This article will reveal how local scientific determination and ambition, in the face of rejection by funders, navigated a path to success and to influence in national policy and international medicine. It will demonstrate that Birmingham, England's ‘second city’, was the key centre for cutting-edge biological psychiatry in Britain in the 1920s and 1930s. The ambitions of Frederick Mott – doyen of biochemistry, neuropathology and neuropsychiatry, until now celebrated as a London figure – to revolutionize psychiatric treatment through science, chimed (...) with those of the City and University of Birmingham's Joint Board of Research for Mental Diseases. Under Mott's direction, shaped by place and inter-professional working, the board's collaborators included psychiatrist Thomas Chivers Graves and world-renowned physiologist J.S. Haldane. However, starved of external money and therefore fresh ideas, as well as oversight, the ‘groupthink’ that emerged created the classic UK focal sepsis theory which, it was widely believed, would yield a cure for mental illness – a cure that never materialized. By tracing the venture's growth, accomplishments and contemporary potential for biochemical, bacterial and therapeutic discoveries – as well as its links with scientist and key government adviser Solly Zuckerman – this article illustrates how ‘failure’ and its ahistorical assessment fundamentally obscure past importance, neglect the early promise offered by later unsuccessful science, and can even hide questionable research. (shrink)