smallpox itself, whether spontaneous in its origin or induced by inoculation.