LIFE OUTSIDE OF ORGANISM CARREL AND BURROWS. 581 



and when all its parts are active, the culture medium becomes pro- 

 gressively modified and undergoes after some time a partial liquefac- 

 tion, or it becomes opaque, and the fibrin becomes more apparent. 

 The rapidly growing organs, like the kidney, the liver, and occa- 

 sionally the thyroid, bring about early modifications of the culture 

 medium, while the slowly growing tissues modify it very slightly. 

 After three or four days, the plasma of a culture of sarcoma or of 

 fetal kidney undergoes often a marked retraction. But the plasma 

 of a culture of peritoneum or of cartilage may be, after 18 days, in 

 perfect condition. 



3. The diminution in the rate of the proliferation of the cells and 

 the death of the culture depend in a large measure on the condition 

 of the culture medium. Death is preceded by a period of slow 

 growth, during which larger granulations appear within the cells. 

 The cellular outline becomes less sharp. Afterwards, the disinte- 

 gration occurs and the cells appear as small spherical bodies. The 

 length of life of the tissues can be increased by secondary and ter- 

 tiary cultures. The new cells can also be transplanted in a new cul- 

 ture medium. If a culture of malignant tumor is grafted under the 

 skin of one animal it may grow and produce a new tumor. Frag- 

 ments of this tumor can be cultivated in vitro and grafted after- 

 wards to another animal. The duration of the life of the cultures is 

 increased by the procedures which permit of giving to the tissue an 

 almost normal nutrition. 



IV. APPLICATIONS. 



The method of cultivating tissues outside of the organism has 

 already permitted Harrison to demonstrate that the nerve fibers 

 are really an outgrowth from a central neurone. But it can be 

 applied also to many other problems. We have already used it in 

 studying the characters of growth of malignant tumor, of the growth 

 of normal tissues, and the laws of their redintegration. 



Experimental and spontaneous malignant tumors grow easily in 

 vitro. Fragments of Rous sarcoma or of Ehrlich sarcoma grow 

 often very rapidly in the plasmatic media. In less than 48 hours the 

 cells cover a large area. Therefore the modifications in the rate of 

 growth brought about by the action of different kinds of plasma or 

 by the substances artificially placed in the culture medium can be 

 studied easily. It is possible also to study the reactions of normal 

 tissues toward the plasma of animals bearing a tumor. The results 

 of the experiments can be controlled by grafting into animals the 

 tissues produced in vitro. It can show whether the tissues have under- 

 gone, during their life outside of the organism, dynamic changes, 

 which persist when they are given back their normal condition of 

 growth inside of the organism. 



