Surgeon Senjee Pulney Andy's trials in treating smallpox using leaves of Azadirachta indica in southern India in the 1860s

Indian people hold Azadirachta indica (Rutales: Meliaceae) (nimba, Sanskrit), a native tree, in high veneration. Its cultural connections with the people of the Indian subcontinent are complex and intense1. References to its use exist in Çaraka, Su'ru'a and Brihat Samhitã-s ' the ancient Sanskrit medical treatises2,3. Today we know of 300 different chemical substances from A. indica (O. Koul, pers. commun.), a majority of which are limonoids in seeds. Several research articles referring to the relevance of these limonoids to humans exist4,5. Azadirchtin, a tetranortriterpenoid, is an environmentally friendly active principle used as a 'pesticide' to manage pestiferous arthropods and pathogenic fungi6,7, thanks to a casual observation of Heinrich Schmuterer on Schistocerca gregaria (Insecta: Orthoptera: Acrididae), while working on the locust plague in northern Africa8 in 1959. A comprehensive summary of diverse medicinal capabilities of A. indica is available in Biswas et al.9.Several commercially available cosmetic products based on A. indica compounds (e.g. Margo bath soap (note 1)) are well known8. People of the Indian subcontinent consider A. indica a 'divine' tree Figure 1. 'Leaves of A. indica relieve the discomfort of smallpox.' (Aikman, L., Nature's Healing Arts: From Folkmedicine to Modern Drugs, The National Geographic Society, Washington, DC, 1977, p. 132.) that protects them from illnesses such as smallpox, chicken pox, measles, mumps, and even herpes, which we know today are caused by viruses (Figure 1). In such a context of cultural and economic relevance of A. indica, we found a short article referring to his trials using leaves of A. indica in treating smallpox by Madras surgeon Senjee Pulney Andy10 (hereafter PA), when he was the Superintendent of Vaccination in Travancore (note 2) in the 1860s. This article appealed to us because only in 1892, two-and-a-half decades later, we ever knew of viruses, with Dmitri Ivanovski (1864'1920) demonstrating the transmission of tobacco-mosaic virus, confirmed by Martinus Beijerinck (1851'1931) in 1898 (ref. 11).