8
E . N . W I L L M E R
In the investigations which were being pursued on metabolism and
growth, the small volume of medium and its inadequate equilibration
with the tissue fragments in Carrel flasks prompted Gey and his coworkers in Baltimore in 1933 to develop the roller tube, in which more
tissue could be planted in an equivalent space, more medium used and
more control exercised over its composition on account of the constant
mixing. This simple step, taken some eleven years after the stationary
Carrel flask was introduced, has since led to the almost complete
obsolescence of the original method and has turned out to be the
initiator of a whole new series of investigations, including among others
the investigation and determination of the nucleoprotein content of
growing cells, thus allowing estimates of biochemical activity to be
placed on a "per cell" basis without the necessity, except for checking
purposes, of actually counting the cells present.
Practically all the techniques developed up to the beginning of the
Second World War depended on the use of pieces of tissue cultured in
plasma, serum, embryo juice or other "natural" medium. As it was,
at that time, extremely difficult to measure the amounts of tissue being
used and because such "natural" media have so many unknown and
indeterminate features, it is not surprising that the knowledge of cell
metabolism in cultures increased but slowly. In fact, Tissue Culture lay
becalmed in the doldrums for a time. T w o things seemed to be required. These were, firstly, more standardized and uniform populations
of cells (i.e. pure strains like those used by the bacteriologists), and,
secondly, the replacement of natural media by those of known and
chemically defined composition.
In the last twenty years, and largely as the result of the germination
of seeds sown many years earlier, both these ends have been in large
measure achieved. Mass-cultures of cells, comparable in many ways
with bacterial cultures, can now be grown in chemically defined,
"synthetic" media, and many strains of cells have been established,
some of which are strict clones, having been derived from single cells.
It is, however, unfortunately true to say that some of these strains,
though perhaps pure in themselves, have in fact turned out, upon
immunological and other tests, to be not what they were thought to be;
and this is a finding which casts a sinister shadow over this whole field
of investigation. It must also be confessed that, on other grounds also,
the promised goals have proved to be somewhat illusory; for example,
from a biochemical point of view, the cells in pure strains have turned
out to be surprisingly uniform in character and very different from the
cells from which they were derived in the body. In other respects,
however, which were probably less foreseen in the beginning, the results
have been of the very greatest practical value, namely in virus research.
E . N . W I L L M E R
In the investigations which were being pursued on metabolism and
growth, the small volume of medium and its inadequate equilibration
with the tissue fragments in Carrel flasks prompted Gey and his coworkers in Baltimore in 1933 to develop the roller tube, in which more
tissue could be planted in an equivalent space, more medium used and
more control exercised over its composition on account of the constant
mixing. This simple step, taken some eleven years after the stationary
Carrel flask was introduced, has since led to the almost complete
obsolescence of the original method and has turned out to be the
initiator of a whole new series of investigations, including among others
the investigation and determination of the nucleoprotein content of
growing cells, thus allowing estimates of biochemical activity to be
placed on a "per cell" basis without the necessity, except for checking
purposes, of actually counting the cells present.
Practically all the techniques developed up to the beginning of the
Second World War depended on the use of pieces of tissue cultured in
plasma, serum, embryo juice or other "natural" medium. As it was,
at that time, extremely difficult to measure the amounts of tissue being
used and because such "natural" media have so many unknown and
indeterminate features, it is not surprising that the knowledge of cell
metabolism in cultures increased but slowly. In fact, Tissue Culture lay
becalmed in the doldrums for a time. T w o things seemed to be required. These were, firstly, more standardized and uniform populations
of cells (i.e. pure strains like those used by the bacteriologists), and,
secondly, the replacement of natural media by those of known and
chemically defined composition.
In the last twenty years, and largely as the result of the germination
of seeds sown many years earlier, both these ends have been in large
measure achieved. Mass-cultures of cells, comparable in many ways
with bacterial cultures, can now be grown in chemically defined,
"synthetic" media, and many strains of cells have been established,
some of which are strict clones, having been derived from single cells.
It is, however, unfortunately true to say that some of these strains,
though perhaps pure in themselves, have in fact turned out, upon
immunological and other tests, to be not what they were thought to be;
and this is a finding which casts a sinister shadow over this whole field
of investigation. It must also be confessed that, on other grounds also,
the promised goals have proved to be somewhat illusory; for example,
from a biochemical point of view, the cells in pure strains have turned
out to be surprisingly uniform in character and very different from the
cells from which they were derived in the body. In other respects,
however, which were probably less foreseen in the beginning, the results
have been of the very greatest practical value, namely in virus research.