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Carol Greider

Carol Greider learned early to ignore obstacles. Her undiagnosed dyslexia landed her in remedial spelling classes as a child, and from the age of six—when her mother died—she had to find support in nontraditional places and chart her own course. Perhaps in part because she grew to expect impediments, Greider honed her ability to maneuver around them. In Germany for a year when she was 12 years old, she earned Fs in English class diction exercises because she spelled words backwards, yet she navigated the city bus system without knowing the language.

In college, Greider explored multiple areas of biological research before finding a home for how she thinks. With a biochemical approach, she could perturb a single experimental component and assess how that change affects the system. This method satisfied her mind’s yearning for decisive answers. Weak GRE scores brought automatic rejections from most graduate schools, but Greider’s research experience and stellar grades caught the attention of the admissions committee at the University of California, Berkeley. At the interview, faculty member Elizabeth Blackburn impressed Greider with her charisma and enthusiasm about an offbeat topic that Greider knew nothing about—telomeres, the protective caps at chromosome ends. Blackburn had proposed that an undiscovered molecular machine adds the repeated DNA sequences that characterize these structures. This idea challenged conventional wisdom. Unsure whether such an enzyme even existed, Greider set about tracking it down—an especially bold move for a graduate student, who might have wanted a safe project.

Greider sought a substance from Tetrahymena thermophila—a single-celled creature found in fresh water—that could add the telomeric sequences to an artificial telomere. After nine months, she came into the lab on Christmas Day 1984 and developed an X-ray film that identified the radioactively labeled DNA molecules in her experimental reaction. Emerging from the darkroom, she saw a ladder pattern that suggested the presence of the substance she sought: Each rung was exactly six DNA-subunits larger than the preceding one. Her heart raced because the result looked so promising, but she didn’t want to be fooled by hope. Over the next six months, she conducted dozens of experiments to rule out dull explanations for the data. Finally her results convinced her that she had unearthed an enzyme that repeatedly adds a particular sequence to the
ends of chromosomal DNA.

Greider and Blackburn discovered that the enzyme is composed not just of protein; it also contains an RNA component. In her own lab, Greider isolated the gene that encodes the RNA module and showed that it is essential for telomerase activity.

Greider and colleagues subsequently established that telomeres shorten progressively in cultured human cells, a process that triggers cell suicide or a state in which the cell neither divides nor dies. This observation led to the idea that telomere attrition contributes to age-related diseases—and that cancer cells owe their immortality in part to reactivation of telomerase. Greider now continues probing connections between telomeres, cancer, stem cells, and age-related human diseases.

Author: Evelyn Strauss, Ph.D.