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Prevention In Inoculation

( Originally Published 1897 )

It has long been recognised that in most cases recovery from one attack of a contagious disease renders an individual more or less immune against a second attack. It is unusual for an individual to have the same contagious disease twice. This belief is certainly based upon fact, although the immunity thus acquired is subject to wide variations. There are some diseases in which there is little reason for thinking that any immunity is acquired, as in the case of tuberculosis, while there are others in which the immunity is very great and very lasting, as in the case of scarlet fever. Moreover, the immunity differs with individuals. While some persons appear to acquire a lasting immunity by recovery from a single attack, others will yield to a second attack very readily. But in spite of this the fact of such acquired immunity is beyond question. Apparently all infectious diseases from which a real recovery takes place are followed by a certain amount of protection from a second attack ; but with some diseases the immunity is very fleeting, while with others it is more lasting. Diseases which pro-duce a general infection of the whole system are, as a rule, more likely to give rise to a lasting immunity than those which affect only small parts. Tuberculosis, which, as already noticed, is commonly quite localized in the body, has little power of conveying immunity, while a disease like scarlet fever, which affects the whole system, conveys a more lasting protection.

Such immunity has long been known, and in the earlier years was sometimes voluntarily acquired ; even today we find some individuals making use of the principle. It appears that a mild attack of such diseases produces immunity equally well with a severe attack, and acting upon this fact mothers have not infrequently intentionally exposed their children to certain diseases at seasons when they are mild, in or-der to have the disease " over with " and their children protected in the future. Even the more severe diseases have at times been thus voluntarily acquired. In China it has sometimes been the custom thus to acquire smallpox. Such methods are decidedly heroic, and of course to be heartily condemned. But the principle that a mild type of the disease conveys protection has been made use of in a more logical and defensible way.

The first instance of this principle was in vaccination against smallpox, now practised for more than a century. Cowpox is doubtless closely related to smallpox, and an attack of the former conveys a certain amount of protection against the latter. It was easy, therefore, to inoculate man with some of the infectious material from cowpox, and thus give him some protection against the more serious smallpox. This was a purely empirical discovery, and vaccination was practised long before the principle underlying it was understood, and long before the germ nature of disease was recognised. The principle was revived again, however, by Pasteur, and this time with a logical thought as to its value. While working upon anthrax among animals, he learned that here, as in other diseases, recovery, when it occurred, conveyed immunity. This led him to ask if it were not possible to devise a method of giving to animals a mild form of the disease and thus protect them from the more severe type. The problem of giving a mild type of this extraordinarily severe disease was not an easy one. It could not be done, of course, by inoculating the' animals with a small number of the bacteria, for their power of multiplication would soon make them indefinitely numerous. It was necessary in some way to diminish their violence. Pasteur succeeded in doing this by causing them to grow in culture fluids for a time at a high temperature. This treatment diminished their violence so much that they could be inoculated into cattle, where they produced only the mildest type of indisposition, from which the animals speedily recovered. But even this mild type of the disease was triumphantly demonstrated to protect the animals from the most severe form of anthrax. The discovery was naturally hailed as a most remarkable one, and one which promised great things in the future. If it was thus possible, by direct laboratory methods, to find a means of inoculating against a serious disease like anthrax, why could not the same principle be applied to human diseases ? The enthusiasts began at once to look forward to a time when all diseases should be thus conquered.

But the principle has not borne the fruit at first expected. There is little doubt that it might be applied to quite a number of human diseases if a serious attempt should be made. But several objections arise against its wide application. In the first place, the inoculation thus necessary is really a serious matter. Even vaccination, as is well known, sometimes, through faulty methods, results fatally, and it is a very serious thing to experiment upon human beings with anything so powerful for ill as pathogenic bacteria. The seriousness of the disease smallpox, its extraordinary contagiousness, and the comparatively mild results of vaccination, have made us willing to undergo vaccination at times of epidemics to avoid the somewhat great probability of taking the disease. But mankind is unwilling to undergo such an operation, even though mild, for the purpose of avoiding other less severe diseases, or diseases which are less likely to be taken. We are unwilling to be inoculated against mild diseases, or against the more severe ones which are uncommon. For instance, a method has been devised for rendering animals immune against lockjaw, which would probably apply equally well to man. But mankind in general will never adopt it, since the danger from lockjaw is so small. Inoculation must then be reserved for diseases which are so severe and so common, or which occur in periodical epidemics of so great severity, as to make people in general willing to submit to inoculation as a protection. A further objection arises from the fact that the immunity acquired is not necessarily lasting. The cattle inoculated against anthrax retain their protective powers for only a few months. How long similar immunity might be retained in other cases we can not say, but plainly this fact would effectually prevent this method of protecting mankind from being used except in special cases. It is out of the question to think of constant and repeated inoculations against various diseases.

As a result, the principle of inoculation as an aid in preventive medicine has not proved of very much value. The only other human disease in which it has been attempted seriously is Asiatic cholera. This disease in times of epidemics is so severe and the chance of infection is so great as to justify such inoculation. Several bacteriologists have in the last few years been trying to discover a harmless method of inoculating against this disease. Apparently they have succeeded, for experiments in India, the home of the cholera, have been as successful as could be anticipated. Bacteriological science has now in its possession a means of inoculation against cholera which is perhaps as efficacious as vaccination is against smallpox. Whether it will ever be used to any extent is doubtful, since, as already pointed out, we are in a position to avoid cholera epidemics by other means. If we can protect our communities by guarding the water supply, it is not likely that the method of inoculation will ever be widely used.

Another instance of the application of preventive inoculation has been made, but one based upon a different principle. Hydrophobia is certainly one of the most horrible of diseases, al-though comparatively rare. Its rarity would effectually prevent mankind from submitting to a general inoculation against it, but its severity would make one who had been exposed to it by the bite of a rabid animal ready to submit to almost any treatment that promised to ward off the disease. In the attempt to discover a means of inoculating against this disease it was necessary, therefore, to find a method that could be applied after the time of exposure—i. e., after the individual had been bitten by the rabid animal. Fortunately, the disease has a long period of incubation, and one that has proved long enough for the purpose. A method of inoculation. against this disease has been devised by Pasteur, which can be applied after the individual has been bitten by the rabid animal. Apparently, however, this preventive inoculation is dependent upon a different principle from vaccination or inoculation against anthrax. It does not appear to give rise to a mild form of the disease, thus protecting the individual, but rather to an acquired tolerance of the chemical poisons produced by the disease. It is a well-known physiological fact that the body can become accustomed to tolerate poisons if inured to them by successively larger and larger doses. It is by this power, apparently, that the inoculation against hydrophobia produces its effect. Material containing the hydrophobia poison (taken from the spinal cord of a rabbit dead with the disease) is injected into the individual after he has been bitten by a rabid animal The poisonous material in the first injection is very weak, but is followed later by a more powerful inoculation. The result is that after a short time the individual has acquired the power of resisting the hydrophobia poisons. Before the incubation period of the original infectious matter from the bite of the rabid animal has passed, the inoculated individual has so thoroughly acquired a tolerance of the poison that he successfully resists the attack of the infection. This method of inoculation thus neutralizes the effects of the disease by anticipating them.

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 doubt-less 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.

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