Research on embryonic stem cell cloning advances
A team of New York scientists has taken a major step toward the goal of creating cloned human embryonic stem cells for therapeutic uses - but many technical hurdles remain before the cells could be used in patients.
The feat also highlights legal, ethical, and financial hurdles that stymied similar research being pursued by Harvard scientists. The New York group was led by a scientist who was trained at Harvard.
In the new work, scientists at the New York Stem Cell Foundation's independent nonprofit laboratory used 270 human eggs from 16 women to create 13 early-stage embryos and two stem cell lines - batches of cells with the capacity to form all the cells in the body. One cell line carried the genome of a patient with type 1 diabetes, the other the genes of a healthy adult. But there was a major caveat: The two stem cell lines also carried the original genetic material of the egg donor. Researchers reported in the journal Nature yesterday that the development of the egg came to a halt if they tried to remove the original genome.
Cells with the extra genetic material could not be used to treat patients, but scientists not involved in the research said it could yield important clues about how to more efficiently and completely reprogram an adult cell into an embryonic stem cell. Scientists envision such cells could be useful for creating patient-specific cells that could one day be used to generate or repair tissue in patients with diseases such as diabetes and Parkinson's. The research also shows how funding by private donors and a unique set of protocols allowed such difficult work to proceed in the first place.
"It's really a testimony to the kind of opportunity they had; it brought together this unusual institutional approval, but also the financing," said Dr. George Q. Daley, a stem cell scientist at Children's Hospital Boston.
Daley led one of two teams of researchers at the Harvard Stem Cell Institute that five years ago received approval from the university to attempt a similar project. But because of restrictions, including a state law prohibiting compensation to egg donors beyond expense reimbursement, those efforts moved slowly, recruiting only one woman as an egg donor and using low-quality eggs from a fertility clinic.
"We stopped in large part because we felt we were hitting our heads against the wall; because the eggs were poor quality, and it was just an expensive process at a time when NIH funding was getting tougher," Daley said.
In a paper published this week in the journal Cell Stem Cell, Harvard scientists - including Dieter Egli, who later moved from Harvard to New York to lead the new research - described the problems the other group encountered. After nearly a year of advertising in newspapers, magazines, public transportation, and on the Internet, the Harvard team received positive response from 239 potential egg donors, 79 of whom met all the criteria for the study. Only one went on to donate, and the most frequently mentioned obstacle in a survey of 52 of the qualified donors was the lack of financial compensation.
Douglas Melton and Kevin Eggan, stem cell scientists at Harvard, published a separate study this week in the journal Nature Communications describing failed attempts to use fertilized human eggs that were more readily available to turn adult cells into embryonic-like ones. Melton said that their work and the New York research demonstrates there are important differences between doing research on human tissue and in mice, where cloning embryonic stem cells and using fertilized eggs to reprogram adult cells had been successful.
"The conclusion is what we've learned from cloning and other mammals is not directly applicable to humans. That doesn't mean it's an unsolvable problem," Melton said. "It's another example of how, by not being able to work on humans, we're missing out on some important biology."
Insoo Hyun, a bioethicist at Case Western Reserve University School of Medicine, said that the new work suggests that prohibiting compensation of women when they donate eggs for research may have been premature. Women can be compensated for donating eggs for in vitro fertilization, but various guidelines - including regulations in California and Massachusetts - prohibit compensation other than for basic expense reimbursement. In New York, compensation for egg donation was allowed and women were paid $8,000, the same amount they would have received for donating eggs for in vitro fertilization.
"The difficulty of the actual biology itself shows that we need to be very careful in our policies not to undermine true science," Hyun said. "It would be one thing if it was really easy to misapply these techniques to bad ends. ..... Just because you create Dolly the sheep, you can't create people."
But some questioned whether the protocols used in the New York study should be more closely examined, especially before a debate is reopened on whether women who donate eggs for research should be allowed to receive compensation.
Judy Norsigian, executive director of Our Bodies Ourselves, a Cambridge-based nonprofit women's health organization, said that the drugs used to suppress ovarian function in egg donors need to first be properly vetted for long-term safety.