Biological differentiation

“ Embryology might almost be termed the science of organic differentiation. Now all that you do, as practising physicians, is to deal with differentiated organs and tissues. You deal with a function, normal or diseased, which is rendered possible by the differentiation of cells. You deal with pathological states, every one of which has its special differentiation. Every phenomenon which you encounter in your professional work is conditioned by the differentiation of the organic living substance. ”

“ But-although they do not contain any of the differentiated structures and functions of the developed organism, they differ from other cells in that they are capable under suitable conditions of producing these structures and functions by the process of development or differentiation, in the course of which the general structures and functions of the germ cells are converted into the specific structures and functions of the mature animal or plant. ”

“ Modern embryology has completely negatived any such view as that of preformation, and as completely established that the evolution is not the unfolding of a miniature germ, but the growth and differentiation of primitively similar cell-elements. In different animals, as might be expected, the manner and course of development are different. ”

“ Viewed as a whole, there can be little doubt that the general tendency of evolution is towards more complete adaptation to more diverse and complex environment. And this tendency is accompanied by a general increase of differentiation and of integration; of differentiation whereby the constituent elements of life, whether cells, tissues, organs, organisms, or groups of organisms, become progressively more specialized and more different from one another ”

“ The form and connections of the nervous system are of particular importance in distinguishing the types (cf. Cuvier) . The second factor in the diversity of organic form is the action of certain laws of progressive development [313] (Entwickelungsgesetze) , which bear the same relation to the development of the animal kingdom as the laws of individual development bear to the development of the embryo, for organs appear in the different animal series in much the same order and manner as they develop in the individual. These laws are (1) progressive differentiation of functions and organs ”

“ But the matter can also be looked at in an opposite light, and then the endless root of the germ-plasm, with its germ-cells ever forming new individuals, may be regarded as the means by which alone nature was able to create multicellular organisms, individuals of higher and higher differentiation and capacity, able to adapt themselves to all possible conditions, and to make the fullest use of all the possibilities of life. ”

“ In order that perfection of the adult structure should be attained, it is necessary that the mere undifferentiated cells, each with a small body of protoplasm, should acquire first an increased amount of protoplasm, and that then from the increased protoplasm should be taken the material to result in differentiation, in specialization.
An undifferentiated cell performs all the fundamental functions of life. An amœba, or any unicellular organism such as I have presented to you upon the screen, does everything which is indispensable to life. It takes food ”

“ Darwin has so admirably explained, give to the individuals of the species a kind of integration that makes possible a mutual aid in the production of vigorous offspring. And it is interesting to observe how, in that dimorphism by which in some cases this mutual aid is made more efficient, the greater degree of integration is dependent on the greater degree of differentiation—not simply differentiation of the fructifying organs from other parts of the plant bearing them, but differentiation of these fructifying organs from the homologous organs of neighbouring individuals of the same race. ”

“ Higher in the scale of animal life the forms will be found still more and more complex, with ever-increasing differentiation of the cells, with the combination of the differentiated cells into distinct organs, and the co-ordination of organs into systems of organs up to the extreme shown by the birds and mammals. And hand in hand with this increasing complexity of structure goes ever-increasing complexity or specialization of function. ”

“ It thus becomes necessary that, in the increasing complexity of animal forms, the process of differentiation should be accompanied by a corresponding integration, that the isolated tissues should be made a whole by bonds uniting them together. ”

“ But in any case, after this process of cell-division has proceeded for a certain time, differentiation begins to set in—some cells become modified in one way, others in another, and from what was a relatively homogeneous mass an organized embryo, with highly differentiated parts, appears. ”

“ There is always a tendency in development to throw back the differentiation of the embryonic cells into definite tissues to as late a date as possible. This takes place in order to enable the changes of form, which every organ undergoes, in repeating even in an abbreviated way its phylogenetic history, to be effected with the least expenditure of energy. ”

“ We have seen that processes of selection take place even between the elements of the germ-plasm in all organisms which possess a germ-plasm as distinguished from the mass of the body, and that through these processes there arise those hereditary individual variations which, under some circumstances, form the basis of transformations in the species. ”

“ But differentiation consists not only in the formation of different kinds of substances in cells, but also in the separation of these substances from one another. This separation is brought about to a great extent by flowing movements within cells which are associated especially with differential cell division. ”

“ If we could conceive of an organism like one of those to which disease may be due becoming actually incorporated with the system of its host, so as to form a constituent of its germ-cells and to take part in the symmetry of their divisions, we should have something analogous to the case of a species which acquires a new factor and emits a dominant variety. ”

“ On this view differentiation is a mechanical process, set in motion by fertilization or some other cause, and, given a certain initial structure of the germ or ovum, given the presence in it of a certain number of parts or substances capable of acting upon one another with a fixed co-ordination or harmony of the stimuli and the responses, given further a proper constitution of the external environment, then a definite result must follow, the production of an organism which is like the parents that gave it birth. ”

“ The factors of evolution fall under two heads—origin and guidance. The origin of variations lies in mechanical stresses, and chemical or physical influences. Whether these act on the body (and are transmitted by inheritance) or only on the germ, is a question which divides biologists into two schools. In the latter case all variations are fortuitous; in the former the development of tissue-variations has been in direct response to the physical or chemical influences. ”

“ Darwin accepted such transmission as subordinate to natural selection, and attempted to account for it by his theory of pangenesis. According to that hypothesis all the component cells of an organism throw off minute gemmules, and these and their like, collecting in the reproductive cells, are the parental germs from which all the cells of the offspring of that organism are developed. ”

“ The variability of germs under changed conditions, and that of their progeny, may be small, but it is indubitable; absolute uniformity being scarcely conceivable in the condition and growth, and, therefore, in the reproduction of any organism. ”

“ The germ cell, like the unicellular organism, on conjugating, divides and redivides many times without conjugation ever occurring again among its descendant cells, the successive generations of which may be compared to successive non-conjugating generations of infusorians, so that the body of a multicellular organism in the successive stages of its ontogeny is comparable to later and later generations of infusorians ”

“ It is clear that the organism that best uses its organs has, other things equal, the best chance of survival. It will therefore hand on to its offspring germinal matter with an inherent tendency to make vigorous use of its faculties.
Those who argue thus deny that the body-cells can in any way affect the germ-cells. To account for any continuous increase in faculty, they invoke variation and the selection of favourable varieties. What, then, we may now ask, is, on their view, the mode of origin of variations? ”

“ We only, I believe, can state the fact that there are relations between morphogenetic causes and effects which are adaptations, that functional disturbances or changes are followed by single histogenetic reactions from the organism, which are compensations of its disturbed or changed functional state. ”

“ But in many cases, with variable organic beings, the mutual affinities of the cells and gemmules become modified, so that parts are transposed or multiplied; and it would appear that a slight change in the constitution of an animal, in connection with the state of the reproductive organs, leads to changed affinities in the tissues of various parts of the body. ”

“ I may in one respect even go further, and affirm, that, if in a species, any part or organ differs remarkably from the same part in its congeners, then if many specimens are examined, especially when collected from different districts, such part or organ will be found eminently variable. ”

“ Now, it is the union of germ-plasms which is required to reproduce new individuals of multicellular organisms that determines congenital variations on the part of such organisms, and thus furnishes natural selection with the material for its work in the way of organic evolution—work, therefore, which is impossible in the case of unicellular organisms, where variation can never be congenital, but always determined by the direct action of surrounding conditions of life. ”

“ If the germ-plasm be a system of determinants, then the same laws of struggle for existence in regard to food and multiplication must hold sway among its parts which hold sway between all systems of vital units—among the biophors which form the protoplasm of the cell-body, among the cells of a tissue, among the tissues of an organ, among the organs themselves, as well as among the individuals of a species and between species which compete with one another. ”

“ Thus, little as there seems in common between the shapes of plants and the shapes of animals, we yet find, on analysis, that the same general truths are displayed by both. The one ultimate principle that in any organism equal amounts of growth take place in those directions in which the incident forces are equal, serves as a key to the phenomena of morphological differentiation. ”

“ I am convinced that the theory of physiological selection is the only one that can explain the facts of inter-specific sterility on the one hand, and, on the other hand, the contrast which these facts display to the unimpaired fertility of our domesticated varieties. ”

“ In order the more thoroughly to investigate these matters it is necessary to consider the mode of growth, and specially the plan of evolution or development of each organ. This is the more needful owing to the common origin of things ultimately very different one from the other, and to the presence of organs which, in the adult state, are identical or nearly so in aspect, but which nevertheless are very unlike in the early stages of their existence. ”

“ Such early differentiations are only the visible proofs of certain highly complex molecular rearrangements in the cells, and the fact appears to indicate that we cannot be far wrong in maintaining that differentiations which appear in the course of ontogeny depend upon the chemical and physical constitution of the molecules in the reproductive cell. ”

“ But it is not equally manifest that, on this hypothesis, alterations of structure caused by alterations of function must be transmitted to offspring. It is not obvious that change in the form of a part, caused by changed action, involves such change in the physiological units throughout the organism that these, when groups of them are thrown off in the shape of reproductive centres, will unfold into organisms that have this part similarly changed in form. ”

“ Furthermore, according to Professor Weismann, natural selection is really working, not on the organism at large, but on the germ-plasm which produces it; and it is [214] conceivable that the variation of one or more of the few cells in early embryonic life may introduce a great number of variations in the numerous derivative cells. ”

“ The number of cell-generations following conjugation differs in different individuals of the same species, and may be made to differ in each individual by variations in nutrition, exercise, &c. It differs enormously in different species of plants and animals; thus the number of cell-generations following conjugation is enormously fewer in minute plants and insects than in such great plants and animals as pines and whales. ”