In 1991, the United Kingdom established the Human Fertilisation and Embryology Authority (HFEA) as a response to technologies that used human embryos. The HFEA is a regulatory power of the Health and Social Services Department in London, UK, that oversees the implementation of reproductive technologies and the use of embryos in research within the United Kingdom. It establishes protocols by which researchers may use human embryos, develops legislation on how human embryos are stored and used, monitors human embryological research and artificial fertilization procedures, and prosecutes those who violate terms of embryo use. The HFEA collects, monitors, and distributes data related to human embryology and embryological research. The HFEA also records international studies involving human embryos and fertilization, hosts ethical debates, and shares collected information with the public and scientific communities.

In 2007, the Human Fertilisation and Embryology Authority in London, UK, published Hybrids and Chimeras: A Report on the Findings of the Consultation, which summarized a public debate about research on, and suggested policy for, human animal chimeras. The HFEA formulated the report after conducting a series of surveys and debates from earlier in 2007. The HFEA issued a statement in September 2007, followed by an official report published on 1 October 2007. Their report on human-animal chimeras set a worldwide precedent for discussions of the ethical use of those embryos in labs. The HFEA's report led the UK government to pass legislature about the use of human-animal cytoplasmic hybrid embryos for research in the UK.

In 2006, bioethicist Jason Scott Robert published “The Science and Ethics of Making Part-Human Animals in Stem Cell Biology” in The FASEB Journal. There, he reviews the scientific and ethical justifications and restrictions on creating part-human animals. Robert describes part-human animals, otherwise known as chimeras, as those resulting from the intentional combination of human and nonhuman cells, tissues, or organs at any stage of development. He specifically criticizes restrictions against creating part-human animals made by the National Academy of Sciences, or NAS, in 2005, arguing that while they ensure that such research is morally justifiable, they might limit scientists from conducting useful science using part-human animals or entities. Robert challenges the moral rationales behind prohibiting chimera research, arguing that they may impede scientists from conducting research that could have important benefits to biology and medicine, and suggests how to balance the conflicting moral and scientific needs of such science.

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.

Beatrice Mintz is a brilliant researcher who has developed techniques essential for many aspects of research on mouse development. She produced the first successful mouse chimeras and meticulously characterized their traits. She has worked with various cancers and produced viable mice from the cells of a teratoma. Mintz participated in the development of transgenic mice by the incorporation of foreign DNA into a mouse genome. Her techniques have been widely applied to other studies of mouse development and are so common that many of the publications that utilize her techniques no longer remember to cite the source.

Through various studies developmental biologists have been able to determine that the muscles of the back, ribs, and limbs derive from somites. Somites are blocks of cells that contain distinct sections that diverge into specific types (axial or limb) of musculature and are an essential part of early vertebrate development. For many years the musculature of vertebrates was known to derive from the somites, but the exact developmental lineage of axial and limb muscle progenitor cells remained a mystery until Nicole Le Douarin and Charles P. Ordahl published "Two Myogenic Lineagues within the Developing Somite" in 1991. This paper describes their experiment, which used chick-quail chimeras to demonstrate the exact lineage of the limb and back musculature.

In November 2007, Masato Nakagawa, along with a number of other researchers including Kazutoshi Takahashi, Keisuke Okita, and Shinya Yamanaka, published "Generation of Induced Pluripotent Stem Cells without Myc from Mouse and Human Fibroblasts" (abbreviated "Generation") in Nature. In "Generation," the authors point to dedifferentiation of somatic cells as an avenue for generating pluripotent stem cells useful for treating specific patients and diseases. They provide background to their research by observing that previous attempts to reprogram somatic cells to a state of greater differentiability with retroviral factors Oct3/4, Sox2, c-Myc, and Klf4 had succeeded in producing induced pluripotent stem (iPS) cells that contributed to viable adult chimeras and possessed germline competency. However, as they note, the c-Myc retrovirus contributes to tumors in generated chimeras, rendering iPS cells produced with c-Myc useless for clinical applications. The authors attempt to overcome this problem by modifying the standard protocol for producing iPS cells in mice in such a way that the c-Myc retrovirus is removed. They identify problems and benefits associated with this method, but most importantly note that their method generated iPS cells that did not cause tumors in chimeric mice. Nakagawa and colleagues also report that they successfully reprogrammed adult dermal fibroblasts to return to a pluripotent state without c-Myc.

The paper "Formation of Genetically Mosaic Mouse Embryos and Early Development of Lethal (t12/t12)-Normal Mosaics," by Beatrice Mintz, describes a technique to fuse two mouse embryos into a single embryo. This work was published in the Journal of Experimental Zoology in 1964. When two embryos are correctly joined before the 32-cell stage, the embryo will develop normally and exhibit a mosaic pattern of cells as an adult. Mosaics were easily characterized by mouse fusions from embryos of different colors; this produced clearly visible color patterns identifying the alternate cell types. Mintz referred to the fused mice as mosaic or later as allophenic, but they are more commonly known today as chimeras.

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.

Subscribe to chimeras