Scientists working with human embryonic stem cells have for the first time successfully spliced out individual genes from the medically promising but politically contentious cells and substituted different genes in their place.
The work is a step toward the biomedical goal of being able to rebuild or regenerate parts of the human body by transplanting either stem cells or tissues grown from stem cells into patients, scientists said. Precise genetic changes in those formative human cells might enhance their therapeutic potential or make them more compatible with patients' immune systems.
Some scientists suggested the success might someday make it unnecessary to pursue "therapeutic cloning," in which cloned embryos would be created as a source of therapeutic tissues that match the genetic signature of the patient.
But the work could escalate concerns among those who fear that stem cell technology will lead to the creation of "designer babies."
Applying genetic engineering techniques to humans is "defensible as long as it's used to cure diseases, but we have to be aware that techniques like these can be abused, too," said John Robertson, a bioethicist at the University of Texas School of Law.
The new work, published in today's issue of the journal Nature Biotechnology, resembles similar studies decades ago in mice. That was when scientists discovered how to "knock out" and replace individual genes in mouse embryo cells.
The technique, called homologous recombination, revolutionized molecular and cellular biology.
By growing animals with those precise genetic changes and seeing what went wrong as they developed, scientists could start to see what individual genes did. They also were able to replace "broken" genes in mouse embryos.
The work with human embryonic stem cells was done by University of Wisconsin researcher James A. Thomson, the scientist who discovered the cells in 1998, and his colleague Thomas P. Zwaka.
They used electrical charges and chemicals to make the cells' membranes porous enough to allow the cells to take in customized genes. Under proper conditions, the new genes find and replace their counterparts in the cell DNA.
In one experiment, they knocked out a gene that in humans causes Lesch-Nyhan syndrome, a rare and fatal genetic disease. They said they hope such work can shed light on the molecular underpinnings of the disease and perhaps someday lead to cures. But others noted that just because a broken cell can be fixed does not mean a cure will be forthcoming soon.
Despite years of efforts, Johns Hopkins University stem cell researcher John Gearhart said, scientists have not been able to make lines of mouse stem cells that are compatible in all mice.
He suggested that therapeutic cloning research, controversial though it is, will remain important in the search for treatments for human disease.