THEORIES OF MECHANISM OF REACTION 85 



lowing protein injections of various kinds in a variety of animals. The 

 leukocytic picture and the temperature curves have been discussed under 

 their respective sections. They noted among other things that the ex- 

 cretion of nitrogen was markedly augmented when the animal was sensi- 

 tized and then injected, or when a very toxic protein such as that derived 

 from the colon or typhoid bacillus was injected. The derivatives of 

 nuclear destruction in particular were found to be increased. While the 

 effect on the temperature might be relatively negligible, such injections, 

 particularly in dogs, might produce a change in the leukocytic picture 

 lasting at least a day and an increased nitrogen metabolism that would 

 cover a period of 4 days. 



In dealing with protein intoxication Weichardt and Schittenhelm em- 

 phasize that the bacterial bodies contain too large a variety of proteins 

 and protein split products to obtain a clear picture; the isolated components 

 had to be studied before conclusions could be drawn. They observed that 

 proteins that were made up largely of monoamino-acids, such as peptones 

 derived from silk, casein, hair or edestin, were practically not toxic to the 

 organism ; on the other hand, the diamino rich complexes, such as histones 

 and protamins, were exceedingly toxic. According to Ruppel these are pres- 

 ent in particularly large amounts in a number of bacteria. When attached 

 to form some other grouping, as for instance a nucleohistone, the histone 

 becomes nontoxic. Detoxication can therefore take place in the direction 

 of synthesis as well as in the further lysis of the protein complexes. Of 

 course, even on lysis toxic amino-acids may be formed, as when beta-imid- 

 azolylethylamin is formed from histidin. (Studied by Barger and Dahl, 

 Biedl and Kraus, Schittenhelm and Weichardt.) 



From their further studies in this direction, Schittenhelm and Wei- 

 chardt concluded that the conjugated proteins such as nucleoprotein, hemo- 

 globin, glutokyrin sulphate, etc., were relatively nontoxic, whereas the pro- 

 tein components of these complexes were manifestly toxic (globin, histone, 

 protamin) as indicated by their effect on the blood pressure, temperature, 

 respiration, coagulability of the blood and lethal effect. It is not necessary 

 to add that this toxicity is just as pronounced when the derived protein is 

 homologous in origin. While in general the richness in the diamino- 

 acids of these compounds is paralleled by their toxicity, this is not the 

 only factor involved. 



Of exceeding interest is their work with hemoglobin, which, apart from 

 a slight temperature effect, was practically nontoxic. They were, however, 

 able to sensitize animals against it. On the other hand, globin was much 

 more toxic. When conjugated with hemochromogen this toxicity again 

 disappeared. This fact is of particular interest in several pathological con- 

 ditions, such as malaria, where the appearance of the chill and the high 

 temperature reaction has been ascribed to the liberation of hemoglobin 

 and its derivatives. Cowie and Calhoun on the other hand are inclined 

 to the belief that it is due to protein derived from the plasmodia. 



Weichardt and Schittenhelm made the further observation that the 

 continued injection of the proteins that caused a toxic reaction was fol- 

 lowed by a definite cachexia and ultimately by death. This protein cachexia 

 seems a fairly constant phenomenon and has been observed by Bold as 

 well. 



