550 GROWTH IN TISSUE CULTURE D 



another. The question of the excitatory and inhibitory effects of one tissue upon 

 another, which was already a subject of much study before tissue cuhure was 

 extensively practiced, led Carleton (1923) to conclude that "many of the pheno- 

 mena of tissue culture would seem to fall into line with this conception of the 

 mutual dependence of tissues'". It is not quite so obvious from analogy with the 

 events of normal tissue behaviour in vivo that, not only unlike cells making up 

 distinct tissues, but also like cells, may interact. There is abundant evidence that 

 such mutual interaction plays an important part in the survival and growth of 

 cells in culture. With the question of mutual dependence is bound up the question 

 whether a tissue culture should be considered simply as a population of single 

 cell units, or whether the colony itself is more than the sum of its parts, i.e. whether 

 it can be thought of as a primitive "organism". There are those who regard the 

 cell as having no true autonomy, but as being inevitably dependent upon other 

 cells in its environment. Fischer (1946) has argued against the theory that the cell 

 is an elementary organism, and the organism a cell colony, because it had proved 

 impossible to induce cell division in single metazoan cells isolated in a medium 

 which, in amount and quality, was fully adequate for proliferation of a larger 

 number of similar cells. In his view, tissue cultures "must be regarded as regener- 

 ating tissue fragments, primitive cell states, or organism-like systems with strong 

 correlations, and not as colonies of independent cell individuals". There are those, 

 on the other hand, like Sinnott (1939), who emphasize the autonomy of the cell 

 which "on its own level . . .displays a unity of organization independent of the 

 organ above or the smaller units below". Both of these apparently contrary views 

 contain part of the trvith. Cell clones can now be obtained from single cells, as 

 will be described below, but these are "colonies of independent cell individuals" 

 only in the sense that each cell can become, under very stringent conditions, the 

 parent of a new colony. Independence is relative — there is no doubt that a single 

 isolated cell requires much more exacting conditions in order to survive or divide 

 than the same cell in the presence of a large number of other cells. If, as Weiss 

 has argued, cells can live only in the presence of the products of their own (or 

 of other adjacent cell) secretions, the independence of the cell is to that extent 

 limited. 



Homogeneous suspensions, not dissimilar in behaviour to yeast or protozoan 

 cultures, can be cultivated from metazoan cells. The most uniform cultures of 

 this type are those derived as clones from single cells. But explants of most kinds 

 of tissue, particularly those containing more than one cell type, are apt to have 

 some degree of overall organization in culture. Abercrombie and Heaysman (1953) 

 considered the colony obtained from fresh explants of chick embryo heart as an 

 "organism" and, taking the cell as the unit, studied the "social behaviour" of the 

 cells, in particular the question of how cell movement is influenced by the prox- 

 imity of other cells. Individual cell velocity was found to fluctuate considerably 

 during an observation period of several hours. Cells in established contact with 

 others have a reduced velocity, and detachment of one cell from another is asso- 

 ciated with acceleration of movement. A positive "contact-inhibition" was also 

 postulated (Abercrombie and Heaysman, 1954a), causing the fibroblasts to move 

 preferentially into unpopulated areas rather than over the surface of other cells. This 



