Korean scandal puts UK stem cell research back on level terms

For some it was like a very bad Greek tragedy, for others a hoax more naive than the Piltdown man. But Hwang Wo-suk's fall from grace puts the UK on level terms with South Korea in the race to generate embryonic stem cells from cloned embryos.

After South Korean scientist Woo-suk Hwang's claims to have produced eleven patient-specific cell lines were denounced as fraudulent, stem cell scientists in the UK pledged to renew their efforts to produce embryonic stem cells from cloned human embryos.

Amid concerns that the fraud will deter egg donors, they now want to seek out alternative sources of oocytes in which to generate human clones. Currently, the only legitimate source is of eggs removed during in vitro fertilisation (IVF) treatment. Suggestions for new supplies include allowing altruistic donations solely for research and using rabbit oocytes as surrogates.

The UK researchers were keen also to stress that therapeutic cloning is a small part of the overall push to translate the promise of stem cells into novel therapies.

A group led by Alison Murdoch at Newcastle University announced it had produced a blastocyst on the same day as Hwang's paper was published in the journal Science last May. "The way we saw it, Hwang was so far ahead of the game this was nothing else than a blip on the horizon," Murdoch told a press conference held in London to discuss reactions. "But it was not a blip in context."

The search for better eggs

The Newcastle researchers did not succeed in generating embryonic stem cells from the blastocyst, and Murdoch believed this was because of the inferior quality of the eggs used. In June she was given permission to approach women having IVF to donate eggs purely for research. "This has increased the supply, but not enough," Murdoch said. She is now seeking permission from the Human Fertilisation and Embryology Authority (HFEA), the UK regulator, to try and attract altruistic donors to provide eggs without the procedure being part of IVF treatment.

Believing that Hwang had cracked the problem of generating embryonic stem cells from cloned blastocysts, Newcastle group had diverted their resources elsewhere. "This changes our approach in that when the paper was published it seemed the techniques would be easier to master than we thought they would be," said Murdoch. "Our impression of the work was it was very difficult."

"We couldn't understand how he made it so easy. Now we know it isn't."

The Newcastle group may have moved into pole position, but for Murdoch nothing positive comes out of Hwang’s fraud. "What happened to Hwang shows us the danger of seeing it as a race. The more people who work at [cloning] the better," she said. "How can the downfall of someone - so horribly - be good?"

"The story will make other parts of the world nervous about doing this work," said Robin Lovell-Badge of the National Institute for Medical Research in London. He was just back from India where moves are afoot to start therapeutic cloning, and found researchers were now unsure about going ahead.

Similarly, Anne McLaren of the Gurdon Institute in Cambridge noted that Japanese researchers have produced embryonic stem cells from IVF embryos and want permission to do cell nuclear transfer. "I'm concerned now that the Hwang story will set them back."

Will donors be deterred?

Because the saga unfolded over the Christmas holiday Murdoch does not know yet if Hwang’s fall from grace will have any impact on women’s willingness to donate eggs in the UK. But Chris Shaw, professor of neurology at the Institute of Psychiatry in London, said, "It is difficult to propose altruistic donation in the current climate."

Shaw, an expert in motor neuron disease, works with Ian Wilmut, cloner of Dolly the sheep. They hold one of the two licences granted in the UK to carry out therapeutic cloning. "It's clear from Hwang's work that even with the very freshest eggs this is a very difficult process," said Shaw. As an alternative he proposes using enucleated rabbit oocytes as surrogates, and he is currently trying to get the HFEA's permission to do this. It is not clear if it is within the HFEA’s jurisdiction to sanction such an experiment.

It is not suggested that embryonic stem cells generated in this way could be used for treatments, but that cell lines carrying genetic defects could be powerful tools in studying a disease process and for use in drug screening.

In 2003 a group in Shanghai, China, led by Hui Sheng, published data showing it had generated human embryonic stem cell lines using embryos generated by inserting the nucleus of an adult human cell into a rabbit oocyte. "If we could get 4 - 5 lines that would be a significant resource," said Shaw. "The scientists in China have shown us that other animals might have oocytes that could promote production [of human embryonic stem cells]."

Intensification worldwide

Away from the spotlight on therapeutic cloning, stem cell research is intensifying world wide, said Stephen Minger of King's College London, citing Iraq, where scientists have generated seven or eight embryonic stem cells and have cloned sheep.

"And," he noted, Hwang's disgrace doesn't discredit Korean stem cell research." Minger has visited Hwang’s laboratory and pointed out that as well as being good at cloning, Hwang had generated stem cell lines from starting points other than cloned embryos. "It may be there is something about cell nuclear transfer that means you can’t get [embryonic] cell lines by this route."

Shaw agreed, "It would be wrong to close the door on South Korea. It would be useful to learn why they failed."