Art. III.—Bacteria and their Relation to Disease.

Transactions and Proceedings of the Royal Society of New Zealand, Volume 22, 1889, Page 31

Art. III.—Bacteria and their Relation to Disease. By Isaiah de Zouche, M.D., Address as President of the Otago Institute. [Read before the Otago Institute, 12th November, 1889.] It will help us to better understand the widespread revolution in pathological views or doctrines occasioned by the discovery of bacterial agency in disease if we glance at some of the theories which were formerly held regarding the nature of disease—theories which still lurk in the belief of certain classes of the people, just as old styles in dress and old-fashioned modes of speech are found amongst them long after they have become obsolete in the centres of fashion and learning. At an early period in the history of medicine disease was attributed to alterations of the humours of the body. Hippocrates, born about 450 years before Christ, who has been justly styled “the father of medicine,” described certain humours known later as the “cardinal humours,” to the derangements of which he attributed various diseases. The humours, according to Hippocrates, were four—namely, blood, phlegm or mucus, yellow bile, and black bile. He held that in order that the body should be maintained in health these humours should be mixed in just proportion as regards quantity and force, but especially that they should be well mixed; that disease results from excess or defect of any of these humours, or from its separation without having been duly mixed with the others. Thus, our word “melancholy,” meaning in Greek black bile, denotes an affection in which black bile is supposed to be in excess; a “phlegmatic” temperament characterizes those in whom the cold or phlegmatic watery humour is overabundant; while the word “dyscrasia,” meaning a faulty admixture (of the humours), is still used

in medicine to signify an unhealthy habit of body. Hippocrates speaks of remedies which act on particular humours—some on bile, others on phlegm or mucus. Even in our own day we have our cholagogues and hydragogues—terms which have been handed down from these teachings. He attributes most fevers to bile. The humours were supposed to be at first crude, then they underwent digestion—or coction, as it was called—and the diseased fluids were expelled by a crisis. It was a beginning of what is known as the humoral pathology, which has influenced medicine up to our own times. This theory of pathology is, indeed, still in favour at certain hydropathic establishments. Prolonged wet-packing, by interfering with the normal functions of the skin, produces an artificial eczema, and when the watery or purulent rash appears the patient is informed that it is a “crisis,” by which the bad humours of the blood are escaping. It is worthy of note that Hippocrates attributed the first cause of diseases to the air (πν∊υ̑μα, spiritus). Air was believed by ancient philosophers to contain the vital principle (spiritus vitalis), from which it was to be inferred that diseases were caused by some abnormal spiritus in the air, although Hippocrates admits that some diseases may be produced by errors of diet. Great influence in the causation of disease was attributed by Hippocrates and his successors to the time of the year, summer and autumn being the seasons when fevers were in the ascendant. The constitution of the atmosphere was held to determine in some degree the constitution of the reigning diseases. The observation was perfectly correct, although the manner in which atmospheric conditions influence disease could not be then understood—nor do I by any means assert that they are yet fully understood. To this I will refer later, when speaking of epidemics. It might be of great interest to trace the slow steps of the growth of medical knowledge, but this would lead us away from our subject without conferring any present benefit. Medicine had its dark ages. Its practice became strangely mixed up with astrology, incantations, invocations, and charms. Here and there was a spark of light from some original thinker, whose means of research were, however, insufficient to enable him to place his views on any sound basis. Theories reigned in place of facts, and medicine had to await the development of auxiliary and sister sciences before she could even distantly hope to attain the position which I believe she is now rapidly acquiring—namely, that of an exact science. But a word about the later theories. The chemical theory of disease prevailed in the fifteenth and sixteenth centuries, with which the name of the clever, egotistic, semi-scientific charlatan, Paracelsus, is associated. Its supporters referred processes

of disease, as well as those of health, to ordinary chemical laws. To these were opposed the vitalists, represented by Van Helmont (born 1577 or 1578), who attributed disease to the disturbances of the vital spirits. These were termed archeus, or, as there were two chief vital principles, archei. They reigned in the stomach and spleen, and dominated the body therefrom, delegating their powers to satraps or minor archei, for the other organs. The belief in a “vital principle” has prevailed since the beginning of medicine, or of biology as a science. The arteries were supposed to contain air, the origin of life, and to convey with it, or in it, the vital spirits throughout the body. Hippocrates, as already mentioned, held the theory of a vital principle, which he believed was in the air, and was drawn in by the breath. Even in the seventeenth century there was not much advance on the Hippocratic pathology. The great English physician, Sydenham (born 1634), attributed the origin of acute diseases, to a latent and inexplicable alteration of the air infecting the bodies of men. He speaks of peccant matter, its concoction, fermentation, and despumation. The humoral theory was opposed by that of the solidists, who referred all diseases to an affection of the solid parts of the body. They held that the solids alone were endowed with vital properties, and alone could receive the impression of agents tending to produce disease. So far for the general theories which influenced medical thought and practice for centuries. They were destined to be undermined or modified by the more accurate study of human anatomy, which had received such an impetus from the labours of Vesalius (born 1514), in the middle of the sixteenth century, the discovery of the circulation of the blood by Harvey (1616), and especially by the use of the microscope, which Leeuwenhoeck improved materially, and employed in physiological and biological investigation, with important results, towards the end of the seventeenth century. Pathology, which may be called the physiology of disease, began to emerge from the cloudland of theory into a clearer day, but there were still many things obscure, and which required better methods than were then at command for their elucidation. The phenomena of inflammation especially occupied the attention of pathologists, who believed that in these lay the key to many or most of the morbid changes in the body. Inflammation, from being regarded as a disease, came to be understood as a condition of an organ or part induced by some irritation—a process sometimes conservative, sometimes destructive. And recent researches have shown the importance of a correct understanding of this process, for in studying inflamed tissues with the aid of the microscope the

property possessed by the white blood-corpuscles of wandering outside of the vessels was discovered, and also their power of removing substances deleterious to the system, bacteria amongst others. In order, therefore, to be able to follow up the fate of bacteria which find their way into the body, or the fate of the body into which bacteria have been introduced, it will be necessary to direct our attention for a moment to some of the phenomena of inflammation. For our present purpose it will be sufficient to consider the blood, the irritated part, and the blood-vessels in its vicinity. The blood consists of water holding in solution albumen, fibrin, and various salts, with an infinite number of minute cells suspended or floating throughout it. These cells are the red and the white corpuscles. With the red blood-corpuscles we have nothing to do for the moment. It is the white corpuscles, or leucocytes, which claim our attention. The white corpuscles are softbodied globular cells about 1/2500in. in diameter, composed of protoplasm, and possessing a nucleus or nuclei and nucleoli. Sometimes vacuoles are seen in their interior. They have been aptly likened to the Amœba. The Amœba is the simplest form amongst the protozoa. It consists of a minute mass of jelly, a simple cell without organs—unless the nucleus be an organ, or the vacuoles which may appear at any time. It possesses the power of movement by shooting out portions of its protoplasm, which serve as arms or feet (pseudopodia). It nourishes itself by investing any small body capable of affording it nutriment with its protoplasmic substance, surrounding the morsel with its body. It can reject any innutritious or noxious particle which it may have enclosed, by simply withdrawing its body from the particle, and leaving it outside. The analogy between the Amœba and the white blood-corpuscle, or leucocyte, seems complete. The leucocytes are little particles of protoplasm, monocellular, and nucleated, and sometimes vacuolated. They are endowed with the power of movement by means of little feet-like processes which can be shot out and again retracted. They can take particles of foreign matter into their interior and digest them or reject them, just as the Amœba can do. We have thus living in our blood little cells possessing a life of their own, having the faculty of movement with which our will has nothing to do, of selecting and digesting food, and, as we shall see afterwards, the power of avoiding some matters which would act as poison to them. And now a few words with regard to inflammation. The definition of Celsus as to the external characteristics of inflammation reigns to this day in our text-books—namely, “redness and swelling, with heat and pain”—“Rubor et

tumor, cum calore et dolore.” To be brief, the redness is due to increased flow of blood to the part, the heat to increased oxidation of tissue, and the pain to pressure on nerve-endings. The smaller blood-vessels, termed capillaries, dilate, yet the blood flows slowly, and has a tendency to stagnate. The swelling is caused partly by the increased blood-supply, and partly by the pouring-out from the capillary blood-vessels of a thickish, glutinous, watery fluid termed liquor sanguinis, or lymph, which under certain conditions becomes changed into matter or pus. The examination of lymph showed it to consist of water, albumen, fibrin, and salts, while under the microscope could be seen spherical nucleated cells termed lymph-corpuscles, which are identical with white blood-corpuscles. The origin of white cells in the liquor sanguinis thrown out by the blood-vessels in inflammation was by no means clear, but a discovery of the highest importance, destined to throw light on this matter, was made by Dr. William Addison, of Malvern, about the year 1843. This was one of the great discoveries in physiology or pathology, and deserves special mention. Dr. Addison saw the white corpuscles migrating from the minute blood-vessels into the tissues outside. His observations were published in the Transactions of the Provincial Medical and Surgical Association of 1843 and 1844* (1.) William Addison, M.D. “Experimental and Practical Researches on the Structure and Function of Blood-corpuscles, on Inflammation, and on the Origin and Nature of Tubercle in the Lungs.”—Prov. Med. Surg. Assoc. Trans., vol. xi., 1843, p. 233. (2.) “The Actual Process of Nutrition in the Living Structures demonstrated by the Microscope, and the Renewal of the Tissues and Secretions from the Blood thereby illustrated.”—Op. cit., vol. xii., 1844, pp. 235–306., which can probably be only found in some of the large medical and scientific libraries in the United Kingdom or in the United States, so that I am unable to give any details of his work. His discovery was fully confirmed in 1846 by Dr. Augustus Waller, an English physiologist, who watched the process of inflammation in a frog's tongue placed under the microscope. His method and description are very complete, and the illustrations give great exactness to them. The mere exposure of the tongue speedily excited inflammation, so that he had the opportunity of seeing the increased flow of blood, and the process of exudation of liquor sanguinis; and now he was able to see the white corpuscles moving slowly against the wall of the small blood-vessels, then coming to a standstill, and finally squeezing themselves through the coats of the vessels with their peculiar amœboid mode of progression, first forcing an arm through, and then, by degrees, the whole body, while the hole through which they had emerged closed

again like indiarubber softened by heat. The full significance of this discovery could not be perceived at the time. The fields of physiology and pathology were still practically unexplored, and the migration or diapedesis of the blood-corpuscles could only be registered as a fact to be made use of on some future occasion. It was one of those discoveries which prove the value of the pursuit of knowledge for its own sake, the scientific worker, with far-seeing vision, looking forward to the time when facts apparently isolated, and to the untrained mind of little value, will find their connection with other facts and form a continuous chain of knowledge. Dr. Addison's discovery was lost sight of for nearly a quarter of a century, when the migration of the white corpuscles was rediscovered by Cohnheim (1867), who studied the process of inflammation in the mesentery of a frog, and added valuable newly-observed facts to the pathology of inflammation. Now, what could impel these white corpuscles to wander out from their natural element? Were they driven by the vis a tergo with the blood-stream? What are these white cells? Here, however, we must leave them for a time, as a novelist sometimes leaves important characters introduced in his earlier chapters, while others occupy the scene, to bring them all together for the dénouement at the end. A few words more concerning theories of disease, and I shall be able to enter on the more immediate subject of this address. The origin of fevers has at all times exercised the minds of physicians. Even up to quite a recent period, twenty years ago, there were some who maintained, and there may be still, for aught I know, some who believe, that certain fevers—typhus and typhoid, for instance—could be generated de novo, and without infection, direct or indirect, from an individual suffering from fever, by privation, fatigue, dirt, and overcrowding. This is the doctrine of heterogenesis from the clinical side. On the other hand, there were some, even as long as fifty years ago, who believed that a specific poison was handed down by descent from a similar poison, and was received into the system, where it multiplied and “fermented,” and was finally cast out by a crisis. It was the old doctrine of crudity, coction, crisis, and despumation a little farther advanced. The theory of an impure state of the blood gave place to one more definite—namely, that of a specific organic body as the poisoning agent—but it was understood that this poison was spread, and infected human beings, by means of the atmosphere. I am indebted to Dr. Aitken's work on medicine for the fact that in 1838 Boehm attributed cholera to the presence of a fungus affecting the intestinal epithelium, and he gave drawings of microfungi which he found. These

could hardly have been the true microbes of cholera, but the idea of a vegetable parasite was there. In 1840 Henle published a remarkable paper, “On Contagion and Miasma, and Miasmatic Contagious Diseases,” in which he “concluded, from theoretical grounds, that contagious diseases must be caused by organized contagia, which he considered were probably of the nature of low vegetable organisms. He further added that these parasites need not necessarily be so small that the magnifying-power of our microscopes was not sufficient to demonstrate them, but perhaps they escaped observation only because of the difficulty of distinguishing them from the surrounding tissues—a supposition which has been brilliantly confirmed by the discovery of the tubercle-bacillus.”—(Fehleisen.) This was the real beginning of the bacterial or ferment theory of disease. As already stated, however, the origin of fevers de novo was maintained by some as late as thirty years after this, and the extraordinary sporadic occurrence of fevers under circumstances which appeared to preclude the possibility of infection in the usual sense seemed to lend confirmation to this view. Before the theories started by Henle were entertained, the word “parasite,” in connection with disease affecting the human species, was understood to apply to distinctly animal organisms, such as entozoa; later the term was extended to the fungi of certain diseases of the skin and hair, such as ringworm. The word “fermentation” had long been in use to denote the febrile process. What was called the effervescence or ebullition of the blood, by which terms the older physicians characterized its condition during the continuance of the high temperature in fevers, before the crisis, was believed to present some analogy with the process of fermentation in vinous or malt liquors, although the exact nature of alcoholic fermentation was still known to or suspected by but few. In 1842 Dr. William Farr introduced the word “zymotic” to designate the poison of specific fevers; but he did not consider the febrile process to be absolutely identical with ordinary fermentation, and even then it was held that the ferment-producing body was or might be some nitrogenous organic substance without more exact definition. While physicians were seeking for the poison of fevers, chemists were endeavouring to discover the cause of alcoholic fermentation. The vegetable nature of ferments was ascertained and asserted by Cagnard de Latour in 1837, but the fact had not obtained acceptance by the scientific world. The theory that ferments were due to an organized body was definitely settled by the researches of M. Pasteur (1857–60), who, in 1857, described the little globules or short segments of the ferment of lactic acid, and in 1858 those of alcoholic fermentation, and came

to the conclusion that there were specific ferments, each producing its own specific fermentation. The teachings of M. Pasteur created a new interest in the search for the ferments of the zymotic fevers. In 1850 Rayer discovered little filiform bodies in the blood of animals which had died from anthrax or charbon. This discovery slept until 1863, when Davaine inoculated rabbits with blood containing these filiform bodies, with the result that they died of anthrax. The little cylindrical rods of butyric fermentation were described by Pasteur in 1861, and Davaine says that it was owing to Pasteur's demonstration of the connection between these “corpuscles” and the butyric fermentation that he conceived the idea that anthrax might be caused by the corpuscles seen in the blood in anthrax. Thus slowly, by years of clinical observation, by years of chemical, microscopical, and botanical researches, the fons et origo mali was found. Physicians, chemists, and biologists had, each in their own department and working in their own way, contributed something to this result. And now the search for specific bacteria in disease may be said to have fairly begun. Hitherto the efforts of the believers in the parasitic—i.e., bacterial—origin of diseases to discover the microbes had been rendered futile by difficulties connected with the means of research. The habits, if I may use the term, of the bacteria were unknown; their behaviour to chemical reagents—in short, the whole scientific method connected with the investigation of their life-history and microscopical demonstration—had to be built up almost from the beginning, and errors unavoidable in the investigation of a new and difficult science had to be eliminated. These difficulties have in the case of many of the specific bacteria been overcome, while other bacteria whose existence was before strongly suspected are being constantly added to the list of those that are known. Cohn showed that bacteria arose in solutions of decaying animal matter, and placed them among the vegetable organisms. But the admission of bacteria to a place in the natural kingdoms as independent living organisms was not to take place without a war of words and scientific tests. As it was believed by clinical physicians that fevers could be generated de novo in an unhygienic environment, so more than one distinguished biologist has argued that bacteria may arise by natural laws and reactions in solutions of organic matter. This opens up the question of so-called spontaneous generation in general; and the subject did not escape the attention of M. Pasteur, who, in 1860–61, after carefully-conducted experiments, came to the conclusion that “all organized productions of infusions take their origin from corpuscles which exist in suspension in the air.” He says in

another place (1860), “What would be most desirable would be to conduct these studies far enough to prepare the way for a serious investigation as to the origin of various diseases.” M. Pasteur's experiments and words such as I have just quoted set Davaine thinking about the connection between the rods seen by Rayer in anthrax and the causation of that disease, and had for immediate effect the experiments in antiseptic surgery by Lister, which have been followed by such brilliant results. We are thus brought back to the views of Hippocrates and his successors as to the πμ∊ὐνα or spiritus in the air with which we inhale the origin of disease as well as the principle of life. We have here, too, the explanation of what Sydenham, in the seventeenth century, termed the “latent and inexplicable alteration of the air infecting the bodies of men.” The views of Bastian may be given as those of one of the most recent supporters of the doctrine of heterogenesis. In a solution containing organic matter he describes the aggregation of minute portions of protoplasm—the plastide particles—in a film—the proligerous pellicle; and he maintains that “bacteria are produced as constantly in a solution of colloidal matter as crystals are produced in a solution containing crystallizable matter.” He says, in his conclusions, “Both observation and experiment unmistakably testify to the fact that ‘living’ matter is constantly being formed de novo in obedience to the same laws and tendencies as those which determine all the most simple chemical combinations, the qualities which we summarise under the word ‘life’ being in all cases due to the combined molecular actions and properties of the aggregate which displays them, just as the properties which we include under the word ‘magnetism’ are due to particular modes of collocation which have been assumed by the molecules of iron.” Bastian, however, neglected to sterilise his flasks by passing them through the flame, and the omission was sufficient to discredit his conclusions with the scientific world. The balance of scientific opinion at the present day is very largely in favour of biogenesis as applied to the origin of bacteria, as well as to all forms of life; indeed, the doctrine of omnis cellulæ cellula is all but universally accepted. Davies (quoted by Hirsch) says, “I would as soon believe in the spontaneous generation of human beings as I would in the spontaneous generation of typhus.” The real discoverer of bacteria was Leeuwenhoeck, of Delft, born A.D. 1632. Without entering into any detailed description of bacteria, which may be found in any of the systematic works on the subject, it will be necessary to give an outline of their general characteristics in order to the better understanding of the manner in which they settle and multiply

in the bodies of men and animals, and of their relation to disease and its cure. The word “bacterium,” the latinised form of βακυήριον, and meaning a staff, refers to the appearance under the microscope of one division of micro-organisms, from which the name has been distributed to designate these small beings in general. The term “microbe,” used by the French, indicates a small living thing. They have been alternately classed as animals and as plants. Ehrenberg, in his work on infusion-animalcules, published in 1838, described them as animal forms, their power of movement, as he says expressly, leading him to place them in the animal kingdom. Under the microscope some forms are seen to dart across the field with very rapid movements; others have spiral, corkscrew, or vacillating or undulatory motion. Cocci have molecular or “Brownian” movements. Many kinds of bacteria are motionless. The exact place of bacteria in a biological classification may be held to be still undetermined. They have been placed among the fungi, inasmuch as bacteria consist of vegetable cells destitute of chlorophyll, and they have other characteristics of fungi. Other observers consider them as algæ, from the fact that some species do contain chlorophyll. Looking on them as plant-forms, perhaps the safest classification is that which refers them to the Thallophyta, in which Sachs places them. Other biologists place them in a separate order, which they term the Protista, to be considered as between the animal and vegetable kingdoms. At the same time, as de Bary says, “it is merely a matter of convention in the case of these simple organisms where and how we shall draw the line between the vegetable and animal kingdoms.” Bacteria consist of cells which are, so far as is known, destitute of nuclei. In form the cells are globular or ovoid, or elongated as cylindrical or spindle-shaped rods. The globular and rod-shaped forms have mostly a diameter of .001 of a millimetre, or about 1/25400in. The length of the rods is from two to four times the transverse diameter. Chemically the cells are composed of protein or mycoprotein, and have a distinct cell-wall, which possesses distinct physical and chemical properties from those of the cell-contents. Various classifications have been made. The classification of bacteria hitherto most commonly followed is that of Cohn, who takes the form of the bacteria as the basis. He gives four classes: 1, Spherobacteria, globular; 2, Microbacteria, short rods; 3, Desmobacteria, long rods; 4, Spirobacteria, spirals. This brings us to the terms used in describing bacteria. The globular cells are called cocci, from κόκκοç, a berry, and from which, again, we have micrococcus and macrococcus.

Two cocci attached to each other are spoken of as a diplococcus, while several cocci attached to each other in the form of a chain are called streptococcus, from αυρέπυοç, a chain. Then there is the vibrio, or bentrod; the spirillum, a corkscrew form; bacillus, a long thin rod, &c. Bacteria multiply by fission and by spores, or by cells which act as spores. From their mode of reproduction by fission they are called schizomycetes or fission-fungi. Bacteria require for their nutrition nitrogen, carbon, potassium, sodium, and phosphoric acid, while water is necessary as a medium for the changes operated by them. Their food is obtained from organic compounds, which they have the faculty of splitting up, but they also grow in solutions of tartrate and acetate of ammonia. Some require the presence of free oxygen; hence Pasteur makes two great divisions of bacteria into (1) aërobic, and (2) anaërobic. Their growth is affected by the soil in which they happen to be planted; also by temperature, by contact with oxygen, &c.; in other words, by their environment. Thus the bacillus of anthrax and the micrococcus of fowl-cholera, so malignant under ordinary circumstances, have been rendered harmless by cultivation in neutralised chicken-broth with a supply of oxygen and in a heightened temperature; or, as some assert, through the action of the heightened temperature alone. Just as human beings and animals may become stunted and deformed by starvation and want of light and warmth, so may bacteria become altered in form, and exhibit a sickly growth; or, on the other hand, with suitable food and other accessories they may grow luxuriantly. We find similar phenomena in the higher plants. “Bishop Heber mentions that in the Botanical Gardens at Calcutta he saw a wretched little oak kept alive with difficulty, under a sky and in a temperature so perpetually stimulating that no time was allowed it to shed its leaves, or to recruit its powers by hibernation.”* “Geograph. Distrib. of Plants.” Relig. Tract Society. Bacteria which grow in living bodies are termed parasites; those growing in dead bodies or decaying organic matter are called saprophytes. That fungi can be parasitic in living bodies we have a striking example in the Cordiceps, which grows at the expense of the caterpillar which it infests, filling the body with its mycelium, and causing the death of the animal. Some bacteria—as anthrax, for example—can live and vegetate either as parasites or as saprophytes; and, further, they can live in decaying vegetable matter, such as potatoes, and this is a special source of danger to animals, which are thus liable to become infected by their vegetable food. They have distinct preferences as to their host, resembling in this respect many

animal parasites. Age influences the predisposition of the host. Young plants are more susceptible to the attack of fungi than older ones; and we all know how much more prone children are to catch scarlatina, and measles, and whooping-cough than adults, and how much more liable they are to be affected with animal parasites. Again, as to preferences, in a consumptive family all the boys may escape and the girls become consumptive, or vice versa, or all the members of a family but one may escape. So, during an epidemic of cholera or of typhus many individuals may be exposed to infection, but the bacteria select by preference those whose tissues are weakened, and so predisposed for their reception, or which are unable to resist the invasion. Others, again, accommodate themselves in various species of host, as the tubercle bacillus for instance, which can live in man, monkeys, cattle, fowls, &c., just as the common mistletoe is able to graft itself on trees so widely different as the apple-tree, the willow, the oak, and the fir. Bacteria have also preferences as to the part or tissue of their host, being found in that part in which the conditions are most favourable to their life and growth. The bacillus of cholera selects the intestines, the spirillum of relapsing fever is found in the blood. In the same way animal parasites choose their home in their host. The Trichina spiralis, being introduced into the intestinal canal, bores its way into the spaces between the fibres of the muscles, while the liver-fluke finds out the channels leading to the liver, where it sets up its home for the time being. Bacteria obtain entrance to the body with the air that we breathe, with our food, and also through wounds. And now we have to consider, in what way can the presence of these minute organisms cause disease? First, they act as foreign bodies. It is an axiom in surgery that the presence of a foreign body is sufficient to produce inflammation. A familiar example of this is the inflammation caused by a grain of sand in the eye. Inflammation is necessary, however inconvenient to the individual, and its use we shall see presently. As parasites, bacteria of course live at the expense of the tissue in which they grow. If they merely absorbed the juices of the part the changes effected by them would only consist in lessening the nutritive substance, and the mischief caused by them would be represented merely by the loss thus-occasioned. But they act as ferments, and it is this action especially which is the cause of disease. And here it may be as well to define what is meant by the word “ferment.” A ferment is defined to be a body which causes a change of composition in organic compounds without itself forming any part of the resulting products. The alcoholic and acetous fermentations

have been known from the earliest times—that is, by their products—but the discovery of the vegetable nature of ferments began with that of the yeast-fungus by Cagnard de la Tour in 1828. It was reserved for M. Pasteur to show the exact relation of the bacterial ferments to their specific fermentations. While the term “ferment” is very commonly applied to the bacteria, or vegetable organisms causing the fermentation, it is now used by many to indicate a substance secreted by the bacteria which is the real ferment or enzyme. This substance may be separated from the bacteria producing it, and cause fermentation, or the bacteria may be destroyed while the ferment remains active. The mode in which the enzyme, or ferment, acts is by the formation of leucomaines in the body, or ptomaines in decomposing animal substances. Our knowledge of these bodies being comparatively recent, I may be permitted to explain that ptomaines are basic bodies resembling alkaloids, developed in decaying animal matters. It may perhaps be right to call them alkaloids. The alkaloids resulting from the decomposition of albumen in the living body are called leucomaines. The poisoning caused by tainted fish, or by “high” meat, is due to ptomaines, and the cramps and spasms of cholera are believed to be caused by the ptomaines—or, perhaps rather, leucomaines—formed by the comma-bacillus in the intestines. Many of the ptomaines and leucomaines are intensely poisonous. Epidemiology. The discovery of bacteria as the cause of disease will doubtless in time elucidate many of the difficulties connected with epidemiology, and perhaps enable us to account for the rapid spreading of an epidemic fever, or its appearance in places far away from the presumed source of infection, or for its spontaneous disappearance. There is, perhaps, no question in connection with the infective fevers of greater interest or importance than that of their mode of spreading as epidemics. The occurrence of cholera in India, for instance, is justly regarded with alarm throughout Europe and America, for with the constant travel and commerce the bacillus is sure to find its way westward and northward. Hitherto the knowledge we have had of epidemics has been chiefly confined to the history of their outbreak and of their line of march, and of the fatalities occasioned by them, while as to the occurrence of sporadic cases of disease we were thrown back on the theory of generation de novo. Influenza, for instance, epidemics of which have been recorded from the year 1173 up to the present time, and which are tabulated in the learned work of Hirsch, is found to travel from east to west, sometimes spreading

so widely as to merit the title of pandemic. Whole countries have been stricken suddenly. Thus, in the epidemic of 1836, during the month of February, influenza appeared in Saxony, Bavaria, Lower Austria, North Italy, Spain and Portugal, France, &c., and this at a time when travelling-communication was not easy or rapid. Again, it has appeared on board ships which had sailed several days previously from un-infected ports. It has occurred at all seasons and in all weathers, hot, cold, moist, and dry. We might suppose that the germs were blown by the wind like an army of locusts, and such a theory may perhaps hold good for some diseases; but influenza has travelled from east to west during a westerly wind. Can it be carried by birds? This might seem a farfetched idea, but, without advancing it seriously, the theory is not quite unreasonable. In his experiments on fowl-cholera M. Pasteur showed that the microbe which produced the disease, if introduced into a guinea-pig, caused merely a local abscess, perfectly closed in by what is called in pathology a pyogenic membrane. The guinea-pigs affected suffered in no way in their general health. The abscess opened of itself, closed again, and the part healed perfectly. But fowls and rabbits living in the same coop or yard as these guinea-pigs were liable to be infected with the disease, which speedily proved fatal to them. M. Pasteur remarks, “An observer of these facts, ignorant of the line of descent of the microbe in this instance, would be astonished to see fowls and rabbits decimated, and might believe in the spontaneous origin of the disease, for he would be far from supposing that it had had its origin in the healthy guinea-pigs, especially if he knew that they were subject to the same affection.” He says, further, “How many mysteries in the history of contagions will one day be solved in a much simpler manner than that which I have just mentioned!” Thus the germs of diseases fatal to one species of animals may be carried in the healthy bodies of a different species. As illustrating some of these mysteries, let us take the course of an epidemic of cholera. The onset of the epidemic is often sudden, and the disease quickly spreads, becoming general in a city or county, but curiously sparing certain localities, even some reputed to be unhealthy. At the height of the epidemic the majority of those attacked die. By degrees the disease declines, both as to the number affected and to the severity of the symptoms, and now there is a great number of recoveries and the disease disappears. Sometimes it returns, however, as if capriciously, raging with quite as much violence as during the former visitation, and again declines and disappears. I do not mean to say that all epidemics follow this course, but that the invasion of cholera

will illustrate some of the peculiarities of the visitation of epidemic disease. Questions will arise as to why the disease should be so much more fatal during the middle or height of the epidemic than toward the end. Bearing on this question is the fact that certain bacteria may, under special conditions, develope intense virulency. Pasteur found that the virulence of rabies became greatly intensified by passing the virus through a series of rabbits; and in swine-plague, if the microbe is inoculated into a pigeon and from this passed through a second pigeon, and from the second to a third, and so on, the microbe became “acclimatised” in the pigeon, “and the blood of the later pigeons in the series proved much more virulent to the pig than even the most infective products from a pig which had died of the so-called spontaneous swine-plague.” Other conditions by which the virus may be modified or destroyed are temperature and the admixture of chemical solutions with the nutrient material, while the virus may be altered according as the bacteria grow in the living body, or out of the body on decomposing matters—that is, as parasites or saprophytes. The bacillus of cholera has been cultivated in gelatine and on potatoes by Koch, and he is of opinion that it can reproduce itself and multiply in decaying animal matters outside the human body. It certainly would appear that the germs of cholera, on being transplanted to a district hitherto unaffected, develope intense virulence. While we are not in a position to give a categorical answer to the question proposed, we see what circumstances might happen to a bacterium by which its virulent properties may be preserved or even intensified. Each specific pathogenic bacterium has its own conditions of temperature, moisture, and nutrient substratum, in which it best flourishes and produces disease, and future researches will doubtless determine what those conditions are for each bacterium outside of the laboratories of investigators. One fact, however, has been well established with regard to zymotic—that is, bacterial—diseases—namely, that they have a preference for individuals whose bodies are in a low state of vitality—a fact known long before the discovery of bacteria. I referred at a former part of this address to the supposed influence of the seasons in the causation of certain epidemic diseases. This is expressed at the present day by the term “epidemic constitution” of the season or year. One year we find pneumonia prevalent, another year pleurisy, another typhoid. With our present knowledge of bacteriology we may explain the occurrence of particular epidemic constitutions by the fact that specific bacteria happen to find at such times the temperature, moisture, and nutrient material—that is, the human body—under fit conditions for their development; and

as long as these conditions exist, so long will they flourish and the diseases continue. Another question arises—namely, Why should an epidemic finally disappear? This brings us to the subject of the attenuation of bacterial virus. It may perhaps be possible to stamp out an epidemic on its first appearance, and before it has spread, by vigorous hygienic measures; but when it has obtained a firm hold in a densely-populated city stamping out becomes practically impossible. Such diseases as cholera, relapsing fever, and typhus rage like a wide-spreading fire, and are more difficult to extinguish or limit. A fire will, of course, become extinguished when the inflammable material is all consumed; but epidemics decline spontaneously without attacking all who might be susceptible. I use the word “spontaneously” provisionally only. It would be difficult to believe that the subsidence of the epidemic was due to increased energy in sanitation, for, to all appearances, the conditions may still exist in many parts of the large towns which are usually held to invite zymotic disease. The word “attenuation,” as applied to the virus of an infectious disease, is understood to mean that the germ or bacterium causing it exists in such a condition that it only produces a poison of mild variety, or that its poisonous properties have been totally extinguished. The most notable example of attenuation is that of the virus of small-pox by inoculation. Inoculation for small-pox was practised in India and the East for centuries before it was known in Western Europe. Introduced into the body in this way the disease was certainly attenuated; but, several deaths having occurred from the inoculated disease, and vaccination with cow-pox lymph being found to be safe, inoculation was made illegal by Act of Parliament in 1841. It is more than probable that many deaths used to occur from inoculation owing to the want of proper precautions in performing the operation, the necessity for which precautions was not then understood. But, notwithstanding the occasionally fatal result of inoculation, it is established that in the great majority of cases the disease was rendered milder than when contracted in the ordinary way. This was an instance of attenuation before the nature of the virus was understood. M. Pasteur, having observed that fowl-cholera in the natural state is not always fatal, concluded that the virus occurred in variable degrees of intensity; and he noted also that fowls which recovered were not again, or, at least, rarely, subject to a second attack. It occurred to M. Pasteur that by artificially attenuating the virus the disease might be rendered milder. By making successive cultures even of the most virulent micrococcus in chicken-broth at prolonged intervals, he was able to produce a true “vaccinal”

virus, which being inoculated into fowls not only does not kill but actually protects from the fatal form of the disease. M. Pasteur communicated these results to the Academy in 1880. Anthrax, also, has been attenuated by M. Pasteur so that he was able to produce virus of different degrees of virulence—a virus which produced anthrax in sheep, cows, and horses, but did not cause death, while it was still fatal to guinea-pigs and rabbits, and, finally, a very attenuated virus, which had lost its virulence for guinea-pigs and rabbits, and protected them against an attack. Further, he was able to keep up the artificial cultivation of the microbes, now rendered inoffensive. But an important exception must be made in the case of guinea-pigs, for the attenuated virus was found to be fatal to a guinea-pig one day old, and the virulence could again be restored by inoculating a series of guinea-pigs, until in the end it was strong enough to kill sheep, and M. Pasteur does not hesitate to say that it would kill even cows and horses; or, as M. Roux expresses it, the bacillus can be made to reascend the steps of virulence down which it has come, and so be rendered once more virulent. Swine-plague virus is fatal to rabbits, and the virulence increases a hundred-fold by passing it through a series of rabbits. But, according as it becomes most deadly to rabbits, it also becomes attenuated for the pig, and may be used to protect that animal from the disease. Some of the questions regarding the cause of epidemics and contagions and their virulence or mildness are thus treated by M. Pasteur. He says, “The above facts may help to explain the appearance of these plagues. An epidemic which has been extinguished by the weakening of its virus may light up again by the strengthening of this virus under certain influences. The accounts which I have read of the spontaneous appearance of the plague appear to me to offer examples of this: witness the plague at Benghazi in 1856–58, where the outbreak could not be traced to any origin by contagion. Plague is a virulent disease peculiar to certain countries. In all those countries its attenuated virus must exist, ready to take on its active form whenever certain conditions of climate, of famine, of poverty again appear. There are other infective diseases which appear spontaneously in all countries: such is the typhus of camps. Without doubt the germs of microbes, the authors of these diseases, are spread about everywhere, … ready to become dangerous when, under conditions of overcrowding, and of successive development on the surface of wounds in weakened bodies, or otherwise, their virulence becomes progressively strengthened…. What is a microscopic organism which is innocuous to man or to some particular animal? It is a being which cannot develope in our body or in

the body of that animal; but nothing proves that, if the microscopic organism penetrates into another of the thousands of species in creation, it will not take possession of it and render it diseased. Its virulence, thus strengthened by successive passages through individuals of that species, might at length attain a condition in which it would be able to attack large animals—man, or certain domestic animals. In this way new virulences and contagions may be created. I am greatly inclined to believe that in this manner have appeared in the course of ages small-pox, the plague, yellow-fever, &c., and that owing to phenomena of this kind certain great epidemics appear, such as typhus, just mentioned.” This mention of the subject of attenuation and vaccination would be incomplete without some notice of M. Pasteur's method of treating hydrophobia, which occurs in the dog as rabies. The natural disease in the dog might take weeks or months to develope. This length of time was practically prohibitive to the experimenter. Judging from the symptoms that the virus would be found chiefly in the central nervous system, he inoculated the brain of rabbits with a portion of the spinal marrow of a dog which had died of rabies, and, passing the virus from rabbit to rabbit, a virus was obtained infinitely more virulent than that procured from the original source—i.e., the diseased dog. By inoculating the virus directly into the brain-membranes the development or incubation of the disease was shortened. It will give some idea of the time and patience consumed in these investigations if I mention that the stage of incubation in the first rabbit was fifteen days. After twenty to twenty-five passages from rabbit to rabbit the incubation-stage became shortened to eight days. This length of incubation-stage was maintained for a new period of twenty to twenty-five passages, when the duration of incubation became lessened to seven days, which was maintained for a series of ninety new passages of virus from rabbit to rabbit. After this the incubation-period is six days, when the virus attains its maximum intensity and becomes “fixed.” By suspending portions of the spinal cord in dry air from one to fourteen days they were found to have lost their virulence in proportion to the time they had been exposed. By very long exposure their virulence became extinct, so that rabbits inoculated with the most attenuated cords—that is, of fourteen days' exposure—were found to be unaffected with the disease. It was thus possible to procure a virus of any desired strength. Dogs inoculated at first with the fourteen-day cord, on the next day with the thirteen-day cord, next day with the twelve-day cord, and so on, were found to bear inoculation with unattenuated virus, and to be fully protected against rabies, whether inoculated with virulent matter or bitten by

a rabid animal. Dogs and animals so protected are said to have been rendered “refractory” to the virus. M. Pasteur now conceived the idea that if dogs had been bitten by rabid dogs the disease already in the system might be attacked and conquered, and the dogs saved, by inoculating portions of the virus in the same manner. The result bore out his anticipations. Dogs which were bitten and inoculated recovered, others not so protected died. What if this method could prevent hydrophobia in man? On the 6th July, 1885, there was brought unexpectedly to the laboratory of M. Pasteur a boy named Joseph Meister, aged nine years. The boy had been bitten in several places—on the hands, on the legs and thighs, so that he walked with difficulty. The same evening M. Pasteur began the treatment by inoculations, continuing them for twelve days, until he had used a virus only one day old. The result was that this boy, who had the seeds of a fatal disease in his system, recovered perfectly without having suffered beyond the mere wounds. Since the memorable date on which Joseph Meister was treated about 150 persons have come each month to the Pasteur Institute for antirabic inoculations. Up to the 21st March, 1889, 6,870 persons have been treated there, many of them very severely wounded. The mortality of persons so treated has been 1 per cent., the usual mortality after the bites of rabid dogs being 15 per cent. The success in these inoculations is due to the slowness with which the virus after a bite usually reaches the nervous centres. In man the average incubation-stage is six or seven weeks. It may, of course, be shorter or much longer. But should the virus reach the brain and the spinal cord very quickly, by means of the bloodstream, inoculative treatment may be too late. Such cases constitute the 1 per cent. of those treated which end fatally, as in bites about the face. In severe cases the treatment has to be very active, spinal cords a few days old being used almost at once, instead of beginning with cords of fourteen days. And here I let M. Roux, M. Pasteur's collaborator, use his own words. He says, “The most remarkable point, however, in the whole discovery of this preventive inoculation against rabies is that it has been carried out, the virus itself being still unknown. Not only do we not know how to cultivate it outside the body, but in allowing it really to be a microbe we can do so by analogy, for as yet no one has been able to isolate it. Notwithstanding this, however, it is daily being attenuated, and made to pass through the various stages of virulence. Unable to cultivate the organism artificially in flasks and tubes, M. Pasteur has been obliged to do so in the rabbit; and so easily and with such perfect regularity are these cultivations in the living animal performed that they are ready

each day for use in the inoculations at a specified time, and in the condition of genuinely pure cultivations. There is no stronger example of the power of the experimental method as applied to medical matters than this one of the prevention of a malady the absolute virus of which is still obscure.” Several antirabic institutions have now been established throughout Europe and America. The United Kingdom has none, although about fifty British subjects have been treated annually in the Paris Institute since 1886. The restrictions as to vivisection, which in experiments on animals are painlessly conducted, have not only rendered us dependent on Continental countries for advances in biological and therapeutical science, but for the care and treatment of such British subjects as may be suffering from a highly dangerous malady. It is within the range of possibility that a parallel method of treatment may be adopted for other infectious diseases in the human subject. Should this come to pass it remains to be seen whether a false sentimentality, which resists merciful experiments by which thousands of lives of animals, as well as of human beings, may be saved, while it allows pigeon-shooting and coursing to be practised as sports, will continue to triumph over true humanity and common-sense. Before considering the bacteria of specific diseases we will inquire—(1) How it is possible for the body to resist an attack of bacteria; (2) How does spontaneous cure of fevers occur? (3) How does vaccination with attenuated virus prevent or cure bacterial disease? (1.) In answer to the first question, we have now to resume our acquaintance with the white blood-corpuscles, which, as we saw, play an important part in the process of inflammation. What are these white corpuscles? In 1883 Dr. Elias Metschnikoff published some important observations on the intracellular digestion of invertebrates, showing, from his own researches and from those of other biologists, that the amœboid cells of the mesoderm are capable of ingesting and absorbing albuminoid particles. By taking function as the standpoint for observation, instead of merely considering form, he traced the white bloodcorpuscle of vertebrates to the same phylogenesis or common origin, as a class or race, as the amœboid cells of the mesoderm in the Metazoa. It is necessary to call to mind the signification of the terms “ectoderm,” “endoderm,” and “mesoderm,” which, of course, mean literally outer layer, inner layer, and middle layer respectively. In the development of the ovum the cells of the blastoderm or germ divide into two layers, the ectoderm and the endoderm. In the orders above Cœlenterata a middle layer of cells appears, probably derived from the other two. This is termed the

mesoderm, and in it are found the blood-vessels, muscles, internal skeleton, and the excretory organs. What we have now to note is that to the mesoderm belongs the vascular system. The mode in which the Amœba envelopes and disintegrates its food gives an example of intracellular digestion. This is the mode of nutrition in the Protozoa, whether singly or aggregated together in colonies. In Plumularia the ectoderm cells are able to take up foreign particles, and to eat up dying or dead portions of the animal or colony to which they belong. In the larvæ of the Actinias also the ectoderm cells have the faculty of ingesting solid food. But already a differentiation of function begins to be observed, and at a later stage of development the number of foreign particles in the ectoderm cells becomes much smaller. The function of intracellular digestion, we shall find, becomes the hereditary property of the amœboid cells of the mesoderm, and in these we should expect to find it in vertebrate animals if it existed in them. These cells have the property of being able to wander about in the body of the animal (as observed by Metschnikoff in Phyllirhoe, a transparent mollusc). They devour all dead or dying matter. In the case of large masses to be eaten, or foreign particles to be removed, the amœboid cells join their forces, becoming fused together in cell-masses termed plasmodia, which are equivalent to giant cells; or the individuals remain distinct, but swarm together in large numbers to the attack. They have a power of selection, eating some objects presented to them and refusing others. Bacteria are attacked and ingested by them, but occasionally the wandering amœboid cells are killed by the bacteria. These cells thus guard the body of the animal to the best of their power against harmful substances, while they, in destroying foreign or dead matters, are simply feeding, as I surmise, primarily for their own individual nutrition as independent cell-animals, secondarily for the nutrition of the colony of cells, or animal, of which they form a part. Metschnikoff calls them, phagocytes, or eating-cells. Thus, in the lowest animal-forms all the cells are amœboid, and all are phagocytes; but as we ascend in the scale we find the cells becoming differentiated, some losing the digestive power, while those of the mesoderm retain it. Following up this line of inquiry, M. Metschnikoff has ascertained the existence of phagocytes in the mesoderm of vertebrates. These are the white blood-corpuscles. The power of these leucocytes to wander outside of the bloodvessels has already been mentioned. When the tails of tadpoles are undergoing absorption, amœboid cells in large numbers may be seen surrounding the muscles and nerve-fibres, which they gradually devour, and

portions of nerve and muscle may be seen in their interior, where they undergo a process of digestion. When a fully-gorged phagocyte dies it is immediately devoured by another. Parasitic bacteria being injected into the mouse, the white blood-corpuscles were seen to contain bacteria. Wherever there is irritation causing death or disease of a part, or a foreign body liable to be injurious to the system, the phagocytes collect to remove the dead tissues or the foreign body. Thus we have within our bodies an army of soldier-cells ready to repel invasion, and in the case of bacteria frequently with success. The prophylactic function of the amœboid cells is shown by a very interesting discovery of M. Metschnikoff of their behaviour in the Daphnia when it is attacked by a yeastlike fungus. The Daphnia being transparent, he was able to see these cells collecting and investing the spores, which they digested and rendered innocuous. Here we see one way in which the body may resist an attack of zymotic disease. Sometimes, however, the spores were able to overpower and kill the leucocytes, causing the death of the animal. In the septicæmia of mice the white blood-corpuscles endeavour to destroy the bacilli. They take them up into their interior; but they find themselves in the position of the husbandman who cherished a snake in his bosom. Koch says, “The bacilli multiply very quickly in the cell, which they burst and destroy, and are then taken up by other leucocytes, only to work the same ruin, so that in a short time the majority of the white blood-corpuscles are occupied by bacilli.” (2.) How does spontaneous cure of fevers occur? It has been mentioned that the growth of many bacteria may be arrested by introducing certain chemical solutions into the medium in which they are growing. The properties of iodine, carbolic acid, and corrosive sublimate are well known as being inimical to the life of bacteria. There are, of course, very many other chemical germicides. It has been found that certain bacteria form chemical products in their own food-material which are poisonous to themselves and arrest their growth. Thus the bacillus or micrococcus which causes lactic-acid fermentation becomes poisoned by the lactic acid formed, and the growth of the microbe ceases, although the nutrient material is not exhausted. There is some reason to believe that in several diseases, at least, a chemical substance is formed in the blood by the bacteria, which substance, when in sufficient quantity, stops the further growth of the bacteria, or causes their death—that is, if the individual survive long enough. This would, perhaps, correspond to the crisis of the disease. If the poison of the disease have not too deeply impaired the vital powers the individual recovers; in the contrary

case, as in malignant scarlatina and malignant cholera, he dies. (3.) The answer to the question as to the cure or prevention of a zymotic disease by vaccinating with attenuated virus may now be perceived. On such theories or facts is founded M. Pasteur's treatment of hydrophobia; and it is claimed that anthrax, typhoid, and septicæmia can be prevented by injecting into the blood some of their poisonous products. The presence of these substances in the blood alters it in such a way as to render it an unfit soil for the growth of the respective bacteria. The white cells do not always at first take up virulent bacteria, but sometimes withdraw from them; but they can gradually become accustomed to some poisonous bacteria, and are able to devour and digest them if they are first fed with the attenuated virus. We will now glance at a few of the specific bacteria. The first microbe discovered as the cause of disease was, as already mentioned, the bacillus of anthrax. Its life-history is therefore invested with peculiar interest, for the demonstration of its presence and of its infecting-power was immediately followed by a search for specific bacteria in other diseases. Bacillus anthracis is interesting on its own account, for it is one of the most malignant of the bacteria, and is capable of retaining its virulence under the most varied circumstances. It can grow in living matter, in dead matter, animal or vegetable. It may preserve its vitality after being frozen in a fluid at—110° C, and the spores may be capable of germination after being boiled for from fifteen minutes to an hour. M. Pasteur found the germs capable of development after they had been kept twenty-two years. Its spores defy the solvent power of the gastric juice. It is capable of attacking rodents, ruminants, omnivora, carnivora, birds, and even batrachians and reptiles under certain conditions of temperature. Mice and guinea-pigs die in from twenty-four to forty-eight hours after infection with the minutest quantity of virus, and if a drop of blood be examined anthrax rods will be found, so rapid is the growth of the microbe. Man does not escape: anthrax, or charbon, in man is known as woolsorters' disease. The spot which it attacks immediately developes a pustule which is well characterized by the term “malignant pustule.” We have here a striking example of a vicious heredity; but, on the other hand, we have a remarkable instance of the manner in which a vicious strain may be modified, and even totally extinguished, by a favourable environment, for this virulent bacillus may be so attenuated by cultivation in mild nutrient media as to become harmless even to animals ordinarily the most susceptible, such as mice and guinea-pigs.

This was not only proved by Pasteur, but the experiment led to inoculation with attenuated virus as a protection against the disease. From 1882 to 1888 there were 1,700,000 sheep vaccinated against anthrax, with a mortality of 0.85 per cent. The mortality of sheep in anthrax districts has gone down from 10 per cent. to less than 1 per cent., while cattle are also protected by vaccination. M. Roux tells us that insurance companies insert a clause in their agreements by which protective inoculation is rendered compulsory. Anthrax might enter the body of a man through a wound, a scratch on the hands in wool-sorting, or the spores might get into the mouth with dust or with food, and so find their way into the stomach and intestinal tract. The bacillus of tuberculosis, or consumption, was discovered by Dr. Robert Koch. It is one which in all probability may be conveyed to human beings from certain of the lower animals. The milk of cows suffering from tubercle of the udder contains bacilli which can infect animals, and it has been suggested by a distinguished pathologist that such milk may be a cause of tubercular disease of the abdominal glands in hand-fed children. At the recent French Congress on Tuberculosis the conclusion was arrived at “that the disease can be transmitted to man from the lower animals by the ingestion of diseased meat and milk.” In consequence of this the French Government have made the exposure of tuberculous meat for sale illegal. In the United Kingdom many high authorities have decided that the meat and milk of tuberculous cattle is dangerous to health. It will be small comfort to those who oppose vaccination by humanised lymph on the ground that a blood-poison is introduced from another individual, to know that a virulent blood-poison may be taken in with animal food. Monkeys, cattle, rabbits, guinea-pigs, fowls, and, in short, all warm-blooded animals, are susceptible to tuberculosis. Consumption was believed to be contagious in Languedoc, Spain, and Portugal, as Dr. Elliotson, writing fifty years ago, informs us, and also in Italy. In these countries the clothes of a consumptive who had died were burned or buried. The direct infectiousness of tuberculosis has been amply proved by experiments on the lower animals, and, accidentally, in the case of man. It would, of course, be impossible in one evening to review the various specific bacteria of disease. I must content myself with naming some of the diseases of which bacteria are known to be the cause, or in which full proof—that is, visual proof—of their existence may be looked for any day, as in hydrophobia. These are erysipelas, pneumonia, leprosy, diphtheria, typhus, typhoid, septicæmia or blood-poisoning, cholera, relapsing fever, two forms of ophthalmia, anthrax, tuberculosis,

whooping-cough, influenza, measles, tetanus yellow-fever, dengue, actinomycosis, &c.; while the fevers of the lower animals are also bacterial in their origin. Many slight febrile affections usually denominated as “colds,” although perhaps occurring at the height of summer, are most probably due to bacterial agency. Disease-bearing bacteria swarm around us, seeking for bodies in a weakened condition into which to enter, or awaiting their opportunity as saprophytes in moist, dark, unwholesome places, where dead organic matter offers them a resting-place. The discovery of pathogenic bacteria is destined to effect changes which we cannot even now foresee in our quarantine laws, in our public and domestic architecture, in our cookery, in the quality of our animal food, in the breeds of our domestic animals, in our intermarriages, in the disposal of our dead, and in many other ways. Bacteriological Institutes are now being established throughout Europe and America. Their importance in relation to public health cannot be overestimated; and in new colonies such as these of Australasia, the question of State Bacteriological Institutes is well worthy the consideration of Governments. It would seem that so much is being discovered as to the causes of sickness and the means of preventing it that disease must ultimately become rare, and, indeed, it is true that many diseases are becoming rare. But civilisation is a slow process. Disease in one class of society may affect all classes; disease in one family may affect several families. Nothing but a widespread liberal education, a socialism of knowledge, can ultimately eradicate disease.