Chapter VI: Part I: The Individual Organism with Regard to Form and Metabolism (3)

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.

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?