送交者: nini 于 2006-3-07, 11:02:29:
News
Nature Medicine
Published online: 1 March 2006; | doi:10.1038/nm0306-265
http://www.nature.com/news/2006/060227/full/nm0306-265.html
Profile: Hui Zhen Sheng
Apoorva Mandavilli
Hui Zhen Sheng is not famous, at least not beyond a small part of the stem cell community—but perhaps she should be.
Sheng's most noteworthy paper is one she published in August 2003 in a relatively little-known Chinese journal called Cell Research. The paper showed for the first time that you can use an animal egg—that of a rabbit—to make an adult human cell revert to an embryonic state (Cell Res. 13, 251–263).
The work had important implications. At the time, scientists were not sure whether adult cells from any primate could be reprogrammed (Science 300, 297; 2003). Because Sheng used rabbit eggs, the paper also raised the tantalizing possibility that scientists could use animal eggs to clone human embryos for research purposes, skirting the need for precious human eggs.
To be sure, there were reasonable questions about the work. Some scientists wondered whether the rabbit mitochondria might not affect the normal development of a human blastocyst. And the cells Sheng derived from the interspecies blastocyst did not form teratomas, the standard test for stem cells.
Still, the results could have been published with appropriate caveats so that others could examine and repeat them, notes Ian Wilmut, who in 1996 cloned Dolly the sheep. "I was very disappointed that her work was not published in a Western journal, I think it's a great shame," Wilmut says.
That was not for lack of trying. For two years and two months, Sheng tried her luck at three top journals. But the doubts of a few influential scientists kept the paper in limbo. "Some of the referees were trying to make her jump through hoops which maybe Western scientists wouldn't have to do," says Robin Lovell-Badge of the UK's National Institute for Medical Research.
After making the rounds at Science and Nature, Sheng submitted her paper to the Proceedings of the National Academy of Sciences (PNAS). There the paper successfully cleared the review process, but at the last minute, the journal asked her for more data.
No one should be blamed. Anyone can, actually should, suspect a research result before enough evidence is shown.
In the meantime, an academy member, whose identity neither Sheng nor PNAS will share, twice went to Sheng's lab—for his own reasons, according to the journal—and watched the team at work. Sheng recalls that at one point he told her, "Well, they don't know, they're not sure whether you have a lab or not." The second time, he spent nearly a week there, questioning her students and collaborators. On his return to the US, he wrote a favorable report, to which the PNAS reviewers had access.
Once again, Sheng was told her paper would be published, and she paid the printing fees and filled out the necessary forms. But once again, the process ground to a halt. At that final stage, the journal consulted an outside expert who strongly advised, "entirely" on scientific grounds, against publishing it, says Nick Cozzarelli, editor-in-chief of PNAS.
It's rare, to say the least, for a paper to be pulled at that point—Cozzarelli estimates that it might happen with perhaps 5 out of every 2,000 papers—but "it does happen," he says. "The important thing is this whole process was extraordinarily unusual."
In any case, it was enough to make Sheng give up. Anxious that others were catching up, she decided to have a record of the work, even if in a Chinese journal. Anyone in her shoes would have ample grounds to complain, but Sheng talks of the events with grace and aplomb, repeatedly saying that she found the reviewers' doubts entirely reasonable. "No one should be blamed," she says. "Anyone can, actually should, suspect a research result before enough evidence is shown."
Everyone who knows Sheng speaks of her as a principled, independent and thorough scientist. When she is not talking about science, Sheng is excitable, even girlish, but also unexpectedly shy. "I've never found a person with the intellectual stature and personal stature that she has," says Nick Hoogenraad, her friend and head of biochemistry at La Trobe University in Melbourne, Australia.
A Shanghai-ness or a native of the city, Sheng spends hours walking alone, which she says helps her think. She completed her medical training at Shanghai Second Medical University. After a three-year stint in immunology at the university, in 1984 she left China for a PhD program at La Trobe.
During her first few years in Australia, Sheng's husband was studying medicine in Japan and their young son had to remain in China. She lived alone in a small room with little furniture, cooking meals for guests who sat on the floor.
Sheng says little about those years, focusing only on what she learned professionally—but that's typical of her, says Hoogenraad. "[Sheng and her husband] had a large slab of their lives stolen by the cultural revolution, but there was no anger or angst, no feelings of regret," he says. "I gained a lot of strength from them, the way they were able to look at things, always looking forward and never looking back."
In 1987, after a conference in Toronto, Sheng traveled to the US for the first time. Deeply impressed, she later returned and spent 11 years at the US National Institutes of Health (NIH). "She became one of the best people I've ever had in my lab," says Heiner Westphal, her boss there for seven years.
While in Westphal's lab, the Shanghai municipal government offered Sheng seven million yuan (about $875,000) to set up a lab. Excited about the chance to work on stem cells when few other people did, Sheng in 1999 moved back to China. Because her family is still in the US, she splits her time between Maryland and Shanghai.
As a postdoc at the NIH, Sheng had never had to deal with administrative matters—and the system in China came as a shock to her. After the debacle with the Cell Research paper, for instance, the government cut back her funds, forcing her to borrow two million yuan from the university hospital. The funding crisis also cost her the student who had done the interspecies experiments. Sheng is now trying to train the newer students in the techniques and is adapting to the Chinese structure. "I'm learning this wisdom very slowly, little by little," she says.
Sheng admits that if she had stayed at the NIH, things might have been easier. Still, she never once sounds bitter and says she has no regrets. "You get angry, you get frustrated, but then you realize you learned a lot through this process," she says. "It's okay now, we survived it."
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http://www.nature.com/news/2006/060227/full/nm0306-265.html