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 1995 and 1996, researchers at the Roslin Institute in Edinburgh, Scotland, cloned mammals for the first time. Keith Campbell, Jim McWhir, William Ritchie, and Ian Wilmut cloned two sheep, Megan and Morag, using sheep embryo cells. The experiments indicated how to reprogram nuclei from differentiated cells to produce live offspring, and that a single population of differentiated cells could produce multiple offspring. They reported their results in the article 'Sheep Cloned by Nuclear Transfer from a Cultured Cell Line' in March 1996. This experiment led the Roslin team to later clone mammals from adult body cells and to genetically engineer mammals.
In 2006, Kazutoshi Takahashi and Shinya Yamanaka reprogrammed mice fibroblast cells, which can produce only other fibroblast cells, to become pluripotent stem cells, which have the capacity to produce many different types of cells. Takahashi and Yamanaka also experimented with human cell cultures in 2007. Each worked at Kyoto University in Kyoto, Japan. They called the pluripotent stem cells that they produced induced pluripotent stem cells (iPSCs) because they had induced the adult cells, called differentiated cells, to become pluripotent stem cells through genetic manipulation. Yamanaka received the Nobel Prize in Physiology or Medicine in 2012, along with John Gurdon, as their work showed scientists how to reprogram mature cells to become pluripotent. Takahashi and Yamanaka's 2006 and 2007 experiments showed that scientists can prompt adult body cells to dedifferentiate, or lose specialized characteristics, and behave similarly to embryonic stem cells (ESCs).
The US President's Council on Bioethics was an organization headquartered in Washington D.C. that was chartered to advise then US President George W. Bush on ethical issues related to biomedical science and technology. In November 2001, US President George W. Bush created the President's Council on Bioethics (PCB). Convened during a nationwide cloning and embryonic stem cell research debate, the Council stated that it worked to address arguments about ethics from many different perspectives. The organization enacted a model for analyzing bioethical issues through deliberation instead of through the consensus approach. US President Barack Obama replaced the PCB in 2009 with his Presidential Commission for the Study of Bioethical Issues.
Dizhou Tong, also called Ti Chou Tung, studied marine animals and helped introduce and organize experimental embryology in China during the twentieth century. He introduced cellular nuclear transfer technology to the Chinese biological community, developed methods to clone organisms from many marine species, and investigated the role of cytoplasm in early development. Tong's administrative and scientific leadership in the fields of marine, cellular, and developmental biology contributed to China's experimental embryology research programs.
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 the second half of the twentieth century, scientists learned how to clone organisms in some species of mammals. Scientists have applied somatic cell nuclear transfer to clone human and mammalian embryos as a means to produce stem cells for laboratory and medical use. Somatic cell nuclear transfer (SCNT) is a technology applied in cloning, stem cell research and regenerative medicine. Somatic cells are cells that have gone through the differentiation process and are not germ cells. Somatic cells donate their nuclei, which scientists transplant into eggs after removing their nucleuses (enucleated eggs). Therefore, in SCNT, scientists replace the nucleus in an egg cell with the nucleus from a somatic cell.
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.