dermatologists that bacterial growth on the skin plays an important role in causing acne. Subsequently, in the 1970s, tretinoin (original trade name Retin A) was found to be an effective treatment. The development of oral isotretinoin (sold as Accutane and Roaccutane) followed in 1980. After its introduction in the United States, scientists identified isotretinoin as a medication highly likely to cause birth defects if taken during pregnancy. In the United States, more than 2,000 women became pregnant while taking isotretinoin between 1982 and 2003, with most pregnancies ending in abortion or miscarriage. Approximately 160 babies were born with birth defects due to maternal use of isotretinoin during pregnancy. Treatment of acne with topical crushed dry ice, known as cryoslush, was first described in 1907 but is no longer performed commonly. Before 1960, the use of X-rays was also a common treatment. Society and culture The costs and social impact of acne are substantial. In the United States, acne vulgaris is responsible for more than 5 million doctor visits and costs over billion each year in direct costs. Similarly, acne vulgaris is responsible for 3.5 million doctor visits each year in the United Kingdom. Sales for the top ten leading acne treatment brands in the US in 2015 amounted to $352million. Acne vulgaris and its resultant scars are associated with significant social and academic difficulties that can last into adulthood. During the Great Depression, dermatologists discovered that young men with acne had difficulty obtaining jobs. Until the 1930s, many people viewed acne as a trivial problem among middle-class girls because, unlike smallpox and tuberculosis, no one died from it, and a feminine problem, because boys were much less likely to seek medical assistance for it. During World War II, some soldiers in tropical climates developed such severe and widespread tropical acne on their bodies that they were declared medically unfit for duty. Research Efforts to better understand the mechanisms of sebum production are underway. This research aims to develop medications that target and interfere with the hormones that are known to increase sebum production (e.g., IGF-1 and alpha-melanocyte-stimulating hormone). Other sebum-lowering medications such as topical antiandrogens, peroxisome proliferator-activated receptor modulators, and inhibitors of the stearoyl-CoA desaturase-1 enzyme are also a focus of research efforts. Particles that release nitric oxide into the skin to decrease skin inflammation caused by C. acnes and the immune system have shown promise for improving acne in