The actual causation of particular forms of disease is in many cases obscure, because of the limitations of our present knowledge. Looking at disease as a whole and the great groups into which the morbid conditions naturally fall, there are certain general facts as to causation which may be summarily stated.

As disease consists in inefficiency of the elements of the body in performing their normal actions, we have to seek for the causes of this inefficiency in agents or conditions which, directly or indirectly, interfere with the integrity of the living structures. The most obvious manner in which this may come about is by direct interference, by forces external to the body or to its individual elements. The body as a whole is exposed to injuries, wounds, bruises., and it is susceptible to the action of poisons and infections of various sorts. But even in this very elementary statement the suggestion at once occurs that, if we regard different individuals, and, still more, if we regard different parts of the body, the effects of such agents vary greatly. Besides the direct cause of the disease or injury there is, commonly, a pre-existing condition which renders certain structures more liable to interference than others. This pre-existing state, which may be inherent in the actual structure of the part, or may be an acquired peculiarity, may be designated Susceptibility or Predisposition. An illustration may give reality to these remarks.

Perhaps the most important of the external agents causing disease is the group of microscopic organisms or bacteria. In the process of self-preservation the elements of the tissue have it as part of their function to resist the intrusion of these microbes or of the poisons produced by them. As microbes are abundant at the mucous and cutaneous surfaces of the body, these surfaces are supplied with continuous layers of cells whose office is to resist the intrusion of the deleterious agents. When the body dies these begin their action on the tissues, and the process of putrefaction leads to the disintegration of the tissue. During life, however, the living epithelial cells restrain their action. There are two ways in which this resistance may be overcome. On the one hand there are certain kinds of microbes which have special ability to overcome the resistance of the tissues, and on the other hand the protecting layer of cells may be removed or breached, and the microbes thus admitted to more susceptible structures, that is, to structures less able to resist. Thus, to give an example of the one form, in an epidemic of cholera the specific microbe, by reason of its inherent powers, obtains a footing in persons previously healthy; and again, on the other hand, wounds or breaches of surface are serious according as they admit the microbes into tissues which are unprepared to resist them. It must be recognized also that, in relation to the same kind of microbe, different persons and different tissues show a remarkable variety in susceptibility. This will be worked out more fully further on, but here attention may be called to it by way of illustration. In an epidemic of cholera, for example, the bulk of the population probably escapes. Thus in the great epidemic in Hamburg in 1892, only about 3 per cent, of the inhabitants were affected, although a much larger proportion must have been exposed to the infection. Again, the microbe of tuberculosis is an exceedingly prevalent one, and it doubtless finds entrance to the bodies of almost all persons living in communities.

But great varieties in the results are manifest. In some persons it obtains no footing, whilst in others it settles in one tissue or another, according to the inherent susceptibility of the person or of the tissue.

The same principles might be illustrated in regard to the ordinary mechanical forces and their influence in the production of morbid conditions. There are injuries which no individual or tissue can resist, but there are lesser injuries which are capable of producing disease, according to the person affected or according to the tissue which has been encountered.

But the causation of disease is not in every case related to the forces external to the body or its individual parts, although the manifestations of disease may be so related. It has been shown above that there are inherent susceptibilities to disease and injury, and it has to be added that there are certain forms of disease whose causation is to be found in an inherent faulty construction or tendency in the living tissue. Varying susceptibility is, as we have seen, related to differences in construction and tendency, but there are also specific morbid conditions whose causation can only be assigned to such inherent, and frequently inborn, faults of structure, growth, or function. A very striking example of this is the disease Haemophilia, in which, from an inherited peculiarity, the blood-vessels are easily ruptured, so that extensive and even fatal bleeding may occur from a trivial injury. A further example may be afforded by the case of a simple tumour. Thus a piece of adipose tissue, from some inherent perverse tendency, may take to growing and may produce a tumour of huge dimensions.

In considering the causation of disease, then, it will be proper to keep in mind a four-fold division. The direct cause may be external or internal, and, preceding the action of the direct cause there may be a susceptibility or predisposition, which again may have its origin in external circumstances or internal construction or tendencies. It is to be noted that such susceptibility or predisposition is to some particular form of disease and not to disease in general. It may exist in a person who is otherwise normal, and it may be present throughout life without the person having been exposed to the direct cause, which is necessary to the production of the disease.