10
E . N . W I L L M E R
rapidly after such treatment. A few years later, in the course of some
investigations on the practicability (or as it turned out, the impracticability) of using tryptic digestion to remove damaged tissue from burns
and other wounds in the Second World War, Willmer made successful
cultures from suspensions of cardiac muscle cells, liver and skin cells
obtained by the action of trypsin on these tissues. About the same time
Medawar (1941) used tryptic digestion to separate epidermis from
dermis in connexion with grafting procedures for wound-healing. It
was not, however, till about ten more years had elapsed that the use of
trypsin as a means of dispersing viable cells from their parent tissues was
developed as a reliable and practical method by Moscona and Moscona
(1952). With the publication of their methods a new era was initiated
and with it much of the modern procedure of growing viruses on sheets
of cultured cells. The Mosconas (1952) demonstrated the almost perfect
viability of embryonic cells when separated from organ and tissue
rudiments, by digestion with trypsin in a Ca++- and M g
+ +
- free
medium, and resuspended in dilute serum. Once again, the seeds for
this last step had been sown more than fifty years earlier when Herbst
(1900) noticed that if the blastulae of echinoderms were suspended in
calcium-free sea-water the blastomeres separated and fell apart.
Rinaldini (1954, 1958), Dulbecco (1952) and Younger (1954) quickly
applied these techniques developed by the Mosconas to the quantitative
growth of cells and to the preparation of monolayers of cells for use in
virus research.
In theory, synthetic media and isolated cells should provide ideal
starting points for all manner of investigations on cellular activity in its
great diversity and the future might now seem to be full of promise for
enormous advances in our understanding of matters which, not many
years ago, seemed to be quite beyond our reach. Nevertheless, while it
is true that the prospect is certainly vast and exciting in its potentialities
there are still some very fundamental difficulties to be overcome.
It is perhaps of some historical interest to note that while this story
had its beginning with Claude Bernard, who was, as we have seen,
primarily responsible for the use of trypsin in the separation of cells, it
is also appropriate to close it with another reference to this great
French physiologist. T o him, of course, we owe the whole concept of the
constant internal environment whose properties and characteristics we
are at pains to repeat in the medium every time we set up tissue
cultures, but, ironically enough, it is Tissue-Culture studies that have
perhaps done more than any others to emphasize an important modification of Claude Bernard's original concept, which at first sight seems
to some extent to falsify the original concept. Tissue cultures emphasize
the existence of not one constant environment for all cells but rather the
E . N . W I L L M E R
rapidly after such treatment. A few years later, in the course of some
investigations on the practicability (or as it turned out, the impracticability) of using tryptic digestion to remove damaged tissue from burns
and other wounds in the Second World War, Willmer made successful
cultures from suspensions of cardiac muscle cells, liver and skin cells
obtained by the action of trypsin on these tissues. About the same time
Medawar (1941) used tryptic digestion to separate epidermis from
dermis in connexion with grafting procedures for wound-healing. It
was not, however, till about ten more years had elapsed that the use of
trypsin as a means of dispersing viable cells from their parent tissues was
developed as a reliable and practical method by Moscona and Moscona
(1952). With the publication of their methods a new era was initiated
and with it much of the modern procedure of growing viruses on sheets
of cultured cells. The Mosconas (1952) demonstrated the almost perfect
viability of embryonic cells when separated from organ and tissue
rudiments, by digestion with trypsin in a Ca++- and M g
+ +
- free
medium, and resuspended in dilute serum. Once again, the seeds for
this last step had been sown more than fifty years earlier when Herbst
(1900) noticed that if the blastulae of echinoderms were suspended in
calcium-free sea-water the blastomeres separated and fell apart.
Rinaldini (1954, 1958), Dulbecco (1952) and Younger (1954) quickly
applied these techniques developed by the Mosconas to the quantitative
growth of cells and to the preparation of monolayers of cells for use in
virus research.
In theory, synthetic media and isolated cells should provide ideal
starting points for all manner of investigations on cellular activity in its
great diversity and the future might now seem to be full of promise for
enormous advances in our understanding of matters which, not many
years ago, seemed to be quite beyond our reach. Nevertheless, while it
is true that the prospect is certainly vast and exciting in its potentialities
there are still some very fundamental difficulties to be overcome.
It is perhaps of some historical interest to note that while this story
had its beginning with Claude Bernard, who was, as we have seen,
primarily responsible for the use of trypsin in the separation of cells, it
is also appropriate to close it with another reference to this great
French physiologist. T o him, of course, we owe the whole concept of the
constant internal environment whose properties and characteristics we
are at pains to repeat in the medium every time we set up tissue
cultures, but, ironically enough, it is Tissue-Culture studies that have
perhaps done more than any others to emphasize an important modification of Claude Bernard's original concept, which at first sight seems
to some extent to falsify the original concept. Tissue cultures emphasize
the existence of not one constant environment for all cells but rather the