This paper provides an argument in favor of a specific pedagogical method of using the history of science to help students develop more informed views about nature of science (NOS) issues. The paper describes a series of lesson plans devoted to encouraging students to engage, "unbeknownst to them", in similar reasoning that led scientists to understand sickle-cell anemia from the perspective of multiple subdisciplines in biology. Students pursue their understanding of a "mystery disease" by means of a series of open-ended problems that invite them to discuss it from the perspective of anatomy, physiology, ecology, evolution, and molecular and cell biology. Throughout this unit, instructors incorporate techniques that invite students to "explicitly" and "reflectively" discuss various NOS issues with reference to this example and more generally. It is argued on the grounds of constructivist tenets that this pedagogy has substantial advantages over more implicit approaches. The findings of an empirical study using an open-ended survey and follow-up, semi-structured interviews to assess students' pre- and post-instruction NOS conceptions support the efficacy of this approach.