Elizabeth Robertson
While Elizabeth Robertson’s scientist father worked at an international research station in Nigeria’s jungle, she explored and learned. Swarming driver ants devoured her pet giant snail collection, and the legs of the family’s furniture sat in gas-containing cans so wood-eating insects couldn’t crawl up and demolish it. These observations provided Robertson with real-life biology lessons—and a fascination for the subject.
Back in Oxford at age eight, she helped her dad with his investigations. In the garage, they soaked protein gels in a blue stain and then exchanged the dye for a liquid that leaches out the color. Proteins hang onto the tinted chemical, Robertson’s father explained, so as the blue washed away from most of the gel, bands that corresponded to particular proteins emerged. The magic of watching them appear enchanted Robertson, as did the suspense of discovering whether the experiment had worked.
After university, Robertson joined Martin Evans’s lab for her Ph.D. and stayed as a postdoc. The group studied peculiar cancers that arise from so-called embryonic carcinoma (EC) cells. Because these cells possess many potential fates, diverse tissues compose the tumors. When scientists injected EC cells that were cultivated in dishes into mouse embryos, the cells could contribute to the resulting “chimeric” animals, so named because of the creatures’ mixed genetic origins. Success varied, however, and researchers struggled to produce animals with the EC DNA in eggs or sperm—a necessity for transmitting the EC genome to subsequent generations. These problems occurred in part because the tumor cells often contained extra chromosomes.
Robertson and graduate student Allan Bradley showed that lab-grown cells from early embryos—embryonic stem (ES) cells, which similarly specialize into all tissue types— possess a normal number of chromosomes. Perhaps, they reasoned, ES cells would perform better than EC cells for constructing chimeric animals.
In 1984, the researchers reported that they could reliably incorporate ES cells into embryos—and the resulting chimeric animals carried eggs or sperm that descended from the introduced cell. Offspring produced by the union of such eggs and sperm held the ES cells’ chromosomes in every cell of their bodies. If scientists could manipulate a gene in cultured ES cells, this new technology would offer massive possibilities: the relatively efficient creation of animals that harbored any desired genetic perturbation in each of their cells.
As a step toward this goal, Robertson and her colleagues infected cultured ES cells with a virus whose DNA jumps into random spots on the genome. In 1986, they generated chimeric mice from these cells. She thus established that scientists could make animals from ES cells whose DNA had been altered in culture.
By this time, others had devised ways to direct incoming genetic changes to particular sites. These methods provided a way to modify specific genes at will. In 1989, having established her own lab, Robertson was among the first investigators to produce reproduction-competent mice that bore targeted mutations. Scientists have since created and studied innumerable “designer” animals, including many that mimic aspects of human disorders.
Author: Evelyn Strauss, Ph.D.