The Immortality Enzyme

A newly discovered gene may help scientist combat cancer and linked to aging.

As the human body ages, it loses bone. Individual cells lose something equally vital. Every time one divides, it sheds tiny snippets of DNA known as telomeres, which serve as protective caps a hundred divisions, a cell’s telomeres become so truncated that its chromosomes- site of the cell’s genes-begin to fray, rather like shoelaces that have lost their plastic tips. Eventually, such age cells die-unless like “immortal” cancer cells, they produce telomeres. Scientists have long dreamed of drugs that would inhibit the immortalizing enzyme because, observes M.I.T. biochemist Robert Weinberg then maybe cancer cells would run out of telomeres and just poop out.

Wishful thinking? Maybe not . In papers published just a week apart in the journals science and cell, two teams of researchers – one led by Nobel-prizewinning biochemist Thomas Cech of the university of Colorado, the other by M.I.T.’s Weinberg have announced a breakthrough that could help bring about such a drug. Both teams have managed to clone a gene that controls the activity of telomerase enzyme in human cells. That could set the stage for development not only of inhibiting drugs but also of substances that switch on the enzyme which might help combat degenerative diseases associated with aging

Such possibilities to be sure are speculative but that didn’t stop Wall Street where the stock of Geron Corp a small biotech company based in Menlo Park California. That helped Chech’s group discover the gene more than double to 16 ¹/₈ a share.

In fact, Geron researchers have been looking for antitelomerase compounds for several years, using indirect-screening methods. Because tumor cells – the main source of the human enzyme – produce it in vanishingly small quantities, the scientists lacked pure telomerase, which could have sped the search for drugs that might be used against it.

With the new gene in hand the researchers should be able to churn out at will the protein for which it provides the genetic blueprint. That protein, they believe, is telomerase’s most important building block. For us, exults Calvin Harley, Geron’s chief scientist, it’s like having access to an organism’s brain.

The new protein, it turns out, bears an intriguing resemblance to an enzyme produced by HIV, the retrovirus that causes AIDS. Indeed, the AIDS dug AZT has already been shown to inhibit telomerase activity. But the viral enzyme and the human enzyme, says Colorado’s Cech, are only 20 % identical, which explains why AZT is not an ideal telomerase inhibitor. What we want, he declares, is a compound that fits telomerase the way a hand fits a glove.

The odds that such a compound will materialize now seem high. But experts caution that it could take years before the first telomerase inhibitors are ready to be tested on humans to determine if they’ll have any serious side effects – or if they’ll actually inhibit tumor growth. Such questions are perhaps one reason Geron’s stock leveled off at week’s end, closing at 12 ¼ share.

By J. Madeleine Nash