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.

Sir John Bertrand Gurdon further developed nuclear transplantation, the technique used to clone organisms and to create stem cells, while working in Britain in the second half of the twentieth century. Gurdon's research built on the work of Thomas King and Robert Briggs in the United States, who in 1952 published findings that indicated that scientists could take a nucleus from an early embryonic cell and successfully transfer it into an unfertilized and enucleated egg cell. Briggs and King also concluded that a nucleus taken from an adult cell and similarly inserted into an unfertilized enucleated egg cell could not produce normal development. In 1962, however, Gurdon published results that indicated otherwise. While Briggs and King worked with Rana pipiens frogs, Gurdon used the faster-growing species Xenopus laevis to show that nuclei from specialized cells still held the potential to be any cell despite its specialization. In 2012, the Nobel Prize Committee awarded Gurdon and Shinya Yamanaka its prize in physiology and medicine for for their work on cloning and pluripotent stem cells.

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.

British embryologist Sir Ian Wilmut, best known for his work in the field of animal genetic engineering and the successful cloning of sheep, was born 7 July 1944 in Hampton Lucy, England. The family later moved to Scarborough, in the north of the country, to allow his father to accept a teaching position. There Wilmut met Gordon Whalley, head of the biology department at Scarborough High School for Boys, which Wilmut attended. Under Whalley's influence, young Wilmut first expressed interest in the life sciences and after graduating high school, he enrolled in the University of Nottingham to study agriculture. It was during his freshman year at Nottingham that Wilmut first came into contact with scientific research. He was mentored by Professor Eric Lamming, an expert in reproductive science and animal physiology, who sparked Wilmut's curiosity with animal genetics. Wilmut 's father, Leonard Wilmut, had diabetes, which eventually brought about blindness and may have been another, more personal factor that stimulated Wilmut's interest in the field. The summer before his graduation from Nottingham, Wilmut completed an eight-week internship at Cambridge in the laboratory of Christopher Polge, a prominent cryobiologist. There, he was introduced to techniques of preserving and manipulating animal cells.

Nuclear transplantation is a method in which the nucleus of a donor cell is relocated to a target cell that has had its nucleus removed (enucleated). Nuclear transplantation has allowed experimental embryologists to manipulate the development of an organism and to study the potential of the nucleus to direct development. Nuclear transplantation, as it was first called, was later referred to as somatic nuclear transfer or cloning.

In 1975 John Gurdon, Ronald Laskey, and O. Raymond Reeves published "Developmental Capacity of Nuclei Transplanted from Keratinized Skin Cells of Adult Frogs," in the Journal of Embryology and Experimental Morphology. Their article was the capstone of a series of experiments performed by Gurdon during his time at Oxford and Cambridge, using the frog species Xenopus laevis. Gurdon's first experiment in 1958 showed that the nuclei of Xenopus cells maintained their ability to direct normal development when transplanted. The goal of Gurdon's experiments was to show that specialized adult cells could maintain the information and capacity to direct normal development. He asked whether cells undergo permanent changes once they become fully specialized. Gurdon, Laskey, and Reeves's publication was important to embryology because it shed light on that very question.

Robert William Briggs was a prolific developmental biologist. However, he is most identified with the first successful cloning of a frog by nuclear transplantation. His later studies focused on the problem of how genes influence development.

British embryologist Sir Ian Wilmut, best known for his work in the field of animal genetic engineering and the successful cloning of sheep, was born 7 July 1944 in Hampton Lucy, England. The family later moved to Scarborough, in the north of the country, to allow his father to accept a teaching position. There Wilmut met Gordon Whalley, head of the biology department at Scarborough High School for Boys, which Wilmut attended. Under Whalley's influence, young Wilmut first expressed interest in the life sciences and after graduating high school, he enrolled in the University of Nottingham to study agriculture. It was during his freshman year at Nottingham that Wilmut first came into contact with scientific research. He was mentored by Professor Eric Lamming, an expert in reproductive science and animal physiology, who sparked Wilmut's curiosity with animal genetics. Wilmut 's father, Leonard Wilmut, had diabetes, which eventually brought about blindness and may have been another, more personal factor that stimulated Wilmut's interest in the field. The summer before his graduation from Nottingham, Wilmut completed an eight-week internship at Cambridge in the laboratory of Christopher Polge, a prominent cryobiologist. There, he was introduced to techniques of preserving and manipulating animal cells.

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.