LECTURE XXI
REGENERATION (continued)
Phyletic origin of the regenerative capacity—The liberating stimuli of regeneration—Production of extra heads and tails in Planarians (Voigt)—Regeneration in the Starfish—Atavistic regeneration in Insects and Crustaceans—Progressive regeneration—Regeneration has its roots in the differentiation of organisms—The nuclear substance of unicellular organisms is the first organ for regeneration—The ultimate roots of regeneration.
In the previous lecture we have considered many different forms of regeneration, and have recognized them as adaptive phenomena; we have now to inquire how such regeneration-adaptations have arisen, and this is a very difficult question even in general, while in particular cases it is often quite unanswerable at present. In regard to the case last discussed, the regeneration of the lens in the eye of Triton, our hypotheses would require to reach back to the time of the primitive vertebrates with an unpaired eye, for the lens of the paired vertebrate eye, from Mammals down to the lowest Fishes, does not arise in embryonic development from the retinal cells, but always from the corneal epithelium, as the elaborate researches of Rabl have recently shown. It is true that the unpaired parietal eye of some reptiles forms its lens from the cells of the retinal layer, but it would be difficult to demonstrate the possibility of a genetic connexion between it and paired eyes, and in the meantime we must refrain from elaborating a hypothesis as to the origin of the marvellous faculty the retinal cells possess of transforming themselves into lens-fibres.
But it is easier to form some sort of picture of the origin and adaptation of the faculty of regeneration in general.
We saw that the power of regenerating a part can be localized, and that it does not belong to all the cells of the body, but only to some of them, and we have to ask how and by what steps it has been imparted to these. The faculty depends on the possession of a regeneration-primordium (Anlage), and this again, in our mode of expression, consists of a definite complex of determinants, and as determinants are the products of an evolution, and thus are vital units which have arisen historically, they can nowhere suddenly originate anew in a species, but must be derived directly or indirectly from the sole basis which, in each species, forms the starting-point of the individual—that is to say, in the Metazoa, from the germ-plasm of the ovum. From it the determinant-complex of every regeneration-rudiment mast in the ultimate instance be derived.
We may think of the matter thus: all the determinants of the germ-plasm vary, grow slowly or quickly, and in certain circumstances may be doubled. In this way there arise what we may call 'supernumerary' determinants, which are not required in the primary building up of the body from the ovum, and which may remain in an inactive state in the nuclei of certain cells, ready to become active under certain circumstances and to produce anew the part which they control. Such regeneration-idioplasm will at first come to lie in the younger cells of the determinate organ, but it is conceivable that under the influence of selection it may be gradually shifted to other cells of a later developmental origin, or, conversely, to others in a less external position, so that, for instance, the regeneration-rudiment for the finger of a newt may be contained not merely in the cells of the hand, but in those of the fore-arm or even of the upper arm.
But all such segregation of determinant-groups cannot have taken place, as we might perhaps be inclined to think, at the periphery in the organ itself during its development; it must take place in the germ-plasm of the ovum, for otherwise it could not be transmissible, and could not be directed and modified by the processes of selection, as is actually the case, as I shall show in more detail later on.
I have already pointed out the importance of the rôle played by liberating stimuli in regeneration, and not only of extra-organismal stimuli, such as gravity, but above all of intra-organismal stimuli that is, the influences exerted in a mysterious manner by other parts of the animal on the parts which are in process of regeneration. It is a great merit of the modern tendency in evolution theory that it has demonstrated the importance of such internal influences. Although we are still far from being able to define the manner in which these influences operate, we may say so much, that it depends essentially on the nature and extent of the loss which parts are reproduced by the regenerating cells, and, also, on the position and direction of the injured surface from which the regeneration starts. The influences, still quite beyond our comprehension, which are exerted on the regenerating part by the uninjured parts constitute the liberating stimuli, which evoke the activity of one or other of the determinants contained in the regeneration-idioplasm.
Fig. 100. Regeneration of Planarians. A, an animal divided into three parts by two oblique cuts. B, the fragments(a, b, c) in process of regeneration. C, an animal with various oblique incisions in the margin of the body, which have induced the new formation of heads (k), of tails (s), and pharynx (ph). A and B after Morgan; C after Walter Voigt.
Walter Voigt has shown, by a series of most interesting experiments, that it is possible not only to cause the development of a new head in Planarians by cutting them, in which case a tail may grow from the anterior portion and a head from the posterior portion, but it is also possible in an intact animal, that is, one with both head and tail, to cause the production of a second head, or a second tail, or both at once, at any part of the body margin at will, according to the direction of the cut. If the margin of the body be cut obliquely forwards (Fig. 100, A) a supernumerary tail arises (C, s), if it be cut obliquely backwards a supernumerary head arises (C, k), and in this way several heads and several tails may be produced in the same animal. It is obvious, then, that the interaction, in the first place, of the cells of the cut surface, but probably also of the deeper-lying cells, decides which determinants are to come into action, those of the head or those of the tail, but both must be present at every part of the cut. How far below the cut surface the cells take part in this determination we cannot make out, but that it cannot be due to the co-operation of all parts is clear in this case at least, since the animal still possesses its original head and tail. The extra heads and tails thus produced prove, at any rate, that there can be no question here of the expression of an adaptive principle, a spiritus rector, or a vital force, which always creates what is good, but that it is rather a purely mechanical process, which takes its course quite independently of what is useful or disadvantageous, and that it must take this course according to the given regeneration-mechanism and the stimulus supplied in the special case. It cannot be supposed that these supernumerary heads and tails are purposeful, but who would expect an adaptive reaction from the animal in a case like this, since cuts of the kind which we make artificially, and must keep open artificially if the deformities are to develop, hardly occur in nature, and, if they did occur, would very quickly close up again? Adaptations can only develop in response to conditions which occur and recur in a majority of cases, and when they have a useful, that is, species-preserving result. The adaptiveness of the organism is blind, it does not see the individual case, it only takes into account the cases in the mass, and acts as it must after the mechanism has once been evolved. The case is the same as that of 'aberrant' or mistaken instincts, whose origin by means of selection is the more clearly proved, since we must recognize such an instinct as a pure mechanism and not as the outcome of purposeful forces.
In the regeneration of Planarians we must think of the regeneration-idioplasm as containing the full complex of the collective determinants of the three germinal layers, and possibly we must add to this cells with the complete germ-plasm for giving rise to the reproductive cells. But when the amputated tail of the newt is regenerated, or its leg, or the arm of a starfish, or the bill of a bird, we have no ground for assuming that the cells, from which regeneration starts, contain the whole germ-plasm, since the determinants of the replaceable parts suffice to explain the facts. We must even dispute the possibility of the presence of the whole germ-plasm in this case, because the faculty of regeneration of the relevant cells is really no longer a general one, but is limited to the reproduction of a particular part. This is seen in the fact that, in the starfish, whose high regenerative capacity is well known, the central disk of the body may indeed give rise to new arms[2]; but an excised arm, to which no part of the disk adheres, is in most starfishes unable to give rise to the body. Thus the arm does not contain in its cells the determinants of the disk, but the latter contains those of the arm. We are not surprised that the amputated tail of the salamander does not reproduce the whole animal, but this can only be because the impelling forces to the regeneration of the whole animal are wanting, that is, that the cut surface only contains the determinants of the tail and not the complete germ-plasm. It might be objected here that the tail-piece is too small to give rise to the whole body, but in Planaria it is only very diminutive heads and tails which grow from the artificial incisions, and the same is true of starfishes when only a single arm and a small piece of the disk have been left. Notwithstanding the small amount of living substance at their disposal, and although they are at first unable to take nourishment, they send out very small new arms (Fig. 101), close up the wounded surface, and, after reconstruction of the mouth and stomach, begin to feed anew. The new arms may then grow to the normal size.
[2] I see now that there are contradictory statements in regard to this case. Possibly these depend on the different behaviour of different species, and this on the varying frequency of mutilation. Starfishes which live on the shore between the rocks, for instance on the movable stones of a breakwater, are very frequently mutilated; in some places it is rare to find a specimen without traces of former wounds. H. D. King counted among 1,914 specimens of Asterias vulgaris 206 in the act of regenerating a part, that is, 10.76 per cent. In the case of the starfishes from deep water this cause of injury does not of course exist.
Fig. 101. A starfish arm,
growing four new arms;
the so-called 'comet-form.'
After Haeckel.
We must therefore assume that, in many cases, the regeneration-primordium consists of cells which only contain a definite complex of determinants in the form of latent regeneration-idioplasm, as, for instance, certain cells of the tail of Triton contain the determinants of the tail, certain cells of its leg the determinants of the leg, and so on. In many cases we can speak even more precisely, and determine from which cells the nerve-centres, from which the muscles, and from which the missing section of the food-canal will be formed, as was recently shown by Franz von Wagner in regard to the worm Lumbriculus, whose regenerative capacity is so extraordinarily high. We must then attribute to each of the relevant cells an equipment of regeneration-idioplasm, which includes only the relevant complex of determinants.
I need not here go further into detail, but I should still like to show that, in reality, as I assumed in regard to the regenerative capacity of a part, the root of the regeneration-idioplasm lies in the germ-plasm, that it is present there as an independent determinant-group, and, like every other bodily rudiment (Anlage), must be handed on from generation to generation. This assumption is necessary, as has been already indicated, on the ground that the faculty of regeneration is hereditary, and hereditarily variable, on the same ground, therefore, as that on which the whole determinant theory is based. The regeneration-determinants must be contained as such in the germ-plasm, otherwise a twofold phyletic development could not have occurred, as it actually has, in many parts. The tail of the lizard is adapted for autotomy; it breaks off when it is held by the tip, and this depends on a special adaptation of the vertebræ, which are very brittle in a definite plane from the seventh onwards. This is thus a very effective adaptation to persecution by enemies. The tail which has been seized remains with the pursuer, but the lizard itself escapes, and the tail grows again. But this regeneration does not take place in the same way as in the embryo; no new vertebræ are formed, but only a 'cartilaginous-tube,' a new structure, a substitute for the vertebral column; the spinal cord with its nerves is not regenerated either, and the arrangement of the scales is somewhat different.
This last point, in particular, indicates that the determinants of the regeneration-rudiment may pursue an independent phylogenetic path of their own, for this scale arrangement of the regenerated tail is an atavistic one, that is, it corresponds to a more primitive mode of scale arrangement in these Saurians. We know quite a number of cases similar to this. It not infrequently happens that cut-off parts regenerate, but that they do so not in the modern form, but in one that is in all probability phyletically older. Thus the legs of various Orthoptera, as of the cockroaches and grasshoppers, regenerate readily, but with a tarsus composed of four joints instead of five[3], and the long-fingered claws of a shrimp (Atyoida potimirim) is replaced by the older short-fingered type of claw, while in the Axolotl an atavistic five-fingered hand grows instead of the amputated four-fingered one.
[3] New investigations, specially directed to this point, by R. Godelmann, have shown that 'in the great majority of cases' the regenerated legs of a Phasmid (Bacillus rossii) exhibit a four-jointed tarsus; but the regeneration of five joints also occurs, though only after autotomy, and only in seven out of fifty cases (Archiv für Entwicklungsmechanik, Bd. xii, Heft 2, July 1901). The regeneration-rudiment in this species seems to be in process of advancing slowly to the five-jointed type.
This last case shows that it is not merely a lesser power of growth that accounts for the difference between the regenerated part and the original, for here more is regenerated than was previously present. There remains nothing for it but the assumption that the regeneration-determinants have remained at a lower phyletic level, while the determinants which direct embryogenesis have varied, and either developed further or retrogressed. It is easy to understand that the regeneration-rudiment must vary phyletically much more slowly than the parts which evolved in the ordinary way and much more slowly than the determinants of these parts, for natural selection means a selection of the fittest, and the speed with which the establishment of a variation is attained depends, ceteris paribus, on the number of individuals that are exposed to selection with respect to the varying part. If in a species of a million living at the same time nine-tenths perish by accident, there will remain only 100,000 from which to select the 1,000 which we will assume constitute the normal number of the species. The more of these 100,000 which possess the useful variation the higher will be the percentage of the normally surviving 1,000 possessing it, and the more rapidly will the useful variation increase. But when it is a question of the variation of the regeneration-primordium, the selection will take place not among all the 100,000 individuals which chance has spared, but only among those of them which have lost a limb by accident, and thus are in a position to regenerate it more or less completely. If we assume that this takes place in 10 per cent. of cases, then selection for the improvement of the regeneration-apparatus will only take place among 1,000 individuals, and thus the process of modification of the regeneration-primordium must go on very much more slowly than that of the limb itself.
I do not see how the opponents of the germ-plasm theory can explain these facts at all, for the appeal to external influences is here entirely futile, and that to internal liberating stimuli does not suffice, since these must be different after a part has been cut off from what they were when the limb developed normally, and also different from those which prevailed at the normal origin of the limb in ancestral forms. The four-jointed tarsus of the ancestors of our cockroaches did not arise as a result of amputation. We cannot therefore avoid referring the processes of regeneration to particular 'regeneration-determinants,' which are contained in the germ-plasm and are handed on in ontogeny with the other determinants from cell-division to cell-division, till ultimately they reach the cells which are to respond, or may have to respond, to the stimulus of injury by some expression of their regenerative capacity. As these determinants, as has been shown, can often only be very slightly subject to the influence of selection processes, they will, in many respects, lag behind in the phyletic development, and will tend to belong to an ancestral type of the relevant part. They will often remain for a long time at this ancestral level, and they will always adapt themselves to new requirements more slowly than the parts which arise in the normal way, and the determinants representing these in the germ. But the regeneration-determinants are variable, and, indeed, are so hereditarily, and independently of the structure of the normal parts. They thus follow their own path of phyletic development, and this one fact is enough to secure a preference for the germ-plasm theory above others that have hitherto been suggested. None of these has even attempted an explanation of this fact; the tendency has rather been to call it in question. This, however, can be done at most only in regard to the explanation of the regenerations as atavistic, certainly not in regard to the progressive variations of the regenerated part, such as have been established by Leydig and Fraisse in regard to the lizard's tail. It may be doubted whether the most primitive insects had only four tarsal joints, but there is no disputing the kainogenetic deviation of the lizard's-tail.
I have interpreted the regenerative capacity as secondary and acquired, not as a primary power of all living substance, and I should like to substantiate this in another way.
Let us go back to the simplest organism conceivable, which must have represented the beginning of life on our earth, and we see that this need not have possessed any special power of regeneration, because, for an organism without differentiation of parts, growth is equivalent to regeneration. But growth is the direct outcome of one of the primary characters of the living substance, the capacity of assimilation. This cannot be an adaptive phenomenon, nor can it have arisen through selection, because selection presupposes reproduction, and reproduction is only a periodic form of growth; but growth follows directly from assimilation. The fundamental characters of the living substance, above all the dissimilation and assimilation which condition metabolism, must have been in existence from the first when living substance arose, and must depend on its unique chemico-physical composition. But the faculty of regeneration could only be acquired when organisms became qualitatively differentiated, so that each part was no longer like every other part or like the whole. As soon as this stage was reached the faculty of regeneration would necessarily be developed, if further multiplication was to take place. For when each fragment could no longer become a whole by simply growing, some arrangement had to be made by which each fragment should receive, in the form of primary constituents, what it lacked to make up the whole. We do not know the first beginning of this adaptation, but, in its further development, it appears in the form of 'nuclear substance,' enclosed in the nucleus of the cell, and, as is well known, it is now to be found in all unicellular organisms. That the nucleus there precedes regeneration in the sense that without a piece of it the cell-soma is not able to complete itself alone, we have already seen, and the explanation of this fact has always seemed to me to be that invisibly minute vital units relating to the regeneration of the injured part leave the nucleus and evoke the development of the missing parts by laws and forces still unknown to us. Loeb has recently claimed that the nucleus is the cell's organ of oxidation; but if that be true it would still not exclude the possibility that the nucleus is also and primarily a storehouse of the material bearers of the primary constituents of a species. It must be regarded as such when we call to mind the phenomena of amphimixis in its twofold aspects as conjugation and as fertilization, and its obvious outcome among higher organisms where it implies the mingling of the parental qualities.
Thus the 'nuclear substance' of unicellular organisms is for us the first demonstrable organ of regeneration, and first of all for normal regeneration, which takes place at every reproduction, for instance, of an Infusorian. For we have already seen that, in the transverse division of a trumpet animalcule (Stentor), the anterior part must develop the posterior half anew, while the posterior half must develop the much more complex anterior half, with mouth region and spiral bands of cilia. But as soon as the arrangement for normal reproduction was elaborated, as soon as the nucleus was present, as a depôt of 'primary constituents,' this implied the possibility of regeneration in exceptional cases, that is, after injury. The mechanism was already there, and it came into operation as soon as a part of the animal was missing.
It is in the first nucleus, therefore, that we have to look for the source of all regenerative capacity, both in unicellular and multicellular organisms. But with the origin of the latter a limitation took place, either quite at the beginning or a little later, for each nucleus of the cell-colony no longer contained the whole complex of 'primary constituents' or determinants of the species, but, in many cases, only the reproductive cell possessed them. As soon as this began to develop into a whole by cell-division the determinant-complex was segregated. Thus the first cell-colonies with two kinds of cells arose, as we have seen in the case of Volvox—the reproductive cells with a complete equipment for regeneration in their nucleus, and the somatic cells with a limited equipment for regeneration in their nuclei. The somatic cell could no longer give rise anew to the whole organism, but could only reproduce itself or its like.
But as many of the lower Metazoa and Metaphyta possess the power of budding, that is, are able not only to produce a new individual from definite cells—the reproductive cells—with or without sexual differentiation, but from other cell-groups also, these must contain the whole complex of determinants appertaining to the reconstruction of the organism, and we have to ask how this is reconcilable with the differentiation of a multicellular organism, whose different kinds of cells depend, according to our interpretation, on the fact that they are controlled by different determinants.
Obviously, there is only one way out of this difficulty, and it is the one we have already indicated, that although the diffuse regenerative capacity which we have just alluded to occurs in species which exhibit gemmation, this does not exclude the control of a cell by a specific determinant; other determinants may be contained in the cell, in a state, however, in which they do not affect it, that is, in an inactive or latent state.
Thus we arrive in this way also at our earlier assumption that an inactive accessory-idioplasm is given to all, or at least to many cell-generations. Only among plants must this necessarily be complete germ-plasm, and among the lower plant-forms, as in Caulerpa among the Algæ, in Marchantia among Liverworts, it must be assumed to be present in nearly all the cells, according to the experiments in regeneration made by Reinke and Vöchting. But in multicellular animals which develop from two different germinal layers equipped with a different complex of determinants budding arises from a combination of at least two different kinds of cells, and we must only ascribe to each of these its own peculiar determinant-complex as regeneration-idioplasm. Higher plants show us that well-marked power of budding is not necessarily associated with a high regenerative capacity, the histologically specialized cells among them will contain no inactive germ-plasm, because they do not need it. But in animals the power of budding is probably always combined with high regenerative capacity, as is shown by the Polyps and Medusoids above all, and in a different way by the Ctenophores, which exhibit no budding and at the same time a very slight regenerative capacity, although they possess an organization scarcely higher than that of the Hydromedusæ. In the Ctenophores each of the first segmentation-cells, when artificially separated, yields only a half-embryo, and we may conclude from this that it contains no complete germ-plasm in an inactive state, or at least very little, and certainly not a sufficient quantity to make it readily regenerative.
Undoubtedly, however, the regenerative capacity occurs apart from the capacity for budding, yet this in no way contradicts the theory. As we have seen, a high regenerative capacity is to be found among many animals which occur only as 'persons' and not as colonies or stocks, but only in those which are readily liable to injury, and only in the manner conditioned by their injury. In the higher Metazoa the regenerative power becomes more and more limited, and in the Mammals it sinks to a mere closing up of wounds.
If we take a survey of the assumptions we have been compelled to make from the standpoint of the theory to explain the development of germ-cells, budding, and regeneration, it would seem as if it were contradictory to assume that, on the one hand, complete germ-plasm should be given to certain cell-series as inactive accessory idioplasm, and, on the other, that very numerous cells, at least in the lower Metazoa, should have received the idioplasm of budding, and still more numerous cells that of regeneration. But it is obvious that among the lower Metazoa the idioplasm of budding and the idioplasm of regeneration are equivalent; the same idioplasm, which, when liberated by stimuli unknown to us, co-operates from two or three germinal layers in the formation of a bud, effects, in response to the known stimulus of injury, the regeneration of the mutilated part. But germ-cells can never arise in the Metazoa from the partial budding-idioplasm or regeneration-idioplasm, because this is not complete germ-plasm, and because it can only give rise to budding or regeneration through the co-operation of two or more kinds of cells, while germ-cells always originate from one cell and never arise from the fusion of cells. Germ-cells can thus only arise from the cells of the germ-track, and in no other way, no matter whether the germ-track lie in the ectoderm, as in the Hydromedusæ, or in the endoderm, as in true jellyfishes (Acalephæ) and the Ctenophores, or in the mesoderm, as in many higher groups of animals. It is only apparently that these cells belong to one particular layer, for in reality they are unique in kind, and they are simply assisted in their development by one or other cell-layer, from which they not infrequently emancipate themselves, as happens so notably in the Hydromedusæ. As we have already said, it is only among plants that we must think of budding as arising from cells which contain complete germ-plasm, for here there are no 'germinal layers' corresponding to those of animal development, and the cells of 'the growing point' must be equipped with the complete germ-plasm. The plant, like the Hydroid stock and the Siphonophore colony, is saved from death, in spite of the frequent loss of its members, mainly by the fact that it is capable of producing, at almost any part above the ground, buds which develop into new shoots, with leaves and the like. This makes a power of regeneration on the part of the individual leaves and flower-parts superfluous, but at the same time it implies that an enormous number of cells must be distributed over the whole surface of the plant, each of which can in certain circumstances become the starting-point of a bud. That is to say, each must contain, in a latent state, the complete germ-plasm which is necessary for the production of an entire plant.
We must therefore assume that, in the higher colony-forming plants, germ-plasm is contained in a great many cells, perhaps in all which are not histologically differentiated, and sometimes even in those which are so, as, for instance, in the leaves of Begonias. I suppose, therefore, that in the higher plants the process of development implies a segregation of the determinant-complexes of the germ-plasm, but that this takes place at a late stage, and that in a much higher degree than among animals the individual or the 'person' carries with it germ-plasm in a latent state. To this must be attributed the fact that the plant is not only able to make good its losses in twigs and branches by sending out new shoots, but that cuttings, that is, detached shoots, are also able to take root, and in general to give rise to what is necessary to complete themselves according to the position of the part in question. In the ontogeny of animals, too, we must assume that it requires a liberating stimulus to rouse the determinants to activity, that this stimulus is to be sought for in the influence exercised by the constitution of the cell on the idioplasm contained within it, and that this constitution in its turn is subject to influences from external conditions, including the cell-soma itself. We may therefore suppose that, among plants also, the germ-plasm latent in numerous cells only becomes active in whole or in part according to the influences exerted on it by the state of the cell at the moment; but this varies with external circumstances, according to whether the cell is exposed to light or lies under ground, according as it is influenced by gravity, by moisture, chemical stimuli, and so on.
It might be objected to this that it would be simpler not to assume a segregation of the germ-plasm into determinant-complexes at all in order to explain the process of development, but rather to credit each cell with a complete equipment of germ-plasm from the beginning to the end of the ontogeny, and to attribute the differences in the cells, which condition the structure of the plant and its differentiation, solely to the different influences, external and internal, to which the cell is exposed, and which rouse some determinants to activity at one part and others at another. Perhaps the botanists would be more readily reconciled to this idea, but it seems to me that there are two points which tell against the possibility of its being correct. In the first place, it is far from being established that every cell in the higher plants is capable of giving rise, under favourable conditions, to a whole new plant; every tree and every higher plant has a multitude of cells in its leaves, its flowers, and so on, which cannot do this, which are in fact differentiated in one particular direction, that is, they contain only one kind of determinants, like the histologically differentiated cells of the tissues of the human body. Secondly, there are other organisms besides plants, and a theory of development cannot be based on the phenomena to be observed among plants alone, any more than a theory of heredity can. There are obvious differences in the processes of life among plants as contrasted with those among animals, but it is improbable that there is any thoroughly fundamental difference. It is, however, indubitable that the cells forming the tissues of higher animals, the nerve, muscle, and glandular cells, are really differentiated in one direction, and are quite incapable, under any circumstances whatever, of growing into an entire organism, and even from this alone we might conclude that they contain only one primordium or determinant. Are we then to assume that the vascular cells, epidermis-cells, wood-cells, and so on, of the higher plants, which are also differentiated in one direction, do nevertheless contain the complete germ-plasm? I do not see any ground for such an assumption.
To conclude what can be said on the subject of regeneration we must return to the question of an ultimate explanation of this marvellous phenomenon. I have declined to attempt any explanation at all, because I do not consider it possible to give a sufficient one as yet, but I should like at least to give an indication as to the direction in which we must look for it.
We assumed that there is a regeneration-idioplasm, and therefore that there are 'primary constituents' at certain positions in the body, but how does it happen that these are able to build up the lost parts in the proper situation and detail? A theoretical formula might well be thought out, according to which the determinants of successive parts would become active successively, and would thus liberate one another in an appropriate order of sequence, but there would not be much gained by this, especially as what we already know in regard to the regrowth of the legs and toes in Triton does not harmonize with such an assumption. It appears to me more important—though even here we must still be very vague as to details—to recognize that, in all vital units, there are forces at work which we do not yet know clearly, which bind the parts of each unit to one another in a particular order and relation. We were obliged to assume such forces even in regard to the lowest units, the biophors, since otherwise they could not be capable of multiplication by division, on which all organic growth depends, unless we are to assume, as Nägeli did, a continual generatio æquivoca of the specific kinds of biophors (his 'micellæ'). But we shall see later, when we come to speak of spontaneous generation, that we cannot acquiesce in such an assumption. If, then, we cannot conceive of a power of division arising from within and depending solely on growth by means of assimilation, without such attractive and repellent forces or 'vital affinities' the internal parts would necessarily fall into disorder at every division. It seems to me therefore that such 'affinities' must be operative at all stages in the life of the vital units, not only in biophors, but also in the cell, and in the 'person' as well as in determinant and id. It is true that 'persons' no longer generally possess the power of multiplying by division, but in plants and lower animals many do possess it; and the power of giving rise anew to certain parts is obviously a part of that power of doubling the whole by division. The ultimate roots of regeneration, then, must lie in these 'affinities' between the parts, which preside over their arrangement and are able to maintain it and to give rise to it anew. In this respect the organism appears to us like a crystal whose broken points always complete themselves again from the mother-lye after the same system of crystallization, obviously in this case too as a result of certain internal directive forces, polarities, which here again we are unable precisely to define. But the difference between the organism and the crystal does not—as people have been hitherto inclined to believe—lie only in the fact that the crystal requires the mother-lye to complete itself, while the vital unit itself procures the material for its further growth; it lies also in the fact that such regeneration is not possible in every organism and at every place, but that special 'primary constituents' are necessary, without which the relevant part cannot arise. The indispensableness of these primary constituents, the determinants, seems to me to depend on the fact that the new structure cannot be built up simply by procuring organic material, but that specially hewn stones, different in every case, are necessary, which can only be supplied in virtue of an historical transmission, or, to abandon the metaphor, because the vital units of which the organ is to be reconstructed possess a specific character and have a long history behind them; thus they can only arise from such vital units as have been handed on through generations, that is, from the determinants. But these primary constituents are given to the different forms of life in very varying degrees and in very unequal distribution, and as far as we can see according to their suitability to an end.