Research on Tissue Culture at the National Cancer Institute, With Special Reference to the Contributions of Dr. Virginia J. Evan

Summary

Tissue culture at the National Cancer Institute (NCI) began with Wilton R. Earle's pioneering studies on spontaneous neoplastic transformation in vitro. Subsequently, the Tissue Culture Section, Laboratory of Biology, NCI, was established to continue investigation of this phenomenon. Quantitative procedures were developed for the propagation and analysis of cell populations in vitro. These advances paved the way for the monolayer systems now widely used for experimental studies. Investigations by Virginia J. Evans and her collaborators led to the formulation of protein-free, chemically defined media for progressive growth of mammalian cells in serial culture. The best known nutrient, NCTC 109 (later modified slightly as NCTC 135), supports growth of mouse, hamster, monkey, and human cells, after a variable period of adaptation. Studies with these chemically defined media offered a reference standardfor functional comparisons of normal and neoplastic cells, and for the detection of changes associated with the shift to malignancy. Serum factors in conjunction with chemically defined media may reinforce or suppress neoplastic transformation in cell cultures. A low-molecularweightfactor from stallion or gelding horse serum leads to early conversion; conversely, fetal calf serum or mare serum retards the onset of neoplastic change. The effect of serum factors seems indirect, since spontaneous neoplastic conversion of C3H mouse cells can take place in a serum-free chemically defined medium. In such a model system, the correlation of neoplastic transformation with altered biosynthetic patterns becomes a distinct posslbility.