Report on the bacteriological diagnosis and the antitoxic serum treatment of cases admitted to the hospitals of the Board during the years 1895 and 1896. / By G. Sims Woodhead.

  • Woodhead, G. Sims (German Sims), Sir, 1855-1921.
Date:
[1899?]
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Licence: Public Domain Mark

Credit: Report on the bacteriological diagnosis and the antitoxic serum treatment of cases admitted to the hospitals of the Board during the years 1895 and 1896. / By G. Sims Woodhead. Source: Wellcome Collection.

Provider: This material has been provided by London School of Hygiene & Tropical Medicine Library & Archives Service. The original may be consulted at London School of Hygiene & Tropical Medicine Library & Archives Service.

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    Antitoxin production a property of nutrition. Typical experiment. Toxoids of Ehrlich. The toxin molecule The naluie of antitoxin. special toxins and enzymes overtiow into the fluids around the toxin-producing bacteria, or the enzyme-producing yeasts. There now seems to be nothing extraordinary in this except as regards the specific interaction, for, as Biitschli and his school have pointed out in connection with the structure of the protoplasm of the cell, we must look upon these special substances as being formed by the cells, and as in some cases remaining in a loose form of combination but in others thrown out beyond the bounds of the protoplasm itself; whether the toxin be in the organism iiself or outside, and whether the antitoxin be within the resisting cells or outside their protoplasm, the anti-bodies appear to act and react, one upon the other, very directly. At this point it was naturally suggested by workers in this field—Fischer, Weigert, and Ehrlich especially—that, as so many different antitoxins could be formed in response to the stimulation of the different toxins, there must be some very special affinity between the specific toxin, say, and certain special cells or even special parts of the protoplasm of these cells. Ehrlich insists that it is only when a substance can be taken into or bound to the cell, and combined with some element in that cell, that any immunity against pathogenetic substances can be gained by the cell. This is a most interesting statement, as its acceptance involves the theory that a toxin must be assimilated by the cell before an antitoxin can be produced; consequently, the whole question of antitoxin production must be closely bound up with the processes of nutrition. As the result of the assimilation of the proteid toxin we have the production and overflow of antitoxic substances from the specially stimulated cell, but the production of immunity against disease or the secretion of antitoxin appears to be only a side issue, as it were, or rather part of a general process going on where albuminoid substances are being assimilated by living protoplasmic cells. Ehrlich maintains that from the standpoint of immunity the toxic action of a toxin is a matter of accident, indeed of indifference, since a toxin does not produce its antitoxin by virtue of its toxic power, but because, being introduced into the animal body in such a way that its immediate destruction is avoided, it is assimilated. To put it more bluntly, the cells of our body are able to acquire immunity against organic toxic substances only because they are capable, in the process of nutrition, of taking these proteid toxic bodies into combination. Indeed, it has recently been demonstrated by Myers, Ehrlich, and others, that specific proteid substances obtained from different sources are, if introduced into the body in such a manner that the}' are not broken up or destroyed, capable of producing in the serum of the animal certain anti-bodies. One of Myers' experiments will serve as an example; he introduced crystallised egg albumen into the peritoneal cavity of a rabbit. After this had been repeated weekly for a period of some six or eight weeks, a small quantity of the blood of the rabbit was taken, and the serum separated from this was added to a solution of the original crystallised egg albumen. This addition resulted in the combination of the two substances, and in the precipitation of the egg albumen, and such quantities of each may be added that every particle enters into combination, the albumen and its anti-body neutralising one another completely and exactly, in this way acting just as do the proteid toxin of the diphtheria bacillus and its antitoxin. If the albumen used in such an experiment be pure, its range of activity appears to be exceedingly limited, whilst if it be a mixed albumen it appears to react against a correspondingly large number of albumens. We have here an analagous condition to that found in connection with toxins and antitoxins—comparatively simple and specific bodies, and bacterial products and antibacterial products—much more complicated substances. As pointed out in the Eeport, however, the proteid poisons of diphtheria are not pure toxic substances; indeed, the toxic factor appears to be of less importance than some other portions of the molecule that give rise to the special stimulation producing antitoxin, and it soon became evident that proteid poisons may become so far modified as regards minor groups of molecules (the main combining molecules remaining the same), that cells may be brought to assimilate or combine with these molecules in such a fashion that they form within their protoplasm substances which, either in the cell or separated from it, may combine with the whole molecules and, along with them, with the secondary and smaller molecules to which the special toxicity may be attributed, and thus neutralise them. That something of this kind may take place, Ehrlich points out, in connection with the neutralising power of antitoxins, as antitoxins neutralise not only true toxins but also what he calls toxoids, i.e., substances apparently formed from toxins, having many of the properties of the toxins but retaining little if any of their lethal activity. He proved this in connection with diphtheria toxins by testing the combining power of an active toxin and then, after keeping this toxin in a warm chamber for some time, again testing both its lethal and combining powers. Its combining power with antitoxin remained the same, but its lethal power had fallen enormously, to one-half or one-third of its original strength. Having determined this, he found that in the case of tetanus toxin he could diminish its activity by adding bisulphide of carbon. He found, however, that this innocuous toxoid still retained its reniarkable immunising and antitoxin-producing constituent. These toxic proteid molecules may be either toxic molecules linked to the proteid molecule or a proteid molecule in which certain replacements have taken place. In any case they appear to be easily linked to the living cell, and to be able to stimulate it to produce antitoxin. They are always formed in larger quantities where albumens are already present, than when the proteid molecule has, as it were, to be built up. If, now, the toxic molecules, produced in these albuminous fluids in such large quantities, can be modified as are the molecules produced in fluids containing less albumen, should it not be possible to obtain large quantities of non-toxic proteid molecules which, assimilated by the cells, will induce the formation and overflowing of antitoxins, antitoxins capable of neutralising not only the principal toxoid or large molecule, but this same toxoid molecule with its linked-on smaller toxic molecules? Cartwright Wood has proved that this is possible, and we have the result in the rapid production of antitoxin by the injection of serum-toxin which contains an exceedingly small amount of the active toxic substance. Bound up with the theories of immunity and the question of the source of antitoxin is the important question of the nature of antitoxin.^ The original theory already mentioned, put forth
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