Medicine - Infection - Its Processes and Results
( Originally Published 1905 )
In the foregoing list of diseases associated with specific bacteria, attention has been drawn to the common modes of infection, or, as they are technically called, "portals of entry," and it now remains to touch upon the main factors, processes, and results following upon the entry into the body of such disease-producing microbes.
It is a well-known fact that the normal blood has of itself to a considerable extent the power of killing germs which may wander into it through various channels. Likewise the tissue cells of the body in general show similar action depending upon the different cell groups, state of health, general robustness, and period of life. The germ-killing power varies in different individuals, though each may be quite healthy. Considered as a whole, this power possessed by the body against germs is known as "general resistance." And when by any means this power of resistance is lost or diminished, we run grave risks of incurring disease.
Granted a case of infection, let us now trace up briefly what occurs. Between the period when the bacteria gain a lodgment and that in which the disease assumes a notice-able form, the patient simply feels out of sorts. It is during this stage that the blood and tissues are deeply engaged in the attempt to repel the attacks of the invading microbes.
With varying speed the germs multiply throughout the body generally, or may be at first localized, or even, as in lockjaw, remain localized throughout the entire disease. Multiplying in the tissues, they generate in increasing amounts their noxious poisons, which soon cause profound changes throughout the body; the patient becomes decidedly ill, and shows the signs of an unmistakable infection.
Does the body now give up the fight entirely? No; on the contrary, the white blood-cells, the wandering cells, and the cells of the tissues most affected still carry on an unequal fight. From the lymphatic glands and spleen, armies of white cells rush to the fray and attempt to eat up and destroy the foe, but possibly in vain; the disease runs its course, to end either in death or recovery.
How, then, in cases of recovery, are the microbes finally overcome?
This question involves many complex processes which at present are by no means thoroughly understood, but we will concern ourselves with the simple principles.
It has been previously mentioned that once the bacteria get a good foothold the body is subjected to the action of generated poisons, which are known as toxins. They give rise to such symptoms as loss of appetite, headache, fever, pains and aches, and even a state of stupor or unconsciousness. In addition to the active warfare of the white blood-cells, groups of cells throughout the body, after recovering from the first rude shock of the toxins, begin to tolerate their presence, then effect a change in the chemical constitution of the toxins, and finally elaborate substances which antagonize the toxins and destroy their action altogether, thus lending aid to the warrior cells, which at last overcome the invading microbes. Recovery is brought about, and a more or less permanent degree of immunity against the special form of disease ensues.
Now if we could use these antagonizing substances, or, as they are called, antitoxins, upon other men or animals sick with a similar disease, would their bodies be at once strengthened to resist and finally overcome the disease? Yes, in a certain majority of cases they would, and this is exactly what scientific observers have noted, worked out, and have successfully applied. A new art in the healing of disease, which is spoken of broadly as serum-therapy, or medication by curative or protective serums, has thus been discovered.
The first observers in this new field were Pasteur and Raynaud in France in 1877-78, and Salmon and Smith in this country in 1886. Raynaud, by injecting serum from a calf which had had an attack of cow-pox, prevented the appearance of the disease in a calf freshly inoculated with the virulent material of the disease. Pasteur, by using feebly infective germs of fowl cholera, conferred immunity upon healthy fowls against the disease, and was able to cure those which were ill. Salmon and Smith injected small and repeated amounts of the elaborated toxins or poisons of the bacillus of hog cholera into healthy swine, and were able to confer immunity upon them.
However, it was not until Behring in 1892 announced his discovery of an antitoxin serum for diphtheria, along with an undisputed proof of its value in treatment, that the attention of the scientific world was finally aroused and stimulated to the appreciation of the great possibilities of serum-therapy.
Strange as it may seem, much opposition arose to this new method of treatment, not alone from the lay portions of the community, but even from the ranks of the medical profession itself. This opposition was due in part to misconceptions of the principles involved in the new doctrine, and in part to the falsely philanthropic prejudices of the pseudo-scientific sections of both parties. But by the per-serving work of the enthusiastic believers in serum-therapy, positive conviction has now replaced misconception and prejudice in the minds of the majority of its former opponents.
The accumulation of statistical evidence, even where all allowance is made for doubtful methods of compilation, shows that the aggregate mortality of diphtheria has been reduced fully fifty per cent. since the introduction of anti-toxic treatment by Behring in 1892.
Since the method of preparation of the commercial diphtheria antitoxin illustrates the general principles involved in the search for the production of curative or protective serums for infectious diseases in general, a summary of the steps in its manufacture will now be given.
A race of diphtheria bacilli, which has been found to yield a poison of great virulence in alkaline beef broth, is grown for a week or ten days in this medium. The toxin is then separated and its virulence exactly determined. It is pre-served in sterile receptacles for immediate or future use. The next step is the inoculation of a suitable animal with the toxin. Of all animals the horse has been found to meet nearly every requirement. Such an animal, in a state of perfect health, receives an injection of twenty cubic centimetres of toxin, along with ten or fifteen of standard anti-toxin, beneath the skin of the neck or forequarters, upon three separate occasions at intervals of five days. After this it receives increasing doses of toxin, alone, at intervals of six to eight days, until, at the end of two months, it is able to stand with little discomfort doses of such strength that if given in the first stage these doses would have quickly caused death.
At this period the horse is bled to a small extent, and its serum tested to ascertain if prospects are good for the production by the animal of a high grade of antitoxin. If satisfactory progress has been made, the injections are continued for another month, when, as a rule, the maximal degree of antitoxic power in the serum will have been attained.
The horse is now bled to the proper extent, the blood being received in a sterile jar and placed in an ice-box. Here it coagulates, and the serum separates from it. When the separation of clot and serum is complete, the latter is drawn off, taken to the laboratory, and standardized. This being finished, an antiseptic fluid is added to preserve the serum from decomposition. It is then bottled, labelled, and sent out for use.
In similar fashion tetanus antitoxin is prepared; and quite recently Calmette has produced an antitoxic serum for use in snake bite, by injecting horses with minute increasing doses of snake venom. His experiments have given some remarkable results, not only in laboratory work, but also in cases of actual snake bite occurring in man. Thus bacteriological scientists, after years of laborious work, in the face of much criticism and severe denunciation, may confidently announce that they have in their possession a magic key to one of nature's secret doors. The lock has been turned. The door stands partly open, and we are permitted a glimpse of the future possibilities to be attained in the great fight against disease.