88 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS evidence for this possibility is in- direct at present and may be sum- marized as follows: 1. Human sebum and unsat- urated components occurring in human sebum inhibit hair growth in laboratory animals. Like other unsaturated, lipold-soluble depila- tory agents, these substances in- activate sulfhydryl groups in vitro. 2. The in vitro observed ratio: sebum concentration/inactivated --SH in tissues, is in the same range as the in vivo calculated ratio: sebum per sq. cm. of skin/epidermal --SH per sq. cm. of skin. 3. Unrelated unsaturated depil- atory compounds (chloroprene di- mers and vitamin A) have been shown to cause hair loss in human beings as well as in animals hence it is not unreasonable to assume that the depilatory action of other un- related unsaturated compounds, such as occur in sebum, may also apply to human subjects under certain conditions. 4. It has been definitely es- tablished by previous authors that male sex hormones are essential for the development of common male baldness. On the other hand, it is known that these hormones are powerful stimulants of sebaceous secretion. It is conceivable that human sebum may be a link in the chain of events leading to hair loss in man and that quantitative or qualitative changes in the sebaceous secretion may be important factors in the development of common male baldness. It must be emphasized that this theory rests solely on indirect evi- dence. At present it can be con- sidered as a working theory only, as a lead which may or may not help in the clarification of the eti- ology of common male baldness. Does human sebum really in- fluence the metabolism of human skin and the process of keratiniza- tion? Clinical evidence tends to support this view. We will men- tion only a few illustrative examples, such as the almost physiologic "dry- ness" of the skin in winter when se- baceous secretion is greatly de- creased and scaling is always pres- ent in a more or less pronounced form similar clinical pictures may be obtained from repeated or pro- longed exposure to detergents or industrial solvents. In acne, ex- cessive sebaceous secretion is usu- ally associated with anomalies in keratinization. Time will tell whether in these and other conditions there is a causal relationship between sebaceous secretion and keratiniza- tion. Possibly the greatest practical value of the new depilatory com- pounds would be their use in the removal of excessive hair in human subjects. Attempts to induce de- pilation in man with any of the un- saturated depilatory agents were uniformly unsuccessful. Although it is still conceivable that, after prolonged application, some of these compounds may interfere with hair growth, it is certain that none of these agents cause loss of hair after a single local application. The reason for the different behavior of

EXPERIMENTAL LOSS OF HAIR 89 animal and human skin toward these agents is not understood. It is possible that the different lengths of the hair cycles in man and in animals may account for this dis- crepancy. The hair cycle is the time required for a single hair to go through the various phases of its development, from the growing through the resting stage to its final extrusion from the follicle and replacement by another hair. In animals the hair cycle lasts for a few weeks or months, while the hair on the human scalp has a life span of several years. It has been recently shown by Montagna and his coworkers that the hair cycle affects not only the growing hair itself, but chemical and morpho- logic aspects of the entire skin. The unsaturated depilatory compounds act on the precursors of keratin, i.e. on the growing hair only. It is possible therefore that human be- ings, with their relatively large number of resting hair follicles, have greater resistance to the action of the unsaturated depilatory com- pounds, than animals with their more actively proliferating cells of the hair matrix. The new depilatory compounds ha•e created new possibilities in investigative dermatology. With these.agents we can transform the thin, hairy animal skin to a thick- ened hairless skin which resembles human skin both in its morphology and behavior. Skins of depilated animals have been used for raising blisters, an accomplishment here- tofore limited to very few species for the study of viruses, of pro- tective ointments, and of allergic skin reactions. It is impossible to state what the future will bring regarding the ap- plication of these compounds in clinical and investigative derma- tology and in the field of cosmetics. As in any other new field, the ques- tions raised by these findings far outnumber those that can be satis- factorily answered at present. Un- doubtedly some of the preliminary conclusions reached by us will have to be modified, as the work pro- gresses. Nevertheless the indica- tions are that the introduction of these compounds into the fields of clinical and investigative derma- tology will bring about radical changes in our basic concepts re- garding the pathology and therapy of a number of skin conditions. BIBLIOGRAPHY Flesch, P., and Hunt, M., "Local Depilatory Action of Some Unsaturated Compounds," z'lrch. Dermatol. $yphiloL, 65, 261 (1952). Flesch, P., and Goldstone, S. B., "Local Depilatory Action of Unsaturated Com- pounds. The Effect of Sebum on Hair Growth," 7. Investigative Dermatol., 18, 267 (1952).