J. Soc. Cosmetic Chemists, 18, 777-784 (Dec. 9, 1967) The Color of Red Hair* PETER FLESCH, M.I)., Ph.D., ELIZABETH J. ESODA, M.D., and SIDNEY A. KATZ, Ph.D.'• Synopsis--The iron pigments extracted with boiling acids from human red hair and chicken feathers are closely related and are possibly identical. Evidence is presented that these unique substances are well-defined chemical entities and not artifacts of keratin hydrolysis. The iron pigment is probably the major pigment of hu•nan red hair. Its limited extracta- bility from red hair is due to its destruction during extraction and not to the small amount present in the hair. In all of its forms the iron pigment has been proved to be a metallo-pro- tein. It can be broken down to a compound with a relatively small molecular size which re- tains all the essential properties of the originally extracted pigment. Synthesis of an iron- protein in melanocytes raises many questions which cannot be answered at present. INTRODUCTION Why is red hair red ? What is the chemical difference between the pigments of blonde and black hair? These natural variations in hair color usually extend to all epidermal pigment cells. For this reason, while ultraviolet light turns the skin of brunettes dark brown, it imparts a copper color to blondes, and burns red individuals. Yet we know very little about the chemistry of these basic types of human pigmentation. Recent chemical studies have led to the conclusion that it will be a most difficult, possibly insurmountable, task to unravel the structure of the black and brown melanins, also called eumelanins, because of the variable course that polymerization may take during pigment formation (1). At least the precursors of eumelanins and the nature of the building stones aggregating to form the black pigment are known. In the case of * Investigation supported by Public Health Service Research Grant No. AM 10046 from the Division of Research Grants, National Institutes of Health. t Department of Dermatology, School of Medicine, University of Pennsylvania, Phila- delphia, Pa. 19104. 777

778 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS the yellow-red pigments (pheomelanins)* not even the chemistry of the mother substance has been clarified. Tryptophane has been suggested as a candidate, but there is no evidence that it has any such role except in lower species (2). Studies to test whether it gives rise to pheomelanins in man have led to negative results (3). There is however in bright red human hair a characteristic entity, the "possible pink constituent" of Sorby who discovered it almost 90 years ago. His classical description (4, 5) lists most of the unique properties of this pigment: its pink color when extracted from bright red human hair with hot "20 times diluted sulfuric acid " the color change and subse- quent precipitation upon addition of alkali to the solution and its broad absorption band in the visible region of the spectrum. Sorby correctly suspected that the pink substance may be a degradation product and not the original form in which the pigment exists in the hair. In 1943 unaware of this early account, Rothman and the senior author isolated this substance again by boiling red hair with 0.1N HC1 for 1-2 hours. The pink solution turned reversibly yellow above pH 2, precipitated at the neutral point, dissolved at an alkaline pH, had an ab- sorption band in acid solution with a maximum at about 535 mu, and contained iron in the trivalent form. Very little information was ob- tained about its chemical composition. Because of its iron content, the material was named trichosiderin (6). Trichosiderin met with a less than unprejudiced acceptance by the scientific world. An attempt was made to relegate it to the status of an artifact of keratin hydrolysis (7). No mention was made of the fact that the pink colored products in keratin hydrolysates turn yellow at pH 7 and can be obtained by boiling horny products (or other proteins with aromatic amino acids) for 4-6 hours with 40-60 times stronger acids than are required for the extraction of trichosiderin. Such procedures de- stroy the red hair pigment. Nevertheless this allegation found its way into the literature (2, 8) casting doubts on the existence of trichosiderin as a valid chemical entity. The belief that trichosiderin was merely an incidental by-product of pigmentation in red hair was reinforced by the observation that after an apparently exhaustive extraction of trichosiderin, the color of red hair was not diminished noticeably. Also, the presence of iron in an epi- dermal pigment seemed incompatible with the copper enzyme-controlled synthesis of the eumelanins. * The distinction between eumelanins and phemnelanins is based on color differences, solu- bility in acids and alkalies and nature of precursors (2).