Читать книгу The Organism as a Whole, from a Physicochemical Viewpoint - Jacques Loeb - Страница 11

2. It is practically impossible to transplant organs or tissues from one species of higher animals to another, unless the two species are very closely related; and even then the transplanta­tion is uncertain and the graft may either fall off again or be destroyed. This specificity of tissues goes so far that surgeons prefer, when a transplanta­tion of skin in the human is intended, to use skin of the patient or of close blood rela­tions. The reason why the tissues of a foreign species in warm-blooded animals cannot grow well on a given host has been explained by the remarkable experi­ments of James B. Murphy of the Rockefeller Institute.32 Murphy discovered that it is possible to transplant successfully any kind of foreign tissue upon the early embryo of the chick. Even human tissue transplanted upon the chick embryo will grow rapidly. This shows that at this early stage the chick embryo does not yet react against foreign tissue. This lack of reac­tion lasts until about the twenty-first day in the life of the embryo; then the growth of the graft not only ceases but the graft itself falls off or is destroyed. Murphy noticed that this critical period coincides with the development of the spleen and of lymphatic tissue in the chick and that a certain type of migrating cells, the so-called lymphocytes, which develop in the lymphatic tissue, gather at the edge of the graft in great numbers, and he suggested that these lymphocytes (by a secre­tion of some substance?) rid the host of the graft. He applied two tests both of which confirmed this idea. First he showed that when small fragments of the spleen of an adult chicken are transplanted into the embryo the latter loses its tolerance for foreign grafts. The second proof is still more interesting. It was known that by treatment with Roentgen rays the lymphocytes in an animal could be destroyed. It was to be expected that an animal so treated would have lost its specific resistance to foreign tissues. Murphy found that this was actually the case. On fully grown rats in which the lymphocytes had been destroyed by X-rays (as ascertained by blood counts) tissues of foreign species grew perfectly well. These experi­ments have assumed a great practical importance since they can also be applied to the immuniza­tion of an animal against transplanted cancer of its own species. Murphy found that by increasing the number of lymphocytes in an animal (which can be accomplished by a mild treatment with X-rays) the immunity against foreign grafts as well as against cancer from the same species can be increased. It is quite possible that the apparent immunity to a transplanta­tion of cancer produced by Jensen, Leo Loeb, and Ehrlich and Apolant through the previous transplanta­tion of tissue in such an animal was due to the fact that this previous tissue transplanta­tion led to an increase in the number of lymphocytes in the animal. The medical side, however, lies outside of our discussion, and we must satisfy ourselves with only a passing notice. The facts show that each warm-blooded animal seems to possess a specificity whereby its lymphocytes destroy transplanted tissue taken from a foreign species.

A lesser though still marked degree of incompatibility exists also in lower animals for grafts from a different species.33 The graft may apparently take hold, but only for a few days, if the species are not closely related. Joest apparently succeeded in making a permanent union between the anterior and posterior ends of two species of earthworms, Lumbricus rubellus and Allolobophora terrestris. Born and later Harrison healed pieces of tadpoles of different species together. An individual made up of two species Rana virescens and Rana palustris lived a considerable time and went through metamorphosis. Each half regained the characteristic features of the species to which it belonged. It seems, however, that if species of tadpoles of two more distant species are grafted upon each other no lasting graft can be obtained, e.g., Rana esculenta and Bombinator igneus. These experi­ments were made at a time when the nature and bearing of the problem of specificity was not yet fully recognized. The rôle of lymphocytes in these cases has never been investigated. The grafted piece always retained the characteristics of the species from which it was taken.

Plants possess no leucocytes and we therefore see that they tolerate a graft of foreign tissues better than is the case in animals. As a matter of fact hetero­c grafting is a common practice in horticulture, although even here it is known that indiscriminate hetero­plastic grafting is not feasible and that therefore the specificity is not without influence. The host is supposed to furnish only nutritive sap to the graft and in this respect does not behave very differently from an artificial nutritive solu­tion for the raising of a plant. The law of specificity, however, remains true also for the grafted tissues: neither in animals nor in plants does the graft lose its specificity, and it never assumes the specific characters of the host, or vice versa. The apparent excep­tions which Winkler believed he had found in the case of grafts of nightshade on tomatoes turned out to be a further proof of the law of specificity. Winkler, after the graft had taken, cut through the place of grafting, after which opera­tion a callus forma­tion occurred on the wound. In most cases either a pure nightshade or a pure tomato grew out from this callus. In some cases he obtained shoots from the place where graft and host had united, which on one side were tomato, on the other side nightshade. What really happened was that the shoots had a growing point whose cells on the one side consisted of cells of nightshade, on the other side of tomato.34 We know of no case in which the cell of a graft has lost its specificity and undergone a trans­forma­tion into the cell of the host.

3. Another manifesta­tion of the incompatibility of distant species is found in the domain of fertiliza­tion. The eggs of the majority of animals cannot develop unless a spermato­zoön enters. The entrance of a spermato­zoön into an egg seems also to fall under the law of specificity, inasmuch as in general only the sperm of the same or a closely related species is able to enter the egg. The writer35 has found, however, that it is possible to overcome the limita­tion of specificity in certain cases by physico­chemical means, and by the knowledge of these means we may perhaps one day be able to more closely define the mechanism of specificity in this case. He found that the eggs of a certain Californian sea urchin, which cannot be fertilized by the sperm of starfish in normal sea water, will lose their specificity towards this type of foreign sperm if the sea water is rendered a little more alkaline, or if a little more Ca is added to the sea water, or if both these varia­tions are effected. Godlewski has confirmed the efficiency of this method for the fertiliza­tion of sea-urchin eggs with the sperm of crinoids.

Fig. 1. Five-days-old larvæ from a sea urchin (Strongy­lo­cen­tro­tus purpuratus) ♀ and a starfish (Asterias) ♂. (Front view.)

Fig. 2. Five-days-old larvæ of Strongylo­cen­tro­tus pur­pur­atus produced by artificial parthenogenesis. (Side view.) The larvæ in Figs. 1 and 2 are identical in appearance, proving that hetero­geneous hybridiza­tion leads to a larva with purely maternal characters.

Fig. 3. Five-days-old larvæ of two closely related forms of sea urchins (S. purpuratus ♀ and S. franciscanus ♂). In this case the larva has also paternal characters as shown by the skeleton.

If such hetero­geneous hybridiza­tions are carried out, two striking results are obtained. The one is that the resulting larva has only maternal characteristics (Figs. 1 and 2), as if the sperm had contributed no hereditary material to the developing embryo. This result could not have been predicted, for if we fertilize the egg of the same Californian sea urchin, Strongylo­centrotus purpuratus, with the sperm of a very closely related sea urchin, S. franciscanus, the hereditary effect of the spermato­zoön is seen very distinctly in the primitive skeleton formed by the larva.36 (Fig. 3.) In the case of the hetero­geneous hybridiza­tion the spermato­zoön acts practically only as an activating agency upon the egg and not as a transmitter of paternal qualities.

The second striking fact is that while the sea-urchin eggs fertilized with starfish sperm develop at first perfectly normally they begin to die in large numbers on the second and third day of their development, and only a very small number live long enough to form a skeleton; and these are usually sickly and form the skeleton considerably later than the pure breed. It is not quite certain whether the sickliness of these hetero­geneous hybrids begins or assumes a severe character with the development of a certain type of wandering cells, the mesenchyme cells; it would perhaps be worth while to investigate this possibility. The writer was under the impression that this sickliness might have been brought about by a poison gradually formed in the hetero­geneous larvæ.

He investigated the effects of hetero­geneous hybridiza­tion also in fishes, which are a much more favourable object. The egg of the marine fish Fundulus hetero­clitus can be fertilized with the sperm of almost any other teleost fish, as Moenkhaus37 first observed. This author did not succeed in keeping the hybrids alive more than a day, but the writer has kept many hetero­geneous hybrids alive for a month or longer,38 and found the same two striking facts which he had already observed in the hetero­geneous cross between sea urchin and starfish: first, practically no transmission of paternal characters, and second, a sickly condi­tion of the embryo which begins early and which increases with further development. The hetero­geneous fish hybrids between, e.g., Fundulus hetero­clitus ♀ and Menidia ♂ have usually no circula­tion of blood, although the heart is formed and beats and blood-vessels and blood cells are formed; the eyes are often incomplete or abnormal though they may be normal at first; the growth of the embryo is mostly retarded. In excep­tional cases circula­tion may be established and in these a normal embryo may result, but such an embryo is chiefly maternal.

This incompatibility of two gametes from different species does not show itself in the case of hetero­geneous hybridiza­tion only, but also though less often in the case of crossing between two more closely related forms. The cross between the two related forms S. purpuratus ♀ and S. franciscanus ♂ is very sturdy and shows no abnormal mortality as far as the writer’s observa­tions go. If, however, the reciprocal crossing is carried out, namely that of S. franciscanus ♀ and S. purpuratus ♂, the development is at first normal, but beginning with the time of mesenchyme forma­tion the majority of larvæ become sickly and die; and again the ques­tion may be raised whether or not the beginning of sickliness coincides with the development of mesenchyme cells. If we assume that the sickliness and death are due to the forma­tion of a poison, we must assume that the poison is formed by the protoplasm of the egg, since otherwise we could not understand why the reciprocal cross should be healthy.

All of these data agree in this one point, that the fusion by grafting or fertiliza­tion of two distant species is impossible, although the mechanism of the incompatibility is not yet understood. It is quite possible that this mechanism is not the same in all the cases mentioned here, and that it may be different when two different species are mixed and when incompatibility exists between varieties, as is the case in the graft on mammals.