io88 NON-SPECIFIC PROTEIN THERAPY 



Second, the "contracoup" theory {ictus morhi) based on the assumption that the 

 summation of disease manifestations in the form of a fastigium will be followed by a 

 rapid reversal to the normal. In its final analysis this rests on the general observance 

 of rhythmicity in biological processes. 



Finally, pharmacological and biochemical observations which lead to the belief 

 that most of the phenomena can be explained on definite alterations in the cells and 

 fluids of the body which follow any procedure such as that under analysis. The obser- 

 vations concern the efi'ects on the autonomic nervous system, on the changes in 

 capillary permeability, the liberation of pharmacologically active substances from 

 the tissues, changes in the ionic equilibria and the hormones. 



While it is obvious that in a review such as this we cannot be restricted to the 

 examination of theories as such, and shall deal with the experimental evidence, it is 

 well to keep in mind that probably all three are of importance, but not necessarily 

 all operative in any one disease condition. So it seems probable that in typhoid the 

 non-specific mechanism of recovery is built up largely on the intensive splanchnic 

 stimulation (parasympathetic status, with increased lymph flow, transfer of pre- 

 formed antibodies from the blood stream to lymph channels, bacteriolysis, etc.), that 

 the chronic infectious process is influenced by the focal reaction (increased permeabil- 

 ity at the focus), while the effect on asthma and gastric ulcer will be through the 

 autonomic apparatus (muscle tonicity, vascularization, etc.). Presumably, cell stimu- 

 lation, especially of the reticuloendothelial system, may influence the more chronic 

 infections such as syphiUs, while simflar changes (liver) may influence metabolic 

 derangements such as diabetes. 



There are qualitative as well as quantitative differences in biological effects which 

 we achieve with protein therapy, the differences depending on the agents, on the 

 dosage, on the patient, and on the disease from which the patient suffers. The reac- 

 tions may vary from mild changes that are within the range of physiological fluctua- 

 tion such as may be associated with menstruation, fatigue, digestion, etc. — produced, 

 for instance, by the intracutaneous injection of bland proteins, the ingestion of pep- 

 tone or glycocoll, or the injection of horse serum — through the range of intramuscular 

 milk injections, nuclein injections, or the innumerable preparations offered in the 

 market, finally to severe "shock" effects following the intravenous injection of 

 typhoid, meningococcus, or gonococcus vaccine. Even with such agents the effect 

 obviously depends on the dosage. 



THE BIOLOGICAL REACTION 



Before reviewing the more recent literature dealing with the effects of protein injections 

 on the organism, three factors should be emphasized. In the first place, the reaction pro- 

 duced is distinctly diphasic. A primary stimulation passes over to a secondary refractory (or 

 rest) phase. Unless the investigator keeps this in mind and follows the reaction continuously 

 for a considerable period of time he may reach quite erroneous conclusions. 



Second, the reaction elicited will depend on the functional (and pathological) status of the 

 individual organ or tissue. Tissues that are already stimulated or fatigued will respond quite 

 differently from tissues in the resting stage. Therapeutically this means that while non- 

 specific therapy in broad outline involves general tissue stimulation, actually the agents may 

 be "organotropic" in so far as organs that are the seat of disease may respond in a more 



