Calls for the "translation" of research from bench to bedside are increasingly demanding. What is translation, and why does it matter? We sketch the recent history of outcome-oriented translational research in the United States, with a particular focus on the Roadmap Initiative of the National Institutes of Health (Bethesda, MD). Our main example of contemporary translational research is stem cell research, which has superseded genomics as the translational object of choice. We explore the nature of and obstacles to translational research and assess the ethical and biomedical challenges of embracing a translational ethos.

Retinal stem cells (RSCs) exist as rare pigmented ciliary epithelial cells in adult mammalian eyes. We hypothesized that RSCs are at the top of the retinal cell lineage. Thus, genes expressed early in embryonic development to establish the retinal field in forebrain neuroectoderm may play important roles in RSCs. Pax6, a paired domain and homeodomain-containing transcription factor, is one of the earliest genes expressed in the eye field and is considered a master control gene for retinal and eye development. Here, we demonstrate that Pax6 is enriched in RSCs. Inactivation of Pax6 in vivo results in loss of competent RSCs as assayed by the failure to form clonal RSC spheres from the optic vesicles of conventional Pax6 knockout embryos and from the ciliary epithelial cells of adult Pax6 conditional knockout mice. In vitro clonal inactivation of Pax6 in adult RSCs results in a serious proliferation defect, suggesting that Pax6 is required for the proliferation and expansion of RSCs.

Early in his career Thomas Hunt Morgan was interested in embryology and dedicated his research to studying organisms that could regenerate. Widely regarded as a regeneration expert, Morgan was invited to deliver a series of lectures on the topic that he developed into a book, Regeneration (1901). In addition to presenting experimental work that he had conducted and supervised, Morgan also synthesized and critiqued a great deal of work by his peers and predecessors. This essay probes into the history of regeneration studies by looking in depth at Regeneration and evaluating Morgan's contribution. Although famous for his work with fruit fly genetics, studying Regeneration illuminates Morgan's earlier scientific approach which emphasized the importance of studying a diversity of organisms. Surveying a broad range of regenerative phenomena allowed Morgan to institute a standard scientific terminology that continues to inform regeneration studies today. Most importantly, Morgan argued that regeneration was a fundamental aspect of the growth process and therefore should be accounted for within developmental theory. Establishing important similarities between regeneration and development allowed Morgan to make the case that regeneration could act as a model of development. The nature of the relationship between embryogenesis and regeneration remains an active area of research.

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