These facts show that the growth of an organ comes to a standstill when a certain size is reached or a certain number of cells are formed. We cannot yet state why this should be, but we are able to add that the formation of a lens of normal size in the regeneration of the eye is in harmony with the phenomena in the embryo. There seems therefore no reason for stating that the regeneration of the lens cannot be explained on a purely physicochemical basis. The only justification for such a statement on the part of Wolf is that he was not in possession of the more complete set of facts now available through the work of Fischel and Uhlenhuth.
The healing of a wound is a process essentially similar to the regeneration of the lens. Normally the cells which begin to proliferate after a wound is made in the skin lie dormant, inasmuch as they neither grow nor divide. When a wound is made certain layers of epidermal cells undergo rapid cell division. Leo Loeb[174] has studied this case extensively. He found that if the skin is removed anywhere, epidermis cells from the wound edge creep upon the denuded spot and form a covering. This may be a tropism (stereotropism) or it may be a mere surface tension phenomenon. Next a rapid process of cell division begins in the cells adjacent to the wound these cells having been heretofore dormant. He is inclined to attribute this increase in the rate of cell division to the stretching of the epithelial cells, and he is supported in this reasoning by the observation that the larger the wound the more rapid the process of healing.[175] During wound healing the mitoses first increase markedly in the old epithelium. With the closure of the wound a sudden fall in the mitoses takes place. The closure of the wound causes an increase in the number of epithelial rows over the defect. This increase is therefore reached at an earlier period in the larger wound since the process of mitosis is more rapid here. Leo Loeb thinks that the pressure of the epithelial cells upon each other leads to a rapid diminution in the mitotic proliferation.[176]
Should it be possible that this is more generally the case, e. g., also in the lens after it has reached a certain size? The conditions limiting growth require further investigation.
It is hardly necessary to point out that in these cases we are seemingly dealing with cases of the inhibition of growth which cannot be explained by the tyranny of the whole over the parts, and that there must be conditions at work other than the mere flow of substances which can cause a cessation of growth. This can be illustrated by certain observations on the egg.
8. The history of the egg shows a reversible condition of rest and of activity. The primordial egg cell multiplies actively until a large number of eggs are formed in the ovary which may reach into the millions in the case of sea urchins or certain annelids. These cell divisions then stop and the egg goes into the resting stage in which it deposits the reserve material for the development of the embryo. From this condition it can only be called into activity again by the spermatozoön or the agencies of artificial parthenogenesis.
It seemed of interest to find out whether or not the development of the egg may be reversed once more after it has been activated. From all that has been said in the chapter on artificial parthenogenesis, such a reversal should take place in the cortical layer. The result of these experiments seems to be that if a complete destruction or change in the cortical layer has once taken place—such as that caused by the entrance of a spermatozoön into the egg—no reversal is possible; although the development of the fertilized egg may be suppressed for a long time by either low temperature or lack of oxygen, or, in the case of seeds and spores, by lack of water. But as soon as the conditions for the chemical reactions in the egg are normal again, the development may go on unless the egg has suffered by the methods used to prevent development or by the long duration of the suppression. With an incomplete destruction of the cortical layer both development as well as reversal of development are possible. Thus the writer has shown that in the egg of Arbacia the effect of the cortical alteration of the egg induced by the butyric acid treatment or by the treatment with bases can be reversed. When unfertilized eggs of Arbacia are put for from two to five minutes into 50 c.c. sea water + 2.0 c.c. N/10 butyric acid they will all form a gelatinous, somewhat atypical fertilization membrane; when put back into normal sea water all will perish in a few hours unless they are submitted to the short treatment with a hypertonic solution mentioned in the previous chapter, while if submitted to this treatment they will develop. If, however, these eggs are transferred from the butyric acid sea water not into normal sea water but into sea water containing some NaCN (10 drops of 1⁄10 per cent. NaCN or KCN in 50 c.c. sea water), and if they remain here for some time (e. g. overnight) they will not perish when subsequently transferred back to normal sea water. Such eggs will develop when fertilized with sperm. The activating effect of the membrane formation has, therefore, been reversed and the eggs have gone back into the resting stage.[177] Wasteneys has found that the rate of oxidation which was raised considerably by the artificial membrane formation goes back to the value characteristic for the resting eggs after the reversal of their developmental tendency.[178] Similar results were obtained in eggs activated with NH4OH. It appears from this as though the change in the cortical layer which leads to the development of the egg and the increase in the rate of oxidations were reversible in the egg of Arbacia.[179]
The writer had previously noticed that eggs of Strongylocentrotus purpuratus, which had been treated for two hours with hypertonic sea water, not infrequently began to divide into two, four, or eight cells (and sometimes more) and then went back into the resting state (except that they possessed the second factor required for development as stated in Chapter V). It may be remarked incidentally that such eggs at the time of cell division contained the centrosomes and astrospheres, and yet went back into a resting state, thus showing that the centrosomes are only transitory organs or organs which are only active under certain conditions. It is quite possible that in these phenomena of reversal not the whole of the cortical layer has undergone alteration.
The writer must leave it undecided whether the changes from the resting to the active state in body cells can also be explained in analogy with these experiments.
9. In the formation of the lens we have already noticed an instance where the adjacent organ influences growth inasmuch as the optic cup controlled the formation of the lens. Such influences are quite commonly observed. A piece of Tubularia when cut out from a stem and suspended in water will regenerate at the aboral pole not a stolon but a polyp, so that we have an animal terminating at both ends of its body in a head. The writer called such cases in which an organ is replaced by an organ of a different kind heteromorphosis.