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 Constitution.—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 Canal, 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 massing 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 massing, 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 zoölogy and botany; it has given birth to the sciences of bacteriology and protozoölogy 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 gods. 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 association 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 assumption 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 constitution, 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 constitution 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 constitution 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 constitution for which various causes were assigned. 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 assumed.
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 illustrations 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 assume that during the prevalence of an epidemic the contagious material undergoes an enormous increase, and this is compatible only with the assumption 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 assumed 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 accumulating. 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 glass 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 pass 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 classify 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,[7] 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 associated 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 associated 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 associated 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 prone 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 bloody fluid in the tissues.
Where the disease is prevalent there are numbers of human cases. Only those become infected who come into close relations with cattle, the infection most commonly taking place from small wounds or scratches made in skinning dead cattle or in handling hides. The wool of sheep who die of the disease finds its way into commerce, and those employed in handling the wool have a form of anthrax known as wool-sorters' disease in which lesions are found in the lungs, the organisms being mingled with the wool dust and inspired. In Boston occasional cases of anthrax appear in teamsters who are employed in handling and carrying hides. The disease in man is not so fatal as in cattle, for it remains local for a time at the site of infection, and this local disease can be successfully treated.
The beginning of our knowledge of the cause dates from 1851, when small rod-shaped bodies (Fig. 17) were found in the blood of the affected cattle, and by the work of a number of observers it was established that these bodies were constantly present. Nothing was known of their nature; some held that they were living organisms, others that they were formed in the body as a result of the disease. Next the causal relation of these bodies with the disease was shown and in several ways. The disease could be caused in other cattle by injecting blood containing the rods beneath the skin, certainly no proof, for the blood might have contained in addition to the rods something which was the real cause of the disease. Next it was shown that the blood of the unborn calf of a cow who died of the disease did not contain the rods, and the disease could not be produced by inoculating with the calf's blood although the blood of the mother was infectious. This was a very strong indication that the rods were the cause; the maternal and foetal blood are separated by a membrane through which fluids and substances in solution pass; but insoluble substances, even when very minutely subdivided, do not pass the membrane. If the cause were a poison in solution, the foetal blood would have been as toxic as the maternal. The blood of infected cattle was filtered through filters made of unbaked porcelain and having very fine pores which allowed only the blood fluid to pass, holding back both the blood corpuscles and the rods, and such filtered blood was found to be innocuous. It was further shown that the rods increased enormously in number in the infected animal, for the blood contained them in great numbers when but a fraction of a drop was used for inoculation. Attempts were also made with a greater or less degree of success to grow the rod shaped organisms or bacilli in various fluids, and the characteristic disease was produced by inoculating animals with these cultures; but it remained for Koch, 1878, who was at that time an obscure young country physician, to show the life history of the organism and to clear up the obscurity of the disease. Up to that time, although it had been shown that the rods or bacilli contained in the blood were living organisms and the cause of the disease, this did not explain the mode of infection; how the organisms contained in the blood passed to another animal, why the disease occurred on certain farms and the adjoining farms, particularly if they lay higher, were free. Koch showed that in the cultures the organisms grew out into long interlacing threads, and that in these threads spores which were very difficult to destroy developed at intervals; that the organisms grew easily in bouillon, in milk, in blood, and even in an infusion of hay made by soaking this in water. This explained, what had been an enigma before, how the fields became sources of infection. The infection did not spread from animal to animal by contact, but infection took place from eating grass or hay which contained either the bacilli or their spores. When a dead animal was skinned on the field, the bacilli contained in the blood escaped and became mingled with the various fluids which flowed from the body and in which they grew and developed spores. It was shown by Pasteur that even when a carcass was buried the earthworms brought spores developed in the body to the surface and deposited them in their casts, and in this way also the fields became infected. From such a spot of infected earth the spores could be washed by the rains over greater areas and would find opportunity to develop further and form new spores in puddles of water left on the fields, which became a culture medium by the soaking of the dead grass. The contamination of the fields was also brought about by spreading over them the accumulations of stable manure which contained the discharges of the sick cattle. The tendency of the disease to extend to lower-lying adjacent fields was due to the spores being washed from the upper fields to the lower by the spring freshets. Meanwhile Pasteur had discovered that by growing the organisms at higher temperatures than the animal body, it was possible to attenuate the virulence of the bacilli so that inoculations with these produced a mild form of the disease which rendered the inoculated animals immune to the fatal disease. The description of Pasteur's work on the disease as given in the account of his life by his son-in-law is fascinating.
Hides and wool taken from dead animals invariably contained the spores which could pass unharmed through some of the curing processes, and were responsible for some of the cases in man. Owing to the introduction of regulations which were based on the knowledge of the cause of the disease and the life history of the organism, together with the prophylactic inoculation devised by Pasteur, the incidence of the disease has been very greatly lessened. Looking at the matter from the lowest point of view, the money which has been saved by the control of the disease, as shown in its decline, has been many times the cost of all the work of the investigations which made the control possible. It is a greater satisfaction to know that many human lives have been saved, and that small farmers and shepherds have been the chief sharers in the economic benefits. The indirect benefits, however, which have resulted from the application of the knowledge of this disease, and the methods of investigation developed here, to the study of the infections more peculiar to man, are very much greater.