07:20 PM ET 12/28/98

'Immortality Enzyme' Is Studied

By JOSEPH B. VERRENGIA AP Science Writer

Appearing forever young like Dick Clark is everybody's dream. But, biologists wonder, what good is immortality if all those extra years are accompanied by cancer?

That's the quandary posed by the discovery earlier this year that a body substance called telomerase is an "immortality enzyme" that encourages cells to keep dividing indefinitely instead of dying with age.

Scientists theorized that telomerase could be used to slow the aging process. At the same time, some feared that the enzyme could cause cancer by allowing cell division to run amok.

Now, new experiments by the same University of Texas team of researchers have concluded that such fears are groundless.

The researchers watched human cells divide hundreds of times in test tubes and concluded that telomerase does not by itself turn healthy cells into malignant ones. In fact, they said the enzyme may offer promising new ways to treat cancer.

"Telomerase does not cause cancer progression," said Woodring Wright of the UT Southwestern Medical Center in Dallas, a co-author of the study, published Tuesday in the January issue of the journal Nature Genetics. "The abnormalities seen in cancer are due to other mutations."

Other researchers said the experiment is too limited to exonerate telomerase.

They said that while telomerase may not cause cancer by itself, it appears to play a fundamental role in the growth of cancerous cells, even if the cancer itself is triggered by, say, radiation or a virus.

"There is no simple statement that telomerase is irrelevant to cancer," said Ronald DiPinho of the Dana Farber Cancer Institute of Harvard University. "It's a very complex subject."

Thomas Cech, a 1989 Nobel laureate and biochemistry professor at the University of Colorado, said the Texas researchers looked only at the effects of adding telomerase to a normal cell, not what happens when telomerase is blocked in a cancer cell.

A year ago, Wright and colleague Jerry Shay published research demonstrating that telomerase enables cells to keep on dividing and avoid the normal process of aging and death. (See section beginning on page 266 of Children of Prometheus for more on telomerase.)

Normally, human cells divide about 75 times over a lifetime. But each time a cell divides, the telomere, or the protective end of a chromosome, erodes. Eventually, the telomere becomes too short to protect the chromosome. When that happens, the cell can no longer divide and eventually dies.

By the time a person is an adult, most of their healthy cells no longer contain any telomerase. But 90 percent of cancer cells have been found to have telomerase, raising suspicions that telomerase is linked to cancer.

In test-tube experiments, Wright and Shay showed that normal cell death can be avoided by inserting a gene that instructs the cell to produce telomerase.

As of late December, the cells had divided as many as 220 times beyond their typical lifespan, and none exhibited cancerous traits such as abnormalities in chromosomes, the researchers said.

At least a dozen pharmaceutical companies are in the early stages of developing drugs that would shut down telomerase and starve cancer of the tumor growth substance critical to its survival.

Telomerase also is being considered for use in unclogging blood vessels, restoring circulation involved in some forms of blindness, and accelerating the healing of skin grafts.