The existence of infectious agents smaller than bacteria was demonstrated already during the 1890s. After this discovery it took more than 50 years before a resilient definition of viruses could be given. There were separate developments of knowledge concerning plant viruses, bacterial viruses and animal viruses. In the mid-1930s, Wendell Stanley at the Rockefeller Institute for Medical Research at Princeton described the purification and crystallization of tobacco mosaic virus. The finding of an "infectious protein" led to him receiving a Nobel Prize in Chemistry in 1946. In studies initiated at the end of the 1930s, bacteriophages were used as a model for replicating genes. They led to important insights into the unique characteristics of virus-cell interactions. However, an understanding of the chemical nature of animal virus particles and their mode of replication was slow in coming. Not until the early 1950s did tissue culture techniques become available, which allowed studies also of an extended number of animal viruses. This article discusses the emergence of concepts which eventually allowed a description of viruses. The unique real-time analyses of the state of knowledge provided by the Nobel Prize archives were used in the investigation. These archives remain secret for 50 years. Besides all of the underlying documents of the Prize to Stanley, comprehensive investigations made in the mid 1950s of Seymour E. Cohen, Max Delbrück, Alfred D. Hershey and Salvador D. Luria (the latter three received a Prize in Medicine in 1969) and of André Lwoff (he shared a Prize in Medicine with Francois Jacob and Jaques Monod in 1965) were reviewed. The final phase of the evolution of our understanding of the virus concept closely paralleled the eventual insight into the chemical nature of the genetic material. Understanding the principle nature of barriers to the development of new concepts is of timeless value for fostering and facilitating new discoveries in science.