THE identity and potentialities of the stem cells of the bone marrow have formed the elusive subject of many discussions and hypotheses in haematological literature. The present communication attempts to deal with oiily a part of the problem: not with the identity of the stem cells, but with some aspects of their behaviour. Our purpose was to construct not merely a theoretical model, but one which could be tested experimentally.PRESENT STATUS OF STEM-CELL KINETICS 'The s t m i cells of the bone marrow are, by definition, the cells which can maintain their own numbers aiid give rise to differentiating cells. The latter may belong to the erythroid, niyeloid, or other series and may divide a number of times during the course of differentiationthey are, however, not self-maintaining, the process of differen.tiation resulting in end cells : erythrocytes or granulocytes.The mechanism by which the stem cells, the self-maintaining population, can maintain themselves and give rise to differentiating cells has intrigued many investigators. The earliest concept was that the stem cells can divide asymmetrically, one daughter cell remaining a stem cell, the other turning into a differentiating cell. Faster or slower rate of division would then result in a greater or smaller production of differentiating cells per unit time, the stemcell numbers remaining the same. It was Osgood who clearly realized that such a system could not recover from a repeated partial depopulation such as that due to radiation damage,: aiid hence he introduced the concept that stem cells can potentially undergo two kinds of division: the 'a-an' division, wh&h is the asymmetric division discussed above, and the 'a-2a' division which is a symmetric division of one stem cell into two stem cells. Under coiiditioiis of regeneration, absolute increase in stem-cell numbers is effected by a preponderance of the 'a-2a' division, whle steady state is maintained by a preponderance of the 'a-an' division (Osgood, 1957'a-an' division (Osgood, , 1959. Hence, it is iniplied that the cells caii choose between the two types of division on demand.Osgood's concept is undoubtedly capable of giving a statistical explanation of many observed phenomena. However, the actual mcchaiiism of the asymmetric 'a-ccn.' division and the rncchanism of changing from 'cx-ccn' division to 'a-2a' division are very difficult to imagine. The 'a-an' division would imply a non-self-reproducing structure which on division is retained in only one of the daughter cells (that which remains a stem cell) ; the 'a-2a' division, however, implies a possibility of reduplicating this structure, in order that it sliould be present in both daughter cells (both remaining, in this case, stem cells).This conceptual difficulty, and its lack of possibility of experimental proof, stimulated a search for an alternative system capable of experimental verification.
