It is a more or less arbitrary distinction to speak of internal in contrast to external organs, since the latter contain internal parts; but the distinction is, for our present purposes, a useful one, especially in regard to the question of regeneration and liability to injury. In this connection we shall find it particularly instructive to examine those cases of regeneration of internal organs that cannot be injured, under natural conditions, without the animal itself being destroyed. An illustration of this may be given. The liver, or the kidney, or the brain of a vertebrate can seldom be exposed to accidental injury without the entire animal being destroyed, although, of course, diseases of various kinds may injure these organs without destroying the animal, but cases of the latter kind are not common.

The experiments made by Ponfick (’90) on the regeneration of the liver in dogs and in rabbits gave the most striking results. Ponfick found after removal of a fourth, or of a half, or even, in a few successful operations, of three-fourths of the liver, that, in the course of four or five weeks, the volume of the remaining part increased, and in the most extreme case, to three times that of the piece that had been left in the body. The first changes were found to have begun as early as thirty hours after the operation, when the liver cells had begun to divide. The maximum number of dividing cells was found about the seventh day, and then decreased from the twentieth to the twenty-fifth day, but cells were found dividing even on the thirtieth day. These dividing cells appeared everywhere throughout the liver, and were no more abundant at the cut-edges than elsewhere. There takes place, in consequence, an increase in the volume of the liver, rather than a replacement of the part that is removed. The increase takes place in the cells of the old part, the lobules swelling up to two, three, or even four times their former size. No new liver lobules seem be formed. The old tubules of the liver also become larger, owing to an increase in the number of their cells. Since the change takes place in the old part, and is due to an increase in size of the lobules, tubes, etc., the process is spoken of as one of hypertrophy rather than of regeneration.

Kretz found a case in which the entire parenchyma of the liver seemed to have been destroyed, presumably by a poison from some micro-organism, and later a regeneration of the tissue had taken place. If this conclusion is correct, it shows that sometimes an internal organ may meet with an injury that does not directly destroy the rest of the body, and the animal may survive.

The regeneration of the salivary gland of the rabbit described by Ribbert is another example of an internal organ that can seldom be injured, and yet can be replaced after artificial removal. Weismann (’93) has recorded an experiment in which half of a lung of triton was cut off. After fourteen months the lung had not been restored in four individuals, and in one “it was doubtful whether a growth of the lung had not taken place, but even in this case it had not recovered its long, pointed form.”

The regeneration of the eye in triton was first made known by Bonnet. The right eye was partly cut out, and after two months it had completely regenerated. Blumenbach, in 1784, removed the anterior part of the bulb of the eye of “Lacerta lacustris.” Six months later a smaller bulb was present. Phillipeaux (’80) found that if the eye of an aquatic salamander was not entirely removed, a new eye regenerated; but if the eye was completely extirpated a new eye did not appear. Colucci, in 1885, described the regeneration of the lens of the eye of triton from the edge of the optic cup. Wolff, later, independently, discovered the same fact, and it has been more recently confirmed by E. MÜller (’96), W. Kochs (’97), P. Rothig (’98), and Alfred Fischel (’98). The most important part of this discovery is that the new lens develops from the margin of the optic cup, and not from the outer ectoderm, as it does in the embryo. This result will be more fully discussed in a later chapter. It is highly probable in this case that the regeneration stands in no connection whatsoever with the liability of the eye to injury, for of the large number of salamanders that have been examined, none has been found with the eye mutilated. The position of the eye is such that it is well protected from external injury, and the tough cornea covering its outer surface would also further protect it from accidental injury. When we recall the high degree of structural complexity of the eye, its capacity to regenerate, if only a portion of the bulb is left, and its power to replace the lens if this is removed are certainly very remarkable facts. We find here, I think, an excellent refutation of the incorrectness of the general assumption of a connection between regeneration and liability to injury. Moreover, since there is no evidence whatsoever to show that the eyes in these animals are ever subject to diseases caused by bacteria, and much evidence to show that they are not so injured, we are still further confirmed in our general conclusion.

It has been known for a long time that even in man the lens of the eye is sometimes regenerated after its removal. The regeneration has been supposed to take place from the old capsule of the lens, or possibly from a piece of the lens left after the operation; but whatever its origin, the fact of its regeneration in man, and in other mammals also, is a point of some interest in this connection.

Podwyssozki (’86) found that regeneration may take place in the kidney of certain mammals,—best in the rat, more slowly in the rabbit. The restoration of the lost part takes place first by replacement of the epithelium. The old canals may then push out into the connective tissue that accumulates in the new part, but there is no new formation of canals or of glomeruli. According to Podwyssozki the regeneration of the kidney is less complete than that of any other gland. Peipers has reinvestigated the subject, and his results agree in the main with those just given. He finds in addition that new canals may grow out from the old ones into the new part.

Podwyssozki and Ribbert (’97) have found that the salivary gland has a remarkable power of regeneration. Ribbert removed a half (or even more than this) of the salivary gland of the rabbit. In the course of two or three weeks new material had developed over the cut-surface. In one case at least five-sixths of the gland had been taken out, and at the end of three weeks the gland had regenerated to its full size. Microscopic examination showed that the greater part of the gland was made up of new lobes, some of which were as large as, others smaller than, the normal lobes. The new part contained new tubes with terminal acini. These had arisen from the tubes of the old part. The connective tissue of the new part also came from that of the old. In this case a true process of regeneration takes place from the cut-surface; in addition a certain amount of enlargement, or hypertrophy, also takes place in the old part. Ribbert believes there is a connection between the process of hypertrophy and of regeneration of such a kind that the more active the one, the less active the other.

Regenerative changes are known to occur in other internal organs besides these glandular ones. Broken bones are united, if brought in contact, by a process that involves a certain amount of regeneration. Although new bony tissue may be formed at the region of union, the bones of mammals and of birds do not seem able to complete themselves, if a part is removed, except to a limited extent. While the broken bones of the leg or of the arm have the power of reuniting if held for some time in place, yet in nature this condition can seldom be fulfilled, and the animal with a broken leg or wing will most probably be killed. Nevertheless, since the bones have this power at whatever level they may be broken (but only if they are kept together artificially), the process can scarcely have been acquired through the liability of the parts to injury. We find here another instance of a useful process existing in animals, but one that could not have been acquired by exposure of the part to injury. It is probable that this same property is found in all the bones of the body,—in those that may occasionally be injured, and in those that are not.

The muscles have also the power of regenerating, although few experiments have been made except in those forms in which the whole leg can regenerate, yet there are a few observations that show that even in mammals, in which the leg or the arm cannot regenerate as a whole, a certain amount of regeneration of the muscles themselves may take place.

It has been known for a long time that if a nerve is cut a new nerve grows out from the cut-end, and may extend to the organs supplied by that nerve. The process takes place more successfully if the peripheral part is left near the cut-end from which the new nerve grows. Whether this old part only serves to guide the new part to its proper destination, or whether it may also contribute something to the new nerve, as, for instance, cells for the new sheath, is not finally settled. The general opinion in regard to the origin of the new nerve fibres is that the central axis or fibril grows from the cut-end. That this power could have been acquired for each nerve as a result of its liability to injury is too improbable to discuss seriously.

The central nervous system of the higher vertebrates seems to have very little power of regeneration, and although in some cases a wounded surface may be covered over and a small amount of connective tissue be formed, the development of new ganglion cells does not seem to occur. In other animals, as the earthworm, planarian, and even in the ascidian, as shown by Loeb, a new entire brain may develop after the removal of the old brain, or of that part of the body in which it is contained.

This examination of the power of regeneration of internal organs in the vertebrates has shown that it is highly improbable that there can be any connection between their power of regeneration and their liability to injury. That the internal organs may be occasionally injured by bacteria, or by poisons made in the body, may be admitted, but that injuries from this source have been of sufficient frequency to establish a connection, if such were indeed possible, between their power of regeneration and their liability to injury from these causes is too improbable a view to give rise to much doubt. These results taken in connection with those discussed in the preceding chapter go far toward disproving the view that the power of regeneration has a connection with the liability of a part to injury.

HYPERTROPHY

The hypertrophy, or unusual enlargement, of organs has long attracted the attention of physiologists, and the extremely interesting observations and experiments that have been made in this connection have an important although an indirect bearing on the problem of regeneration. Ribbert, as has been pointed out, holds that the processes of hypertrophy and of regeneration stand in a sort of inverse relation to each other, but it is doubtful, I think, if any such general relation exists. Two kinds of hypertrophy are now generally distinguished: functional hypertrophy, which takes place when a part becomes enlarged through use; and compensating hypertrophy, which takes place when one organ being removed another enlarges. The enlargement in the latter case may, of course, be brought about by the increased use of the parts that enlarge, but as this is not necessarily the case, the distinction between the two processes is a useful one. The causes of compensating hypertrophy are by no means simple, and several possibilities have been suggested to account for the enlargement. The best ascertained facts in connection with hypertrophy relate almost entirely to man and to a few other mammals.[51]

By hypertrophy is meant an increase of the substance of which an organ is composed. Swelling due to the imbibition of water or of blood-serum is not, in a technical sense, a process of hypertrophy. Virchow distinguishes two kinds of hypertrophy: (1) Hypertrophy in a narrower sense in which the enlargement is due to an increase in the size of the cells of which an organ is composed. This enlargement of the individual cells leads of course to an increase in the size of the whole organ. (2) Hyperplasy due to an increase in the number of cells of which an organ is composed, which also causes an enlargement of the whole organ if the cells retain the normal size. The division into functional and compensating hypertrophy given above is a physiological distinction, and both of these processes might occur in Virchow’s subdivisions.

Giants may be looked upon as hypertrophied individuals, since all the organs of the body are larger than the normal. The enlargement is, in this case, not due to external influences, but to some peculiarity of the organism itself. Whether the size is due to more cells being present, as seems probable, or to the cells being larger, or to both, has not, so far as I know, been determined for man. In a mollusk, Crepidula fornicata, in which large and small adult individuals occur, it has been shown by Conklin (’98) that the difference is due entirely to the larger number of cells in the larger individual. In this case external conditions, in so far as they retard the maximum possible growth of the individual, are responsible for the differences in size. The distinction is, in this case, rather between large normal individuals and dwarfs, than between giants and normal or average individuals.

The voluntary muscles of the body of man grow larger, and may be said to hypertrophy, as a result of doing certain kinds of work. The muscles of the hand and arm grow large through use, and become smaller again if not used; but the muscles of the fingers of a musician do not hypertrophy, although the total amount of work done may be very large. It is only when muscular work is done against great resistance that enlargement of the muscles takes place. The factors that may bring about the enlargement will be discussed later.

The kidneys seem to give the most satisfactory evidence of compensating hypertrophy. Nothnagel[52] states that it has been shown in man, in the rabbit, and in the dog, that when one kidney has been removed the other enlarges; and that this takes place both for young animals, in which the kidneys have not reached their full size, and in adult animals, in which the remaining kidney becomes larger than normal. In the adult the enlargement is due to hypertrophy, in Virchow’s sense, in the tubules and in the epithelium of the canals. In the young animal there is, in addition, a hyperplastic growth that leads to an increase in the number of glomeruli, etc.

Experiments have shown that the same amount of urea is excreted by the animal after the removal of one kidney as before; in fact, this is true immediately after the operation, before any increase in the size of the organ has taken place. This means that, under normal conditions, the kidneys do not perform their maximum of work. It is important to observe in this connection that the remaining kidney gets more blood than it would get if the other were present. Nothnagel sums up the changes that take place in this way: First, the removal of one kidney; second, an increase in the flow of blood in the remaining kidney; third, an increase in the functional activity and excretion of this kidney; fourth, along with the increase in the flow of blood, there is a necessary increase in the amount of food that is brought to the kidney in the blood; fifth, this food is taken up in larger amount than before by the cells, which leads to an increase in the growth of the cells, which produces hypertrophy. The increase in size, looked at from this point of view, Nothnagel says, has nothing mysterious about it. The enlargement seems to be an adaptation; but the enlargement does not take place because it is an adaptive process, but because it cannot be helped under the conditions that arise. We shall return again to Nothnagel’s interpretation, when we come to consider other views.

Experiments of the sort just described are most easily carried out on the paired organs of the body, such as the salivary glands, the tear glands, the mammÆ of the female, and the testes of the male. In regard to the latter two organs the evidence, especially in the case of the testes, is conflicting, but the recent experiments of Ribbert seem to give definite results. Nothnagel had found that after the removal of one testis there is no hypertrophy of the other. He pointed out that this result does not stand in contradiction to his hypothesis in regard to the kidneys, for the loss of one testis does not lead to a greater functional activity in the other. Each acts for itself alone. The result shows further, he adds, that the process of hypertrophy is not an adaptive one, but a physical or a physiological process. Ribbert on the contrary thinks that even Nothnagel’s statistics give evidence of hypertrophy, and Ribbert’s own experiments give unmistakable evidence of a considerable enlargement of the remaining testis. In his experiments, young rabbits were used that were born of the same mother and in the same litter. One of the testes was removed from some of the individuals, and after some months the remaining testis was taken out and its weight compared with that of the control animal. In sixteen out of seventeen experiments there was found to be a noticeable increase in the single testis as compared with either testis of the control animal. The results show that in some cases the single testis weighs almost as much as the two together of the control animal. It is important also to notice that in this case the enlargement has taken place in an organ that has not been active, as was the case with the kidney.

Ribbert has also shown that hypertrophy takes place in the mammÆ of the rabbit after the removal of some of them. Five out of the eight mammÆ were removed in three cases, and seven out of the eight in two other cases from young rabbits about two months old. Ribbert found that if the operator is not careful to remove completely all the tissue of a mamma an active regenerative process takes place from the part that remains. After five and a half months the single remaining mamma of one animal measured six and one-half by three and four-fifths centimetres, and the corresponding one in the control animal five and three-fourths by three and one-half centimetres. The glandular tissue was also found less developed in the control animal.

In another experiment the rabbit experimented upon bore young when it was six and a half months old. Soon after the birth of the young and before the mamma had been used the animal was killed and the single mamma that had been left was measured. It was much enlarged and projected more than the normal mammÆ. It measured nine by five centimetres. In a normal control animal[53] the corresponding mamma measured seven by five centimetres. The number of acini was in the proportion of sixteen in the animal operated upon to ten in the normal. The results show a distinct compensating hypertrophy, due to a hyperplastic increase in the number of elements of the gland.

A further example of compensating hypertrophy has been found after the removal of the spleen, when the lymphatic glands of other parts of the body become enlarged. There are also observations which go to show that after the removal of some of the lymphatic glands others undergo an enlargement.

Ziegler[54] has given a critical review of the various opinions and hypotheses that have been advanced to account for the process of hypertrophy. According to Cohnheim[55] hypertrophy in bones, muscles, spleen, and glands is due to hyperÆmia, i.e. increased blood supply. He thinks that neither mechanical nor chemical stimuli can cause directly new processes of growth. Recklinghausen[56] thinks that hypertrophy is not due to any extent to an increase in the food supply. Samuel[57] explains hypertrophy as due to a removal of, or to a decrease in, the resistance to growth and also to the influence of the nerves. Klebs[58] thinks that three factors enter into the problem, (a) inherited peculiarities, (b) overfeeding, (c) a removal of the controlling influences. Weigert believes that reparative processes are due to the removal of influences that prevent growth, and not to a direct stimulus. He thinks that a stimulus may start a functional act, but can never start a nutritive or a formative one. Good nourishment, for instance, may bring a tissue to a maximum development that is predetermined by innate peculiarities, but “idioplastic forces” are not thereby increased. Pekelharing[59] thinks that hypertrophy is due to a disappearance of a resistance to growth, and also to a stimulus causing proliferation.

We see from these various opinions how little is really known; how little has been determined as yet by experiment as to the causes that bring about hypertrophy. Many of the views are more or less plausible in the absence of direct, experimental evidence, but it remains for the future to decide as to the correctness of all of them. They are valuable as suggestions, in so far as they show the different possibilities that must be taken into account.

Ziegler first advocated the view, in the first edition of his Lehrbuch, that hypertrophy is due to a lessening of the resistance to growth. He thinks that while hyperÆmia and transudation may support the new growth, they are never the only cause of the formation of new tissue. While Virchow’s view that any injury to the body or to an organ excites proliferation finds support in the work of Stricker and Grawitz, yet the view has been combated by Cohnheim and by Weigert, and is no longer held by many pathologists. Ziegler points out that as a result of his own work, and that of his students, traumatic and chemical lesions are not followed at once by new growth of the tissue, but by degeneration of the tissue, and by changes in the circulation that lead to exudations. The new growth begins, at the earliest, eight hours after the operation, and generally only after twenty-four hours. Also after mechanical, chemical, or thermal injuries, a long interval elapses before phenomena of growth begin. The injury itself does not appear to produce the growth, but brings about those conditions that lead to cell-multiplication. Ziegler discusses what is meant by the idea of a lessening of the resistance to growth. He himself does not mean by this that hypertrophy depends on changes in the physical conditions, because it is known that living phenomena are the outcome of chemical processes and it is, therefore, À priori probable that the effect is brought about by chemical substances in the fluids of the tissues. These substances affect functional actions, and may even bring about regenerative changes. This action of chemical substances on the formative activity of the cell is theoretically possible in either of two ways; first, chemical substances of definite concentration are set free, or, second, chemical substances are present in the normal condition that prevent proliferation, but if their influence should be counteracted by other substances the conditions become favorable to growth. It is known in the case of certain unicellular organisms, that derive their nourishment from the surrounding medium, that their increase in number may be retarded by the presence of certain chemical substances. It is also known that certain organisms may themselves produce chemical substances that prevent their own multiplication. It is, therefore, at least conceivable that after a part has been injured a new substance may be produced that acts upon and destroys in the organ itself the substances there present that have prevented its further growth. The other interpretation is that in the breaking down of the tissue of the organ a substance is produced that excites the cells to proliferation.

Klebs suggested that the accumulation of the leucocytes at the wounded surface may act as a stimulus to growth, and that the chromatin of their nuclei might be absorbed by the cells of the tissue, and combining with the nuclei of these cells bring about the new growth. But Ziegler points out that we now know that although the leucocytes are dissolved and absorbed over the wounded surface, no process of absorption, of the sort postulated by Klebs, takes place. Ziegler thinks that Nothnagel is wrong in supposing that an increase in the blood supply, bringing with it an increase in the nourishment, can account for the hypertrophy of the kidney. On the contrary he believes that the growth is the result of an increase in the function of the organ due to the increase of the chemical substance, urea, that is brought to the secreting cells. The muscles of the body also hypertrophy as a result of their activity and not as a result of the additional blood supply.

In connection with these problems of hypertrophy it may be pointed out that, under certain conditions, blood vessels may enlarge and their walls become thickened. To cite a single example, Nothnagel found that if the femoral artery of the rabbit is tied, the blood vessels, that come off immediately above the ligature, and which have already, through their subdivisions, connections in the muscles with other branches of the same femoral artery (that come off below the ligature), grow larger after a time. This he believes to be due, in the first instance, to the increased speed of the blood in the vessels, and thereby the bringing to these arteries of an increased food supply. Other writers have given different interpretations. Ziegler himself believes that several factors may be capable of bringing about the result. He thinks it improbable that the increase in the food supply can alone be the cause, and thinks it much more probable that the increased work that the vessels must perform while carrying more blood will account for the enlargement.

In connection with this discussion it may not be unprofitable to recall that in the regeneration of the lower animals we find simpler conditions in which proliferation of the cells takes place under circumstances where many of the factors suggested in the above discussion are absent. In the first place we find that new growth may occur without any increase in the nourishment that is brought to the organ. Regeneration takes place in the entire absence of food, except so far as it may be stored up in the tissues. Even in a planarian that is starving and decreasing in size, proliferation of new cells will take place if a part is removed. In many of the lower forms there may be proportionately even a much greater proliferation than in the regeneration and hypertrophy in the mammalian organs. It is true that proliferation may be more active if the tissues are well fed, but this does not show that the presence of food is a factor in the proliferation except so far as it keeps the proliferating cells in their best condition for growth. It is possible in many animals, more especially in some of the lower forms, to force them to grow rapidly by supplying them with a large amount of food, and conversely by decreasing the food to delay the growth. While this shows that the rate of growth is, within certain limits, a function of the amount of food, there may be also other factors that enter into the result, and in all cases there is an upper limit beyond which it is not possible to make the animal grow any larger.

That the presence of certain substances may bring about the enlargement of a part must be admitted as probable. It has been shown, for instance, that after the removal of certain lymphatic glands other glands may become larger. This appears to be due to the greater activity of the gland, brought about probably by the presence of an increased amount of some specific substance. In this instance the result can scarcely be due to a decrease in the physical resistance to growth or to an increase in the blood flow, except so far as this is brought about by the increased activity. It is, of course, possible, even if it cannot be positively shown in the case of the lymphatic glands, that a substance in the blood causes the hypertrophy in certain organs, while in others, as in the kidney, an increase in the blood flow may be also a factor in its hypertrophy.

The view held by several pathologists, that hypertrophy and regeneration may be caused by the removal of a physical resistance to growth, cannot be looked upon as a very probable hypothesis. The experiments in grafting of hydra and lumbriculus show that regeneration may still take place when the physical resistance has been reËstablished by grafting two pieces together. These results, which are more fully described in a later chapter, demonstrate that the growth is due to other influences.

A comparison with the lower animals shows that proliferation takes place when all but three of the factors considered in connection with hypertrophy and regeneration in the higher forms have been eliminated. These are, first, the action of substances that act either directly or as counteracting some substance already present, as Ziegler suggests; second, an innate tendency in the organism to complete itself; and, third, the use of the organ. It is impossible that the second factor enters into the problem of hypertrophy. In those cases in which regeneration takes place when a part of an organ is removed, as in the case of the liver, for example, the result may possibly also involve the second of the two factors, for the process is much like that of morphallaxis in the lower animals.

If it be granted that the growth in a hypertrophied organ is brought about by some substance that increases the function of that organ, can we suppose the phenomenon of regeneration to be due to similar factors? In other words, can we reduce both phenomena to the same principle? The case is complicated by two facts that may be illustrated by concrete examples. If a piece is cut from the middle of the body of lumbriculus new cells are produced at both ends of the piece. If we suppose the proliferation is brought about by the accumulation of certain substances in the piece, we must still invoke other factors to account for the differentiation of the proliferated material, since a head forms at one end and a tail at the other. All the hypothesis can do in itself is to account for a proliferation, not for the differentiation, and, both in the case of hypertrophy and in that of regeneration, it is the formation of new structures that we are chiefly concerned with, rather than the simple act of growth or of proliferation. If a piece of a hydra is cut off, the whole piece changes into the typical hydra form. Here there is no extensive process of proliferation, and the change is in the old part. It seems highly improbable that the production of substances in the piece could account for its change of form. These examples will suffice to show that in the process of regeneration it is very improbable that the change is brought about by special substances that may develop or be present in the part. We must suppose that during regeneration the formation of the typical form is not the result of a stimulus originating in a chemical substance acting upon the living material, but due to changes brought about directly in the living part itself. We must conclude, therefore, that despite the apparently close connection between the phenomena of hypertrophy of uninjured organs and of regeneration, they may often involve different factors.

If specific substances can bring about the hypertrophy of an organ, it is still not clear at present whether they do so by directly causing new growth, or whether their presence only stimulates the organ to greater activity and the activity of the organ is the cause of its growth. Since it must be supposed that in each organ a different specific substance brings about its activity and the consequent hypertrophy, it seems more probable that the result is due to the activity itself rather than to a stimulus from the substance. This view is further supported by the fact that in the case of the muscles and of the blood vessels the hypertrophy is directly connected with their use. The greater use brings about a larger supply of blood, but the blood is only different in amount and not in its quality. It must be confessed that it is difficult to see how the use of a part could make its growth increase, for by use the tissues break down; and we are not familiar with any other processes within the body that make for the building up of an organ in more than an inverse ratio to its breaking down. We are, however, familiar with phenomena of building up due to an increase in the food supply. It might appear from this to be more in accordance with what we find, to assume that the hypertrophy is solely due to an increase in the food supply; yet there are other facts known that show that an organ does not increase in size simply because it gets more blood, and that this occurs only when the organs have a greater functional activity. It is a safer conclusion, I think, at present to assume that both the activity of the organ and the increase in its supply of food acting together are factors in the result. On the other hand we are so much in the dark concerning the functioning and growth of organs that we can do little more, as the preceding pages show only too clearly, than speculate in the vaguest sort of way as to what changes take place; but since the processes seem to be within reach of experimental methods we can hope in the near future to learn more of how the processes of hypertrophy are brought about.

ATROPHY

It would not be profitable to enter into a general discussion of the many cases of absorption, or of atrophy of parts of the organism, but a few examples may be given that have a general bearing on the topics discussed in this chapter. The more noticeable cases arise through disuse of an organ, as shown, for example, in the decrease in size of the muscles of man when they are not used. Since this may take place in a single group of disused muscles, when no such change occurs in other muscles of the same individual that are in use, the most obvious explanation is that the decrease is due directly to disuse. Since the blood that goes to all the parts is the same, the diminution cannot be ascribed to any special substance in the blood. The flow of blood into the disused muscle is less than when the muscle is used, and it might be supposed that atrophy is directly caused by the lessened nourishment that the muscle receives. There is also the possibility that the decrease is brought about by the accumulation of certain substances in the disused muscle itself, but since, in general, the breaking down of the muscle is most active when it is used, it seems improbable that the result can be due directly to this cause, unless indeed it could be shown that the substances produced by a disused muscle are different from those in an active muscle.

Lack of food, as is known, may cause organs to decrease, the fat first disappearing, and then in succession in vertebrates, the blood, the muscles, the glands, the bones, and the brain. Certain poisons may also affect definite organs and bring about a decrease in size, as when the thymus and mammÆ decrease from iodine poisoning, and certain extensor muscles after lead poisoning. Atrophy may also be brought about by pressure on a part, as when the feet or waist are compressed. In old age there may be a decrease in some of the organs, as in the bones, the testes and ovary, and even in the heart.

Degenerative changes appear even in the young stages of some animals, as when the tail of the tadpole is absorbed and the arms of the pluteus of the sea-urchin are absorbed by the rest of the embryo.

Especially interesting are the cases of absorption that take place when organs are transplanted to unusual situations in the body. Zahn transplanted a foetal femur to the kidney, where it continued to grow but was later absorbed. Fischer transplanted the leg of a bird’s embryo to the comb of a cock, where it continued at first to grow, but after some months degenerated. The spleen, the kidney, and the testis have been transplanted, but they degenerate, and, in general, the larger the transplanted piece the more probable its degeneration. Small pieces of the skin have been transplanted from one individual to another, and it has been found that small pieces maintain themselves better than large pieces. Ribbert’s recent experiments in transplanting small pieces of different organs have been more successful than earlier experiments in which larger pieces were used. The first difficulty seems to be in establishing a blood supply to the new part, in order to nourish it. If the piece is quite small, it can absorb the substances, necessary to keep it alive, from the surrounding tissues, until the new blood supply has developed.

In the lower animals grafting experiments have been more successful, because the parts can remain alive for a longer time. It is important to find, however, that even in these cases, a part grafted upon an abnormal region of the body is usually absorbed. Rand shows that if the tentacles of hydra become displaced, as sometimes happens when a piece containing the old tentacles regenerates (Fig. 48, A-A³), the misplaced tentacles are absorbed; and I can confirm this result. In hydra, the hollow tentacles are in direct communication with the central digestive tract, and a displaced tentacle seems to be in as good a position as a normal one, as far as its nourishment is concerned, yet it becomes absorbed.

Rand also found, in other experiments, that when the anterior end of a hydra is grafted upon the wall of another hydra, the piece may maintain itself if it is large; but it is slowly shifted toward the base of the hydra to which it is grafted, and then the two separate in this region. If the graft is small, it may be entirely absorbed into the wall of the animal to which it is attached.

Marshall found that if the head of a hydra is partially split in two, each half-head completes itself (as Trembley had already shown). The body then begins slowly to separate into two parts, beginning at the angle between the two heads, until finally the two parts completely separate. King (1900) has repeated the experiment in a large number of cases with the same result. It seemed that the division might be brought about by the weight of the halves causing the gradual separation of the body, but King has shown that this is not the case, for, when a double form remained hanging with its head down, it still divided into two parts (Fig. 47, A). In this case, the weight of the two heads would cause the parts to come together rather than to separate, if gravity had any influence of the sort suggested. Marshall and King have also shown that if the posterior end of a hydra is split in two, the two parts do not continue to separate, but one of the two, if the pieces have been split some distance forward, may become constricted from the other, and, producing new tentacles at its apical end, become a new individual.

I have carried out a series of experiments on planarians of a somewhat similar nature. If the posterior end is split in two, the separation extending into the anterior part of the worm (Fig. 44, C), each half completes itself, but the halves do not separate unless they happen to tear themselves apart. If one of the pieces is cut off, not too near the region of union with the other half, a new posterior end, replacing that cut off, regenerates. If, however, the piece is cut off quite near the region or union of the halves, the piece that is left may be absorbed.

The absorption of misplaced parts in the lower animals cannot be explained, I think, by any lack of nutrition, especially in the case of the tentacles of hydra. The result may be due either to the displaced part not receiving exactly those substances, perhaps food substances, that it gets in its normal position, or it may be due to some formative influence. At present we are not in a position to decide between these alternatives, and, while the former view seems more tangible, and the latter quite obscure, the latter may nevertheless be found to contain the true explanation. If the view that I have adopted in regard to the organization—namely, that it can be thought of as acting through a system of tensions peculiar to each kind of protoplasm—is correct, it may be possible to account for the absorption of misplaced parts by some such principle as this.

INCOMPLETE REGENERATION

A somewhat unusual process of regeneration takes place when the jelly-fish, Gonionemus vertens, is cut into pieces. As first shown by Hargitt, the cut-edges come together and fuse, and the pieces

assume the form of a bell, but the missing parts are not replaced.[60] I have worked on the same form and obtained substantially the same results. If the jelly-fish is cut in two, as indicated by the dotted line in Fig. 39½, A and A¹, each half closes in and assumes the form shown in B, B. Each new jelly-fish has only the two original radial canals that each half had when separated from the other. A faint line along the region of fusion of the pieces seems to represent a new radial canal,—it is not represented in the figures,—and each half-proboscis has completed itself. There are not formed any new tentacles, except perhaps one, or a few more, where the cut-edges meet. Thus there is actually very little regeneration, although the typical jelly-fish form is assumed by the half-piece. If a jelly-fish is cut into four pieces, each piece containing one of the radial canals, the pieces also assume the bell-like form, as shown in C, C¹. A new proboscis develops from the proximal end of the old radial canal, and since this end is often carried to one side during the closing in of the piece, the new proboscis lies not at the top of the sub-umbrella space, but, as seen in the figure, quite to one side. Pieces even smaller than these one-fourth jelly-fish will assume the bell-like form, especially if they contain a bit of the margin of the old bell and a part of one of the radial canals, as shown in Fig. 39½, D. Although I have kept these partial medusÆ for several weeks, and have fed them during this time, I have found that the missing organs do not come back. That these pieces do undergo a certain amount of regeneration is shown by the formation of a new proboscis, and, in certain cases, a new radial canal. Even the tentacles may be partially regenerated, as Hargitt has shown,—especially, as I have found, if the margin of the bell is cut off very near the base of the line of tentacles. Small knobs appear along the cut-edge, but the pieces die before regeneration goes very far. If, however, the margin is cut off in only one quadrant, new tentacles may be produced along the cut-edge.