Since the 1950s, scientists have developed interspecies blastocysts in laboratory settings, but not until the 1990s did proposals emerge to engineer interspecies blastocysts that contained human genetic or cellular material. Even if these embryos were not permitted to mature to fetal stages, their ethical and political status became debated within nations attempting to use them for research. To study cell differentiation and embryonic development and causes of human diseases, interspecies-somatic-cell-nuclear-transfer -derived (iSCNT) humanesque blastocysts provided opportunities for research and therapy development. Such a technology also involved ethical debates.

In 1962 researcher John Bertrand Gurdon at the University of Oxford in Oxford, England, conducted a series of experiments on the developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. In the experiments, Gurdon conducted nuclear transplantation, or cloning, of differentiated cells, or cells that have already specialized to become one cell type or another, in tadpoles. Gurdon's experiment showed that differentiated adult cells could be induced to an undifferentiated state, where they could once again become multiple cell types. Gurdon's experiment disproved the theory that differentiated cells could not be undifferentiated or dedifferentiated into a new type of differentiated cell. Gurdon's experiment demonstrated nuclear transplantation, also called cloning, using differentiated cells.

In 2009, Shoukhrat Mitalipov, Masahito Tachibana, and their team of researchers developed the technology of mitochondrial gene replacement therapy to prevent the transmission of a mitochondrial disease from mother to offspring in primates. Mitochondria contain some of the body's genetic material, called mitochondrial DNA. Occasionally, the mitochondrial DNA possesses mutations. Mitalipov and Tachibana, researchers at the Oregon National Primate Research Center in Beaverton, Oregon, developed a technique to remove the nucleus of the mother and place it in a donor oocyte, or immature egg cell, with healthy mitochondria. The resulting offspring contain the genetic material of three separate individuals and do not have the disease. Mitalipov and Tachibana's technology of mitochondrial gene replacement built on decades of research by different scientists and enables researchers to prevent the transmission of human mitochondrial diseases from mother to offspring.

Thomas Joseph King Jr. was a developmental biologist who, with fellow scientist Robert Briggs, pioneered a method of transplanting nuclei from blastula cells into fresh egg cells lacking nuclei. This method, dubbed nuclear transplantation, facilitated King's studies on cancer cell development. King's work was instrumental for the development of cloning of fish, insects, and mammals.