THE BACTERIA OF DISEASE. BY ZEZEZSTIVZ- IZTTXT, Zv'E.ZD., Professor of Dis'eases of the Nervous System, Albany Medical College. REPRINTED EROM "ALBANE MEDICAL ANNALS." ' ALBANY, N. Y.: Burdick A Taylor, Printersx 4S1 Broadway. 18S6. I 2 3 4 5 6 9 7 8 10 II 12 13 14 15 BACTERIA i. Bacillus Subtilis. 2. Multiplication by Fission. 3. Reproduction by Spores. 4. Bacillus Septicus (rabbit). 5. Micrococcus Septicus (rabbit). 6. Spirillum of Relapsing Fever (Spirochaate Obermeyeri). 7. Bacillus of Anthrax. 8. Bacil- lus of Tuberculosis. 9. Bacillus of Leprosy. 10. Bacillus of Asiatic Cholera. 11. Bacillus of Cholera Nostras (Finkler and Pryor). 12. Bacillus of Typhoid Fever. 13. Micrococcus of Pneumonia. 14. Micrococcus of Erysipelas. 15. Micrococcus of Diphtheria. Magnified about 700 Diameters. The Bacteria of Disease." HENRY HUN, M.D., Professor of Diseases of the .Nervous System, Albany Medical College. So much has been said and written during the past few years about bacteria and about their relationship to disease that it must be a matter of interest to every physician to see these little organisms which are daily becoming of greater and greater importance in pathology. It was my intention this evening to have exhibited under high microscopic powers a number of dif- ferent kinds of bacteria, but I find at the last moment that I cannot get a satisfactory light for the microscopes, and therefore we must content ourselves with this plate (frontispiece), which is copied from the specimens that I had intended to exhibit. I regret this the more because I have very few remarks prepared, as I wished rather to devote the evening to a microscopic study of the bacteria. You all know that in the air we breathe, in the water we drink, and in the earth under us, there are a great number of globular, cylindrical or filiform bodies, which are so minute that they can be seen only under the higher powers of the microscope, and which, when placed in a suitable medium, absorb food, move about, grow larger, reproduce themselves, and give other mani- festations of life. These little bodies are, therefore, living organisms, and upon close examination they are found to consist of a central mass of protoplasm enclosed in a membrane or cell wall. They are really small cells, which, however, differ very much in appearance from the cells with which we are familiar as occurring in the human body. Many of the little cellular bodies have the shape of little rods, and in consequence the whole class ♦Read before the Medical Society of the County of Albany, February 10,1886. 2 have received the name bacteria, from the Greek word flaHTTjpiov; " a little rod." The class of bacteria stands very near the border line of the animal and vegetable kingdoms; and although at the present time there is a general unanimity of opinion that they belong to the vegetable kingdom, yet there is still some dispute whether they should be classed among the algae or fungi. It has not as yet been possible to classify all the different kinds of bacteria, but there are three great groups into which they can be divided according to their form. They are, micro- cocci, bacilli, and spirilla. Micrococci are spherical or elliptical bodies which very rarely exceed 2 /<* in diameter. They occur either in separate granules, or in rows like a chain of beads, or in quite large groups im- bedded in a gelatinous mass, such a group being called a zooglcea, from the Greek Zgoov, " animal," yXoia, " glue." Bacilli are rods, varying in length from about 1 to 6 y and in diameter from 2 y down to a diameter too small to be measured. They occur either as separate rods or in the form of dense groups, called swarms, or arranged end to end in long chains, which are called leptothrix, from the Greek ActtfoS, "fine," and " hair." Spirilla are undulating or spiral filaments varying in length from 4 to 40 p. They occur either singly or matted together in clusters. The conditions requisite for the life and development of bacte- ria are (1) warmth; (2) water; (3) oxygen, either free or in combination; and (4) a sufficient quantity of organic matter to serve as food. When all these conditions are fulfilled, the bac- teria develop with great rapidity until they have exhausted their supply of food; that is, until they have converted the complex organic molecules either into inorganic molecules or into simpler organic molecules, according as there is an abundant or an insuf- ficient supply of oxygen present. When the organic matter is in solution, and when air or oxygen is artificially supplied to this solution in such abundance that there is always free oxygen present, then the bacteria convert the organic matter into car- bonic acid, water and ammonia directly, without the production of any evil-smelling compounds.* When, however, the supply of oxygen is limited, as is always the case in nature, then in the decomposition of the organic matter through the agency of bac- *p =mlcrominimeter = one thousandth of a millimeter. 3 terial life certain bad-smelling compounds, such as sulphuretted hydrogen, etc., are formed, and the process is called putrefaction. From numerous experiments it appears that all putrefaction is directly caused by bacterial life. All the dead organic matter in the world, except what is burned and what is consumed by animals as food, is converted back into inorganic matter by means of putrefaction. Were it not for the bacteria, the dead organic matter would remain in the world unchanged; and, although organic matters sometimes putrefy sooner than is desired, yet, in general, the bacteria perform a very useful and necessary work in removing the dead organic matter from the world and returning it to the inorganic kingdom. They are the great scavengers of nature. Figure 1 repiesents one of the useful bacteria. It is called the bacillus subtilis, and sometimes the hay bacillus,because it is found abundantly on the surface of hay. It is found very commonly in putrefying matters, and is about 2 to 6/t in length and about 2 broad. Under high magnifying powers (700 diameters) the bacillus subtilis appears as a short rod, but under the very high- est powers (4,000 diameters), and with suitable illumination, it exhibits at each end flagella, which are constantly lashing back- wards and forwards during the life of the bacillus. Similar flagella exist on all or almost all of the bacilli and spirilla, but not on the micrococci. The bacteria subtilis, as almost all of the bacteria, can be cultivated artificially either in solutions of organic matter or on a slice of potato or in a solid mixture of gelatin and blood serum. They can be best studied when grow- ing in the solid gelatin, and it is seen that the different kinds of bacteria grow in groups or colonies, which always present the same appearance in the same kind of bacteria, and which differ so greatly in appearance in the different kinds that, in many cases, they can be distinguished from each other by the naked eye. When their growth and development are carefully observed, it is found that bacteria reproduce themselves in one of two ways-either by fission or by sporification. In the process of fission, the bacterium grows larger, a constriction appears at its middle and becomes so deep that it divides the bacterium into two precisely similar bacteria, which may in turn subdivide. Sometimes before the bacteria separate from each other they * Hoppe-Seyler, Zeitschrift fur Physiol. Chemle, VIII., S. 214. 4 each subdivide again, and thus a long chain of bacteria may be formed. The process of fission is shown in figure 2. In the process of sponfication, small glistening particles, called spores, appear in the substance of the bacterium, and are set free by the disintegration of the bacterium. They resist injury, such as high temperatures, much more strongly than do the bacteria, and when placed in favorable circumstances they become elongated at one end, grow rapidly, and develop into the adult bacterium. The process of sporification is shown in figure 3. " As far as observation goes, young bacilli invariably grow and multiply by division for some time before they produce spores. Continued vegetation without change of soil is usually termi- nated by the formation of spores, and these spores, as a rule, will not germinate in the unchanged soil where they are pro- duced " (Gradle). The bacillus subtilis stands as a representative of the bacteria which are not only harmless, but are extremely useful to the world and to man. Such bacteria surround the body on all sides. They are found in abundance in the mouth, in the intes- tines and in all parts of the alimentary tract. The tissues of the human body offer such a resistance to them that they cannot penetrate into the human body proper, and they are never found in the blood nor tissues of a healthy person.* There is, however, another class of bacteria, the members of which, under certain conditions, enter into the body and produce there disturbances which we call disease. There are many dis- eases each one of which is due solely to the entrance into the body of one or more bacteria of a certain distinct kind. As long as these bacteria are kept out of the human system the cor- responding disease will never occur, but whenever these bacteria enter into the body then the disease may occur. The remaining twelve figures of the frontispiece represent some of the bacteria which produce disease, or pathogenic bacteria, as they are called. Each of these species of bacteria is distinct from every other,, and although they have been cultivated under a great variety of conditions, it has not as yet been possible to convert one species of bacteria into another, and no matter through how many gen- erations it has been cultivated, the last generation is as virulent as the first, and produces the same disease when inoculated in * Virch. Archly., Vol. 95, p. 401. 5 animals. It is possible, however, to render the bacteria less virulent. There are a number of species of bacteria which, when allowed to remain for a long time in the same culture fluid at a rather high temperature, suffer a loss of vital power, and when these weakened bacteria are inoculated into animals, they produce the definite specific disease in a mild form. Such inoculations render the animal more or less insusceptible to the disease thereafter, and this is the principle of preventive inocula- tion for disease. Figures 4 and 5 represent the bacillus septicus and the micro- coccus septicus respectively. The former is about 1.4 in length and 0.7 in breadth, and the latter is about 0.5 // in diameter. Either of these bacteria injected under the skin of rabbits, birds, and some other animals, will cause death in from sixteen to forty hours, with the symptoms and lesions of septicaemia, and in the blood of the animals thus destroyed are found many bacteria similar to those injected, and these bacteria can be cultivated outside of the body through many generations without losing any of their virulent powers. These two specimens will serve as examples of the bacteria of septicaemia, although there are other bacteria which cause this disease. The bacterium causing pyaemia is a micrococcus somewhat similar to those represented in figure 5. Figure 6 represents the spirillum of relapsing fever, called the spirochaete Obermeyeri after its discoverer. These spirilla make their appearance in the blood a few hours before the fever, and increase so rapidly in number that during the height of the fever they may even exceed the red blood discs in number, and then disappear as the fever passes off. Although it is probable that the presence of these spirilla in the blood causes the fever, yet it has been impossible to cultivate them outside of the body, so that the experiment of injecting some of a pure culture of them into animals cannot be tried. The spirilla vary from 12 to 43 >x in length and are shaped like a corkscrew, exhibiting from four to ten turns* In figures 4, 5 and 6 we have examples of each of the great groups of bacteria-the bacillus, the micro- coccus and the spirillum. Figure 7 represents the bacillus anthracis, the bacillus of anthrax, the disease called splenic fever in cattle and sheep and, in man, malignant pustule. The bacillus has a length of from 3 to 6/i and a breadth of a little more than 1 /z, and has been 6 more thoroughly studied than any other bacillus of disease. In the bodies of animals this bacillus multiplies only by fission, but when cultivated or growing outside of the body it multiplies by sporification. The bacillus of anthrax introduced into the body causes first a local abscess, then a swelling of the neighboring lymphatic glands, and then the bacilli appear in great numbers in the blood and death soon results. Like all infectious diseases, anthrax has a period of incubation, which varies in different ani- mals, seeming to depend in part on the size of the animal. Figure 8 represents the bacillus tuberculosis, which are ex- tremely thin rods varying in length from 2 to 4/z. These bacilli are found in all tuberculous growths. In young tubercles they are especially abundant in the giant cell. In old tubercles they are found in the periphery, which is the part of most active growth. In the dried or caseous matter no bacilli, but only spores, are present. The bacillus tuberculosis is present in the expectoration of persons suffering from pulmonary tuberculosis. The bacilli tuberculosis can be cultivated outside of the body. They increase in number only very slowly and only when kept at a temperature between 30° and 41° C. When a very few bacilli tuberculosis are introduced into the aqueous humor of the eye of an animal, small gray miliary tubercles appear on the iris and neighboring parts. These increase in number, coalesce, and lead to a general tuberculous inflammation, which destroys the eye. Later, miliary tubercles appear in the neighboring lymphatic glands, and afterwards in the other organs of the body. Figure 9 represents the bacillus of leprosy, which is a little thicker and longer than the bacillus tuberculosis. This bacillus is always found in the new growths of leprosy, but it has not as yet been possible to inoculate it in animals. Figure 10 represents the bacillus of Asiatic cholera (the comma bacillus of Koch), which is found in the dejections, in the contents of the intestines, and in the intestinal glands, in cases of cholera. This bacillus has the form of a written comma, and is about 2 long and 0.5 // thick. It is destroyed by acids, and only thrives in alkaline solutions. It can readily be culti- vated outside of the body. The normal acidity of the gastric juice kills it, and in order to successfully inoculate it in animals it must be injected into the intestines, where it will meet with an alkaline fluid. When thus injected, it speedily causes death, 7 with all the symptoms and lesions of cholera. The comma bacillus of Koch has been the subject of much dispute, and many observers have claimed that they have found precisely similar bacilli of a more or less harmless nature. One by one, however, these various bacilli have been shown to bear only a very superficial resemblance to the true comma bacillus, and now only one bacillus remains which bears any close resemblance to the comma bacillus. Figure 11 represents the bacillus which is called the comma bacillus of Finkler and Prior, and which, it is claimed, is found in the contents of the intestines and in the recent dejections of cases of cholera morbus. These bacilli are a little thicker than the comma bacilli of Koch, and differ from these latter also in their manner of development and in the effects produced when they are injected into the intestines of animals. Figure 12 represents the bacillus of typhoid fever. It is shorter and much thicker than the bacillus tuberculosis, and is rounded at its extremities. It has been found in the intestinal follicles, mesenteric glands and spleen in about half of the cases of typhoid fever in which it has been sought. It can be culti- vated, but it has not as yet been successfully inoculated in ani- mals, so that its causal connection with typhoid fever has not been satisfactorily established. Figure 13 represents the micrococcus of pneumonia, or the micrococcus of Friedlaender. This micrococcus is surrounded by a gelatinous capsule, which usually encloses two or three micrococci, two being thus enclosed with Especial frequency. These micrococci occur in the exudation in the alveoli, especially near the walls of the alveoli, and in the expectoration. They can be cultivated outside of the body, and when inoculated in animals pneumonia is produced. Figure 14 represents the micrococcus of erysipelas, which has a tendency to form curved lines like a chain of beads. It can be cultivated outside of the body, and when inoculated erysipelas results. It has, indeed, been inoculated in man for therapeutic purposes, in the hope of arresting the growth of tumors, etc. From such inoculations it has been learjied that an attack of erysipelas protects the person for a variable period from another attack. The immunity usually lasts for three months. Figure 15 represents a micrococcus which is always found in diphtheritic membranes, although up to the present time it has not been possible to satisfactorily isolate it. 8 These figures do not exhaust all the varieties of the bacteria of disease which are known. The micrococcus of gonorrhoea and the bacillus of syphilis, of xerosis conjunctivte, of glanders, have all been isolated, and in all probability cause the diseases from which they derive their names, while many other bacteria have been discovered which probably, although not certainly, cause certain diseases, such as trachoma, rhinosclerma, small-pox, whooping-cough, etc. Whenever any of these pathogenic bacteria enter into the body, they absorb their food and oxygen from the tissues, and grow and multiply. If this growth and multiplication were unchecked, they would consume all the tissues and soon cause the death of the animal. The animal system, however, possesses the power of acting upon the bacteria and destroying them more or less completely, and as a result of this action a complex of symptoms is produced which is called disease. The essence of many forms of disease consists in a struggle for existence between the bacteria and the animal tissues. In the case of the simplest animals this struggle can be observed under the micro- scope. The simplest form of animal life is the amoeba, which is altogether similar to the lymph corpuscles of animals, and when a little lymph from a frog is placed together with a few bacilli of anthrax on a warm stage and observed under the microscope, some very noteworthy phenomena take place, which have been described by Prof. Metschnikoff, of Odessa,* and which are in Lymph Cells Destroying Bacteria (Metschnikoff). part represented in the accompanying figures. Figure 1 shows a white corpuscle of the frog's lymph which is taking a bacillus into its interior. Figure 2 shows the same corpuscle ten minutes later, when it has not only taken the bacillus into its interior, but has caused its disappearance. Figure 3 shows the * Virchow's Archiv., Vol. XCVII., p. 502. 9 same corpuscle a quarter of an hour latei- trying to take a whole group of bacilli into its interior. Figure 4 shows the same cor- puscle a quarter of an hour later when another corpuscle has come to its aid. Figure 5 shows the same two corpuscles ten minutes later when they have taken the whole group of bacilli into their interior. From these figures it appears that the lymph corpuscles possess not only the power of taking the bacteria into their interior, but also of causing them to disappear (figure 2). Other figures of Metschnikoff show how this disappearance or destruction of the bacteria within the corpuscle is accom- plished-the bacilli either break up into small fragments or granules or else their outlines become more and more indistinct till they disappear. In this way the lymph cells destroy the bacilli. In other cases the bacilli destroy the lymph cell, causing it to burst and disappear. By further researches Prof. Metschnikoff finds that the bacilli are not destroyed by the fluids in the tissues, but only by the white corpuscles, and it appears that when a white corpuscle has eaten one or more bacilli it thereby becomes changed so that thereafter it is able to destroy the bacilli more easily. Finally, Metschnikoff finds that at cer- tain temperatures the white corpuscles act more strongly and the bacilli less strongly, so that the latter are destroyed by the for- mer, while at other temperatures the reverse is the case. From these experiments it would appeal- that there is a mutual antago- nism between the lymph cells, or white blood corpuscles, on the one hand and the bacteria on the other, and that when the latter enter into the human body the former tend to destroy them. Another set of experiments by Strauss* definitely prove what has long been a matter of doubt, that chemical irritants, such as turpentine, croton oil, etc., cannot produce suppuration without the presence of bacteria. In the light of these two sets of experiments (first, that without the presence of bacteria, pus is never formed, and, second, that the pus cells, or white blood cor- puscles, can destroy the bacteria), we are able to understand a little more clearly the meaning of some of the phenomena of septicaemia in the broadest sense of the word. When the fresh surface of a wound is free from all septic bacteria, the wound heals quickly without suppuration or consti- tutional disturbance. When, on the other hand, septic bacteria are present on the surface of a wound, then the wound does not * Revue de Chirurgie, No. 2; Bulletins de la Soclete de Biologle, 1883, p. 651. 10 heal quickly, and suppuration and other symptoms of disease appear. Pus is poured out on the surfaces of the wound and prevents their uniting, and, although this formation delays the healing of the wound, yet it is of great value in the preservation of the well-being and the life of the individual, and is really curative in its nature. It is the only barrier which can be thrown out against the general infection of the body. The pus cells are the only elements which can destroy the bacteria. If these lat- ter are few in number, they are quickly destroyed by the cells, little or no destruction or decomposition of tissue is produced, the flow of pus ceases, and the wound heals. If, on the other hand, the bacteria are in great abundance, they grow and multi- ply, and not only destroy many of the cells and the tissues, but in so doing produce decomposition and putrefaction, so that the pus and discharge from the wound has a very unpleasant odor. In such a case many of the bacteria pass beyond the barrier of cells poured out to destroy them, and, entering the lymph chan- nels, reach the nearest lymphatic glands. Here the same process is repeated. There is a curative hyperplasia of the glands; that is, there is within the glands an increase in the number of lymph cells, which may destroy the bacteria, so that with the hyperpla- sia of the lymph glands the disease may terminate. In severer cases, however, the bacteria are so numerous or so virulent that they pass beyond the lymph glands and enter the general circu- lation. Then appears a remarkable symptom which is called fever, and which consists essentially in an increase in the heat of the body. The fever which is produced by the entrance of bacteria into the blood causes much discomfort, and is at times dangerous to life, and yet in all probability it fulfills a most useful purpose. The bacillus anthracis has its greatest activity and produces spores only between the temperatures of and F. Pasteur claims that anthrax cannot be inoculated in a fowl, because its normal temperature is too high for the life and growth of the bacillus, but when the normal temperature of the fowl is lowered by immersing its legs in cold water, then it can be inoculated with the bacillus successfully. The bacillus tuberculosis can be cultivated only between the temperatures of 86° and 106? F. The spirilla of relapsing fever are rendered motionless in a very few hours by a temperature of 104° F., and it is probable that a temperature of 103? to 106° F. will weaken 11 all the bacteria of disease so greatly that they are readily destroyed by the white corpuscles of the blood, while at the normal temperature of the body the bacteria might destroy the white corpuscles. It seems, therefore, altogether probable that the fever of septicaemia, as well as every other form of fever, is curative in its nature, in the same way that the suppuration and the hyperplasia of the lymph glands are curative. In cases of septic poisoning the system reacts against the pathogenic bacteria by suppuration, hyperplasia of the lymphatic glands and fever. These are the three great symptoms of septic poisoning, and they are all curative in their nature. The treat- ment of any case, therefore, should be directed, not against the symptoms, but should be calculated to weaken the vitality of the bacteria and increase that of the white corpuscles. In a manner quite similar to that described for septicaemia, almost all the other pathogenic bacteria, when introduced into the system, produce at first a local inflammation, then a hyper- plasia of the neighboring lymphatic glands, and finally fever. Each of the symptoms causes discomfort, and each may become so excessive as to destroy the life of the patient; yet in their essential nature they are curative, and our therapeutic efforts should be directed, if possible, against the cause of the disease and towards maintaining the strength of the patient, while an attempt should be made to modify the symptoms of disease only when they are manifestly excessive. In the light of our present knowledge, it seems to me that we can hardly attach too much importance to the following sentence with which, in the middle of the seventeenth century, Sydenham commenced his medical essays: "A disease, in my opinion, how prejudicial soever its causes may be to the body, is no more than a vigorous effort of nature to throw off the morbific matter, and thus recover the patient."