Scientific American, 6/97, Steve Mirsky and John Rennie, page 102

What Cloning Means for Gene Therapy

The recently debuted technology for cloning is usually discussed as a means of creating genetic copies of whole adult individuals. This is far from its only use, however. Cloning could be combined with other biotechnologies, either to achieve more novel goals or to improve on previous methods. Although the technique is still in its infancy, and needs to be studied and developed much further, educated musings about cloning's ability to inform gene therapy are already being brought to the table. An area that might particularly benefit is germ-line gene therapy genetic modifications that could correct a problem for future generations. "I think cloning is going to be used as a tool that will make gene therapy work," comments Lee Silver, a molecular biologist at Princeton University and an expert on reproductive technologies. "For the first time, germ-line gene therapy becomes realistic."

Germ-line therapy , which is not yet being studied in humans, could ideally prevent deadly or debilitating disorders such as sickle cell anemia or cystic fibrosis. Such diseases are typically transmitted silently from generation to generation by people carrying one copy of a defective gene; the disease be comes manifest when two carriers have a child who inherits two copies.

Today prenatal genetic testing can re veal whether a fetus or embryo is affected with many of these conditions. The parents then have the option of aborting and rolling the genetic dice again with another pregnancy. In some cases, how ever, the dice are guaranteed to come up snake eyes. "If both parents are sickle cell diseased," Silver says, "then all of their embryos will also carry the disease. You can't select, because there are no good embryos." But gene therapy, aided and abetted by cloning, could theoretically correct the condition for their children, and all subsequent progeny as well.

The recipe would begin with a fertilized egg growing, in the laboratory, into a mass of early embryonic tissue. A functioning gene-say, for the blood's oxygen-carrying protein, beta globin, which is mutated in sickle cell anemia-would then be inserted into the embryonic cells by tailored viruses or other vectors. (A marker sequence inserted along with the gene might help identify which cells took up the gene correctly.) The DNA of one of those cells could then be implanted into a new egg cell from the mother, be ginning the pregnancy afresh. In effect, this last step replaces the original embryo with a healthier clone of itself.

Germ-line therapy does not require a cloning step, but cloning might make it far easier. Very early stage embryonic cells, if separated, retain the ability to regenerate into whole embryos (indeed, that is how identical twins, triplets and quadruplets arise). Gene therapists could therefore alter the DNA of the embryonic cells and return one to the mother for gestation. The problem is that embryonic cells lose their "pluripotent" capacity after a few cell divisions