782 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS With each successive step more and more of the brown, nondialyzable component is removed and the ½hromophore becomes increasingly purple with sharpened absorption bands and a threefold increase in iron content. The dialyzable chromophore passes through a Sephadex G-50 column as a single sharp band, and its ultraviolet and visible bands are in the same fractions. Present experiments suggest that further diminution of its molecular size may be achieved the size already obtained is smaller than that of any heretofore described human epidermal pigment. Amino acid analyses may reveal much about the nature of the chromophore. By comparing hair pigments with feather pigments and by analyzing the iron-free and iron-rich portions, it should be possible to single out those amino acids which combine with iron to form the chro- mophore group. Preliminary amino acid analyses already have revealed regularities in some of the split products. BIOLOGICAL IMPLICATIONS The synthetic pathway of this pigment raises many questions. If the iron pigment is elaborated by pigment cells, then the synthesis of an iron- protein by nucleic acids must follow a radically different course than the copper-catalyzed polymerization of eumelanin in the melanosomes. This view must be reconciled with everyday observations and clinical ex- perience which strongly suggest that these two pathways must coexist (2). Here only a few pertinent observations will be mentioned. There is a whole gamut of red shades, ranging from "carrot-red" or "orange" through Titian-red to red-brown (16). While these varieties could be explained with differences in the chromophore content of the iron pig- ment, it is conceivable that a varying admixture of eumelanin pigment also is present. The frequently observed gradual darkening of red (and blonde) individuals with advancing age favors the view that the two pig- mentary processes coexist. The strongest proof for this theory is the occasional irreversible conversion of red hair to brown after the adminis- tration of chloroquine (2). Is it then the same pigment cell which produces a metallo-protein and a melanin ? The answer is not known. Although red pigment cells in man and fowl appear to differ from the melanocytes synthesizing black melanins (17, 18), the data are too fragmentary to permit a definite con- clusion. It is also possible that macroscopic red color occasionally may be produced without iron. From time to time the authors have obtained specimens of bright red hair which did not yield any iron pigment. A case in point also may be the reddening of the hair of infants suffering

THE COLOR OF RED HAIR 783 from kwashiorkor, a severe nutritional deficiency (19). That redness does not necessarily presuppose an iron pigment is proved by the Irish setter whose red hair contains no trichosiderin. Although two pigmentary pathways must be postulated, there is no reason why these pathways must follow a common initial course, as sug- gested by Fitzpatrick et al. (2). All the available facts may be explained by assuming two coexisting but independent pathways for red and black pigments. Another unsolved problem is presented by the "missing links" be- tween chicken and man. Trichosiderin may occur in other species as well, but as yet none has been found. Red-haired individuals may be biologically inferior. The hair cover- ing the entire body of our ancestors regardless of its color, offered ade- quate protection against ultraviolet light. As hair became a rudimen- tary structure, the epidermis became exposed to sun against which the iron pigment apparently does not offer adequate protection. The pres- ent scarcity of red-haired people may be due to their suppression by the more viable dark-colored races. Discovery of a previously unknown substance, such as the iron pig- ment of red hair, always raises more questions than can be answered. Most of these problems are accessible to experimental study. It is hoped that their solution will be attempted before another 25 years will elapse. (Received February 3, 1967) REFERENCES (1) Wertz, J. E., et al., Electron Spin Resonance Studies of Antoxidation of $,4-dihydroxy- phenylalanine, in Blois, M. S., Jr., et al., Free Radicals in Biological Systems, Academic Press, New York, N.Y., 1961, pp. 183-193. (2) Fitzpatrick, T. B., et al., ]'he Nature of Hair Pigment, in Montagna, W., and Ellis, R. A., Biology of Hair Growth, Academic Press, New York, N.Y., 1958, pp. 255-301. (3) Fitzpatrick, T. B., Personal communication. (4) Sorby, H. C., On the colouring matters found in human hair, J. Anthropol. Inst. Gt. Brit., 8, 1-14 (January 1878). '(5) Fleseh, P., and Rothman, S., Isolation of an iron pigment from human red hair, J. Invest. Dermatol., 6,257-270 (August 1945). (6) Rothman, S., and Fleseh, P., Isolation of an iron pigment from human red hair, Proc. Soc. Exptl. Biol. Med., 53, 134-135 (June 1943). (7) Hanna, B. L., Production of pigments similar to those from hair from amino acid and keratin interaction, Ibid., 80, 28•-287 (June 1952). (8) Rothman, S., Physiology and Biochemistry of the Skin, The University of Chicago Press, Chicago, II1., 1954, pp. 518-519. (9) Nickerson, N., Relation between black and red melanin pigments in feathers, Physiol. Zool., 19, 66-77 (January 1946).