New Round of Criticism

December 10, 2005

New Criticism Rages Over South Korean Cell Research
By NICHOLAS WADE, New York Times

A new round of criticism has broken out in South Korea over the accuracy of a recent article that reported a striking advance in human stem cell research.

In the June 17 article, Hwang Woo Suk, a veterinary researcher at Seoul National University, reported that he had developed embryonic stem cell colonies from 11 patients. The article, published in the journal Science, was hailed as a major step toward the goal of treating patients suffering from many serious diseases with their own, regenerated tissues. But Dr. Hwang's research, though praised by the South Korean government, faces mounting criticism from some Korean scientists. The newest questions about the paper concern DNA fingerprint tests carried out to prove that the embryonic stem cell colonies were indeed derived from the patient in question. The test, demanded by referees for Science, was necessary because cell colonies often get mixed up or overgrown by other cells in even the best laboratories.

Usually any two DNA fingerprint traces will have peaks of different heights and alignment and different background noise. But in several cases the pairs of traces in the Science article seem identical in all three properties, suggesting that they are the same trace and not, as represented, two independent ones. If so, there could have been yet another innocent mixing up of data, as seems to have been the case with duplicate photos - an error that came to light earlier this week. But it is also possible that the cell colonies never existed and that a single DNA fingerprint from a patient was falsely represented as two traces, one from the patient and one from the embryonic cell line allegedly derived from him.

Monica Bradford, the deputy editor of Science, said that the journal had asked Dr. Hwang for an explanation and that experts probably needed to examine the original data in Dr. Hwang's possession before any conclusions could be drawn.

The new charges have also attracted attention in South Korea. Thirty faculty members at Seoul National University wrote Dec. 7 to the university president, Chung Un Chan, saying that, as experts in the life sciences, "we find a significant part of the DNA fingerprinting data is inexplicable."
They asked Dr. Chung to create a committee to investigate possible misconduct and added, "We are extremely worried that, by keeping silent, we are endangering the international credibility of the Korean scientific community, which in turn will cause irreversible damage to our country."

The University of Pittsburgh, where Dr. Hwang's American co-author, Gerald Schatten, is based, has asked its office that investigates research misconduct to look into this and other problems with the Science article.

Earlier this week the critics noted that several photographs, issued online by Science as a supplement to the June 17 article, were duplicates of one another, though they ostensibly showed 11 different cell colonies. But the duplication appeared to have an innocent explanation. The editors of Science announced that the originally submitted manuscript had 11 different photos and that the duplicates were submitted later, presumably by accident, after a request for higher-resolution copies.

Dr. Hwang did not respond to an e-mail inquiry sent yesterday. He has been hospitalized with an ulcer, said Lorenz Studer, a stem cell specialist at the Sloan-Kettering Institute in New York.

Dr. Studer, who has visited the lab several times, said Dr. Hwang had a large operation with 65 people working around the clock, many of them specializing in minute points of detail in the cloning process, and had made evident progress on cloning human cells. Noting the attacks on Dr. Hwang's work by other Korean scientists, Dr. Studer said, "It is really difficult for us to judge if there is a problem or someone who has an agenda."

Dr. Studer is studying two of Dr. Hwang's human cell lines in his laboratory but said he had not tested them and had no way of knowing if they were derived from the cloning of patient's cells or from embryos from a fertility clinic.

Though the experiments reported in the Science article were done in Seoul, the person formally most responsible for the data is Dr. Schatten, whose name appears last on the Science article, the position reserved for the senior author. Dr. Schatten recently stated that his involvement was limited to analyzing data and preparing the manuscript. Such services do not usually merit senior co-authorship, raising the question of why Dr. Hwang offered it and why Dr. Schatten accepted. Dr. Arthur Levine, the dean of the University of Pittsburgh medical school, said that Dr. Schatten was a scientist of stature and had contributed ideas to Dr. Hwang, but that "discussion doesn't ordinarily eventuate in senior authorship." He added that he knew for certain that Dr. Schatten "must be deeply regretting" having accepted the co-authorship. Dr. Schatten was not available for comment yesterday, a university spokeswoman said.

The new critique was first raised Dec. 7 by an anonymous posting on a Korean-language Web site, the Biological Research Information Center. The writer commented on the improbability of two independent DNA fingerprints' being so similar and concluded, "I cannot help but to say that there were no stem cells from the very beginning because the nearly identical fingerprinting patterns raises strongly the possibility of serious misconduct in experiments." The letter and its translation were provided by a Korean scientist at an American university who asked not to be identified because of the possibility of recrimination from the South Korean government.

Dr. Hwang has published three significant cloning advances since 2004, including the first cloning of a human embryo, and is somewhat of a national hero in South Korea. The current furor over his work arose last month when PD-Notebook, an investigative program on MBC-TV, a South Korean network, obtained human stem cell samples from Dr. Hwang and had them tested by an independent laboratory.
The results apparently did not match Dr. Hwang's, and he then refused to cooperate further with the program. The 30 young scientists who signed the letter to the president of the Seoul National University asked him to follow the University of Pittsburgh's example and set up a committee to inquire into possible misconduct. Dr. Levine agreed that Pittsburgh's committee may not be able to get very far, given that all the data is in Seoul, and that it could be logical for the two universities to work together.

If misconduct in any part of the Science paper were established, it could well cast doubt over all of Dr. Hwang's work. But his evident expertise and his generosity in helping other researchers have deeply impressed American visitors like Dr. Studer and Dr. Schatten. So the possibility that the issues raised by his critics are due to careless handling of data, in a scientific paper that has received far more careful public scrutiny than is usual, cannot be ruled out.