describe first an experiment which is carried out at a later stage of
our well-known form. This experiment will easily lead to a few new
concepts, which we shall want later on, and will serve, on the other
hand, as a basis of explanation for some results, obtained from the
youngest germs of some other animal species, which otherwise would seem
to be rather irreconcilable with what our Echinus teaches us.
You know, from the second lecture, what a gastrula of our sea-urchin
is. If you bisect this gastrula, when it is completely formed, or
still better, if you bisect the gastrula of the starfish, either along
the axis or at right angles to it, you get complete little organisms
developed from the parts: the ectoderm is formed in the typical manner
in the parts, and so is the endoderm; everything is proportionate and
only smaller than in the normal case. So we have at once the important
results, that, as in the blastula, so in the ectoderm and in the
endoderm of our Echinus or of the starfish, the prospective potencies
are the same for every single element: both in the ectoderm and in
the endoderm the prospective value of each cell is a “function of its
position” (Fig. 9).
[Illustration: Fig. 9.--The Starfish, *Asterias*.
*a*^1. Normal gastrula; may be bisected along the main axis or at right
angles to it (see dotted lines).
*a*^2. Normal larva, “*Bipinnaria*.”
*b*^1. Small but whole gastrula that results by a process of regulation
from the parts of a bisected gastrula.
*b*^2. Small *but whole* “*Bipinnaria*,” developed out of *b*^1.]
But a further experiment has been made on our gastrula. If at the moment
when the material of the future intestine is most distinctly marked in
the blastoderm, but not yet grown into a tube, if at this moment the
upper half of the larva is separated from the lower by an equatorial
section, you will get a complete larva only from that part which bears
the “Anlage” of the endoderm, while the other half will proceed in
morphogenesis very well but will form only ectodermal organs. By another
sort of experiment, which we cannot fully explain here, it has been
shown that the endoderm if isolated is also only able to form such
organs as are normally derived from it.
And so we may summarise both our last results by saying: though
ectoderm and endoderm have their potencies equally distributed amongst
their respective cells, they possess different potencies compared one
with the other. And the same relation is found to hold for all cases of
what we call elementary organs: they are “equipotential,” as we may say,
in themselves, but of different potencies compared with each other.
*Explicit and Implicit Potencies: Primary and Secondary Potencies*
We shall first give to our concept of “prospective potency” a few words
of further analytical explanation with the help of our newly obtained
knowledge.
It is clear from what we have stated that the prospective potencies of
the ectoderm and of the endoderm, and we may add, of every elementary
organ in relation to every other, differ between themselves and also in
comparison with the blastoderm, from which they have originated. But the
diversity of the endoderm with respect to the ectoderm is not of the
same kind as its diversity in respect to the blastoderm. The potency
of the endoderm and that of the ectoderm are both specialised in their
typical manner, but compared with the potency of the blastoderm they
may be said not only to be specialised but also to be *restricted*: the
potency of the blastoderm embraces the whole, that of the so-called
germ-layer embraces only part of the whole; and this species of
restriction becomes clearer and clearer the further ontogeny advances:
at the end of it in the “ultimate elementary organs” there is no
prospective potency whatever.
A few new terms will serve to state a little more accurately what
happens. Of course, with regard to all morphogenesis which goes on
*immediately* from the blastoderm, the potency of the blastoderm is
restricted as much as are the potencies of the germ layers. We shall
call this sort of immediate potency *explicit*, and then we see at
once that, with regard to their explicit potencies, there are only
differences among the prospective potencies of the elementary organs;
but with respect to the *implicit* potency of any of these organs, that
is with respect to their potency as embracing the faculties of all their
derivations, there are also not only differences but true morphogenetic
restrictions lying at the very foundations of all embryology.
But now those of you who are familiar with morphogenetic facts will
object to me, that what we have stated about all sorts of restrictions
in ontogeny is not true, and you will censure me for having overlooked
regeneration, adventitious budding, and so on. To some extent the
criticism would be right, but I am not going to recant; I shall only
introduce another new concept. We are dealing only with *primary*
potencies in our present considerations, *i.e.* with potencies which
lie at the root of true embryology, not with those serving to regulate
disturbances of the organisation. It is true, we have in some way
disturbed the development of our sea-urchin’s egg in order to study
it; more than that, it would have been impossible to study it at all
without some sort of disturbance, without some sort of operation.
But, nevertheless, no potencies of what may properly be called the
*secondary* or restitutive type have been aroused by our operations;
nothing happened except on the usual lines of organogenesis. It is
true, some sort of regulation occurred, but that is included among the
factors of ontogeny proper.
We shall afterwards study more fully and from a more general point of
view this very important feature of “primary regulation” in its contrast
to “secondary regulation” phenomena. At present it must be enough to
say that in speaking of the restriction of the implicit potencies in
form-building we refer only to potencies of the primary type, which
contain within themselves some properties of a (primary) regulative
character.
*The Morphogenetic Function of Maturation in the Light of Recent
Discoveries*
Turning again to more concrete matters, we shall first try, with the
knowledge acquired of the potencies of the blastoderm and the so-called
germ layers of Echinus, to understand certain rather complicated
results which the experimental morphogenetic study of other animal
forms has taught us. We know from our historical sketch that there are
some very important aberrations from the type, to which the Echinus
germ belongs,[27] *i.e.* the type with an equal distribution of the
potencies over all the blastomeres. We know not only that in cases where
a regulation of the intimate structure of the protoplasm fails to occur
a partial development of isolated cells will take place, but that there
may even be a typical disposition of typical cells for the formation of
typical organs only, without any regulability.
[27] The reader will remember (see page 65, note 1), that even the germ
of Echinus is not quite equipotential along its main axis, but it is
equipotential in the strictest sense around this axis. The germs of
certain medusae seem to be equipotential in every respect, even in their
cleavage stages.
Let us first consider the last case, of which the egg of mollusca is a
good type: here there is no equal distribution of potencies whatever,
the cleavage-cells of this germ are a sort of real “mosaic” with regard
to their morphogenetic potentialities. Is this difference between the
germ of the echinoderms and the molluscs to remain where it is, and
not to be elucidated any further? Then there would be rather important
differences among the germs of different animals, at least with regard
to the degree of the specification of their cleavage cells, or if we
ascribe differences among the blastomeres to the organisation of the
fertilised egg ready for cleavage, there would be differences in the
morphogenetic organisation of the egg-protoplasm: some eggs would be
more typically specialised at the very beginning of morphogenesis than
others.
In the first years of the study of “Entwickelungsmechanik” I pointed out
that it must never be forgotten that the egg itself is the result of
organogenesis. If, therefore, there are real mosaic-like specifications
in some eggs at the beginning of cleavage, or during it, there may
perhaps have been an *earlier* stage in the individual history of
the egg which did not show such specifications of the morphogenetic
structure. Two American authors share the merit of having proved
this hypothesis. Conklin showed, several years ago, that certain
intracellular migrations and rearrangements of material do happen in
the first stages of ovogenesis in certain cases, but it is to E. B.
Wilson[28] that science owes a proper and definitive elucidation of the
whole subject. Wilson’s researches, pursued not only by descriptive
methods,[29] but also by means of analytical experiment, led him to the
highly important discovery that the eggs of several forms (nemertines,
molluscs), which after maturation show the mosaic type of specification
in their protoplasm to a more or less high degree, fail to show any
kind of specification in the distribution of their potencies before
maturation has occurred. In the mollusc egg a certain degree of
specification is shown already before maturation, but nothing to be
compared with what happens afterwards; in the egg of nemertines there is
no specification at all in the unripe egg.
[28] *Journ. Exp. Zool.* 1, 1904.
[29] Great caution must be taken in attributing any specific
morphogenetic part to differently coloured or constructed materials,
which may be observed in the egg-protoplasm in certain cases. They may
play such a part, but in other cases they certainly do not (see Lyon,
*Arch. Entw. Mech.* 23, 1907). The final decision always depends on
experiment.
Maturation thus becomes a part of ontogeny itself; it is not with
fertilisation that morphogenesis begins, there is a sort of ontogeny
anterior to fertilisation.
These words constitute a summary of Wilson’s researches. Taken together
with the general results obtained about the potencies of the blastula
and the gastrula of Echinus, they reduce what appeared to be differences
of degree or even of kind in the specification of the egg-protoplasm *to
mere differences in the time of the beginning of real morphogenesis*.
What occurs in some eggs, as in those of Echinus, at the time of the
definite formation of the germ layers, leading to a specification and
restriction of their prospective potencies, may happen very much earlier
in other eggs. But there exists in *every* sort of egg an *earliest*
stage, in which all parts of its protoplasm are equal as to their
prospectivity, and in which there are no potential diversities or
restrictions of any kind.
So much for differences in the *real material* organisation of the germ
and their bearing on inequipotentialities of the cleavage cells.
*The Intimate Structure of Protoplasm: Further Remarks*
Where a typical half- or quarter-development from isolated blastomeres
happens to occur, we know already that the impossibility of a regulation
of the *intimate polar-bilateral* structure may account for it. As this
impossibility of regulation probably rests on rather simple physical
conditions[30] it may properly be stated that equal distribution of
potencies is not wanting but is only overshadowed here. In this respect
there exists a logical difference of fundamental importance between
those cases of so-called “partial” or better, “fragmental” development
of isolated blastomeres in which a certain embryonic organ is wanting
on account of its specific morphogenetic material being absent, and
those cases in which the “fragmental” embryo lacks complete “halves” or
“quarters” with regard to general symmetry on account of the symmetry
of its intimate structure being irregularly disturbed. This logical
difference has not always received the attention which it undoubtedly
deserves. Our hypothetical intimate structure in itself is, of course,
also a result of factors concerned in ovogenesis. Only in one case do
we actually know anything about its origin: Roux has shown that in the
frog it is the accidental path of the fertilising spermatozoon in the
egg which, together with the polar axis, normally determines the plane
of bilateral symmetry; but this symmetry may be overcome and replaced
by another, if gravity is forced to act in an abnormal manner upon the
protoplasm; the latter showing parts of different specific gravity in
the eggs of all Amphibia.
[30] It seems that these physical conditions also--besides the real
specifications in the organisation of the egg--may be different before
and after maturation or (in other cases) fertilisation. (See Driesch,
*Archiv f. Entwickelungsmechanik*, 7, p. 98; and Brachet, *ibid.* 22, p.
325.)
*The Neutrality of the Concept of “Potency”*
Now we may close our rather long chapter on the distribution of
potencies in the germ; it has been made long, because it will prove to
be very important for further analytical discussion; and its importance,
in great measure, is due to its freedom from prepossessions. Indeed,
the concept of prospective potency does not prejudice anything; we
have said, it is true, that limitations of potencies may be due to
the presence of specific parts of organisation in some cases; that,
at least, they may be connected therewith; but we have not determined
at all what a prospective potency really is, what the term really is
to signify. It may seem that such a state of things gives an air of
emptiness to our discussions, that it leaves uncertain what is the most
important. But, I think, our way of argument, which tries to reach the
problems of greatest importance by degrees, though it may be slow, could
hardly be called wrong and misleading.
β. THE “MEANS” OF MORPHOGENESIS
We now proceed to an analysis of what may properly be called the *means*
of morphogenesis, the word “means” being preferable to the more usual
one “conditions” in this connection, as the latter would not cover the
whole field. It is in quite an unpretentious and merely descriptive
sense that the expression “means” should be understood at present; what
is usually called “conditions” is part of the morphogenetic means in our
sense.
β′. *The Internal Elementary Means of Morphogenesis*
We know that all morphogenesis, typical or atypical, primary or
secondary, goes on by one morphogenetic elementary process following the
other. Now the very foundation of these elementary processes themselves
lies in the elementary functions of the organism as far as they result
in the formation of stable visible products. Therefore the elementary
functions of the organism may properly be called the internal “means” of
morphogenesis.
Secretion and migration are among such functions; the former happening
by the aid of chemical change or by physical separation, the latter by
the aid of changes in surface tension. But hardly anything more concrete
has been made out about these or similar points at present.
We therefore make no claim to offer a complete system of the internal
elementary means of morphogenesis. We shall only select from the whole
a few topics of remarkable morphogenetic interest, and say a few words
about each.
But, first of all, let us observe that the elementary means of
morphogenesis are far from being morphogenesis themselves. The word
“means” itself implies as much. It would be possible to understand each
of these single acts in morphogenesis as well as anything, and yet to be
as far from understanding the whole as ever. All means of morphogenesis
are only to be considered as the most general frame of events within
which morphogenesis occurs.
*Some Remarks on the Importance of Surface Tension in
Morphogenesis.*--There are a few purely physical phenomena which have
a special importance in organic morphology, all of them connected
with capillarity or surface tension. Soap-lather is a very familiar
thing to all of you: you know that the soap-solution is arranged here
in very thin planes separated by spaces containing air: it was first
proved by Berthold[31] that the arrangement of cells in organic tissues
follows the same type as does the arrangement of the single bubbles of
a soap-lather, and Bütschli[32] added to this the discovery that the
minute structure of the protoplasm itself is that of a foam also. Of
course it is not one fluid and one gas which make up the constituents
of the structure in the organisms, as is the case in the well-known
inorganic foams, but two fluids, which do not mix with one another. One
general law holds for all arrangements of this kind: the so-called law
of least surfaces, expressed by the words that the sum of all surfaces
existing is a minimum; and it again is a consequence of this law, if
discussed mathematically, that four lines will always meet in one point
and three planes in one line. This feature, together with a certain law
about the relation of the angles meeting in one line to the size of the
bubbles, is realised most clearly in many structures of organic tissues,
and makes it highly probable, at least in some cases, that capillarity
is at work here. In other cases, as for instance in many plants, a kind
of outside pressure, the so-called tissue tension, may account for the
arrangement in surfaces *minimae areae*. Cleavage stages are perhaps
the very best type in which our physical law is expressed: and here
it may be said to have quite a simple application whenever all of the
blastomeres are of the same physical kind, whilst some complications
appear in germs with a specialised organisation and, therefore,
with differences in the protoplasm of their single blastomeres. In
such instances we may say that the physical law holds as far as the
conditions of the system permit, these conditions ordinarily consisting
in a sort of non-homogeneity of the surfaces.
[31] *Studien über Protoplasmamechanik*, Leipzig, 1886.
[32] *Unters. üb. mikroskopische Schäume und das Protoplasma*, Leipzig,
1892.
It seems, from the researches of Dreyer,[33] that the formation of
organic skeletons may also be governed by the physically conditioned
arrangement of protoplasmatic or cellular elements, and some phenomena
of migration and rearrangement among cleavage cells, as described by
Roux, probably also belong here.
[33] *Jena. Zeitschr.* 26, 1892.
But let us never forget that the laws of surface tension only give
us the most general type of an arrangement of elements in all these
cases, nothing else. A physical law never accounts for the Specific!
Capillarity gives us not the least clue to it. As the organic substance,
at least in many cases, is a fluid, it must of course follow the general
laws of hydrostatics and hydrodynamics, but life itself is as little
touched by its fluid-like or foam-like properties as it is by the fact
that living bodies have a certain weight and mass.
All indeed that has been described may be said to belong, in the
broadest meaning of the word, to what is called by Roux “correlation of
masses,” though this author originally intended to express by this term
only some sorts of passive pressure and deformation amongst embryonic
parts as discovered especially by His.
We must be cautious in admitting that any organic feature has been
explained, even in the most general way, by the action of physical
forces. What at first seems to be the result of mechanical pressure may
afterwards be found to be an active process of growth, and what at first
seems to be a full effect of capillarity among homogeneous elements may
afterwards be shown to depend on specialised metabolic conditions of the
surfaces as its principal cause.[34]
[34] According to Zur Strassen’s results the early embryology of
*Ascaris* proceeds almost exclusively by cellular surface-changes: the
most typical morphogenetic processes are carried out by the aid of this
“means.” As a whole, the embryology of *Ascaris* stands quite apart and
presents a great number of unsolved problems; unfortunately, the germ of
this form has not been accessible to experiment hitherto.
There are other physical phenomena too, which assist morphogenesis;
osmotic pressure for instance, which is also well known to operate in
many purely physiological processes. But all these processes are only
means of the organism, and can never do more than furnish the general
type of events. They do not constitute life; they are *used* by life;
let it remain an open question, for the present, how the phenomenon of
“life” is to be regarded in general.[35]
[35] Rhumbler has recently published a general survey of all attempts to
“explain” life, and morphogenesis in particular, in a physico-chemical
way (“Aus dem Lückengebiet zwischen organismischer und anorganismischer
Natur,” *Ergeb. Anat. u. Entw.-gesch.* 15, 1906). This *very
pessimistic* survey is the more valuable as it is written by a convinced
“mechanist.”
*On Growth*.--Among the internal morphogenetical means which are of
a so-called physiological character, that is, which nobody claims to
understand physically at present, there is in the first place *growth*,
which must be regarded as a very essential one.
Analytically we must carefully discriminate between the increase in the
size of the cavities of an organism by a passive extension of their
surfaces and the proper growth of the individual cells, which again
may be due either to mere extension or to real assimilation. Osmotic
pressure, of course, plays an important part both in the growth of the
body-cavities and in simple cellular extension. We repeat the caution
against believing too much to be explained by this phenomenon: it is the
organism which by the secretion of osmotic substances in the cavities or
the protoplasm of the cells prepares the ground for growth even of this
osmotic sort. The real cellular growth which proceeds on the basis of
assimilation cannot, of course, be accounted for by osmotic events, not
even in its most general type.
Ontogenetical growth generally sets in, both in animals and in plants,
after the chief lines of organisation are laid out; it is only the
formation of the definite histological structures which usually runs
parallel to it.
*On Cell-division.*--We have already said a good deal about the
importance of cell-division in ontogeny: it accompanies very many of the
processes of organisation in all living beings. But even then, there are
the Protozoa, in the morphogenesis of which it does not occur at all,
and there have also become known many cases of morphogenesis in higher
animals, mostly of the type of regulation, in which cellular division
is almost or wholly wanting. Therefore, cellular division cannot be
the true reason of differentiation, but is only a process, which
though necessary in some cases, cannot be essential to it. It must be
conceded, I believe, that the same conclusion can be drawn from all our
experiments on very young stages of the germ.
The investigations of the last few years have made it quite clear that
even in organisms with a high power of morphogenetic regulation it is
always the form of the whole, but not the individual cell, which is
subjected to the regulation processes. Starting from certain results
obtained by T. H. Morgan, I was able to show that in all the small but
whole larvae, reared from isolated blastomeres, the size of the cells
remains normal, only their number being reduced; and Boveri has shown
most clearly that it is always the size of the nucleus--more correctly,
the mass of the chromatin--which determines how large a cell of a
certain histological kind is to be. In this view, the cell appears even
more as a sort of material used by the organism as supplied, just as
workmen can build the most different buildings with stones of a given
size.
β″. *The External Means of Morphogenesis*
We now know what internal means of morphogenesis are, and so we may
glance at some of the most important “outer means” or “conditions” of
organisation.
Like the adult, the germ also requires a certain amount of heat, oxygen,
and, when it grows up in the sea, salinity in the medium. For the germ,
as for the adult, there exists not only a minimum but also a maximum
limit of all the necessary factors of the medium; the same factor which
at a certain intensity promotes development, disturbs it from a certain
other intensity upwards.
Within the limits of this minimum and this maximum of every outside
agent there generally is an increase in the rate of development
corresponding to the increase of intensity of the agent. The
acceleration of development by heat has been shown to follow the law of
the acceleration of chemical processes by a rise of temperature; that
seems to prove that certain chemical processes go on during the course
of morphogenesis.
Almost all that has been investigated of the part played by the external
conditions of development has little bearing on specific morphogenesis
proper, and therefore may be left out of account here: we must, however,
lay great stress on the general fact that there *is* a very close
dependence of morphogenesis on the outside factors, lest we should be
accused afterwards of having overlooked it.
Of course all “external” means or conditions of morphogenesis can
actually relate to morphogenetic processes only by becoming in some way
“internal,” but we unfortunately have no knowledge whatever how this
happens. We at present are only able to ascertain what must necessarily
be accomplished in the medium, in order that normal morphogenesis may go
on, and we can only suppose that there exist certain specific internal
general states, indispensable for organogenesis but inaccessible to
present modes of investigation.[36]
[36] Compare the analytical discussions of Klebs, to whom we owe a great
series of important discoveries in the field of morphogenetic “means”
in botany. (*Willkürliche Entwickelungsänderungen bei Pflanzen*, Jena,
1903; see also *Biol. Centralblatt*, vol. xxiv., 1904, and my reply to
Klebs, *ibid.* 23, 1903.)
*The Discoveries of Herbst.*--There are but few points in the doctrine
of the external means or conditions of organogenesis which have a
more special bearing on the specification of proper form, and which
therefore require to be described here a little more fully. All
these researches, which have been carried out almost exclusively by
Herbst,[37] relate to the effect of the chemical components of sea-water
upon the development of the sea-urchin. If we select the most important
of Herbst’s results, we must in the first place say a few words on
the part taken by lime or calcium, not only in establishing specific
features of form, but in rendering individual morphogenesis possible at
all. Herbst has found that in sea-water which is deprived of calcium the
cleavage cells and many tissue cells also completely lose contact with
each other: cleavage goes on quite well, but after each single division
the elements are separated; at the end of the process you find the 808
cells of the germ together at the bottom of the dish, all swimming about
like infusoria. There seems to be some influence of the calcium salts
upon the physical state of the surfaces of the blastomeres.
[37] *Arch. Entw. Mech.* 17, 1904.
It is not without interest to note that this discovery has an important
bearing on the technical side of all experiments dealing with the
isolation of blastomeres. Since the separation of the single cleavage
elements ceases as soon as the germs are brought back from the mixture
without lime into normal sea-water, it of course is possible to separate
them up to any stage which it is desired to study, and to keep them
together afterwards. Thus, if for instance you want to study the
development of isolated cells of the eight-cell stage, you will leave
the egg in the artificial mixture containing no calcium until the
third cleavage, which leads from the four- to the eight-cell stage, is
finished. The single eight cells brought back to normal sea-water at
this point will give you the eight embryos you want. All researches
upon the development of isolated blastomeres since the time of Herbst’s
discovery have been carried out by this method, and it would have been
quite impossible by the old method of shaking to pursue the study into
such minute detail as actually has been done. It may be added that
calcium, besides its cell-uniting action, is also of primary importance
in the formation of the skeleton.
Among all the other very numerous studies of Herbst we need only mention
that potassium is necessary for the typical growth of the intestine,
just as this element has been found necessary for normal growth in
plants, and that there must be the ion SO_4, or in other terms,
sulphur salts present in the water, in order that the germs may acquire
their pigments and their bilateral symmetry. This is indeed a very
important result, though it cannot be said to be properly understood. It
is a fact that in water without sulphates the larvae of Echinus retain
the radial symmetry they have had in the very earliest stages, and may
even preserve that symmetry on being brought back to normal sea-water if
they have spent about twenty-four hours in the artificial mixture.
We may now leave the subject of Herbst’s attempts to discover the
morphogenetic function of the single constituents of normal sea-water,
and may devote a few words to the other branch of his investigations,
those dealing with the morphogenetic effects of substances which are not
present in the water of the sea, but have been added to it artificially.
Here, among many other achievements, Herbst has made the most
important discovery that all salts of lithium effect radical changes
in development.[38] I cannot describe fully here how the so-called
“lithium larva” originates; let me only mention that its endoderm is
formed outside instead of inside, that it is far too large, that there
is a spherical mass between the ectodermal and the endodermal part of
the germ, that a radial symmetry is established in place of the normal
bilateralism, that no skeleton exists, and that the mesenchyme cells
are placed in a quite abnormal position. All these features, though
abnormal, are typical of the development in lithium. The larvae present
no really pathological appearance at all, and, therefore, it may indeed
be said that lithium salts are able to change fundamentally the whole
course of morphogenesis. It detracts nothing from the importance of
these discoveries that, at present, they stand quite isolated: only with
lithium salts has Herbst obtained such strange results, and only upon
the eggs of echinids, not even upon those of asterids, do lithium salts
act in this way.
[38] *Zeitschr. wiss. Zool.* 55, 1902; and *Mitt. Neapel.* 11, 1903.
γ. THE FORMATIVE CAUSES OR STIMULI
*The Definition of Cause*
We cannot begin the study of the “causes” of the differentiation of
form without a few words of explanation about the terminology which we
shall apply. Causality is the most disputed of all categories; many
modern scientists, particularly in physics, try to avoid the concept of
cause altogether, and to replace it by mere functional dependence in
the mathematical meaning of the term. They claim to express completely
by an equation all that is discoverable about any sort of phenomena
constantly connected.
I cannot convince myself that such a very restricted view is the right
one: it is very cautious, no doubt, but it is incomplete, for we *have*
the concept of the acting “cause” in our Ego and are *forced* to search
for applications of it in Nature. On the other hand, it does not at all
escape me that there are many difficulties, or rather ambiguities, in
applying it.
We may call the “cause” of any event, the sum total of all the
constellations of facts which must be completed in order that the event
may occur; it is in this meaning, for instance, that the first principle
of energetics applies the term in the words *causa aequat effectum*.
But, by using the word only in this very general sense, we deprive
ourselves of many conveniences in the further and more particular study
of Nature. Would it be better to say that the “cause” of any event is
the very last change which, after all the constellations necessary for
its start are accomplished, must still take place in order that the
event may actually occur? Let us see what would follow from such a use
of the word causality. We here have an animal germ in a certain stage,
say a larva of Echinus, which is just about to form the intestine; all
the internal conditions are fulfilled, and there is also a certain
temperature, a certain salinity, and so on, but there is no oxygen in
the water: the intestine; of course, will not grow in such a state of
things, but it soon will when oxygen is allowed to enter the dish.
Is, therefore, oxygen the cause of the formation of the intestine of
echinus? Nobody, I think, would care to say so. By such reasoning,
indeed, the temperature, or sodium, might be called the “cause” of
any special process of morphogenesis. It, therefore, seems to be of
little use to give the name of cause to that factor of any necessary
constellation of events which accidentally happens to be the last that
is realised. But what is to be done then?
Might we not say that the cause of any morphogenetic process is that
typical property, or quality, or change, on which its specific character
depends, on which depends for example, the fact that now it is the
intestine which appears, while at another time it is the lens of the
eye? We might very well, but we already have our term for this sort
of cause, which is nothing else than our prospective potency applied
to that elementary organ from which the new process takes its origin.
The prospective potency indeed is the truly immanent cause of every
specification affecting single organogenetic processes. But we want
something more than this.
We may find what we want by considering that each single elementary
process or development not only has its specification, but also has
its specific and typical place in the whole--its locality. Therefore
we shall call the “cause” of a single morphogenetic process, that
occurrence on which depends its *localisation*, whether its specific
character also partly depends on this “cause” or not.[39]
[39] In certain cases part of the specific feature of the process in
question may also depend on the “cause” which is localising it, *e.g.*
in the galls of plants.
This definition of “cause” in morphology may be artificial; in any
case it is clear. And at the same time the concepts of the prospective
potency and of the “means” of organogenesis now acquire a clear and
definite meaning: potency is the real basis of the specific character
of every act in morphogenesis, and “means,” including conditions, are
the sum of all external and internal general circumstances which must be
present in order that morphogenetic processes may go on, without being
responsible for their specificity or localisation.
It is implied in these definitions of cause and potency, that the former
almost always will be of that general type which usually is called a
stimulus or “Auslösung,” to use the untranslatable German word. There is
no quantitative correspondence between our “cause” and the morphogenetic
effect.
*Some Instances of Formative and Directive Stimuli*
Again it is to Herbst that we owe not only a very thorough logical
analysis of what he calls “formative and directive stimuli”[40] but also
some important discoveries on this subject. We cannot do more here than
barely mention some of the most characteristic facts.
[40] Herbst, “Ueber die Bedeutung die Reizphysiologie für die kausale
Auffassung von Vorgängen in der tierischen Ontogenese” (*Biol.
Centralblatt*, vols. xiv., 1894, and xv., 1895); *Formative Reize in der
tierischen Ontogenese*, Leipzig, 1901. These important papers must be
studied by every one who wishes to become familiar with the subject. The
present state of science is reviewed in my articles in the *Ergebnisse
der Anatomie und Entwickelungsgeschichte*, vols. xi. and xiv., 1902 and
1905.
Amongst plants it has long been known that the direction of light or of
gravity may determine where roots or branches or other morphogenetic
formations are to arise; in hydroids also we know that these factors
of the medium may be at work[41] as morphogenetic causes, though most
of the typical architecture of hydroid colonies certainly is due to
internal causes, as is also much of the organisation in plants.
[41] Compare the important papers by J. Loeb, *Untersuchungen zur
physiologischen Morphologie der Tiere*, Würzburg, 1891-2.
Light and gravity are external formative causes; beside that they are
merely “localisers.” But there also are some external formative stimuli,
on which depends not only the place of the effect, but also part of its
specification. The galls of plants are the most typical organogenetic
results of such stimuli. The potencies of the plant and the specific
kind of the stimulus equally contribute to their specification; for
several kinds of galls may originate on one sort of leaves.
Scarcely any exterior formative stimuli are responsible for animal
organisation; and one would hardly be wrong in saying that this
morphogenetic independence in animals is due to their comparatively
far-reaching functional independence of those external agents which
have any sort of direction. But many organogenetic relations are known
to exist between the single parts of animal germs, each of these parts
being in some respect external to every other; and, indeed, it might
have been expected already *a priori*, that such formative relations
between the parts of an animal embryo must exist, after all we have
learned about the chief lines of early embryology. If differentiation
does not go on after the scheme of Weismann, that is, if it is not
carried out by true “evolutio” from within, how could it be effected
except from without? Indeed, every embryonic part may in some respect be
a possible cause for morphogenetic events, which are to occur on every
other part: it is here that the very roots of epigenesis are to be found.
Heliotropism and geotropism are among the well-known physiological
functions of plants: the roots are seen to bend away from the light and
towards the ground; the branches behave just in the opposite way. It now
has been supposed by Herbst that such “directive stimuli” may also be
at work among the growing or wandering parts of the embryo, that their
growth or their migration may be determined by the typical character of
other parts, and that real morphogenetic characters can be the result of
some such relation; a sort of “chemotropism” or “chemotaxis” may be at
work here. Herbst himself has discussed theoretically several cases of
organogenesis in which the action of directive stimuli is very probable.
What has become actually known by experiment is not very much at
present: the mesenchyme cells of Echinus are directed in their migration
by specified places in the ectoderm, the pigment cells of the yolk-sac
of the fish fundulus are attracted by its blood vessels, and nerves
may be forced to turn into little tubes containing brain substance;
but of course only the first two instances have any bearing on typical
morphogenesis.
The first case of an “internal formative stimulus” in the proper sense,
that is, of one embryonic part causing another to appear, was discovered
by Herbst himself. The arms of the so-called pluteus of the sea-urchin
are in formative dependence on the skeleton--no skeleton, no arms; so
many skeleton primordia,[42] in abnormal cases, so many arms; abnormal
position of the skeleton, abnormal position of the arms: these three
experimental observations form the proof of this morphogenetic relation.
[42] I use the word “primordia” for the German “Anlage”; it is better
than the word “rudiment,” as the latter may also serve to signify
the very last stage of a certain formation that is disappearing
(phylogenetically).
It may be simple mechanical contact, or it may be some chemical
influence that really constitutes the “stimulus” in this case;
certainly, there exists a close and very specific relation of the
localisation of one part of the embryo to another. Things are much the
same in another case, which, after having been hypothetically stated
by Herbst on the basis of pathological data, was proved experimentally
by Spemann. The lens of the eye of certain Amphibia is formed of their
skin in response to a formative stimulus proceeding from the so-called
primary optic vesicle. If this vesicle fails to touch the skin, no lens
appears; and, on the other hand, the lens may appear in quite abnormal
parts of the skin if they come into contact with the optic vesicle after
transplantation.
But formative dependence of parts may also be of different types.
We owe to Herbst the important discovery that the eyes of crayfishes,
after being cut off, will be regenerated in the proper way, if the optic
ganglion is present, but that an antenna will arise in their place
if this ganglion has also been removed. There must in this case be
some unknown influence of the formative kind on which depends, if not
regeneration itself, at least its special character.
In other cases there seems to be an influence of the central nervous
system on the regenerative power in general. Amphibia, for instance,
are said to regenerate neither their legs (Wolff), nor their tail
(Godlewski), if the nervous communications have been disturbed. But
in other animals there is no such influence; and in yet others, as
for instance, in Planarians, it must seem doubtful at present whether
the morphogenetic influence of the nervous system upon processes of
restoration is more than indirect; the movements of the animal, which
become very much reduced by the extirpation of the ganglia, being one of
the main conditions of a good regeneration.
Of course, all we have said about the importance of special materials
in the ripe germ, as bearing on specifically localised organisations,
might be discussed again in our present chapter, and our intimate
polar-bilateral structure of germs may also be regarded as embracing
formative stimuli, at any rate as far as the actual poles of this
structure are concerned. This again would bring us to the problem of
so-called “polarity” in general, and to the “inversion” of polarity,
that is to a phenomenon well known in plants and in many hydroids and
worms, viz., that morphogenetic processes, especially of the type of
restitutions, occur differently, according as their point of origin
represents, so to speak, the positive or the negative, the terminal or
the basal end of an axis, but that under certain conditions the reverse
may also be the case. But a fuller discussion of these important facts
would lead us deeper and deeper into the science of morphogenesis
proper, without being of much use for our future considerations.
And so we may close this section[43] on formative stimuli or “causes”
of morphogenesis by shortly adding, more on account of its factual
than of its logical interest, that the phenomenon of the determination
of sex,[44] according to the latest researches, seems to depend on
cytological events occurring in the very earliest embryonic stages,
say even before ontogeny, and not on formative stimuli proper[45]: it
seems, indeed, as if the sexual products themselves would account for
the sex of the individual produced by them, particularly if there were
differences in their chromatin.[46]
[43] A full analysis of the subject would not only have to deal with
formative stimuli as inaugurating morphogenetic processes, but also with
those stimuli which terminate or stop the single acts of morphogenesis.
But little is actually known about this topic, and therefore the reader
must refer to my other publications. I will only say here, that the end
of each single morphogenetic act may either be determined at the very
beginning or occur as an actual stopping of a process which otherwise
would go on for ever and ever; in the first case some terminating
factors are included in the very nature of the morphogenetic act itself.
[44] A full account of the present state of the subject will be found in
Morgan’s *Experimental Zoology*, New York, 1907.
[45] But there certainly exist many formative relations between the real
sexual organs and the so-called secondary sexual characters. Herbst has
given a full analytical discussion of all that is known on this subject;
but the facts are much more complicated than is generally supposed, and
do not lend themselves therefore to short description. See also Foges,
*Pflüger’s Arch.* 93, 1902.
[46] It seems that in some cases (*Dinophilus*, certain Arthropods)
the sexual products are invariably determined as “arrenogennetic”
or as “thelygennetic” (Wilson, *Journ. Exp. Zool.* ii. and iii.
1905-6), whilst in others (Amphibia) the state of maturation or
“super”-maturation determines the sex of the future organism (R.
Hertwig, *Verh. D. Zool. Ges.* 1905-7).
δ. THE MORPHOGENETIC HARMONIES
Let us now turn again to considerations of a more abstract kind: we have
become acquainted with some morphogenetic interactions among the parts
of a developing embryo; and, indeed, we can be sure that there exist far
more of such interactions than we know at present.
But it is far from being true that the development of each embryonic
part depends on the existence or development of every other one.
On the contrary, it is a very important and fundamental feature
of organogenesis that it occurs in separate lines, that is to
say, in lines of processes which may start from a common root, but
which are absolutely independent of one another in their manner of
differentiation. Roux has coined the term “self-differentiation” to
denote this phenomenon, and we admit that this term may be conveniently
used for the purpose, if only it can be kept in mind that its sense is
always relative, and that it is also negative. Suppose a part, *A*,
shows the phenomenon of self-differentiation: this means that the
further development of *A* is not dependent on certain other parts,
*B*, *C*, and *D*; it does *not* mean at all that *A* has not been
formatively dependent on some other parts, *E* or *F* at the time of
its first appearance, nor does it imply that there might not be many
formative actions among the constituents of *A* itself.
We indeed are entitled to say that the ectoderm of Echinus shows
“self-differentiation” with regard to the endoderm; it acquires its
mouth, for instance, as has been shown by experiment, even in cases
where no intestine is present at all (Fig. 10); but ectoderm and
endoderm both are formatively dependent on the intimate and the material
organisation of the blastoderm. It further seems from the most recent
experiments that the nerves and the muscles of the vertebrates are
independent of each other in their differentiation, but that their fate
is probably determined by formative processes in the very earliest
stages of ontogeny.
[Illustration: Fig. 10.--Pluteus-larva of Sphaerechinus.
The Intestine (i) is developed outside instead of inside (by means of
raising the temperature); but the mouth (r) is formed in its normal
place. S = Skeleton.]
The phenomenon of self-differentiation, properly understood, now may
help to the discovery of one most general character of all development.
If the phenomenon of self-differentiation really occurs in ontogeny
in its most different aspects, and if, on the other hand, in spite
of this relative morphogenetic independence of embryonic parts, the
resulting organism is one whole in organisation and in function, some
sort of *harmony of constellation*, as it may properly be styled, must
be said to be one of the most fundamental characters of all production
of individual form. In establishing this harmony we do nothing more
than describe exactly what happens: the harmony is shown by the fact
that there is a whole organism at the end, in spite of the relative
independence of the single events leading to it.
But still another sort of harmony is revealed in morphogenesis, by an
analysis of the general conditions of the formative actions themselves.
In order that these actions may go on properly the possibility must be
guaranteed that the formative causes may always find something upon
which to act, and that those parts which contain the potencies for the
next ontogenetic stage may properly receive the stimuli awaking these
potencies: otherwise there would be no typical production of form at
all. This, the second species of harmonious relations to be described in
ontogeny, may be called *causal harmony*; the term simply expresses the
unfailing relative condition of formative causes and cause-recipients.
Finally, in *functional harmony* we have an expression descriptive
of the unity of organic function, and so we may state, as the latest
result of our analytical theory of development up to this point, that
individual morphogenesis is marked by a *threefold harmony* among its
parts.
ε. ON RESTITUTIONS[47]
[47] Driesch, *Die organischen Regulationen*, Leipzig, 1901; Morgan,
*Regeneration*, New York, 1901.
At this stage we leave for a while our analytical studies of ontogeny
proper. We must not forget that typical ontogenesis is not the only form
in which morphogenesis can occur: the organic form is able to restore
disturbances of its organisation, and it certainly is to be regarded as
one of the chief problems of analytical morphogenesis to discover the
specific and real stimulus which calls forth the restoring processes.
For simply to say that the disturbance is the cause of the restoration
would be to evade the problem instead of attacking it. But there are
still some other problems peculiar to the doctrine of restitutions.
*A few Remarks on Secondary Potencies and on Secondary Morphogenetic
Regulations in General*
We have only briefly mentioned in a previous chapter that there
exist many kinds of potencies of what we call the secondary or truly
restitutive type, and that their distribution may be most various and
quite independent of all the potencies for the primary processes
of ontogeny proper. Let us first add a few words about the concept
of “secondary restitution” and about the distribution of secondary
potencies in general.
Primary ontogenetic processes founded upon primary potencies may *imply*
regulation, or more correctly, restitution in many cases: so it is,
when fragments of the blastula form the whole organism, or when the
mesenchyme cells of Echinus reach their normal final position by an
attraction on the part of specific localities of the ectoderm in spite
of a very abnormal original position enforced upon them by experiment.
In these cases we speak of primary regulations or restitutions;
disturbances are neutralised by the very nature of the process in
question. We speak of secondary restitution whenever a disturbance
of organisation is rectified by processes foreign to the realm of
normality; and these abnormal lines of events are revealed to us in the
first place by the activity of potencies which remain latent in ontogeny
proper.
We know already that a certain kind of secondary restitution has
been discovered lately, very contradictory to the theoretical views
of Weismann; the process of restoration being carried out not by any
definite part of the disturbed organisation, but by all the single
elements of it. The problem of the distribution of secondary potencies
in these cases of so-called “re-differentiation” is to form our special
study in the next chapter. In all other cases restoration processes
start from specific localities; if they occur on the site of the
wound which caused the disturbance, we speak of regeneration; if they
occur at some distance from the wound, we call them adventitious
processes. Besides these three types of processes of restitution there
may be mentioned a fourth one, consisting in what is generally called
compensatory hypertrophy; the most simple case of such a compensatory
process is when one of a pair of organs, say a kidney, becomes larger
after the other has been removed.[48] Finally, at least in plants, a
change of the directive irritability, of so-called “geotropism” for
instance, in certain parts may serve to restore other more important
parts.
[48] But real compensatory differentiation occurs in the cases of
so-called “hypertypy” as first discovered by Przibram and afterwards
studied by Zeleny: here the two organs of a pair show a different degree
of differentiation. Whenever the more specialised organ is removed the
less developed one assumes its form. Similar cases, which might simply
be called “compensatory heterotypy,” are known in plants, though only
relating to the actual fate of undifferentiated “Anlagen” in these
organisms. A leaf may be formed out of the Anlage of a scale, if all the
leaves are cut off, and so on.
In two of these general types of restitution, in regeneration proper and
in the production of adventitious organs, the potencies which underlie
these processes may be said to be “complex.” It is a complicated series
of events, a proper morphogenesis in itself, for which the potency
has to account, if, for instance, a worm newly forms its head by
regeneration, or if a plant restores a whole branch in the form of an
adventitious bud.
Such generalisations as are possible about the distribution of complex
potencies are reserved for a special part of our future discussion.
Secondary restitution is always, like ontogeny, a process of
morphogenesis, and therefore all the questions about single formative
stimuli, and about internal and external conditions or means, occur
again. But of course we cannot enter into these problems a second time,
and may only say that, especially in regeneration proper, the specific
type of the regenerative formation of any part may differ very much from
the ontogenetic type of its origin: the end of both is the same, but the
way can be even fundamentally different in every respect.
*The Stimuli of Restitutions*[49]
[49] For a fuller analysis compare my opening address delivered before
the section of “Experimental Zoology” at the Seventh Zoological
Congress, Boston, 1907: “The Stimuli of Restitutions” (see Proceedings
of that Congress).
But now we turn to the important question: what is the precise
stimulus[50] that calls forth processes of restitution; or, in other
words, what must have happened in order that restitution may occur?
[50] The problem of the stimulus of a secondary restitution as a
whole must not be confused with the very different question, what the
single “formative stimuli” concerned in the performance of a certain
restitutive act may be. With regard to restitution as a *whole* these
single “formative stimuli” might properly be said to belong to its
“internal means”--in the widest sense of the word.
That the operation in itself, by its removing of mechanical obstacles,
cannot be the true stimulus of any restitutions, is simply shown by all
those restitutions that do not happen at the place of the wound. If we
took a narrower point of view, and if we only considered regeneration
proper from the wound itself, we might probably at first be inclined to
advocate the doctrine that the removing of some obstacles might in fact
be the stimulus to the process of restoration; but, even then, why is
it that just what is wanted grows out? Why is there not only growth,
but specific growth, growth followed by specification? The removing
of an obstacle could hardly account for that. But, of course, taking
account of all the adventitious restitutions--that is, all restorations
not beginning at the wound itself--the theory that the removing of
obstacles is the stimulus to restoration becomes, as we have said, quite
impossible.[51]
[51] T. H. Morgan is very right in stating that, in regeneration, the
“obstacle” itself is newly formed by the mere process of healing,
previous to all restitution, and that true restitution happens all the
same.
But where then is the stimulus to be found? There is another rather
simple theory of the “Auslösung” of restitutions,[52] which starts
from the phenomena of compensatory hypertrophy and some occurrences
among plants. The removal of some parts of the organism, it is said,
will bring its other parts into better conditions of nutrition, and
therefore these parts, particularly if they are of the same kind, will
become larger. Granted for the moment that such a view may hold in cases
when one of a pair of glands becomes larger after the other has been
removed, or when pruning of almost all the leaves of a tree leads to the
rest becoming larger, it certainly must fail to explain the fact that
in other cases true *new* formations may arise in order to restore a
damaged part, or that the latter may be regenerated in its proper way.
For *merely quantitative* differences in the mixture of the blood or of
the nourishing sap in plants can never be a sufficient reason for the
highly typical and *qualitative* structure of newly-formed restitutions.
And even in the most simple cases of a mere increase in the size of
some parts, that is, in the simplest cases of so-called compensatory
hypertrophy,[53] it is at least doubtful, if not very improbable, that
the compensation is accomplished in such a purely passive way, because
we know that in other cases it is usually the growth of the young parts
that actively attracts the nourishment: there is first differentiation
and growth, and *afterwards* there is a change in the direction of the
nourishing fluids.
[52] I merely mention here the still “simpler” one--applicable of course
to regeneration proper exclusively--that for the simple reason of being
“wounded,” *i.e.* being a surface open to the medium, the “wound” brings
forth all that is necessary to complete the organism.
[53] That compensatory hypertrophy cannot be due to “functional
adaptation”--to be analysed later on--was proved by an experiment of
Ribbert’s. Compensation may occur before the function has made its
appearance, as was shown to be the case in the testicles and mammae of
rabbits. (*Arch. Entw. Mech.* 1, 1894, p. 69.)
The process of true regeneration, beginning at the locality of the wound
itself, has been shown by Morgan, even as regards its rate, to occur
quite irrespectively of the animal being fed or not.[54] There could
hardly be a better demonstration of the fundamental fact that food
assists restitution, but does not “cause” it in any way.
[54] At any given time only the absolute size of the regenerated part is
greater in animals which are well fed; the degree of differentiation is
the same in all. Zeleny has found that, if all five arms of a starfish
are removed, each one of them will regenerate more material in a given
time than it would have done if it alone had been removed. But these
differences also only relate to absolute size and not to the degree
of differentiation. They possibly may be due in fact to conditions of
nourishment, but even here other explanations seems possible (Zeleny,
*Journ. exp. Zool.* 2, 1905).
But in spite of all we have said, there seems to be some truth in
regarding the nutritive juices of animals and plants as somehow
connected with the stimulus of restitutions: only in this very cautious
form, however, may we make the hypothesis. It has been shown for both
animals and plants, that morphogenesis of the restitutive type may be
called forth even if the parts, now to be “regenerated” have not been
actually removed; *e.g.* in the so-called super-regeneration of legs
and tails in Amphibia, of the head in Planarians, of the root-tip in
plants and in some other cases. Here it has always been a disturbance
of the normal connection of some parts with the rest of the organism
which proved to be the reason of the new formation. This shows that
something to do with the communication among parts is at least connected
with restitution, and this communication may go on either by the unknown
action of specific tissues or by the aid of the blood or sap.[55] But
in what this change or break of specific communication consists, is
absolutely unknown. One might suppose that each part of the organisation
constantly adds some sort of ferment to the body fluids outside or
inside the cells, that the removing of any part will change the
composition of these fluids in this particular respect, and that this
change acts as a sort of communication to summon the restituting parts
of the whole to do their duty.[56]
[55] For a good discussion of “super-regeneration” in the roots of
plants see Němec, *Studien über die Regeneration*, Berlin, 1905. Goebel
and Winkler have succeeded in provoking the “restitution” of parts which
were not removed at all by simply stopping their functions (leaves of
certain plants were covered with plaster, etc.). (*Biol. Centralbl.* 22,
1902, p. 385; *Ber. Bot. Ges.* 20, 1902, p. 81.) A fine experiment is
due to Miehe. The alga *Cladophora* was subjected to “plasmolysis,” each
cell then formed a new membrane of its own around the smaller volume of
its protoplasm; after that the plants were brought back to a medium of
normal osmotic pressure, and then each single cell grew up into a little
plant (all of them being of the same polarity!). Two questions seem
to be answered by this fact: loss of communication is of fundamental
importance to restitution, and the removal of mechanical obstacles plays
no part in it, for the mechanical resistances were the same at the end
of the experiment as they had been at the beginning. (*Ber. Bot. Ges.*
23, 1905, p. 257.) For fuller analysis of all the problems of this
chapter see my Organische Regulationen, my reviews in the *Ergebnisse
der Anatomie und Entwickelungsgeschichte*, vols. viii. xi. xiv., and
my Boston address mentioned above. Compare also Fitting, *Ergebn. d.
Physiol.* vols. iv. and v.
[56] The so-called “inner secretion” in physiology proper would offer a
certain analogy to the facts assumed by such an hypothesis. Compare the
excellent summary given by E. Starling at the seventy-eighth meeting of
the German “Naturforscherversammlung,” Stuttgart, 1906.
But I see quite well that such a theory is very little satisfactory;
for what has to be done in restitution in each case is not a simple
homogeneous act, for which one special material might account, but is
a very complicated work in itself. It was the defect of the theory of
“organ-forming substances” as advocated by Sachs, that it overlooked
this point.
So all we know about the proper stimuli of restitutions is far from
resting on any valid grounds at all; let us not forget that we are
here on the uncertain ground of what may be called the newest and
most up-to-date branch of the physiology of form. No doubt, there
will be something discovered some day, and the idea of the “whole” in
organisation will probably play some part in it. But in what manner that
will happen we are quite unable to predict.
This is the first time that, hypothetically at least, the idea of the
whole has entered into our discussion. The same idea may be said to
have entered it already in a more implicit form in the statement of the
threefold harmony in ontogeny.
Let us now see whether we can find the same problem of the “whole”
elsewhere, and perhaps in more explicit and less hypothetical form.
Let us see whether our analytical theory of development is in fact as
complete as it seemed to be, whether there are no gaps left in it which
will have to be filled up.
3. THE PROBLEM OF MORPHOGENETIC LOCALISATION
α. THE THEORY OF THE HARMONIOUS-EQUIPOTENTIAL SYSTEM
FIRST PROOF OF THE AUTONOMY OF LIFE
We have come to the central point of the first part of these lectures;
we shall try in this chapter to decide a question which is to give life
its place in Nature, and biology its place in the system of sciences.
One of the foundation stones is to be laid upon which our future
philosophy of the organism will rest.
*The General Problem*
Our analytical theory of morphogenesis has been founded upon three
elementary concepts: the prospective potency, the means, and the
formative stimulus. Its principal object has been to show that all
morphogenesis may be resolved into the three phenomena expressed by
those concepts; in other terms, that morphogenesis may be proved to
consist simply and solely of what is expressed by them. Have we indeed
succeeded in attaining this object? Has nothing been left out? Is it
really possible to explain every morphogenetic event, at least in the
most general way, by the aid of the terms potency, means, and stimulus?
All of these questions are apt to lead us to further considerations.
Perhaps these considerations will give us a very clear and simple result
by convincing us that it is indeed possible to analyse morphogenesis in
our schematic way.
But if the answer were a negative one? What would that suggest?
The full analysis of morphogenesis into a series of single formative
occurrences, brought about by the use of given means and on the basis of
given potencies, might assure us, perhaps, that, though not yet, still
at some future time, a further sort of analysis will be possible: the
analysis into the elemental facts studied by the sciences of inorganic
nature. The organism might prove to be a machine, not only in its
functions but also in its very origin.
But what are we to say if even the preliminary analysis, which possibly
might lead to such an ultimate result, fails?
Let us then set to work. Let us try to consider most carefully the topic
in which our concept of the formative cause or stimulus may be said
to be centred, the *localisation* of all morphogenetic effects. Is it
always possible in fact to account for the typical localisation of every
morphogenetic effect by the discovery of a single specific formative
stimulus? You will answer me, that such an analysis certainly is not
possible at present. But I ask you again, are there any criteria that it
is possible, at least in principle; or are there any criteria which will
render such an aim of science impossible for all future time?
*The Morphogenetic “System”*
We know from our experimental work that many, if not all, of the
elementary organs in ontogeny show one and the same prospective
potency distributed equally over their elements. If we now borrow a
very convenient term from mechanics, and call any part of the organism
which is considered as a unit from any morphogenetic point of view, a
morphogenetic “*system*,” we may sum up what we have learnt by saying
that both the blastoderm of the echinoderms, at least around its
polar axis, and also the germ-layers of these animals, are “systems”
possessing an equal potentiality in all of their elements, or, in short,
that they are *equipotential systems*.
But such a term would not altogether indicate the real character of
these systems.
Later on we shall analyse more carefully than before the distribution
of potencies which are the foundation both of regeneration proper and
of adventitious growth, and then we shall see that, in higher plants
for instance, there is a certain “system” which may be called the
organ proper of restitutions, and which also in each of its elements
possesses the same restoring potency; I refer to the well-known cambium.
This cambium, therefore, also deserves the name of an “equipotential
system.” But we know already that its potencies are of the complex
type, that they consist in the faculty of producing the *whole*, of
such a complicated organisation as a branch or a root, that the term
“equipotential system” is here only to signify that such a complicated
unit may arise out of each of the cells of the cambium.
The potencies we have been studying in the blastula or gastrula of
echinoderms are not of the complex type: our systems are equipotential
to the extent that each of their elements may play every *single* part
in the totality of what will occur in the whole system; it is to
this *single* part that the term “function of the position” relates.
We therefore might call our systems equipotential systems with single
potencies; or, more shortly, singular-equipotential systems.
But even this terminology would fail to touch precisely the very
centre of facts: it is not only the simplicity or singularity of
their potencies which characterises the rôle of our systems in
morphogenesis,[57] but far more important with respect to the production
of form are two other leading results of the experimental researches.
The proper act to be performed by every element in each actual case is
in fact a single one, but the potency of any element as such consists
in the possibility of many, nay of indefinitely many, single acts:
that then might justify us in speaking of our systems as “indefinite
equipotential,” were it not that another reason makes another title seem
still more preferable. There are indeed indefinite singular potencies at
work in all of our systems during ontogeny: but the sum of what happens
to arise in every case out of the sum of the single acts performed by
all of the single equipotential cells is not merely a sum but a unit;
that is to say, there exists a sort of harmony in every case among the
*real products* of our systems. The term *harmonious-equipotential
system* therefore seems to be the right one to denote them.
[57] The name of singular-equipotential systems might also be applied
to elementary organs, the single potencies of which are awaked to
organogenesis by specific formative stimuli from without; but that is
not the case in the systems studied in this chapter.
We now shall try first to analyse to its very extremes the meaning of
the statement that a morphogenetic system is harmonious-equipotential.
*The “Harmonious-Equipotential System”*
We have an ectoderm of the gastrula of a starfish here before us; we
know that we may cut off any part of it in any direction, and that
nevertheless the differentiation of the ectoderm may go on perfectly
well and result in a typical little embryo, which is only smaller in
its size than it would normally be. It is by studying the formation of
the highly complicated ciliary band, that these phenomena can be most
clearly understood.
Now let us imagine our ectoderm to be a cylinder instead of being
approximately a sphere, and let us imagine the surface of this cylinder
unrolled. It will give us a plane of two definite dimensions, *a* and
*b*. And now we have all the means necessary for the analytical study of
the differentiation of an harmonious-equipotential system.
Our plane of the dimensions *a* and *b* is the basis of the normal,
undisturbed development; taking the sides of the plane as fixed
localities for orientation, we can say that the actual fate, the
“prospective value” of every element of the plane stands in a fixed and
definite correlation to the length of two lines, drawn at right angles
to the bordering lines of the plane; or, to speak analytically, there
is a definite actual fate corresponding to each possible value of *x*
and of *y*. Now, we have been able to state by our experimental work,
that the prospective value of the elements of our embryonic organ is not
identical with their “prospective potency,” or their possible fate, this
potency being very much richer in content than is shown by a single case
of ontogeny. What will be the analytical expression of such a relation?
Let us put the question in the following way: on what factors does
the fate of any element of our system depend in all possible cases
of development obtainable by means of operations? We may express our
results in the form of an equation:--
*p.v. (X) = f( ... )*
*i.e.* “the prospective value of the element *X* is a function of
...”--of what?
We know that we may take off any part of the whole, as to quantity, and
that a proportionate embryo will result, unless the part removed is of
a very large size. This means that the prospective value of any element
certainly depends on, certainly is a function of, the *absolute size*
of the actually existing part of our system in the particular case. Let
*s* be the absolute size of the system in any actual experimental case
of morphogenesis: then we may write *p.v. (X) = f(s ... )*. But we
shall have to add still some other letter to this *s*.
The operation of section was without restriction either as to the
amount of the material removed from the germ, or as to the direction of
the cut. Of course, in almost every actual case there will be both a
definite size of the actual system and a definite direction of the cut
going hand-in-hand. But in order to study independently the importance
of the variable direction alone, let us imagine that we have isolated
at one time that part of our system which is bounded by the lines *a_1
b_1*, and at another time an equal amount of it which has the lines
*a_2 b_2* as its boundaries. Now since in both cases a typical small
organism may result on development, we see that, in spite of their equal
size the prospective value of every element of the two pieces cut
out of the germ may vary even in relation to the direction of the cut
itself. Our element, *X*, may belong to both of these pieces of the same
size: its actual fate nevertheless will be different. Analytically, it
may be said to change in correspondence to the actual position of the
actual boundary lines of the piece itself with regard to the fundamental
lines of orientation, *a* and *b*; let this actual position be expressed
by the letter *l*, *l* marking the distance of one[58] of the actual
boundary lines of our piece from *a* or *b*: then we are entitled to
improve our formula by writing *p.v. (X) = f(s, l ... )* (Fig.
11).
[58] The distance of the other boundary line from *a* or *b* would be
given by the value of *s*.
[Illustration: Fig. 11.--Diagram to show the Characteristics of an
“Harmonious-equipotential System.”
The element *X* forms part of the systems *a b* or *a_1 b_1* or
*a_2 b_2*; its prospective value is different in each case.]
But the formula is not yet complete: *s* and *l* are what the
mathematicians call variables: they may have any actual value and there
will always be a definite value of *p.v.*, *i.e.* of the actual fate
which is being considered; to every value of *s* and *l*, which as
we know are independent of each other, there corresponds a definite
value of the actual prospectivity. Now, of course, there is also a
certain factor at work in every actual case of experimental or normal
development, which is *not* a variable, but which is the same in all
cases. This factor is a something embraced in the prospective potency
of our system, though not properly identical with it.
The prospective potency of our system, that is to say of each of its
elements, is the sum total of what can be done by all; but the fact
that a typically proportionate development occurs in every possible
case, proves that this sum comes into account, not merely as a sum,
but as a sort of order: we may call this order the “relation of
localities in the absolutely normal case.” If we keep in mind that the
term “prospective potency” is always to contain this order, or, as we
may also call it, this “relative proportionality,” which, indeed, was
the reason for calling our systems “harmonious,” then we may apply it
without further explanation in order to signify the *non-variable*
factor on which the prospective value of any element of our systems
depends, and, if we denote the prospective potency, embracing order,
by the letter *E*, we are now able to complete our formula by saying
*p.v. (X) = f(s, l, E)*. So far the merely analytical study of the
differentiation of harmonious-equipotential systems.[59]
[59] A far more thorough analysis of this differentiation has been
attempted in my paper, “Die Localisation morphogenetischer Vorgänge. Ein
Beweis vitalistischen Geschehens,” Leipzig, 1899.
*Instances of “Harmonious-Equipotential Systems”*
We must try at first to learn a few more positive facts about our
systems, in order that we may know how important is the part which they
play in the whole animal kingdom, and in order that our rather abstract
analysis may become a little more familiar to us. We know already that
many of the elementary morphogenetic organs have been really proved to
be harmonious-equipotential systems, and that the same probably is true
of many others; we also know that the immature egg of almost all animals
belongs to this type, even if a fixed determination of its parts may
be established just after maturation. Moreover, we said, when speaking
about some new discoveries on form-restitution, that there are many
cases in which the processes of restitution do not proceed from single
localities, the seat of complex potencies in the organism, but in which
each *single* part of the truncated organism left by the operation has
to perform one *single* act of restoration, the full restitution being
the result of the totality of all. These cases must now be submitted to
a full analysis.
All of you have seen common sea-anemones or sea-roses, and many of you
will also be familiar with the so-called hydroid polyps. *Tubularia*
is one genus of them: it looks like a sea-anemone in miniature placed
on the top of a stem like a flower. It was known already to Allman
that *Tubularia* is able to restore its flower-like head when that
is lost, but this process was taken to be an ordinary regeneration,
until an American zoologist, Miss Bickford, succeeded in showing that
there was no regeneration process at all, in the proper sense of the
word, no budding of the missing part from the wound, but that the new
tubularian head was restored by the combined work of many parts of the
stem. Further analysis then taught us that *Tubularia* indeed is to be
regarded as the perfect type of an harmonious-equipotential system: you
may cut the stem at whatever level you like: a certain length of the
stem will always restore the new head by the co-operation of its parts.
As the point of section is of course absolutely at our choice, it is
clear, without any further discussion, that the prospective value of
each part of the restoring stem is a “function of its position,” that
it varies with its distance from the end of the stem; and so at once
we discover one of the chief characteristics of our systems. But also
the second point which enters into our formula can be demonstrated in
*Tubularia*: the dependence of the fate of every element on the actual
size of the system. You would not be able to demonstrate this on very
long stems, but if you cut out of a *Tubularia* stem pieces which are
less than ten millimetres in length, you will find the absolute size
of the head restored to be in close relation to the length of the stem
piece, and this dependence, of course, includes the second sort of
dependence expressed in our formula.
The figures will serve to show you a little more concretely what has
been described. The head of *Tubularia* consists of a sort of broad base
with a thin proboscis upon it, both bearing a large number of tentacles;
these tentacles are the first things to be seen as primordia (“Anlagen”)
in the process of restitution. You notice two rings of longitudinal
lines inside the stem; the lines will become walls and then will
separate from the stem until they are only connected with it at their
basal ends; the new tentacles are ready as soon as that has happened,
and a process of growth at the end will serve to drive the new head out
of the so-called perisarc or horny skeleton, which surrounds the stem.
By comparing the two figures, 12 *e*, and *g*, you easily find out that
the absolute lengths of the two tentacle rings are very different, and
that both are in proportion[60] to the actual size of the stem (Fig. 12).
[60] This statement is *not strictly* correct for *Tubularia*. I found
(*Archiv f. Entwickelungsmechanik*, ix. 1899), that a reduction of the
length of the stem is always followed by a reduction of the size of the
hydranth-primordium, but there is no real proportionality between them.
It is only for theoretical simplification that a strict proportionality
is assumed here, both in the text and the diagram. But there is an
almost strict proportionality in all cases of “closed forms.”
[Illustration: Fig. 12.--Tubularia.
*a.* Diagram of the “Hydranth,” with its short and long tentacles.
*b.* Restitution of a new hydranth inside the perisarc (*p*).
*c.* The same--later stage; the tentacles are complete; the whole
hydranth will be driven out of the perisarc by a process of growth that
occurs at the locality marked ⬆.
*d.* A stem of *Tubularia* cut either at *a_1 b_1* or at *a_2 b_2*,
or at *a_1 c*.
*e.* Position of tentacles in the piece cut at *a_1 b_1*.
*f.* Position of tentacles in the piece cut at *a_2 b_2*,
which is equal in length to *a_1 b_1*.
*g.* Position of tentacles in the piece cut at *a_1 c*,
which is half as long as *a_1 b_1*.]
So we find our formula *p.v. (X) = f(s, l, E)* very well
illustrated in *Tubularia*. The formula indeed may help us to predict,
in any case, where a certain part of the polyp’s organisation is
to originate, at least if we know all that is included under our
letter *E*, *i.e.* the normal proportion of our form. Of course such
prediction would not have much practical importance in all our cases of
morphogenesis, but nevertheless I should like to state here that it is
possible; for many scientific authors of recent times have urged the
opinion that prediction of, and domination over, what will happen, can
be the only true aims of sciences at all. I myself judge these aims to
be of second or third-rate importance only, but, if they may be reached
by what our purely theoretical study teaches, so much the better.
Another very typical case of a morphogenetic system of the harmonious
type is supplied by the phenomena of restoration in the ascidian
*Clavellina*. I cannot fully describe the organisation of this form
(Fig. 13a), and it must suffice to say that it is very complicated,
consisting of two very different chief parts, the branchial apparatus
and the so-called intestinal sac; if these two parts of the body of
*Clavellina* are separated one from the other, each may regenerate the
other in the typical way, by budding processes from the wound. But, as
to the branchial apparatus, there may happen something very different:
it may lose almost all of its organisation and become a small white
sphere, consisting only of epithelia corresponding to the germ-layers,
and of mesenchyme between them, and then, after a certain period of
rest, a new organisation will appear. Now this new organisation is
not that of a branchial apparatus but represents a very small but
complete ascidian (Fig. 13). Such a fact certainly seems to be very
important, not to say very surprising; but still another phenomena may
be demonstrated on the animal which seems to be even more important. You
first isolate the branchial apparatus from the other part of the body,
and then you cut it in two, in whatever direction you please. Provided
they survive and do not die, as indeed many of them do, the pieces
obtained by this operation will each lose their organisation, as did the
whole branchial apparatus, and then will each acquire another one, and
this new organisation is also that of a *complete* little *Clavellina*.
So we see that not only is the branchial apparatus of our animal capable
of being transformed into a whole animal by the co-operative work of
all its parts, but even each part of it may be transformed into a small
*whole*, and it is quite at our disposal how large this part shall be,
and what sort of a fragment of the original branchial apparatus it shall
represent.
[Illustration: Fig. 13.--Clavellina.
*a.* Diagram of the normal animal: *E* and *J* = openings; *K* =
branchial apparatus; *D* = intestine; *M* = stomach; *H* = heart.
*b.* The isolated branchial apparatus.
*c-e.* Different stages of reduction of the branchial apparatus.
*f.* The new *whole* little ascidian.]
We could hardly imagine a better instance of an harmonious-equipotential
system.
I cannot give you a description of all the other types of our systems
subservient to restitution, and I can only mention here that the common
hydra and the flatworm *Planaria* are very fine examples of them. But
to one special case of harmonious equipotentiality you must allow me to
direct your further attention.
It has been known for many years that the Protozoa are also capable of
a restoration of their form and organisation after disturbances, if at
least they contain a certain amount of their nuclear substance. This
process of restoration used to be regarded as belonging to the common
type of regeneration proper, until T. H. Morgan succeeded in showing
that in the genus *Stentor* it follows just the very lines which we know
already from our study of embryonic organs or from *Tubularia*; that
an harmonious-equipotential system is at the basis of what goes on.
Now, you know that all Protozoa are but one highly organised cell: we
have therefore here an instance where the so-called “elements” of our
harmonious-morphogenetic system are not cells, but something inside of
cells; and this feature must appear to be of very great moment, for it
first shows, as we have already pointed out on another occasion, that
morphogenesis is not dependent on cell-division, and it states at the
same time that our concept of the harmonious-equipotential system may
cover a very great area--that, in fact, it is a scheme of a very wide
extent.
*The Problem of the Factor* E
We turn back again to considerations of a more abstract form. We left
our analysis of the differentiation of the harmonious-equipotential
systems, and particularly of the phenomena of localisation during this
differentiation, at the point where we had succeeded in obtaining an
equation as the expression of all those factors on which the prospective
value, the actual fate, of any element of our systems depends, *p.v. (X)
= f(s, l, E)* was the short expression of all the relations involved;
*s* and *l*, the absolute size of the system and the relative position
of the element with respect to some fixed points, were independent
variables; *E* was a constant, namely, the prospective potency, with
special regard to the proportions embraced by it.
We shall now study the significance of the factor *E*.
What does this *E* mean? Is it a short expression merely for an actual
sum of elemental agents having a common resultant? And, if so, of what
kind are these agents? Or what may *E* mean, if it can be shown *not* to
be a short sign for a mere sum?
*No Explanation Offered by “Means” or “Formative Stimuli”*
For practical purposes it seems better if we modify the statement of our
question. Let us put it thus: *E* is one of the factors responsible,
among variables, for the localisation of organic differentiation;
what then do we actually know about the causal factors which play a
localising part in organogenesis? We, of course, have to look back to
our well-studied “formative stimuli.” These stimuli, be they “external”
or “internal,” come from without with respect to the elementary organ
in which any sort of differentiation, and therefore of localisation,
occurs: but in our harmonious systems no localising stimulus comes from
without, as was the case, for instance, in the formation of the lens of
the eye in response to the optical vesicle touching the skin. We know
absolutely that it is so, not to speak of the self-evident fact that the
general “means” of organogenesis have no localising value at all.[61]
[61] One might object here that in a piece of a *Tubularia* stem, for
instance, the tissues are in direct contact with the sea-water at
the two points of the wounds only, and that at these very points a
stimulus might be set up--say by a process of diffusion--which gradually
decreases in intensity on its way inward. And a similar argument might
apply to the small but whole blastula of Echinus, and to all other
cases. But, in the first place, stimuli which only differ in intensity
could hardly call forth the typical and typically localised single
features realised in differentiation. On the other hand--and this will
overthrow such an hypothesis completely--the dependence of the single
localised effects in every case on the *absolute size* of the fragment
or piece chosen for restoration renders quite impossible the assumption
that all the singularities in the differentiation of the harmonious
systems might be called forth by single stimuli originating in two
fixed places in an *independent* way. These would never result in any
“harmonious,” any proportionate structure, but a structure of the
“normal” proportionality *and size* at its two ends and non-existent in
the middle!
So we see there is nothing to be done, either with the means or with the
formative stimuli; both are entirely unable to account for those kinds
of localisation during differentiation which appear in our harmonious
systems.