Without Cloning, They Aren't Likely To Work

http://www.sciam.com/2001/1201issue/1201scicit6.html

December 2001
BY CAROL EZZELL

New pancreatic cells for people with diabetes. Regenerated hearts for those who have suffered heart attacks. Repaired spinal cords for paraplegics. These were the hopes in everyone's mind following President George W. Bush's announcement this past August that the federal government would begin providing funds for scientists to study human embryonic stem cells--or at least the 64 colonies of stem cells that have already been isolated in laboratories worldwide.

But immediately after Bush's proclamation, scientists began to question whether all of the 64 existing colonies, or cell lines, were sufficiently established and viable for research. Indeed, U.S. Secretary of Health and Human Services Tommy G. Thompson subsequently admitted before Congress that only 24 or 25 of the lines were ready for use in experiments.

Now some researchers are expressing doubts that any of the stem cell lines will be useful for human therapies. The promise of stem cell research, they say, will be fulfilled only if they are allowed to isolate stem cells from cloned embryos created for individual patients. Under such a scenario, a patient's skin cell would be injected into a donated egg that had been stripped of its genetic material. The fused cell would then be prompted to divide into a clump of cells from which stem cells could be isolated.

Although the current stem cell lines were derived from very early embryos that had not developed beyond hollow balls of cells that fit on the tip of a needle, the cells nonetheless bear proteins on their surfaces that could cause them to be rejected as foreign by the immune system. "We've been saying all along [that stem cells] have to match the patient 100 percent" to be useful therapeutically, says Jose Cibelli, vice president of Advanced Cell Technology in Worcester, Mass., which is pursuing human therapeutic cloning. Even if scientists could generate 1,000 off-the-shelf stem cell lines for use in transplantation, he claims, they would not be able to match the cells to patients closely enough. Recipients would still face rejection risks and would need to take immune-suppressing drugs of the kind given to people with organ transplants. (The problem would not exist for adult stem cells isolated from patients, but these have been hard to find.)

Other investigators point out that even cloned or adult stem cells would not be adequate unless they had their genetic defects fixed before they were given back to a patient. Pancreatic cells derived from stem cells cloned from someone who has diabetes would still contain the genes that contributed to the person's disease in the first place, the researchers maintain. "It's one thing to re-create a pancreas, but if you have to regenerate from diseased tissue, the gene is still defective," says Inder M. Verma of the Salk Institute for Biological Studies in San Diego, Calif. "You have to correct the defect; otherwise cloning will get you what you started out with."

Verma predicts there will be "a hue and cry" for the federal government to fund studies of newly generated stem cells if animal studies using the currently available stem cell lines show promise. Cibelli hopes that one day people will have cloned embryos of themselves created and used to derive stem cells that can be frozen until needed. "It's like buying insurance," he says. Such cells could be the "perfect vehicle" for gene therapy as well, he foresees. But therapeutic human cloning is a political hot potato right now, with bills forbidding it pending in the House and Senate. Votes on those bills may be postponed until next year because of the terrorist attacks of September 11. In the meantime, a lot of sick people who have read the headlines are pinning their hopes on this potentially revolutionary course of treatment.

THE NATIONAL ACADEMY WEIGHS IN 

The specter of immune rejection is "a substantial obstacle" to the use of stem cells for therapies, declared a panel of experts convened by the National Academy of Sciences in a report issued on September 11. The researchers and ethicists raised concerns about the potential health risks of using stem cell lines because such cells could contain mutations and have been grown in the presence of mouse cells, which could harbor viruses. Cloned stem cells "should be actively pursued," the report concluded.