ON THE NATURE OF TOXINS 4Q 



this is done we find they obey the law of multiple proportions 

 with great accuracy. Thus the exotoxins differ from the enzymes 

 mainly in the fact that each molecule of the former acts once, and 

 once only. We shall subsequently meet another group of sub- 

 stances, of very similar nature but of animal origin, which have 

 an enzyme-like action, but are destroyed in the process. They 

 are the complements (alexins, etc.), which resemble the exotoxins 

 in many respects, and might well be called the animal toxins. 



On investigating more closely the action of the exotoxins, we 

 find that certain of them exert their pathogenic action mainly on 

 certain cells of the body. The most marked example of this is 

 in tetanus, which practically only affects the cells of the central 

 nervous system, causing in them definite histological changes, 

 and having a pharmacological action almost exactly like that of 

 strychnine. In the case of diphtheria also the action is most 

 marked on these cells ; this is best shown by the occurrence of 

 diphtheritic paralysis (associated with histological changes in the 

 ganglion cells similar to those of tetanus, and subsequent degene- 

 ration of the nerves), which occurs after the action of minute 

 doses of the toxin. 1 We may fairly assume that when but an 

 excessively small amount of toxin is present, it will unite with 

 the cells with which it has most affinity in this case with those 

 of the central nervous ganglia. But diphtheria toxin is not 

 limited in its action, as tetanus toxin is, and can act upon the 

 tissue cells almost without exception. Thus we find that the 

 injection of a large dose of toxin subcutaneously is followed by 

 the production of an acute inflammatory swelling, showing that 

 it can poison the connective tissues, and after death there may be 

 focal necrosis of the liver, degenerative changes in the renal 

 epithelium, fatty degeneration of the heart, etc., showing that 

 the toxin may act on all these organs and tissues. We may 

 regard it as a good example of a general protoplasmic toxin 

 having, as is so frequently the case, a special action on certain 

 cells. The toxins of most diseases come under this heading, the 

 specialized action of the tetanus toxin being unique. 



In some cases we can study the action of the exotoxins and 

 allied substances on isolated cells in vitro, and these are of especial 

 interest from the ease with which they can be investigated, and 

 are of some importance in disease. They are the leucolysins, or 

 leucotoxins, and the haemolysins. 



1 If we accept Arrhenius's view of the interaction of toxin and antitoxin. 



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