In 1975, Elizabeth Blackburn more or less backed into the work that launched her career as a molecular biologist. After completing a doctorate in the lab of Fred Sanger at Cambridge University, she followed her fiancé, John Sedat, to Yale University, where she made a last-minute plea for cell biologist Joe Gall to take her on as a postdoctoral fellow. She didn’t arrive empty-handed: her state-of-the-art credentials in sequencing DNA—she and Sedat were among the first to sequence DNA of any kind—felicitously dovetailed with Gall’s recent discovery of how to purify linear minichromosomes of the pond-dwelling protozoan Tetrahymena. These chromosomes had proportionately plentiful end regions, or telomeres, making it possible to sequence them for the first time. Somewhat nonplussed, Gall agreed to find a place in his lab for Blackburn. When she sequenced these telomeres, she took the first step in solving a puzzle that had stumped molecular biologists for some time: If the enzymes that copied DNA could not copy to the end of the strand, how did chromosomes survive intact for cell division after cell division?

 

Five years later, as a professor at the University of California, Berkeley, Blackburn met molecular yeast geneticist Jack Szostak at a Gordon Research Conference, and they married their expertise in a farfetched attempt to insert telomeres from an unrelated species, Tetrahymena, into yeas cells. Initially, they just wanted to see if it could be done; according to Blackburn, this was a “cockamamie idea,” pursued “just for the fun of it.” The results of this collaboration led Blackburn to challenge accepted scientific wisdom and pursue the possibility that an unknown enzyme added telomeres to the DNA strand. Working with her graduate student Carol Greider, she identified this quirky enzyme, telomerase, which contains an internal RNA template that enables it to create telomeres from scratch.

 

 

Reserved, introspective, uncomfortable with head-to-head competition, Blackburn might seem an unlikely role model and mentor for young scientists. But her predilection for exploring unconventional explanations and her aversion to jostling for position in a crowded race led her to a seemingly obscure byway that became a thriving research field with significant implications for human health. The function of telomeres and telomerase in the aging of cells influences human aging, and telomerase also plays a role in the growth and metastasis of cancer. In her early years as a primary investigator, Blackburn quickly came to doubt a cutthroat approach. “The old model of mentoring was, ‘tear them down and build them back up,’ she said. “Only some people don’t get built back up. I’m too softhearted to do that.”

 

This idealism has a surprising payoff: Blackburn has trained many of the leaders of the field. Her former lab members characterize her as having a voracious appetite for data, any data. In her lab the smell of the chemical fixer used to develop autoradiograms, essentially an X-ray that tracks radioactively labeled molecules, usually cued her appearance on the scene. Carol Greider spoke of Blackburn materializing to see the “dripping gels,” fresh from development, and Dorothy Shippen, who also worked in Blackburn’s Berkeley lab, recalled that “Liz would come out of her office and say, ‘I smell fixer. Who has results?’” Shippen added, “Even with stuff that didn’t work out the way you hoped—no big results—you didn’t sense disappointment in her. Instead, her response was, ‘Oh! That’s the way it works.’” If a natural human investment in getting desired results can impede scientific objectivity, Blackburn’s open response to information created an atmosphere in which it was safe to take a smart risk. Greider spoke of this flexibility as a key to originality: “Just because there was some established dogma in the field didn’t mean she would abide by it. If you don’t believe something is really established, then you can think about more possibilities.”