Taking as its starting point a little-known text by George Buck entitled The Third Universitie (1615) and as its endpoint the early years of the Royal Society, this chapter explores seventeenth-century knowledge exchange, research networks and innovation. What began as a civic challenge to Oxbridge ended in an outward-facing institutional sphere that drew its inspiration, founding figures and key personnel from the archipelagic and colonial contexts within which its pioneering interests developed. The Royal Society’s origins lie in a range of institutions identified by Buck, including Gresham College; in later developments such as the Invisible College and the Hartlib Circle; and in the idea for a directory of expertise, or ‘Office of Address’. Colonial investors and adventurers hard-wired into emerging networks of experts working across collaborative communities of scholar-practitioners ensured the advancement of knowledge was intimately intertwined with political intelligence and economic exploitation. There was no new medicine without frontiers, no new husbandry without fresh fields to plant, and, crucially, no knowledge exchange without satire.