Before dealing with the historical stages of the gene concept's tangled development, we will have to see how it came into being. It was only in the nineteenth century that heredity became a major problem to be dealt with in biology (López Beltrán 2004; Müller-Wille and Rheinberger 2007 and 2012). With the rise of heredity as a biological research area the question of its material basis and of its mechanism took shape.

In the second half of the nineteenth century, two alternative frameworks were proposed to deal with this question. The first one conceived of heredity as a force whose strength was accumulated over the generations, and which, as a measurable magnitude, could be subjected to statistical analysis. This concept was particularly widespread among nineteenth-century breeders (Gayon and Zallen 1998) and influenced Francis Galton and the so-called “biometrical school” (Gayon 1998, 105-146).

The second framework saw heredity as residing in matter that was transmitted from one generation to the next. Two major trends are to be differentiated here. One of them regarded hereditary matter as particulate and amenable to breeding analysis. Charles Darwin, for example, called the presumed hereditary particles “gemmules”; Hugo de Vries, “pangenes”. None of these nineteenth- century authors, however, thought of associating these particles with a particular hereditary substance.

They all believed that they consisted of the very same stuff that the rest of the organism was made of, so that their mere growth, recombination and accumulation en masse would make visible the particular traits for which they were responsible. A second category of biologists in the second half of the nineteeenth century, to whom Carl Naegeli and August Weismann belonged, distinguished the body substance, the “trophoplasm” or “soma”, from a specific hereditary substance, the “idioplasm” or “germ plasm”, which was assumed to be responsible for intergenerational hereditary continuity. However, they took this idioplasmic substance as being, not particulate, but highly organized. In the case of Weismann it remained intact in the germ cells, but irreversibly differentiated in the body cells during development. In the case of Naegeli it extended even from cell to cell and throughout the whole body, a capillary hereditary system analogous to the nervous system (Robinson 1979; Churchill 1987, Rheinberger 2008).

Mendel stands out among these biologists, although he worked within a well-defined botanical tradition of hybrid research. He is generally considered as the precursor to twentieth-century genetics (see, however, Olby 1979 and, for a more recent discussion, Orel and Hartl 1997). As Jean Gayon has argued, Mendel's 1865 paper attacked heredity from a wholly new angle, interpreting it not as a measurable magnitude, as the biometrical school did at a later stage, but as “a certain level of organization,” a “structure in a given generation to be expressed in the context of specific crosses.” This is why Mendel applied a “calculus of differences,” i.e., combinatorial mathematics to the resolution of hereditary phenomena (Gayon 2000, 77-78).

With that, he introduced a new formal tool for an analysis of hybridization experiments that was at the same time based on a new experimental regime: the selection of pairs of alternative and “constant” (i.e., heritable) traits. Mendel believed that these traits were related by a “constant law of development” to certain “elements” or “factors” in the reproductive cells from which organisms developed. An analysis of the distribution of alternative traits in the progeny of hybrids could therefore reveal something about the relationship that the underlying “factors” entered when united in the hybrid parent organism (Müller-Wille and Orel 2007).