484 The University Science Bulletin. 



While they are migrating and the coaguhition is taking place they 

 disintegrate in the absence of oxygen. They suffer a coagulative 

 necrosis. After they come to rest they suffer no change in the 

 absence of gas. In the same way, these cells suspended in* a liquid 

 are unaffected by the absence of oxygen. In a liquid they do not 

 metabolize any more than in the presence of a fully formed fibrin. 

 Any slight stimulus which occasions their movement occasions also 

 their disintegration in an atmosphere of nitrogen. 



There seemed little doubt, therefore, that in the identification of 

 this "L" substance the regulator of the metabolism of these cells 

 had been found. It is not something which is continuously washed 

 away by the blood stream, but, quite to the contrary, it has very 

 specific affinities, -and when brought into contact with fibrinogen it 

 forms an insoluble fibrin. This suggested strongly, therefore, that 

 continuous activity in these cells must depend not alone on food and 

 oxygen, but also upon very special conditions for removing these 

 primary products from the cell.^ The only plentiful substance 

 which I have been able to find in the adult body capable of such 

 removal is fibrinogen. This is transferred by the "L" substance 

 into fibrin. In the body the messenchyme cells of older embryos 

 and the connective-tissue cells of adults lay down extracellular 

 fibrils. Hertzler^^ has shown very definitely that fibrin forms the 

 basic proteins of these extracellular or collagen fibrils. ^^ These 

 results of Hertzler have been confirmed by Baitsell-^ and myself.^^ 



These observations indicate that the connective-tissue cells of the 

 body are not in any sense continuously active. Their only function 

 is the production of extracellular fibrils. They do not secrete these 

 fibers, but coagulate certain proteins formed elsewhere in the organ- 

 ism. The increase in these fibrils is alone indicative of an active 

 metabolism in them. The dynamic state of the organism is in no 

 sense, therefore, an elaboration of the dynamic state of these cells. 

 It must depend on other conditions. This led me to investigate more 

 carefully the process of rhythmical contraction as it is seen in heart- 

 muscle cells. 



In my earlier studies of the tissue culture I had already shown 

 that differentiation in heart muscle is a purely reversible phenome- 

 non.^^ The actively contracting heart-muscle cells are derived pri- 

 marily from the undifferentiated mesenchyme. When the fragments 

 of this tissue are brought into contact with the plasmatic medium of 

 the culture the heart-muscle cells at the edge of the fragment which 

 had been contracting lose this property at once. They migrate into 



