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C H A R I T Y W A Y M O U T H
I I . D E S I G N OF C O M P L E T E S Y N T H E T I C M E D I A
The degree of complexity of a medium, that is the number of components necessary to make it complete, bears an inverse relation to
the synthetic capabilities of the cells for which it is designed. Cells
equipped with a very full range of enzymes, and capable of building
up all the components of their substance (including their own enzymatic
and genetic apparatus) from inorganic salts and simple carbon and
nitrogen sources, can be sustained upon very simple media. Microorganisms which have this equipment are able to grow in media of
minimal complexity. The division of labour which has accompanied
diversification of function in the cells and tissues of higher organisms
has restricted the capacities of cells in diverse ways. It is this fact that
makes the design of synthetic media for the cells of higher animals a
problem of relative complexity, and one which, moreover, had to
await solution until the major and most of the minor nutrients needed
by whole animals had been chemically identified and the composition
of cells themselves had been fairly completely worked out.
It was a fortunate historical circumstance that, at the time when
metabolic cycles were being elucidated, pioneer work on the nutrition
of the tissues of higher plants was being carried out (White, 1934;
Gautheret, 1934). The isolated tissues, roots or cambium, of these
plants conveniently fall in between the metabolically highly efficient
micro-organisms, and the highly dependent and interdependent cells
of vertebrate animals, in the complexity of their nutritional needs.
Thus, White demonstrated that tomato roots could subsist and multiply
indefinitely in a medium containing only salts, sucrose, glycine, thiamine, nicotinic acid and pyridoxine. At this time, i.e. thirty years ago,
indefinite multiplication of animal cells was only feasible in biological
media, and the commonly accepted view was that protein, nucleic
acids and other macromolecular substances were essential components
of media for animal cell nutrition. The fact that these plant cells could
derive everything necessary for long-continued proliferative growth
from simple, chemically known molecules certainly influenced White
(1946) himself, and probably others also, in their attempts to apply
the same principles to the more difficult case of animal cells.
If the approach to synthetic nutrients for animal cells was influenced
by the parallel work on plant cells, it was certainly also affected by
advances in knowledge of the nutrition of whole animals. A major
advance in animal nutrition which led to new thinking about nutrition
at the cell level was represented by the demonstration that rats could
be maintained in nitrogen balance if the protein of the diet was re-
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