EVEN as the ink is drying on her latest paper, Hui Zhen Sheng’s work is provoking wildly different responses. It has been hailed as an important advance, questioned for its scientific rigour and sensationalised as a bizarre mixing of human and animal.
Sheng’s team at Shanghai Second Medical University claims to have created human embryonic stem cells by fusing adult human cells with rabbit eggs stripped of their nuclei – a form of cloning. What’s more, her team claims, the resulting cells can form a variety of human tissues, including muscle and nerve cells.
The goal is to create a new source of embryonic stem cells (ESCs) for research and ultimately medical applications. At the moment, ESCs can only be derived by destroying human embryos, which some regard as unacceptable. But most researchers think ESCs’ potential for treating diseases as diverse as diabetes and Alzheimer’s outweighs such concerns. And generating embryos by cloning cells from a patient would allow doctors to obtain genetically identical ESCs that would not trigger rejection.
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The attraction of interspecies cloning is that it overcomes the great shortage of human eggs. And few experts think that embryos cloned from such disparate species will be viable, so no potential human life is being destroyed. Attempts to use interspecies cloning to rescue endangered species, for example, have failed to produce viable embryos except where the two species are closely related, such as a bid to clone wild oxen called gaurs using cow eggs. And even with such a close match, the sole gaur produced died two days after birth, says Robert Lanza of Advanced Cell Technology of Massachusetts, which carried out the experiments.
So with disparate species such as rabbits and humans, it seems certain that no “rabbit-human hybrid” could develop. As for tabloid visions of floppy-eared humans, the embryos contain only a tiny fraction of rabbit DNA, in some of the mitochondria that supply cells with chemical power.
Lanza’s team has not been able to derive ESCs from human-cow and human-rabbit embryos: the embryos usually die after a few divisions, long before ESCs can be harvested, he says. So Sheng seems to have made a big advance.
Rumours of her success have been circulating for two years. Her work has now finally been published in Cell Research (vol 13, p 251), a peer-reviewed journal of the Chinese Academy of Sciences. It describes how her team inserted donor cells from the foreskins of a five-year-old boy and two men, and from a woman’s face, into rabbit eggs. From the resulting embryos, the team harvested cells with the ability to transform into a variety of tissue types.
“If this is true it’s very important,” says Lanza. “But their results are very hard to believe.” He is convinced that such experiments are doomed for very basic biological reasons. For one, mitochondria don’t communicate well with nuclei from distantly related species. So any interspecies embryo – and any tissues derived from it – could be starved of energy.
Even taking the work at face value it has failings, says Douglas Melton of Harvard University. For example, while true ESCs can reproduce indefinitely, the Chinese team didn’t keep the cells it derived growing long enough to prove they had this property.
“Even so, the results are well worth publishing,” Melton says. While he isn’t convinced the cells are ESCs, their ability to transform into a variety of tissues is remarkable given that they started out as human skin cells. “That says rabbit eggs can reprogram them to switch on genes for muscle and neurons and grow longer than I would have guessed,” he says. “That’s surprising.” He hopes the researchers continue their work.
And Lanza says Sheng could easily win over doubters by allowing other labs to test the interspecies cells for the telltale presence of human nuclei, rabbit mitochondria and ESC-like properties. “It would be very straightforward for them to convince everyone,” he says.
