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Korean Scientist Said to Admit Fabrication in a Cloning Study
By NICHOLAS WADE
The South Korean scientist who claimed a stunning series of advances in cloning and stem cell research has admitted that critical parts of one discovery had been fabricated, a colleague said yesterday.
The colleague, Dr. Roh Sung Il, a co-author of a paper in the journal Science last June in which the scientist, Dr. Hwang Woo Suk, claimed to have created stem cells from 11 patients, told the Korean television station MBC, "Hwang today made statements totally contrary to what we have believed is right. " Dr. Roh added, "Nine of the 11 stem-cell lines he had said he created didn't even exist."
Efforts to reach Dr. Hwang by e-mail and telephone have been unsuccessful. A spokesman for Seoul National University Hospital told The Associated Press that he had been undergoing treatment for stress there for a week.
Associates said he would address the issue at a news conference today.
Barbara Rice, a spokeswoman for Science, said the journal had asked all of the co-authors of the disputed paper "to clarify these unconfirmed rumors that we are getting." As of early Thursday afternoon, "we have not received a response," she said.
Until the matter has been investigated, she said, "there is no rush to judgment by Science based on unconfirmed rumors."
Over the past two years, Dr. Hwang, a veterinary medical researcher who turned 53 yesterday, became a hero in South Korea and an international celebrity.
Last year he claimed to be the first to clone a human cell, inserting an adult cell's nucleus into a human egg to make embryonic cells. This year he said he had done the same thing in 11 patients, the first step to the dream of treating people with their own regenerated tissues. And for good measure he said he had cloned a dog as well, a feat that has long frustrated other clone researchers.
The first hints of trouble with Dr. Hwang's research came earlier this year, when reports emerged that women who worked in his laboratory may have donated eggs for an experiment in cultivating stem cells from a cloned human embryo. Last month, an American collaborator, Dr. Gerald Schatten of the University of Pittsburgh, severed ties with his group, citing "ethical violations" over the way the eggs were obtained.
All these achievements, and his earlier work as well, are now under suspicion.
Dr. Hwang's new troubles were presaged earlier this week when Dr. Schatten, the senior co-author of the Science article, wrote to the journal asking that his name be withdrawn from the article and urging Dr. Hwang and the other co-authors to retract it. Dr. Schatten wrote that he had "substantial doubts about the paper's accuracy" and had heard that some of the experiments had been fabricated.
Although the new disclosures are being presented as a blow for Korean science, they can also be seen as a triumph for a cadre of well-trained young Koreans for whom it became almost a pastime to turn up one flaw after another in his work. All or almost all the criticisms that eventually brought him down were first posted on Web sites used by young Korean scientists.
The young scientists were more skeptical of Dr. Hwang than was Dr. Schatten, who agreed to be senior co-author on Dr. Hwang's article this June in Science, even though all the experiments had been done in Seoul. The referees and editors at Science accepted the Schatten-Hwang article without spotting the problems that later came to light, although they did ask for extra tests that may have contributed to the denouement. Science's rival journal, Nature, accepted Dr. Hwang's report on cloning a dog.
The debacle is particularly surprising to the many American scientists who visited Dr. Hwang's lab at the Seoul National University and were impressed by the dedication of his 65 colleagues, the specialization of his lab into separate units for each aspect of cloning, and the technical skill of those who worked the micromanipulators used to suck the nucleus out of human cells.
The event that led to Dr. Hwang's downfall, after a month of sniping at certain puzzling aspects of his published work, was the posting of a pair of duplicate photos on two Korean Web sites.
One of the new duplicate photos appears in the June Science article about the 11 patients and a second in the Oct. 19 issue of a lesser-known journal, The Biology of Reproduction, where it was reported as being of a different kind of cell.
In the Science article, the cell colony was labeled as being the fifth of Dr. Hwang's human embryonic cell lines derived from a patient's cells, but in the Biology of Reproduction article it was designated as an ordinary embryonic cell line generated in the MizMedi hospital in Korea, presumably from surplus embryos created in a fertility clinic.
Critics cited the duplication as confirming suspicions that Dr. Hwang had never successfully cloned any adult human cell and that his Science photos might instead show just human embryonic cell lines derived in the usual way from fertility clinic embryos.
Dr. Roh, the superintendent of MizMedi, was asked by The New York Times on Wednesday to say which type of cell was represented in the photos. Dr. Roh was the senior author of the article in Biology of Reproduction, which Dr. Hwang did not sign. Dr. Roh replied by e-mail that the photo had come from a large computer file of stem cell colonies and that a colleague had accidentally chosen one of the patient-derived colonies to illustrate the Biology of Reproduction article.
Dr. Roh had heard about the error just two hours previously, he wrote in his e-mail message, and had already written to the editor of the journal requesting that the article be withdrawn immediately. "I really apologize again to have made a big mistake as a principal investigator," Dr. Roh wrote.
Critics had already begun to screen Dr. Hwang's previous research for errors. A few days ago they began questioning an article he published in Science last year, in which he announced the first establishment of a human embryonic cell line from an adult cell. The paper in Science this year claimed a greatly improved efficiency in the same technique, and was presented as the first step toward treating patients with their own regenerated tissues.
The criticism of the 2004 paper was that in the published DNA fingerprints of the donor and the cell colony derived from her cells, the trace moves backward a little at certain points. But since the trace is made by a pen moving across a paper strip, the pen cannot usually reverse its movement. The reversals, if real, would point to an abnormality in the machine or to the traces being hand-drawn, in the view of critics. Manual changes would be potential evidence of data manipulation.
John Gearhart, a stem cell specialist at Johns Hopkins University, said the trace was "certainly odd, to say the least."
Robert Lanza, of Advanced Cell Technology, said, "The traces appear to be hand-drawn." But another stem cell researcher, Rudolf Jaenisch of the Whitehead Institute, said that, though not an expert in such matters, he could not detect any problem with the traces.
If there were a serious flaw with the 2004 paper, that would apparently mean that no human embryonic stem cell line has yet been created by nuclear transfer, the insertion of an adult cell's nucleus into a human egg. Dr. Jaenisch said he could not recall any other published paper on the subject besides Dr. Hwang's.
But the fact that no one else has yet replicated Dr. Hwang's work does not imply it cannot be reproduced, said Dr. George Daley of Harvard University. He has been waiting a year to get the necessary approvals to proceed along the same lines but he could see no technical obstacles to cloning human cells.
Dr. Daley said he had been impressed during a visit to Dr. Hwang's lab in Seoul at the scale of the operation and the speed and efficacy of the people who worked there. "I have no reason to doubt their technical efficiency," he said. "If there was any lab capable of doing what they said they did, it would be his lab."
Monica Bradford, who as executive editor of Science oversees its selection and publication of research papers, said the situation was distressing for people at the journal, "because this was such a significant result and held so much hope for a lot of people and particularly for Korean science," and also because "it's spinning out in the press and no one knows the truth."
But she said even if the work ended up being retracted, it would not challenge the journal's review process, in which other experts are asked to assess the strengths and weaknesses of research reports submitted for publication. Though the system has its flaws, "there is no other process that has worked as well," she said.
She added that "basically a reviewer has to begin with a position of trust, that everything they are seeing is real and not fabricated. And if someone is good at fabricating, it would be hard to know the difference."
She said Science publishes 800 to 900 papers a year and, on average 4 or 5 end up retracted, usually "because of human error," not fraud or deception.
Ms. Bradford said she did not believe reviewing standards had slipped even as journals compete for papers that will make news. "I have been at Science now for 17 years and I have been through quite a lot of hot papers and I don't think the practices have changed any," she said.
She conceded that the choice of reviewers can have a powerful influence on whether a paper is accepted or rejected for publication, but said it would be unethical for journal editors to choose reviewers with an expectation that they would decide one way or another.
In any event, she went on: "No journal wants to be in a situation where their hot papers turn out to be wrong. You don't stay at the top long if you are publishing bad science."
And defects in findings eventually turn up as other researchers try to replicate or build on them, she said. "If that cannot happen, scientists start to question the data."
Cornelia Dean and James Brooke contributed reporting for this article. |
