Unlike many scientists, Gail Martin was not feeding her curiosity when she took her fateful step into the lab. She wanted a bicycle.
Martin had landed as an undergraduate at the University of California, Berkeley, with a passion for culture. Her favorite course was Russian folklore. She applied for a lab-assistant job to make money for the bike so she could get around town.
As she prepared solutions and plated bacteria, she talked to postdoc Joan Sonneborn. The year was 1962. The women’s movement had not yet germinated, but Sonneborn encouraged Martin to pursue science, arguing that it would provide an interesting career. Inspired by Sonneborn and the interactive bustle of the lab, Martin decided to give biology a shot.
She struggled during graduate school, dropped research after earning her Ph.D., and moved to London. She almost took a low-level post at the British Museum, but it was a civil service position; because she was an American citizen, the offer fell through.
Martin drifted back toward the lab. As a postdoc, she joined Martin Evans, who was studying unusual testicular tumors in mice. These so-called teratocarcinomas consist of many tissues—hair, skin, muscle, teeth, and sometimes tiny appendages or organs. When cells from the cancers were cultured in lab dishes and reinjected into animals, growths similar to the original ones arose. This observation indicated that the cells that spawn the tumors—embryonal carcinoma (EC) cells—were pluripotent: They could develop into any of the body’s tissue types. They thus acted like cells from early embryos that scientists had not yet isolated.
Researchers wanted to use EC cells to investigate how specialization occurs. However, no one had observed EC cells undergoing this differentiation process in culture dishes, where it could be scrutinized more easily than during tumor formation in a mouse.
To tackle this challenge, Martin grew single cells from teratocarcinomas and observed their behavior. One night, hunched over the microscope, she saw something that made her sit up. In high-population areas, the cells were clumping and detaching from the dish. Moreover, the outsides of these bundles looked different from their insides. The conglomerations, Martin realized, resembled early embryos, with their two distinct layers.
By manipulating environmental conditions and aspects of the culture dish’s surface, she coaxed these “embryoid bodies” to develop further. Additional experiments confirmed that the process she was witnessing mirrored that of differentiation in mouse embryos.
After she established her own lab, Martin wanted to extract pluripotent cells from normal embryos. Reasoning that EC cells release goodies that would help their embryonic counterpart survive, she grew EC cells and collected the broth. Then she extracted the inside of mouse embryos and placed the cells into the pre-seasoned growth medium. This strategy worked: The cells proliferated. Furthermore, two-layered bundles again developed—but this time they derived from a normal embryo.
Wanting a moniker that distinguishes these pluripotent cells from EC cells, she coined the term embryonic stem cells when she published the results in 1981. The name stuck.
These findings and similar ones from Martin Evans offered new approaches for analyzing early mammalian development. They also provided tools for creating mice with specific genetic perturbations, an advance that has fueled tremendous biomedical progress.
Author: Evelyn Strauss, Ph.D.