In ancient Greece, immortality was the province of gods who spun the length of each lifetime. The myth has a kernel of truth, because the ends of chromosomes are protected by specialized stretches of DNA called telomeres. Once these are snipped too much by imperfect copying, a cell goes into senescence and stops dividing. Now two reports show that, with the help of an enzyme called telomerase, human cells can divide forever in the laboratory without turning cancerous. The findings, reported in the January issue of Nature Genetics, could ease the way to new treatments for burn victims, diabetics, and patients with other diseases.
Researchers hoped that adding telomerase would keep cells dividing long enough to replace tissues lost to injury or disease. Normal cells often have proved impractical because they can only divide a limited number of times in culture, and once returned to the body they're often too old to do much good. The limitation may be that normal cells do not produce active telomerase, which can rebuild the telomeres and keep cells from becoming senescent.
In fact, about a year ago, Jerry Shay and his colleagues at the University of Texas Southwestern Medical Center in Dallas showed that adding the enzyme to normal connective tissue cells called fibroblasts extends their life-span (ScienceNOW, 13 January 1998). These cells have now lived three times longer than normal in the lab, and they are still going strong. But because cancer cells contain telomerase and also live forever, scientists worried that the newly immortal cells would become malignant when implanted in humans.
To allay that fear, Shay and his colleagues checked the newly immortal cells for other telltale traits of cancer cells. They found none. Unlike cancer cells, the telomerase-containing fibroblasts stopped growing when deprived of blood serum and a solid surface they can adhere to; they also stopped growing when their DNA was damaged or when they brushed up against other cells; and, also unlike cancer cells, they contained the correct number of chromosomes. Likewise, Choy-Pik Chiu and her co-workers at Geron Corp. in Menlo Park, California, did similar tests--with similar results--on both fibroblasts and retinal cells that had been immortalized by telomerase addition. The Geron group also showed that the death-defying cells fail to form tumors, either in culture dishes or in susceptible mice.
"The results are fascinating," says cancer biologist Al Klingelhutz of the Fred Hutchinson Cancer Research Center in Seattle. But he and other experts caution that while the immortal cells retain growth controls in culture, they may still be predisposed to cancer in humans. Nevertheless, says cancer biologist John Sedivy of Brown University, so far the prospect of using telomerase-immortalized cells in new therapies "looks extremely promising."