84 PROTEIN THERAPY 



various substances we were stimulating the organism late in dis- 

 ease, in an exhausted patient, stimulation would naturally be un- 

 availing. The fact that the degree of stimulation and reaction de- 

 termined the therapeutic effect was evidence of one of the frequently 

 observable biological balances in which the end reaction (recovery in 

 this case) seems proportionately greater than the stimulus (intoxi- 

 cation) . 



Weichardt 's Theory. Weichardt, whose work with protein in- 

 toxication and fatigue intoxication is well known, based his explana- 

 tion of the nonspecific reaction on these two basic observations and 

 the term "Plasmaactivation" or "Omnicellular Plasmaactivation" with 

 which Weichardt has sought to designate the mechanism involved in 

 nonspecific therapy is perhaps a satisfactory one in that we may 

 include under it the many possible and probable alterations that are 

 inaugurated by the reaction without limiting our conception to any 

 one feature. Bessau has but recently pointed out that the favorable 

 therapeutic action corresponds to Pfeiffer's older conception of means 

 to increase the resisting power of the organism, for Pfeiffer showed 

 that a variety of interventions in acute infections induced an im- 

 mediate increase in the resisting power. 



Inasmuch as few investigators in this field of research have had the 

 experience that Weichardt has had, it may be well to go back for a mo- 

 ment to the fundamental observations that underlie his conception of 

 "Plasmaactivation/- 7 Gamaleia, in 1888, had observed the pyrogenic effect 

 of bacteria and noted that the degree of temperature rise produced by the 

 injection of bacteria had an intimate relation to the state of digestion of 

 the bacterial cells. Later Charrin and Ruffer noted that when bacteria 

 were heated to a temperature of 110 C. they still retained this property 

 of causing a rise in the temperature, while other nonbacterial proteins also 

 caused an increase in the temperature (bouillon and organ extracts). As 

 a matter of fact, the observation that such substances were pyrogenic was 

 made previously by Roux and Lepine. Later Buchner worked along the 

 same line, incidentally observing the fact that on reinjection the animal 

 may respond differently than after the first injection (one of the early 

 observations of sensitization and anaphylaxis). Ott and Collmar had tried 

 out a variety of protein split products albumoses, peptone, and neurin 

 in the smaller laboratory animals, but had obtained very irregular pyro- 

 genic effects. Then Krehl and Matthes published a series of observations 

 concerning the effect of bacterial and other split products on animals 

 (normal, and sensitized by some infection such as tuberculosis), the results 

 of which have already been discussed. Krehl noticed particularly that the 

 experimental animals varied in their sensitiveness to the protein split prod- 

 ucts. The guinea pig was most susceptible to deuteroalbumose, the rabbit 

 less ^so and the dog least, quite the same relation that we find in anaphy- 

 lactic shock. 



Schittenhelm and Weichardt and their associates Hartmann, Greiss- 

 hammer, Strobel, etc. made intensive studies of the temperature curve, 

 the leukocytosis, the nitrogen excretion and general clinical picture fol- 



