Rodents as standardized test animals were developed for commercial distribution in the USA between 1910 and the 1930s. The selective breeding of rats (Rattus norvegicus) and pure-bred mice (Mus musculus) at the Wistar Institute and the Jackson Memorial Laboratories eventually led to a decline in the diversity of species used in American medical and life sciences. The early driving figures, science administrator Milton Greenman and the scientists Henry Donaldson and Clarence Little, sought to standardize animals to render science and its application to humanity more precise. But their efforts were exaggerated in the USA through an expanding industrial and engineering ideal, culminating in a preference for Big Science. I explore the nineteenth century origins of this ideal in Emil Du Bois-Reymond’s neurophysiology. This foundation later merged with increasing standardization, American commercialism, and the success of Big Science to transform animal laboratory “standards” into “model animals.” Recent accounts of research with commercially bred mice reveal how findings can be co-constructed using human clinical data, as animal research is applied to humans. The neglect of evolutionary perspectives and the dominance of “models” may even have begun with the government’s post-war emphasis on funding greater species access for large-scale biomedical research.