FOOTNOTES: [1] By cachexia is understood a condition of malnutrition and emaciation which is usually accompanied by a pale sallow color of the skin.

[2] By trauma is understood a wound or injury of any sort.

CHAPTER IV

THE REACTIONS OF THE TISSUES OF THE BODY TO INJURIES.--INFLAMMATION.-- THE CHANGES IN THE BLOOD IN THIS.--THE EMIGRATION OF THE CORPUSCLES OF THE BLOOD.--THE EVIDENT CHANGES IN THE INJURED PART AND THE MANNER IN WHICH THESE ARE PRODUCED.--HEAT, REDNESS, SWELLING AND PAIN.--THE PRODUCTION OF BLISTERS BY SUNBURN.--THE CHANGES IN THE CELLS OF AN INJURED PART.--THE CELLS WHICH MIGRATE FROM THE BLOOD-VESSELS ACT AS PHAGOCYTES.--THE MACROPHAGES.--THE MICROPHAGES.--CHEMOTROPISM.--THE HEALING OF INFLAMMATION.--THE REMOVAL OF THE CAUSE.--CELL REPAIR AND NEW FORMATION.--NEW FORMATION OF BLOOD-VESSELS.--ACUTE AND CHRONIC INFLAMMATION.--THE APPARENTLY PURPOSEFUL CHARACTER OF THE CHANGES IN INFLAMMATION.

Injury and repair have already been briefly considered in their relation to the normal body and to old age; there are, however, certain phenomena included under the term inflammation which follow the more extensive injuries and demand a closer consideration than was given in Chapter II. These phenomena differ in degree and character; they are affected by the nature of the injurious agent and the intensity of its action, by the character of the tissue which is affected and by variations in individual resistance to injury. A blow which would have no effect upon the general surface of the body may produce serious results if it fall upon the eye, and less serious results for a robust than for a weak individual.

Most of the changes which take place after an injury and their sequence can be followed under the microscope. If the thin membrane between the toes of a living frog be placed under the microscope the blood vessels and the circulating blood can be distinctly seen in the thin tissue between the transparent surfaces. The arteries, the capillaries and veins can be distinguished, the arteries by the changing rapidity of the blood stream within them, there being a quickening of the flow corresponding with each contraction of the heart; the veins appear as large vessels in which the blood flows regularly (Fig. 11). Between the veins and arteries is a large number of capillaries with thin transparent walls and a diameter no greater than that of the single blood corpuscles; they receive the blood from the arteries and the flow in them is continuous. The white and red blood corpuscles can be distinguished, the red appearing as oval discs and the white as colorless spheres. In the arteries and veins the red corpuscles remain in the centre of the vessels appearing as a rapidly moving red core, and between this core and the wall of the vessels is a layer of clear fluid in which the white corpuscles move more slowly, often turning over and over as a ball rolls along the table.

If, now, the web be injured by p.r.i.c.king it or placing some irritating substance upon it, a change takes place in the circulation. The arteries and the veins become dilated and the flow of blood more rapid, so rapid, indeed, that it is difficult to distinguish the single corpuscles. In a short while the rapidity of flow in the dilated vessels diminishes, becoming slower than the normal, and the separation between the red and white corpuscles is not so evident. In the slowly moving stream the white corpuscles move much more slowly than do the red, and hence acc.u.mulate in the vessels lining the inner surface and later become attached to this and cease to move forward.

The attached corpuscles then begin to move as does an amoeba, sending out projections, some one of which penetrates the wall, and following this the corpuscles creep through. Red corpuscles also pa.s.s out of the vessels, this taking place in the capillaries; the white corpuscles, on the other hand, pa.s.s through the small veins. Not only do the white corpuscles pa.s.s through the vessels, but the blood fluid also pa.s.ses out. The corpuscles which have pa.s.sed into the tissue around the vessels are carried away by the outstreaming fluid, and the web becomes swollen from the increased amount of fluid which it contains.

The injured area of the web is more sensitive than a corresponding uninjured area and the foot is more quickly moved if it be touched. If the injury has been very slight, observation of the area on the following day will show no change beyond a slight dilatation of the vessels and a great acc.u.mulation of cells in the tissue.

Everyone has experienced the effect of such changes as have been described in this simple experiment. An inflamed part on the surface of the body is redder than the normal, swollen, hot and painful. The usual red tinge of the skin is due to the red blood contained in the vessels, and the color is intensified when, owing to the dilatation, the vessels contain more blood. The inflamed area feels hot, and if the temperature be taken it may be two or three degrees warmer than a corresponding area. The increased heat is due to the richer circulation. Heat is produced in the interior of the body chiefly in the muscles and great glands, and the increased afflux of blood brings more heat to the surface. A certain degree of swelling of the tissue is due to the dilatation of the vessels; but this is a negligible factor as compared with the effect of the presence of the fluid and cells of the exudate.[1] The fluid distends the tissue s.p.a.ces, and it may pa.s.s from the tissue and acc.u.mulate on surfaces or in the large cavities within the body. The greatly increased discharge from the nose in a "cold in the head" is due to the exudation formed in the acutely inflamed tissue, and which readily pa.s.ses through the thin epithelial covering. Various degrees of inflammation of the skin may be produced by the action of the sun, the injury being due not to the heat but to the actinic rays. In a mild degree of exposure only redness and a strong sense of heat are produced, but in prolonged exposure an exudate is formed which causes the skin to swell and blisters to form, these being due to the exudate which pa.s.ses through the lower layers of the cells of the epidermis and collects beneath the impervious upper layer, detaching this from its connections. If a small wad of cotton, soaked in strong ammonia, be placed on the skin and covered with a thimble and removed after two minutes, minute blisters of exudate slowly form at the spot.

The pain in an inflamed part is due to a number of factors, but chiefly to the increased pressure upon the sensory nerves caused by the exudate. The pain varies so greatly in degree and character that parts which ordinarily have little sensation may become exquisitely painful when inflamed. The pain is usually greater when the affected part is dense and unyielding, as the membranes around bones and teeth.

The pain is often intermittent, there being acute paroxysms synchronous with the pulse, this being due to momentary increase of pressure when more blood is forced into the part at each contraction of the heart. The pain may also be due to the direct action of an injurious substance upon the sensory nerves, as in the case of the sting of an insect where the pain is immediate and most intense before the exudate has begun to appear.

When an inflamed area is examined, after twenty-four hours, by hardening the tissue in some of the fluids used for this purpose and cutting it into very thin slices by means of an instrument called a microtome, the microscope shows a series of changes which were not apparent on naked eye examination. The texture is looser, due to the exudate which has dilated all the s.p.a.ces in the tissue. Red and white corpuscles in varying numbers and proportions infiltrate the tissue; all the cells which belong to the part, even those forming the walls of the vessels, are swollen, the nuclei contain more chromatin, and the changes in the nuclei which indicate that the cells are multiplying appear. The blood vessels are dilated, and the part in every way gives the indication of a more active life within it. There are also evidences of the tissue injury which has called forth all the changes which we have considered. (Fig. 15.)

[Ill.u.s.tration: FIG. 15--A SECTION OF AN INFLAMED LUNG SHOWING THE EXUDATE WITHIN THE AIR s.p.a.cES. Compare this with Fig 6. Fig 15 is from the human lung, in which the air s.p.a.ces are much larger than in the mouse.]

The microscopic examination of any normal tissue of the body shows within it a variable number of cells which have no intimate a.s.sociation with the structure of the part and do not seem to partic.i.p.ate in its function. They are found in situations which indicate that these cells have power of active independent motion. In the inflamed tissue a greatly increased number of these cells is found, but they do not appear until the height of the process has pa.s.sed, usually not before thirty-six or forty-eight hours after the injury has been received. The numbers present depend much upon the character of the agent which has produced the injury, and they may be more numerous than the ordinary leucocytes which migrate from the blood vessels.

All these changes which an injured part undergoes are found when closely a.n.a.lyzed to be purposeful; that is, they are in accord with the conditions under which the living matter acts, and they seem to facilitate the operation of these conditions. It has been said that the life of the organism depends upon the coordinated activity of the living units or cells of which it is composed. The cells receive from the blood material for the purpose of function, for cell repair and renewal, and the products of waste must be removed. In the injury which has been produced in the tissue all the cells have suffered, some possibly displaced from their connections, others may have been completely destroyed, others have sustained varying degrees of injury.

If the injury be of an infectious character, that is, produced by bacteria, these may be present in the part and continue to exert injury by the poisonous substances which they produce, or if the injury has been produced by the action of some other sort of poison, this may be present in concentrated form, or the injury may have been the result of the presence of a foreign body in the part. Under these conditions, since the usual activities of the cells in the injured part will not suffice to restore the integrity of the tissue, repair and cell formation must be more active than usual, any injurious substances must be removed or such changes must take place in the tissue that the cell life adapts itself to new conditions.

[Ill.u.s.tration: FIG. 16.--PHAGOCYTOSIS. _a_, _b_, _c_ are the microphages or the bacterial phagocytes. (_a_) Contains a number of round bacteria, and (_b_) similar bacteria arranged in chains, and (_c_) a number of rod-shaped bacteria (_d_) Is a cell phagocyte or macrophage which contains five red blood corpuscles.]

All life in the tissues depends upon the circulation of the blood.

There is definite relation between the activity of cells and the blood supply; a part, for instance, which is in active function receives a greater supply of blood by means of dilatation of the arteries which supply it. If the body be exactly balanced longitudinally on a platform, reading or any exercise of the brain causes the head end to sink owing to the relatively greater amount of blood which the brain receives when in active function. The regulation of the blood supply is effected by means of nerves which act upon the muscular walls of the arteries causing, by the contraction or the relaxation of the muscle, diminution or dilatation of the calibre of the vessel. After injury the dilatation of the vessels with the greater afflux of blood to the part is the effect of the greatly increased cell activity, and is a necessity for this. In many forms of disease it has been found that by increasing the blood flow to a part and producing an active circulation in it, that recovery more readily takes place and many of the procedures which have been found useful in inflammation, such as hot applications, act by increasing the blood flow. So intimate is the a.s.sociation between cell activity, as shown in repair and new formation of cells, and the blood flow, that new blood vessels frequently develop by means of which the capacity for nutrition is still more increased. The cornea or transparent part of the eye contains no blood vessels, the cells which it contains being nourished by the tissue fluid which comes from the outside and circulates in small communicating s.p.a.ces. If the centre of the cornea be injured, the cells of the blood vessels in the tissue around the cornea multiply and form new vessels which grow into the cornea and appear as a pink fringe around the periphery; when repair has taken place the newly formed vessels disappear.

The exudate from the blood vessels in various ways a.s.sists in repair.

An injurious substance in the tissue may be so diluted by the fluid that its action is minimized. A small crystal of salt is irritating to the eye, but a much greater amount of the same substance in dilute solution causes no irritation. The poisonous substances produced by bacteria are diluted and washed away from the part by the exudate. Not only is there a greater amount of tissue fluid in the inflamed part, but the circulation of this is also increased, as is shown by comparing the outflow in the lymphatic vessels with the normal. The fluid exudate which has come from the blood and differs but slightly from the blood fluid exerts not only the purely physical action of removing and diluting injurious substances, but in many cases has a remarkable power, exercised particularly on bacterial poisons, of neutralizing poisons or so changing their character that they cease to be injurious.

We have learned, chiefly from the work of Metschnikoff, that those white corpuscles or leucocytes which migrate from the vessels in the greatest numbers have marked phagocytic properties, that is, they can devour other living things and thus destroy them just as do the amoebae. In inflammations produced by bacteria there is a very active migration of these cells from the vessels; they acc.u.mulate in the tissue and devour the bacteria. They may be present in such ma.s.ses as to form a dense wall around the bacteria, thus acting as a physical bar to their further extension. The other form of amoeboid cell, which Metschnikoff calls the macrophage, has more feeble phagocytic action towards bacteria, and these are rarely found enclosed within them. It is chiefly by means of their activity that other sorts of substances are removed. They often contain dead cells or cell fragments, and when haemorrhage takes place in a tissue they enclose and remove the granules of blood pigment which result. They often join together, forming connected ma.s.ses, and surround such a foreign body as a hair, or a thread which the surgeon places in a wound to close it. They may destroy living cells, and do this seemingly when certain cells are in too great numbers and superfluous in a part, their action tending to restore the cell equilibrium. The foreign cells do even more than this: they themselves may be devoured by the growing cells of the tissue, seemingly being actuated by the same supreme idea of sacrifice which led Buddha to give himself to the tigress.

The explanation of most of the changes which take place in inflammation is obvious. It is a definite property of all living things that repair takes place after injury, and certain of the changes are only an accentuation of those which take place in the usual life; but others, such as the formation of the exudate, are unusual; not only is the outpouring of fluid greatly increased, but its character is changed. In the normal transudation[2] the substances on which the coagulation of the blood depends pa.s.s through the vessel wall to a very slight extent, but the exudate may contain the coagulable material in such amounts that it easily clots. The interchange between the fluid outside the vessels and the blood fluid takes place by means of filtration and osmosis. There is a greater pressure in the vessels than in the fluid outside of them, and the fluid filters through the wall as fluid filters through a thin membrane outside of the body. Osmosis takes place when two fluids of different osmotic pressure are separated by animal membrane.

Difference in osmotic pressure is due to differences in molecular concentration, the greater the number of molecules the greater is the pressure, and the greater rapidity of flow is from the fluid of less pressure to the fluid of greater pressure. The molecular concentration of tissue and blood fluid is constantly being equalized by the process of osmosis. In the injured tissue the conditions are more favorable for the fluid of the blood to pa.s.s from the vessels: by filtration, because owing to the dilatation of the arteries there is increased amount of blood and greater pressure within the vessels, and the filtering membrane is also thinner because the same amount of membrane (here the wall of the vessel) must cover the larger surface produced by the dilatation. It is, moreover, very generally believed that there are minute openings in the walls of the capillaries, and these would become larger in the dilated vessel just as openings in a sheet of rubber become larger when this is stretched. Osmosis towards the tissue is favored because, owing to destructive processes the molecular pressure in the injured area is increased; an injured tissue has been shown to take up fluid more readily outside of the body than a corresponding uninjured tissue. The slowing of the blood stream, in spite of the dilatation of the vessels, is due to the greater friction of the suspended corpuscles on the walls of the vessels. This is due to the loss from the blood of the outstreaming fluid and the relative increase in the number of corpuscles, added to by the unevenness of surface which the attached corpuscles produce.

The wonderful migration of the leucocytes, which seems to show a conscious protective action on their part, takes place under the action of conditions which influence the movement of cells. When an actively moving amoeba is observed it is seen that the motion is not the result of chance, for it is influenced by conditions external to the organism; certain substances are found to attract the amoebae towards them and other substances to repel them. These influences or forces affecting the movements of organisms are known as _tropisms_, and play a large part in nature; the attraction of various organisms towards a source of light is known as _heliotropism_, and there are many other instances of such attraction. The leucocytes as free moving cells also come under the influence of such tropisms. When a small capillary tube having one end sealed is partially filled with the bacteria which produce abscess and placed beneath the skin it quickly becomes filled with leucocytes, these being attracted by the bacteria it contains. Dead cells exert a similar attraction for the large phagocytes. Such attraction is called _chemotropism_ and is supposed to be due in the cases mentioned, to the action of chemical substances such as are given off by the bacteria or the dead cells. The direction of motion is due to stimulation of that part of the body of the leucocyte which is towards the source of the stimulus. The presence in the injured part of bacteria or of injured and dead cells exerts an attraction for the leucocytes within the vessels causing their migration. When the centre of the cornea is injured, this tissue having no vessels, all the vascular phenomena take place in the white part of the eye immediately around the cornea, this becoming red and congested. The migration of leucocytes from the vessels takes place chiefly on the side towards the cornea, and the migrated cells make their way along the devious tracts of the communicating lymph s.p.a.ces to the area of injury. The objection may be raised that it is difficult to think of a chemical substance produced in an injured area no larger than a millimeter, diffusing through the cornea and reaching the vessels outside this in such quant.i.ty and concentration as to affect their contents, nor has there been any evidence presented that definite chemical substances are produced in injured tissues; but there is no difficulty in view of the possibilities. It is not necessary to a.s.sume that an actual substance so diffuses itself, but the influence exerted may be thought of as a force, possibly some form of molecular motion, which is set in action at the area of injury and extends from this. No actual substance pa.s.ses along a nerve when it conveys an impulse.

We have left the injured area with an increased amount of fluid and cells within it, with the blood vessels dilated and with both cells and fluid streaming through their walls, and the cells belonging to the area actively repairing damages and multiplying. The process will continue as long as the cause which produces the injury continues to act, and will gradually cease with the discontinuance of this action, and this may be brought about in various ways. A foreign body may be mechanically removed, as when a thorn is plucked out; or bacteria may be destroyed by the leucocytes; or a poison, such as the sting of an insect, may be diluted by the exudate until it be no longer injurious, or it may be neutralized. Even without the removal of the cause the power of adaptation will enable the life of the affected part to go on, less perfectly perhaps, in the new environment. The excess of fluid is removed by the outflow exceeding the inflow, or it may pa.s.s to some one of the surfaces of the body, or in other cases an incision favors its escape. The excess of cells is in part removed with the fluid, in part they disappear by undergoing solution and in part they are devoured by other cells. With the diminishing cell activity the blood vessels resume their usual calibre, and when the newly formed vessels become redundant they disappear by undergoing atrophy in the same way as other tissues which have become useless.

When these changes take place rapidly the inflammation is said to be acute, and chronic when they take place slowly. Chronic inflammation is more complex than is the acute, and there is more variation in the single conditions. The chronicity may be due to a number of conditions, as the persistence of a cause, or to incompleteness of repair which renders the part once affected more vulnerable, to such a degree even that the ordinary conditions to which it is subjected become injurious. A chronic inflammation may be little more than an almost continuous series of acute inflammations, with repair continuously less perfect. Chronic imflammations are a prerogative of the old as compared with the young, of the weak rather than the strong.

FOOTNOTES: [1] The term exudation is used to designate the pa.s.sing of cells and fluid from the vessels in inflammation; the material is the exudate.

[2] By transudation is meant the constant interchange between the blood and the tissue fluid.

CHAPTER V

INFECTIOUS DISEASES.--THE HISTORICAL IMPORTANCE OF EPIDEMICS OF DISEASE.--THE LOSSES IN BATTLE CONTRASTED WITH THE LOSSES IN ARMIES PRODUCED BY--INFECTIOUS DISEASES.--THE DEVELOPMENT OF KNOWLEDGE OF EPIDEMICS.--THE VIEWS OF HIPPOCRATES AND ARISTOTLE.--SPORADIC AND EPIDEMIC DISEASES.--THE THEORY OF THE EPIDEMIC CONSt.i.tUTION.--THEORY THAT THE CONTAGIOUS MATERIAL IS LIVING.--THE DISCOVERY OF BACTERIA BY LOEWENHOECK IN 1675.--THE RELATION OF CONTAGION TO THE THEORY OF SPONTANEOUS GENERATION.--NEEDHAM AND SPALLANZANI.--THE DISCOVERY OF THE COMPOUND MICROSCOPE IN 1605.--THE PROOF THAT A LIVING ORGANISM IS THE CAUSE OF A DISEASE.--ANTHRAX.--THE DISCOVERY OF THE ANTHRAX BACILLUS IN 1851.--THE CULTIVATION OF THE BACILLUS BY KOCH.--THE MODE OF INFECTION.--THE WORK OF PASTEUR ON ANTHRAX.--THE IMPORTANCE OF THE DISEASE.

These are diseases which are caused by living things which enter the tissues of the body and, living at the expense of the body, produce injury. Such diseases play an important part in the life of man; the majority of deaths are caused directly or indirectly by infection. No other diseases have been so much studied, and in no other department of science has knowledge been capable of such direct application in promoting the health, the efficiency and the happiness of man. This knowledge has added years to the average length of life, it has rendered possible such great engineering works as the Panama Ca.n.a.l, and has contributed to the food supply by making habitation possible over large and productive regions of the earth, formerly uninhabitable owing to the prevalence of disease. It is not too much to say that our modern civilization is dependent upon this knowledge. The ma.s.sing of the people in large cities, the factory life, the much greater social life, which are all prominent features of modern civilization, would be difficult or impossible without control of the infectious diseases.

The rapidity of communication and the increased general movement of people, which have developed in equal ratio with the ma.s.sing, would serve to extend widely every local outbreak of infection. The principles underlying fermentation and putrefaction which have been applied with great economic advantage to the preservation of food were many of them developed in the course of the study of the infectious diseases. Whether the development of the present civilization is for the ultimate advantage of man may perhaps be disputed, but medicine has made it possible.

The infectious diseases appearing in the form of great epidemics have been important factors in determining historical events, for they have led to the defeat of armies, the fall of cities and of nations. War is properly regarded as one of the greatest evils that can afflict a nation, since it destroys men in the bloom of youth, at the age of greatest service, and brings sorrow and care and poverty to many. But the most potent factor in the losses of war is not the deaths in battle but the deaths from disease. If we designate the lives lost in battle, the killed and the wounded who die, as 1, the loss of the German army from disease in 1870-71 was 1.5, that of the Russians in 1877-78 was 2.7, that of the French in Mexico was 2.8, that of the French in the Crimea 3.7, that of the English in Egypt 4.2. The total loss of the German army in 1870-71 from wounds and disease was 43,182 officers and men, and this seems a small number compared with the 129,128 deaths from smallpox in the same period in Prussia alone. In the Spanish American war there were 20,178 cases of typhoid fever with 1,580 deaths. In the South African war there were in the British troops 31,118 cases of typhoid with 5,877 deaths, and 5,149 deaths from other diseases while the loss in battle was 7,582. The Athenian plague which prevailed during the Peloponnesian war, 431-405 B.C., not only caused the death of Pericles, but according to Thucydides a loss of 4,800 Athenian soldiers, and brought about the downfall of the Athenian hegemony in Greece. In the Crimean war between 1853-56, 16,000 English, 80,000 French and 800,000 Russians died of typhus fever. The plague contributed as much as did the arms of the Turks to the downfall of Constantinople and the Eastern Empire in 1453. It was the plague which in 1348 overthrew Siena from her proud position as one of the first of the Italian cities and the rival of Florence, and broke the city forever, leaving it as a phantom of its former glory and prosperity. The work on the great cathedral which had progressed for ten years was suspended, and when it was resumed it was upon a scale adjusted to the diminished wealth of the city, and the plan restricted to the present dimensions. As a little relief to the darkness the same plague saw the birth of the novel in the tales of Boccaccio, which were related to a delighted audience of the women who had fled from the plague in Florence to a rural retreat.

The knowledge which has come from the study of infectious disease has served also to broaden our conception of disease and has created preventive medicine; it has linked more closely to medicine such sciences as zoology and botany; it has given birth to the sciences of bacteriology and protozoology and in a way has brought all sciences more closely together. Above all it has made medicine scientific, and never has knowledge obtained been more quickening and stimulating to its pursuit.

Although the dimensions of this book forbid much reference to the historical development of a subject, some mention must still be made of the development of knowledge of the infectious diseases. It was early recognized that there were diseases which differed in character from those generally prevalent; large numbers of people were affected in the same way; the disease beginning with a few cases gradually increased in intensity until an acme was reached which prevailed for a time and the disease gradually disappeared. Such diseases were attributed to changes in the air, to the influence of planets or to the action of offended G.o.ds. The priests and charlatans who sought to excuse their inability to treat epidemics successfully were quick to affirm supernatural causes. Hippocrates (400 B.C.), with whom medicine may be said to begin, thought such diseases, even then called epidemics, were caused by the air; he says, "When many individuals are attacked by a disease at the same time, the cause must be sought in some agent which is common to all, something which everyone uses, and that is the air which must contain at this time something injurious."

Aristotle recognized that disease was often conveyed by contact, and Varro (116-27 B.C.) advanced the idea that disease might be caused by minute organisms. He says, "Certain minute organisms develop which the eye cannot see, and which being disseminated in the air enter into the body by means of the mouth and nostrils and give rise to serious ailments." In spite of this hypothesis, which has proved to be correct, the belief became general that epidemics were due to putrefaction of the air brought about by decaying animal bodies, (this explaining the frequent a.s.sociation of epidemics and wars,) by emanations from swamps, by periods of unusual heat, etc.

With the continued study of epidemics the importance of contagion was recognized; it was found that epidemics differed in character and in the modes of extension. Some seemed to extend by contact with the sick, and in others this seemed to play no part; it was further found impossible in many cases to show evidence of air contamination, and contamination of the air by putrefactive material did not always produce disease. Most important was the recognition that single cases of diseases which often occurred in epidemic form might be present and no further extension follow; this led to the a.s.sumption in epidemics of the existence of some condition in addition to the cause, and which made the cause operative. In this way arose the theory of the epidemic const.i.tution, a supposed peculiar condition of the body due to changes in the character of the air, or to the climate, or to changes in the interior of the earth as shown by earthquakes, or to the movements of planets; in consequence of this peculiar const.i.tution there was a greater susceptibility to disease, but the direct cause might arise in the interior of the body or enter the body from without. The character of the disease which appeared in epidemic form, the "Genius epidemicus," was determined not by differences in the intrinsic cause, but by the type of const.i.tution which prevailed at that time. The first epidemic of cholera which visited Europe in 1830-37 was for the most part referred to the existence of a peculiar epidemic const.i.tution for which various causes were a.s.signed. It was only when the second epidemic of this disease appeared in 1840 that the existence of some special virus or poison which entered the body was a.s.sumed.

Meanwhile, by the study of the material of disease knowledge was being slowly acquired which had much bearing on the causes. The first observations which tended to show that the causes were living were made by a learned Jesuit, Athanasius, in 1659. He found in milk, cheese, vinegar, decayed vegetables, and in the blood and secretions of cases of plague bodies, which he described as tiny worms and which he thought were due to putrefaction. He studied these objects with the simple lenses in use at that time, and there is little doubt that he did see certain of the larger organisms which are present in vinegar, cheese and decaying vegetables, and it is not impossible that he may have seen the animal and vegetable cells.

The first description of bacteria with ill.u.s.trations showing their forms was given by Loewenhoeck, a linen dealer in Amsterdam in 1675.

The fineness of the linen being determined by the number of threads in a given area, it is necessary to examine it with a magnifying lens, and he succeeded in perfecting a simple lens with which objects smaller than had been seen up to that time became visible. It must be added that he was probably endowed with very unusual acuteness of vision. He found in a drop of water, in the fluid in the intestines of frogs and birds, and in his evacuations, objects of great minuteness which differed from each other in form and size and in the peculiar motion which some of them possessed. In the year 1683 he presented to the Royal Society of London a paper describing a certain minute organism which he found in the tartar of his teeth. After these observations of Loewenhoeck became known to the world they quickly found application in disease, although the author had expressed himself very cautiously in this regard. The strongest exponent of the view of a living contagion was Plenciz, 1762, a physician of Vienna, basing his belief not only on the demonstration of minute organisms by Loewenhoeck which he was able to verify, but on certain shrewdly conceived theoretical considerations. He was the first to recognize the specificity of the epidemic diseases, and argued from this that each disease must have a specific cause. "Just as a certain plant comes from the seed of the same plant and not from any plant at will, so each contagious disease must be propagated from a similar disease and cannot be the result of any other disease." Further he says, "It is necessary to a.s.sume that during the prevalence of an epidemic the contagious material undergoes an enormous increase, and this is compatible only with the a.s.sumption that it is a living substance."

But as is so often the case, speculation ran far ahead of the observations on which it is based. There was a long gap between the observations of Loewenhoeck and the theories of Plenciz, justified as these have been by present knowledge. In the spirit of speculation which was dominant in Europe and particularly in Germany in the latter half of the eighteenth and the first half of the nineteenth centuries, hypotheses did not stimulate research, but led to further speculations. As late as 1820 Ozanam expressed himself as follows: "Many authors have written concerning the animal nature of the contagion of disease; many have a.s.sumed it to be developed from animal substance, and that it is itself animal and possesses the property of life. I shall not waste time in refuting these absurd hypotheses." The theory of a living contagion was too simple, and not sufficiently related to the problems of the universe to serve the medical philosophers.

Knowledge of the minute organisms was slowly acc.u.mulating. The first questions to be determined were as to their nature and origin. How were they produced? Did they come from bodies of the same sort according to the general laws governing the production of living things, or did they arise spontaneously? a question which could not be solved by speculation but by experiment. The first experiments, by Needham, 1745, pointed to the spontaneous origin of the organisms. He enclosed various substances in carefully sealed watch crystals from which the air was excluded, and found that animalculi appeared in the substance, and argued from this that they developed spontaneously. In 1769, Spallanzani, a skilled experimental physiologist, in a brilliant series of experiments showed the imperfect character of Needham's work and the fallacy of his conclusions. Spallanzani placed fluids, which easily became putrid, in gla.s.s tubes, which he then hermetically sealed and boiled. He found that the fluid remained clear and unchanged; if, however, he broke the sealed point of such a tube and allowed the air to enter, putrefaction, or in some cases fermentation, of the contents took place. He concluded that boiling the substances destroyed the living germs which they contained, the sealed tubes prevented the air from entering, and when putrefaction or fermentation of the contents took place the organisms to which this was due, being contained in the air, entered from without. Objection was made to the conclusions of Spallanzani that heating the air in the closed tubes so changed its character as to prevent development of organisms in the contents. This objection was finally set aside by Pasteur, who showed that it was not necessary to seal the end of the tube before boiling, but it could be closed by a plug of cotton wool, which mechanically removed the organisms from the air which entered the tube, or if the tube were bent in the shape of a _U_ and the end left open, organisms from the air could not pa.s.s into the tube against gravity when air movement within the tube was prevented by bending. The possibility of spontaneous generation cannot be denied, but that it takes place is against all human experience.

It was not possible to attain any considerable knowledge of the bacteria discovered by Loewenhoeck until more perfect instruments for studying them were devised. Lenses for studying objects were used in remote antiquity, but the compound microscope in which the image made by the lens is further magnified was not discovered until 1605, and when first made was so imperfect that the best simple lenses gave clearer definition. With the betterment of the microscope, increasing the magnifying power and the sharpness of the image of the object seen, it became possible to cla.s.sify the minute organisms according to size and form and to study the separate species. The microscope has now reached such a degree of perfection that objects smaller than one one hundred thousandth of an inch in diameter can be clearly seen and photographed.

Great impetus was given to the biological investigation of disease by the discoveries which led to the formulation of the cell theory in 1840 and the brilliant work of Pasteur on fermentation,[1] but it was not until 1878 that it was definitely proved that a disease of cattle called anthrax was due to a species of bacteria. What should be regarded as such proof had been formulated by Henle in 1840. To prove that a certain sort of organism when found a.s.sociated with a disease is the cause of the disease, three things are necessary:

1. The organism must always be found in the diseased animal and a.s.sociated with the changes produced by the disease.

2. The organism so found must be grown outside of the body in what is termed pure cultures, that is, not a.s.sociated with any other organisms, and for so long a time with constant transfers or new seedings that there can be no admixture of other products of the disease in the material in which it is grown.

3. The disease must be produced by inoculating a susceptible animal with a small portion of such a culture, and the organism shown in relation to the lesions so produced.

It is worth while to devote some attention to the disease anthrax.

This occupies a unique position, in that it was the first of the infectious diseases to be scientifically investigated. In this investigation one fact after another was discovered and confirmed; some of these facts seemed to give clearer conceptions of the disease, others served to make it more obscure; new questions arose with each extension of knowledge; in the course of the work new methods of investigation were discovered; the sides of the arch were slowly and painfully erected by the work of many men, and finally one man placed the keystone and anthrax was for a long time the best known of diseases. Men whose reputation is now worldwide first became known by their work in this disease. It was a favorable disease for investigation, being a disease primarily of cattle, but occasionally appearing in man, and the susceptibility of laboratory animals made possible experimental study.

Anthrax is a disease of domestic cattle affecting particularly bovine cattle, horses and sheep, swine more rarely. The disease exists in practically all countries and has caused great economic losses. There are no characteristic symptoms of the disease; the affected cattle have high fever, refuse to eat, their pulse and respiration are rapid, they become progressively weaker, unable to walk and finally fall. The disease lasts a variable time; in the most acute cases animals may die in less than twenty-four hours, or the disease may last ten or fourteen days; recovery from the disease is rare and treatment has no effect. It does not appear in the form of epidemics, but single cases appear frequently or rarely, and there is seemingly no extension from case to case, animals in adjoining stalls to the sick are not more p.r.o.ne to infection than others of the herd. On examination after death the blood is dark and fluid, the spleen is greatly enlarged (one of the names of the disease "splenic fever" indicates the relation to the spleen) and there is often b.l.o.o.d.y fluid in the tissues.