mTBODUCTKOT 29 



It should always be borne in mind that a gland extract is a hetero- 

 geneous mixture of many substances. Living tissue is made up of systems 

 of highly labile components. Many of these undoubtedly are changed 

 both physically and chemically during the progress of the death processes 

 in the tissues. The disintegration and recombination of these various com- 

 ponents may give rise to a great variety of end products which in the 

 living gland were nonexistent or occurred to a much less extent than in 

 the gland extract. Furthermore, even though a given product found 

 in the gland extract exist as such in the living organs, it does not necessar- 

 ily follow that this product as such is discharged into the circulation. It 

 might be merely an intermediate product in process of further elaboration. 

 It is obvious in the nature of the situation that in addition to any hormone 

 that might occur in a given gland extract numerous nonspecific substances 

 are certainly present. When given by mouth these substances may be 

 digested or otherwise disposed of and play a negligible or relatively unim- 

 portant part, but when the extracts are introduced directly into the circu- 

 lation, as commonly is the case, they often play a predominant role in the 

 reactions. 



One such nonspecific substance which is likely to be found in any 

 tissue extract is cholin. This is a powerful vasodepressant. This sub- 

 stance has received much attention at the hands of investigators and ob- 

 servers are likely to be on their guard concerning it. More recent work 

 shows, however, that it plays a less important role in injection experiments 

 than was formerly supposed. Nucleoproteins also are always found, but 

 these have come to be recognized as relatively unimportant in that they 

 do not give rise to any immediate striking reactions. Histamin is another 

 highly potent substance which can be demonstrated in gland extracts 

 from a variety of sources. This may play an important part in the reac- 

 tions to the extract. Indeed, so struck was Abel by this possibility that 

 he for a time regarded histamin as the actual "active principle" in ex- 

 tracts of the posterior lobe of the hypophysis. Largely through the work 

 of Vaugjian and his collaborators, we have come to recognize that the 

 most harmless protein substances may, during the process of their dis- 

 integration, give rise to highly toxic material. It is not unlikely that the 

 split protein toxins have played a significant part in experiments on gland 

 injections. The work of Jobling, Bronfenbrenner and others has brought 

 out clearly the importance of the tryptic enzymes of the blood in the forma- 

 tion of such toxins. Unless one is on his guard in making gland extracts, 

 these toxins can readily be formed, and can either give rise to reactions in 

 the experimental animal or can mask the effects of any specific substance 

 which may be present in the extract. Anaphylactic shock, which may be 

 merely a special phase of protein intoxication, may enter in as a disturb- 

 ing factor in case the experimental animal has been previously sensi- 

 tized to any protein present in the gland extract, There is ground for 



