Antitoxin

“ In addition to the measures of prevention and suppression which have been mentioned reference should be made to the preparation and distribution of antitoxin by boards of health. Here we have an application of the laboratory principle applied to the production of a remedy rather than to the discovery of the cause of disease. Antitoxin is a curative measure which may be and is applied more often than not to isolated cases of diphtheria. ”

“ If the disease is early recognized and a proper amount of antitoxin injected, that is, forced in under the skin so that it may be absorbed by the blood, the probability is that in all cases the patient will recover. It is equally useful with vaccine as a preventative of disease, and in a school, for instance, where diphtheria has broken out, it is only a reasonable precaution to use antitoxin freely to prevent infection of those exposed to the disease. ”

“ The action of antitoxin on toxin, as tested by neutralization effects, takes place more quickly in concentrated than in weak solutions, and more quickly at a warm (within certain limits) than at a cold temperature. (b) Antitoxin acts more powerfully when injected along with the toxin than when injected at the same time in another part of the body; if its action were on the tissue-cells one would expect that the site of injection would be immaterial. ”

“ This production of antitoxin on the part of the infected body is a vital, protective mechanism of a chemical order; it is the chemical reply to a chemical insult. If the attacked body-cells can provide sufficient of this antitoxin to neutralize all the toxin made by the bacteria, the individual will not merely get well, but will remain immune from that particular infection for a long time, because, when once the body-cells begin making antitoxin they make a great deal more than is needed to neutralize all the toxin which the invaders have manufactured. ”

“ Of such probably are the toxins and antitoxins of certain infections, which, anchoring themselves not by any means indiscriminately, but to particular and concerted molecules, by such anchorage antagonize them or turn them to favourable or unfavourable issues. Toxins may thus become so closely keyed into their corresponding atom groups, as for instance in tetanus, that they are no longer free to combine with the antitoxin; or, again, an antitoxin injected before a toxin may anticipate it and, preventing its mischievous adhesion, dismiss it for excretion. ”

“ If the phagocytes and similar cells in the blood of a man or animal exposed to the poison produced by localised microbes (such as those of tetanus, diphtheria and septic growths) cannot produce enough antitoxin so as to quickly destroy the poison, we can, and do, nowadays, save his life, by injecting into his blood the required antitoxin, obtained from another animal which we have caused (by injection [Pg 248] of the toxin) to produce the antitoxin in excess. That is one sort of "immunity" or "resistance" which we can confer, and is largely in use at the present day—the "antitoxin" treatment. ”

“ It has been shown by C. J. Martin and Cherry, and by A. A. Kanthack and Cobbett, that in certain instances the toxin can be made to pass through a gelatine membrane, whereas the antitoxin cannot, its molecules being of larger size. If, however, toxin be mixed with antitoxin for some time, it can no longer be passed through, presumably because it has become combined with the antitoxin. ”

“ Now, if the cells in your body make antitoxin when you have diphtheria, it is probable that antitoxin is the very thing needed. And if you can help these cells by giving them antitoxin, ready-made, does it not seem a reasonable thing to do? People who give the name of poison to a substance which is known to have saved many lives are not worthy of attention. Anything may prove a poison if taken in excess; too much play will prove a poison, and too much work also. ”

“ It is sufficient to add the quantity of soda or of ammonia necessary for the neutralisation of the acid, in order to see the antitoxin reappear in its original strength.
It is therefore possible, by causing hydrochloric acid (in a solution not stronger than 3 per cent.) to act on a neutral mixture of cobra-hæmolysin (toxin) and antitoxin, to set the former at liberty in the form of lecithide, to withdraw the latter from the action of the antitoxin, and to demonstrate its presence, owing to its hæmolytic properties. ”

“ Animals treated with injections of these antitoxins are immune to the poison itself when subsequently injected with it, or, if already suffering from the poison (as, for instance, by snake-bite) , are readily shown by experiment to be rapidly cured by the injection of the appropriate antitoxin. This is, as all will admit, an intensely interesting bit of biology. The explanation of the formation of the antitoxin in the blood and its mode of antagonising the poison is not easy. ”

“ Inasmuch as we possess an antitoxin that unquestionably has the power of preventing lockjaw, if given sufficiently early, it is the part of [Pg 234] wisdom to administer at once a sufficient dose of this substance to any child who has received a penetrating wound from some dirty object, or from the explosion of fire-crackers. Statistics show that under such circumstances lockjaw may be prevented in almost all cases. If we wait until the disease develops, the antitoxin is of no value. ”

“ By the introduction of fresh toxin the process is repeated and the regeneration of side-chains is increased. Ultimately the regeneration becomes an over-regeneration and free side-chains produced in excess are set free and appear in the blood as antitoxin molecules. In other words the substances, which when forming part of the cells fix the toxin to the cells, constitute antitoxin molecules when free in the serum. ”

“ The number of primary abscesses has undoubtedly been reduced by the use of antitoxin. It may also be accepted that antitoxic serum has some effect in temporarily raising the temperature, but only during the periods of joint-pains and serum rashes; all these, however, are of comparatively slight importance as compared with the effect the antitoxin has in diminishing the percentage mortality and alleviating the more severe symptoms.
"It is of importance to observe that amongst the cases of paralysis following diphtheria the death-rate (32 per cent.) ”

“ The principal obstacle to the securing of antitoxins like that of diphtheria for all our infectious diseases is, that their germs form their poison so slowly that it is difficult to collect it in sufficient amounts to produce a strong concentrated antitoxin in the animal into which it is injected. ”

“ In specific germ diseases a similar antitoxin forms, and in cases which recover it counteracts the toxin, while the germs are destroyed by the tissues. Antitoxins can be prepared by immunizing a large animal, such as a horse, by injecting gradually increasing doses of specific toxins into its subcutaneous tissue. In due time the horse is bled, the serum is filtered free of blood corpuscles, and then constitutes the antitoxic serum, which can be standardized to a certain potency. ”

“ Treatment.—Diphtheria antitoxin is the specific treatment of this malady, and should be given early in the disease. The chances of recovery decrease in proportion to the length of time existing between the onset of the affection and the time of administration of the drug. Antitoxin may be repeated in six hours after the initial injection if improvement is not noticed, but ordinarily twenty-four hours should elapse between doses. It is well to remember that it is safer to give too much antitoxin than too little. ”

“ Now, in either case, antitoxin is administered at the very outset of the attack, with the result that the poisons are counteracted, the temperature drops rapidly, the membrane is apparently at once affected and lessened, and the child recovers at once. No greater boon to the human race in the matter of disease has ever been discovered, and it is certainly most absurd for parents to refuse the use of this wonderful antidote. ”

“ If an animal that is immune to a toxin is bled and the serum collected, the antitoxin in it may be injected into a healthy animal and render it immune. Ricin and abrin are vegetable protein toxins of enormous potency and exert a narcotic action. Guinea-pigs fed on them in proper doses attain such a degree of immunity that, in a short time, they can tolerate four hundred times the fatal dose. The serum also can be used to neutralize the toxin in another animal, to a certain extent."
We crowded about Kennedy and the doctor, our eyes riveted on the drawn face before us. Would the antitoxin work? ”

“ As a preventive against tetanus, in man or in animals, the antitoxin has proved of the very utmost value. This has been shown in a striking way in America. “One of the wounds most commonly followed by lock-jaw is the blank-cartridge wound of the hand common on the glorious Fourth of July. The death-rate from these wounds is appalling. An active campaign has been conducted throughout the medical profession to reduce this mortality. All over the country, surgeons and medical journals have advised the injection of tetanus antitoxin in every case of blank-cartridge wound. ”

“ Examples of this method include the use of antitoxin as a protection against diphtheria, of sera in pneumonia and other infections, and vaccination against smallpox and typhoid fever whereby a slight form of the disease is artificially induced. Laboratory research goes on constantly, and doubtless many more substances will eventually be discovered that will reduce human misery as vaccines and antitoxin have already reduced it. ”

“ Another important element involved in a speedy diagnosis is, that we must not take any chances of infecting other children. So important are these conditions that it is the proper treatment to give antitoxin at once in every case of tonsilitis that in the slightest way resembles diphtheria. An examination of the throat contents,—a culture of which is taken during the first visit of the physician,—will, of course, reveal the true condition and dictate the future use of the antitoxin. ”

“ He claims to have extracted this in a pure form, and upon successive injections of it for a period of time into the bodies of other animals their tissues have produced, he claims, an antidote to it in the form of a real antitoxin. This antitoxin of fatigue, if administered to fatigued animals or even human beings, is said to bring about prompt recovery; if administered to fresh organisms it is said to greatly prolong their working period. ”

“ Antiseptics and tonics have been freely employed, including phenol, salicylic acid, sodium salicylate, potassium iodide, quinia, alcohol, phosphorated oil, ammonia acetate, and as an eliminant soda sulphate, but with no very good result. Locally, scarification, antiseptics and caustics, have been employed.
Another line of treatment which deserves to be further exploited is the use of antitoxins on infected animals. An immunized animal may be again and again inoculated at intervals of a week or two until it has been stimulated to produce antitoxin in large amount. ”

“ Further, these molecules in the nervous system present the same susceptibility to heat and other physical agencies as does tetanus antitoxin. There is therefore strong evidence that antitoxin molecules do exist as part of the living substance of nerve cells. It has, moreover, been found that the serum of various animals has a certain amount of antitoxic action, and thus the basis for antitoxin production, according to Ehrlich's theory, is afforded. ”

“ These soluble toxins affect, stimulate, the tissues of the victim, which, being living cells, react, and the expression of their reaction is the outpouring of a chemical something, appropriately called an antitoxin which, uniting with the bacterial toxin, neutralizes it and prevents it exercising its injurious powers. The infected organism thus works out its own chemical salvation by a vital, but no less chemical, response to the poison of the infection. ”

“ We will suppose that the blue is due to the toxin produced by the diphtheria germ, and that the lemon juice is the antitoxin produced by the cells in the body. If the antitoxin is made fast enough, the blue disappears; but if the toxin is made faster than the antitoxin, the blue remains. It is the same way in the body, only it is not litmus and acids and alkalies that we have to deal with. If the toxin is made faster than the antitoxin, the germs grow, and we get sicker and sicker ”

“ There is another argument against diphtheria-antitoxin; we may call it, for brevity, the death-rate argument. It is this. The doctors say that the antitoxin does save lives; they give us statistics from every part of the world. But, if it saves lives, then the total mortality ought to go down. But the Registrar-General's returns do not go down; indeed, they tend to go up. Therefore diphtheria-antitoxin is useless, or worse than useless. ”

“ Lastly it may be mentioned that when a toxin has some action which can be demonstrated in a test-tube experiment, for example, a dissolving action on red corpuscles, this action may be annulled by previously adding the antitoxin to toxin; in such a case the intervention of the living tissues is excluded. ”