THE SKIN AS A COMMUNITY OF STRUCTURES The origin of the melanocytes of the mouse has been beautifully demon- strated by Rawles. Grafts of the presumptive epidermis and dermis of embryo mice were transferred to a suitable part of an incubating chicken's egg when development proceeded in association with the chick (RaMes, 1953). The eggs were those of the White Leghorn and the tissues of the chick develop no melanin pigmentation. The grafts were taken from embryos before and after migration of the neural crest and in addition neural crest material itself was cultivated. The mice used were of a strain which de- veloped black hair, but formed no melanin in the skin. Under the conditions of cultivation, dermis and epidermis with hairs were developed normally, but grafts removed before migration of the neural crest grew white hairs only. Those removed after migration gave rise to black hairs. Moreover, the cultivated neural crest cells were found to migrate in the epithelia of the chick host and assume their normal form and pigmentary activity. There are many questions remaining to be answered concerning the factors controlling the migration and distribution of the prospective melanocytes, and also concerning their subsequent behaviour. It seems established that these cells undergo growth and division as do other cells, and also that they are included in the outward movement and shedding of the epidermis. Likewise they move outward from the hair bulb in the growth of the hair. During the period of rest of the hair bulb in which a hair club is formed the fate of the melanocytes in that bulb is not known precisely. Later, when the follicle and papilla become active and the complete structure is recon- stituted, it is likely that the melanocytes which pigment the new hair arise from precursors in the residue of the previously active hair bulb (Chase et al.). The presence of melanocytes in tissue can be demonstrated by certain staining techniques, and such methods have shown that there are similar numbers per unit area in white and negro human skin. The difference in racial colour in this and other instances is due to differences in the activity of the cells and is genetically controlled. In the condition of albinism, melanocytes are present in the skin, but remain incapable of forming melanin. Difference in activity as shown by the colour of the melanin pro- duced is responsible for the colour pattern in certain guinea-pigs which possess numbers of melanocytes in red areas of skin similar to those in black areas (Billingham & Medawar, 1953). In common with other living tissues, the pigment-producing cells function through the activity of bio-catalysts, the enzymes. One enzyme associated particularly with the formation of melanin is tyrosinase, which can convert the amino acid tyrosine to dihydroxyphenyla!anine, the precursor of melanin. Although emphasis is placed on the particular chemical reactions involving the oxidation and polymerisation of these single amino acids, tyrosine and dihydroxyphenylalanine, melanin is associated with protein in the living 277

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS animal. It is not known how far such protein contributes to melanin formation in vivo or the continued distribution of melanin to the epidermal tissue. The importance of inherited factors in the activity of the melanocytes has been stressed, but there are other influences, hormonal and nutritional, for example, on this activity. In the succeeding sections the influence of local treatments and of certain nutritional factors will be discussed in illus- tration of the differences and similarities of behaviour of the melanocytes in comparison with the keratin-producing cells. INDEPENDENCE OF PIGMENT FORMATION AND KERATIN PRODUCTION It has already been noted that normal development of hair takes place in the absence of any potential melanocytes and that the melanocytes of the mouse were able to develop and function normally independently of the keratinising mouse tissues. Many observations of human hair illustrate this degree of independence of pigment and keratin formation. In the human of the white races it frequently happens that the scalp hair in childhood is almost white, but becomes darker particularly in the years of puberty when a general increased activity of the skin structures takes place. In later life, the loss of pigmentation can take place while the hair grows vigorously. The earliest biological effect of X-rays to be noted was that of hair loss from a site to which they have been applied. The effect has been investigated using different animals, but the most detailed and careful work has been carried out on mice (Chase, 1949). It was shown for mice growing black hair that a dose of radiation could be given which appeared to destroy the activity of the pigment-producing cells while allowing hair growth to continue in the normal manner. Irradiation of skin where the hair follicles were in a resting condition produced the most marked effect. The new hail s growing in that area were grey. This effect is permanent and so reproducible that it has been suggested as a biological standard for radiation. As the amount of radiation to which the area is exposed is increased, temporary epilation as well as loss of melanocyte activity is observed, but a point is reached when hair ceases to be formed and the loss of hair is permanent. Similar observations have been made with other animals, the hamster, which gives results similar to those obtained with the mouse, the rabbit, the cat and the guinea-pig. As the coarseness of the hair increases, the dose level at which greying occurs approaches that at which loss of hair takes place, and in the human the level at which temporary loss of hair occurs does not lead to loss of pigmentation. In fact, the effect of low levels of X-ray dosage can produce an increase in pigmentation of the skin which is observed, of course, also by exposure to ultra-violet light. Thus, it appears that, in the human, X-radiation at low levels of dosage can stimulate the activity of the melanocytes, but temporary loss of hair occurs before a level 278