Creating stem cells without embryos.

In November, scientists turned human skin cells into what appear to be embryonic stem cells without having to make or destroy an embryo. The groundbreaking work could circumvent the ethical debate troubling the field of embryonic stem cell research.

Embryonic stem cells are "blank slates" that have the ability to turn into any of the 220 cell types of the human body. The cells are plucked from a human embryo created specifically for this purpose, and just four to five days after fertilization. The embryos are hollow, microscopic balls of cells called blastocysts. Nevertheless, because the embryo is destroyed in the process, concerns over the sanctity of human life have severely limited the ability for researchers to explore the extremely promising uses for stem cells to prevent human suffering, including in patients with Parkinson's, Alzheimer's, and other degenerative diseases.

The scientists published their findings in the journals Cell and Science, explaining that the process involves adding four genes to the skin cells, effectively reprogramming the chromosomes of the cells and turning them into blank-slate cells. The genes in question are known as master regulator genes, and their role is to turn other genes on or off. The reprogrammed cells, the scientists report, appear to behave exactly like human embryonic stem cells. Further testing is needed to determine with certainty whether the resulting "pluripotent" stem cells are entirely equivalent to embryonic stem cells.

The new method also includes potentially risky steps. The scientists currently use a retrovirus to insert the genes into the cells' chromosomes. Retroviruses slip genes into chromosomes at random, sometimes causing mutations that can make normal cells turn into cancers. And in one of the two independent research groups, the researchers introduced a known cancer-causing gene as one of the four master regulators. But researchers are optimistic about perfecting the method and say that in the near future it ought to be possible to reprogram cells without using the retrovirus. It is already possible to reprogram cells without the cancer-causing gene.

The two independent teams, from Japan and Wisconsin, also note that their method creates stem cells that genetically match the donor without having to resort to the controversial step of cloning. For use as replacement cells and tissues in patients, it is invaluable to have genetically matched cells because they would not be rejected by the patient's immune system.

The scientists also say that genetically matched cells from patients with Alzheimer's and Parkinson's will enable them to study these complex diseases in the lab. The new method, therefore, would circumvent both the need for human cloning and for human embryos.

Stem cells are so malleable that they may pose a risk of cancer, even without the insertion of the cancer-causing gene. But the new method may in itself at last allow the field to overcome this and other problems, as it provides a way for research to resume without ethical complications--and the consequent shortage of human embryonic stem cells or restrictions on federal funding.

(Cell, 2007, Vol. 131, No. 5, pp. 861-872; Stem Cell Information, National Institutes of Health, http://stemcells.nih.gov/info/basics/basics3.asp; The New York Times, Nov., 21, 2007, "New Stem Cell Method Could Ease Ethical Concerns," by Gina Kolata)