A trio of researchers whose work on telomeres and telomerases has helped explain how chromosomes are copied during cell division will receive the 2009 Nobel Prize in Physiology or Medicine. Their findings have advanced medical research in cancer, inherited diseases, and aging.

Elizabeth Blackburn Image: Gerbil, Licensed by Attribution Share Alike 3.0

Elizabeth Blackburn, a biochemist at the University of California, San Francisco, Carol Greider, a geneticist at Johns Hopkins School of Medicine, and Jack Szostak, a geneticist at Harvard Medical School will share the prize equally. It is the first time two women have shared the Nobel.

"I think this is a victory for curiosity-driven science," Greider, who got the call at 5AM on her way to spinning class, told The Scientist. "We are fortunate to live in a place where we can still get funding for conducting basic research to answer fundamental questions. I feel very privileged to have been able to follow my curiosity for the past 30 years."

Scientists began to understand how genes are copied, base by base, in the 1950s, but no one could figure out why the very end of a DNA strand could not be duplicated. As a young researcher at the University of California, Berkeley, studying the chromosomes of Tetrahymena, a single cell organism that commonly lives in water, Blackburn noticed a DNA sequence, CCCCAA, that was repeated several times at the ends of the chromosomes.

While presenting her findings at a conference in 1980, Blackburn met Szostak, who had just observed that minichromosomes, linear DNA molecules, rapidly degrade when introduced to yeast cells. The two decided to join forces - introducing the CCCCAA sequence into the minichromosomes and then injecting them into yeast cells. The sequence, named telomere, protected the minichromosomes from degradation by keeping their ends intact, indicating the existence of a previously unknown mechanism in DNA replication. The pair of researchers published their results in 1982 in Cell.

Carol Greider Image: Gerbil, Licensed by Attribution Share Alike 3.0

Soon after, Blackburn and her then-graduate student, Carol Greider, found that an enzyme, telomerase, was responsible for the formation of the telomere DNA sequence. The enzyme's RNA component contained the CCCCAA sequence and served as a template for replication. Its presence allowed a DNA strand to copy itself completely from end to end. The two scientists published their findings in Cell in 1985, and Nature in 1989.

"This research was actually Greider's PhD thesis," said Jeremy Berg, director of the National Institute of General Medical Sciences. "Graduate students who do fundamental research are often overlooked, but their work can make a big impact, as evidenced by today's announcement."

Blackburn and Szostak went on to discover that mutations in the RNA of the telomerase enzyme led to the gradual shortening of telomeres and eventual inhibiting of cell division in Tetrahymena and yeast, respectively. Greider also showed that the aging of human cells is delayed by telomeres.

The principal papers on telomeres and telomerase activity have been cited more than 2000 times, according to ISI Web of Knowledge, and have had resounding impacts on several areas of medical research. Some inherited diseases of the skin, lungs, and bone marrow, such as anemia, have been shown to be caused by telomerase defects. Scientists also initially thought the shortening of telomeres caused aging. Although aging is now believed to be the result of several different factors, research on the role of telomeres in the process remains intense.

Jack Szostak Image: Harvard Medical School

"I am delighted, but not at all surprised," said Berg. "Their work has certainly been on the list of likely Nobel Prizes for years. It is a classic example of a fundamental problem in basic biology that was addressed in very elegant way and had renowned impact in biological and medical research."

Cancer research has also benefited from the Nobel-winning trio's work. Cancer cells are able to preserve their telomeres no matter how many times they divide, unlike normal human cells that gradually lose telomeres as they age. Studies have also shown that cancer cells have increased telomerase activity. Several clinical studies are currently under way to see if destroying telomerase enzymes could help stop the spread of cancer cells.

"This award was well deserved," said Jerry Shay, a cellular biologist at the UT Southwestern Medical Center whose work investigates the use of telomerase and telomeres in disease therapies. "We're absolutely thrilled Blackburn, Greider, and Szostak were honored, and I'm excited about what it will do to help recruit new students and researchers to such a fascinating area of science."

"For them to win the Nobel is fabulous," Mark Muller, a molecular biologist at the University of Central Florida who studies telomerase as an anticancer drug target, added. "Beyond cancer research, their fundamental findings have impacted our ability to study stem cells and reproductive cloning."

Blackburn, Greider, and Szostak also won the 2006 Lasker Award, often referred to as the "American Nobel." They will be presented with the Nobel Prize Medal, Diploma and $1.4 million award -- to be split three ways -- at a ceremony in Stockholm on December 10.

The 2009 Nobel Prize in Chemistry will be awarded Wednesday, October 7.


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