One possible glitch with using a patient's adult cell to make replacement tissue is that the cells in that tissue may be prematurely aged. In other words, the cells, though new, start life at the age of the cell from which they were derived. Indeed, although stem cells can divide indefinitely, once they are differentiated, they are locked into a limited life-span, counted down by the number of divisions they undergo. With each division, the stretches of DNA at the ends of their chromosomes--regions called telomeres--begin to fray and shorten, leaving the remaining DNA more liable to errors and mutations.

Image: GERON CORPORATION STEM CELL-DERIVED TRANSPLANTS can be made in a variety of tissue types. Moreover, when they are created using the genes from a patient's adult cells, they make a perfect tissue match, described by scientists as histocompatible.

A report in the May 27th issue of Nature confirmed that Dolly the clone is in fact chromosomally older than she is chronologically. Her telomeres are shorter than they should be for a three-year old ewe. They are instead the length expected of a six-year old animal, which is the age of the sheep from whom Dolly was cloned. (Otherwise, Dolly--who just completed her second successful pregnancy, delivering triplets in March--is completely healthy.)

It is unclear whether shrinking telomeres will be problematic in culturing human tissue transplants, but if it turns out they are, Geron has an answer for that too. In August, 1997, Nobelist Thomas Cech of the University of Colorado at Boulder and colleagues at Geron isolated the human gene for telomerase reverse transcriptase (hTRT)--an enzyme that reknits loosening telomeres and extends a cell's life. And five months later, Jerry Shay and Woodring Wright of University of Texas Southwestern Medical Center, also working with Geron collaborators, published additional findings, showing that, by introducing the hTRT gene to cells, they could make those cells repair unraveling telomeres. By reactivating telomerase activity in stem-cell derived tissue transplants, Geron could provide patients with a life-time warranty on their new parts.

In the final analysis, it seems clear that Geron is not going for the obvious play, pairing stem cells and nuclear transfer to pursue human clones. Instead, Roslin's technology is just another card they need to shoot the moon in the game of developing a new generation of potent medical therapeutics.

Comments