THE SKIN AS A COMMUNITY OF STRUCTURES community of these structures and to bring together some of the information which illustrates this point of view. The paper is in three parts, the first of which considers the extent to which the development and growth of the skin structures have been shown to take place in the absence of the whole animal. It is an account of some of the work carried out by tissue-culture techniques upon tissue from embryos and upon adult mammalian skin. The second part of the paper will consider some of the characteristics of the growth of hair and the production of pig- ment in order to demonstrate some of the similarities and differences in the activities of the hair follicles and the pigment-producing cells. It will attempt to show what requirements these structures have in common and in what circumstances the functioning of one structure is markedly affected without apparent effect on the other structure. Finally, these considerations will be extended to the relation between the hair follicles and the sebaceous glands with the additional object of weighing evidence for competition and a balance of activity between them. It is obvious that the discussion of such questions is relevant in any consideration of the possibility of treatments affecting only certain of the skin structures, particularly by local application of such treatment. Part I THE DEVELOPMENT OF SKIN STRUCTURES INDEPENDENT OF THE MAMMALIAN BODY When the responses of an organ or a tissue to a certain treatment are studied while that organ or tissue remains part of the intact animal, it is very difficult to distinguish between effects which are produced by direct action and those which result through the mediation of some other organ in the animal. Thus, a change in the activity of an endocrine gland as a result of the treatment can affect a number of organs, including, perhaps, the organ which is being studied. In order to separate the direct from the indirect effects and so obtain information about the intrinsic potentialities of the tissue, many studies have been made of small pieces of tissue growing in isolation from the whole animal. The tissues can be cultivated as organs, that is, organised assemblies of cells, and it is such studies relating to the skin which are considered below. ¾.MBRYO TISSUES The main development of the mammalian epidermis and its associated structures takes place in the embryo. In the mouse, for example, the hair follicles are formed before birth and for some time shortly afterwards, but in the human most follicles are formed before birth. Studies of the develop- 119

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS ment of skin structures in mice have been carried out by removing portions of the skin from the trunk of embryos and cultivating these upon clots prepared from equal parts of fowl plasma and chicken embryo extract (Hardy, 1949 and 1951). Some of the embryonic skin was removed before hair follicle development had apparently begun. The cultures were continued until past the time when the mice would have been born and a comparison was made of the structures which developed in the cultures with those appearing in normal young mice of the same age. The cultivated material showed normally developed epidermis, hair follicles and some differentiation of cells in sebaceous glands. Close similarity with the same structures in normal young mice was observed in the hair papillae, root-sheaths and the growing hairs, the last consisting of a cortex and cuticular scales which developed with normal changes in the constituent cells. The rate of cell division was high and even after 25 days' cultivation, dividing cells were present in the epidermis, dermis and hair follicles. When the cultures were prepared from the embryos of coloured mice, pigment-producing cells and pigmented hairs were easily distinguished. Pigment cells were active in some cases where hair follicles failed to form keratinising fibres, and these cells produced pigment as if a hair were present to receive it. Hardy concluded that the dermis and epidermis together were sufficient for forming and maintaining the hair follicles, no other cellular structures being required. Neither circulating blood nor nervous stimulation appeared necessary for follicle formation and the absence of blood circulation affected only the quantity of keratin produced by the hair follicles and the epidermis. The effect of blood supply on the quantity of keratin formed by the skin of the adult mouse is seen when the wave of activity passes through the coat during the cycle of hair growth, the blood supply increasing markedly with active growth in a certain area. The increased blood supply is required for maximum production of keratin only. The potentialities for diverse development of embryonic tissues prevent the results obtained with them being necessarily applicable to adult tissues. However, the fact that the development of embryonic skin tissues can be influenced by external conditions is shown by the growth of skin from the chick embryo (Fell, Mellanby & Pelc, 1954). When comparable fragments from the trunk and limbs were cultivated in media with and without the addition of excess vitamin A alcohol then marked differences were observed in the development of the skin. The tissue expected to form a keratinising epidermis did so in the absence of excess vitamin whereas when excess vitamin A was present a mucus-secreting membrane resulted. A mucous membrane readily takes up sulphate to form polysaccharide sulphates, but the animal uses very little to form sulphur amino acids such as the cystine in keratin. Addition to the media of sulphate containing a radio-active isotope of sulphur revealed that the keratinising epithelium took up very little sulphate whereas 120