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precursors supplied in the medium. Since it is now apparent that preformed protein per se does not play a necessary role in cellular nutrition,
it may reasonably be concluded that the essential amino acids, supplemented by glucose, salts, vitamins, and a few additional and as yet
unidentified dialyzable compounds, provide the cultured cell with all
the building blocks and energy sources necessary for its biosynthetic
processes.
It is not yet clear to what degree the biochemical activities of cultured
cells can safely be extrapolated to cells in vivo. Certain of their metabolic
characteristics may be associated with their ability to survive and grow
indefinitely under the special conditions of growth in vitro, at a rate
enormously greater than that observed in most tissues in vivo. Conversely, however, some of the functional activities of organized tissues
are known to disappear when cells deriving from those tissues are
propagated in dispersed cell culture.
Certain aspects of the cultured cell are relevant to this problem.
Some 80 °/o of the cell's weight is water, in which relatively large pools
of metabolites are dissolved. The constituents of this intracellular pool,
including both nutritionally essential compounds originating from the
medium, and metabolites synthesized by the cell, are in dynamic
equilibrium with the medium on the one hand, and with the cell's
macromolecules on the other (cf. p. 290). Under the usual conditions
of cell culture, there is an enormous disparity between the volume of
the medium and the volume of the intracellular water. In a population
of 250,000 cells/ml of medium, the ratio of the volume ofthe medium
to the volume of intracellular water is approximately 1000 : 1, and at
lower densities of populations the disparity is correspondingly greater.
This circumstance imposes on the cultured cell the necessity, as a
condition for survival and growth, of retaining a sufficient concentration
of all its necessary metabolites against loss to the medium.
In the following pages, a number of examples of apparent differences
in metabolic pattern between cells in vivo and in vitro are described.
In certain of these cases, it is clear that a special nutritional requirement
reflects the inability of the cultured cell to retain an adequate intracellular concentration of the compound in question, rather than any
fundamental alteration of its metabolic capacities. Other special biochemical characteristics of cultured cells are explicable on different
grounds, and again, no unusual metabolic capacities have been
demonstrated and only a few metabolic defects (cf. p. 289). While
the serially cultured cell may thus be considered to resemble the undifferentiated cell in vivo, this is probably a misleading analogy. The
process of "dedifferentiation" in culture apparently involves the loss,
perhaps irreversible, of enzymatic apparatus necessary for specialized
H A R R Y E A G L E A N D L E O N L E V I N T O W
precursors supplied in the medium. Since it is now apparent that preformed protein per se does not play a necessary role in cellular nutrition,
it may reasonably be concluded that the essential amino acids, supplemented by glucose, salts, vitamins, and a few additional and as yet
unidentified dialyzable compounds, provide the cultured cell with all
the building blocks and energy sources necessary for its biosynthetic
processes.
It is not yet clear to what degree the biochemical activities of cultured
cells can safely be extrapolated to cells in vivo. Certain of their metabolic
characteristics may be associated with their ability to survive and grow
indefinitely under the special conditions of growth in vitro, at a rate
enormously greater than that observed in most tissues in vivo. Conversely, however, some of the functional activities of organized tissues
are known to disappear when cells deriving from those tissues are
propagated in dispersed cell culture.
Certain aspects of the cultured cell are relevant to this problem.
Some 80 °/o of the cell's weight is water, in which relatively large pools
of metabolites are dissolved. The constituents of this intracellular pool,
including both nutritionally essential compounds originating from the
medium, and metabolites synthesized by the cell, are in dynamic
equilibrium with the medium on the one hand, and with the cell's
macromolecules on the other (cf. p. 290). Under the usual conditions
of cell culture, there is an enormous disparity between the volume of
the medium and the volume of the intracellular water. In a population
of 250,000 cells/ml of medium, the ratio of the volume ofthe medium
to the volume of intracellular water is approximately 1000 : 1, and at
lower densities of populations the disparity is correspondingly greater.
This circumstance imposes on the cultured cell the necessity, as a
condition for survival and growth, of retaining a sufficient concentration
of all its necessary metabolites against loss to the medium.
In the following pages, a number of examples of apparent differences
in metabolic pattern between cells in vivo and in vitro are described.
In certain of these cases, it is clear that a special nutritional requirement
reflects the inability of the cultured cell to retain an adequate intracellular concentration of the compound in question, rather than any
fundamental alteration of its metabolic capacities. Other special biochemical characteristics of cultured cells are explicable on different
grounds, and again, no unusual metabolic capacities have been
demonstrated and only a few metabolic defects (cf. p. 289). While
the serially cultured cell may thus be considered to resemble the undifferentiated cell in vivo, this is probably a misleading analogy. The
process of "dedifferentiation" in culture apparently involves the loss,
perhaps irreversible, of enzymatic apparatus necessary for specialized