Heteroplasty

HETEROPLASTY, the cross-transplantation of tissues or organs between individuals belonging to different species. This, of course, also includes the transplantation of tissues or organs from animals to humans. In relation to the entire world of plants and animals, it must be said that compared to autoplasty and homoplasty, heteroplasty yields the worst results. Since the process of fertilization can be considered a kind of free transplantation (of a sperm cell onto an egg cell), and the latter is possible only between closely related species, and even then in limited dimensions, one can expect in advance that the possibilities of heteroplastic transplantations cannot exceed these same limits. Observations fully confirm this assumption. The study of heteroplastic transplantations in plants yields extremely interesting results. Grafts of artichoke onto thistle, tomato onto potato, melon onto cucumber, etc., are successful. The possibility of such cross-grafting (i.e., transplantations), along with cross-pollination, is the main factor in improving breeds and obtaining new varieties in cultural gardening and vegetable growing. At the same time, paradoxical facts are sometimes observed: grafts onto more distant species (of a different family) sometimes yield better results than onto closer ones; Cytisus hirsutus on the same plant grows only up to 1/4 m in two years, but on Laburnum it produces a richly branched shoot a whole meter long in the same amount of time. The apple tree and pear tree, which are close to each other, graft and grow on each other worse than the more distant quince and apple tree. Botanists speak of harmonic and disharmonic combinations, and, with few comparative exceptions, the degree of harmony is generally determined by the degree of kinship. Disharmony is not always complete; in some cases, the graft initially takes root but then grows poorly, becomes diseased, and finally dies or puts out its own roots, as if in search of its own nourishing soil. In animals, heteroplastic transplantations generally do not succeed, but in lower animals, quite a few cases of successful transplantations between very closely related species have been described. Cross-transplantations between Hydra fusca and Hydra viridis did not produce a lasting union, but a lasting union was obtained between parts of the more closely related Hydra polypus and Hydra oligactis. Transplantations on closely related species of earthworms were successful. Leypoldt succeeded in transplanting a skin-muscle flap of the common earthworm (Lumbricus terrestris) onto a corresponding defect of another worm, Holodrilus longus. True, he also had to observe for the most part that these engrafted parts were resorbed or rejected after fairly long periods (up to 21 months). Harms transplanted ovaries in worms and not only found them preserved after several months but also observed their fertilization, with the birth of hybrids. Crampton succeeded in similar transplantations between butterfly larvae. As for vertebrates, until now, heteroplastic transplantations have succeeded only in amphibians, and even then at the very early stage of their development—in larvae, capable

The larvae of Rana silvatica with the body of Rana palustris. The drawing depicts this animal 2 hours, 26 1/2 hours, and 4 days after the operation. In adult animals, transplantations between closely related species of newts were successful, as well as between a newt and an axolotl, but the observation periods were short, not exceeding a few months, so it is not yet possible to speak with great certainty about permanent engraftment. Numerous attempts to transplant skin on different species of frogs have never been successful. In mammals, heteroplastic transplantations are never successful. In surgical literature, mainly of the second half of the 19th century, one can find very numerous cases of transplantations of tissues and organs of various animals to replace corresponding defects in humans. Since the fate of the transplants was judged only by the clinical (anatomical or functional) result obtained, it was very often said that such transplantations were a complete success. For example, when filling a defect in the cranial bones with animal bone and obtaining a bony closure of the defect as a result, it was said that the transplanted bone had engrafted. When transplanting frog skin onto a skin ulcer and obtaining healing of the ulcer under a scab, it was said that this skin had engrafted. The same was true for the transplantation of tendons, muscles, and vessels, and now it often happens with the transplantation of endocrine glands. Marchand was the first to draw attention to the fact that the fate of a transplant can be judged only on the basis of histological examination in the immediate period after transplantation. Examinations carried out under such control always lead to the invariable conclusion that heteroplastic transplantations in higher animals are so far completely impossible. There is not a single histologically proven case of engraftment of animal tissues or organs in humans. Even malignant tumors, consisting of the least differentiated and most prone to rapid growth and reproduction cells, are completely incapable of heteroplastic transplantation. The question of the reasons for the impossibility of heteroplastic transplantations in animals is of great biological interest, and a whole series of considerations can be cited to explain this fact. In the first place is the question of the nutrition of the transplant. Any engraftment, and especially a permanent, long-term one, is possible only if the transplant is provided with nutrition. Meanwhile, the biochemical processes occurring in representatives of different species undoubtedly differ from each other. It can now be considered proven that foreign proteins are not assimilated directly by the organism; during normal digestion, they are first broken down in the intestine, and from the products of decomposition in the walls of the intestine itself, the protein characteristic of the given organism is built. The organism reacts rather violently to the parenteral administration of foreign protein and excretes it as unsuitable material, so that it is impossible to nourish an animal by parenteral administration of proteins. With aseptic slow resorption of a heteroplastic transplant, this resorption can be considered as the death of tissues from starvation. Plants are in better conditions in this respect, as their individual parts are more independent; they feed on inorganic substances, from which they themselves build their proteins. The plant onto which the graft is made supplies only these inorganic substances and replaces the missing root for the grafted part. Therefore, the boundaries of possible cross-transplantations here must be wider than in animals. Biochemical discrepancies not only disrupt the nutrition of the transplant; in many cases, one can speak of a directly poisonous effect of some tissues on other, foreign ones. In cross-transplantations between distant species, one has to observe acutely occurring gangrene of the transplant and a sharp inflammatory reaction at the site of transplantation. This poisonous effect (or rather, interaction) of some tissues on other, foreign ones manifests itself, for example, in hemolysis and agglutination when mixing foreign bloods; these same processes are observed in other tissues. It goes without saying that with such a relationship, there can be no talk of engraftment of the transplant. If the indicated phenomena can be called primary poisonings, then one must also mention secondary poisonings, proceeding according to the type of immunity. The organism reacts to the introduction of foreign substances by forming corresponding antibodies, which, in turn, are directed against the transplant. It is by the action of these antibodies that one can explain cases where the transplant initially engrafts, but after some time either resorbs or is rejected; it obviously took some time to produce the necessary protective substances, antibodies. This is also confirmed by specially conducted experiments: if a rat is prepared by injections of an emulsion of mouse tissues, then a flap of mouse skin transplanted onto such a rat dies sooner than when transplanted onto an unprepared rat. Some authors also point to the importance of chemotaxis in the processes of engraftment: if there is negative chemotaxis between the cells of the transplant and the host, then even under other favorable conditions, fusion is obviously impossible. Summarizing the above, it must be said that if we understand successful transplantations as long-term engraftment of the transplant with the preservation of its morphological features, then the possibility of such between different species has so far been proven only for plants and lower animals, and even then within very limited boundaries. Among vertebrates, this was successful only in some cases in very young amphibians, although the engraftment was still not permanent. As for higher vertebrates, including humans, there is not a single proven case of successful heterogeneous transplantation in the literature so far; and in the present state of this question, such transplantations must be recognized as impossible. This does not mean, of course, that they will never become possible. In view of the fact that science is penetrating deeper and deeper into the laboratory of the living cell, ways may perhaps be found to influence the transplant or the host in such a way that their mutual fusion and long-term coexistence will become possible. If secondary formation of harmful antibodies is possible, then perhaps an influence of the reverse order will also prove possible. Some attempts in this regard are already being made, but hints of positive results have so far been achieved only in the field of homoplasty (see). From what has been said, it is clear that the use of heteroplasty in practical surgery is very limited. But, not possessing the ability for true engraftment, heterotransplants can serve a useful purpose in some cases. By filling tissue defects, they serve as a stimulus for the regeneration of the host's own tissues and direct this regeneration along the right path. When filling, for example, bone defects with foreign bone, regeneration of young bone tissue from the edges of the defect occurs well along the dead transplant, as a result of which the defect is filled with living bone tissue, which would not happen if the defect were simply filled with a scar. The same is observed in inflammation of long tendons, sometimes even skin. The situation is different with the transplantation of endocrine glands. Animal glands undoubtedly cannot engraft in humans, although there are quite a few reports and claims of the opposite character in the literature. But it cannot be denied that a functional result is often observed in such transplantations. The first attempts at thyroid transplantation were made precisely with animal glands with a positive, but usually very short-lived, functional effect. This positive effect must obviously be interpreted as meaning that the transplanted gland possesses a certain reserve of specific hormone, which, in the process of slow resorption of the transplant, gradually enters the host's organism and produces the corresponding effect, as in simple organotherapy. Upon exhaustion of this reserve, the effect ceases. But cases have been described, albeit few, of long-term success after such transplantations, which can be explained by the fact that the host's own gland, which had been working insufficiently until then, stimulated by the new hormone, recovered and began to work better. Not once yet after such transplantations of thyroid and other animal glands has it been possible to find remnants of these glands after any significant length of time. The same must be said about the now so fashionable transplantations of sex glands. All the available clinical and experimental material on this subject speaks of the great brevity of success, if it occurs at all. Only Voronoff speaks of actual engraftment of monkey testicles in humans, but his claims arouse great doubt.

V. Pokotilo