That little bottle of retinol serum sitting on your bathroom counter – what do you know about its history? This week, we’re digging deep into the man behind the medicine, renowned dermatologist Dr. Albert Kligman, and the unethical research he conducted at Holmesburg Prison in the mid-20th century. Kligman’s research program at Holmesburg spanned decades, involved dozens of experiments (including tretinoin) and thousands of individuals, received ample funding from public universities and many pharmaceutical companies, and was generally praised until it all came crashing down in the early 1970s. But, as we’ll discover, the unethical behavior persisted even after the program’s closure as Kligman fought to get tretinoin to market. The murky history of retinoids might be a bit too long to include on the label, but this episode forces us to consider the human cost of a household product and the importance of acknowledging that history.
| History | Biology |
| Hornblum, Allen M. Acres of skin: Human experiments at Holmesburg prison. Routledge, 2013. | Draelos, ZK, editor. Cosmetic Dermatology: Products and Procedures. John Wiley & Sons, Inc, 2022. |
| Kligman, Albert M., et al. “Oral vitamin A in acne vulgaris Preliminary report.” International Journal of Dermatology 20.4 (1981): 278-285. | Burgess, C.M. ed., 2005. Cosmetic dermatology (p. 170). Heidelberg, Germany: Springer. |
| Kligman, Albert M., Otto H. Mills Jr, and James J. Leyden. “Acne vulgaris: A treatable disease.” Postgraduate Medicine 55.2 (1974): 99-105. | Mechanisms: |
| Wolf, George. “A history of vitamin A and retinoids.” The FASEB Journal 10.9 (1996): 1102-1107. | Sporn, M.B., Roberts, A.B., Roche, N.S., Kagechika, H. and Shudo, K., 1986. Mechanism of action of retinoids. Journal of the American Academy of Dermatology, 15(4), pp.756-764. |
| Vreeland, Leslie N. “The Selling of Retin-A.” Money (April 1989). | Blomhoff, R. and Blomhoff, H.K., 2006. Overview of retinoid metabolism and function. Journal of neurobiology, 66(7), pp.606-630. |
| Fisher GJ, Voorhees JJ. Molecular mechanisms of retinoid actions in skin. FASEB J. 1996 Jul;10(9):1002-13. doi: 10.1096/fasebj.10.9.8801161. PMID: 8801161. | |
| Layton, A., 2009. The use of isotretinoin in acne. Dermato-endocrinology, 1(3), pp.162-169. | |
| Amichai, B. and Grunwald, M.H., 2000. Isotretinoin in dermatology. Journal of dermatological treatment, 11(4), pp.219-240. | |
| Risks of retinoids: | |
| Hoofnagle, J.H., 2013. Retinoids from: LiverTox: a website on drug-induced liver injury. In Drug-induced liver disease (pp. 725-732). Academic Press. | |
| Choi, J.S., Koren, G. and Nulman, I., 2013. Pregnancy and isotretinoin therapy. Cmaj, 185(5), pp.411-413. | |
| Lammer, E.J., Chen, D.T., Hoar, R.M., Agnish, N.D., Benke, P.J., Braun, J.T., Curry, C.J., Fernhoff, P.M., Grix Jr, A.W., Lott, I.T. and Richard, J.M., 1985. Retinoic acid embryopathy. New England Journal of Medicine, 313(14), pp.837-841. | |
| Panchaud, A., Csajka, C., Merlob, P., Schaefer, C., Berlin, M., De Santis, M., Vial, T., Ieri, A., Malm, H., Eleftheriou, G. and Stahl, B., 2012. Pregnancy outcome following exposure to topical retinoids: a multicenter prospective study. The Journal of Clinical Pharmacology, 52(12), pp.1844-1851. | |
| Williams, A.L., Pace, N.D. and DeSesso, J.M., 2020. Teratogen update: topical use and third‐generation retinoids. Birth defects research, 112(15), pp.1105-1114. | |
| Evidence for Tret alone: | |
| Kang, S., Bergfeld, W., Gottlieb, A.B., Hickman, J., Humeniuk, J., Kempers, S., Lebwohl, M., Lowe, N., McMichael, A., Milbauer, J. and Phillips, T., 2005. Long-term efficacy and safety of tretinoin emollient cream 0.05% in the treatment of photodamaged facial skin: a two-year, randomized, placebo-controlled trial. American journal of clinical dermatology, 6, pp.245-253. | |
| Sitohang, I.B.S., Makes, W.I., Sandora, N. and Suryanegara, J., 2022. Topical tretinoin for treating photoaging: A systematic review of randomized controlled trials. International journal of women’s dermatology, 8(1), p.e003. | |
| Schmidt, N. and Gans, E.H., 2011. Tretinoin: a review of its anti-inflammatory properties in the treatment of acne. The Journal of clinical and aesthetic dermatology, 4(11), p.22. | |
| OTC vs RX (reviews): | |
| Levin, J. and Momin, S.B., 2010. How much do we really know about our favorite cosmeceutical ingredients?. The Journal of clinical and aesthetic dermatology, 3(2), p.22. (LIKED THIS ONE TOO) | |
| Tetali, B., Fahs, F.M. and Mehregan, D., 2020. Popular over‐the‐counter cosmeceutical ingredients and their clinical efficacy. International Journal of Dermatology, 59(4), pp.393-405. (I REALLY LIKED THIS ONE) | |
| Babamiri, K. and Nassab, R., 2010. Cosmeceuticals: the evidence behind the retinoids. Aesthetic Surgery Journal, 30(1), pp.74-77. | |
| Serri, R. and Iorizzo, M., 2008. Cosmeceuticals: focus on topical retinoids in photoaging. Clinics in dermatology, 26(6), pp.633-635. | |
| Spierings, N.M., 2021. Evidence for the efficacy of over-the-counter vitamin A cosmetic products in the improvement of facial skin aging: a systematic review. The Journal of clinical and aesthetic dermatology, 14(9), p.33. | |
| Milosheska, D. and Roškar, R., 2022. Use of retinoids in topical antiaging treatments: a focused review of clinical evidence for conventional and nanoformulations. Advances in therapy, 39(12), pp.5351-5375. | |
| Kligman, A.M., 1998. The growing importance of topical retinoids in clinical dermatology: a retrospective and prospective analysis. Journal of the American Academy of Dermatology, 39(2), pp.S2-S7. | |
| *not peer reviewed but useful for sources* Wong M. 2023. Is Retinol a Scam? The Science. Lab Muffin Beauty Science. https://labmuffin.com/does-retinol-work-skincare-science-scam/ | |
| OTC vs RX (data papers): | |
| Kang, S., Duell, E.A., Fisher, G.J., Datta, S.C., Wang, Z.Q., Reddy, A.P., Tavakkol, A., Jong, Y.Y., Griffiths, C.E., Elder, J.T. and Voorhees, J.J., 1995. Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation. Journal of Investigative Dermatology, 105(4), pp.549-556. | |
| Bagatin, E., Gonçalves, H.D.S., Sato, M., Almeida, L.M.C. and Miot, H.A., 2018. Comparable efficacy of adapalene 0.3% gel and tretinoin 0.05% cream as treatment for cutaneous photoaging. European Journal of Dermatology, 28, pp.343-350. | |
| Kang, S., Goldfarb, M.T., Weiss, J.S., Metz, R.D., Hamilton, T.A., Voorhees, J.J. and Griffiths, C.E., 2003. Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial. Journal of the American Academy of Dermatology, 49(1), pp.83-90. | |
| Creidi, P., Vienne, M.P., Ochonisky, S., Lauze, C., Turlier, V., Lagarde, J.M. and Dupuy, P., 1998. Profilometric evaluation of photodamage after topical retinaldehyde and retinoic acid treatment. Journal of the American Academy of Dermatology, 39(6), pp.960-965. | |
| Bouloc, A., Vergnanini, A.L. and Issa, M.C., 2015. A double‐blind randomized study comparing the association of Retinol and LR 2412 with tretinoin 0.025% in photoaged skin. Journal of cosmetic dermatology, 14(1), pp.40-46. | |
| Kafi, R., Kwak, H.S.R., Schumacher, W.E., Cho, S., Hanft, V.N., Hamilton, T.A., King, A.L., Neal, J.D., Varani, J., Fisher, G.J. and Voorhees, J.J., 2007. Improvement of naturally aged skin with vitamin A (retinol). Archives of dermatology, 143(5), pp.606-612. | |
| Kong, R., Cui, Y., Fisher, G.J., Wang, X., Chen, Y., Schneider, L.M. and Majmudar, G., 2016. A comparative study of the effects of retinol and retinoic acid on histological, molecular, and clinical properties of human skin. Journal of cosmetic dermatology, 15(1), pp.49-57. | |
| Bellemère, G., Stamatas, G.N., Bruère, V., Bertin, C., Issachar, N. and Oddos, T., 2009. Antiaging action of retinol: from molecular to clinical. Skin Pharmacology and Physiology, 22(4), pp.200-209. Which shows significance, which also does some ex vivo studies looking at abdominal skin samples and measuring things like epidermal thickness and various growth factor concentrations. | |
| Kikuchi, K., Suetake, T., Kumasaka, N. and Tagami, H., 2009. Improvement of photoaged facial skin in middle-aged Japanese females by topical retinol (vitamin A alcohol): a vehicle-controlled, double-blind study. Journal of dermatological treatment, 20(5), pp.276-281. | |
| Li, W.H., Wong, H.K., Serrano, J., Randhawa, M., Kaur, S., Southall, M.D. and Parsa, R., 2017. Topical stabilized retinol treatment induces the expression of HAS genes and HA production in human skin in vitro and in vivo. Archives of dermatological research, 309, pp.275-283. | |
| Several papers from this journal I could not get in full but provide them for additional resource: | |
| Draelos, Z.D. and Peterson, R.S., 2020. A Double-Blind, Comparative Clinical Study of Newly Formulated Retinol Serums vs Tretinoin Cream in Escalating Doses: A Method for Rapid Retinization With Minimized Irritation. Journal of drugs in dermatology: JDD, 19(6), pp.625-631. | |
| Babcock, M., Mehta, R.C. and Makino, E.T., 2015. A randomized, double-blind, split-face study comparing the efficacy and tolerability of three retinol-based products vs. three tretinoin-based products in subjects with moderate to severe facial photodamage. Journal of drugs in dermatology: JDD, 14(1), pp.24-30. |
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