HX21 Scars of confinement: the dark history of tretinoin

Abstract Topical retinoids such as tretinoin are widely known for the treatment of acneiform conditions and their antiageing properties, making them key ingredients in the medical and cosmetic industries. However, the discovery of tretinoin is all but glamorous. It began in Holmesburg Prison, Philadelphia, when Albert Montgomery Kligman (1916–2010), an American dermatologist. preformed unethical experimentation on inmates. Dr Kligman, who held a PhD in Botany, later trained as a doctor and subsequently joined the dermatology department at the University of Pennsylvania. Given Kligman’s background knowledge in botany, particularly fungi, he was contacted when an outbreak of tinea pedis emerged in the Holmesburg Prison in 1964. The unique design of the prison contributed to making it an ideal environment to start experimenting on inmates. Two years later Kligman mentioned in an interview: ‘All I saw before me was acres of skin’. His subjects, who were predominantly male and of African American ethnicity, were offered USD 30–50 for participation in such experiments. These experiments all violated the Nuremberg Code of medical ethics and research conduct. Kligman began experimentation with the vitamin A derivative for its antiageing and pigmentary effects. He applied the derivative in varying doses and formulations on the skin of African American inmates. The author of Acres of Skin, Alan M. Hornblum, writes that some experiments included taking adhesive tape and applying it to an inmate’s back, and ripping it off repeatedly until the skin became raw. He describes various chemicals being applied to inmates’ backs, which were then covered with a plaster, subsequently leading to blistering, chemical burns and severe cutaneous drug eruptions. In 1969, Kligman and two colleagues patented topical tretinoin, and in 1971 it became licensed for the use of acne vulgaris. Kligman was attributed as being the first to describe the link between sun exposure, skin damage and premature skin ageing (now termed photoageing), in 1971. He then published an article in 1975 called ‘A new formulation for depigmenting the skin’. In the article he states that complete depigmentation was reached by applying tretinoin 0.1%, hydroquinone 5.0%, dexamethasone 0.1% and hydrophilic ointment for 5–7 weeks. This was proposed as the treatment for melasma, ephelides and postinflammatory hyperpigmentation. Although Kligman made a significant contribution to the dermatology field as we know it today some of his methods were undoubtedly unethical and culminated in an apology from the City of Pennsylvania in 2022.