June 6, 2007 -- Stem cell researchers may have taken the first steps toward conducting stem cell research without having to take the controversial step of destroying human embryos.
If the results can be replicated in human cells, the development could one day silence the arguments of those opposed to embryonic stem cell research on the basis that it violates the sanctity of human life.
"This research in fact lowers the level of ethical concern over reprogramming studies," said Dr. Martin Pera of the University of Southern California Keck School of Medicine. "If it is no longer necessary to make embryos or use eggs to create patient or disease-specific stem cell lines, there are few ethical barriers to the work."
Even those who have been outspoken in their opposition to stem cell research in the past were pleased with the new findings.
"Because [this research] does not raise the moral problem of creating or destroying embryos, it may offer a way for people of all faiths and all ethical backgrounds to study, use, subsidize, and enjoy any therapeutic benefits of...stem cell research," said Richard Doerflinger, secretariat for Pro-Life Activities, U.S. Conference of Catholic Bishops.
"This would be a 'win' for science, ethics and society."
Scientists in the field hail the findings, presented in the form of four new studies, as the most promising stem cell work in years.
Rudolf Jaenisch of MIT's Whitehead Institute, Shinya Yamanaka of Kyoto University and Konrad Hochedlinger of the Harvard Stem Cell Institute published papers in Nature and the new journal Cell Stem Cell that reveal a genetic fountain of youth that "rewinds the clock" on adult mouse cells.
In doing so, the researchers were able to use adult tissue to yield cells that look and act like stem cells.
They hope that the findings will one day lead to the creation of human stem cell equivalents that could be used in medical research.
MIT study co-author Marius Wernig explained that adult mouse skin cells were "reprogrammed" back to a stem cell-like state using a kind of genetic deception. Viruses similar to the HIV virus inserted four key genes into the cells. The proteins made by the genes encouraged pluripotency -- the ability of the cells to be morphed into different types of tissues.
Pluripotency is the basis of stem cells' potential to grow new tissues and organs under the guidance of scientists.
"We can basically reverse the development [of adult cells]," Wernig said. "We ran the cells through a battery of tests, and there was no difference between them and embryonic stem cells."
In contrast, he added, "Nuclear transfer [to grow new stem cells] is ethically challenging, and it involves the destruction of an embryo."
Dr. William Hurlbut, a Stanford University professor and a member of the President's Council on Bioethics, added, "Direct reprogramming is way to go. No eggs are involved. It doesn't go all the way to the beginning [of the cell's life]. It's like going from 12th grade to first grade, not kindergarten."
Hurlbut envisions a future in which stem cell treatments will help many people and where the treatments will be derived in ethically sound ways that do not trouble deeply religious patients.
But challenges still exist. Tumors developed frequently in mice that were cloned from the altered cells, because the genes that make them pluripotent also cause cancer later in life. The researchers agreed that the technique would have to be modified before it could be used on human cells.
Harvard's Hochedlinger, publishing in Cell Stem Cell, demonstrated that the reprogrammed cells retained crucial "epigenetic markers" that are important for the cell's function.
"There should be no fear," he stated, that the reprogramming itself would make cellular processes go awry. His team also found that these markers showed up in subsequent generations of the unique mouse cell line, and that the faux "stem cells" could be coaxed into "therapeutically relevant cell types, like heart tissue and blood."
Dr. George Daley of the Harvard Children's Hospital expressed concern about the political implications of the work. "It is important to note that the opponents of stem cell research will seize upon these studies as cause to stop funding human [embryonic stem] cell research...that these alternatives obviate the need to use embryos in research."
Fertilized Eggs May Also Be Used
Meanwhile, Dr. Kevin Eggan of Harvard University's Stem Cell Institute has a paper in Nature that debunks the scientific belief that only unfertilized eggs can have their genetic material swapped out in place of new DNA.
This means that scientists may one day use fertilized human eggs to create clones, from which stem cells could be harvested for research.
In a phone interview, Eggan explained that, for over a year, he had had funding and review board approval to create genetic clones -- and human stem cell lines -- from human eggs, just like Dolly the sheep was created by plucking the gene-containing nucleus out of an egg and replacing it with an adult sheep's DNA.
But he needed human eggs. While women readily respond to advertisements for egg donation in newspapers of elite colleges -- "$10,000 if you're blond and blue-eyed with a high SAT score" -- medical researchers cannot compensate women in the same way that infertile couples can.
Despite thousands of dollars in ads running in paid Boston-area publications, Eggan couldn't find a single donor. When they heard they wouldn't be paid for the months of hormonal treatment and sometimes painful egg retrieval, all the women declined.
"That left us with a lot of time to get back to first principles, to think about why we needed unfertilized eggs in the first place," said Eggan.
At a conference, it clicked -- human frozen fertilized eggs are plentiful. In the lab, mouse fertilized eggs, halted at a crucial step in cell division, received new nuclei from other mouse cells. The new embryos -- clones -- continued to develop into baby mice.
The paper notes that even eggs with severe defects accepted the new genetic material and developed.
"[On their own] these eggs would never have made a viable fetus," said Eggan, adding that he hopes that fertility clinics that would normally throw away such defective cells will instead donate them to research.
"There are a half million fertilized eggs created every year in the U.S., and 3-10 percent of those will not develop. The embryologist can see that they don't have the right number of chromosomes, even at the one-celled stage."
Currently, couples who choose to donate their unneeded or defective embryos for medical research go through a separate process of consent from the consent for in vitro fertilization. Eggan said, "We as a scientific community want to be especially sensitive" at this time of personal decision-making. Eggan has already received donations of fertilized eggs, or zygotes, from such couples.
Eggan, Hochedlinger and Wernig emphasized that they support the current efforts in stem cell research, and that their experiments were not designed to create a way out of stem cell and cloning controversy.
Rather than moving away from using traditional methods for stem cell research, the new methods in mice offer additional options for researchers. Hochedlinger stated, "[Genetic reprogramming] does not make other approaches obsolete. We haven't applied the results to humans. It would be a mistake to ban somatic cell nuclear transfer."
Other scientists were enthusiastic about the findings.
Sean Morrison of the University of the Michigan Center for Stem Cell Biology wrote of the genetic reprogramming work: "This is a remarkable achievement that contributes important new insights to our understanding of pluripotency. Nonetheless, it would be premature to conclude that this represents a replacement for traditional embryonic stem cell research."
Hochedlinger agreed. "We have to study human embryonic stem cells to understand how they work, to achieve reprogramming in human cells."