On Christmas Day in 1984, Carol Greider, in her first year as a molecular biology doctoral student at Berkeley, returned home from her campus lab and danced, for a long time, to the Bruce Springsteen album “Born in the USA.”
She had hit paydirt on an intensive project she began earlier that year. After months of 12-hour days, holidays included, she had found biochemical evidence that a theorized enzyme did, in fact, exist. She knew she had helped solve a critical scientific puzzle, and that it would open many doors.
What she could not know for sure, back then as a 25-year-old grad student, was that this discovery would win her — and her mentor, Elizabeth Blackburn, now at UCSF — a Nobel Prize. She learned that momentous fact nearly a quarter of a century later, around five a.m. on October 5, 2009. An early riser, she was already up sorting laundry at her home in suburban Baltimore. Greider is, these days, a professor at nearby Johns Hopkins University Medical School.
Her graduate adviser, Liz Blackburn, who had posed the problem for Greider’s experiments, analyzed Greider’s results, and agreed with her conclusion. Together, they named the new enzyme telomerase. Greider based her Ph.D. dissertation on that discovery, and the world began to learn how important it was. Michael Botchan, a Berkeley professor of molecular and cell biology, was on her prelim committee: “I remember when she came in with evidence of the telomerase enzyme, and I remember my jaw dropped. It was a wonderful experience, because you don’t often get to examine a student on work you know is paradigm-shifting.”
Greider and Blackburn shared the medical prize with Jack Szostak, a biologist at Harvard Medical School and a collaborator on the early work on telomerase. Their combined work represents the discovery of a fundamental mechanism in the cell. They solved the mystery of how chromosomes, which carry the complexity of DNA, manage to protect themselves from degrading when cells divide in reproduction. That chromosomes had caps, like shoelace tips, at their ends was already known, but much remained unknown. Blackburn and Greider’s enzyme telomerase turned out to be the key. The enzyme adds DNA to those chromosome tips, replacing genetic material that has eroded away. This both reduces the likelihood of mutations and extends the life of the chromosomes.
Work stemming from the Nobel-winning trio has had an explosive impact on medical science, opening new avenues toward understanding diseases like cancer and anemia, knowledge that will help develop alleviative drugs and cures. Defects in telomerase have been shown to cause inherited diseases of the skin, lungs, and bone marrow, and telomeres appear to play a significant role in the aging process itself. These discoveries have also unlocked new avenues into the study of stem cells and reproductive cloning.
The three researchers received copious honors prior to the Nobel coronation, among them in 2006, the Lasker Prize for basic medical research (often called “America’s Nobel”).
When Greider was in the market for a graduate program, after earning her B.A. at UC Santa Barbara, Berkeley was in her final two choices, narrowed not for the usual reasons, but because those were the ones that would have her. She had excellent research experience, letters of recommendation, and grades, but had done poorly on the Graduate Record Examination — the vital GRE. Only CalTech and Berkeley even offered her an interview. (She hadn’t known it growing up, but she is dyslexic, and that affected her scores on standardized tests.)
She interviewed with ten or so professors in Pasadena, then came to Berkeley for a similar round. One of her stops here was Liz Blackburn’s lab. “I had a great time in my conversation with Liz,” Greider says. “She was just very excited about what she was doing. I was having such a great time talking to her that the time went by so fast, and I really wanted to know more. That was the sort of thing that clinched for me that what I wanted to do was go to Berkeley and to work in Liz’s lab.” Blackburn had just become tenured, had research money, and felt she was free to choose what to work on. Looking back, the two of them were perhaps “young and naive,” as Greider says. Blackburn re-spins it as “young and hopeful,” and adds that she had the confidence to direct the lab, and their energies, into something new. “‘New’ translates as ‘might not be feasible’.” Both saw the enzyme-search project as daring and exciting. Blackburn says, in retrospect, that “to look for something new is not something that wise people — prudent people — would normally do.”
Writing in Nature Medicine on the occasion of winning the Lasker Prize in 2006, Greider and her colleagues said, “the quiet beginnings of telomerase research emphasize the importance of basic, curiosity-driven research. At the time that it is conducted, such research has no apparent applications. Our understanding of the way the world works is fragmentary and incomplete, which means that progress does not occur in a simple, direct, and linear manner. It is important to connect the unconnected, to make leaps and to take risks, and to have fun talking and playing with ideas that might seem outlandish.”