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.
Advanced Cell Technology (ACT), a stem cell biotechnology company in Worcester, Massachusetts, showed the potential for cloning to contribute to conservation efforts. In 2000 ACT researchers in the United States cloned a gaur (Bos gaurus), an Asian ox with a then declining wild population. The researchers used cryopreserved gaur skin cells combined with an embryo of a domestic cow (Bos taurus). A domestic cow also served as the surrogate for the developing gaur clone. The successful procedure opened the opportunity to clone individuals from species for which there are few or zero live specimens. The official release of this experiment's data was published in the paper 'Cloning of an Endangered Species (Bos gaurus) Using Interspecies Nuclear Transfer,' in October 2000. In the article, the researchers presented data collected from several cloned fetuses that were aborted before the full term of 283 days. At the time of publication, the gaur bull fetus, named Noah at birth, had developed for greater than 180 days. Noah was born on 8 January 2001, but died two days later due to dysentery. The development, birth, and death of Noah became a platform for conservationists and ethicists to critique the role of cloning in society and as a method to conserve species.
In the 1990s, researchers working at the Roslin Institute in Edinburgh, Scotland, performed cloning experiments in collaboration with PPL Therapeutics in Roslin, Scotland, on human coagulation factor IX, a protein. The team of scientists used the methods identified during the Dolly experiments to produce transgenic livestock capable of producing milk containing human blood clotting factor IX, which helps to treat a type of hemophilia. By using a cell's resting state, called quiescence, or G0, and transferring modified nuclear material from one cell to an egg cell that had had its nuclear material removed, the researchers developed a method to produce genetically modified mammals, including humans. Angelika E. Schnieke, Alexander J. Kind, William A. Ritchie, Karen Mycock, Angela R. Scott, Marjorie Ritchie, Ian Wilmut, Alan Colman, and Keith H. S. Campbell published the results of their experiments as Human Factor IX Transgenic Sheep Produced by Transfer of Nuclei from Transfected Fetal Fibroblasts (hereafter called Human Factor IX). The article details the methods that produced the cloned sheep named Polly, as well as other cloned and genetically altered sheep.
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.
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.
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.
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.