In 1952 Robert Briggs and Thomas J. King published their article, "Transplantation of Living Nuclei from Blastula Cells into Enucleated Frogs' Eggs," in the Proceedings of the National Academy of Sciences, the culmination of a series of experiments conducted at the Institute for Cancer Research and Lankenau Hospital Research Institute in Philadelphia, Pennsylvania. In this paper Briggs and King examined whether nuclei of embryonic cells are differentiated, and by doing so, were the first to conduct a successful nuclear transplantation with amphibian embryos. Previously nuclear transplantation had only been performed using amoebae cells. Briggs and King believed that by removing the egg nucleus and replacing it with a differentiated cell, they could study nuclear differentiation. During the experiment, they used two different species of frogs, Rana pipiens and Rana catesbeiana, to study and test whether the nucleus is differentiated. The nuclear transplantations performed in the experiment would later be referred to as cloning.

In 1980 Janet Rossant and William I. Frels published their paper, "Interspecific Chimeras in Mammals: Successful Production of Live Chimeras Between Mus musculus and Mus caroli," in Science. Their experiment involved the first successful creation of interspecific mammalian chimeras. Mammalian chimeras are valuable for studying early embryonic development. However, in earlier studies, clonal analysis was restricted by the lack of a cell marker, present at all times, that makes a distinction between the two parental cell types in situ. To battle this limitation, Rossant and Frels decided to make chimeras from embryos of two different species in order to have sufficient genetic differences so that, in any tissue type, the two cell types could be clearly identified. In their paper Rossant and Frels describe the successful creation of live chimeras between Mus musculus and Mus caroli. These two species of mice are more closely related than chimeras produced previously. The chimeras created in the experiment showed no sign of selection against one cell type or the other. Therefore, they are valuable for clonal analysis of development. Rossant and Frels were the first to successfully produce an interspecific mammalian chimera that experienced normal development.

In 1984 Sabine Meinecke-Tillmann and Burkhard Meinecke published their article "Experimental Chimeras - Removal of Reproductive Barrier Between Sheep and Goat" in Nature. Their study conquered the reproductive barrier between sheep and goats through embryo manipulation. Their article appeared in Nature on the same day that a similar experiment, conducted by Carole Fehilly, Steen Willadsen, and Elizabeth Tucker was published regarding reproductive barriers between sheep and goats. In previous experiments involving the transplantation of sheep embryos into recipient goats or vice versa, the embryos did not survive past the initial weeks of pregnancy. Hybridization experiments had also failed between the species. Although scientists were unsure of the reasons that hybrid eggs from donor sheep did not survive, they attributed the death of the hybrid eggs from donor goats to immunological responses. Meinecke-Tillmann and Meinecke created interspecific chimeric embryos in order to address the reproductive obstacles between the species. These embryos were transferred to sheep, and a sheep successfully brought a goat kid to term.