THE RELATIONS OF THE ORGANITES.

133. In enumerating among the obstacles to research the tendency to substitute hypothetic deductions in place of objective facts, I had specially in my mind the wide-reaching influence of the reigning theories of the nerve-cell. Had we a solidly established theory of the cell, equivalent, say, to our theory of gas-pressure, we should still need caution in allowing it to override exact observation; but insecure as our data are, and hypothetical as are the inferences respecting the part played by the cell, the reliance placed on deductions from such premises is nothing less than superstition. Science will take a new start when the whole question is reinvestigated on a preliminary setting aside of all that has been precipitately accepted respecting the office of the cell. This exercise of the imagination, even should the reigning theories subsequently be confirmed, would not fail to bring many neglected facts into their rightful place.

I am old enough to remember when the cell held a very subordinate position in Neurology, and now my meditations have led me to return, if not to the old views of the cell, at least to something like the old estimate of its relative importance. Its existence was first brought prominently forward by Ehrenberg in 1834, who described its presence in the sympathetic ganglia; and by Remak in 1837, who described it in the spinal ganglia. For some time afterwards the ganglia and centres were said to contain irregular masses of vesicular matter which were looked on as investing the fibres; what their office was, did not appear. But there rapidly arose the belief that the cells were minute batteries in which “nerve-force” was developed, the fibres serving merely as conductors. Once started on this track, Hypothesis had free way, and a sort of fetichistic deification of the cell invested it with miraculous powers. In many works of repute we meet with statements which may fitly take their place beside the equally grave statements made by savages respecting the hidden virtues of sticks and stones. We find the nerve-cells credited with “metabolic powers,” which enable them to “spiritualize impressions, and materialize ideas,” to transform sensations into movements, and elaborate sensations into thoughts; not only have they this “remarkable aptitude of metabolic local action,” they can also “act at a distance.”162 The savage believes that one pebble will cure diseases, and another render him victorious in war; and there are physiologists who believe that one nerve-cell has sensibility, another motricity, a third instinct, a fourth emotion, a fifth reflexion: they do not say this in so many words, but they assign to cells which differ only in size and shape, specific qualities. They describe sensational, emotional, ideational, sympathetic, reflex, and motor-cells; nay, Schröder van der Kolk goes so far as to specify hunger-cells and thirst-cells.163 With what grace can these writers laugh at Scholasticism?

134. The hypothesis of the nerve-cell as the fountain of nerve-force is supported by the gratuitous hypothesis of cell-substance having greater chemical tension and molecular instability than nerve-fibre. No evidence has been furnished for this; indeed the only experimental evidence bearing on this point, if it has any force, seems directly adverse to the hypothesis. I allude to the experiments of Wundt, which show that the faint stimulus capable of moving a muscle when applied directly to its nerve, must be increased if the excitation has to pass through the cells by stimulation of the sensory nerve.164 Wundt interprets this as proving that the cells retard every impulse, whereby they are enabled to store up latent force. The cells have thus the office of locks in a canal, which cause the shallow stream to deepen at particular places. I do not regard this interpretation as satisfactory; but the fact at any rate seems to prove that so far from the cells manifesting greater instability than the fibres, they manifest less.

135. The hypothesis of nerve-force being developed in the ganglia, gradually assumed a more precise expression when the nerve-cells were regarded as the only important elements of a ganglion. It has become the foundation-stone of Neurology, therefore very particular care should be taken to make sure that this foundation rests on clear and indisputable evidence. Instead of that, there is absolutely no evidence on which it can rest; and there is much evidence decidedly opposed to it. Neither structure nor experiment points out the cells as the chief agents in neural processes. Let us consider these.

Fig. 22 shows the contents of a molluscan ganglion which has been teased out with needles.

The cells are seen to vary in size, but in all there is a rim of neuroplasm surrounding the large nucleus, and from this neuroplasm the fibre is seen to be a prolongation. The dotted substance in the centre is the neuroglia. Except in the possession of a nucleus, there is obviously here no essential difference in the structure of cell and fibre.

Now compare this with Fig. 23, representing three fibres from the auditory nerve.

Here the cell substance, as Max Schultze remarks, “is a continuation of the axis cylinder, and encloses the nucleus. The medulla commonly ceases at the point where the axis enters the cell, to reappear at its exit; but it sometimes stretches across the cell to enclose it also: so that such a ganglion cell is in truth simply the nucleated portion of the cylinder axis.”165 There are many places in which fibres are thus found with cells inserted in their course as swellings: in the spinal ganglia of fishes these are called bipolar cells; they are sometimes met with even in the cerebellum; but oftener in peripheral nerves, where they are mostly small masses of granular neuroplasm from which usually a branching of the fibre takes place. The point to which attention is called is that in some cases, if not in all, the nerve-fibre is structurally continuous with the cell contents. The two organites—fibre and cell—differ only as regards the nucleus and pigment. Haeckel, who affirms that in the crayfish (Astacus fluviatilis) he never saw a cell which did not continue as a fibre, thinks there is always a marked separation of the granular substance from its “hyaline protoplasm,” and that only this latter forms the axis cylinder. But although my observations agree with this as a general fact, I have seen even in crayfish the granular substance prolonged into the axis cylinder; and in other animals the granular substance is frequently discernible.

Indeed it may be said that anatomists are now tolerably unanimous as to the axis cylinder being identical with the protoplasmic cell substance. If this be so, we have only to recall the principle of identity of property accompanying identity of structure, to conclude that whatever properties we assign to the cells (unless we restrict these to the nucleus and pigment) we must assign to the axis cylinders. We can therefore no longer entertain the hypothesis of the cells being the fountains or reservoirs of Neurility; the less so when we reflect that cells do not form the hundredth part of nerve-tissue: for even the gray substance bears but a small proportion to the white; and of the gray substance, Henle estimates that one half is fibrous, the rest is partly cellular, partly amorphous. Those who derive Neurility from the cells, forget that although the organism begins as a cell, and for some weeks consists mainly of cells, yet from this time onwards there is an ever-increasing preponderance of cell-derivatives—fibres, tubes, and amorphous substance—and corresponding with this is the ever-increasing power and complexity of the organism.

136. From another point of view we must reject the hypothesis. Not only does the evidence which points to the essential continuity in structure of nerve cell and fibre discredit the notion of their physiological diversity, but it is further supported by the fact that although the whole nervous system is structurally continuous, an immense mass of nerve-fibres have no immediate connection with ganglionic cells:—neither springing from nor terminating in such cells, their activity cannot be assigned to them. To many readers this statement will be startling. They have been so accustomed to hear that every fibre begins or terminates in a cell, that a doubt thrown on it will sound paradoxical. But there is an equivoque here which must be got rid of. When it is said that every fibre has its “origin” in a cell, this may be true if origin mean its point of departure in evolution, for “cells” are the early forms of all organites; but although every organite is at first a cell, and in this sense a nerve-fibre must be said to originate in a cell, we must guard against the equivoque which arises from calling the highly differentiated organite, usually designated ganglionic cell, by the same name as its starting-point. On this ground I suggest the term neuroblast, in lieu of nerve-cell, for the earlier stages in the evolution of cell and fibre. Both Embryology and Anatomy seem to show that cell and fibre are organites differentiated from identical neuroblasts, with a somewhat varying history, so that in their final stages the cell and fibre have conspicuous differences in form with an underlying identity; just as a male and female organism starting from identical ova, and having essential characters in common, are yet in other characters conspicuously unlike. The multipolar cell is not necessarily the origin of a nerve-fibre, although it is probable that some short fibres have their origin in the prolongations of cells. Although the latter point has not, I think, been satisfactorily established, except in the invertebrata, I see no reason whatever to doubt its probability; what seems the least reconcilable with the evidence is the notion that all fibres arise as prolongations from ganglionic cells, instead of arising independently as differentiations from neuroblasts. The reader will observe that my objection to the current view is purely anatomical; for the current view would suit my physiological interpretations equally well, and would be equally irreconcilable with the hypothesis of the cell as the source of Neurility, so long as the identity of structure in the axis cylinder and cell contents is undisputed.

137. The evidence at present stands thus: There are numerous multipolar cells which have no traceable connection with nerve-fibres; and fibres which have no direct connection with multipolar cells. By the first I do not mean the disputed apolar cells, I mean cells in the gray substance of the centres which send off processes that subdivide and terminate as fibrils in the network of the Neuroglia (Figs. 16, 18). It is indeed generally assumed that these have each one process—the axis-cylinder process—which is prolonged as a nerve-fibre; nor would it be prudent to assert that such is never the case; though it would be difficult to distinguish between a fibre which had united with a process and a fibre which was a prolongation of a process, in both cases the neuroplasm being identical. I only urge that the assumption is grounded not on anatomical evidence, but on a supposed necessary postulate. All that can be demonstrated is that some processes terminate in excessively fine fibrils; and occasionally in thousands of specimens processes have been traced into dark-bordered fibres. It is true that they often present appearances which have led to the inference that they did so terminate—appearances so deceptive that Golgi and Arndt independently record observations of unbranched processes having the aspect of axis cylinders being prolonged to a considerable distance (600 μ in one case), yet these were found to terminate not in a dark-bordered fibre, but in a network of fibrils.166

138. While it is thus doubtful whether dark-bordered fibres are always immediately connected with cells, it is demonstrable that multitudes of fibres have only an indirect connection with cells, being developed as outgrowths from other fibres. Dr. Beale considers that in each such outgrowths have their origin in small neuroplasmic masses (his “germinal matter”). That is another question. The fact here to be insisted on is that we often find groups of cells with only two or three fibres, and groups of fibres where very few cells exist. Schröder van der Kolk says that in a sturgeon (Accipenser sturio) weighing 120 pounds he found the spinal cord scarcely thicker than that of a frog; the muscles of this fish are enormous, and its motor nerves abundant; yet these nerves entered the cord by roots no thicker than a pig’s bristle; and in the very little gray matter of the cord there was only a cell here and there found after long search. Are we to suppose that these rare cells were the origins of all the motor and sensory nerves? A similar want of correspondence may be noticed elsewhere. Thus in the spinal cord of the Lamprey my preparations show very few cells in any of the sections, and numerous sections show none at all. Stieda counted only eight to ten cells in each horn of some osseous fishes, except at the places where the spinal roots emerged. In the eel and cod he found parts of the cord quite free from cells, and in other parts found two, three, never more than ten. In birds he counted from twenty-five to thirty. Particular attention is called to this fact of the eel’s cord being thus deficient, because every one knows the energetic reflex action of that cord, each separate segment of which responds to peripheral stimulation.

It may indeed be urged that these few cells were the origin of all the fibres, the latter having multiplied by the well-known process of subdivision; and in support of this view the fact may be cited of the colossal fibres of the electric fishes, each of which divides into five-and-twenty fibres, and in the electric eel each fibre is said by Max Schultze to divide into a million of fibrils. But I interpret this fact otherwise. It seems to me to prove nothing more than that the neuroplasm has differentiated into few cells and many fibres. And my opinion is grounded on the evidence of Development, presently to be adduced. If we find (and this we do find) fibres making their appearance anywhere before multipolar cells appear, the question is settled.

139. Dr. Beale regards the large caudate cells of the centres as different organites from the oval and pyriform cells, and thinks they are probably stations through which fibres having different origins merely pass, and change their directions; and Max Schultze says that no single fibril has been found to have a central origin; every fibril arises at the periphery, and passes through a cell, which is thus crossed by different fibrils.167 (Comp. Fig. 17.)

The teaching of Development is on this point of supreme importance. Unhappily there has not yet been a sufficient collection of systematic observations to enable us to speak very confidently as to the successive stages, but some negative evidence there is. The changes take place with great rapidity, and the earliest stages have hardly been observed at all. Although for several successive years I watched the development of tadpoles, the difficulties were so great, and the appearances so perplexing, that the only benefit I derived was that of being able the better to understand the more successful investigations of others. Four or five days after fecundation is the earliest period of which I have any recorded observation; at this period the cerebral substance appeared as a finely granular matter, having numerous lines of segmentation marking it off into somewhat spherical and oval masses, interspersed with large granules and fat globules. Here and there hyaline substance appeared between the segments. Similar observations have since been recorded by Charles Robin in the earliest stages of the Triton.168 He says that when the external gills presented their first indications, nuclei appeared, each surrounded by a rim of hyaline substance, from which a pale filament was prolonged at one end, sometimes one at both ends, and this filament subdivided as it grew in length until it had all the appearance of an axis cylinder. This, however, he says, is a striation, not a fibrillation; he refuses to admit that the axis cylinder is a bundle of fibrils. He further notices the simultaneous appearance of amorphous substance; and as this is several days before there is any trace of a pia mater, or proper connective tissue, he urges this among the many considerations which should prevent the identification of neuroglia with connective tissue.

In a very young embryo of a mole (I could not determine its age) the cortex of the hemispheres showed granular amorphous substance, in which were embedded spherical masses of somewhat paler color, which had no nuclei, and were therefore not cells. Besides these, there were nucleated masses (apolar cells, therefore) and more developed cells, unipolar, bipolar, and tripolar. Not a trace of a nerve-fibre was visible. In agreement with this are the observations of Masius and Van Lair, who cut out a portion of the spinal cord in a frog, and observed the regenerated tissue after the lapse of a month. It contained apolar, bipolar, and multipolar cells, together with “corpuscles without processes, for the most part larger than the cells, and appearing to be mere agglomerations of granules,”—these latter I suppose to have been what I describe as segmentations of the undeveloped substance. Gray fibres, with a few varicose fibres, also appeared.169

140. The admirable investigations of Franz Boll have given these observations a new significance. He finds in the cerebral substance of the chick on the third or fourth day of incubation a well-marked separation between the neuroglia and nerve-tissue proper. Fig. 24, A, represents three nerve-cells, each with its nucleus and nucleolus, and each surrounded with its layer of neuroplasm. The other four masses he regards as nuclei of connective tissue. Three days later the distinction between the two is more marked (Fig. 24, B). Not only have the nerve-cells acquired an increase of neuroplasm, they also present indications of their future processes, which at the twelfth day are varicose (Fig. 24, C). (All this while the connective corpuscles remain unchanged.) Although Boll was unable to trace one of these processes into nerve-fibres, he has little doubt that they do ultimately become (unite with?) axis cylinders.

It is difficult to reconcile such observations with the hypothesis of the cells being simply points of reunion of fibrils. We see here multipolar cells before any fibrils appear. Respecting the development of the white substance, i. e. the nerve-fibres, Boll remarks that in the corpus callosum of the chick the first differentiation resembles that of the gray substance.

The polygonal and spindle-shaped cells represented in Fig. 25, A, are respectively starting-points of connective and neural tissues. The spindle-shaped cells elongate, and rapidly become bipolar. This is supposed to result in the whole cell becoming transformed into a fibre, the nucleus and nucleolus vanishing; but the transformation is so rapid that he confesses that he was unable to trace its stages; all that can positively be asserted is that one or two days after the appearance presented in Fig. 25, B, the aspect changes to that of fibrils. The columns of polygonal cells between which run these fibrils, he regards as the connective corpuscles described by several anatomists in the white substance both of brain and cord, and which are sometimes declared to be multipolar nerve-cells.170

141. Dr. Schmidt’s observations on the human embryo were of course on tissue at a very much later stage. According to him, the fibrils of the axis cylinders are formed by the linear disposition and consolidation of elementary granules. The fibrils thus formed are separated by interfibrillar granules which in time become fibrils. Not earlier than three months and a half does the formation of individual axis cylinders begin by the aggregation of these fibrils into minute bundles, which are subsequently surrounded by a delicate sheath.171

142. With respect to the transition of the spindle-shaped cells into fibrils, since there is a gap in the observations of Boll, and since those of Schmidt are subsequent to the disappearance of the cells, and in both cases all trace of nucleus has disappeared, I suggest that we have here an analogy with what Weismann has recorded of the metamorphoses of insects. In the very remarkable memoir of that investigator172 it is shown that the metamorphoses do not take place by a gradual modification of the existing organs and tissues, but by a resolution of these into their elements, and a reconstruction of their elements into tissues and organs. The muscles, nerves, tracheæ, and alimentary canal, undergo what may be called a fatty degeneration, and pass thence into a mere blastema. It is out of these ruins of the old tissues that the new tissues are reconstructed. On the fourth day the body of the pupa is filled with a fluid mass—a plasma composed of blood and dissolved tissues. The subsequent development is thus in all essential respects a repetition of that which originally took place in the ovum.173

Two points are especially noticeable: First, that in this resolved mass of granules and fat globules there quickly appear large globular masses which develop a fine membrane, and subsequently nuclei. A glance at the figure 51 of Weismann’s plates reveals the close resemblance to the earliest stages of nerve-cells; and the whole process recalls the regeneration of nerves and nerve-centres after their fatty degeneration.

Secondly, the nerves reappear in their proper places in the new muscles, and this at a time when the nerve-centres are still unformed; so that the whole peripheral system is completely rebuilt in absolute independence of the central system. The idea, therefore, that nerve-fibres are the products of ganglia must be relinquished. This idea is further discountenanced by Boll’s observations, which show that the fibre-cells are from the first different from the ganglionic cells; and by the observations of Foster and Balfour, that “fibres are present in the white substance on the third day of incubation”; whereas cell processes do not appear until the eighth day. Foster and Balfour are inclined to believe “that even on the seventh day it is not possible to trace any connection between the cells and fibres.” In the later stages, the connection is perhaps established.174

143. We may, I think, conclude from all this that in the higher vertebrates the white substance of brain and cord is not the direct product of the gray substance; in other words, that here nerve-fibres, even if subsequently in connection with the ganglionic cells, have an independent origin. They may grow towards and blend with cell processes; they are not prolongations of those processes. They may be identical in structure and property, as one muscle is identical with another, but one is not the parent of the other.

144. Sigmund Mayer emphatically declares that in no instance has he traced a cell process developed into a dark-bordered nerve-fibre. The process, he says, may often be traced for a certain distance alongside of a fibre; but it then suddenly ceases, whereas the fibre is seen continuing its course unaltered. Still more conclusive is the evidence afforded by nerves having only very few fibres (2–4 sometimes in the frog), which have, nevertheless, a liberal supply of cells, visible without preparation. Valentin counted twenty-four cells in a nerve which had but two fibres.175 Now although it is possible to explain the presence of numerous fibres with rare cells either as due to subdivisions of fibres, or to the fibres having cells elsewhere for their origin, it is not thus that we can explain the presence of numerous cells which have no fibres developed from their processes.

145. With regard to this observation of the cell process running alongside of the fibre, the recent researches of Ranvier may throw some light on it. He describes the cells in the spinal ganglia as all unipolar; each single process pursues a more or less winding course as a fibril, often blending with others, till it reaches one of the fibres from the sensory root. It blends with this fibre at the annular constriction of the fibre, becoming here incorporated with it, so that a T-shaped fibre is the result.176 If this should be confirmed, it would reconcile many observations; but it would greatly disturb all current interpretations. Ranvier remarks that it is no longer tenable to suppose that the ganglionic cell is a centre, sensory or motor, receiving the excitation or sending forth a motor impulse; for if the fibril issuing from a cell becomes laterally soldered to a nerve-fibre, there is no possibility of saying in which direction this cell receives the excitation, nor in which it transmits the impulse.

146. We have seen good reason to conclude that the essential element of the nerve—the axis cylinder—is the same substance as the neuroplasm which forms the essential element of the cell. At any rate, we are quite certain that the cell process is neuroplasm. On this ground there is no difficulty in understanding that a cell process may sometimes be drawn out into an axis cylinder (as indeed we see to be the case in the invertebrata and electric fishes); while again in numerous other cases the nerve-fibre has an independent origin, being, in short, a differentiation from the neuroplasm which has become a fibre instead of a cell. It is clear from the observations of Rouget on Development, and of Sigmund Mayer on Regeneration, that fibres, nuclei, and cells become differentiated from the same neuroplasm, those portions which are not converted into fibres remaining first as lumps of neuroplasm, then acquiring a nucleus, and some of these passing into cells. I mean that between fibres, nuclei, and cells there are only morphological differences in an identical neuroplasm.177 If this is in any degree true, it will not only explain how fresh fibres may be developed in the course of fibres, branching from them as from trunks, and branchlets from branchlets, twigs from branchlets, the same conditions of growth being present throughout; it will also completely modify the notion of any physiological distinction between cell and fibre greater than can be assigned to the morphological differences. We shall then no longer suppose that the cell is the fountain whence the fibre draws its nutrition and its “force”; and this will be equally the case even if we admit that a cell is, so to speak, the germ from which a whole plexus of fibres was evolved, for no one will pretend that the “force” of an organism is directly derived from the ovum, or that the ovum nourishes the organism.

147. At this stage of the discussion it is needful to consider a point which will spontaneously occur to every instructed reader, I mean the interesting fact discovered by Dr. Waller, that when a sensory root was divided, the portion which was still in connection with the ganglion remained unaltered, whereas the portion which was only in connection with the spinal cord degenerated; and vice versa, when a motor root was divided, the portion connected with the cord remained unaltered, the portion severed from the cord degenerated. The observation has been frequently confirmed, and the conclusion drawn has been that the cells in the ganglion of the posterior root are the nutritive centres of posterior nerves, the cells in the anterior horn of the cord being the nutritive centres of the anterior nerves. Another interpretation is however needed, the more so because the fact is not constant.178 True of some nerves, it is not true of others. Vulpian found that when he cut out a portion of the lingual nerve, and transplanted it by grafting under the skin of the groin, where of course it was entirely removed from all ganglionic influence, it degenerated, but it also regenerated. Pathological observations convinced Meissner that the ganglia are wholly destitute of an influence on the nutrition of the vagus; and Schiff proved experimentally that other ganglia were equally inoperative, since motor nerves could be separated from the spinal cord without degeneration.179 Not however to insist on this, nor on the other facts of regeneration, in the absence of ganglionic influence, let us remark that Dr. Waller’s examples would not be conclusive unless the teaching of Embryology could be disproved. That nerves degenerate when separated from ganglia is a fact; but it is also a fact that muscles degenerate when separated from a nerve-centre; yet we do not suppose the nerve-centre to nourish the muscles. And against the fact that the sensory nerve remains unaltered only in that portion which is connected with the ganglion, we must oppose the observations of Kölliker and Schwalbe,180 who affirm that none of the fibres which enter the posterior columns of the spinal cord have any direct connection with the cells of the ganglion on the posterior root. The cells of this ganglion they declare to be unipolar (in the higher vertebrates), and the fibres in connection with these cells are not those which pass to the cord, but all of them pass to the periphery. According to Ranvier, the fibres from the cells join the fibres of the posterior root. Schwalbe found that if the spinal nerve be firmly grasped and steadily drawn, it will often be pulled from its sheath, and the ganglion laid bare;181 in this ganglion all the cells are found undisturbed, which could not be the case had fibres from those cells entered the cord, since the traction would necessarily have disturbed them.