CHAPTER VIII

BACTERIA AND DISEASE

Probably the most universally known fact respecting bacteria is that they are related in some way to the production of disease. Yet we have seen that it was not as disease-producing agents that they were first studied. Indeed, it is only within comparatively the latest period of the two centuries during which they have been more or less under observation that our knowledge of them as causes of disease has assumed any exactitude or general recognition. Nor is this surprising, for although an intimate relationship between fermentation and disease had been hinted at in the middle of the seventeenth century, it was not till the time of Pasteur that the bacterial cause of fermentation was experimentally and finally established.

In the middle of the seventeenth century men learned, through the eyes of Leeuwenhoek, that drops of water contained "moving animalcules." A hundred years later Spallanzani demonstrated the fact that putrefaction and fermentation were set up in boiled vegetable infusions when outside air was admitted, but when it was withheld from these boiled infusions no such change occurred. Almost a hundred years more passed before the epoch-making work of Tyndall and Pasteur, who separated these putrefactive germs from the air. Quickly following in their footsteps came Davaine and Pollender, who found in the blood of animals suffering from anthrax the now well-known specific and causal bacillus of that disease. Improvements in the microscope and in methods of cultivation (Koch's plate method in particular) soon brought an army of zealous investigators into the field, and during the last twenty years first this disease and then that have been traced to a bacterial origin. We may summarise the vast mass of historical, physiological, and pathological research extending from 1650 to 1898 in three great periods: the period of detection of living, moving cells (Leeuwenhoek and others in the seventeenth century); the period of the discovery of their close relationship to fermentation and putrefaction (Spallanzani, Schulze, Schwann, in the eighteenth century); and, thirdly, the period of appreciation of the rôle of bacteria in the economy of nature and in the production of disease (Tyndall, Pasteur, Lister, Koch, in the nineteenth).

But we must look less cursorily at the growth of the idea of bacteria causing disease. More than two hundred years ago Robert Boyle (1627–91), the philosopher, who did so much towards the foundation of the present Royal Society, wrote a learned treatise on The Pathological Part of Physic. He was one of the earliest scientists to declare that a relationship existed between fermentation and disease. When more accurate knowledge was attained respecting fermentation, great advance was consequently made in the etiology of disease. The preliminary discoveries of Fuchs and others between 1840 and 1850 had relation to the existence in diseased tissues of a large number of bacteria. But this was no proof that such germs caused such diseases. It was not till Davaine had inoculated healthy animals with bacilli from the blood of an anthrax carcass, and had thus produced the disease, that reliance could be placed upon that bacillus as the vera causa of anthrax. Too much emphasis cannot be laid upon this idea, that unless a certain organism produces in healthy tissues the disease in question, it cannot be considered as proven that the particular organism is related to the disease as cause to effect. In order to secure a standard by which all investigators should test their results, Koch introduced four postulates. Until each of the four has been fulfilled, the final conclusion respecting the causal agent must be considered sub judice. The postulates are as follows:

(a) The organism must be demonstrated in the circulation or tissues of the diseased animal.

(b) The organism thus demonstrated must be cultivated in artificial media outside the body, and successive generations of a pure culture of that organism must be obtained.

(c) Such pure cultures must, when introduced into a healthy and susceptible animal, produce the specific disease.

(d) The organism must be found and isolated from the circulation or tissues of the inoculated animal.

It is evident that there are some diseases—for example, cholera, leprosy, and typhoid—which are not communicable to lower animals, and therefore their virus cannot be made to fulfil postulate (c). In such cases there is no choice. They cannot be classified along with tubercle and anthrax. Bacteriologists have little doubt that Hansen's bacillus of leprosy is the cause of that disease, yet it has not fulfilled postulates (b) and (c). Nor has the generally accepted bacillus of typhoid fulfilled postulate (c), yet by the majority it is provisionally accepted as the agent in producing typhoid. Hence it will be seen that, though there is an academical classification of causal pathogenic bacteria according as they respond to Koch's postulates, yet nevertheless, there are a number of pathogenic bacteria which are looked upon as causes of disease provisionally. Anthrax and tubercle, with perhaps the organisms of suppuration, tetanus, plague, and actinomycosis, stand in the first order of pathogenic germs. Then comes a group awaiting further confirmation. It includes the organisms related to typhoid, cholera, malaria, leprosy, diarrhœa,and pneumonia. Then comes in a third category, a long list of diseases, such as scarlet fever, small-pox, rabies, and others too numerous to mention, in which the nature of the causal agent is still unknown. Hence it must not be supposed that every disease has its germ, and without a germ there is no disease. Such universal assertions, though not uncommonly heard, are devoid of accuracy.

In the production of bacterial disease there are two factors. First, there is the body tissue of the individual; secondly, there is the specific organism.

Whatever may be said hereinafter with regard to the power of micro-organisms to cause disease, we must understand one cardinal point, namely, that bacteria are never more than causes, for the nature of disease depends upon the behaviour of the organs or tissues with which the bacteria or their products meet (Virchow). Fortunately for a clear conception of what "organs and tissues" mean, these have been reduced to a common denominator, the cell. Every living organism, of whatever size or kind, and every organ and tissue in that living organism, contains and consists of cells. Further, these cells are composed of organic chemical substances which are not themselves alive, but the mechanical arrangement of which determines the direction and power of their organic activity and of their resistance to the specific agents of disease. With these facts clearly before us, we may hope to gain some insight into the reasons for departure from health.

The normal living tissues have an inimical effect upon bacteria. Saprophytic bacteria of various kinds are normally present on exposed surfaces of skin or mucous membrane. Tissues also which are dead or depressed in vitality from injury or previous disease, but which are still in contact with the tissues, afford an excellent nidus for the growth of bacteria. Still these have not the power, unless specific, to thrive in the normal living tissue. It has been definitely shown that the blood fluids of the body have in their fresh state the germicidal power (alexines) which prevents bacteria from flourishing in them. Such action does undoubtedly depend in measure upon the number of germs as well as their quality, for the killing power of blood and lymph must be limited. Buchner has pointed out that the antagonistic action of these fluids depends in part possibly upon phagocytosis, but largely upon a chemical condition of the serum. The blood, then, is no friend to intruding bacteria. Its efforts are to a certain extent seconded by the lymphoid tissue throughout the body. Rings of lymphoid tissue surround the oral openings of the trachea (windpipe) and œsophagus (gullet); the tonsils are masses of lymphoid tissue. Composed as it is of cells having a germicidal influence when in health, the lymphoid tissue may afford formidable obstruction to intruding germs.

All the foregoing points in one direction, namely, that if the tissues are maintained in sound health, they form a very resistant barrier against bacteria. But we know from experience that a full measure of health is not often the happy condition of human tissues; we have, in short, a variety of circumstances which, as we say, predispose the individual to disease. One of the commonest forms of predisposition is that due to heredity. Probably it is true that what are known as hereditary diseases are due far more to a hereditary predisposition than to any transmission of the virus itself in any form. Antecedent disease predisposes the tissues to form a nidus for bacteria; conditions of environment or personal habits frequently act in the same way. Damp soils must be held responsible for many disasters to health, not directly, but indirectly, by predisposition; dusty trades and injurious occupations have a similar effect. Any one of these three different influences may in a variety of ways affect the tissues and increase their susceptibility to disease. Not infrequently we may get them combined. For example, the following is not an unlikely series of events terminating in consumption (tuberculosis of the lungs):—(a) The individual is predisposed by inheritance to tuberculosis; (b) an ordinary chronic catarrh, which lowers the resisting power of the lungs, may be contracted; (c) the epithelial collections in the air vesicles of the lung—i. e., dead matter attached to the body—afford an excellent nidus for bacteria; (d) owing to occupation, or personal habits, or surroundings, the patient comes within a range of tubercular infection, and the specific bacilli of tubercle gain access to the lungs. The result, it is needless to state, will be a case of consumption more or less acute according to environment and treatment.

The channels of infection by which organisms gain the vantage-ground afforded by the depressed tissues are various, and next to the maintenance of resistant tissues they call for most attention from the physician and surgeon. It is in this field of preventive medicine—that is to say, preventing infective matter from ever entering the tissues at all—that science has triumphed in recent years. It is, in short, applied bacteriology, and therefore claims consideration in this place.

1. Pure Heredity. By this term may be understood the actual transmission from the mother to the unborn child of the specific virus of the disease. That such a conveyance may occur is generally admitted by pathologists, but it is impossible to enter fully into the matter in such a book as the present. Summarily we may say that, though this sort of transmission is possible, it is not frequent, nor is disease appreciably spread through such a channel. Sixty per cent. of consumptives, it has been estimated, have tuberculous progenitors, and this is the highest figure. Many would be justified from experience in placing it at half that number.

2. Inoculation, or inserting virus through a broken surface of skin, is itself a sufficiently obvious mode of infection to call for little comment. Yet it is under this heading that a word must be said of that remarkable application of preventive medicine known as the antiseptic treatment of wounds. When Lord Lister was Professor of Surgery in Glasgow, he was impressed with the greatness of the evil of putrefaction in wounds, which was caused, not by the oxygen of the air, as Liebig had declared, but by the entrance into the wound of fermentative organisms from the air. This was demonstrated by Pasteur, who pointed out that they could not arise de novo in the wound. Hence it appeared to Lister that these fermentative bacteria which produce putrefaction in wounds must either be kept out of the wound altogether, or killed, or their action prevented, in the wound. To keep air away from wounds is an almost impossible task, and thus it came about that wounds were dressed with a solution of carbolic acid.

From time to time examples occur of bacterial disease being directly inoculated in wounds made with polluted instruments, or in cuts made by contaminated broken glass, or in gunshot wounds. Tetanus is, of course, one of the most marked examples.

3. Contagion is a term which has suffered from the many ways in which it has been used. Defined shortly and most simply, we should say a disease is contagious when it can be "caught" by contact, through the unbroken surfaces, between diseased and healthy persons. Ringworm is an example, and there are many others.

4. The Alimentary Canal: Food. The recent Royal Commission on Tuberculosis has collected a large mass of evidence in support of the view that tubercle may be spread by articles of food. Milk and meat from tuberculous animals naturally come in for the largest amount of condemnation. To these matters we refer elsewhere.

5. The Respiratory Tract: Air. The air may become infected with germs of disease from dusty trades, dried sputum, etc. If such infected air be inhaled, pathogenic results will follow, especially if the bacteria are present in sufficient numbers, or meet with devitalised, and therefore non-resisting, tissues.

These, then, are the five possible ways in which germs gain access to the body tissues. The question now arises, How do bacteria, having obtained entrance, set up the process of disease? For a long time pathologists looked upon the action of these microscopic parasites in the body as similar to, if not identical with, the larger parasites sometimes infesting the human body. Their work was viewed as a devouring of the tissues of the body. Now, it is well known that, however much or little of this may be done, the specific action of pathogenic bacteria is of a different nature. It is twofold. We have the action of the bacteria themselves, and also of their products or toxins. In particular diseases, now one and now the other property comes to the front. In bacterial diseases affecting or being transmitted mostly by the blood, it is the toxins which act chiefly. The convenient term infection is applied to those conditions in which there has been a multiplication of living organisms after they have entered the body, the word intoxication indicating a condition of poisoning brought about by their products. It will be apparent at once that we may have both these conditions present, the former before the latter, and the latter following as a direct effect of the former. Until intoxication occurs there may be few or no symptoms, but directly enough bacteria are present to produce in the body certain poisons in sufficient amount to result in more or less marked tissue change, then the symptoms of that tissue change appear. This period of latency between infection and the appearance of the disease is known as the incubation period. Take typhoid, for example. A man drinks a typhoid-polluted water. For about fourteen days the bacilli are making headway in his body without his being aware of it. But at the end of that incubation period the signs of the disease assert themselves. Professor Watson Cheyne and others have maintained that there is some exact proportion between the number of bacteria gaining entrance and the length of the incubation period.

Speaking generally, we may note that pathogenic bacteria divide themselves into two groups: those which, on entering the body, pass at once, by the lymph or blood stream, to all parts of the body, and become more and more diffused throughout the blood and tissues, although in some cases they settle down in some spot remote from the point of entrance, and produce their chief lesions there. Tubercle and anthrax would be types of this group. On the other hand, there is a second group, which remain almost absolutely local, producing only little reaction around them, never passing through the body generally, and yet influencing the whole body eventually by means of their ferments or toxins. Of such the best representatives are tetanus and diphtheria. The local site of the bacteria is, in this case, the local manufactory of the disease.

Whilst the mere bodily presence of bacteria may have mechanical influence injurious to the tissues (as in the small peripheral capillaries in anthrax), or may in some way act as a foreign body and be a focus of inflammation (as in tubercle), the real disease-producing action of pathogenic bacteria depends upon the chemical poisons (toxins) formed directly or indirectly by them. Though within recent years a great deal of knowledge has been acquired about the formation of these bodies, their exact nature is not known. They are allied to albuminous bodies and proteoses, and are frequently described as tox-albumens. It may be found, after all, that they are not of a proteid nature. Sidney Martin has pointed out that there is much that is analogous between the production of toxins and the production of the bodies of digestion. Just as ferments are necessary in the intestine to bring about a change in the food by which the non-soluble albumens shall be made into soluble peptones and thus become absorbed through the intestinal wall, so also a ferment may be necessary to the production of toxins. Such ferments have not as yet been isolated, but their existence in diphtheria and tetanus is, as we have seen, extremely likely. However that may be, it is now more or less established that there are two kinds of toxic bodies, differing from each other in their resistance to heat. It may be that the one most easily destroyed by heat is a ferment and possibly an originator of the other. A second division which has been suggested for toxic bodies, and to which reference has been made, is intracellular and extracellular, according to whether or not the poison exists within or without the body of the bacillus.

Lastly, we may turn to consider the action of the toxins on the individual in whose body-fluids they are formed. It is hardly necessary to say that any action which bacteria or toxins may have will depend upon their virulence, in some measure upon their number, and not a little upon the channel of infection by which they have gained entrance. It could not be otherwise. If the virulence is attenuated, or if the invasion is very limited in numbers, it stands to reason that the pathogenic effects will be correspondingly small or absent. The influence of the toxins is twofold. In the first place (i.) they act locally upon the tissues at the site of their formation, or at distant points by absorption. There is inflammation with marked cell-proliferation, and this is, more or less rapidly, followed by a specific cell-poisoning. The former change may be accompanied by exudation, and simulate the early stages of abscess formation; the latter is the specific effect, and results, as in leprosy and tubercle, in infective nodules. The site in some diseases, like typhoid (intestinal ulceration, splenic and mesenteric change) or diphtheria (membrane in the throat), may be definite and always the same. But, on the other hand, the site may depend upon the point of entrance, as in tetanus. The distant effects of the toxin are due to absorption, but what controls its action it is impossible to say. We only know that we do find pathological conditions in certain organs at a distance and without the presence of bacteria. We have a parallel in the action of drugs; for example, a drug may be given by the mouth and yet produce a rash in some distant part of the body. In the second place (ii.) toxins produce toxic symptoms. Fever and many of the nervous conditions resulting from bacterial action must thus be classified. We have, it is true, the chemical symptoms of the pathological tissue change, for example, the large spleen of anthrax or the obstruction from diphtheritic membrane. But, in addition to these, we have general symptoms, as fever, in which after death no tissue change can be formed.

We may now consider briefly some of the more important types of disease produced by bacteria:

1. Tuberculosis.90 As far back as 1794 Baillie drew attention to the grey miliary nodules occurring in tuberculous tissue which gave rise to the term "tubercles." This preliminary matter was confirmed by Bayle in 1810.

In 1834 Laennec described all caseous deposits as "tubercles," insisting upon four varieties:

(1) Miliary, which were about the size of millet seeds, and in groups;

(2) Crude, miliary tubercles in yellow masses;

(3) Granular, similar to the last, but scattered;

(4) Encysted, a hard mass of crude tubercle with a fibrous or semi-cartilaginous capsule.

The tubercle possesses in many cases a special structure, and certain cell-forms frequently occur in it and give it a characteristic appearance. The central part of the tubercle usually contains giant cells with numerous nuclei. The uninuclear cells are partly lymphoid, partly large epithelial or endothelial cells; these are called epithelioid cells.

It was not till 1865 that the specific nature of tuberculosis was asserted by Villemin. Burdon Sanderson (1868–69) in England confirmed his work, and it was extended by Connheim, who a few years later laid down the principle that all is tubercular which by transference to properly constituted animals is capable of inducing tuberculosis, and nothing is tubercular unless it has this capability.

Klebs (1877) and Max Schiller (1880) described masses of living cells or micrococci in many tuberculous nodules in the diseased synovial membrane and in lupus skin. In 1881 Toussaint declared he had cultivated from the blood of tubercular animals and from tubercles an organism which was evidently a micrococcus, and in the same year Aufrecht stated that the centre of a tubercle contained small micrococci, diplococci, and some rods. But it was not till the following year, 1882, that Koch discovered and demonstrated beyond question the specific Bacillus tuberculosis.

It is now held to be absolutely proved that the introduction of the bacillus, or its spores or products, is the one and only essential agent in the production of tuberculosis. Its recognised manifestations are as follows:

The disease may occur generally throughout the body or locally in the suprarenal capsules, prostate, intestine, larynx, membranes of the heart, bones, ovaries, pleura, kidneys, spleen, testicles, Fallopian tubes, uterus, etc.

We may summarise the history of the pathology of tubercle thus:

1794. Baillie drew attention to grey miliary nodules occurring in tuberculosis, and called them "tubercles."

1834. Laennec described four varieties: miliary; crude; granular; encysted.

1843. Klencke produced tuberculosis by intravenous injection of tubercular giant cells.

1865. Villemin demonstrated infectivity of tubercular matter by inoculation of discharges; Connheim, Armanni, Burdon Sanderson, Wilson Fox, and others showed that nothing but tubercular matter could produce tuberculosis.

1877. Living cells were found in tubercles, "micrococci" (Klebs, Toussaint, Schiller).

1882. Koch isolated and described the specific bacillus, and obtained pure cultivations (1884).

The Bacillus of Koch, 1882. Delicate cylindrical rods, measuring 1.5–4 micromillimetres in length and about .2 µ in breadth; non-motile. Many are straight with rounded ends; others are slightly curved. They are usually solitary, but may occur in pairs, lying side by side or in small masses. They are chiefly found in fresh tubercles, more sparingly in older ones. Some lie within the giant cells; others lie outside; shorter in tissue sections of bovine tuberculosis, but longer in the milk (Crookshank).

When stained they appear to be composed of irregular cubical or spherical granules within a faintly stained sheath. In recent lesions the protoplasm appears more homogeneous, and takes on the segmented or beaded character only in old lesions, pus, or sputum.

Morphological differences are found under different circumstances, and within limits variation occurs according to the environment.

Cultivation on Various Media. Koch inoculated solid blood serum with tubercular matter from an infected lymphatic gland of a guinea-pig, and noticed the first signs of growth in ten or twelve days in the form of whitish, scaly patches. These enlarged and coalesced with neighbouring patches, forming white, roughened, irregular masses. Nocard and Roux showed that by adding 5/8 per cent. of glycerine to the media commonly used in the laboratory, such as nutrient agar or broth, the best growth is obtained.

On glycerine broth or glycerine agar abundant growth appears at the end of seven or eight days. By continuous sub-culture on glycerine agar the virulence of the bacillus is diminished. But in fifteen days after inoculation of the medium the culture equals in extent a culture of several weeks' age on blood serum.

Sub-cultures from glycerined media will grow in ordinary broth without glycerine (Nocard, Roux, Crookshank).

In alkaline broth to which a piece of boiled white of egg was added Klein obtained copious growths, and found that continued sub-culturing upon this medium also lessens the virulence.

Description of Cultivations:—On glycerine agar minute white colonies appear in about six days, raised and isolated, and coalescing as time advances, forming a white lichenous growth, fully developed in about two months.

On glycerine broth a copious film appears on the surface of the liquid, which if disturbed falls to the bottom of the flask as a deposit.

Spore Formation. In very old cultivations spore-like bodies can be observed both in stained and unstained preparations, but neither the irregular granules within the capsule nor the unstained spaces between the granules are spores (Babes and Crookshank). That the bacilli possess spores is believed on account of the following facts:

1. That tubercular sputum, when thoroughly dried, maintains its virulent character (Koch, Schill, Fischer, etc.). No sporeless bacillus is known which can survive through drying.

2. That tubercular matter and cultures survive temperature up to 100° C. Non-spore-bearing bacilli and micrococci are killed by being exposed for five minutes to a temperature of 65–70° C., whereas spores of other bacilli withstand much higher temperatures.

3. Tubercular sputum distributed in salt solution does not lose its virulence by being kept at 100° C. for one or two minutes; sporeless bacilli certainly would (Klein).

4. A solution of per-chloride of mercury does not kill the tubercle bacilli, as it does sporeless bacilli (Lingard and Klein).

Koch and many bacteriologists have declared the bacillus to be a "true parasite." Koch based this view upon the belief which he entertained that the bacillus can grow only between 30° C. and 41° C., and therefore in temperate zones is limited to the animal body and can originate only in an animal organism. "They are," he said, "true parasites, which cannot live without their hosts. They pass through the whole cycle of their existence in the body." But at length Koch and others overcame the difficulties and grew the bacillus as a saprophyte.

Schottelius92 has observed that tubercle bacilli taken from the lung of phthisical persons buried for years still retains its virulence and capability of producing tuberculosis upon inoculation. He further shows that tubercular lung kept in soil (enclosed in a box) shows a marked rise in temperature. Klein quotes these experiments as indications that "tubercle bacilli are not true parasites, but belong to the ectogenic microbes which can live and thrive independent of a living host."

It has now been abundantly proved that the bacillus of tuberculosis is capable of accommodating itself to circumstances much less favourable than had been supposed, especially as regards temperature.

Temperature of Growth of Bacillus. 30–41° C. have been laid down by Koch as the limits of temperature at which the bacillus will grow in culture medium outside the body. The generally accepted temperatures as most favourable to the growth of the bacillus are between 36° C. and 38° C.

Sir Hugh Beevor, however, was able to grow the bacillus upon glycerine agar at 28° C. (82° F.), obtaining an ample culture which developed somewhat more slowly than on blood serum, and to a less extent than at 37° C. In both Beevor succeeded in growing the bacillus at a lower temperature even than on agar, viz., at a temperature rarely above 60° F. Sheridan Delépine and others have also been successful in obtaining growths at room temperature both in summer and winter.

Although, speaking generally, there is an actual cessation of growth at low temperature, the bacillus may be exposed to very low temperatures for a considerable time without losing its power of again becoming active when returned to a favourable environment (Woodhead).

The Relation of the Bacillus to the Disease. All four of Koch's postulates have been fulfilled in the case of Bacillus tuberculosis. Hence we are dealing with the specific cause of the disease. Yet, whilst this is so, we may usefully ask ourselves: How does the bacillus set up the changes in normal tissues which result in tubercular nodules? In arriving at a solution of this problem we are materially aided if we bear in mind the fact that such an organism in healthy tissues has a double effect. First, there is an ordinary inflammatory irritation, and secondly, there is a specific change set up by the toxins of the bacillus. Directly the invading bacilli find themselves in a favourable nidus they commence multiplication. In three or four days this acts as an irritant upon the surrounding connective-tissue cells, which proliferate, and become changed into large cells known as epithelioid cells. At the periphery of this collection of epithelioid cells we have a congested area. This change has been accomplished by the presence of the bacilli themselves. The production of their specific poisons changes the epithelioid cells in the centre of the nodule, some of which become fused together, whilst others expand and undergo division of nucleus. By this means we obtain a series of large multi-nucleated cells named giant cells. If the disease is very active, these soon caseate and break down in the centre. In a limb we get a discharge; in a lung we get an expectoration. Both discharge and expectoration arise from a breaking down of the new cell formation. Previously to breaking down we have in a fully developed nodule healthy tissue, inflammatory zone, epithelioid cells, giant cells, containing nuclei and bacilli. The sputum or the discharge will, during the acute stage of the disease at all events, contain countless numbers of the bacilli, which may thus be readily detected, and their presence used as evidence of the disease. It is obvious that if the centre of the nodule degenerates and comes away as discharge a cavity will be left behind. By degrees this small cavity may become a very large one, as is frequently the case in the lung, which particularly lends itself to such a condition. Hence, though at the outset a tubercular lung is solid, at the end it is hollow.

The exact period of giant-cell formation depends on the rapidity of the formative processes. Thus different conditions occur. Inside the giant cells the bacilli are arranged in relation to the nuclei in one of three ways: (a) polar, (b) zonal, or (c) mixed. The breaking down of the nodule is partly due to the cell-poisons, and partly because the nodule is non-vascular, owing to the fact that new capillaries cannot grow into the dense nodule, and the old ones are all occluded by the growth of the nodule.

From the local foci of disease the tubercle process spreads chiefly by three channels:

(a) By the lymphatics, affecting particularly the glands. Thus we get tuberculosis set up in the bronchial, tracheal, mediastinal, and mesenteric glands, and it is so frequently present as to be a characteristic of the disease. This is the common method of dissemination in the body.

(b) By the blood-vessels, by means of which bacilli may be carried to distant organs.

(c) By continuity of tissues, infective giant-cell systems encroaching upon neighbouring tissues, or discharge from lungs or bronchial glands obtaining entrance to the gullet and thus setting up intestinal disease also.

It has been abundantly proved that the respiratory and digestive systems are principally affected by Koch's bacillus. Wherever the bacilli are arrested, they excite formation of granulations or miliary tubercular nodules, which increase and eventually coalesce. The lymphatic glands which collect the lymph from the affected region are the earliest affected, always the nearest first, and then the disease appears to be appreciably stopped on its invading march. Each lymphatic gland acts as a temporary barrier to progress until the disease has broken its structure down. It remains local, in spite of increase in number and importance of the foci of disease, as long as the bacilli have not gained access to the blood stream.

Toxins and Tuberculin. Koch, Crookshank, and Herroun, Hunter, and others have isolated products from pure cultures of the tubercle bacillus. These have comprised chiefly albumoses, alkaloids, and various extractives. Koch's observations led him to suppose that in pure cultures of tubercle a substance appeared having healing action on tuberculosis, and an extract of this in glycerine he termed "tuberculin." It was made as follows: A veal broth containing peptone and glycerine was inoculated with a pure culture of the bacillus and incubated at 38° C. for six or eight weeks. An abundant growth with copious film formation appeared. The culture was then concentrated by evaporation over a water-bath until reduced to about one-tenth of its volume.

The announcements in 1890 and 1891 to the effect that a "cure" had been discovered for consumption will be remembered. The hopes thus raised were unfortunately not to be realised. Koch advocated injections of this tuberculin in cases of skin tubercle (lupus) and consumptive cases. In many of these benefit was apparently derived, but its general application was not founded upon any substantial basis. Dead tissue, full of bacilli, could not thus be got rid of; nor could the career of the isolated bacilli distributed through the body be thus checked.

Tuberculin has, however, found a remarkable sphere of usefulness in causing reaction in animals suffering from tuberculosis. Indeed, tuberculin is the most valuable means of diagnosis that we possess (MacFadyen). When injected (dose, 30–40 centigrammes) it causes a rise of one and a half to three degrees. The fever begins between the twelfth and fifteenth hour after injection, and lasts several hours. The duration and intensity of the reaction have no relation to the number and gravity of the lesions, but the same dose injected into healthy cattle causes no appreciable febrile reaction. The tuberculous calf reacts just as well as the adult, but the dose is generally 10–20 centigrammes. Injections of tuberculin have no troublesome effect on the quantity or quality of the milk of cows or on the progress of gestation.

Tuberculosis of Animals. Cattle come first amongst animals liable to tubercle. Horses may be infected, but it is comparatively rare, and among small ruminants the disease is rarer still. Dogs, cats, and kittens may be easily infected. Amongst birds, fowls, pigeons, turkeys, and pheasants, the disease assumes almost an epidemic character. Especially do animals in confinement die of tubercle, as is illustrated in zoölogical gardens. Respecting the lesions of bovine tuberculosis, it will be sufficient to say that nothing is more variable than the localisation or form of its attacks. The lungs and lymphatic glands come first in order of frequency, next the serous membranes, then the liver and intestines, and lastly the spleen, joints, and udder (Nocard).

The anatomical changes in bovine tubercle are mostly found in the lungs and their membranes, the pleuræ. It also affects the internal membrane lining, the abdomen and its chief organs, the peritoneum, and the lymphatic glands. In both these localities a characteristic condition is set up by small grey nodules appearing, which increase in size, giving an appearance of "grapes." Hence the condition is called grape disease, or Perlsucht. The organs, as we have said, are equally affected, and when we add the lymphatic glands we have a fairly complete summary of the form of the disease as it occurs in cattle. As has been clearly pointed out by Martin, Woodhead, and others in their evidence before the Royal Commission, the organs, glands, and membranes are the sites for tubercle, not the muscles (or "meat"). This latter is most liable to convey infection when the butcher smears it with the knife which he has used to remove tubercular organs.

As regards the udder in its relation to milk infection, it may be desirable to state that the initial lesion, according to Nocard and Bang, takes the form of a progressive sclerosis. The interlobular connective tissue, normally scanty, becomes thickened, fibrous, and infiltrated by minute miliary granulations. The granular tissue is thus "smothered by the hypertrophy and fibrous transformation of the interstitial connective tissue" (Nocard). The walls of the ducts are thickened and infiltrated, the lumen frequently dilated by masses of yellow caseous material. On the whole it may be said that tubercle of the udder is rare. Usually only one quarter is attacked, and by preference the posterior. For some time the milk remains normal, but gradually it becomes serous and yellow, and contains coagula holding numbers of bacilli. Lastly, it becomes purulent and dries up altogether. While the milk is undergoing these changes the lesion of the udder is becoming more marked, the tissue becomes less supple, and the toughness increases almost to a wooden hardness.

The general anatomical characteristics of the disease are similar to those occurring in man.

The percentage of cattle suffering from tubercle varies. In Germany it appears to vary from 2 to 8 per cent. of all cattle, in Saxony 17 to 30 per cent., in England 22 per cent. approximately (in London 40 per cent.), in France 25 per cent. Lowland breeds are much more infected than mountain breeds, which possess stronger constitutions.

Tuberculosis of the pig is less common than that of cattle, but not so rare as that of the calf (Nocard). In nine out of ten cases the pig is infected by ingestion, particularly when fed on the refuse from dairies and cheese factories. The disease follows the same course as in cattle. The finding of the bacillus is difficult, and the only safe test is inoculation (Woodhead).

Sheep are very rarely tuberculous by nature, though there is evidence to believe that very long cohabitation with tuberculous cattle would succeed in transmitting tuberculosis to some sheep.

Tuberculosis in the horse is relatively very rare. It attacks the organs of the abdominal cavity, especially the glands; it affects the lung secondarily as a rule. The cases are generally isolated ones, even though the animal belongs to a stud. Nocard holds that the bacillus obtained from the pulmonary variety is like the human type, whilst the abdominal variety is more like the avian bacillus.

Nocard says93:

Tuberculosis is a common disease among the birds of the poultry-yard: poultry, pigeons, turkeys, pea-fowl, guinea-fowl, etc. They are infected almost exclusively through the digestive tract, generally by devouring infected secretions of previous tubercular fowls. Whatever the position or form of avian tuberculosis, the bacilli are present in enormous numbers, and are often much shorter and sometimes much longer than those met with in tuberculous mammalia, and grow outside the body at a higher temperature (43° C.). They are also said to be more resistant and of quicker growth. The species is probably identical with Koch's bacillus, though there are differences. In the nodule, which is larger than in human tuberculosis, there are few or no giant cells, and it does not so readily break down.

Nocard and others have demonstrated the fact that the Bacillus tuberculosis of Koch is the common denominator in all tubercular disease, whatever and wherever its manifestations, in all animals. The bacillus, they hold, may, however, experience profound modifications by means of successive passages through the bodies of divers species of animals. But if the modifications which it undergoes as a result of transmissions through birds, for example, are profound enough to make the bacillus of avian tubercle a peculiar variety of Koch's bacillus, they are not enough, it is generally believed, to make these bacilli two distinct species.

We may, therefore, take it for granted that tuberculosis is one and the same disease, with various manifestations, common to man and animals, intercommunicable, and having but one vera causa: the Bacillus tuberculosis of Koch.

The Prevention of Tuberculosis. At the present time much attention is being directed to the administrative personal control of tuberculosis. How greatly this is needed in so preventable a disease is evident from a perusal of the following quotation from the Registrar-General's reports. (See opposite page.)

These figures show a marked decline in the three worst forms of the disease. But this decline is apparently less marked in tabes than in phthisis or tubercular meningitis, i. e., less in the kind of tubercle due to the ingestion of infected milk. Fortunately the State is beginning to realise its duty in regard to preventive measures. The abolition of private slaughter-houses, the protection of meat and milk supplies, the seizure of tuberculous milch cows, and such like measures fall obviously within the jurisdiction of the State rather than the individual, and claim the earnest and urgent attention of the public health departments of states.94

ENGLISH DEATH-RATES FROM ALL TUBERCULAR DISEASES

THE FOLLOWING IS A TABLE OF DEATH-RATES TO A MILLION LIVING (ENGLAND), 1877–1897 (Reg.-Gen. Annual Reports):—