In eighteenth century Germany, Johann Friedrich Blumenbach studied how individuals within a species vary, and to explain such variations, he proposed that a force operates on organisms as they develop. Blumenbach used metrical methods to study the history of humans, but he was also a natural historian and theorist. Blumenbach argued for theories of the transformation of species, or the claim that new species can develop from existing forms. His theory of Bildungstrieb (formative drive), a developmental force within all organisms, influenced the conceptual debates among many late nineteenth and early twentieth century embryologists and naturalists.

Paul Kammerer conducted experiments on amphibians and marine animals at the Vivarium, a research institute in Vienna, Austria, in the early twentieth century. Kammerer bred organisms in captivity, and he induced them to develop particular adaptations, which Kammerer claimed the organismss offspring would inherit. Kammerer argued that his results demonstrated the inheritance of acquired characteristics, or Lamarckian inheritance. The Lamarckian theory of inheritance posits that individuals transmit acquired traits to their offspring. Kammerer worked during a period in which scientists debated how variation between organisms and within species was caused, and how organisms could inherit that variation from their parents. Kammerer contended that the inheritance of acquired characteristics occurs during embryological development, but several scientists argued that he provided poor evidence for his claims.

In the first decade of the twentieth century, Paul Kammerer, a zoologist working at the Vivarium in Vienna, Austria, conducted research on developmental mechanisms, including a series of breeding experiments on toads (Alytes obstetricans). Kammerer claimed that his results demonstrated that organisms could transmit acquired characteristics to their offspring. To explain how evolution occurred, biologist Jean-Baptiste Lamarck in France suggested in his 1809 book that offspring inherited the features their ancestors acquired throughout the lives of those ancestors, a process termed the inheritance of acquired characteristics. Kammerer conducted breeding experiments to test the theory of inheritance of acquired characteristics, which he said described the mechanics of evolution. Additionally, Kammerer's experiments aimed at explaining how development shaped evolutionary processes.

Richard Woltereck first described the concept of Reaktionsnorm (norm of reaction) in his 1909 paper 'Weitere experimentelle Untersuchungen uber Art-veranderung, speziell uber das Wesen quantitativer Artunterschiede bei Daphniden' ('Further investigations of type variation, specifically concerning the nature of quantitative differences between varieties of Daphnia'). This concept refers to the ways in which the environment can alter the development of an organism, and its adult characteristics. Woltereck conceived of the Reaktionsnorm as the full range of potentialities latent in a single genotype, evocable by the environmental circumstances of a developing organism. Biologists used variants of Woltereck's concept of Reaktionsnorm, often called the reaction norm or norm of reaction, throughout the twentieth century in attempts to explain how developmental responses to the environment can evolve, and even alter the tempo and direction of evolutionary change.

In 1868 in England, Charles Darwin proposed his pangenesis theory to describe the units of inheritance between parents and offspring and the processes by which those units control development in offspring. Darwin coined the concept of gemmules, which he said referred to hypothesized minute particles of inheritance thrown off by all cells of the body. The theory suggested that an organism's environment could modify the gemmules in any parts of the body, and that these modified gemmules would congregate in the reproductive organs of parents to be passed on to their offspring. Darwin's theory of pangenesis gradually lost popularity in the 1890s when biologists increasingly abandoned the theory of inheritance of acquired characteristics (IAC), on which the pangenesis theory partially relied. Around the turn of the twentieth century, biologists replaced the theory of pangenesis with germ plasm theory and then with chromosomal theories of inheritance, and they replaced the concept of gemmules with that of genes.