The method of treatment of hydrophobia met with extraordinarily violent opposition. For several years it was regarded as a mistake. But the constantly accumulating statistics from the Pasteur Institute have been so overwhelmingly on one side as to quiet opposition and bring about a general conviction that the method is a success.

The method of preventive inoculation has not been extensively applied to human diseases in addition to those mentioned. In a few cases a similar method has been used to guard against diphtheria. Among animals, experiment has shown that such methods can quite easily be obtained, and doubtless the same would be true of mankind if it was thought practical or feasible to apply them. But, for reasons mentioned, this feature of preventive medicine will always remain rather unimportant, and will be confined to a few of the more violent diseases.

It may be well to raise the question as to why a single attack with recovery conveys immunity. This question is really a part of the one already discussed as to the method by which the body cures disease. We have seen that this is in part due to the development of chemical substances which either neutralize the poisons or act as germicide upon the bacteria, or both, and perhaps due in part to an active destruction of bacteria by cellular activity (phagocytosis). There is little reason to doubt that it is the same set of activities which renders the animal immune. The forces which drive off the invading bacteria in one case are still present to prevent a second attack of the same species of bacterium. The length of time during which these forces are active and sufficient to cope with any new invaders determines the length of time during which the immunity lasts. Until, therefore, we can answer with more exactness just how cure is brought about in case of disease, we shall be unable to explain the method of immunity.

LIMITS OF PREVENTIVE MEDICINE.

With all the advance in preventive medicine we can not hope to avoid disease entirely. We are discovering that the sources of disease are on all sides of us, and so omnipresent that to avoid them completely is impossible. If we were to apply to our lives all the safeguards which bacteriology has taught us should be applied in order to avoid the different diseases, we would surround ourselves with conditions which would make life intolerable. It would be oppressive enough for us to eat no food except when it is hot, to drink no water except when boiled, and to drink no milk except after sterilization; but these would not satisfy the necessary conditions for avoiding disease. To meet all dangers, we should handle nothing which has not been sterilized, or should follow the handling by immediately sterilizing the hands; we should wear only disinfected clothes, we should never put our fingers in our mouths or touch our food with them; we should cease to ride in public conveyances, and, indeed, should cease to breathe common air. Absolute prevention of the chance of infection is impossible. The most that preventive medicine can hope for is to point out the most common and prolific sources of infection, and thus enable civilized man to avoid some of his most common troubles. It becomes a question, therefore, where we will best draw the line in the employment of safeguards. Shall we drink none except sterilized milk, and no water unless boiled? or shall we put these occasional sources of danger in the same category with bicycle and railroad accidents, dangers which can be avoided by not using the bicycle or riding on the rail, but in regard to which the remedy is too oppressive for application?

Indeed, when viewed in a broad philosophical light it may not be the best course for mankind to shun all dangers. Strength in the organism comes from the use rather than the disuse of our powers. It is certain that the general health and vigour of mankind is to be developed by meeting rather than by shunning dangers. Resistance to disease means bodily vigour, and this is to be developed in mankind by the application of the principle of natural selection. In accordance with this principle, disease will gradually remove the individuals of weak resisting powers, leaving those of greater vigour. Parasitic bacteria are thus a means of preventing the continued life of the weaker members of the community, and so tend to strengthen mankind. By preventive medicine many a weak individual who would otherwise succumb earlier in the struggle is enabled to live a few years longer. Whatever be our humanitarian feeling for the individual, we can not fail to admit that this survival of the weak is of no benefit to the race so far as the development of physical nature is concerned. Indeed, if we were to take into consideration simply the physical nature of man we should be obliged to recommend a system such as the ancient Spartans developed, of exposing to death all weakly individuals, that only the strong might live to become the fathers of future generations. In this light, of course, parasitic diseases would be an assistance rather than a detriment to the human race. Of course such principles will never again be dominant among men, and our conscience tells us to do all we can to help the weak. We shall doubtless do all possible to develop preventive medicine in order to guard the weak against parasitic organisms. But it is at all events well for us to remember that we can never hope to develop the strength of the human race by shunning evil, but rather by combating it, and the power of the human race to resist the invasions of these organisms will never be developed by the line of action which guards us from attack. Here, as in other directions, the principles of modern humanity have, together with their undoubted favourable influence upon mankind, certain tendencies toward weakness. While we shall still do our utmost to develop preventive medicine in a proper way, it may be well for us to remember these facts when we come to the practical question of determining where to draw the limits of the application of methods for preventing infectious diseases.

CURATIVE MEDICINE.

Bacteriology has hitherto contributed less to curative than to preventive medicine. Nevertheless, its contributions to curative medicine have not been unimportant, and there is promise of much more in the future. It is, of course, unsafe to make predictions for the future, but the accomplishments of the last few years give much hope as to further results.

DRUGS.

It was at first thought that a knowledge of the specific bacteria which cause a disease would give a ready means of finding specific drugs for the cure of such disease. If a definite species of bacterium causes a disease and we can cultivate the organism in the laboratory, it is easy to find some drugs which will be fatal to its growth, and these same drugs, it would seem, should be valuable as medicines in these diseases. This hope has, however, proved largely illusive. It is very easy to find some drug which proves fatal to the specific germs while growing in the culture media of the laboratory, but commonly these are of little or no use when applied as medicines. In the first place, such substances are usually very deadly poisons. Corrosive sublimate is a substance which destroys all pathogenic germs with great rapidity, but it is a deadly poison, and can not be used as a drug in sufficient quantity to destroy the parasitic bacteria in the body without at the same time producing poisonous effects on the body itself. It is evident that for any drug to be of value in thus destroying bacteria it must have some specially strong action upon the bacteria. Its germicide action on the bacteria should be so strong that a dose which would be fatal or very injurious to them would be too small to have a deleterious influence on the body of the individual. It has not proved an easy task to discover drugs which will have any value as germicides when used in quantities so small as to produce no injurious effect on the body.

A second difficulty is in getting the drug to produce its effect at the right point. A few diseases, as we have noticed, are produced by bacteria which distribute themselves almost indiscriminately over the body; but the majority are somewhat definitely localized in special points. Tuberculosis may attack a single gland or a single lobe of the lung. Typhoid germ is localized in the intestines, liver, spleen, etc. Even if it were possible to find some drug which would have a very specific effect upon the tuberculosis bacillus, it is plain that it would be a very questionable method of procedure to introduce this into the whole system simply that it might have an effect upon a very small isolated gland. Sometimes such a bacterial affection may be localized in places where it can be specially treated, as in the case of an attack on a dermal gland, and in these cases some of the germicides have proved to be of much value. Indeed, the use of various disinfectants connected with abscesses and superficial infections has proved of much value. To this extent, in disinfecting wounds and as a local application, the development of our knowledge of disinfectants has given no little aid to curative medicine.

Very little success, however, has resulted in the attempt to find specific drugs for specific diseases, and it is at least doubtful whether many such will ever be found. The nearest approach to it is quinine as a specific poison for malarial troubles. Malarious diseases are not, however, produced by bacteria but by a microscopic organism of a very different nature, thought to be an animal rather than a plant. Besides this there has been little or no success in discovering specifics in the form of drugs which can be given as medicines or inoculated with the hope of destroying special kinds of pathogenic bacteria without injury to the body. While it is unwise to make predictions as to future discoveries, there seems at present little hope for a development of curative medicine along these lines.

VIS MEDICATRIX NATURAE.

The study of bacterial diseases as they progress in the body has emphasized above all things the fact that diseases are eventually cured by a natural rather than by an artificial process. If a pathogenic bacterium succeeds in passing the outer safeguards and entering the body, and if it then succeeds in overcoming the forces of resistance which we have already noticed, it will begin to multiply and produce mischief. This multiplication now goes on for a time unchecked, and there is little reason to expect that we can ever do much toward checking it by means of drugs. But after a little, conditions arise which are hostile to the further growth of the parasite. These hostile conditions are produced perhaps in part by the secretions from the bacteria, for bacteria are unable to flourish in a medium containing much of their own secretions. The secretions which they produce are poisons to them as well as to the individual in which they grow, and after these have become quite abundant the further growth of the bacterium is checked and finally stopped. Partly, also, must we conclude that these hostile conditions are produced by active vital powers in the body of the individual attacked. The individual, as we have seen, in some cases develops a quantity of some substance which neutralizes the bacterial poisons and thus prevents their having their maximum effect. Thus relieved from the direct effects of the poisons, the resisting powers are recuperated and once more begin to produce a direct destruction of the bacteria. Possibly the bacteria, being now weakened by the presence of their own products of growth, more readily yield to the resisting forces of the cell life of the body. Possibly the resisting forces are decidedly increased by the reactive effect of the bacteria and their poisons. But, at all events, in cases where recovery from parasitic diseases occurs, the revived powers of resistance finally overcome the bacteria, destroy them or drive them off, and the body recovers.

All this is, of course, a natural process. The recovery from a disease produced by the invasion of parasitic bacteria depends upon whether the body can resist the bacterial poisons long enough for the recuperation of its resisting powers. If these poisons are very violent and produced rapidly, death will probably occur before the resisting powers are strong enough to drive off the bacteria. In the case of some diseases the poisons are so violent that this practically always occurs, recovery being very exceptional. The poison produced by the tetanus bacillus is of this nature, and recovery from lockjaw is of the rarest occurrence. But in many other diseases the body is able to withstand the poison, and later to recover its resisting powers sufficiently to drive off the invaders. In all cases, however, the process is a natural one and dependent upon the vital activity of the body. It is based at the foundation, doubtless, upon the powers of the body cells, either the phagocytes or other active cells. The body has, in short, its own forces for repelling invasions, and upon these forces must we depend for the power to produce recovery.

It is evident that all these facts give us very little encouragement that we shall ever be able to cure diseases directly by means of drugs to destroy bacteria, but, on the contrary, that we must ever depend upon the resisting powers of the body. They teach us, moreover, along what line we must look for the future development of curative medicine. It is evident that scientific medicine must turn its attention toward the strengthening and stimulating of the resisting and curative forces of the body. It must be the physician's aim to enable the body to resist the poisons as well as possible and to stimulate it to re-enforce its resistant forces. Drugs have a place in medicine, of course, but this place is chiefly to stimulate the body to react against its invading hosts. They are, as a rule, not specific against definite diseases. We can not hope for much in the way of discovering special medicines adapted to special diseases. We must simply look upon them as means which the physician has in hand for stimulating the natural forces of the body, and these may doubtless vary with different individual natures. Recognising this, we can see also the logic of the small dose as compared to the large dose. A small dose of a drug may serve as a stimulant for the lagging forces, while a larger dose would directly repress them or produce injurious secondary effects. As soon as we recognise that the aim of medicine is not to destroy the disease but rather to stimulate the resisting forces of the body, the whole logic of therapeutics assumes a new aspect.

Physicians have understood this, and, especially in recent years, have guided their practice by it. If a moderate dose of quinine will check malaria in a few days, it does not follow that twice the dose will do it in half the time or with twice the certainty. The larger doses of the past, intended to drive out the disease, have been everywhere replaced by smaller doses designed to stimulate the lagging body powers. The modern physician makes no attempt to cure typhoid fever, having long since learned his inability to do this, at least if the fever once gets a foothold; but he turns his attention to every conceivable means of increasing the body's strength to resist the typhoid poison, confident that if he can thus enable the patient to resist the poisoning effects of the typhotoxine his patient will in the end react against the disease and drive off the invading bacteria. The physician's duty is to watch and guard, but he must depend upon the vital powers of his patient to carry on alone the actual battle with the bacterial invaders.

ANTITOXINES.

In very recent times, however, our bacteriologists have been pointing out to the world certain entirely new means of assisting the body to fight its battles with bacterial diseases. As already noticed, one of the primal forces in the recovery, from some diseases, at least, is the development in the body of a substance which acts as an antidote to the bacterial poison. So long as this antitoxine is not present the poisons produced by the disease will have their full effect to weaken the body and prevent the revival of its resisting powers to drive off the bacteria. Plainly, if it is possible to obtain this antitoxine in quantity and then inoculate it into the body when the toxic poisons are present, we have a means for decidedly assisting the body in its efforts to drive off the parasites. Such an antidote to the bacterial poison would not, indeed, produce a cure, but it would perhaps have the effect of annulling the action of the poisons, and would thus give the body a much greater chance to master the bacteria. It is upon this principle that is based the use of antitoxines in diphtheria and tetanus

It will be clear that to obtain the antitoxine we must depend upon some natural method for its production. We do not know enough of the chemical nature of the antitoxines to manufacture them artificially. Of course we can not deny the possibility of their artificial production, and certain very recent experiments indicate that perhaps they may be made by the agency of electricity. At present, however, we must use natural methods, and the one commonly adopted is simple. Some animal is selected whose blood is harmless to man and that is subject to the disease to be treated. For diphtheria a horse is chosen. This animal is inoculated with small quantities of the diphtheria poison without the diphtheria bacillus. This poison is easily obtained by causing the diphtheria bacillus to grow in common media in the laboratory for a while, and the toxines develop in quantity; then, by proper filtration, the bacteria themselves can be removed, leaving a pure solution of the toxic poison. Small quantities of this poison are inoculated into the horse at successive intervals. The effect on the horse is the same as if the animal had the disease. Its cells react and produce a considerable quantity of the antitoxine which remains in solution in the blood of the animal. This is not theory, but demonstrated fact. The blood of a horse so treated is found to have the effect of neutralizing the diphtheria poison, although the blood of the horse before such treatment has no such effect. Thus there is developed in the horse's blood a quantity of the antitoxine, and now it may be used by physicians where needed. If some of this horse's blood, properly treated, be inoculated into the body of a person who is suffering from diphtheria, its effect, provided the theory of antitoxines is true, will be to counteract in part, at least, the poisons which are being produced in the patient by the diphtheria bacillus. This does not cure the disease nor in itself drive off the bacilli, but it does protect the body from the poisons to such an extent as to enable it more readily to assert its own resisting powers.

This method of using antitoxines as a help in curing disease is very recent, and we can not even guess what may come of it. It has apparently been successfully applied in diphtheria. It has also been used in tetanus with slight success. The same principle has been used in obtaining an antidote for the poison of snake bites, since it has appeared that in this kind of poisoning the body will develop an antidote to the poison if it gets a chance. Horses have been treated in the same way as with the diphtheria poison, and in the same way they develop a substance which neutralizes the snake poison. Other diseases are being studied to-day with the hope of similar results. How much further the principle will go we can not say, nor can we be very confident that the same principle will apply very widely. The parasitic diseases are so different in nature that we can hardly expect that a method which is satisfactory in meeting one of the diseases will be very likely to be adapted to another. Vaccination has proved of value in smallpox, but is not of use in other human diseases. Inoculation with weakened germs has proved of value in anthrax and fowl cholera, but will not apply to all diseases. Each of these parasites must be fought by special methods, and we must not expect that a method that is of value in one case must necessarily be of use elsewhere. Above all, we must remember that the antitoxines do not cure in themselves; they only guard the body from the weakening effects of the poisons until it can cure itself, and, unless the body has resisting powers, the antitoxine will fail to produce the desired results.

One further point in the action of the antitoxines must be noticed. As we have seen, a recovery from an attack of most germ diseases renders the individual for a time immune against a second attack. This applies less, however, to a recovery after the artificial inoculation with antitoxine than when the individual recovers without such aid. If the individual recovers quite independently of the artificial antitoxine, he does so in part because he has developed the antitoxines for counteracting the poison by his own powers. His cellular activities have, in other words, been for a moment at least turned in the direction of production of antitoxines. It is to be expected, therefore, that after the recovery they will still have this power, and so long as they possess it the individual will have protection from a second attack. When, however, the recovery results from the artificial inoculation of antitoxine the body cells have not actively produced antitoxine. The neutralization of the poisons has been a passive one, and after recovery the body cells are no more engaged in producing antitoxine than before. The antitoxine which was inoculated is soon eliminated by secretion, and the body is left with practically the same liability to attack as before. Its immunity is decidedly fleeting, since it was dependent not upon any activity on the part of the body, but upon an artificial inoculation of a material which is rapidly eliminated by secretion.

CONCLUSION.

It is hoped that the outline which has been given of the bacterial life of Nature may serve to give some adequate idea of these organisms and correct the erroneous impressions in regard to them which are widely prevalent. It will be seen that, as our friends, bacteria play a vastly more important part in Nature than they do as our enemies. These plants are minute and extraordinarily simple, but, nevertheless, there exists a large number of different species. The number of described forms already runs far into the hundreds, and we do not yet appear to be approaching the end of them. They are everywhere in Nature, and their numbers are vast beyond conception. Their powers of multiplication are inconceivable, and their ability to produce profound chemical changes is therefore unlimited. This vast host of living beings thus constitutes a force or series of forces of tremendous significance. Most of the vast multitude we must regard as our friends. Upon them the farmer is dependent for the fertility of his soil and the possibility of continued life in his crops. Upon them the dairyman is dependent for his flavours. Upon them important fermentative industries are dependent, and their universal powers come into action upon a commercial scale in many a place where we have little thought of them in past years. We must look upon them as agents ever at work, by means of which the surface of Nature is enabled to remain fresh and green. Their power is fundamental, and their activities are necessary for the continuance of life. A small number of the vast host, a score or two of species, unfortunately for us, find their most favourable living place in the human body, and thus become human parasites. By their growth they develop poisons and produce disease. This small class of parasites are then decidedly our enemies. But, taken all together, we must regard the bacteria as friends and allies. Without them we should not have our epidemics, but without them we should not exist. Without them it might be that some individuals would live a little longer, if indeed we could live at all. It is true that bacteria, by producing disease, once in a while cause the premature death of an individual; once in a while, indeed, they may sweep off a hundred or a thousand individuals; but it is equally true that without them plant and animal life would be impossible on the face of the earth.

THE END