THE ORIGIN OF THE PLANT TUMOR CELL 613 



altered in a 50-hour period required that the basic medium be supple- 

 mented with an auxin, glutamine, and meso inositol to achieve a 

 growth rate equal to that of the rapidly growing, fully transformed 

 tumor-cell type. These represented the minimum requirements neces- 

 sary for optimal growth. In addition to these three compounds, the very 

 slowly growing benign tumor cells transformed in a 34-hour period 

 required cytidylic acid for rapid growth in culture. 



These results clearly demonstrate, then, that as the crown-gall 

 tumor cell becomes more autonomous, its requirements in terms of ex- 

 ternally supplied growth factors become less exacting. They demon- 

 strate further that a series of well-defined but quite distinct growth- 

 substance-synthesizing systems gradually become activated, and the 

 degree of activation of these biosynthetic systems determines the rate 

 of growth of the tumor cell. 



Normal cells of the type from which the tumor cells were derived 

 do not grow on the basic medium. Thus, although, as indicated, the 

 difference between the three types of tumor cells is quantitative, the 

 difference between the tumor cell and the normal cell is qualitative. 

 One qualitative difference found to exist was the absolute requirement 

 of the normal cells for a factor normally limiting for cell division in 

 such cells. This requirement was satisfied by 6-furfurylaminopurine or 

 a naturally occurring equivalent of that substance. The normal cells, 

 unlike the tumor cells, also possessed an absolute requirement for an 

 external source of an auxin for their continued growth in culture. It 

 thus appears that, as a result of the transition from a normal cell to a 

 fully altered, rapidly growing crown-gall tumor cell, a series of quite 

 distinct but well-defined growth-substance-synthesizing systems be- 

 come progressively activated. This leads to the production by the 

 affected cells of greater than regulatory amounts of these growth- 

 promoting substances. The continued production of these substances 

 in greater than regulatory amounts by the tumor cell could and most 

 probably does account for the continued unregulated and autonomous 

 j^rowth of those cells. Thus autonomy, in this instance, finds its ex- 

 planation in terms of cellular nutrition. Precisely how the diverse bio- 

 synthetic systems become permanently activated, as a result of the 

 action of the tumor-inducing principle associated with this disease, re- 

 mains unanswered. 



The concept of growth autonomy presented above finds additional 

 support in other directions. It has been possible to reproduce, under 

 precisely defined experimental conditions and with the use of certain 

 normal cell types as the test object, not only the morphological growth 

 pattern but also the histological (hypertrophy, hyperplasia, leading to 

 disorganization and loss of function) as well as cytological (aberrant 

 nuclear behavior— multinuclear giant cells, etc.) events that character- 



