From their arrival in the Danish-Norwegian colony of Tranquebar in South India at the beginning of the eighteenth century the missionaries of the protestant Danish-Halle mission were engaging with many different kinds of knowledge present in Tamil society. This paper will focus on the activities in the field of natural knowledge or ‘science,’ especially medicine and botany, from the time of the arrival of the mission doctor Samuel Benjamin Cnoll in 1732. As a case study, it presents a window into the complex connections between medicine, science, religion and economy in the early eighteenth century, both locally in colonial South India and in global networks. The case shows how the mission in Tranquebar was a ‘node’ in the circulation of knowledge in such a global network. As part of the circulation process, new scientific knowledge about the colonial ‘periphery’ of India was constructed in a contingent local fusion of knowledge negotiated with Tamil ‘experts’ and the concerns of the scientific ‘centres’ of Europe. In this way, the new scientific knowledge about Indian nature was not just collected locally; it was made in a complex global process.