BioWorld International Correspondent

LONDON - Stem cell scientists in the UK want permission to use rabbit oocytes for generating human clones, following confirmation that the 11 patient-specific embryonic stem cell (ESCs) lines supposedly produced by South Korean scientist Woo-suk Hwang were fraudulent.

Hwang's failure to generate ESC lines through cell nuclear transfer, despite a plentiful supply of fresh human eggs and success in producing blastocysts, should prompt a search for alternative routes, said Chris Shaw, a professor of neurology at King's College London.

Shaw, who is a specialist in motor neurone disease, plans to apply for permission to use enucleated rabbit eggs as surrogates, to create human embryonic stem cell lines. He is collaborating with Ian Wilmut, the scientist behind Dolly the cloned sheep, and they hold one of two licenses to carry out therapeutic human cloning granted in the UK.

According to the report of the committee that investigated Hwang, he had a 10 percent success rate in generating blastocysts from human eggs subjected to cell nuclear replacement.

"Under normal conditions you would expect a 10 percent success in getting cell lines from [in vitro fertilization-derived] blastocysts," Shaw said. "The fact that [Hwang] didn't get any is of great concern - there may be problems that are innate.

"Hwang has 2,000 eggs to work with - it would be difficult for people [in the UK] to get that sort of resource together. We should maybe think about an alternative source of oocytes - adult cells could be transferred into rabbit oocytes," Shaw said at a press conference in London, called to discuss the reaction of UK researchers to the Hwang debacle.

The aim would be to develop disease-specific cell lines.

"If we could get four to five lines, they will be a significant resource," Shaw said. He is in discussions with the Human Fertilization and Embryology Authority, but it is not clear if it has the jurisdiction to give approval. Among the vexed issues is the question of the status of any embryos that might be generated.

In 2003, Hui Sheng, a researcher at Shanghai Medical University in China, published data showing she had generated human stem cell lines from embryos produced by inserting the nucleus of an adult human cell into an enucleated rabbit oocyte.

Stephen Minger, a professor at King's College London who has visited Sheng's laboratory, told BioWorld International: "She was vilified for the work in the West, particularly in the U.S., where the objective of the work was not understood. I was really impressed. She spent more than 15 years working at [the U.S. National Institutes of Health] and has a very large research group [in Shanghai]."

Minger thinks that using rabbit oocytes would be a good way of enabling scientists to perfect their cloning techniques without using the rare resource of human eggs.

In theory, Hwang's fall from grace puts the UK in the lead in therapeutic cloning: A group led by Alison Murdoch, professor of reproductive medicine at Newcastle University, announced it had produced a blastocyst last May on the same day Hwang's grander claims were published in Science.

Murdoch's group did not manage to generate embryonic stem cell lines from its blastocyst. She was convinced that was because of the quality of the eggs used, which were left over from in vitro fertilization treatments. Given the apparent success of the South Koreans, the Newcastle group diverted its resources elsewhere.

"When [Hwang's] paper was published, it seemed that the techniques would be easier than we thought they would be - as long as you had a good supply of human eggs," Murdoch said. "We have problems with the supply of eggs in the UK, and so we worked on developing other sources - now it transpires the techniques are difficult."

Murdoch said the Hwang affair has set her research back a little, adding: "It's a bit uncomfortable; now the focus is back on us again. We're working in a bit of a goldfish bowl, which is pushing us to get answers, and that is not conducive to good science."

Overall, UK scientists are keen to stress that therapeutic human cloning is a very small element of the overall picture of translating stem cells into cell-replacement therapies.

"Hwang has no impact per se," Minger said. "From our perspective, cloned cell lines were on the fringe. As a scientist, this whole affair has been deeply distressing, but it doesn't affect stem cell biology, it affects science in general."

Robin Lovell Badge, an expert in developmental genetics at the National Institute of Medical Research in London, agreed. "This story is a big distraction from ongoing work. Papers are coming out regularly on new methods for producing [stem] cells, and this is being missed."

Murdoch concluded: "Nuclear transfer and cloning is a small part of the whole field. If we end up just concentrating on cell nuclear transfer, we will miss the bigger picture."