One of the significant, recent studies of malignant neoplasms has been a series of animal experiments by Fidler and associates [1, 2] who have shown that in the primary neoplasm of the long-established mouse melanoma there are subpopulations of cells differing in metastatic capability. By subculture and cloning techniques these authors were able to isolate clones with varying metastatic potential from the primary tumor, some with low, others with very high and still others with intermediate ability to metastasize.

These studies showed that in spite of the different clones present in the primary neoplasms there was present in the primary tumor a stability which gave it a distinctive behavioral characteristic. When the equilibrium of the population of clones in the tumor was disturbed, eg, as might happen with progression of the tumor, or clinical therapy, destruction of one or more populations of cells might lead to the growth and expansion of other clones. Genetic instability and mutation may have been responsible for the emergence of new clones, as postulated earlier by Nowell in the progression of leukemias [3].