Picked up by Boston Globe:By Richard Saltus, Globe Staff, 08/15/97
n a discovery with profound implications for research on cancer and aging, scientists have isolated part of the body's 'clock'' that consigns normal cells to eventual death, but which cancer cells manipulate to multiply without limit.
With the genetic nugget in hand, researchers say, it may
be possible to design drugs that would attack all types of cancer cells, yet do no harm to normal cells in the body.
And a biotech company plans to use the findings in efforts to slow the aging of cells and extend the human ''healthspan.''
Two research teams, one from cancer researcher Robert
Weinberg's lab at the Whitehead Institute in Cambridge, are announcing
today that they have isolated the gene that enables cells to make a crucial component of the enzyme telomerase.
The discovery of this telomerase gene is the culmination of research that began in the early 1960s when a California scientist, Leonard Hayflick,showed that most human cells have a preprogrammed lifetime - they can divide only a limited number of times before dying.
Exception are reproductive cells and cancer cells.
But how the cells ''knew'' when their allotted number of divisions was up was a mystery.
The discovery of telomerase about a decade ago found that it was the key part of the body's biological clock that ''counts'' how many times a cell has divided.
''It's very exciting, because it has been a long 30-year search for this gene'' since the discovery of predetermined limits on cell
division, said Michael Davis, vice president for new technology at Geron Corp. in Menlo Park, Calif.
Geron scientists, along with Nobel Laureate Thomas R.Cech at the
University of Colorado in Boulder, made up the other team that cloned the gene. Their report, which calls the gene HTRT, is in today's issue of the journal Science.
The telomerase gene is turned off in normal cells, and as a result the cells' chromosomes lose DNA from their tips, or telomeres, every
time they divide. Eventually the telomeres lose so much DNA the
cell can divide no more, and dies.
But in cancer cells the telomerase gene is switched on, and the cell makes genetic sequences that protect the ends of telomeres from
shortening. This ''rewinds'' the clock and permits the cells to divide indefinitely, which is why tumors continue to grow and invade crucial organs. ''Cancer cells find a way of switching telomerase activity on, which gives them a tremendous competitive advantage ... they become immortalized,'' said Weinberg.
With the gene isolated and sequenced, scientists may be able to find drugs that would turn telomerase off wherever it was active, making cancer cells mortal once more. It could be used in combination with
other drugs that would actually kill the cells, said Weinberg.
''We think that is the Holy Grail'' of using the telomerase discovery to attack cancer, Weinberg said in an interview. And because telomerase is expressed almost universally in cancer cells, it makes an ideal target for drug attack, Weinberg said.
Davis, the Geron official, concurred. ''Our goal is to make telomerase
inhibitors that will eliminate telomerase from the body and would leave normal cells and tissues alone,'' he said. Such a cancer therapy in theory would be relatively nontoxic, because normal cells, lacking telomerase, would not be attacked.
The discovery might also lead to improved drugs for cancer diagnosis.
In an even bolder strategy, Davis said, Geron scientists envision turning on the telomerase gene in cells that have exhausted their
lifetime - say, in brain cells to prevent degenerative diseases like Parkinson's and Alzheimer's. This would have to be done in a way that would not trigger unbridled cell division and cause cancer, Davis acknowledged.
The aim is not to increase human longevity, Davis said. ''Our goal is to extend the `health span' - the time you are free of disease,'' he said.
The paper from the Whitehead Institute is set for
publication in the journal
Cell on Aug. 22.
This story ran on page A01 of the Boston Globe on
08/15/97.
? Copyright 1997 Globe Newspaper Company. |
