The
vitamin A acid story began when topical application of
vitamin A (
retinol) produced no therapeutic results in dyskeratotic conditions. It was logical to try metabolites of
retinol topically. I published results of studies in 1962 that showed that topical
tretinoin was beneficial in
ichthyosis,
actinic keratoses, and other hyperkeratotic conditions. It was reported in 1969 that topical
tretinoin was effective in
acne vulgaris, principally by preventing and dislodging comedones. It was subsequently demonstrated that
tretinoin produced a distinctive kind of
hyperplasia of human epidermis that was associated with early shedding of horny cells. Knowledge that the keratinization process was being profoundly altered stimulated interest in synthesizing
retinol derivatives (
retinoids) that could be administered orally. The development of
13-cis-retinoic acid was an outcome of this interest, a compound that astonished dermatologists by often producing permanent clearing of
acne conglobata. The antitumor effects of
tretinoin were already demonstrated by 1974, when it was shown to cause regression in many
basal cell cancers. Today the
cancer chemopreventive capability of
retinoids is being intensively investigated in various organs. An international symposium held in Flims, Switzerland in 1975 demonstrated keen awareness of the therapeutic potential of
tretinoin and the rapid growth of basic knowledge of the pharmacology of
retinoids. From extensive clinical experience new applications for topical
tretinoin came to light, ranging from the treatment of flat
warts,
lichen planus, and
Darier's disease, and most recently in retarding photoaging. Perhaps for the first time in history, dermatologists can take credit for pioneering a
drug development program that has had a profound influence on medical practice.