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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

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