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Pitt honors discoverer of cells' aging enzyme

Thursday, April 13, 2000

By Byron Spice, Science Editor, Post-Gazette

Elizabeth Blackburn wasn't looking for a cancer cure 25 years ago when she began scrutinizing the odd bits of DNA located on the ends of each chromosome. She didn't set out to find a way to halt the aging process.

And the Australian-born molecular biologist is quick to note that she hasn't found either of those things -- yet. When she and a student finally identified the enzyme that keeps those chromosome tips in good repair, however, they uncovered important insights into how cells divide, how they turn malignant and how they grow old and die.

The discovery of the enzyme, called telomerase, launched the career of Blackburn, who has since won a number of major scientific awards. She will accept the most recent, the University of Pittsburgh's Dickson Prize in Medicine, this afternoon when she delivers a lecture in Oakland.

The prize, which this year totals $50,000, recognizes individuals who have made significant, progressive contributions to the field of medicine.

Telomerase has yet to be translated into a treatment for anything, but its impact on molecular genetics has been profound. "It's been very important for understanding how chromosomes are replicated," the process by which cells pass on their genetic instructions, said William Saunders, a Pitt biologist who studies how cancers arise when that process goes awry.

Genes are made of DNA and packed into bundles called chromosomes, which are found in the nuclei of most of the body's cells. Human cells contain 23 pairs of chromosomes. In the mid '70s, when Blackburn was a postdoctoral fellow at Yale University, she became fascinated by chromosome tips. Tools for studying the structure of these molecules had just become available to biologists "and there were hints that the ends were special," she recalled. "But that could have meant anything."

As it turned out, the tips, called telomeres, act much like the sleeves at the ends of shoelaces, keeping the chromosomes from fraying. This is particularly important when cells divide; as chromosomes copy themselves, the telomeres keep chromosomes from sticking to each other, which can cause a cell to turn malignant, Saunders said. In most cells, the telomeres get shorter each time the cell divides until they finally disappear and the cell dies.

Telomerase, which Blackburn discovered with student Carol Greider in 1980 at the University of California at Berkeley, is an enzyme that works to rebuild those caps.

It thus helps keep telomeres young, allowing them to reproduce indefinitely. Normally, it's actively made in only a few types of cells, such as hair follicles, the intestinal lining and sperm cells.

Most cancer cells also produce telomerase. Activation of the gene that produces telomerase is not something that would harm a cell. But in cells undergoing other genetic changes that lead to malignancy, "telomerase is one of the things that gives them a push, a green light to keep dividing," Blackburn said.

Simply eliminating telomerase or its gene does not cure cancer. Saunders noted experiments with genetically engineered mice that lack the telomerase gene show that these "knockout" mice can develop cancer.

Still, it seems reasonable that an agent that blocks telomerase or inactivates its gene could be used with other treatments, said Blackburn, now a professor at the University of California, San Francisco.

In other cases, scientists may want to increase telomerase activity, restoring the youth of the telomeres and thus extending the reproductive life of cells. Earlier this year, researchers at Dana-Farber Cancer Institute in Boston reported that liver cirrhosis was more severe in telomerase-deficient mice than in regular mice and that giving these mice the telomerase gene seemed to slow the progression of the disease.

Telomerase is an unlikely fountain of youth; the aging process involves many other genes, so telomerase gene therapy may do little to increase longevity. But Blackburn suspects telomerase may find use in treating various types of organ failure, not just liver cirrhosis. Telomerase gene therapy might help damaged hearts or kidneys regenerate themselves. The danger, of course, is that such therapy might also unleash a cancer.

All that can be said with any certainty is that telomerase research has created some new opportunities.

"It just opens some really promising doors," Blackburn said. "Lots and lots of doors. We're all very interested in what we can do, but it's not clear how it will play out."

Blackburn will deliver a public lecture, "Telomere Capping and Cell Proliferation," at 4 p.m. today in lecture room 6 of Scaife Hall, 3550 Terrace St., Oakland. A reception will follow in the Scaife Hall lobby.

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