1. I N T R O D U C T I O N
11
constancy of many different environments which are enjoyed by the
various cells and tissues of the body. In cell cultures, and more particularly in tissue and organ cultures, "one man's meat is another man's
poison" and "chacun a son gout" are the guiding principles; indeed,
the environment of every cell, and almost every part of every cell, is
different from that of every other. Thus cells have their own microenvironments. The body as a whole, by the integrated action of all its
organs, keeps a fluid circulating which is so strictly regulated as to be
effectively constant, and because of this unifying fluid the immediate
local environment of each and every cell is enabled to be kept similarly
constant, though different from that of other cells. The internal environment, as first envisaged by Bernard, may therefore be regarded as much
more constant in time than in space; the modern concept is to split up
the single internal environment into innumerable localized cellular or
micro-environments, which though differing from each other, are
integrated and kept, individually, as nearly constant as possible by
their relationship with a circulating fluid of controlled and regulated
temperature and composition. If we provide all the cells of a culture
with the same environment, strains of rather uniform cells are produced.
If we allow local environments to develop and to persist, as in organ
cultures, then we encourage differentiation and function.
Some interesting new aspects of the mass culture of cells arise from
the observation that, contrary to what had been previously supposed,
some cells at least are capable of living and multiplying like bacteria,
when kept actually suspended in a stirred fluid medium and unattached
to any substrate. The early cultures from cell suspensions, which were
obtained either mechanically or with the aid of trypsin, and many
successful cell-lines derived from them, were made by allowing the cells
to settle down on the bottoms of flat flasks or Roux bottles; and this
settling of the cells was regarded as a necessary part of the procedure.
Now, however, large populations of certain types of cells, e.g. strain-L
mouse-fibroblasts (Earle, Schilling, Bryant and Evans, 1954) and
lymphoblasts (Owens, Gey and Gey, 1954) have been kept in a state of
growth as actual suspensions in large gyrating flasks, in shaker flasks or
in tumbler tubes for a very considerable time. The strain-L cells can be
continuously propagated in this way in a purely synthetic medium
(Evans et al., 1956; Waymouth, 1956). Such cultures can thus provide
masses of free-living cells for experimental purposes; though perhaps
one should not enquire too closely about the exact nature of these cells,
nor to what cells in the body they correspond (see pp. 66, 170).
These developments of massed cell culture, by one method or
another, have been responsible for many new techniques for growing
and titrating viruses and have thus been of inestimable value, not only
11
constancy of many different environments which are enjoyed by the
various cells and tissues of the body. In cell cultures, and more particularly in tissue and organ cultures, "one man's meat is another man's
poison" and "chacun a son gout" are the guiding principles; indeed,
the environment of every cell, and almost every part of every cell, is
different from that of every other. Thus cells have their own microenvironments. The body as a whole, by the integrated action of all its
organs, keeps a fluid circulating which is so strictly regulated as to be
effectively constant, and because of this unifying fluid the immediate
local environment of each and every cell is enabled to be kept similarly
constant, though different from that of other cells. The internal environment, as first envisaged by Bernard, may therefore be regarded as much
more constant in time than in space; the modern concept is to split up
the single internal environment into innumerable localized cellular or
micro-environments, which though differing from each other, are
integrated and kept, individually, as nearly constant as possible by
their relationship with a circulating fluid of controlled and regulated
temperature and composition. If we provide all the cells of a culture
with the same environment, strains of rather uniform cells are produced.
If we allow local environments to develop and to persist, as in organ
cultures, then we encourage differentiation and function.
Some interesting new aspects of the mass culture of cells arise from
the observation that, contrary to what had been previously supposed,
some cells at least are capable of living and multiplying like bacteria,
when kept actually suspended in a stirred fluid medium and unattached
to any substrate. The early cultures from cell suspensions, which were
obtained either mechanically or with the aid of trypsin, and many
successful cell-lines derived from them, were made by allowing the cells
to settle down on the bottoms of flat flasks or Roux bottles; and this
settling of the cells was regarded as a necessary part of the procedure.
Now, however, large populations of certain types of cells, e.g. strain-L
mouse-fibroblasts (Earle, Schilling, Bryant and Evans, 1954) and
lymphoblasts (Owens, Gey and Gey, 1954) have been kept in a state of
growth as actual suspensions in large gyrating flasks, in shaker flasks or
in tumbler tubes for a very considerable time. The strain-L cells can be
continuously propagated in this way in a purely synthetic medium
(Evans et al., 1956; Waymouth, 1956). Such cultures can thus provide
masses of free-living cells for experimental purposes; though perhaps
one should not enquire too closely about the exact nature of these cells,
nor to what cells in the body they correspond (see pp. 66, 170).
These developments of massed cell culture, by one method or
another, have been responsible for many new techniques for growing
and titrating viruses and have thus been of inestimable value, not only