168
E . N . W I L L M E R
sorts of cells, nor is there any explanation of how, in the few successful
instances, the difficulties of survival in isolation have been overcome.
Do fibroblasts differ so much amongst themselves that some are just
within the range of viability in isolation and are thus selected for
survival? Do certain cells mutate and become adaptable to the new
conditions? Are the few cells which do survive genuine mechanocytes,
or are they some contaminating cells, e.g. epithelial cells or the like?
Some form of adaptive or mutational change seems to be the most
likely in view of the reports by Sanford, Likely and Earle (1954) and
Earle (1957), that when two clones were established from the daughter
cells resulting from the division of an L-strain fibroblast, one of the
clones developed malignant characteristics while the other did not.
Thus, the nature of the "adaptation" which takes place in tissue and
cell cultures is by no means certain, and there are perhaps three possibilities worth considering. The individual cells could genuinely adapt
themselves to the new conditions; i.e. they could alter the nature of
their surfaces, cortical layers, mitochondria, etc., and perhaps produce
new enzymes more suited to the conditions. This might be called
"somatic mutation" and would be comparable to the sort of effects
which Raven (1961) has postulated as occurring in the ovary to impose
upon the ova the cortical and cytoplasmic qualities which will carry
them through early embryogenesis without much in the way of interference from the chromosomal mechanism.
Alternatively the culture as a whole could do the adapting by selection of the most favoured cell types originally present in the strain and
by the gradual elimination of the cells less suited to their new environment. This is selection of existing cell forms and may well apply to so
called pure strains and even to the establishment of clones, but cannot
apply to events occurring within a genuine clone.
Thirdly, there is the possibility of genetic mutation occurring in the
cells, perhaps, though by no means necessarily, hastened by the abnormal conditions of culture, and then the selection of the most favoured
mutants. When two strains originally derived from the same clone
show very different properties, it is very difficult to rule out the possibility of genetic adaptation by selection of some sort of mutation,
natural or induced; at the same time it should be remembered that it
is by no means necessarily genetic in the true sense; if, as Curtis (1960)
and Raven (1961) suppose the cell surface is a carrier of information,
the adaptation could be in the nature of the cell surfaces, and the
change could be handed on simply by the normal growth of the cell
surface during interkinesis and its subdivision during mitosis.
When the morphology and properties of the cells in strains which have
been isolated from fibroblasts are examined, it is quite clear that changes
E . N . W I L L M E R
sorts of cells, nor is there any explanation of how, in the few successful
instances, the difficulties of survival in isolation have been overcome.
Do fibroblasts differ so much amongst themselves that some are just
within the range of viability in isolation and are thus selected for
survival? Do certain cells mutate and become adaptable to the new
conditions? Are the few cells which do survive genuine mechanocytes,
or are they some contaminating cells, e.g. epithelial cells or the like?
Some form of adaptive or mutational change seems to be the most
likely in view of the reports by Sanford, Likely and Earle (1954) and
Earle (1957), that when two clones were established from the daughter
cells resulting from the division of an L-strain fibroblast, one of the
clones developed malignant characteristics while the other did not.
Thus, the nature of the "adaptation" which takes place in tissue and
cell cultures is by no means certain, and there are perhaps three possibilities worth considering. The individual cells could genuinely adapt
themselves to the new conditions; i.e. they could alter the nature of
their surfaces, cortical layers, mitochondria, etc., and perhaps produce
new enzymes more suited to the conditions. This might be called
"somatic mutation" and would be comparable to the sort of effects
which Raven (1961) has postulated as occurring in the ovary to impose
upon the ova the cortical and cytoplasmic qualities which will carry
them through early embryogenesis without much in the way of interference from the chromosomal mechanism.
Alternatively the culture as a whole could do the adapting by selection of the most favoured cell types originally present in the strain and
by the gradual elimination of the cells less suited to their new environment. This is selection of existing cell forms and may well apply to so
called pure strains and even to the establishment of clones, but cannot
apply to events occurring within a genuine clone.
Thirdly, there is the possibility of genetic mutation occurring in the
cells, perhaps, though by no means necessarily, hastened by the abnormal conditions of culture, and then the selection of the most favoured
mutants. When two strains originally derived from the same clone
show very different properties, it is very difficult to rule out the possibility of genetic adaptation by selection of some sort of mutation,
natural or induced; at the same time it should be remembered that it
is by no means necessarily genetic in the true sense; if, as Curtis (1960)
and Raven (1961) suppose the cell surface is a carrier of information,
the adaptation could be in the nature of the cell surfaces, and the
change could be handed on simply by the normal growth of the cell
surface during interkinesis and its subdivision during mitosis.
When the morphology and properties of the cells in strains which have
been isolated from fibroblasts are examined, it is quite clear that changes