Despite a surge of recent scholarship on the long and broad history of biotechnology, the use of biological controls such as fungal and insect vectors does not immediately spring to mind when considering early attempts to engineer life. Yet the early twentieth century saw an ambitious attempt to artificially cultivate and disseminate the parasitic Empusa muscae fungus to destroy the housefly (Musca domestica). This paper argues that E. muscae represented an early twentieth-century disconnect between the promised hopes of biological control and the problematic reality of its use. During the late nineteenth century, bacteriological techniques established that the housefly spread disease, while biological controls were trialled against locusts and other insects in North America and South Africa. In 1912, Edgar Hesse successfully cultivated E. muscae at the Working Men’s College in London. His ambition to use the fungus to exterminate the housefly was short-lived, thwarted by technical difficulties and the realization that the fungus also carried harmful pathogens. Although the use of E. muscae ultimately proved a failure, its history offers us a glimpse of a little-known, yet surprisingly familiar, world of biotechnological aspiration and controversy.