Like the adult, the germ also requires a certain amount of heat, oxygen, and, when it grows up in the sea, salinity in the medium. For the germ, as for the adult, there exists not only a minimum but also a maximum limit of all the necessary factors of the medium; the same factor which at a certain intensity promotes development, disturbs it from a certain other intensity upwards.
Within the limits of this minimum and this maximum of every outside agent there generally is an increase in the rate of development corresponding to the increase of intensity of the agent. The acceleration of development by heat has been shown to follow the law of the acceleration of chemical processes by a rise of temperature; that seems to prove that certain chemical processes go on during the course of morphogenesis.
Almost all that has been investigated of the part played by the external conditions of development has little bearing on specific morphogenesis proper, and therefore may be left out of account here: we must, however, lay great stress on the general fact that there is a very close dependence of morphogenesis on the outside factors, lest we should be accused afterwards of having overlooked it.
Of course all “external” means or conditions of morphogenesis can actually relate to morphogenetic processes only by becoming in some way “internal,” but we unfortunately have no knowledge whatever how this happens. We at present are only able to ascertain what must necessarily be accomplished in the medium, in order that normal morphogenesis may go on, and we can only suppose that there exist certain specific internal general states, indispensable for organogenesis but inaccessible to present modes of investigation.[36]
The Discoveries of Herbst.—There are but few points in the doctrine of the external means or conditions of organogenesis which have a more special bearing on the specification of proper form, and which therefore require to be described here a little more fully. All these researches, which have been carried out almost exclusively by Herbst,[37] relate to the effect of the chemical components of sea-water upon the development of the sea-urchin. If we select the most important of Herbst’s results, we must in the first place say a few words on the part taken by lime or calcium, not only in establishing specific features of form, but in rendering individual morphogenesis possible at all. Herbst has found that in sea-water which is deprived of calcium the cleavage cells and many tissue cells also completely lose contact with each other: cleavage goes on quite well, but after each single division the elements are separated; at the end of the process you find the 808 cells of the germ together at the bottom of the dish, all swimming about like infusoria. There seems to be some influence of the calcium salts upon the physical state of the surfaces of the blastomeres.
It is not without interest to note that this discovery has an important bearing on the technical side of all experiments dealing with the isolation of blastomeres. Since the separation of the single cleavage elements ceases as soon as the germs are brought back from the mixture without lime into normal sea-water, it of course is possible to separate them up to any stage which it is desired to study, and to keep them together afterwards. Thus, if for instance you want to study the development of isolated cells of the eight-cell stage, you will leave the egg in the artificial mixture containing no calcium until the third cleavage, which leads from the four- to the eight-cell stage, is finished. The single eight cells brought back to normal sea-water at this point will give you the eight embryos you want. All researches upon the development of isolated blastomeres since the time of Herbst’s discovery have been carried out by this method, and it would have been quite impossible by the old method of shaking to pursue the study into such minute detail as actually has been done. It may be added that calcium, besides its cell-uniting action, is also of primary importance in the formation of the skeleton.
Among all the other very numerous studies of Herbst we need only mention that potassium is necessary for the typical growth of the intestine, just as this element has been found necessary for normal growth in plants, and that there must be the ion SO4, or in other terms, sulphur salts present in the water, in order that the germs may acquire their pigments and their bilateral symmetry. This is indeed a very important result, though it cannot be said to be properly understood. It is a fact that in water without sulphates the larvae of Echinus retain the radial symmetry they have had in the very earliest stages, and may even preserve that symmetry on being brought back to normal sea-water if they have spent about twenty-four hours in the artificial mixture.
We may now leave the subject of Herbst’s attempts to discover the morphogenetic function of the single constituents of normal sea-water, and may devote a few words to the other branch of his investigations, those dealing with the morphogenetic effects of substances which are not present in the water of the sea, but have been added to it artificially. Here, among many other achievements, Herbst has made the most important discovery that all salts of lithium effect radical changes in development.[38] I cannot describe fully here how the so-called “lithium larva” originates; let me only mention that its endoderm is formed outside instead of inside, that it is far too large, that there is a spherical mass between the ectodermal and the endodermal part of the germ, that a radial symmetry is established in place of the normal bilateralism, that no skeleton exists, and that the mesenchyme cells are placed in a quite abnormal position. All these features, though abnormal, are typical of the development in lithium. The larvae present no really pathological appearance at all, and, therefore, it may indeed be said that lithium salts are able to change fundamentally the whole course of morphogenesis. It detracts nothing from the importance of these discoveries that, at present, they stand quite isolated: only with lithium salts has Herbst obtained such strange results, and only upon the eggs of echinids, not even upon those of asterids, do lithium salts act in this way.
γ. THE FORMATIVE CAUSES OR STIMULI
The Definition of Cause