13. D I F F E R E N T I A T I O N
465
the enormously sharpened and deepened perception possible with the
electron microscope—which is making ever clearer the fact that significant structure is function viewed in a single time plane. Morphological
criteria fell into disrepute in the early period of tissue culture when it
was found that the shape, size, granule content, staining reactions, etc.
of cells were altered readily in culture without any seeming change in
fundamental properties. One of the disappointments ofthe first stage of
tissue culture was the inability to maintain the abstract pattern of shapes
and colors familiar to the classical morphologists who viewed stained
sections of fixed tissues. Fear was expressed that the cultures—rather
than the slides—were artifacts. When the culturists were able to
convince themselves that their morphologically simplified cells preserved at least some original properties, and hence were not complete
"artifacts", they turned on morphology and virtually eliminated it as a
useful criterion for judging differentiation in culture. It remains true
today that culture and cell morphology are slippery ground on which
to evaluate differentiation, particularly in those marginal cases where
the application of critical criteria is most needed. But it is also true that
the recognition of characteristic striated fibers, for example, is one of
the most certain—and frequently most convenient—diagnoses of muscle
differentiation. Moreover, the possibility of much more precise ultrastructural characterization of differentiation has already risen above the
horizon. It must be kept in mind that morphological criteria are to be
used with caution and discrimination, but that they frequently are
extremely convenient and useful for wide-range recognition of differentiation in its franker forms. Their special power comes in their
applicability to individual cells, and parts of cells, and in the fact that
by detecting as a single product the resultant of multiple processes they
are convenient screening procedures for subtle irregularity in any of the
multiple contributors. This is particularly well seen where mutation
alters the morphology of differentiated cells, e.g. in sickle cell anemia or
in inherited retinal dystrophy which Sidman (1961) has been examining
in vitro.
The uncertainties of morphological identification turned the attention of pioneer tissue culturists toward "more fundamental" functional
characteristics. At the level of analysis possible in the first several
decades of tissue culture this meant concentration on behaviorally
obvious functions, i.e. cell migration, contractility, adhesiveness, clot
digestion, conduction, etc. In special instances, the contractility of
heart muscle for example, behavioral characteristics were extremely
useful and made certain tissues favorite objects of study. In general,
however, it has become clear that behavioral characteristics of specialized cell types are little more persistent than morphological ones.
465
the enormously sharpened and deepened perception possible with the
electron microscope—which is making ever clearer the fact that significant structure is function viewed in a single time plane. Morphological
criteria fell into disrepute in the early period of tissue culture when it
was found that the shape, size, granule content, staining reactions, etc.
of cells were altered readily in culture without any seeming change in
fundamental properties. One of the disappointments ofthe first stage of
tissue culture was the inability to maintain the abstract pattern of shapes
and colors familiar to the classical morphologists who viewed stained
sections of fixed tissues. Fear was expressed that the cultures—rather
than the slides—were artifacts. When the culturists were able to
convince themselves that their morphologically simplified cells preserved at least some original properties, and hence were not complete
"artifacts", they turned on morphology and virtually eliminated it as a
useful criterion for judging differentiation in culture. It remains true
today that culture and cell morphology are slippery ground on which
to evaluate differentiation, particularly in those marginal cases where
the application of critical criteria is most needed. But it is also true that
the recognition of characteristic striated fibers, for example, is one of
the most certain—and frequently most convenient—diagnoses of muscle
differentiation. Moreover, the possibility of much more precise ultrastructural characterization of differentiation has already risen above the
horizon. It must be kept in mind that morphological criteria are to be
used with caution and discrimination, but that they frequently are
extremely convenient and useful for wide-range recognition of differentiation in its franker forms. Their special power comes in their
applicability to individual cells, and parts of cells, and in the fact that
by detecting as a single product the resultant of multiple processes they
are convenient screening procedures for subtle irregularity in any of the
multiple contributors. This is particularly well seen where mutation
alters the morphology of differentiated cells, e.g. in sickle cell anemia or
in inherited retinal dystrophy which Sidman (1961) has been examining
in vitro.
The uncertainties of morphological identification turned the attention of pioneer tissue culturists toward "more fundamental" functional
characteristics. At the level of analysis possible in the first several
decades of tissue culture this meant concentration on behaviorally
obvious functions, i.e. cell migration, contractility, adhesiveness, clot
digestion, conduction, etc. In special instances, the contractility of
heart muscle for example, behavioral characteristics were extremely
useful and made certain tissues favorite objects of study. In general,
however, it has become clear that behavioral characteristics of specialized cell types are little more persistent than morphological ones.