The New York Times / May 5, 1999 / By NICHOLAS WADE
Geron Corp., developer of human embryonic stem cells and the cell-rejuvenating enzyme telomerase, said on Tuesday that it was forming a $20 million research alliance with the Roslin Institute of Scotland, cloner of Dolly the sheep.
Geron is a leader in what has been called regenerative medicine, the concept of repairing the body not with scalpels and harsh drugs but with its own cells and signaling systems.
The company's alliance with the Roslin Institute is intended to sidestep the problem of immune rejection by cloning the patient's own cells and deriving rejuvenated tissues.
Contrary to science fiction scenarios of making cloned versions of a patient to harvest as organ donors, the process envisaged by Geron would occur at the level of individual cells grown in the laboratory. The concept is promising research, but far from being a practical reality.
Biologists supported by Geron have developed embryonic stem cells, derived from human embryos or fetuses, and these could in principle generate every tissue of the body. But the tissues derived from these cells would not be a perfect genetic match for most patients and may be rejected.
Meanwhile, other companies, like Osiris Pharmaceuticals, plan to repair tissues with a more specialized type of stem cell, which can be derived from the patient and would present no problem of immune rejection.
To get around the rejection problem, Geron's idea is to use the central technique of animal cloning, which is to take the nucleus of a cell from one animal and inject it into the egg of another, whose own nucleus has been removed. The cell body, or cytoplasm, of an egg cell seems to be able to "reprogram" the genes in the inserted nucleus.
"The lesson of Dolly is that adult nuclei can be reprogrammed by cytoplasm," said Dr. Thomas Okarma, Geron's vice president for research. "Our objective with Roslin is to learn the molecular biology of that process so that we can confer the reprogramming ability of cytoplasm to cells other than eggs."
It is well established that eggs can reprogram a nucleus taken from cells of a fetus, but some biologists still doubt their ability to reprogram adult cells, despite the widespread belief that adult animals can be cloned.
"I am not convinced that any adult nucleus has been reprogrammed completely enough to give a fully viable animal, and certainly not with any efficiency," said Dr. Norton D. Zinder, a Rockefeller University biologist who has taken a skeptical interest in cloning.
"The Dolly people haven't done it again," Zinder said, referring to the Roslin Institute's failure to show that the cloning of its sheep was a repeatable scientific experiment, "and in the mice and cow experiments there were many deaths both before and after birth."
In Okarma's scheme, an adult cell would be taken from a patient, its nucleus removed and inserted into a recipient human cell deprived of its own nucleus. The patient's cell nucleus would take over the hybrid cell, creating an embryonic stem cell almost identical to those from which the patient himself had been generated. Although human embryonic stem cells can form every tissue in the body, they are probably not equivalent to an embryo because another kind of cell is required to organize the tissues correctly.
Okarma said that the specialized stem cells obtained by companies like Osiris could divide only a limited number of times and that tissues generated from these cells would be already aged. But Geron has discovered an enzyme, known as human telomerase, that enables cells to grow and divide an unlimited number of times. Geron hopes not only to derive any desired type of cells by the nuclear reprogramming method, but also to rejuvenate them with telomerase before clinical use.
But some scientists doubt the wisdom of implanting telomerase-treated cells in the body because the division-limiting mechanism that telomerase overrides seems to be a prime defense against cancer.
