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.
To educate its citizens about research into chimeras made from human and non-human animal cells, the United Kingdom's Human Fertilisation Embryology Authority published the consultation piece Hybrids and Chimeras: A Consultation on the Ethical and Social Implications of Creating Human/Animal Embryos in Research, in 2007. The document provided scientific and legal background, described ethical and social issues associated with research using part-human part-animal embryos, supplied a questionnaire for citizens to return to the HFEA with their opinions, and offered a list of resources for further reading to stimulate public debate. The strategy of surveying the public provided a template for developing further policy in the United Kingdom and other countries, as well as for educating citizens on embryological research.
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.
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare and understudied cancer with a dismal prognosis. SCCOHT's infrequency has hindered empirical study of its biology and clinical management. However, we and others have recently identified inactivating mutations in the SWI/SNF chromatin remodeling gene SMARCA4 with concomitant loss of SMARCA4 protein in the majority of SCCOHT tumors. Here we summarize these findings and report SMARCA4 status by targeted sequencing and/or immunohistochemistry (IHC) in an additional 12 SCCOHT tumors, 3 matched germlines, and the cell line SCCOHT-1. We also report the identification of a homozygous inactivating mutation in the gene SMARCB1 in one SCCOHT tumor with wild-type SMARCA4, suggesting that SMARCB1 inactivation may also play a role in the pathogenesis of SCCOHT. To date, SMARCA4 mutations and protein loss have been reported in the majority of 69 SCCOHT cases (including 2 cell lines). These data firmly establish SMARCA4 as a tumor suppressor whose loss promotes the development of SCCOHT, setting the stage for rapid advancement in the biological understanding, diagnosis, and treatment of this rare tumor type.