Scientists Give Cell Apparent Immortality
Breaking a biological barrier once thought out of reach, scientists for the first time have apparently endowed healthy human cells growing in a dish with a quality that alchemists, explorers and mystics have vainly sought for ages: immortality.
In the new research, due to be published Friday in the journal Science, the scientists genetically altered cells, enabling them to keep dividing long past their allotted life span. The work opens a new path to the treatment of cancer and a variety of degenerative ailments, including heart disease and age-related vision loss. Such “immortalized” healthy human cells might also serve as biological factories for churning out genetically engineered drugs.
Most tantalizing, scientists say, the finding offers a glimpse of the molecular gears and springs that make up the human biological clock, thus renewing the ancient hope that the outer limit of the human life span may not be absolutely fixed after all.
The new study--by scientists at Geron Corp. in Menlo Park, Calif., and the University of Texas Southwestern Medical Center in Dallas--is “an important discovery,” said Anna McCormick, chief of the biology of aging program at the National Institute on Aging. “It opens another door to understanding the mechanisms of aging at the cellular level.”
Leonard Hayflick, a cell biologist at UC San Francisco who pioneered the field nearly 40 years ago, said the study represented a “monumental advance in understanding the genetics of aging.” Hayflick, a member of Geron’s scientific advisory board, said he never thought he would live long enough to see such progress. “I’m just amazed,” he said.
The study addresses a question that has been at the center of aging research since Hayflick and his co-workers discovered that most healthy animal cells are programmed to divide a particular number of times before they reach the end of the line and stop dividing, a crucial step in aging. Certain cells in the retina, for example, have the capacity to divide only about 60 times.
The question has always been, what controls that clocklike mechanism?
The new research supports the idea that an animal cell’s innate “division potential” is largely controlled by a particular stretch of DNA at the tips of chromosomes. Called telomeres, these DNA stretches do not appear to contain hereditary information but instead consist of a cluster of six chemical bases repeated over and over again.
Each time a cell divides, a chunk of telomere is snipped off. Dividing ceases when the telomere is shortened to a particular amount.
As simple as the “telomere-clock model” sounds, proponents have found it impossible to prove--until now. The Geron and Texas researchers used a gene that blocks telomere shortening and inserted it into laboratory cultures of two healthy human cells--retina cells and a type of skin cell. The gene produces an enzyme called telomerase, which maintains the length of telomeres or adds to it.
After the cells were grown in the laboratory, those with telomerase kept on dividing long after the unendowed versions of the same cells reached the end of the line. Usually, the cultured retina cells stop dividing after 60 divisions, but the genetically engineered ones are still going after nearly 40 more divisions, almost doubling their life span, said Woodring Wright, a molecular biologist at Texas Southwestern and a co-author of the paper.
The results are “strikingly unequivocal,” Titia de Lange, a cell biologist at Rockefeller University in New York City, wrote in an accompanying editorial.
Calvin Harley, Geron’s chief scientific officer, suggested a number of ways in which the finding might be exploited. The first application most likely will be to use cell cultures genetically engineered with the telomerase enzyme to produce quantities of drugs like blood factors needed to fight heart attacks. Previously, human cell lines had been impractical for such uses because they peter out after a limited time.
Beyond that, he speculated that gene therapy involving telomerase might be a possibility. Cells bearing the ravages of time and due to expire could be surgically removed, endowed with the enzyme, then replanted into the tissue.
“We’re optimistic that this discovery will have far-reaching applications in medicine, but we cannot predict how long it will take to develop any products,” said Calvin B. Harley, Geron’s chief scientific officer.
Cancer researchers are also excited about the finding, because a tumor is a mass of cells that have somehow lost the ability to stop dividing. The enzyme telomerase appears to be a key there, too; in 90% of cancers tested so far, the telomerase enzyme is already active, and presumably involved in the wild growth and division. Indeed, cell biologists have long been able to coax cancer cells to divide indefinitely--giving the cells a quality they refer to as immortality.
One new strategy in cancer control is to develop drugs that specifically block the activity of telomerase, thus restoring the innate tendency to stop dividing.
But because cancer cells are rife with telomerase, researchers cautioned that simply inserting the gene for that enzyme into aging cells may backfire and make them cancerous rather than youthful. “Resetting the telomere clock may come at a price,” de Lange said.
Although the finding has been promoted by the University of Texas as a “fountain of youth,” Geron’s Harley said he objected to that description, because nothing in the work implies an ability to reverse aging. Still, some researchers say the finding does challenge the notion that maximum life span could never be stretched, even a bit.
Geron stock rose 4 3/8 on word of the study, closing at 14 3/8.
