IV. ACTION
OF MORPHOSTATIC
SUBSTANCES
185
expected in order to support mitosis and growth. The development of
this morphogenetic system of the hyaloplasm precedes, in each system
capable of growth or mitosis, the actual phenomena of growth and
mitosis. Swann (1957) has created the term 'reservoir' to include all the
biochemical compounds which have to be present before mitosis can
start.
It seems to be characteristic of morphostatic substances or efficient
antimitotic substances that they interfere with the partial processes
which are essentially involved in the development of the morphogenetic
hyaloplasm or the biochemical reservoir. It seems to be conceivable that
synergistic combinations are better able than single substances to
interfere with the development of the complex system of morphogenetic
cytoplasm. In growing tissues or in a tumour it may then happen that in
optimal cases growth and mitosis may be suppressed selectively at the
same time. Two sectors of metabolism seem to play the main supporting
role: the metabolism of proteins and the metabolism of purines. Several
workers have tried to interfere with the metabolism of purines by
antimetabolites which were expected to act as antimitotic substances
and suppressors of malignant growth at the same time (Biesele, 1958).
The success in this direction was not too convincing because no one had
taken into account the requirements of protein metabolism. The firsi
results with antagonists of purines induced several workers, to investigate
tumour inhibition simply by mitotic poisoning. Although these experiments did not give spectacular results they produced partial effects of
considerable interest in tumour biology.
The protein metabolism, which is unfortunately at present not so well
known, shows a very different situation. There is a greater relationship
between proteins and morphogenesis than is generally supposed. The
protein content of tissues seems to be an important factor in larval
tissues. Such tissues are more ready for mitosis if their protein content
has been increasing, whereas decrease of proteins by starvation inhibits
mitotic activity. However, starvation and protein regression are not
absolute antagonists of growth and of a high morphogenetic potential.
It is first necessary to shift the central tendency of the morphogenetic
potential so that breakdown of proteins takes place instead of synthesis.
If the degradation of proteins is dominating in the whole system, a
failure of growth and a suppression of mitotic activity is to be expected
to occur in the hyaloplasm of all cells involved. In this situation however
all other stimuli coming from outside have to be kept away from such a
deficient system.
If experimental factors can be found which induce, in a tumour, a
dominance of protein degradation over protein synthesis, then the
essential basis for an increase of the cytoplasm of tumour cells and also
OF MORPHOSTATIC
SUBSTANCES
185
expected in order to support mitosis and growth. The development of
this morphogenetic system of the hyaloplasm precedes, in each system
capable of growth or mitosis, the actual phenomena of growth and
mitosis. Swann (1957) has created the term 'reservoir' to include all the
biochemical compounds which have to be present before mitosis can
start.
It seems to be characteristic of morphostatic substances or efficient
antimitotic substances that they interfere with the partial processes
which are essentially involved in the development of the morphogenetic
hyaloplasm or the biochemical reservoir. It seems to be conceivable that
synergistic combinations are better able than single substances to
interfere with the development of the complex system of morphogenetic
cytoplasm. In growing tissues or in a tumour it may then happen that in
optimal cases growth and mitosis may be suppressed selectively at the
same time. Two sectors of metabolism seem to play the main supporting
role: the metabolism of proteins and the metabolism of purines. Several
workers have tried to interfere with the metabolism of purines by
antimetabolites which were expected to act as antimitotic substances
and suppressors of malignant growth at the same time (Biesele, 1958).
The success in this direction was not too convincing because no one had
taken into account the requirements of protein metabolism. The firsi
results with antagonists of purines induced several workers, to investigate
tumour inhibition simply by mitotic poisoning. Although these experiments did not give spectacular results they produced partial effects of
considerable interest in tumour biology.
The protein metabolism, which is unfortunately at present not so well
known, shows a very different situation. There is a greater relationship
between proteins and morphogenesis than is generally supposed. The
protein content of tissues seems to be an important factor in larval
tissues. Such tissues are more ready for mitosis if their protein content
has been increasing, whereas decrease of proteins by starvation inhibits
mitotic activity. However, starvation and protein regression are not
absolute antagonists of growth and of a high morphogenetic potential.
It is first necessary to shift the central tendency of the morphogenetic
potential so that breakdown of proteins takes place instead of synthesis.
If the degradation of proteins is dominating in the whole system, a
failure of growth and a suppression of mitotic activity is to be expected
to occur in the hyaloplasm of all cells involved. In this situation however
all other stimuli coming from outside have to be kept away from such a
deficient system.
If experimental factors can be found which induce, in a tumour, a
dominance of protein degradation over protein synthesis, then the
essential basis for an increase of the cytoplasm of tumour cells and also