Martin Evans - Stem Cell Research

Stem Cell Research

Evans and Kaufman isolated the embryonic stem cells from early embryos (embryoblasts) of mice and established them in cell cultures. These early embryonic cells have the potential to differentiate into any of the cells of the adult organism. They modified these stem cells genetically and placed them in the wombs of female mice so they would give birth to genetically modified offspring.

In 1981, Evans and Kaufman published results for experiments in which they described how they isolated embryonic stem cells from mouse blastocysts and grew them in cell cultures. This was also achieved by Gail R. Martin, independently, in the same year. Eventually, Evans was able to isolate the embryonic stem cell of the early mouse embryo and establish it in a cell culture. He then genetically modified it and implanted it into adult female mice with the intent of creating genetically modified offspring, the forbearers of the laboratory mice that are considered so vital to medical research today. The availability of these cultured stem cells eventually made possible the introduction of specific gene alterations into the germ line of mice and the creation of transgenic mice to use as experimental models for human illnesses.

Evans and his collaborators showed that they could introduce a new gene into cultured embryonic stem cells and then use such genetically transformed cells to make chimeric embryos. In some chimeric embryos, the genetically altered stem cells produced gametes, thus allowing transmission of the artificially induced mutation into future generations of mice. In this way, transgenic mice with induced mutations in the enzyme Hypoxanthine-guanine phosphoribosyltransferase (HPRT) were created. The HPRT mutations were produced by retroviral insertion; it was proposed that by taking advantage of genetic recombination between the normal HPRT gene and an artificial gene sequenced added to the cultured embryonic stem cells, "it may also eventually be possible to produce specific alterations in endogenous genes through homologous recombination with cloned copies modified in vitro". The production of transgenic mice using this proposed approach was accomplished in the laboratories of Oliver Smithies, and of Mario Capecchi.