By Rick Weiss
Washington Post Staff Writer
Thursday, August 14, 2003; Page A04
Scientists in China have, for the first time, used cloning techniques to create hybrid embryos that contain a mix of DNA from both humans and rabbits, according to a report in a scientific journal that has reignited the smoldering ethics debate over cloning research.
More than 100 of the hybrids, made by fusing human skin cells with rabbit eggs, were allowed to develop in laboratory dishes for several days before the scientists destroyed them to retrieve so-called embryonic stem cells from their interiors. Although scientists in Massachusetts had previously mixed human cells and cow eggs in a similar attempt to make hybrid embryos as a source of stem cells, those experiments were not successful.
Researchers said yesterday they were hopeful that the rabbit work would lead to a new and plentiful source of embryonic stem cells for research and, eventually, for medical use. But theologians and others decried the work as unethical.
Some wondered aloud what, exactly, such a creature would be if it were transferred to a womb to develop to term.
The vast majority of the DNA in the embryos is human, with a small percentage of genetic material -- called mitochondrial DNA -- contributed by the rabbit egg. No one knows if such an embryo could develop into a viable fetus, though some experiments with other species suggest it would not.
Congress has been mulling legislation for years that would outlaw certain human cloning experiments, with some opposed to any creation of cloned embryos for research and others sympathetic to research uses as long as the embryos are not allowed to grow into cloned babies. No law has been passed, however, in part because of researchers' warnings that the proposed restrictions are so far-reaching that they would hobble development of new medical treatments.
The new work, led by Hui Zhen Sheng of Shanghai Second Medical University, appears in the latest issue of Cell Research and was highlighted in a news report in the journal Nature. Cell Research is a peer-reviewed -- if little-known in the United States -- bimonthly scientific journal affiliated with the Shanghai Institute of Cell Biology and the Chinese Academy of Sciences. Some researchers yesterday said they were frustrated by the lack of details in the paper.
The team said it retrieved foreskin tissue from two 5-year-old boys and two men, and facial tissue from a 60-year-old woman, as a source of skin cells. They fused those cells with New Zealand rabbit eggs from which the vast majority of rabbit DNA had been removed. More than 400 of those new, fused entities grew into early embryos, and more than 100 survived to the blastocyst stage -- the point at which coveted stem cells begin to form.
The approach could help scientists wishing to mass-produce human embryos as sources of human embryonic stem cells. Stem cells can morph into all kinds of tissues and may be able to reverse the effects of various degenerative diseases. But to make cloned embryos, scientists need both normal body cells -- such as skin cells -- and egg cells, which have the unique capacity to "reprogram" the genes in body cells and make them behave as though they were embryo cells.
Because human egg cells are difficult and costly to retrieve from women's ovaries -- and because human egg retrieval poses risks to the donors -- scientists have been wanting to know whether animal eggs may serve as well. A major question has been whether the remnants of mitochondrial DNA that typically remain in an animal egg would be compatible with the nuclear DNA contributed by the human cell.
The new work suggests that the answer to that question is yes, scientists said -- though with a number of caveats. Most important, researchers said, the paper stops short of proving beyond a doubt that the stem cells retrieved from the hybrid embryos are truly capable of growing for long periods of time in lab dishes, and that they can turn into every known kind of cell.
Even so, said Douglas Melton, a Harvard University cell biologist and cloning expert, the work is a big advance because it offers a new system for exploring the mechanisms by which egg cells get adult cells to act in embryonic ways. That could provide deep insights into human development, wound healing and tissue regeneration.
He noted that although this is the first creation of a human "chimeric" embryo -- a reference to the fabulous chimera of Greek mythology, which had a lion's head, a goat's body and a serpent's tail -- it is not the first time scientists have blended human cells into lab animals. Some mice, for example, have been endowed with human brain cells or portions of the human immune system for research.
The Chinese work, Melton said, is "extremely interesting, and I hope they pursue it."
R. Alta Charo, an associate dean of law and professor of bioethics at the University of Wisconsin at Madison, noted that the work passed muster with Chinese ethics authorities, who had demanded, among other things, that the embryos not be allowed to grow more than 14 days.
"Short of putting one of these embryos into a woman's body for development to term, I don't think this work harms anyone alive," Charo said.
She said the experiments should force opponents of cloning research to identify more clearly than they have until now exactly where they would draw the line against human embryo cloning -- in effect: How human does an embryo have to be to have the moral standing these advocates confer on embryos?
Richard Doerflinger, of the U.S. Conference of Catholic Bishops, said he felt certain that the human-rabbit embryos were human enough to deserve protections.
"I think because all the nuclear DNA is human," Doerflinger said, "we'd consider this an organism of the human species."
Aug 13, 2003