Toxin

“ A third method is by injections of the separated toxins of a bacterium, the resulting immunity being not only against the toxin, but, so far as present knowledge shows, also against the living organism. In the development of toxin-immunity the doses, small at first, are gradually increased in successive inoculations; or, as in the case of very active toxins, the initial injections are made with toxin modified by heat or by the addition of various chemical substances. ”

“ 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. ”

“ On this theory, susceptibility to a toxin will imply both a chemical affinity of certain tissues for the toxin molecule and also sensitiveness to its actions, and, furthermore, non-susceptibility may result from the absence of either of these two properties.
A bacterial infection when analysed is seen to be of the nature of an intoxication. There is, however, another all-important factor concerned, viz. the multiplication of the living organisms in the tissues; this is Bacterial infection.essential to, and regulates, the supply of toxins. ”

“ It is certainly not necessary in every case that the poisonous substance, the so-called toxin, should originate in the cell of the micro-organism itself; it is just as likely that it is formed, outside the cell, by ferments given off by the latter. When we introduce substances out of harmony with the species or the plasma, we have similarly to reckon with the presence of stages of decomposition, which may be disharmonious with the organism, and capable of producing injurious effects. ”

“ In these days of toxin and anti-toxin—of poison in sausages, oysters, canned beef, ice cream—of anti-toxin serums (that often are more deadly than the original toxin) for the prevention and cure of tuberculosis, leprosy, pneumonia, typhoid fever, tetanus, bubonic plague, diphtheria, and the rest of the list, it requires courage to call the attention of the public to a new "toxin," even if at the same time we furnish an anti-toxin that "anti-toxicates." ”

“ When the body is enervated, elimination is checked. This, in turn, results in a retention of toxins in the blood--the condition which we speak of as toxemia. This state produces a crisis which is nothing more than heroic or extraordinary efforts by the body to eliminate waste or toxin from the blood. It is this crisis which we term disease. Such accumulation of toxin when once established, will continue until nerve energy has been restored to normal by removing the cause. So-called disease is nature's effort to eliminate toxin from the blood. All so-called diseases are crises of toxemia. ”

“ Finally, they came to be looked upon as protective substances produced in the body cells as a result of toxin action, and held in solution in the blood, and there and elsewhere exerting their influence in opposition to the toxins.79 The progress of disease is therefore a struggle between the toxins 247and the antitoxins: when the toxins are in the ascendency we get an increase of the disease; when the antitoxins are in the ascendency we get a diminution of disease. If the toxins triumph, the result is death; if the antitoxins and resistance of the tissues triumph, the result is recovery. ”

“ Their presence constitutes a means of defence against the harmful effects the toxins would otherwise produce. The marvellous part of the defence is that, although we all have a certain amount of antitoxin in our blood, the amount increases in proportion to the amount of toxin. ”

“ 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. ”

“ It is also to be noted that, as in the case of poisons of known constitution, each toxin has a minimum lethal dose which is proportionate to the weight of the animal and which can be ascertained with a fair degree of accuracy.
The action of toxins is little understood. It consists in all probability of disturbance, by means of the chemical affinities of the toxin, of the highly complicated molecules of living cells. ”

“ The last word of science, after exact research in all the domains, is that alcohol is a poison. It has been found to be a hydrocarbon of the formula , that is produced by the process of fermentation, and is the toxin or liquid excretion or waste product of the yeast or ferment germ. According to the universal law cf biology that the toxin of one form of life is a poison to all forms of life of a higher alcohol, the toxin of the low yeast germ, is a protoplasmic poison to all life, whether plant, animal or man, and to all the living tissues and organs. ”

“ A marked difference between enzymes and toxins is that the former may bring about a very great chemical change and still may be recovered from the mixture of substances acted on and produced, while the toxin seems to be permanently used up in its toxic action and cannot be so recovered. Toxins seem very much like enzymes whose action is restricted to living cells.
Just as enzymes are probably produced by all kinds of cells and not by bacteria alone, so toxins are produced by other organisms. ”

“ Underneath all this storm and stress of the fever paroxysm, nature is quietly at work elaborating her antidote. In some marvelous fashion, which we do not even yet fully understand, the cells of the body are producing in ever-increasing quantities an anti-body, or antitoxin, which will unite with the toxin or poison produced by the hostile germs and render it entirely harmless. By a curious paradox of the process, it does not kill the germs themselves. It may not even stop their further multiplication. Indeed, it utilizes part of their products in the formation of the antitoxin ”

“ No adequate explanation of the formation of the toxin in the immense majority of the cases, in which there is no tapeworm, has yet been given. It is certain that no organism as yet known is concerned. ”

“ “The toxin generates the anti-toxin. The end lies concealed in the beginning. All bodies grow around a skeleton. Life is a petticoat about death. ”

“ Sometimes the effects depend merely upon the mode of entrance of the poison into the body. Tetanus toxin, diphtheria toxin and snake venom have no effect on mammals when swallowed unless the intestinal epithelium has been injured. These poisons can not pass through the epithelium to reach the blood, where alone they can exert their action. The toxin of the dysentery bacillus passes readily in the rabbit from the blood into the intestine, which it injures, but can not pass from the intestine into the blood. ”

“ In these cases there is apparently a real chemical relationship, as there is also between the toxins of bacteria and certain tissue cells (tetanus toxin and nerve cells) . Whether “chemotherapy” will ever profit from a knowledge of such chemical relationships remains to be developed. It appears that a search for these specific chemical substances with the object of combining poisons with them so that the organisms might in this way be destroyed, would be a profitable line of research. ”

“ It is only when they find their proper food, decaying matter, that they begin to multiply, and in that act they secret a poison, toxin, which is absorbed, and, entering the circulation, causes in the individual a special class of symptoms peculiar to that toxin, or poison. ”

“ 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. ”

“ Pharmacology is a branch of biology; it is also closely connected with pathology and bacteriology, for certain drugs produce structural as well as functional changes in the tissues, and in germ diseases the peculiar symptoms are caused by foreign substances (toxins) formed by the infective organisms present in the body. The effects of many of these toxins bear a close resemblance to the action of certain well-known drugs, as in the case of tetanus toxin and strychnine, and are studied by the same methods of observation and research. ”

“ He terms these haptophor groups, and the groups to which these are attached in the cells he terms receptor groups. The introduction of a toxin stimulates an excessive production of receptors, which are finally thrown out into the circulation, and the free circulating receptors constitute the antitoxin. The comparison of the process to assimilation is justified by the fact that non-toxic substances like milk introduced gradually by successive doses into the blood-stream cause the formation of anti-substances capable of coagulating them. ”

“ Other methods of preparing an animal for producing the antitoxin have been resorted to as injecting it with a mixture of toxin and antitoxin in increasing doses, or again injecting with a mixture of toxin and thyroid extract in increasing doses. ”

“ 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. ”

“ There exist, therefore, different mechanisms for excluding poisons from the sensitive and reacting cells and among them are certain quantities of neutralizing, or antitoxic substances, normally contained in the blood. We know at least one such definite antitoxin, namely, the diphtheria antitoxin, which exists in minimal quantities in the blood of man and the horse.
The absence of numerical relation between the mechanism which destroys bacteria and neutralizes poisons sometimes works sad havoc for the body. ”

“ 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. ”

“ Group XXVI. Antitoxins.—These are substances which antagonize the toxins formed in the body by pathogenic organisms, the toxins of snake venom and other animal poisons, and vegetable toxins such as abrin, ricin, &c. A healthy person can be rendered insusceptible by gradually accustoming him to increasing doses of these poisons, and this immunity is due to antitoxins which are found in the blood-serum and which are products of the blood cells. The nature of these antitoxic substances is not definitely known, but they combine with and destroy the poisons. ”

“ Repeat the experiment at least once. In the event of a positive result estimate the minimal lethal dose of "killed" culture for each of the species of animals experimented upon.
(b) Extracellular or Soluble Toxins: [Pg 319]
1. Filter the cultivation through a porcelain filter candle (Berkefeld) into a sterile filter flask, arranging the apparatus as in the accompanying figure (Fig. 160) .
2. Inoculate mice, rats, guinea-pigs, and rabbits subcutaneously with that quantity of toxin corresponding to 1 per cent. ”

“ Dirty, grimy wounds filled with the dust of stable yard or garden soil, and such as contain splinters 314of wood, stones, thorns, straw and the like can only be considered quite safe after thorough disinfection. It has been shown that the toxin is easily neutralized at the time of infection, whereas, after the disease is developed it will require 1,000 or 100,000 times as much antitoxin to produce the same effect. ”

“ According to this view, then, a part at least of the directly toxic substance is produced in the living body by enzymes present in the so-called toxin obtained from the bacterial culture. Recent researches go to show that enzymes play a greater part in fermentation by living ferments than was formerly supposed, and by analogy it is likely that they are also concerned in the processes of disease. But this has not been proved, and hitherto no enzyme has been separated from a pathogenic bacterium capable of forming, by digestive or other action, the toxic bodies from proteids outside the body. ”

“ We know that, following the intake even of non-purin-containing foodstuffs, an increase in uric acid excretion ensues, and that the same is the outcome of the stimulation of general nuclein metabolism. [199] Is it not conceivable that the responsible toxin acts in like fashion, and haply by disturbing the orderly sequence of those exquisitely delicate enzymatic reactions which culminate in the formation of uric acid, and with which potentialities every living cell in the organism is dowered? ”