152 TOXINES AND ANTITOXINES. 



And the cholera vibrio retains such ferment within itself in 

 firm combination, but capable of isolation by drastic means, as 

 was shown by GERET and HAHN when they isolated a proteolytic 

 enzyme. In like manner, then, the toxine also appears to be 

 firmly combined with the living cell, to be an endotoxine analo- 

 gous to the endoenzymes. After the death of the cell, however, 

 it passes, partially at all events, into the culture medium, just 

 like yeast invertase, so that, as PFEIFFER has shown, cultures 

 killed by thymol, &c., or by drying, give indications of the poison 

 they contain. But that the toxine, after the death of the 

 vibriones, is really free, dissolved in the medium, and diffusible, 

 is shown, again, by the experiments of METSCHNIKOFF, Roux, 

 and TAURELLI-SALIMBENI, in which it was found that living 

 vibriones enclosed in a collodion capsule exerted their toxic 

 activity outside the membrane. For, without doubt, in an ex- 

 periment on these lines, of luxuriant growth on a restricted 

 culture medium, a process of death and decomposition would 

 take place simultaneously with the development of new vibriones. 

 And since in this case the toxine can, immediately after its 

 production, exert its activity upon the organism, while itself 

 protected from every injurious influence, we may conclude with 

 some degree of probability that here the primary true cholera 

 toxine is the active agent. Probably this presumably true toxine 

 is also active in cases of real cholera in the living organism. 

 And this toxine ought, therefore, also to produce an antitoxic 

 reaction in the organism. That this reaction is so slight ought 

 not to excite surprise, for, in the first place, the amount of toxine 

 thus set free can only be very trifling, so that a high degree of 

 immunisation is not to be expected ; and, further, this degree 

 of antitoxic activity is lacking in a complete poison that has 

 undergone secondary alterations, and, as we shall see below, 

 probably contains numerous toxoids, the result being that the 

 antitoxic power of the serum must appear too small. Thus the 

 cholera vibriones, after death and decomposition, give up part of 

 their endotoxine to the culture media ; at the same time it is 

 highly probable that they still retain the larger proportion of the 

 toxine, just as zymase is retained by yeast. Possibly the method 

 of aseptic autolysis tried by CONRAUI l upon typhoid bacilli may 

 enable us to prepare the primary cholera poison. 



This primary poison, a true toxine, is extraordinarily sensitive 

 to external influences, in which respect it resembles zymase, and 

 its full activity can therefore only be demonstrated under con- 



1 Conradi, "Ueber losliche, durch Autolyse erhaltene Giftstoffe," 

 Deutsch. med. Woch., 1903, No. 2. 



