THE PIGMENT MELANIN OF THE SKIN AND HAIR* By S2•4uv,•, M. PF, CK, M.D. New York, N.Y. IN THE higher vertebrates, especially in man, most of the mela- notic pigment is to be found in the ectordermal elements of the skin, where it plays a much more impor- tant role than the mesodermal pig- ment. The pigment building cells (melanoblasts) of the epidermis are the ordinary basal cells, sometimes cells lying directly above them, and cells living at about the basal cell level but showing dendritic proc- esses. Melanoblasts are also found in the hair matrix cells of the bulb, in the epidermal hair sheets, the epi- dermal parts of the sebaceous glands, the excretory. ducts of the sweat and sebaceous glands and in certain mucous membranes. With the paper of Kolliker in 1860 there began a controversy that lasted for many years as to whether the epidermis built its own pigment or whether it obtained this pigment from the curls. According to Kol- liker, Aebi, Halpern, Riehl and Karg (1860 to 1891), cells from the cutis (connective tissue cells or leukocytes) filled with pigment wandered up to the epidermis and gave up their melanin to it (1). Ehrmann (2), in his comprehensive * Presented at the December 6, 1946, Meeting, New York City. monograph on pigment in 1896, con- cluded that melanin was formed in special cells, "melanoblasts," which were not identical with leukocytes, connective tissue cells or epidermal elements. These melanoblasts were of mesodermal origin, and they were capable of wandering into the epi- dermis and functioning there. By means of their dendrites they trans- ferred their pigment to the other epidermal cells. I•oeb, Mertsching, Garcia, Schwalbe and Post (3), in a series of papers (all published before 1900) based on experimental and embryologic studies, disagreed with the authors mentioned, and main- rained that the epidermis was capable of building its own pigment without any help from roesoder- really derived elements. Investigation of the embryology of formation of pigment in the skin of the higher vertebrates, including man, by Meirowsky (4), Wietipg and Hamdi (5), Adachi (6), Bloch (7), Miescher (8), Steiner- Wourlisch (9), Dawson (10) and others during the last thirty years has shown that this formation was autochthonous in the epidermis. They all agreed that from the earli- est embryohal life the ectodermal 33

34 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS melanoblasts were seen only at the beginning of pigment formation in the area where pigment was found in postuterine life (7). The mesodermal melanoblasts of the skin in man are but rudimen- tarily developed, as in the blue nevus and mongolian spot but in certain animals, such as the mon- keys, guinea pigs, the gray house mouse and the negro fowl, they form an important system of cells. These cells, however, never com- municate with the ectodermal melanoblasts, and they have an origin and period of development different from those of the ecto- dermal cells. They are perhaps akin to those cells that play such an important role in the coldblooded animals. The independence of the development of these two types was especially brought out by Bjoch (7) ' and Steiner-Wourlisch (9). It seems probable from the in- vestigations of Schmidt (11) on reptiles, and especially from those of Kornfeld (12) (Anuren) that in coldblooded animals, pigment cells of mesodermal origin can wander into the epidermis and function there. CHEMISTRY OF PIGMENT (MELANIN) FORMATION Modern investigators of pigment agree that the formation of pigment in the melanoblasts of ectodermal and mesodermal origin is due to the oxidation of a colorless propigment by an enzyme. Fuerth has shown that this melanogen is most prob- ably a cyclic protein component. Fuerth, Przibram, Onslow and others first proposed tyrosine as the melanogen. Free tyrosine has been demonstrated in the circulation of the higher vertebrates, but tyro- sinase has been found in insects and coldblooded animals only. There is no positive evidence that tyrosine is the mother substance of melanin in animals, especially in man. In recent years, a number of Italian arithors (Augeli, Saccardi, Rondoni, Gallerani, Quattrini and Introzzi) have maintained that pyrrole and its derivatives, such as methylindole and scatole, are also propigments. The fallacy of their conclusions has been brought out by the work of Bloch and Schaaf (7) and of Peck (13). Bloch (7) has shown that another aromatic amino acid, namely, B-3-4 dioxyphenylalanine, is the probable propigment in warmblooded ani- mals. The' main support for this assumption is his discovery of the reaction to dioxyphenylalanine in the melanoblasts. This reaction consists in the change of dioxy- phenylalanine into a melanin. Since the reactions take place in .sections of skin, Bloch was able to study microscopically the process of the formation of pigment (dopa reaction). He and his school demonstrated that the reaction to dioxyphenylalanine is specific and enzymatic. It is positive only with B-3-4 dioxyphenylalanine and cannot be elicited with tyrosine, epinephrine or other related dioxy- phenyl derivatives. There is a strict parallelism be- tween the reaction to dioxyphenyl-