In this article we analyze the classic Hodgkin and Keynes 1955 paper describing investigations of the independence principle, with the expectation that there is much students and educators can learn from such exercises, most notably how the authors applied their diverse skill set to tackling the numerous obstacles that the study presented. The paper encompasses three of the physiology core concepts, cell membranes, flow down gradients, and scientific reasoning, which were recently assigned to the classes The Biological World, The Physical World, and Ways of Looking at the World, respectively. Thus, analysis of such a paper illuminates the relationships that exist between distinct concepts and encourages a holistic approach to understanding physiology. In-depth analysis of the paper allows us to follow the authors' thought processes from their realization that previous methods lacked the resolution to answer a fundamental question relating to ion movement across membranes to the application of a more sensitive technique and ultimately the development of a novel model describing ion flux. This paper was the culmination of work started in the mid-1930s, strongly supported the ionic theory of nervous conduction proposed by Hodgkin and Huxley, and predicted the presence of ion channels as narrow pores through which ions move sequentially four decades before these features were convincingly demonstrated.