168 PRINCIPLES OF BACTERIOLOGY 



toxin was required to kill this animal than a normal guinea-pig of 

 equal size. If, on the contrary, they waited one to three days, it was 

 found that then a dose of tetanus toxin which would not even tetanize 

 an untreated guinea-pig was sufficient to kill this one. 



If their explanation of the above experiments is correct, then we have 

 for the first time proof of the existence of the first two of the three 

 stages demanded by Ehrlich's theory. The first stage, the binding 

 of the haptophore group, is demonstrated with the toxoid; the second 

 stage, the increased production of receptors, is demonstrated by the 

 second series of experiments just described ; the third stage is the thrust- 

 ing off of the receptors. Close attention to these experiments will show 

 that with a completely non-poisonous toxoid no receptors were thrust 

 off at all. The serum of the rabbit treated with this toxoid contained 

 no antitoxin whatever. Hence it follows that the thrusting off of the 

 receptors into the blood serum does not necessarily follow from their 

 overproduction, but that something additional is required. This "some- 

 thing," which we may term a stimulus, is a function of the toxophore 

 group. Because of these experiments Wassermann conceives the 

 mechanism of the presence of the specific antibodies in the serum to be 

 as follows: 1. The haptophore group is bound by the receptor. 2. 

 The consequence of this binding is a proliferation of the receptors. In 

 this stage, however, they are still attached to the organ. 3. In order 

 that they be thrust off, a certain stimulus is required. The haptophore 

 group is incapable of exerting this, so that, in the case of tetanus toxin, 

 this is exerted by the toxophore group. These experiments, although 

 important, do not appear to me to establish as much as Wassermann 

 conceives. There is no proof that additional receptors in the cells of 

 an animal so sensitive as a guinea-pig would in fact make it respond 

 to a smaller dose of toxin. It would be equally easy to argue that it 

 would be less sensitive, since fewer cells might absorb all the toxin. 

 The fact that the cells combining with the toxoid yielded up no anti- 

 toxin might be taken to prove that the cells specifically attacked were 

 not the ones that produced the antitoxin. 



Other Explanations of the Production of Antitoxins. Gruber along with 

 others consider that the antitoxins are not normal constituents of the 

 cells but simply secretions of the cells under the stimulus of the toxin, 

 and the cells secreting are not the cells sensitive to the toxin, but 

 others e. g., the blood-producing organs. Gruber claims that the power 

 to poison highly immunized animals with toxin is against Ehrlich's 

 ideas. This objection can be met in several ways. Ehrlich believes 

 that the receptors while still in the cell may have a greater affinity 

 for the toxin than after being thrown into the circulation. Gruber 

 claims that the latent period in toxin poisoning is due to the slow 

 absorption of the toxin by the circulation, and does not need the 

 elaborate explanation of the toxophore group acting through the 

 haptophore. The idea that antitoxin is simply the toxin modified has 

 been given up for one reason because the antitoxin developed is several 

 thousand times enough to neutralize the toxin injected. 



