Ralph L. Brinster
University of Pennsylvania
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Primary Section: 22, Cellular and Developmental Biology Membership Type:
Member
(elected 1987)
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Research Interests
In the 1960s, our research involved studies on mammalian germ cells and early embryos. Initially, we developed a culture system and manipulation techniques for mouse eggs that are the foundation for all subsequent mammalian egg and embryo experiments in the field, including nuclear transfer and in vitro fertilization of human eggs. We then used these methods and reported in 1974 that mouse blastocysts can be colonized by foreign stem cells and result in chimeric adults. The introduction of foreign cells and new genes into these chimeric mice generated the first prototype transgenic animals. In addition, this discovery stimulated the search for embryonic stem cells and ultimately led to the development of the "knock-out mouse”. In 1981, we reported the generation of transgenic mice using these culture and manipulation techniques, and one year later reported generation of giant mice (See Giant Mouse Photo Above). During the 1990s, our research focused on male germline stem cells, and these studies demonstrated that spermatogonial stem cells (SSCs) from a fertile male mouse can be transplanted to the testes of an infertile male where they will colonize the seminiferous tubules and generate donor cell-derived spermatozoa, thereby restoring fertility. The ability to culture, transplant and cryopreserve SSCs makes the germline of individual males immortal. The transplantation and freezing methods are readily transferrable to the SSCs of all mammalian species.
