"The critical role of the nucleolus in cell differentiation and stem cell development - the concept as it applies to the malignant cell.".

Whereas growth prior to organ formation in the embryo is by replication of primitive cells, growth subsequent to organ formation is assumed to be due to replication of differentiated cells. The replication of both primitive cells and differentiated cells is said to conform to the classical mitotic cycle. But the cycle does not show how differentiation takes place, and to remedy this an alternative cycle incorporating clonal division is postulated. In order to explain malignant growth on the basis of the mitotic cycle, traditionalists have had to introduce the concept of dedifferentiation but the concept does not quite stand up to a critical analysis. Malignant change appears to be due to a nucleolar fault rather than a chromosomal one, and the behaviour of the malignant cell in adenocarcinoma of the lung confirms this. Smears made from the tumour mass indicate that the malignant stem cells are transformed into "specialised cells" by the same process of clonal division as already postulated for normal tissue growth. The presence of differentiating cells in adenocarcinoma greatly lessens the likelihood of dedifferentiation playing a part in malignancy. On the other hand, the presence of abnormal stem cells with bizarre nucleoli strengthens the case for malignancy being due primarily to a nucleolar fault.