The first principle in the etiological investigation of all vital processes, and therefore of those concerned in infectious diseases caused by micro-organisms, is thus formulated by Darwin: “That which is of the same origin belongs to the same species.” Two infectious agents may resemble each other ever so closely, but if they have not the same genealogy, i.e., if they are phylogenetically widely separated, then, biologically, they belong to different species. And conversely, size, form, and other properties of certain micro-organisms may be ever so different. If, however, the organisms are of the same origin, then, biologically, they belong to the same species. The virus of anthrax occurs in two forms: as bacilli, and as oval spores. The quotidian malaria parasite has an extraordinarily complicated cycle of development. Nevertheless we have no hesitancy in speaking of either an anthrax virus or of a malaria parasite.[2]
The virus of human tuberculosis, the tubercle bacillus of Koch, possesses narrowly limited morphological characteristics. It is readily recognized since Koch published his very accurate description of it in 1882, and especially since Ehrlich, shortly afterward, published a specific staining procedure. The tubercle bacilli are familiar to us as rods of varying length, but of fairly constant thickness, which occasionally show granular degeneration. I believe it is now everywhere accepted that the presence of these bacilli in a lesion in the human body indicates the tubercular character of that lesion. Leprous lesions with somewhat similar bacilli must, of course, be taken into account, but these, as a rule, can already be differentiated macroscopically.
Recognizing this significance of the presence of Koch’s bacilli and applying all other known methods for the identification of tuberculosis, Dr. Naegeli of Zürich, working under the direction of Prof. Ribbert, was unable to discover at autopsy a single body over thirty years old in which there were not some signs of the occurrence of a tubercular infection. Between the ages of 18 and 30 there were 96%; between 14 and 18, 50%; between 5 and 14, 33%; and between 1 and 5 years, 17%, which showed the presence of tubercular lesions. In the bodies of infants under one year, on the other hand, definite tubercular signs were invariably absent.
The astonishing results of these careful anatomical investigations have been verified by reports from pathological anatomists in other cities; yet at first sight, they seem to contradict all medical and other experience, for according to these results all of us assembled in this hall are tuberculous! But the perfected diagnosis of tuberculosis in the living person leaves no doubt that Naegeli’s figures, at least for thickly populated centers, possess general applicability. To be sure, if we count only the patients who come to the physician because of tubercular or supposedly tubercular symptoms, then our figures do not agree with Naegeli’s; nor will the statistics of living persons in whom we can discover tubercle bacilli agree with the autopsy statistics. The agreement, however, becomes very close if we make use of a diagnostic method furnished us by the second of Koch’s above-mentioned discoveries, the tuberculin injection.
Koch’s tuberculin is a water-soluble tubercular toxin, given off from the bodies of the tubercle bacilli to the culture medium, and concentrated together with glycerine. Injected either subcutaneously or intravenously it causes no reaction in persons free from tubercular infection. On the other hand, it is one of the strongest poisons for those who are under the influence of such an infection. Even before the infection has led to clearly recognizable lesions, and long before there are any symptoms of tubercular disease, and even if the most careful physical examination fails to discover a suspicion of tuberculosis during the entire lifetime of the individual, his peculiar susceptibility to this tuberculin injection shows that somewhere in his tissues or body fluids tubercle bacilli are producing their peculiar changes.
The nature of these changes is becoming somewhat clear to us since there have been discovered in the extra-vascular blood of tubercularly infected men and animals coagulation and agglutination phenomena which are entirely absent in the blood of non-infected individuals. It appears that the activities of the tubercle bacilli in the body of the host excite the production of a soluble anti-body. When this anti-body comes into contact with the water-soluble substances derived from the tubercle bacilli, Koch’s tuberculin, it is transformed into an insoluble body. According to my own researches I believe it probable that this anti-body is formed by the smallest arterioles in the neighborhood of the infected area. The extent of the agglutination phenomena varies according to the amount of anti-body and of the tuberculin with which it comes into contact. This manifests itself clinically, by the degree of fever, and anatomically, by intravascular coagulations. The latter, in some cases may lead to exudations or to the escape of blood from the pathologically altered vessels. As a result of the tubercular poisoning, we would then have, at autopsy, the typical picture of a tuberculin reaction.
Tuberculin, in its action as a blood poison for an individual infected with tuberculosis, behaves like many other infectious poisons. Very small fractions of the amount sufficient to threaten life cause a distinct reaction. This is manifested by a rise of temperature preceded by a sharp fall. I know, through personal experience, of a case of human tuberculosis in which more than a hundred times the usual diagnostic dose of tuberculin was administered. But aside from several days of high fever and a considerable feeling of illness, it had no damaging influence on the patient’s general condition. Koch, the discoverer of tuberculin, once took a strong dose of tubercular poison in the form of dead tubercle bacilli and became very ill. In his case probably a hundredth of the amount would have sufficed to cause transient temperature changes and thus have demonstrated that he also had once been infected with tubercle bacilli. Ten years ago I myself reacted to a dose of 4 mg. with fever and a pronounced feeling of illness which confined me to my bed for several days in San Remo. Therefore I have no doubt about the tubercular infection of my body.
The most instructive evidence to confirm the general truth of Naegeli’s figures is furnished by the results of investigations made by the Austrian army surgeon, Dr. Franz, on soldiers of two regiments of infantry. In order to avoid injuring the health of the individuals tested, Franz used only very small doses of tuberculin, 1 to 3 mg., which, in case the injection was repeated, was increased to 5 mg. In spite of this, and in spite of the fact that the soldiers represented the healthiest individuals of the population, he found in one regiment in the first year of service (1901) 61%, and in the second year of service 68% of tubercularly infected cases. Franz adds to his report, which at present I have only in manuscript, that when he employed the dose originally recommended by Koch, namely one centigram, his percentage for the twenty-first year of life approached Naegeli’s very closely, 96%!
On the other hand the Hungarian investigator Dr. Nikolaus Berend has not obtained a single positive tuberculin reaction in ninety-six very young children, in spite of the fact that among these were some very feeble individuals, and children of parents manifestly tubercular; and further, despite doses as high as 1 cg. We see then that herein also the statistics coincide with Naegeli’s post-mortem statistics.
Another proof that human tuberculosis is much more widely disseminated than was heretofore believed is furnished us by a diagnostic method devised by the French clinician André Jousset, namely “inoscopy.” By means of inoscopy we can examine microscopically, for tubercle bacilli, coagulable inflammatory exudates and the blood of suspected cases of tuberculosis, even though only very few bacilli are distributed in large amounts of fluid. And we examine these fluids directly, not indirectly by means of cultures. As a result of the coagulation the bacilli are fixed by the fibrin, from which they are freed by dissolving the fibrin with an appropriate digesting fluid.[3] The bacilli are then separated by centrifuge and can be examined directly in microscopical preparations. With the aid of this very valuable diagnostic method we are enabled to demonstrate the tubercular origin of almost all serous pleurisies, of many exudative peritonites, of accumulations of fluid in the peritoneal cavity of alcoholic individuals with liver cirrhosis, of joint inflammations, of exudative meningites, of many cases of heart-disease and of other classes of symptomatic affections, where formerly most physicians did not think of the possibility of these affections being tubercular.