•2 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS occur without preceding inflamma- tory reaction. A number of guinea pigs were fed approximately 12 grams of mono- benzyl ether of hydroquinone over a period of 5 months. This was well tolerated but no pigmentary changes were observed. Local application over a period of months, just as in the human subjects, caused de- pigmentation. The disappearance of the pigment was accompanied by a negative "dopa" reaction in the affected areas. This observation only applied to the previously pig- mented epidermis whereas the hair bulbs were not affected. This was probably due to a lack ofp4netration of the monobenzyl compound to the melanoblasts in the hair matrix. CAN PIGMENT ENZYME ACTIVITY BE STIMULATED IN UNPIGMENTED SKIN .• (42) The results of our experiments (42) have confirmed the observa- tions of Saxton, S•hmekebier and Kelley (43), as well as the earlier work of Loeb (44), Carnot and Deftandre (45) that the transplanta- tion of a black graft into a white skin resulted in the "extension" of the pigment into the surrounding un- pigmented host area while a white graft transplanted in a black skin ß was "invaded" by pigment from the ß host area. It was perfectly obvious from our histologic studies that the pigment formation in the white host area as well as in the non- pigmented grafts in no way differed from the ordinary mechanism of pig- ment formation. The. concept of the older authors of actual invasion by melanoblasts or other pigment- bearing cells from the surrounding pigmented areas into non-pigmented areas was no more true than when it was proposed years ago for melanin formation in general. Nor was there any support for the concep- tion of Rand (4t3) that the epidermis of the graft was replaced by the host with its own epidermis so that na- turally it finally assumes the same color as the host skin. It was clearly seen both macro and microscopically that the grafts always remained recognizable. It remained as a definite entity out- lined by a scar. One of us (47), in previous experi- ments was able to show that the un- pigmented epidermis in gray rabbits had the latent power to form mela- nin. Under proper conditions, such as wound healing and radiant energy, the ordinary basal cells of the epidermis readily assumed melanoblastic function. It was also shown that the relatively unpig- mented human epidermis (48), even in total darkness was able to assume v. ery active melanoblastic function under certain inflammatory stimuli which resulted in epidermal re- generation. We believed that a mechanism similar to the last mentioned would not serve adequately to explain the pigmentary changes noted in our experiments. However, with such an explanation for the pigment fc•r- marion, in the unpigmented or rela- tively unpigmented skin of either the host or the graft, an assumption

THE PIGMENT MELANIN OF THE SKIN AND HAIR 43 had to be made that the epidermis of the white skin of the guinea pigs was able to assume pigment for- mation under stimuli such as radiant energy or as a part of the process of epidermal regeneration such as wound healing. We exposed the shaved white skin of guinea pigs to ultra-violet light from 3 to 6 minutes at a distance of about 13 inches. The same type and area of skin from which white transplants were made was u. sed. A marked inflammatory reaction with redness and desquamation re- sulted but no temporary or perma- nent pigmentation could be demon- strated clinically or histologically. To study the effect of wound heal- ing as a stimulus to latent pigment formation a white graft was trans- planted into a defect in the white skin but again pigment could not be demonstrated. We also allowed wounds to heal spontaneously but no pigment formation could be noted. That such a procedure was capable of stimulating pigment for- mation in an already pigmented skin could readily be demonstrated in similar experiments on black skin. Apparently we are at a loss to explain the initiating stimulus which caused the pigmentation to occur. Contact of an unpigmented skin with an already pigmented epi- dermis was necessary since pig- mentation first occurred at points of junction and then slowly extended outward or in the case of a white graft, inward, like ripples in a pond. It is interesting to speculate on the possible mechanism of the pig- ment formation. In the modern theory of pigment formation we have a melanoblast which contains an enzyme. This enzyme converts the colorless propigment "dopa" or a closely allied chemical substance through various stages into melanin. The propigment reaches the cell from the circulation. The enzyme is apparently found only in melano- blasts and has never been demon- strated to be transported through the cell membrane and thus convert other cells into melanoblasts. We would demonstrate by means of the dopa reaction that the ordi- nary mechanism of pigment for- mation took place in the newly pig- mented areas. We must be led to the conclusion, therefore, that in some way, because of close proxim- ity to pigmented skin, enzymatic action, as far as pigment formation is concerned, is suddenly assumed by the unpigmented epidermis. It is curious that if this enzyme were present in the unpigmented skin it could not be stimulated into activity by radiant energy. Unless our failure to stimulate pigment for- mation by the use of radiant energy was based on an experimental error or on an error of interpretation, it would seem to prove that the pig- ment enzyme as we ordinarily find it was not previously present in unpigmented guinea pig skin. The above experiments are re- ported because it is of interest to the cosmetic chemist to have an insight into possible avenues of investi- gation which would lead to formu- lation of chemical or biologic prod-