POTENTIAL IMMORTALITY OF TISSUES 193 



fibrous stroma. The primary degenerative changes in the parenchyma may 

 stimulate the connective tissue or glia to increased activity. These changes in 

 the stroma impair still more the preservation and functioning of the 

 parenchyma, which then may undergo further degeneration. 



However, if we select very closely inbred strains of mice, where all the 

 individuality differentials approach the character of autogenous differentials — 

 although this state has not yet been completely attained — the prospects of a 

 successful serial transplantation even of whole organs such as thyroid gland 

 are greatly improved. Moreover, in the mouse the host cells, whose function 

 it is to attack the tissues possessing strange differentials, are often less active 

 than they are in rat and guinea pig. Hence it has been possible in our experi- 

 ments to prolong the life of serially transplanted organs beyond the usual 

 length of life of the mouse, and there are indications that it may be possible, 

 by carrying out serial transplantations in closely inbred strains, to keep alive 

 and growing indefinitely not only cells which are more or less independent of 

 each other, such as connective tissue cells, but also whole organs. 



The potential immortality of mammalian cells has then so far been demon- 

 strated by two methods, in both of which the cells are subjected to unceasing, 

 intensified growth stimulation — namely (1) the serial transplantation of 

 tumors and (2) the continued transfer of cells in tissue culture. In the first 

 method specific tumor stimuli, and in the latter stimuli characteristic of 

 regenerative and embryonal growth are active. The constant renewal of the 

 cells by mitosis, under the influence of these stimuli, prevents undue dif- 

 ferentiation and production of paraplastic substances, which would injure the 

 cells and in the end prematurely destroy them. Cells which have gained in 

 differentiation beyond a certain limit and, correspondingly, lost in the power 

 of propagation, such as ganglia cells or certain leucocytes, either slowly 

 undergo gradual atrophy or degenerative processes or they die at an early pe- 

 riod. Cells which, as a result of processes of differentiation, have lost, not yet 

 entirely but to a certain degree, their power of propagation, undergo abnormal 

 changes of further differentiation when acted upon by growth stimuli origi- 

 nating from the outside or within the cells themselves. The same process 

 may therefore function both as growth stimulator and, in a certain sense, also 

 as differentiator of cells, if it acts on a cellular substratum in which an in- 

 termediate degree of differentiation has taken place. Eut, as stated, if the 

 differentiation has reached a further advanced stage, growth stimuli may 

 induce alterations in the cell equilibrium so great that they lead to cell death, 

 which thus represents the endstage of the differentiating process. 



While both methods, which have been used so far for the demonstration 

 of the potential immortality of tissues of higher organisms, require the 

 constant action of growth-promoting factors, there remains the possibility 

 that certain organs, such as the thyroid gland, in which the units composing 

 the organ are closed cell complexes, forming acini or similar structures, 

 may through well-timed serial transplantation be kept alive indefinitely, 

 without a very active cell proliferation taking place. This can, however, be 

 accomplished only if the individuality differentials of the host and transplant 



