The term “translational science” has recently become very popular with its usage appearing to be almost exclusively related to medicine, in particular, the “translation” of biological knowledge into medical practice. Taking the perspective that translational science is somehow different than science and that sound science is grounded in an epistemology developed over millennia, it seems imperative that the meaning of translational science be carefully examined, especially how the scientific epistemology manifests itself in translational science. This paper examines epistemological issues relating mainly to modeling in translational science, with a focus on optimal operator synthesis. It goes on to discuss the implications of epistemology on the nature of collaborations conducive to the translational investigative process. The philosophical concepts are illustrated by considering intervention in gene regulatory networks.