Purpose: In this series of articles--"Research Ethics I", "Research Ethics II", and "Research Ethics III"--the authors provide a comprehensive review of the 9 core domains for the responsible conduct of research (RCR) as articulated by the Office of Research Integrity. In "Research Ethics I", they present a historical overview of the evolution of RCR in the United States then examine the evolution of human and animal experimentation from the birth of scientific medicine through World War II to the present day. Method: They relied on authoritative documents, both historical and contemporary, insightful commentary, and empirical research in order to identify current issues and controversies of potential interest to both faculty and students. Conclusions: The authors have written this article from a historical perspective because they think all readers interested in RCR should appreciate how the history of science and all the good--and harm--it has produced can inform how researchers practice responsible research in the 21st century and beyond.