Physiology of Development [in German, _Entwicklungsmechanik_ (W. Roux),
_Entwicklungsphysiologie_ (H. Driesch), _physiologische Morphologie_ (J.
Loeb)] is, in the broadest meaning of the word, the experimental science
of morphogenesis, i.e. of the laws that govern morphological
differentiation. In this sense it embraces the study of regeneration and
variation, and would, as a whole, best be called rational morphology.
Here we shall treat of the Physiology of Development in a narrower
sense, as the study of the laws that govern the development of the adult
organism from the egg, REGENERATION and VARIATION AND SELECTION forming
the subjects of special articles.
After the work done by W. His, A. Goette and E.F.W. Pfluger, who gave a
sort of general outline and orientation of the subject, the first to
study developmental problems properly in a systematical way, and with
full conviction of their great importance, was Wilhelm Roux. This
observer, having found by a full analysis of the facts of "development"
that the first special problem to be worked out was the question when
and where the first differentiation appeared, got as his main result
that, when one of the two first blastomeres (cleavage cells) of the
frog's egg was killed, the living one developed into a typical
half-embryo, i.e. an embryo that was either the right or the left part
of a whole one. From that Roux concluded that the first cleavage plane
determined already the median plane of the adult; and that the basis of
all differentiation was given by an unequal division of the nuclear
substances during karyokinesis, a result that was also attained on a
purely theoretical basis by A. Weismann. Hans Driesch repeated Roux's
fundamental experiment with a different method on the sea-urchin's egg,
with a result that was absolutely contrary to that of Roux: the isolated
blastomere cleaved like half the egg, but it resulted in a whole
blastula and a whole embryo, which differed from a normal one only in
its small size. Driesch's result was obtained in somewhat the same
manner by E.B. Wilson with the egg of Amphioxus, by Zoja with the egg of
Medusae, &c. It thus became very probable that an inequality of nuclear
division could not be the basis of differentiation. The following
experiments were still more fatal to the theories of Roux and of
Weismann. Driesch found that even when the first eight or sixteen cells
of the cleaving egg of the sea-urchin were brought into quite abnormal
positions with regard to one another, still a quite normal embryo was
developed; Driesch and T.H. Morgan discovered jointly that in the
Ctenophore egg one isolated blastomere developed into a half-embryo, but
that the same was the case if a portion of protoplasm was cut off from
the fertilized egg not yet in cleavage; last, but not of least
importance, in the case of the frog's egg which had been Roux's actual
subject of experiment, conditions were discovered by O. Schultze and O.
Hertwig under which one of the two first blastomeres of this egg
developed into a whole embryo of half size. This result was made still
more decisive by Morgan, who showed that it was quite in the power of
the experimenter to get either a half-embryo or a whole one of half
size, the latter dependent only upon giving to the blastomere the
opportunity for a rearrangement of its matter by turning it over.
Thus we may say that the general result of the introductory series of
experiments in the physiology of development is the following:--In many
forms, e.g. Echinoderms, Amphioxus, Ascidians, Fishes and Medusae, the
potentiality (_prospective Potenz_--Driesch) of all the blastomeres of
the segmented egg is the same, i.e. each of them may play any or every
part in the future development; the prospective value (_prosp.
Bedeutung_--D.) of each blastomere depends upon, or is a function of,
its position in the whole of the segmented egg; we can term the "whole"
of the egg after cleavage an "aequipotential system" (Driesch). But
though aequipotential, the whole of the segmented egg is nevertheless
not devoid of orientation or direction; the general law of causality
compels us to assume a general orientation of the smallest parts of the
egg, even in cases where we are not able to see it. It has been
experimentally proved that external stimuli (light, heat, pressure, &c.)
are not responsible for the first differentiation of organs in the
embryo; thus, should the segmented egg be absolutely equal in itself, it
would be incomprehensible that the first organs should be formed at one
special point of it and not at another. Besides this general argument,
we see a sort of orientation in the typical forms of the polar or
bilateral cleavage stages.
Differentiation, therefore, depends on a primary, i.e. innate,
orientation of the egg's plasma in those forms, the segmented eggs of
which represent aequipotential systems; this orientation is capable of
a sort of regulation or restoration after disturbances of any sort; in
the egg of the Ctenophora such a regulation is not possible, and in
the frog's egg it is facultative, i.e. possible under certain
conditions, but impossible under others. Should this interpretation be
right, the difference between the eggs of different animals would not
be so great as it seemed at first: differences with regard to the
potentialities of the blastomeres would only be differences with
regard to the capability of regulation or restoration of the egg's
protoplasm.
The foundation of physiological embryology being laid, we now can
shortly deal with the whole series of special problems offered to us by
a general analysis of that science, but at present worked out only to a
very small extent.
We may ask the following questions:--What are the general conditions
of development? On what general factors does it depend? How do the
different organs of the partly developed embryo stand with regard to
their future fate? What are the stimuli (_Reize_) effecting
differentiation? What is to be said about the specific character of
the different formative effects? And as the most important question of
all: Are all the problems offered to us in the physiology of
development to be solved with the aid of the laws known hitherto in
science, or do we want specifically new "vitalistic" factors?
Conditions of differentiation.
Energy in different forms is required for development, and is provided
by the surrounding medium. Light, though of no influence on the cleavage
(Driesch), has a great effect on later stages of development, and is
also necessary for the formation of polyps in Eudendrium (J. Loeb). That
a certain temperature is necessary for ontogeny has long been known;
this was carefully studied by O. Hertwig, as was also the influence of
heat on the rate of development. Oxygen is also wanted, either from a
certain stage of development or from the very beginning of it, though
very nearly related forms differ in this respect (Loeb). The great
influence of osmotic pressure on growth was studied by J. Loeb, C.
Herbst and C.H. Davenport. In all these cases energy may be necessary
for development in general, or a specific form of energy may be
necessary for the formation of a specific organ; it is clear that,
especially in the latter case, energy is shown to be a proper factor for
morphogenesis. Besides energy, a certain chemical condition of the
medium, whether offered by the water in which the egg lives or
(especially in later stages) by the food, is of great importance for
normal ontogeny; the only careful study in this respect was carried out
by Herbst for the development of the egg of Echinids. This investigator
has shown that all salts of the sea water are of great importance for
development, and most of them specifically and typically; for instance,
calcium is absolutely necessary for holding together the embryonic
cells, and without calcium all cells will fall apart, though they do not
die, but live to develop further.
What we have dealt with may be called external factors of development;
as to their complement, the internal factors, it is clear that every
elementary factor of general physiology may be regarded as one of them.
Chemical metamorphosis plays, of course, a great part in
differentiation, especially in the form of secretions; but very little
has been carefully studied in this respect. Movement of living matter,
whether of cells or of intracellular substance, is another important
factor (O. Butschli, F. Dreyer, L. Rhumbler.) Cell-division is another,
its differences in direction, rate and quantity being of great
importance for differentiation. We know very little about it; a
so-called law of O. Hertwig, that a cell would divide at right angles to
its longest diameter, though experimentally stated in some cases, does
not hold for all, and the only thing we can say is, that the unknown
primary organization of the egg is here responsible. (Compare the papers
on "cell-lineage" of E.B. Wilson, F.R. Lillie, H.S. Jennings, O.
Zurstrassen and others.) Of the inner factors of ontogeny there is
another category that may be called physical, that already spoken of
being physiological. The most important of these is the capillarity of
the cell surfaces. Berthold was the first to call attention to its role
in the arrangement of cell composites, and afterwards the matter was
more carefully studied by Dreyer, Driesch, and especially W. Roux, with
the result that the arrangement of cells follows the principle of
surfaces _minimae areae_ (Plateau) as much as is reconcilable with the
conditions of the system.
Potentialities of embryonic cells.
It has already been shown that in many cases the embryo after cleavage,
i.e. the blastula, is an "aequipotential system." It was shown that in
the egg of Echinids there existed such an absolute lack of determination
of the cleavage cells that (a) the cells may be put in quite abnormal
positions with reference to one another without disturbing development;
(b) a quarter blastomere gives a quite normal little pluteus, even a
sixteenth yields a gastrula; (c) two eggs may fuse in the early blastula
stage, giving one single normal embryo of double size. Our next question
concerns the distribution of potentiality, when the embryo is developed
further than the blastula stage. In this case it has been shown that the
potentialities of the different embryonic organs are different: that,
for instance, in Echinoderms or Amphibians the ectoderm, when isolated,
is not able to form endoderm, and so on (Driesch, D. Barfurth); but it
has been shown at the same time that the ectoderm in itself, the
intestine in itself of Echinoderms (Driesch), the medullary plate in
itself of Triton (H. Spemann), is as aequipotential as was the blastula:
that any part whatever of these organs may be taken away without
disturbing the development of the rest into a normal and proportional
embryonic part, except for its smaller size.
Formative stimuli.
If the single phases of differentiation are to be regarded as effects,
we must ask for the causes, or stimuli, of these effects. For a full
account of the subject we refer to Herbst, by whom also the whole
botanical literature, much more important than the zoological, is
critically reviewed. We have already seen that when the blastula
represents an aequipotential system, there must be some sort of primary
organization of the egg, recoverable after disturbances, that directs
and localizes the formation of the first embryonic organs; we do not
know much about this organization. Directive stimuli (_Richtungsreize_)
play a great role in ontogeny; Herbst has analysed many cases where
their existence is probable. They have been experimentally proved in two
cases. The chromatic cells of the yolk sac of Fundulus are attracted by
the oxygen of the arteriae (Loeb); the mesenchyme cells of Echinus are
attracted by some specific parts of the ectoderm, for they move towards
them also when removed from their original positions to any point of the
blastocoel by shaking (Driesch). Many directive stimuli might be
discovered by a careful study of grafting experiments, such as have been
made by Born, Joest, Harrison and others, but at present these
experiments have not been carried out far enough to get exact results.
Formative stimuli in a narrower meaning of the word, i.e. stimuli
affecting the origin of embryonic organs, have long been known in
botany; in zoology we know (especially from Loeb) a good deal about the
influence of light, gravitation, contact, &c., on the formation of
organs in hydroids, but these forms are very plant-like in many
respects; as to free-living animals, Herbst proved that the formation of
the arms of the pluteus larva depends on the existence of the calcareous
tetrahedra, and made in other cases (lens of vertebrate eye, nerves and
muscles, &c.) the existence of formative stimuli very probable. Many of
the facts generally known as functional adaptation (_functionelle
Anpassung_--Roux) in botany and zoology may also belong to this
category, i.e. be the effects of some external stimulus, but they are
far from having been analysed in a satisfactory manner. That the
structure of parts of the vertebrate skeleton is always in relation to
their function, even under abnormal conditions, is well known; what is
the real "cause" of differentiation in this case is difficult to say.
Specific characters.
It is obvious that we cannot answer the question why the different
ontogenetic effects are just what they are. Developmental physiology
takes the specific nature of form for granted, and it may be left for a
really rational theory of the evolution of species in the future to
answer the problem of species, as far as it is answerable at all. What
we intend to do here is only to say in a few words wherein consists the
specific character of embryonic organs. That embryonic parts are
specific or typical in regard to their protoplasm is obvious, and is
well proved by the fact that the different parts of the embryo react
differently to the same chemical or other reagents (Herbst, Loeb). That
they may be typical also in regard to their nuclei was shown by Boveri
for the generative cells of Ascaris; we are not able at present to say
anything definite about the importance of this fact. The specific nature
of an embryonic organ consists to a high degree in the number of cells
composing it; it was shown for many cases that this number, and also the
size of cells, is constant under constant conditions, and that under
inconstant conditions the number is variable, the size constant; for
instance, embryos which have developed from one of the two first
blastomeres show only half the normal number of cells in their organs
(Morgan, Driesch).
Self-differentiation.
We have learnt that the successive steps of embryonic development are to
be regarded as effects, caused by stimuli, which partly exist in the
embryo itself. But it must be noted that not every part of the embryo is
dependent on every other one, but that there exists a great independence
of the parts, to a varying degree in every case. This partial independence
has been called self-differentiation (_Selbstdifferenzierung_) by Roux,
and is certainly a characteristic feature of ontogeny. At the same time it
must not be forgotten that the word is only relative, and that it only
expresses our recognition of a negation.
For instance, we know that the ectoderm of Echinus may develop further
if the endoderm is taken away; in other words, that it develops by
self-differentiation in regard to the endoderm, that its differentiation
is not dependent on the endoderm; but it would be obviously more
important to know the factors on which this differentiation is actually
dependent than to know one factor on which it is not. The same is true
for all other experiments on "self-differentiation," whether analytical
(Loeb, Schaper, Driesch) or not (grafting experiments, Born, Joest,
&c.).
Vitalism.
Can we understand differentiation by means of the laws of natural
phenomena offered to us by physics and chemistry? Most people would say
yes, though not yet. Driesch has tried to show that we are absolutely
not able to understand development, at any rate one part of it, i.e. the
localization of the various successive steps of differentiation. But it
is impossible to give any idea of this argument in a few words, and we
can only say here that it is based on the experiments upon isolated
blastomeres, &c., and on an analysis of the character of aequipotential
systems. In this way physiology of development would lead us straight on
into vitalism.
REFERENCES.--An account of the subject, with full literature, is given
by H. Driesch, _Resultate und Probleme der Entwicklungsphysiologie der
Tiere in Ergebnissen der Anat. u. Entw.-Gesch._ (1899). Other works
are: C.H. Davenport, _Experimental Morphology_ (New York, 1897-1899);
Y. Delage, _La Structure du protoplasma_, &c. (1895); Driesch,
_Mathem. mech. Betrachtung morpholog. Probleme_ (Jena, 1891);
_Entwicklungsmechan. Studien_ (1891-1893); _Analytische Theorie d.
organ. Entw._ (Leipzig, 1894); _Studien uber d. Regulationsvermogen_
(1897-1900), &c.; C. Herbst, "Uber die Bedeutung d. Reizphysiologie
fur die kausale Auffassung von Vorgangen i. d. tier. Ontogenese,"
_Biolog. Centralblatt_, vols. xiv. u. xv. (Leipzig, 1894). Many papers
on influence of salts on development in _Arch. f. Entw.-Mech._; O.
Hertwig, Papers in _Arch. f. mikr. Anat._, "Die Zelle und die Gewebe,"
ii. (Jena, 1897); W. His, _Unsere Korperform_ (Leipzig, 1875); J.
Loeb, _Untersuch. z. physiol. Morph._ (Wurzburg, 1891-1892). Papers in
_Arch. f. Entw.-Mech._ and Pfluger's _Archiv_; T.H. Morgan, _The
Development of the Frog's Egg_ (New York, 1897); Papers in _Arch. f.
Entw.-Mech._; Roux, _Gesammelte Abhandlungen_ (Leipzig, 1895); Papers
in _Arch. f. Entw.-Mech._; A. Weismann, _Das Keimplasma_ (Jena, 1892);
E.B. Wilson, papers in _Journ. Morph._, "The Cell in Development and
Inheritance" (New York, 1896). (H. A. E. D.)