DISEASE.

sult from the presence, growth, and multiplication of living organisms. Following the publication and discussion of these statements arose the theory of spontaneous generation of minute animal and vegetable organisms, advocated by Needham, in 1749, after loosely conducted experiments. Bonnet, in 1762, Lazarus and Spallanzani in 1769, Schultze in 1836, Schwann in 1837, Helmholtz in 1843, Schroeder and Von Dusch in 1854, Hoffmann in 1860, Chevreul and Pasteur in 1861, all contributed results of accurate scientific experiments which showed the absolute falsity of the theory of spontaneous generation. But, incredible as it may now seem, it was not till 1876 that the combined results, philosophical, chemical, and biological, of Tyndall and Cohn set the question at rest and established the fact that "all life comes from life," to use the words of Harvey's law. About 1873 the germ theory of disease was authoritatively restated, and germ causation became an accepted principle.

GERMS IN THE BODY. The question as to how germs enter the body and the means of defense against them which the body possesses is one of extreme importance. When we think of the omnipresence of germs, in the air we breathe, in the water we drink, in much of the food we eat, in the soil upon which we walk, in fact in or upon almost everything we touch or with which we come in contact, the question why bacteria do not oftener enter the body tissues would seem to be more rational than why they sometimes do so enter. Fortunately most germs are harmless; but many are capable of producing the most severe forms of disease. There are constantly present in the mouth, nose, and upper airpassages, as well as throughout the entire gastrointestinal canal, micro-organisms which, under ordinary conditions, are perfectly harmless. Then, too, the body is so built as to offer very powerful resistance to the entrance into it of most germs. First in importance of the body defenses against germ invasion is the skin. The unbroken skin offers an almost impassable barrier to the passage of most forms of germs. Being the most exposed, it is also the strongest of the body defenses against the entrance into it of micro-organisms. Few, if any, germs have the power to penetrate it, if healthy and intact. Any person accustomed to dissecting, operating, or performing autopsies with ungloved hands, noting with what impunity highly infectious material may be handled provided there is no broken surface, and how serious are often the results of an overlooked wound or a chance scratch, realizes the importance of the skin as a protection against germs. There are, however, certain normal openings in the skin. These are: (a) those of the digestive tract-the mouth and anus, communicating with the œsophagus, stomach, intestines, and rectum; (b) those of the respiratory tract, the mouth and nose-leading into the larynx, trachea, bronchi, and lungs; (c) those of the genito-urinary tract, the urethra and vagina-leading to the bladder, ureter, kidney, uterus, and Fallopian tubes; (d) the eye. These openings and tracts are lined by mucous membranes which may be considered as forming a second line of defense against germ invasion. Being less exposed than the skin, the mucous membranes are also less resistant than the skin

to the entrance of germs. Indeed, to certain

species of germs the mucous membranes are especially susceptible; as the mucous membrane of the intestine to the bacillus of typhoid fever, that of the respiratory tract to the diphtheria bacillus and to the bacillus of pneumonia, and that of the genito-urinary tract to the gonococcus. To a great many of the most dangerous species of germs, however, the healthy mucous membrane, like the unbroken skin, presents an impassable line of defense. Nor is the body helpless against the activities of germs even after they have entered its tissues. While the lymphatic system often furnishes the channels by means of which germs are carried from one part of the body to another, the lymphatic glands themselves undoubtedly act as filters arresting the progress of the germs, while the lymph-cells probably possess certain germ-destroying powers. Then, too, the white corpuscles of the blood are endowed with properties which enable them to take up germs and destroy them. It is largely for this purpose, in all probability, that the white blood-corpuscles leave the vessels and pass out into the surrounding tissues in inflammatory conditions. Certain other cells probably possess this same power of destroying germs. Such cells are known as phagocytes, and the process of germ destruction by them is called phagocytosis. There are also developed in the body during the progress of germ infections certain substances which appear to be in solution in the fluids of the blood. These substances are known as antitoxins (q.v.), and have a distinctly inhibitory effect on the further development of the germs.

The effects upon the body mechanism of the activities of disease-producing germs vary, of course, greatly for the different germs. Certain general modes of action may, however, be mentioned. (1) The direct (usually local) effect of the presence of the germs. Thus, in diphtheria the direct local effect of the germ in the throat is death of parts of the mucous membrane and the formation of what is known as a false membrane. In a similar manner the ulcers in the intestines in typhoid fever are due to the direct local action of the typhoid bacillus. Another local effect which germs may sometimes have consists in the formation of infectious emboli in different parts of the body. Thus, for instance, in infectious endocarditis with bacterial growth in the heart valves, a little mass of bacteria may become detached, and carried through the circulation until it reaches a vessel too small for it to pass through. Here it stops, forming an infectious embolus and thus setting up a new focus of infection. (2) The production of toxins (q.v.). These are poisons produced in the body by the activities of bacteria. They seem to be largely present in the plasma of the blood and are consequently distributed throughout the body. It is to these toxins that the systemic symptoms of an infectious disease are due, e.g. the fever, prostration, delirium, etc. These toxins differ for different bacteria, a particular toxin probably being specific for each species of germs. That a disease may be accepted as positively proved to be of germ origin, it must fulfill certain very rigid conditions. One single species of germ must always be found present in the diseases. This germ must not be found regularly in connection with any other disease. It must be possible to cultivate this germ artificially, and to separate it in what is

known as a pure culture, i.e. a growth of this germ absolutely free from any other living substance. It must be possible to induce the same or a similar disease in animals by injecting them with this pure culture. Comparatively few diseases as yet fulfill all of these requirements. Among the most important of the diseases which have been proved to be of germ origin may be mentioned anthrax, actinomycosis, Asiatic cholera, bubonic plague, acute cerebrospinal meningitis, diphtheria, erysipelas, glanders, gonorrhoea, influenza, leprosy, malaria, pneumonia, relapsing fever, tetanus, tuberculosis, and typhoid. Of the more important of the diseases which from their behavior are believed to be of germ origin, but in which the germs have not as yet been found, are hydrophobia, measles, scarlet fever, smallpox, typhus, and whooping-cough.

BACTERIOLOGICAL TECHNIQUE. In many cases of disease a determination of the species of bacteria present may be made by means of a bacterial examination of pathological material during life. This is done in one of three ways: first, by cover-glass preparation; second, by culture; third, by animal inoculation. In some cases a little pathological material may be obtained on a sterilized platinum loop; in others a piece of absorbent cotton wound about a stiff wire and forming a 'swab' is used, by means of which pus or exudates may be obtained and transported in a sterile test-tube into which the swab is thrust; in still other cases fluid material may be obtained by aspiration. A coverglass preparation is thus made: A very small amount of material is smeared over a cover-glass in such a way as to leave streaks of it and not a continuous layer. After being dried by being held in the fingers, charged side uppermost, over a Bunsen burner, it is passed rapidly three times directly through the flame of the burner by means of a forceps, to 'fix' it. The coverglass is then held in the grasp of the forceps, charged side up and level, and the chosen staining fluid is dropped on it from a dropping bottle, till it is completely covered. The coverglass is then heated over the flame and washed in water, and any other necessary processes are concluded, according to the method of staining employed. The cover-glass with the charged side down, and wet thoroughly with water, is placed on a microscopic slide, and the excess of water is removed by means of filter paper in the usual way. An oil-immersion lens is then used, for examination of the specimen.

Culture mediums differ in different cases. Potato, agar-agar, litmus-milk, glucose agar-agar, and glucose gelatin are used; but the best culture medium for general purposes is coagulated blood serum. At the slaughter-house blood is obtained as it runs from the vessels of the beeves, preferably that which flows from the carotid artery, as it clots more quickly. The jar in which it is received is left in a cool place for twenty-four hours. After a few hours the clot is gently loosened from the sides of the jar, to facilitate its contraction, and after this the jar is not agitated. After about twenty-four hours the serum is removed with a pipette. Three parts of blood serum and one part of glucose bouillon are mixed to form the culture medium, which is run into test tubes in small quantities. The tubes are placed in a tilted position in the hot-air sterilizer and when withdrawn the serum

is found to be coagulated in a slanting position. Material obtained on a 'swab,' e.g. from the throat of a suspected diphtheria patient, is lightly smeared over the whole exposed surface of the blood serum in a culture-tube. The culturetube is then placed in an incubator or thermostat, and the bacteria are allowed to grow on the nutrient surface, for subsequent examination with the microscope.

A

Animal inoculations are made as follows: small piece of suspected material may be inserted under the skin of a mouse by means of a platinum wire, or a little fluid may be injected under the skin of a guinea-pig or rabbit. After the death of the animal an autopsy is made, and various organs and tissues are examined microscopically.

SPECIAL EXAMINATIONS. In examining sputum for tubercle bacilli, a cover-glass preparation is made from a dense grayish-white particle taken from the morning sputum. The tubercle bacillus is a slender rod varying from 1.5 micromillimeters to 4 micromillimeters in length, and about 0.4 micromillimeter in breadth, generally slightly curved. The bacilli occur singly, though in cultures they are sometimes found in chains of four to six links. Club-like forms and branches have been seen also. It must be differentiated from the smegma bacillus, Lustgarten's bacillus of syphilis, and certain others.

SPUTUM CONTAINING TUBERCLE BACILLUS (X 1000).

In examining for the bacillus of diphtheria, a blood-serum culture-tube is inoculated by means of a 'swab' with exudate from the tonsils of the patient, and is placed in the incubator for about fifteen hours. The resulting growth is examined by means of a stained cover-glass preparation. Mounted on a slide, the specimen is examined with a high-power lens. The bacilli will be found to be of varying size, from 1 to 6 micromillimeters long and 0.5 to 1 micromillimeter broad, straight or slightly curved, with rounded ends, singly or in pairs. The ends may be enlarged. Irregular forms are common. Clusters or bundles and rarely branching forms are found. For the detection of the plasmodium of malaria, a fresh specimen of blood is taken from the lobule of the ear, and received on a cover-glass. This is inverted on a slide so as to spread the specimen evenly, and all superfluous blood is removed. Fixation may be secured by heating, or by im

DISEASE.

mersing in a mixture of absolute alcohol and ether. The preparation is stained to secure contrast between the parasite and the blood-disks. Under the microscope, the plasmodic appear about the size of red blood-corpuscles, discoid, starshaped, in odd forms with prolongations, flagellæ and branches, nucleated, granular, etc. If

DIPHTHERIA BACILLUS FROM TRACHEA (X 500). not fixed, the parasites show rapid amoeboid movements in a fresh preparation. Other microorganisms are described under the titles of the diseases they cause. Consult: Friedländer, Mikroskopische Technik (Berlin, 1900); Thoma, Lehrbuch der pathologischen Anatomie, trans. by Bruce (London, 1896); Günther, Bakteriologie (Leipzig, 1898); Abbott, Principles of Bacteriology (Philadelphia, 1905); Mallory and Wright, Pathological Technique (Philadelphia, 1904); Sternberg, Bacteriology (New York, 1901); Park, Bacteriology (New York and Philadelphia, 1900); Bowhill, Bacteriology (Edinburgh, 1899); Newman, Bacteriology and The Public Health (Philadelphia, 1904); Muir and Ritchie, Manual of Bacteriology (New York, 1903). See BACTERIA; MICROSCOPY; MALARIA.

DISEASES OF ANIMALS. In the general discussion of the diseases which affect animals, various systems of classification have been adopted by different writers. The scheme here presented is that most commonly adopted. Animal diseases may be grouped under the following five heads: (1) infectious; (2) poisoning; (3) constitutional; (4) organic; and (5) diseases caused by animal parasites. Infectious diseases are due to the action of minute organisms (bacteria) in the blood or vital organs and tissues. Such diseases may be communicated from one animal to another by means of infected blood, by tissues, or by animal secretions containing the disease-producing organism.

The most important infectious diseases of animals are abortion, actinomycosis, contagious agalactia, anthrax, asthenia, blackleg, braxy, cattle-plague, cerebro-spinal meningitis, dog distemper, foot-and-mouth disease, fowl cholera, glanders, influenza, contagious pleuropneumonia, rabies, roup, swine-plague, tetanus, Texas fever, and tuberculosis. Each of these is discussed in a separate article. These diseases are due to the action of bacteria, with the exception of Texas fever, which is caused by an animal blood para

site, and rabies, of which the causative agent has not been determined.

Under diseases of poisoning are included cases of poisoning of an acute or chronic nature by mineral, plant, or animal poisons. The more common mineral poisons to which animals may gain access are compounds of arsenic, lead, copper, zinc, phosphorus and mercury, mineral acids, and caustic alkaline substances. Among plant poisons mention may be made of strychnine, opium, aconite, and various wild plants, such as water-hemlock, larkspur, loco, veratrum, deathcamass, and lupine. The eating of large quantities of ergot produces the symptoms of ergotism (q.v.). Smuts and molds sometimes cause digestive disturbances of a more or less serious nature. Animal poisons include snake-poison, bee-stings, and the sting of certain other insects, such as the tsetse-fly, buffalo gnat, etc.

Diseases caused by animal parasites include those which are produced by parasitic worms, insects, mites, etc. Every species of domestic animals is infested to some extent with parasitic round or flat worms. The lung and stomach worms (q.v.) of sheep are periodically the cause of great losses to the sheep industry. The fluke-worm, which causes liver-rot (q.v.) of sheep and other animals, is of great economic importance. The nodular disease of fowls is due to the presence of tapeworms in the walls of the intestines. Trichinosis of hogs is due to infestation by the round worm, trichina. Beef and pork measles are conditions produced by the presence of tapeworms in an immature condition in the meat. The kidney-worm, which usually lies imbedded in the fat tissue of hogs, occasionally penetrates the kidney and causes death. Besides the examples already given there is a considerable variety of round and flat worms which infest the intestines of domestic animals without causing any marked disturbance except when present in unusually large numbers.

Nearly all domestic animals are subject to mange or scab. This disease is due to the attacks. of various species of mites. One species with several varieties causes one form of scab on sheep, cattle, horses, and goats. A few species of flies live, during a portion of their life cycle, as parasites on or in animals. Chief among these are the horse bot-fly, sheep bot-fly, ox warblefly, and horn-fly. The last three occasionally cause serious disease. Various species of ticks and fleas are well-known pests on domestic animals.

Under the head of constitutional diseases reference is ordinarily made to such pathological conditions as anæmia, scurvy, and diabetes, which occasionally prevail in animals as well as in man.

The term 'organic diseases' includes diseases. of the skin, digestive organs, respiratory organs, circulatory organs, nervous system, and urinogenital organs. Some of the numerous diseases. which fall in this category are infectious.

It will be understood that the system of classification here proposed cannot be followed too strictly, and that the different categories are not mutually exclusive. The various forms of scab and itch may readily be transmitted from one animal to another by contact, and are, therefore, contagious. The terms infection and contagion, however, usually have reference to diseases which are due to the action of bacteria.