Correction Appended
Dr. Hwang Woo Suk has been under fire because of questions surrounding the validity of papers he helped write on stem cell research.
A microscopic photo of what a South Korean research team had claimed showed cloned human embryos used to generate stem cells.
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 were 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."
But in a press conference this morning in Seoul, Dr. Hwang defended his work, saying he had proof of his success. He said the patient-tailored stem cells had become badly contaminated but that five frozen stem cells were being thawed for analysis.
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." Dr. Hwang, at his news conference, said he had asked Science to withdraw the article as a result of the uproar.
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.
This morning, Seoul National University Hospital said Dr. Hwang had been hospitalize there for a week for treatment for stress and was released today. Later, when asked at the press conference why Dr. Roh would have said he had faked some of his work, Dr. Hwang said that Dr. Roh had visited him at the hospital yesterday and raised concerns about the research. Dr. Hwang said he had agreed that some of the work needed to be verified, and that he expected to accomplish that in 10 days. But he said: "We retain our original core technology. We found out later that our management had been poor and as the head of research I feel a grave responsibility."
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 to 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, although vigorous reporting by MBC television and the online newspaper Pressian also played a leading role.
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.
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's statements make that now seem exactly what happened.
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 earlier, 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," he wrote.
He did not reply to an e-mail message seeking his comment on critics' demonstration of how the 11 photos in the Science article could have been generated from just two cell colonies. But yesterday he told the Korean news media that Dr. Hwang had confessed to him that the Science photos in fact showed Dr. Roh's fertility clinic cells, and not cells derived by Dr. Hwang from the adult cells of patients.
In an interview this week on MBC, Dr. Kim Sun Jong, a junior colleague of Dr. Hwang, said his boss had instructed him to take two photos of Dr. Roh's clinic-derived stem cells and present them as evidence in the Science paper that 11 cell colonies had been successfully derived from patients.
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 was 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. "Right now it is very confusing for all of us and very sad," said Jose Cibelli, a cloning expert at Michigan State University and a co-author of the 2004 article.
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."
Dr. Hwang reported in August this year that he had cloned a dog. His brief article in the journal Nature, also with Dr. Schatten, shows two look-alike dogs but offers very little data to prove they are true clones and not identical twins produced by embryo splitting. Dr. Arthur Levine, the dean of the University of Pittsburgh medical school, said that a university committee exploring possible misconduct with the June 2005 Science article would include the Nature dog paper in its inquiry.
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.
