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-

44 JOURNAl. OF THE SOCIETY OF COSMETIC CHEMISTS ucts to stimulate pigment formation in cosmetic defects resulting from poor pigment formation. The problem is more than academic when hyperpigmentation re.sults in the vicinity of skin grafts by just such mechanisms as have been de- scribed. The rim of hyperpigmen- tation around such grafts often causes serious cosmetic defects. BIBLIOGRAPHY 1. A detailed review of the papers on pig- ment written before 1900 will be found in the works of Ehrmann, Post and Meirowsky (see 2, 3 and 4). 2. Ehrmann, S.: Das melanotische Pig- ment und die pigmentbildenden Zellen des Menschen und der Wirbbeltiere in' ihrer Entwicklung, Bibliotheca medica, Jena, Gustav Fischer, 1886. 3. Post, H.: Ueber normale und path- ologische Pigmentierung der Oberhaut- gebilde, Virchows Arch. f. path. Anat., 1894, vol. 135. 4. Meirowsky, E.: Ueber den Ursprung des melanotischen Pigmentes der Haut und des Auges, Leipzig, A. Kleinhardt, 1908. 5. Wiedng and Hamdi: Ueber die physi- ologische und pathologische Melanin- pigmentierung und den epithelialen Ursprung der Melanoblasten, Beitr. z. path. Anat. u. z. allg. Path. 42: 84, 1907. 6. Adachi, B., cited by Schwalbe: Das Hautpigment beim Menschen und bei den Affen, Ztschr. f. Morphol. u. Anthropol. 6: 1, 1903. 7. The complete literature on pigment will be found in Block, B.: Das Pigment, in Jadassohn, J.: Handbuch der Haut- und Geschlechtskrankheiten, Berlin, Julius Springer, 1927, vol. 1. 8. Miescher, G.: Die Pigmentgenese im Auge nebst Bemerkungen uber die Natur des Pigmentkorns, Arch. f. mikr. Anat. 97: 326, 1922. 9. Steiner-Wourlisch, A.: Das melano- tische Pigment der Haut bei der grauen Hausmaus, Ztschr. f. Zellforsch. u. mikr. Anat. 97: 326, 1922. 10. Dawson, J.: The Melanomata, Edin- burgh M. J. 32: 501, 1925. 11. Schmidt, W., cited by Bloch (see 7). 12. Kornfeld, cited by Bloch (see 7). 13. Peck, S. M.: Arch. of Dermat. and Syph., 157: 234, 1929. 14. Peck, S.M.: Pigment Melanin Studies of Human Skin after application of Thorium X, Arch Dermat. and Syph., 21:916 (June) 1930. Melanotic Pig- ment in Skin, Hair and Eye of Gray Rabbit, ibid. 23:705 (May) 1931. 15. Raper, N.S.: Blochem. J. 21: 89,1927. 16. Bloch, Bruno and Peck, S. M.: Folia haemat 41: 166, 1930. 17. Oppenheimer, C.: Die Fermente, Leip- zig, Georg Thieme, 1926, Vol. 2, p. 1793. 18. Mulzer, P. and Schmalfuss, H.: Med. Klin. 17: 1099, 1931. 19. Aberhalden, E. and Guggenheim, M.: Ztschr. f. physiol. Chem. 54: 331, 1908. 20. Peck, S. M., Sobotka, H. and Kahn, J.: Optical Specificity of Dioxyphenyl- alanine Oxidase, the Melanogenic En- zyme of the Skin Arch. Derm. and Syph., Vol. 26, p'. 499-503 (Sept.) 1932. 2l. For a preliminary report, see Peck, S. M. Sobotka, H. and Kahn, J.: Zur optischen Spezifitat der Dopa Oxydase, Klin. Wchnschr. 11:14 (Jan. 2) 1932. 22. Dr. C. R. Harrington supplied a sample of dextrorotatory dioxyphenylalanine which was prepared for the first time by him, with Dr. Randall. A sample of synthetic racemic dioxyphenylalanine was obtained through the courtesy of Dr. M. Guggenheim of the Hoffman La Roche Laboratories, Nutley, N.J. 23. Lichtman, S.S. and Sobotka, H.: J. Biol. Chem. 85: 261, 1929. 24. Riehl: Cited by Adachi (see 25). 25. Adachi, B.: Hautpigment beim Men- schen und Affen, Zischr. f. Morphol. und Anthrop. 6: 1, 1913. 26. Becker, S.W.: Melanin Pigmentation, Arch. Derm. and Syph. 16:259 (Sept.) 1927. 27. In my series of observations the den- dritic processes extended only up to the lower layer of the stratum granulosum. 28. Masson, M.P.: Les tumeurs, Paris, A. Maloine et fils, 1923. 29. Miescher, G.: Die Entstchung der bosartigen Melanome der Haut, Vir- chows Arch. f. path. Anat. 264: 86, 1927. 30. Biederman, H.: Vergleichende Physi- ologie des Integuments der Wirbeltiere, Ergebn. d. Biol. 1: 1, 1926. 31. Ballowitz, E.: Ueber die Pigment- stromung in den Farbstoffzellen und die Kanalchenstruktur des chromatophoren Protoplasma%'Arch. f. d. ges. Physiol. 157: 165, 1914. 32. Dendritic cells containing a small amount of pigment usually have the pigment granules situated along the periphery of the cell and its dendrites. 33. Del Rio Hortega: Algunos observa- clones los cromoblasto de la piel humana, R. Soc. Esp. de Hist. nat. Toma del 50' Aniv. 1921. March 15, p.i.