George Sarton had a strong influence on modern history of science. The method he pursued throughout his life was the method he had discovered in Ernst Mach's "Mechanics" when he was a student in Ghent. Sarton was in fact throughout his life implementing a research program inspired by the epistemology of Mach. Sarton in turn inspired many others (James Conant, Thomas Kuhn, Gerald Holton, etc.). What were the origins of these ideas in Mach and what can this origin tell us about the history of science and science education nowadays? Which ideas proved to be successful and which ones need to be improved upon? The following article will elaborate the epistemological questions, which Darwin's "Origin" raised concerning human knowledge and scientific knowledge and which led Mach to adapt the concept of what is "empirical" in contrast to metaphysical a priori assumptions a second time after Galileo. On this basis Sarton proposed "genesis and development" as the major goal of "Isis." Mach had elaborated this epistemology in "La Connaissance et l'Erreur" ("Knowledge and Error"), which Sarton read in 1913 (Hiebert 1905/1976; de Mey 1984). Accordingly for Sarton, history becomes not only a subject of science, but a method of science education. Culture--and science as part of culture--is a result of a genetic process. History of science shapes and is shaped by science and science education in a reciprocal process. Its epistemology needs to be adapted to scientific facts and the philosophy of science. Sarton was well aware of the need to develop the history of science and the philosophy of science along the lines of this reciprocal process. It was a very fruitful basis, but a specific part of it, Sarton did not elaborate further, namely the psychology of science education. This proved to be a crucial missing element for all of science education in Sarton's succession, especially in the US. Looking again at the origins of the central questions in the thinking of Mach, which provided the basis and gave rise to Sarton's research program, will help in resolving current epistemic and methodological difficulties, contradictions and impasses in science education influenced by Sarton. The difficulties in science education will prevail as long as the omissions from their Machian origins are not systematically recovered and reintegrated.