Although it was not found to be anti-diabetic in double blinded controlled studies. While initial studies for its use in diabetes mellitus were disappointing, the discovery that it caused myelosuppression (decreased activity of the bone marrow) led to its study in mice with leukemia, whose lifespan was prolonged by the use of a vinca preparation. Treatment of the ground plant with Skellysolve-B defatting agent and an acid benzene extract led to a fraction termed "fraction A". This fraction was further treated with aluminium oxide, chromatography, trichloromethane, benz-dichloromethane, and separation by pH to yield vincristine. Vincristine was approved by the US Food and Drug Administration (FDA) in July 1963 under the trade name Oncovin and was marketed by Eli Lilly Company. The drug was initially discovered by a team at Lilly Research Laboratories where it was demonstrated that vincristine cured artificially induced leukemia in mice. Vincristine also induced remission of acute leukemias of childhood. Production of vincristine required one ton of dried periwinkle leaves to produce one ounce of vincristine. Periwinkle was grown on a ranch in Texas. Society and culture Suppliers Until recently, two generic drug makers were suppliers of vincristine in the United States: Teva and Pfizer. In 2019 Teva stopped producing vincristine, leaving Pfizer as the only company in production. Teva has said that they will restart production, and expect it to be available in 2020. Shortage In October 2019 an impending shortage was reported; no adequate substitute is known for treating childhood-cancers. By 2022, the shortage of vincristine continued. Controversy Pharmaceutical bioprospecting Vincristine's origins are debated as an example of pharmaceutical bioprospecting in the fields of ethnobotany and ethnomedicine. Some consider the Catharanthus roseus plant from which vincristine is derived, and its folk remedies to be endemic to Madagascar, and that Madagascar was denied royalties from vincristine sales. However, Catharanthus roseus has a documented history in folk medicine treatments in other locations. In 1963, Lilly researchers acknowledged that the plant was used in Brazil to treat hemorrhage, scurvy, toothaches, and chronic wounds; in the British West Indies to treat diabetic ulcers; and in the Philippines and South Africa as an oral hypoglycemic agent – but not as a treatment for cancer. Catharanthus roseus has been a cosmopolitan species since before the Industrial Revolution and the plant's use in folk remedies suggested general bioactivity for diabetes treatment, not cancer. In the mid-eighteenth century, botanist Judith Sumner recorded the