This study combines archival research and oral history interview data to construct a single case temporal comparison of organizational reforms in the National Cancer Institute (NCI) that were designed to foster innovation by directing basic science findings around virally induced cancers toward the development of vaccines. This project is poised to make a significant contribution by addressing an unresolved theoretical problem: how can sociologists and interdisciplinary science, technology, and society (STS) scholars understand how formal organizations affect scientific knowledge production and innovation? My work contributes to sociological theory and the sociology of culture by offering a coherent theoretical framework that unifies process theories of organization and pragmatist social theory. I develop this “pragmatist process theory of organization” to analyze organizational culture as a temporal process comprising iterative cycles of meaning-making anchored in sequences of organizational problem-solving. I apply this pragmatist process theory of organization to analyze virus-cancer research programs under organizational cultures of “targeted research” in 1961-1976 and “translational research” in 1991-2008. In each period, I show how NCI researchers drew upon local understandings of the relationship between basic and applied science articulated in these organizational cultures to address the scientific and administrative problems they faced around routine organizational events. Over time, sequences of problem-solving fed back into strategic planning and collaborative scientific practices to further articulate these organizational cultures in ways that affected science going forward. In the first period, this process yielded consensus around a limited number of RNA and herpes-like viruses identified early in the development of the program. Priority-setting around operational reporting and contract funding allowed virus-cancer program scientists to justify de-prioritizing DNA viruses more promising for vaccine development, such as hepatitis-B. In the second period, the ambiguity of cultural understandings of translation encouraged a more dispersed collaborative structure. This cultivated an environment of distributed cognition based on fluid and dynamic collaborations that utilized emerging technologies to develop a biomedical innovation—the HPV vaccine. Arguing against existing models, I show how the substantive understandings embedded in organizational cultures as they are produced over time provide centripetal or centrifugal forces that make a difference in the possibilities for innovation.