The first and last authors of a paper, published in Sciencexpress in May 2005 and hailed at the time as a major advance in producing therapeutically useful stem cells, asked to retract the work Friday, even as the first author continues to insist that the stem cell lines it shows are not a fabrication, as two of his collaborators now claim.

Science editors said they would retract the paper if all authors agree that it should happen. As of Friday afternoon, the retraction marked the latest, though surely not the last, development regarding research that has become mired in ethics and data controversies.

The paper is one of two published in Science by South Korean researcher Woo-Suk Hwang and his colleagues describing supposed methodological advances in cloning research. The first paper purported to show proof of principle that the scientists had developed stem cells from a cloned human embryo, using somatic-cell nuclear transfer; the second, that they had managed to make the process efficient enough to consistently derive a stem cell line in fewer than 20 trials. (See BioWorld Today, Feb. 13, 2004, and May 20, 2005.)

Gerald Schatten, of the University of Pittsburgh, a senior author of the second paper, and another collaborator, Roh Sung-Il, of MizMedi Hospital, have accused Hwang of forging nine of the 11 cell lines he presented in the second paper.

According to South Korean media reports, in a press conference Friday Hwang said he would retract the paper, though he continued to insist that the cell lines were not forged and problems in documentation were due to inadequate storage at MizMedi hospital. He also said that he would thaw out stem cell lines kept for cross-checking purposes and would validate his research in about 10 days.

Michael West is the chief scientific officer, chairman and president at Advanced Cell Technology Inc., of Worcester, Mass., and one of eight authors of a letter to Science, also published last week, urging Hwang to cooperate with an independent verification of his work. Asked whether 10 days would be a realistic time frame for Hwang to provide verification, West told BioWorld Today that such a reproduction would not lay to rest doubts about the work. To satisfy the scientific community, the work would have to be verified by an independent group.

"The problem is that Dr. Hwang keeps saying, Let me go back to my lab and reproduce the results.' And that misses the point," West said. "Nobody doubts that this is a workable technique. The question is whether he has actually done it or not."

Data Problems Last Straw For Paper

The announcement follows a month and a half of problems with the research bobbing to the surface; at a Science press conference Friday, editor-in-chief Donald Kennedy called it "a long and confusing and eventually disappointing few weeks."

The first problem arose in November, when it became clear that for the first paper, two of the egg donors were employees in Hwang's laboratory, and donors had been paid by a co-author of Hwang's. In response to those findings, Schatten, who was not a co-author on the 2004 paper but was senior author on the 2005 paper, announced that he would no longer work with Hwang because he had been misled. Hwang also resigned from his official posts in South Korea in late November.

In early December, it was discovered that four images in the supporting online material for the second paper were duplicates, despite supposedly showing different cell lines. At that time, though the University of Pittsburgh launched an investigation into the incident, forgery was not suspected, at least not officially; Science called the mix-up an "honest mistake," and Editor-In-Chief Kennedy said that "there is no reason to believe at the moment that it is a problem that affects the scientific outcome of the paper."

A few weeks later, though, accusations of actual forgery emerged, and Schatten demanded that his name be removed from the Science paper because of concerns that part of the data might be fabricated, and he asked first author Hwang to retract the paper. Science editors at first refused to unilaterally remove Schatten from the paper.

Although Kennedy said that "it is premature to conclude there was research misconduct," if such misconduct is found, West said it will be "the sort of thing the scientific community hates to see," because it undeniably gives embryonic stem cell critics "an excellent platform."

Nevertheless, West said ultimately it will not hinder therapeutic cloning. The technique "is a cornerstone of regenerative medicine," he said, and if Hwang's lab has not actually done the work it claimed, "there are a lot of people prepared to take up the reins on this, including our own, and do it well."

How Skeptical Is Skeptical Enough?

At the Science press conference, there was some discussion of whether the reviewers had been sufficiently skeptical of the data; Kennedy defended the peer reviewers, noting that their level of skepticism had been appropriate and there is no way to make the peer-review process absolutely foolproof. West concurred with Kennedy: "Could they have caught it? Should they have caught it? Perhaps, but reviewers are not primarily looking for fraud," he said.

Instead, the focus tends to be on whether the data support the conclusions, and whether the experimental controls were appropriate. West agreed with that focus.

"For every forger, there are 99 dedicated and honest people out there, undoubtedly including many post-docs and researchers in Hwang's lab," he said. He also noted a disquieting truth: That it is nearly impossible to catch a sufficiently committed forger - a dedicated person "could create an image almost pixel by pixel."

West also said that if it is discovered that Hwang's work is fraudulent, it would actually clarify a confusing scientific point. Basically, Hwang's big technological advance was that he tore the zona pellucida of the egg. "That gave him this amazing efficiency that no one else had seen," West said. But "none of us could make sense of that." If the report turns out to be false, it could actually advance the field in terms of scientific understanding.

Then West chuckled, and added, "I guess I'm always looking for the silver lining in things."