Elizabeth H. Blackburn, a pioneer in the study of telomeres—the ends of chromosomes, which play a role in aging and cancer—has always taken the unexpected path. Growing up in a family of physicians in Tasmania, Australia, she chose to enter medical research rather than medicine. Instead of studying the animals she had loved as a gift, she became fascinated with the chemical machinery of cells. At the University of Melbourne, where she lived in a women's residential college, she majored in biochemistry. For graduate school, she ventured abroad, in 1972, to the University of Cambridge. While there, Blackburn immersed herself in genetics under the mentorship of the Nobel laureate biochemist Frederick Sanger.
After three years at Cambridge, Ph.D. in hand, Blackburn was bound for a postdoctoral appointment at the University of California, San Francisco, to sequence viral DNA. But her fiancé, John W. Sedat, was headed for Yale. She switched projects and opted for Yale. Thus began a lifelong passion for telomeres.
The early-twentieth-century American geneticist Hermann J. Muller coined the term "telomere" from the Greek words telos (end) and meros (part). Muller and the American geneticist Barbara McClintock independently theorized that telomeres must serve a protective function for chromosomes, somehow keeping them separated from one another (the "naked" ends of two long, string-like chromosomes would otherwise fuse end to end). "McClintock did an amazing thing in the 1930s," Blackburn notes with admiration. No one knew about DNA at the time, but McClintock "could see and study chromosomes under the light microscope. She correctly surmised that the chromosome ends somehow stabilized the structure [of the chromosomes] during replication." Forty years after McClintock, when Blackburn decided to apply the DNA sequencing skills she had picked up at Cambridge, she was the only scientist studying telomeres. "I thought, 'Wow, I wonder what they're like?' Nobody knew. There was no hypothesis."
Blackburn's encounter with telomeres, and their associated biochemistry, began a life's work that has placed her among the world's leading cell biologists today. Telomeres have turned out to be a far more fascinating, and more important, line of biomedical research than even Blackburn originally suspected they would be. In her three decades of research and more than 120 peer-reviewed papers on the once-neglected subject, Blackburn has played a key part in major discoveries in the field of telomeres. Having joined the faculty at the University of California, San Francisco, after a fifteen-year delay in her original plans to go there, she is a mentor herself, to a number of young scientists. Together, Blackburn and her students, both former and current, have helped explain how telomeres act in protecting chromosomes from damage, in regulating cell division and cell death, and in such processes as aging and its associated diseases.
For her innovative and groundbreaking work, Blackburn has been recognized by peers, and richly honored. She is a member of the National Academy of Sciences and an elected fellow of the Royal Society of London, as well as the American Association for the Advancement of Science. She served on the President's Council on Bioethics during President George W. Bush's first administration but was dismissed in 2003 for her vocal objections to reports on aging and on stem cell research, among others. The reports, she felt, were neither balanced nor accurate reflections of the scientific fields from which they purported to draw. This April she will receive the Benjamin Franklin Medal in Life Sciences, presented annually by the venerable Franklin Institute in Philadelphia; the award has become one of the nation's most prestigious honors conferred on a scientist. Many Franklin Medal winners in science are also past or future recipients of the Nobel Prize.
For the first decade of her career, however, Blackburn toiled in relative obscurity. At her postdoctoral fellowship at Yale she joined the laboratory of cell biologist Joseph G. Gall. Gall had seen the value of working with a model organism, Tetrahymena, a pond-dwelling, single-celled ciliated protozoan. Like all eukaryotic organisms (organisms whose cells have a nucleus), including people, Tetrahymena has linear chromosomes inside the cell nucleus. What sets ciliated protozoans apart, though, is the sheer number of their chromosomes: Tetrahymena has as many as 40,000 in a single cell. (Each somatic cell of a human being carries just forty-six chromosomes.) The abundance of chromosome ends makes Tetrahymena an ideal organism for the study of telomeres, and so Blackburn set about determining their genetic sequence.
What she discovered was very curious: Telomeric DNA is made up of short, simple, repeating sequences of nucleic acids. (Much longer, more complex runs of nucleic acids make up the DNA sequences that constitute genes.) Soon she and other investigators found similar patterns of repeating DNA segments in the telomere sequences of other species though the number of repeats varied from organism to organism. For instance, Tetrahymena has strings of TTGGGG repeated about 50 times, and humans have strings of TTAGGG repeated about 2,000 times. (T, A, and G stand for the nucleic acids thymine, adenine, and guanine, respectively.)
That evidence and some other results led Blackburn to suspect that the simple sequences were performing a more complex function, and that something else in the cell was controlling the telomeres. Her colleagues remained politely interested but unimpressed, even as she was working out how the sequences were maintained over time. "After we described this work, I would go to meetings and be the last speaker, in the last session of the day" Blackburn says.