Part 33

Though but fifty years old, the science of Bacteriology has itself undergone repeated subdivision. Noteworthy though the results of this process of constant subdivision have proved, it must be emphasized that the state of scientific subdivision cannot be final, and is indeed without meaning unless it lead to a subsequent synthesis--an event which we still await. It is the general Laws reached by these special sciences that are philosophically important, and the specialist himself is often ill-placed and ill-equipped for the estimation of the true significance of such Laws. The philosophic thinker who deals with generalities and centuries must often be content to pass the details in silence. Nor is this true only of the professed philosopher. It applies no less to the philosophical physician. It is his task to try to see life steadily and see it whole. He must think both in terms of the individual life and of the community life, and for him the results of the bacteriologist, the physiologist, and of all their colleagues are as means to an end. It is from this standpoint that we should seek to visualize the fruits that bacteriological science in this last age has laid at the feet of humanity.

With Koch’s work on Anthrax in 1876, on the bacteria that commonly infect wounds in 1878, and with his great discovery of the bacillus of Tuberculosis in 1882, the study of the infective diseases entered on a new stage. The enemy had been seen and was now known for what he was. The bacteriologist had succeeded in making prisoners. These had been isolated and made to live in test-tubes. Moreover, the organisms had been compelled to dwell alone without mixing with other species. They had been obtained, as bacteriologists say, in ‘pure cultures’, and delicate methods of detecting and differentiating them had been developed. With a pure culture in his hands, the bacteriologist can determine the influences favorable or unfavorable to the growth of the disease organism, and he can investigate conditions that can exalt, destroy, or modify its activity (p. 233).

An important series of criteria established by Koch have remained the tests by which the disease-bearing character of these organisms can be established. To prove that an organism is the inseparable cause of any disease we need to demonstrate:

1. The constant presence of the organism in every case of the disease.

2. The preparation of a pure culture, which must be maintained for repeated generations.

3. The reproduction of the disease in animals by means of a pure culture removed by several generations from the organisms first obtained.

These conditions have been fulfilled for many diseases. Evidently the third test can be applied only in conditions to which animals other than man are susceptible. Now in this matter the organisms that produce disease vary greatly. Some, for instance those of Anthrax, are easily conveyed to a variety of species of animals; others, for instance those of Syphilis, are with difficulty conveyed to very few species of animal; yet others, for instance human Malaria, cannot be conveyed to any animal save man.

Some light is thrown on the life-history of the second and third classes by recent discoveries. The science of Comparative Pathology, that is the knowledge of the relations of the diseases of different species of animals, is of very recent growth. It has already demonstrated, however, the existence of organisms bearing some resemblance, for instance, to those of human Syphilis and human Malaria as the cause of disease in animals. By studying the life-history of these organisms in animals and by studying their effect on animals, valuable side-lights have often been thrown on the allied diseases in man. Moreover, in exceptional cases and in some special diseases, it has been possible to convey a disease experimentally to man.

A second important factor has gradually come into prominence with the extension of bacteriological knowledge. It is evident that not all men are subject to all human diseases. Even in the most destructive epidemic there are some that escape. These lucky ones may be naturally ‘immune’. Many diseases, such as Measles, seldom recur in individuals who have been infected, so our lucky ones may thus have an ‘Acquired Immunity’.

The general nature of Immunity we shall presently discuss (p. 259), but we note here that Immunity may be relative or absolute, and may, moreover, vary according to the circumstances of the individual. Thus, for instance, a well-fed, well-housed person of temperate habits, living an open-air life, is unlikely to develop consumption. Restrict his diet, confine him in an office, deteriorate his mode of life, and he may well fall a victim to it. The investigation of facts such as these on a large scale has demonstrated that the soil in which disease grows is of no less import than the seed from which it grows. The problem of disease causation is thus immensely complex. We are only just beginning to draw up general laws on the subject, and in approaching it we are beyond the frontiers of our positive knowledge. Turned back from this difficult borderland, we must content ourselves with surveying a part of the better-known territory and considering a few specific bacteriological achievements. These we may now consider under the headings of the diseases associated with them.

§ 11. Some Important Bacteriological Results.

Diphtheria is a disease for which physicians now habitually demand a bacteriological diagnosis. Bretonneau of Tours (p. 185), working on clinical and post-mortem material, and without the use of a microscope, was able to distinguish Diphtheria as a specific disease (1826). Half a century later (1883) Edwin Klebs (1834-1913) of Zürich, a pupil of Virchow, described the specific organism of the disease. In the following year Friedrich Loeffler (1852-1915), a Prussian and an assistant of Koch, succeeded in cultivating it. The organism has since been known as the ‘Klebs-Loeffler Bacillus’. Its study has thrown much light on the nature of bacterial action in general and has, moreover, led to important therapeutic developments (p. 263).

Of all diseases destructive of human life, none is so dramatic as Plague, the scourge of mankind throughout history. The bacillus of Plague was discovered independently by the Japanese Shibasaburo Kitasato (c. 1860-), a pupil of Koch, and by the Frenchman Alexandre Yersin (1863-), a pupil of Pasteur, during an epidemic at Hong Kong in 1894. These two observers cultivated the organism and reproduced the disease by inoculation of pure cultures in animals. It had long been observed that outbreaks of a deadly disease of rats and mice were liable to precede Human Plague. These ‘epizootics’ which precede ‘epidemics’ are now known to be due to the bacillus of Plague. A mass of evidence has been collected to show that the normal carrier of the Plague infection is the rat flea. This knowledge has led to the formulation of effective measures for the control of Plague. These measures are based on the wholesale extermination of the rat population which harbors the infective fleas. The study of the Natural History of the Plague Bacillus has also led to prophylactic measures for the safety of individuals.

FIG. 114. BACILLI OF DIPHTHERIA FROM A CULTURE. Highly magnified. In cultures these bacilli are liable to degenerate into thick club-shaped forms several of which are here seen.

Malta Fever is a disease of much wider distribution than its name implies. Not only is it found throughout the Mediterranean area, but it is also encountered in China, South Africa, and parts of both North and South America. It is a long, tedious and wearing disease, and though the mortality from it is low, yet it was at one time one of the main causes of disability in the British army at Malta. In 1887 an English military surgeon, David Bruce (1855-), succeeded in cultivating a characteristic bacillus from the spleen of a patient dead of the disease, and he established its causal relation to Malta Fever. In 1904 its mode of propagation was studied by a British Government Commission. The goat was shown to be the normal host of the bacillus, and in Malta 50 per cent. of these animals were found to be infected. The disease, it was discovered, is usually transmitted by goat’s milk. The knowledge has led to the application of very effective precautions (Fig. 116).

FIG. 116. DIAGRAM SHOWING THE INCIDENCE OF MALTA FEVER in the British garrison at Malta immediately before and immediately after the institution of the preventive measure of cutting off the supply of unboiled goats’ milk. The figures of 1905--before the new regulation came into force--are represented in black. The figures in the margin refer to the number of cases per ten thousand of strength. The figures for 1907 are represented in white on the same scale. There is a drop in the maximum monthly incidence from 94 to 2. The size of the garrison itself remained almost constant throughout the period. ]

Among the most anciently described diseases is the condition known as Tetanus or ‘Lockjaw’. There are unmistakable references to it in the Hippocratic Collection and notably in the Aphorisms. Two of these

references we have already quoted (p. 23). A general association of Tetanus with wounds has long been recognized. In the eighties the disease was shown to be transmissible from animal to animal. It was, moreover, experimentally produced in animals by the inoculation into them of garden mold. In 1889 Koch’s pupil, Kitasato, obtained the Bacillus of Tetanus in pure culture and conveyed the disease to animals. He found the organism would grow only in the absence of Oxygen. It is, in fact, a type of a large and now well-known group, the ‘anaerobic’ bacteria. The natural habitat of the Tetanus Bacillus has been proved to be soil, and especially richly manured soil. The knowledge of the bacillus, of its habitat, and of its mode of growth has led to the development of a valuable protective process.

Looking backward from the standpoint of present-day knowledge we can trace Typhoid Fever far back in history. Nevertheless, it was not till 1837 that the distinction between the two distinct conditions known now as ‘Typhoid’ and ‘Typhus’ was first clearly made. This was the work of an American physician, William Gerhard (1809-72), of Philadelphia. The English were backward in adopting the distinction. The organic cause of Typhoid Fever was first seen in 1880 by Karl Joseph Eberth (1835-1927), a pupil of Virchow, and after him it is known as ‘Eberth’s Bacillus’. It was not isolated, however, until some years later. It is an inhabitant of the intestine, and its natural history was obscured by confusion with certain other and very similar organisms, which also dwell in the intestine. These have now been fairly differentiated from each other, and in the course of this process the ‘flora’, both normal and pathological, of the intestinal canal has become well known. Moreover, it has been shown that typhoid organisms are not always of the same species, but that several closely allied forms produce several closely allied diseases. Lastly, certain of the effects wrought by the typhoid group of organisms on the body, which is their host, have been exactly investigated. These investigations have led to improved methods of recognition of the disease, that is to say, diagnosis, and also of prevention of its incidence, that is to say, prophylaxis. To these methods of diagnosis and of prophylaxis we now turn.

FIG. 117. BACILLI OF TETANUS FROM A CULTURE. Highly magnified. The drum-stick forms are very typical.

FIG. 118. BACILLI OF TYPHOID FEVER FROM A CULTURE. Highly magnified. The long flagellae, which are constantly in motion and are very characteristic of these organisms, are well seen. ]

§ 12. The Study of Immunity.

In the production of disease by living organisms two main factors are involved. There is, firstly, the multiplication of the organisms themselves, and there is, secondly, the production by the organisms of poisonous substances or toxins. The former phenomena are spoken of as infection, the results of the latter come under the title of intoxication or toxic effects. The first toxins to be investigated were those isolated from putrefying substance and named ptomaines (1876, by false formation from Greek ptoma ‘a corpse’). These are, in fact, definite chemical substances of the group known to chemists as ‘alkaloids’ (p. 325). Later, toxins were prepared from actual disease organisms such as those of Typhoid and Tetanus (1888). The method was introduced of filtering the bacteria away from their fluid cultures and thus obtaining a bacterium-free liquid containing the poisonous bacterial products. This was the starting point of the scientific study of toxins. These, it soon became clear, were either substances which were normally sent out by the bacteria, exotoxins, or they were normally retained within the bacteria and could only be obtained in solution by breaking up the bodies of the bacteria, endotoxins. The use of these toxins has been essential for the scientific study of Immunity.

The word Immunity is derived from a Latin word which means ‘exemption from military service’. In Medicine it indicates an exemption, relative or absolute, from the incidence of a disease. Immunity in the medical sense is of various kinds. There is ‘species immunity’, some species not being liable to diseases to which others fall victims. There is relative and there is absolute immunity. There is innate and acquired immunity. Of acquired immunity there is a natural immunity resulting from the ordinary contraction of a disease, and there is an ‘artificial immunity’. It is only artificial immunity that is in the hands of the physician.

Artificial immunity itself is of two kinds, and both kinds are of use and of importance in Medicine. There is an Active Immunity, which is produced directly by injection of disease organisms or their products. It is found, however, that if a high degree of active immunity be attained the blood serum of the immunized animal, when injected into a second animal, may itself produce a state of immunity. The state thus indirectly produced is described as Passive Immunity.

The early observers found that when organisms are cultivated outside the body they lose their virulence to a greater or less degree. Pasteur found this for Chicken Cholera (p. 234). He found, moreover, that such ‘attenuated cultures’, when inoculated, protect against the disease. By the use of attenuated cultures he succeeded in establishing a state of ‘Active Immunity’ against Chicken Cholera. But there are many other ways of attenuating the virulence of an organism. Thus, in 1882, Pasteur showed that to grow Anthrax bacilli at a high temperature would reduce their virulence. These bacilli of reduced virulence could be injected into a sheep. They would give the animal the disease in a mild form and protect it against further attacks of the disease. They acted, in fact, in the same way as did the old ‘Inoculation’ of Small-Pox (p. 183).

It has been found, however, that the same kind of immunity which is produced by administering attenuated cultures is sometimes given even by dead cultures. Nearly all active immunization is therefore done by inoculating such killed cultures. These are usually called ‘Vaccines’ from the analogy which they bear to vaccination. The most familiar and effective ‘vaccine’ is that against Typhoid. Moreover, it has been found that in certain cases the principle of the induction of Active Immunity may be applied directly in the treatment of disease. The conditions that respond best to this line of treatment are those which present some localized infection, such as a boil or carbuncle. In such cases we must suppose that, while the local capacity for resistance is lowered, yet reserves of resistance in other parts of the body can be brought into play. These reserves are called up by the signal that reaches them by the reaction of the body against the Vaccine.

It has been shown that, for the production of Active Immunity, the actual bodies of the disease organisms are not always necessary. In some cases, toxins obtained from these disease organisms are themselves sufficient to induce Active Immunity. The matter may become of great medical importance in the future and is already applied for Diphtheria (p. 265).