Science takes stock after clone row

By Paul Rincon
BBC News science reporter

The revelations about Dr Hwang Woo-suk, South Korea's cloning and stem cell pioneer, have built into one of the biggest scientific scandals of recent memory.

Professor Hwang was a national hero in South Korea

His fall from grace began with allegations about the practices he employed to procure eggs for his work.

Dr Hwang subsequently stepped down as professor at Seoul National University (SNU) after an investigating panel said a key paper on custom stem cells was, in large part, fabricated.

Now, the panel has concluded that his landmark claim in 2004 to have produced the first stem cell line from a cloned human embryo was also false.

The fields of cloning and stem cell research could clearly have done without such revelations, given the controversy they already stoke.

But how much impact has the affair had on research in these areas?

"I don't think it has set back research, but clearly we weren't as far forward as we thought we were," says Jack Price, professor of developmental neurobiology at the Institute of Psychiatry in London.

Writing on the BBC News website, Dr Stephen Minger, a stem cell biologist at King's College London, agreed with these sentiments.

But he commented: "In a way, this sorry affair damages science more than it damages stem cell research - it could have been cosmology, or physics or any other area of cell biology."

The fallout from the revelations about Hwang's human cloning work make little difference to that field, scientists say, because another group at Newcastle University has since cloned its own embryo.

"Whether or not the cloning works has very little impact on most of the research going on into human embryonic stem cells," Professor Peter Andrews, a stem cell expert at the University of Sheffield, told the BBC News website.

"Most of the work on understanding the biology of these cells, how to use them, how to turn them into particular cell types for eventual applications, will come out of work on cell lines derived from surplus embryos not cloned ones."

Master cells

Stem cells are the body's "master cells" and have the ability to produce all manner of tissues.

This has led scientists to investigate their potential to be used to replace the cells that are missing or destroyed in conditions such as heart disease and diabetes.

Dr Hwang had enjoyed national hero status since 2004, when he announced that his research team cloned 30 human embryos and used them to produce stem cells that could one day help treat a range of diseases.

I don't think it has set back research, but clearly we weren't as far forward as we thought we were Professor Jack Price, Institute of Psychiatry

In May 2005, Dr Hwang and his colleagues claimed to have used a cloning technique known as somatic cell nuclear transfer to make stem cells that were tailored to match individual patients.

But by November allegations had surfaced that the SNU professor used unacceptable practices to acquire eggs from human donors.

Other groups have since produced cloned embryos

The following month, Dr Hwang was forced to resign as professor after a panel of colleagues concluded he had fabricated research on custom stem cells. They concluded there was no evidence the stem cells came from patient-specific clones as Dr Hwang reported.

In January, the panel completed Dr Hwang's disgrace, judging that research in his landmark paper from 2004 was also fake. The nine-member panel concluded it was "written on fabricated data to show that the stem cells match the DNA of the provider although they didn't."

The researcher, however, has maintained that the science behind his work was sound, and that his country's scientists were still leading the field.

"I emphasise that patient-specific stem cells belong to South Korea and you are going to see this," Hwang said in December.

Efficiency question

And from a biological standpoint, says Jack Price, there are no fundamental reasons why embryonic stem cells cannot be tailored to individual patients. So it should simply be a matter of time before a team repeats Dr Hwang's "first".

But the efficiency with which such cell lines are made will determine whether such a technique can be of clinical use.

Some Koreans have rallied in support of Dr Hwang

"I personally have doubts whether creating personalised stem cell lines will be a practical and cost-effective means of treating most serious diseases, as and when we get to using embryonic stem cells in regenerative medicine," says Peter Andrews.

"But there may be particular conditions in which that could still be important."

Dr Huseyin Mehmet, reader in developmental neurobiology at Imperial College London concurs, adding: "It's good to have a fall-back treatment where nothing else can be done," he said.

"For example, you might have a patient with a very problematic immune system. There are certain diseases that one can imagine might be very difficult to match.

"But it has been worked out that for the vast majority of patients, 500 different stem cell lines will be enough to cover the whole population of the world in terms of our immunological diversity."

Other obstacles

However, deriving embryonic stem cells from somatic cell nuclear transfer is likely to be of importance in understanding the mechanisms which cause cells to switch back and forth between the undifferentiated and differentiated states.

They should also be useful for creating "disease models" in the lab. This involves making stem cells from patients with genetic characteristics of particular diseases in order to develop therapies.

Researchers are keen to point out that Dr Hwang and his colleagues did not address many of the biggest obstacles to the development of therapies based on embryonic stem cells.

Reliably directing the differentiation of stem cells into other tissue types remains a significant hurdle for researchers. Animal studies have shown that simply injecting "naive" stem cells into the body can cause the formation of tumours.

Whatever the effect of the scandal on the fields of cloning and stem cell research, questions are now being directed at Science magazine, which published the 2004 and 2005 manuscripts; and at the process of "peer review" which it, and other leading journals, use to screen papers before they publish them.

That process is supposed to ensure that any study's methodology is sound and that interpretation of data does not go beyond what can be reasonably justified. But, as the Hwang affair shows, it is not foolproof and certain things have to be taken on trust.

But it has been suggested that on particularly contentious or high profile studies, reviewers should do more than just read through manuscripts to check they add up; could materials also be submitted for independent analysis and verification?

Some in the field think that insisting on replication of data by an independent group as part of the review process could be a step too far.

Colin McGuckin, professor of regenerative medicine at Newcastle University, UK, commented: "We don't want to become bureaucratic, because that will hold up everything. But sometimes as a scientist, your biggest critics will be in the organisation you work at. They're the ones you should look to for advice."

The affair may also force scientists to look afresh at how scientific success is measured.

"There is so much pressure internationally on a scientist to publish their research in peer-reviewed journals. You get nothing for coming second," says Dr Mehmet.

"If you publish, like Hwang did, in a high impact journal, it gets very widely read. And unfortunately, advancement in the university sector and research financing from grant-funding bodies rely heavily on the impact factor of an individual's research."

Amazing facility

Impact factor is a measure of importance of scientific journals. It is calculated each year by the Institute for Scientific Information for those journals which it tracks.

Dr Mehmet points out that this system can be unfair because considered, detailed work that can take a long time to complete is published in specialist journals with lower impact factors.

Scientists admit that few people raised suspicions about Dr Hwang's work.

In fact, there was good reason to believe that Hwang might have succeeded in an area where others were making slower progress, experts say. The South Korean government had reportedly ploughed more than 26 billion won ($26m) into Dr Hwang's research.

In 2004, Professor Price visited Hwang's facility in South Korea: "It was amazing," he says, "as close to a cottage industry in stem cells as you can get. So many people, so many resources. They were working very hard on this. I was prepared to take that on face value."