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Dr. Paul Ehrlich. 



solitary exception of snake-venom — the toxophore group comes into 

 activity after the lapse of a longer or shorter incubation period, 

 which may, e.g., in the case of diphtheria toxine, extend to several 

 weeks. It is in the highest degree interesting that it is possible, by 

 voluntarily influencing certain of the outside conditions, to exclude 

 absolutely the action of the toxophore group. Courmont has shown 

 that frogs, when kept at a temperature lower than 20° C, manifest no 

 sign of tetanus, even after very large doses of tetanus toxine, but they 

 succumb to fatal tetanus if they are placed in surroundings of a higher 

 temperature. Dr. Morgenroth, working in my Institute, has thrown 

 light on this behaviour by proving that in frogs maintained in cold 

 surroundings the tetanus toxine is fixed in their central nervous 

 system, and that the absence of action at lower temperatures can only 

 be explained by the toxophore group of tetanus toxine having its 

 action restricted within a certain temperature minimum, while inde- 

 pendent of this the haptophore group exercises its action on the 

 nervous system at all temperatures. 



The theory above developed allows of an easy and natural ex- 

 planation of the origin of antitoxines. In keeping with what has 

 already been said, the first stage in the toxic action must be regarded 

 as being the union of the toxine by means of its haptophore group 

 to certain " side-chains " of the cell protoplasm. This union is, as 

 animal experiments with a great number of toxines show, a firm and 

 enduring one. The side-chain involved, so long as the union lasts, 

 caimot exercise its normal physiological nutritive function — the taking 

 up of definite food-stuff's. It is as it were shut out from participat- 

 ing, in the physiological sense, in the life of the cell. We are there- 

 fore now concerned with a defect which, according to the principles so 

 ably worked out by Professor Carl Weigert, is repaired by regenera- 

 tion. These principles, in fact, constitute the leading conception in 

 my theory. If, after union has taken place, new quantities of toxine 

 are administered at suitable intervals and in suitable quantities, the 

 side-chains, which have been reproduced by the regenerative process, 

 are taken up anew into union with the toxine, and so again the process 

 of regeneration gives rise to the formation of fresh side-chains. In 

 the course of the progress of typical systematic immunisation, as this is 

 practised in the case of diphtheria and tetanus toxine especially, the 

 cells become, so to say, educated or trained to reproduce the necessary 

 side-chains in ever-increasing quantity. As Weigert has confirmed by 

 many examples, this, however, does not take place as a simple replace- 

 ment of the defect ; the compensation proceeds far beyond the neces- 

 sary limit ; indeed, over-compensation is the rule. Thus the lasting and 

 ever-increasing regeneration must finally reach a stage at which such 

 an excess of side-chains is produced that, to use a trivial expression, 

 the side-chains are present in too great a quantity for the cell to carry, 



