CAROLGREIDER

Nobel Prize in Physiology or Medicine 2009

© Johns Hopkins Medicine

Carol Greider achieved success in molecular biology in the same way she overcame dyslexia as a child: with persistence and creativity. She discovered telomerase, an enzyme that is key to the ageing process and the growth of cancer cells, and has major implications for medical research.

An image showing the increased copy number of the telomerase gene in cancer. © National Institutes of Health

Born in 1961 to two scientists, Carol Greider struggled at West Davis (California) Elementary School. Because of difficulty spelling and sounding out words, she was put in remedial classes.

I thought of myself as ‘stupid’ because I needed remedial help.

CAROL GREIDER

Since she couldn’t learn to read the traditional way, she found another: she taught herself to memorise words and letter order, circumventing her inability to sound out words.

Carol and her brother walked to school every day. They were independent children, even more so after their mother died in 1967, when Carol was six. When she was ten, the family spent a year in Heidelberg, Germany, where her father had a research sabbatical. Her grades were bad, especially in English, but she relished taking the city bus to school and learning her way around a new place. In junior high and high school, Greider found that her memorisation skills, honed by necessity, gave her an advantage in history and biology.

Beatrice Sweeney, a professor at the University of California, Santa Barbara, guided Carol Greider early in her education as a scientist. © UCSB

After high school, she decided to study Marine Ecology at the College of Creative Studies at UC Santa Barbara, under the watchful eye of a former colleague of her mother’s: Beatrice Sweeney. Sweeney guided Greider to her first position in a laboratory. Greider took to it at once: “I saw that laboratory work was about people and interactions as well as about science.”

Anytime we do... experiments, there are going to be three or four new questions that come up when you think you've answered one.

CAROL GREIDER

Carol Greider in the laboratory at the University of California, Berkeley in 1985 © Berkeley

After a year abroad spent in part at a lab at the Max Planck Institute, Greider decided to pursue a graduate degree. Her dyslexia again proved to be an obstacle – her graduate school entrance test scores were low – and again proved ultimately to be a boon, in determining her course of study. Of the eight programs she applied to, only two accepted her: Caltech and UC Berkeley.

When she visited Berkeley, she met Elizabeth Blackburn, and her choice was made. She would go join Blackburn’s lab and her study of telomeres.

Carol Greider as a grad student in Elizabeth Blackburn's lab at UC Berkeley, USA © Nobel Media. Blakeway Productions.

Carol Greider with another grad student in Elizabeth Blackburn's lab at UC Berkeley, USA © Nobel Media. Blakeway Productions.

By the early 1980s, Blackburn had described the molecular structure of the telomere, the pieces of DNA at the ends of chromosomes that protect the chromosomes from shortening when it replicates. But she wanted to know how telomeres themselves keep from getting shorter during cell division – or if they do get shorter, how they get long again.

Using Tetrahymena, a fresh-water single-celled organism with a large number of telomeres, Greider set out to look for a hypothetical enzyme that relengthened shortened telomeres.

(Left) Greider used telomerase RNA clones from previous experiments in order to sequence the DNA that was extracted from the Tetrahymena cells. This had the added effect of producing significantly darker bands than before. The third gel in this sequence of gels posted here. (Center) This electrophoresis gel had an enzyme, PCG1, incorporated into it. The enzyme allowed Greider to label certain areas of the gel that corresponded to certain nucleotides, specifically Adenine, Guanine, Thymidine, and Cytosine. Second in this sequence of gels posted here. (Right) Greider was sequencing DNA strands and labelling the DNA repeats in each gel. The seventh gel in this sequence. Courtesy of BGI Nobel Laureates Archives at Cold Spring Harbor Laboratory

Single-celled Tetrahymena, shown here under a 4K microscope, for her research on telomeres Pond5

She made extracts from Tetrahymena cells and examined whether artificial telomeres could be elongated by enzymes present in the extracts. After about nine months of trying variations on these experiments, she identified the first signs of her enzyme on Christmas Day, 1984. They named it “telomerase” and published their findings in the scientific journal Cell.

At the age of 23, before she’d even earned her PhD, Greider had made the discovery that would earn her the 2009 Nobel Prize in Physiology or Medicine.

Carol Greider in the 1980s at the Cold Spring Harbor Laboratory © Cold Spring Harbor Laboratory Archives

But that honour wouldn’t come for another 25 years. Meanwhile, Greider’s continued work with telomerase made the enzyme’s impact on medical research abundantly clear. With her PhD in molecular biology at 27, she took a fellowship at Cold Spring Harbor Laboratory (CSHL).

She discovered that shortened telomeres were implicated in many diseases and played a role in the inability of cells to divide after a certain number of divisions – and therefore in cellular ageing. She also found that telomerase activity factored in cancer cell growth. In other words, telomeres and telomerase lay at the heart of major topics of medical research: ageing and cancer.

Carol Greider at the American Academy of Achievement Program in San Antonio in 2001 © American Academy of Achievement

Carol Greider holds a flask of mouse tumour cells in culture media, for a study examining how telomeres change in tumour cells. © Matt Roth

During her time at Cold Spring Harbor, Greider met science writer Nathaniel Comfort, whom she married in 1992. In 1997, when Greider was 36, they moved to Baltimore, when Johns Hopkins University hired her as associate professor of molecular biology and genetics. She is still at Johns Hopkins, now as the Director of Molecular Biology and Genetics. Her lab continues to focus on understanding telomerase and the consequences of telomere dysfunction.

Press conference with the 2009 Medicine Laureates: Carol Greider, Elizabeth Blackburn and Jack Szostak. © Prolineserver 2010 / Wikipedia/Wikimedia Commons (cc-by-sa-3.0)

When it was announced that she had been awarded the Nobel Prize in 2009, Greider brought her two children with her to the press conference. Being a mother is important to her, as are institutional policies that support mothers.

Carol Greider in her laboratory at Johns Hopkins University, 2009 © JHU Gazette 2009. Photo: Will Kirk

In 1996, when Greider was pregnant with their son she convinced CSHL to open a childcare facility. And she has appreciated the flexible work environment of her lab, which gives her time with her children.

Despite the Nobel Prize for her and Blackburn, Greider is still concerned with, as she puts it, “under-representation of the 50% of the brain power of this world.” She encourages women who want to have a career they love and a family to “find a way to do it. And there’s not one way.” She learned that back in elementary school.