In the same degree that observations of cases and epidemics increased in number, the nature of the disease and its cause commenced to be studied. The assumption that the latter was a chemical poison was soon doubted, and the parasitic nature of diphtheria considered by many as proven.
After Henle had (1840) expressed his belief in the existence of a contagium animatum, and morbid processes had for some time been compared with the phenomena of fermentation, Schwann demonstrated the presence of lower organisms in fermentation and putrefaction. The discovery of the cause of the silk-worm disease by Bassis, of the achorion by Schönlein, of the acarus by Simon, of bacteria in malignant pustule by Pollender, Brauell, and, above all, by Davaine, in relapsing fever by Obermeier, the teachings of Pasteur concerning the conditions under which putrefaction occurs,—all tended to explain the various infectious and contagious diseases by analogy also, and to stimulate the search for a vegetable organism in diphtheria. Buhl was the first to discover schizomycetæ in diphtheritic membrane, but expressed no opinion as to the part they played in the process. Hüter found them in the gray diphtheritic covering of wounds, in the surrounding apparently healthy tissues, and in the blood. Hüter and Tomasi found them in the diphtheritic membranes of the pharynx and larynx, inoculated them on the mucous membranes of animals, and described them as small, round or oval, dark-colored, active little bodies. The latter observers look upon these organisms as a part of the infectious element. Oertel found them in diphtheritic membrane and in inflamed mucous membranes in the lymphatic vessels, lymphatic glands, kidneys, and other organs; he considers them as the contagious element of diphtheria. Nassiloff, too, after inoculations in the cornea resulted in an enormous multiplication of the microscopic organisms and their appearance with pus-cells in the lacteals and in the lymphatics of the palate, and even in the bones and cartilages, asserts that the development of organisms is the primary step in the diphtheritic process. Eberth made successful inoculations in living tissues; the micro-organisms, introduced into the cornea, proliferated actively and caused an inflammation of irritative character in the surrounding tissue. He asserts, with the positiveness of an evangelist, that diphtheria cannot occur without bacteria. Klebs inoculated the micrococci in pigeons and dogs, and found them in the blood of the animals after death. Orth found them in the pleura, lungs, kidneys, and urinary bladder. But what their action is, whether they are directly pernicious, or deprive the body of certain elements (as of oxygen in malignant pustule, according to Bollinger), or injure mechanically by acting on the coats of the blood-vessels (either directly or by means of altering the blood), thus depriving whole territories of their blood-vessels, is a question upon which the principal advocates of the parasitic theory have not yet agreed. Even Oertel acknowledges the impossibility of explaining the manner in which bacteria act (Ziemssen, Handbuch, ii., 1, p. 581, 2d ed.). This much is positive, at any rate: that no one has yet proven that the vegetable organisms alone, and not other, free or fixed, parts of the diphtheritic membrane, are the vehicles of the infecting elements (Steudener); and even now the question has not been decided whether the bacteria met with in diphtheria constitute the cause of the disease, or are a part of the process, or co-effects of the poisonous action—whether they are the carriers of the poison or entirely indifferent entities.
The most important observations made by those who deny a direct etiological connection between micro-organisms and septic diseases in general, and diphtheria in particular, are those of Hiller and Billroth. The latter has proven the morphological identity of the various kinds of bacteria, although it cannot be denied that the apparent similarity may mask a yet unknown difference. Hiller calls attention to the fact that large numbers of micrococci have been found in the cadaver where death has not been the result of septic disease, and also that septic infection is not always severest where the bacteria most abound, but where an extensive chemical decomposition or a mass of putrefying tissue is found. This would indicate that the septic process is rather dependent on chemical decomposition than on the presence of bacteria.
Panum, Bergmann, and Schmiedeberg have isolated poisons that contained no bacteria. Rawitsch and many others prove that septic infection is not dependent on the existence of bacteria. Davaine has shown that an infinitely small amount of a chemical poison, free from bacteria, can kill quickly.
The presence of cocco-bacteria (Billroth) in the blood during life has not once been proven, not even in pyæmia or septicæmia. Yet their being swept into the lungs with the atmospheric air is indisputable. It would therefore seem as though living blood had a greater tendency to destroy bacteria than to allow itself to be decomposed by them. Not only, however, would it seem so, but P. Grawitz (Virch. Arch., vol. lxx., p. 546) proves that sporules do not grow in the (tissue and) blood, but that they are in part dissolved, in part eliminated through the kidneys, and that this result is accomplished through the combination of the following four factors—viz. the elasticity of the blood, its constant motion, the absence of oxygen in sufficient quantity in the circulating blood, and the presence of living animal cells. All of these factors appear to be of great importance. Thus it is that, where the constant motion of the blood and the animal living cells are not present (as in the anterior chamber of the eye or in the humor vitreous) a rapid proliferation and accumulation of bacteria can take place. They are also known to increase rapidly and emigrate into the liver when deposited in the abdominal cavity.
The destruction of bacteria in the circulating blood, into which they may have penetrated, accounts for some microscopical facts in connection with (actually or apparently morbid) blood. Their remnants are probably the pale and dark particles which are discovered in the blood alongside the red and white blood-corpuscles. They could not be identified as micrococci, while in the tissue they are more recognizable. In autopsies they have been found in the urinary tubules, pressing forward and piercing the walls, not occupying a nidus of inflammation, however, and probably are even here a post-mortem phenomenon. A direct necrosis or inflammation by the inoculation of diphtheritic elements can only be produced in the cornea, as was shown by Recklinghausen, and particularly Eberth. Besides, there is nothing characteristic in the cocco-bacteria of diphtheria, with the exception, perhaps, of their browner color, to justify their being looked upon as a distinct variety, certainly not as another species. It is more likely that a difference of action is not so much to be sought for in a different parasite as in the peculiarity of the corneal tissue. When fluid containing cocco-bacteria was injected into the eye of a rabbit, in twenty-four hours the eye was destroyed. If injected into the eye of a dog or guinea-pig, only a slight inflammation resulted (Billroth and Ehrlich). If these experiments were continued on a larger scale, we might eventually, by analogy, infer, and even prove, that the immunity against certain diseases enjoyed by some animals is owing to peculiarities in the very structure of their own tissues. In a similar manner I shall prove hereafter that even peculiarities and variations in the tissue and epithelium of the human body give rise to different shades and variable clinical symptoms in the diphtheritic processes.
The views of Curtis, Satterthwaite, and Charlton Bastian fully agree with those of the above observers. The latter is rather inclined to look upon bacteria as an effect of the disease than as a cause. Similar views were expressed by Burdon Sanderson.
Nor are the researches of Weissgerber and Terls, Lukomsky, Weigert, Lücke, any more conclusive; and, finally, Fürbringer, in his most recent and careful studies of diphtheritic nephritis, insists upon this, that it is not caused by immigration of fungi into the kidneys, that the very best methods employed for the finding of parasites result in the absence of micrococci from the inflamed organ, and that the renal inflammation following diphtheria is the result of a chemical process.
H. C. Wood and Henry F. Formad, in Supplement 7 of the National Board of Health Bulletin (1880), declare it altogether improbable that bacteria have any direct function in diphtheria—i.e. that they enter the system as bacteria and develop as such in the system, and cause the symptoms. It is, however, possible that they may act upon the exudations of the trachea as the yeast-plant acts upon sugar, and cause the production of a septic poison which differs from that of ordinary putrefaction, and bears such relations to the system as to, when absorbed, cause the systemic symptoms of diphtheria. Now, these bacteria may be always in the air, but not in sufficient quantities to cause tracheitis, but enough when lodged in the membrane to set up the peculiar fermentation; whilst during an epidemic they may be sufficiently numerous to incite an inflammation in a previously healthy throat.
The same authors publish a number of other experiments and conclusions in Suppl. 17 (Jan., 1882): "There is no proof as yet that the micrococci are the cause of the disease. Their presence in the exposed dead tissue is no evidence, for the membrane represents but the necrotic mucous lining.... Indeed, when the healthy mucous membrane of the mouth or trachea is destroyed by caustics—for instance, ammonia—the eschar into which it is converted—really a pseudo-membrane—contains the same micrococci as are found in true diphtheria, as Wood and Formad have learned. Moreover, in the scrapings of the healthy tongue the same micrococci can be seen. Of more significance is the detection of the same or similar micrococci in the blood of the living patients during severe attacks. But since these parasites were found only in the more severe cases, and not in all instances of the disease, were seen also in the blood of other septic disorders, and since no cultures have been made with the fresh blood, there is not yet enough evidence for any decision. In the internal organs bacteria are not found with any regularity in diphtheria."6