64 THE NEGATIVE PHASE 



All these methods have their advocates, and good results can 

 apparently be obtained by all. 



On ceasing to inject toxin, it usually happens that the antitoxic 

 value of the serum commences to decline, and, in the absence of 

 further injections, would probably continue to do so until it had 

 entirely disappeared from the blood. In a few cases, however, 

 a period of antitoxic equilibrium is maintained for some time, the 

 amount of antitoxin lost by the excretions or destroyed in the 

 system being compensated for by a fresh production of the same 

 amount. When this is the case the phenomena resulting from 

 the injection of a single dose of toxin can be traced with ease, and 

 is of great importance, as will appear subsequently. The first 

 effect of the injection is the production of a negative phase, in which 

 the amount of antitoxin in the blood is suddenly and greatly 

 diminished. This production of a negative phase is apparently 

 a general phenomenon, and is found to occur in the development 

 of nearly all antibodies in which it has been investigated. If the 

 dose of the primary substance (toxin, etc.) is very small, the 

 negative phase may be short in duration and very slight in extent, 

 and may be overlooked, or may possibly be omitted altogether. 

 Its explanation is very uncertain and cannot be discussed here, 

 but it must be pointed out that it is not due to the neutralization 

 of the antitoxin in the blood by the toxin injected ; the proof of 

 this is that it is large out of all proportion to the latter. Thus in 

 one reported case the fall in antitoxic value of the serum which 

 occurred in the negative phase would have required an injection 

 of toxin 12,000 times as large as was actually given if it were due 

 to simple neutralization. The length of the negative phase varies 

 in different animals, and can only be learnt by experiment. It 

 appears to be roughly proportional (in the same animal) to the 

 amount of primary substance injected : the larger the doses of 

 toxin, the greater the fall and the longer its duration. It is, 

 of course, synchronous with the toxic symptoms, if any, of the 

 substance injected, since both are due to the action of this sub- 

 stance on the blood and tissues ; but the two do not appear to be 

 mutually dependent : a well-marked negative phase may appear 

 without any other symptoms of disease. 



The negative phase is succeeded by a rise, the positive phase, 

 in which the antitoxic value of the blood reaches and usually 

 surpasses its previous level. It commonly reaches its maximum 

 in about a week, and then commences to decline ; hence it is 



