Climate Audit

I’ve planning to discuss Nature and Science policies on archiving and due diligence, I’ve got lots else to do, but have gotten sidetracked in the fascinating details of the unfolding of the Hwang controversy. Here’s a preliminary account.

Nature and Science
Hwang’s fame is based on three articles in Nature and Science. On March 12, 2004 in Science, Hwang et al., in a a paper entitled “Evidence of a Pluripotent Human Embryonic Stem Cell Line Derived from a Cloned Blastocyst”, reported the first stem cells obtained from a cloned human embryo. This was named by Nature at the end of 2004 as one of the top scientific events of the year. Earlier this year, on June 17, 2005, he followed this up with a claim to have the first patient-matched embryonic stem cells, having produced 11 new human embryonic stem (ES) cell lines that carried the genetic signature of patients with diabetes, spinal cord injury, or a genetic blood disorder (titled “Patient-Specific Embryonic Stem Cells Derived from Human SCNT Blastocysts”. Abstract. The paper not only seemed to validate the group’s claim a year earlier that it had created a single cell line from a cloned human embryo, but it also reported a huge increase in efficiency for the technique. Gerald Schatten of the University of Pittsburgh was a senior coauthor of this paper. A few months later on August 4, 2005, he reported in Nature (Lee et al.) that he had cloned a dog (“Snuppy”) from adult somatic cells B.C. Lee et al., “Dogs cloned from adult somatic cells,” Nature, 436:641 August 4, 2005.

In October 2005, Seoul National University (SNU), where Hwang was a professor, launched the World Stem Cell Hub, headed by Hwang.

Buying Eggs
After Hwang and his colleagues announced in 2004 that they had derived stem cells from a cloned human embryo, a news article in Nature a couple of months later quoted a Ph.D. student from Hwang’s lab saying that she and another junior colleague donated eggs for the experiments. She later retracted her statement and, in a subsequent Science story, Hwang and a colleague denied that any lab members had donated eggs. In a subsequent Science story, Hwang and a colleague denied that any lab members had donated egg. Reference The matter seemed to peter out.

Korean Times reported that, in June 2005, an investigative reporting program of MBC, a major broadcaster in South Korea, received a tip that there is a chance that Hwang’s team had violated ethics codes and his 2005 paper in Science on tailormade stem cells is fraudulent. Their investigation led to the preparation of two documentaries, only one of which (the one on eggs) was shown and to great controversy in Korea and the unravelling of Hwang.

The first international indication of problems came on November 12, when Gerald Schatten of the University of Pittsburgh ended a 20-month collaboration after learning that Hwang had “misrepresented” facts about where donated oocytes had come from. Schatten declined to comment to The Scientist, but other representatives of institutions such as Harvard and the University of California, San Francisco, told The Scientist at the time they would also be hesitant to collaborate with Hwang.

A few weeks later, South Korea’s JoongAng Ilbo newspaper reported that Schatten had asked Hwang for a half share in the patent for patient-specific stem cell cloning six weeks before his withdrawal from the project.

On Nov. 21, 2005, on the eve of screning of a documentary by MBC network in Korea, Roh Sung-Il, a senior co-author of Hwang’s and head of a Seoul fertility clinic (MizMedi Hospital), admitted compensating 16 donors of the ova used in Hwang’s stem cell research. He stressed that Hwang had no prior knowledge of this. Sung Il Roh, chief of the MizMedi fertility clinic, said he paid for the eggs out of his own pocket, according to a report in Chosun Ilbo. He said he did so without informing Woo Suk Hwang, the high-profile stem cell biologist who used the eggs in his research and has been embroiled in controversy in the 10 days since his American collaborator broke off relations and charged the Korean team with unethical behavior. … According to Roh’s published comments, the payments were not illegal at the time, though such payments have been banned since January 2005. Science magazine’s editor in chief, Donald Kennedy, said that the journal would run a correction if it proved true that the published disclaimer about egg payments was false. Emphasizing that he had no information to suggest the science Roh described in that report is invalid, he said no retraction would be called for. At the time, it was noted that it was still at issue whether any of the women who gave up eggs for the research were junior members of Hwang’s laboratory staff, as some unconfirmed reports have suggested — an arrangement widely judged as unethical because of the possibility of coercion.

On Nov. 22, 2005, the first segment of the PD Diary documentary was broadcast by MBC, including strong evidence that Hwang’s team used ova extracted from its junior researchers.

This led to an immediate reaction by Hwang (reported by Korean Times – see also here).

On Nov. 24, 2005, Hwang admitted to ethical lapses and announced that he will resign from all public posts. Hwang, who conducts his research at Seoul National University, admitted on Thursday (November 24) that two women working in his lab as junior scientists had given their eggs for stem cell research in 2002 and 2003, a fact he had been aware of, but denied–in May 2004. According to reports from Korean news outlets, Hwang told a press conference that, to take full responsibility for the scandal, he would resign from “all posts,” including leading positions at the Seoul stem cell team and the World Stem Cell Hub, which opened last month. He said he would, however, continue his research. “I am very sorry that I have to tell the public words that are too shameful and horrible,” he was quoted as saying by the BBC. Hwang said the staff donations had taken place without his knowledge, when the researchers suggested making voluntary donations to ease ova shortages. “I clearly turned it down.” Hwang said at the press conference that he later learned that the women had donated the eggs under false names.

There was a huge backlash to the program in Korea and international support for Hwang. The Korea Herald reported:

On Nov 28, Sunday night, some 100 or more advocates held a vigil in front of the MBC-TV television channel building, threatening to boycott advertisers on the channel, which had broadcast a program questioning the source of the eggs used in his research, the Korea Herald reported. The paper also reported that more than 700 women had expressed a wish to donate ova since the launch of a private foundation last Tuesday to facilitate legal and ethical donations of human eggs for research purposes.

The next day, on Dec 1, 2005, MBC was being widely criticized for being unpatriotic and all of its advertising for the Tuesday program was dropped.

On Sunday, Dec 4, 2005, rival television network YTN reported that MBC had supposedly intimidated junior researchers, further fueling the backlash against MBC:

One of the junior staffers under Korean stem cell pioneer Hwang Woo-suk on Sunday said the nation’s broadcaster MBC threatened him to get information unfavorable to Hwang. Kim Son-jong, the feeder cell expert who is now at the University of Pittsburgh, on Sunday made the remarks during an interview with the all-news cable channel YTN. “MBC producers visited me on Oct. 20 and insisted Hwang’s research is all fake and his two papers published by Science will be canceled. He even said Hwang will be arrested,” Kim said. “Then he argued the police investigation would start in the United States and urged me to reveal everything I know under condition of protecting me from the probe,” he added. His comments are expected to hurt the credibility of MBC, which has questioned the authenticity of Hwang’s research, as well as the scientist’s ethics.

On the same day (Dec 4) in its 9 pm newscast, MBC apologized for its actions. By Dec 7, MBC faced a full-fledged crisis. It announced that it had put the weekly news magazine “PD Notebook” on hold indefinitely, three days after the broadcaster apologized for the use of threats in the process of investigating Prof. Hwang Woo-suk’s stem cell cloning research. The crisis was summarized by Joongang Daily as follows:

A Sunday report by TV news channel YTN featured Dr. Hwang’s former co-researchers saying they had been threatened by the producers to speak unfairly about the stem cell researcher. MBC quickly apologized for the producers’ unethical practices but the aftermath has been severe. Advertisers are deserting the TV network and its ratings are plummeting. An Internet movement has urged viewers boycott MBC. Alarmed by the situation, the broadcaster decided at an executive meeting yesterday it will cancel PD Notebook. The program was suspended earlier this week and the corporation had said it would resume airing its weekly broadcast on Tuesday. PD Notebook’s fate, however, changed after the in-house meeting. “The measure should be interpreted as terminating the program,” a spokesman for MBC said. The program has aired for 15 years. MBC President Choi Moon-soon indicated yesterday that he may step down from his post. “I will try to resolve this situation, without clinging to my post,” Mr. Choi said. It may be too late for MBC to regain its audience. Ratings for News Desk, MBC’s main 9 p.m. news program, dropped to 5.8 percent Tuesday, according to TNT Media Korea. The program formerly rated around 10 percent or more. MBC also faces investigations by the prosecution. The Seoul Central District Public Prosecutors Office said yesterday it has launched investigations after receiving a petition from a civic group. Park Eui-jeong, a 77-year-old activist, filed a petition to the prosecution, saying MBC has hindered Dr. Hwang’s work and defamed him. “We will carry out the probe under the regular procedures,” a prosecution source said.

As a result of the backlash, the second instalment of the exposé, about scientific fabrication was cancelled, with its key staff receiving suspensions.

In addition to the backlash within Korea, Hwang received international support. Bloomberg reported:

As South Koreans rallied behind Hwang, scientists and ethicists said his mistakes can be overcome and he is likely to return to stem cell research. Hwang’s lab “is ready to be the world’s leader in the field,” said Leonard Zon, a Harvard Medical School stem cell researcher who is also former president of the International Society of Stem Cell Research, in a telephone interview. “It’s up to Dr. Hwang to convince the world that future research is going to be done in an ethical way.” … Working in Hwang’s favor is that his scientific integrity remains intact, ethicists said. “The guy didn’t fudge any scientific research,” said Richard Bernstein, a University of Chicago law professor. “It sounds like a personal tragedy, but it doesn’t sound like a hanging offense.”…
Guidelines released in April by the U.S. National Academy of Sciences say that stem cell researchers should know the source of all the eggs and tissues they use. The guidelines also say that egg donors should never be paid or compensated. “You don’t want rich people living off poor people who are selling body parts to stay alive,” said George Annas, a Boston University ethicist, in a telephone interview. Expecting women who go through the pain and trouble of donating eggs without payment is unrealistic, said Robert Lanza, medical director of Worcester, Massachusetts-based Advanced Cell Technology Inc. As a lack of egg sources pushed him behind Hwang in the race to produce stem cells for biomedical research, Lanza formed an advisory board to set guidelines on how to compensate egg donors. The board decided that about $4,000 was enough to compensate donors for pain, lost time and child care when necessary, said Ronald Green, who helped develop the guidelines. The payments encourage women to be up-front about their motives for donation, and researchers to document their sources, said Green, director of Dartmouth College’s Ethics Institute.

Ronald Bailey at reason.com said “Paying for eggs is not illegal in the United States and the case that it is ethically wrong is far from clear”, noting that Korea had no applicable law until January 2005. Bailey also noted payments were allowed in the U.S. (as long as it wasn’t too much.) Only in mid-2005 had the National Academy of Sciences promulgated guidelines against any payments.

Hwang himself attempted to contain the damage with a number of interviews, including a Dec 5 interview with Time Asia.

The Korean Blogs
While Western scientists were still supporting Hwang, young Korean scientists posting on a blog and (perhaps) interacting with PD Diary at MBC, are credited with actually looking through the details of his work and finding evidence of fabrication.

The New York Times reported that, already in November, PD Diary 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.

On Nov. 30, the producer of PD Diary said that the (cancelled) second program would expose problems in the authenticity of Hwang’s results. In response, Hwang’s coauthor, Lee, offered up peer review by Science as support for their findings.

Choi also hinted Science did not sufficiently examine the authenticity of Hwang’s paper on genetically tailored stem cell batches, printed as a cover story by the illustrious peer-reviewed weekly in May. “Science cannot do everything. Our program will also shed light on that (the review process by Science)”, Choi said. He added everything will become clear after his team televises the program. Choi said he is sure of his case because his team has delved into it for longer than six months.

In response, Hwang’s team members such as professor Lee Jeong-ryul at Seoul National University flatly downplayed the claim. “The experiment was reviewed and confirmed by Science through very strict processes. If we cannot believe it, what other journals can we believe?” Lee said.

By early December, the Korean blogs were aflame with problems – three of which seem to have been identified by this point: identical panels in the 2005 Science paper; suspicious DNA fingerptinting in the 2005 Science paper; suspicious duplicate photos in the 2004 Science paper.

Duplicate Photos in the Online SI to the 2005 Science Paper
On Dec. 10, the Ney York Times reported:

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.

The Scientist reported that Hwang himself alerted Science to the fact that there were duplicate panels in the article on December 4.

On Dec 6, Katrina Kelner, Science’s deputy editor for life sciences, said that it appeared the duplicate panels were not part of the original submission but had been sent in response to a request for high-resolution images after the paper had been reviewed. “From the information that we have so far, it seems that it was an honest mistake,” she says. “We have no evidence that there was any intent to deceive.”.

Science itself reported:

The figure in question is supposed to show patterns of expression for a range of ES cell markers in the 11 cell lines. But it contains four pairs of apparently duplicated images, even though they are labeled as showing different cell lines. Gerald Schatten of the University of Pittsburgh in Pennsylvania, who was the corresponding author on the paper and provided the high-resolution images to Science, declined to comment. A university spokeswoman said that the university’s office of research integrity had begun an investigation. Schatten and his lab members are cooperating, she said, “and are carefully going through the data we have access to determine how it could have happened.” Rudolf Jaenisch of the Whitehead Institute at the Massachusetts Institute of Technology in Cambridge, says he still has confidence in the reported results. “I believe that this is an extremely important study and I have no reason whatsoever to question any of the published data,” he says. Kelner says that Science’s inquiries are ongoing and that the journal would issue a correction once the editors were satisfied they understood.

This problem was reported here as follows:

But she [Kelner] said a review of the journal’s files had shown that in Hwang’s original submission, the photos of the 11 human cell colonies were all different. The journal’s referees were sent the original submission, so they could not have spotted the duplicate photos that were later published. The duplicates must have been substituted at some later stage, but how the change occurred is not yet known. The journal is about to publish a correction to Hwang’s 2004 article, which said that donors of the human eggs had not been compensated. The correction will say that each donor was paid $1,400.

A more critical view of this problem was reported in an English-language blog on December 6 here.

The most recent tidbit about Hwang’s controversy is that some pictures sent to the Science along with the second article were found to be wrong. Some pictures were generated from others by shooting from different angles and enlarging. Hwang’s team acknowledged that those pictures are from the same sample. They claim that those were simple mistakes. Hardly! These are pictures of their prized stem cells. And, these pictures prove the state of those cells. How can they mix up such important experimental results? What other simple mistakes were made? Maybe some observations? Additional experiments done to verify these are indeed stem cells?

DNA Fingerprinting
The next shoe to drop related to issues concerning DNA fingerprints, again first raised on Korean blogs. The New York Times reported on Dec. 10:

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.

Elsewhere they reported:

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 blog postings led immediately to a demand by faculty members at Seoul National University for an investigation reported here:

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.”

By now, even Science was seeking an explanation:

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.

Nicholas Wade’s New York Times article of December 10 is a good contemproary report.

On Dec 11, Perssian, an online Korean source, reported fabrication.

The Scientist reported that, on Dec. 12, Seoul National University had undertaken an investigation of the 2005 paper:

Seoul National University (SNU) has agreed to the request of stem cell researcher Hwang Woo-suk to investigate claims his team had fabricated photographs of stem cell samples in a groundbreaking paper in Science in May. In the meantime, scientists are questioning whether the seemingly ever-growing controversy over Hwang’s work will have lasting repercussions on stem cell research overall. At a press conference today (December 12), Roe Jung-hye, dean of SNU’s Office of Research Affairs, said that a 10-member investigation panel would focus on whether the Korean researcher fabricated figures of 11 personalized stem cell samples described in the paper — and whether the patient-specific stem cells really exist, according to local media….But Pressian, a Seoul-based online news site, reported on Sunday that Hwang had ordered a subordinate to fabricate photos of nine stem cell batches from just two cell lines for submission to Science. The news service made the claim on the basis of transcripts it acquired from an interview between a member of Hwang’s team and reporters for “PD Notebook,” an investigative news program for Korean national broadcaster MBC. The Korea Herald reported that the transcript included the following quote from the team member: “This April, Hwang made me create many pictures with two stem cell lines.” MBC decided not to broadcast the program, citing the fact that PD Notebook staffers had used coercion and other unethical practices when interviewing other Hwang researchers.

On Dec. 14, 2005, Schatten asked Science to remove his name from the list of co-authors of the paper.(info received on weekend10-11)

“My careful re-evaluations of published figures and tables, along with new problematic information, now casts substantial doubts about the paper’s accuracy,” Schatten wrote. “Over the weekend, I received allegations from someone involved with the experiments that certain elements of the report may be fabricated.”

On Dec. 15, coauthor Roh Sung-il gave an interview reported here and here and here that 9 of 11 stem cell lines were faked:

Roh also told MBC television that Hwang had pressured a former scientist at his lab to fake data to make it look like there were 11 stem cell colonies. Roh said nine of the embryonic stem cell lines Hwang had claimed were cloned in the paper were faked, and the authenticity of the other two was unknown.

The New York Times reported this as follows: , also here

In an interview yesterday (December 15) on the Korean national broadcaster MBC, Hwang’s research collaborator and co-author, Sung Il Roh, said no patient-specific stem cells exist. “When I visited Hwang in hospital early this morning (Thursday), Hwang said there were no cloned embryonic stem cells at all,” said Roh, head of infertility clinic Mizmedi Women’s Hospital, in an interview quoted in the Korea Times. “I have waited, thinking that Hwang would announce everything himself since only he is eligible to put a halt to all the suspicions,” Roh said. “But I decided to go public because Hwang today made comments totally contrary to what we have believed is right. I need to clear away people’s suspicion and anguish.”

On another Korean television channel, Roh said 9 of 11 stem cell lines reported in the paper were faked, while two had been frozen and their current status was unknown. … The Korean Times also quoted Wang-jae Lee at Seoul National University (SNU) as confirming Roh’s claims. Lee was expected to lead the university’s investigation panel into Hwang’s research. “We already learned there are no embryonic stem cells and Prof. Ahn Cu-rie (Hwang’s associate) also knows it. We can declare today as a day of national infamy,” Lee said in the paper. Hwang publicly admitted that, after more than a year of denial, he had violated international ethics guidelines by using eggs from two female scientists in his lab.

But one of his co-authors, Roh Sung Il, said the data were fraudulent. One question was whether photographs, described in the paper as stem cells derived from cloned human embryos, were frauds. Roh said they were from a computer file of stem cells and not derived from cloning experiments

On Dec. 16, 2005, Hwang held a press conference and said that he has asked for approval of the paper’s retraction from Science from its co-authors after admitting partial data manipulation. However, he argued that the team did produce the stem cells and hinted that some coresearchers may have switched the stem cells provided to MBC with different stem cells from MizMedi Hospital.

The Washington Post reported that Roh then called his own press conference:

Roh called his own televised news conference after Hwang’s, in which he called Hwang a “liar” looking for a scapegoat. Hwang “tries to beat truth with hypocrisy and cheap tricks,” Roh was quoted as saying in the International Herald Tribune. “Dr. Hwang is a narrow-minded man who doesn’t have the courage to admit that his paper was made with fabrication.”

On Dec. 16, Science said that Hwang had requested a retraction of a headline-grabbing paper on patient-specific human stem cells noting that Hwang’s team had earlier told Science some duplicate photos of the same stem cell colonies were accidentally printed in the journal and presented as separate colonies, a mistake the editors have said did not affect the findings. Also see here.

On Dec 22, Hwang reportedly submitted a request for investigations at a Seoul prosecution office. In the request, Hwang claimed that stem cell lines were stolen from his lab, arguing that “his patient-tailored stem cells were changed with ordinary stem cells stored at MizMedi Hospital.”

The Seoul University Panel issued its first preliminary report on December 23, stating that 9 of 11 stem-cell lines had been fabricated, raising doubts on the others:

Investigators found that Hwang had used two stem-cell lines to fabricate data that made it appear as though he had produced 11 lines matched to specific patients by using cloned human embryos. Even the other two stem-cell lines must be examined to determine if they were produced by cloning or taken from existing human embryos.

Reuters reported this as follows:

The committee designated to review ethical and scientific aspects of the landmark 2005 paper by Hwang and co-authors in Science has determined that the material was intentionally fabricated. Specifically, Reuters reports that the panel found that “key findings in their paper on producing tailored embryonic stem cells were fabricated.” The investigatory results are preliminary, awaiting confirmation from DNA testing that will also help determine the validity of the two remaining cell colonies.

Bloomberg Asia:

But only two of Hwang’s 11 claimed stem-cell lines existed when he submitted his landmark 2005 paper to the journal Science magazine, said Roe Jung Hye, dean of research of affairs at Seoul National University said during a press briefing today. AP: “Based on these facts, the data in the 2005 Science paper cannot be some error from a simple mistake, [and] cannot be but seen as a deliberate fabrication to make it look like 11 stem-cell lines using results from just two,” the university panel said. Schatten remains silent as does Pitt.

Korean Times:

South Korea’s cloning scientist Hwang woo-suk fabricated data for his 2005 paper on tailor-made stem cells in the U.S. journal Science in May, an investigation panel said on Friday.

Making an announcement of its initial probe, the panel organized by Seoul National University (SNU) said Hwang faked results of at least nine of 11 stem cell lines he claimed to have created and called Hwang’s deliberate deception an act that “damages the foundation of science.”

“As of March 15, when Hwang presented the paper to Science, his team inflated the number of tailor-made stem cells to 11 with only two cell lines,” said SNU Prof. Roe Jung-hye, who made the announcement at a press conference. Roe said Hwang’s team doctored data such as photographs for 11 cells with just two cell batches and conducted DNA fingerprinting tests by splitting the same cells from a patient into two tubes, which will show the same fingerprint traces as if they were cloned cells. “We are not sure whether or not the two cell lines are cloned ones from patients. Since we asked for DNA fingerprinting tests for them on Thursday, the question will be solved in days to come,” she added. This means Hwang’s team might have the ability to get embryonic stem cells cloned from patients, the technology that would open the door to customized cell therapy for incurable diseases.

Duplicate 2004 Photos
The Korean blogs had also identified problems with a photo in the 2004 Science paper reported here by the Korean Times. The photo is shown below:

Original Caption: The lower part of picture B, a stem cell obtained from a fertilized egg at Mizmedi Women’s Hospital, exactly overlaps with the upper part of picture D, a cloned stem cell. This shows photos of the two cells were taken in the same culture dish. [Update: SM – I’ve been informed that the original caption should have referred to “stem cell colonies“]

The Korean Times reported this as follows on Dec. 19:

it was a group of young Koreans scientists who assiduously brought all the charges to light, posting their criticisms of Hwang on a Web site. Tenacious reporting by MBC and online outlet Pressian also dogged the story, the Times noted. It all broke open when someone posted a pair of duplicate photos to two Korean Web sites. One was from Science and claimed to represent one of the lines Hwang’s team had derived from a cloned embryo using somatic cell nuclear transfer. The other, identical, photo was from the journal The Biology of Reproduction and was labeled as an ordinary embryonic cell line derived from fertility clinic embryos.

The nation’s young scientists made the allegation at the Web site of the state-backed Biological Research Information Center (bric.postech.ac.kr), which played a pivotal role in pinpointing manipulations at Hwang’s 2005 paper on patient-specific stem cells. They claimed a cloned human embryonic stem cell photo in the 2004 paper exactly overlaps with that of a stem cell made by Mizmedi Women’s Hospital, which was presented to another journal before Hwang’s.

The scientists at the BRIC site argued that the overlapping means Hwang’s team took a picture of a cloned stem cell with a Mizmedi stem cell, which is not at all probable….

A research lab at Seoul National University College of Veterinary Medicine is disorganized and empty as the university’s investigation panel accelerates the probe on the stem cell data fabrication scandal, Monday. “If you made a cloned embryonic stem cell for the first time in the world, would you take its picture with another ordinary stem cell? This shows Hwang also doctored photos in the 2004 paper,” said a scientist who posted the picture in question.

In another Korean Web site, biologists also demonstrated a stem cell picture from the 2004 paper, which they contend is a duplicate of that of a Mizmedi stem cell. The allegations stunned Hwang supporters such as Maria Biotech head Park Se-pill who established stem cells from frozen embryos in 2000 for the third time in history. “Up until now, I have believed Hwang did derive cloned embryonic stem cells although he admitted to misconduct in his follow-up paper on patient-specific stem cells,” Park said. “But my trust is seriously shaken by the doubts on the 2004 paper. Now, I am not sure whether the cloned stem cell really existed,” he added.

The Boston Globe picked up this aspect of the story on Dec. 20 as follows:

Two photos in the 2004 paper, published to great fanfare in the journal Science, claim to show batches of the world’s first cloned human embryonic stem cells. Yet the same photos appear in the journal Molecules and Cells, in a research article by another Korean team, submitted before the Science paper, and in that paper both photos are labeled as cells created without cloning. The Globe showed the photos to four stem cell experts, and all said they appeared to be identical, down to the smallest detail. The two photos were used in the Science paper as evidence that the cells were cloned embryonic stem cells. The duplication, the scientists said, raised doubts about two of seven tests done to prove the cells were legitimate, but also raises serious questions about the legitimacy of the overall paper, especially after the questions raised about other work done by the team.

Fallout
On Dec. 21, 2005, Nature reported that it has begun a re-examination of the research surrounding the cloning of Snuppy.

Nature said in a statement that it had no information casting doubt on Hwang’s paper, in which he described how his laboratory had purportedly produced an Afghan hound named “Snuppy.” But given allegations that Hwang faked results on other research, the journal said that there is “sufficient uncertainty … for us to wish to remove any doubts over the Nature paper.” Nature said its investigation probably wouldn’t be complete before January

On Dec 21, Science announced a probe of the 2004 paper.

Scientific American de-listed Hwang as one of its 50 Visionaries.

Peer Review

Philip Campbell, the editor of Nature, stated:

“Peer review is not set up to test for fraud,” Dr. Campbell said. “It is set up to provide expert assessment of the scientific credibility and reliability of what scientists report, taking the report itself in good faith.” … Nature’s reviewers did not ask Dr. Hwang to provide evidence that would have proved Snuppy was cloned from another dog. Dr. Campbell said that Nature, as part of its investigation of the article, would consider whether its standards of proof should be changed in the future.

The San Francisco Chronicle reported:

Just because a paper appears in a prestigious scientific journal doesn’t guarantee it’s correct, although outright fraud is rare. Submitted papers are subjected to peer review, which means experts examine the manuscript to look for logical errors and whether its methods are reliable, for example. “It’s not a forensic review, it’s a review that assumes that the authors submitting the research are telling the truth,” said Curt Civin of Johns Hopkins University Medical School, editor of the journal Stem Cells and a reviewer for other journals. Once a significant paper is published, other scientists try to reproduce the results or carry out other experiments that will indicate whether the finding is valid. If those experiments don’t support the original one, questions arise. “Science is a self-correcting enterprise and it’s very hard for fraud or wrong results to be propagated. In fact, it’s impossible,” Fischbach said.

Monica Bradford of Science stated:

“We work on the assumption that the data are real,” said Science’s executive editor, Monica Bradford. “The question is, do the data support the conclusions?” Bradford also told the Times that the drama surrounding this case was unprecedented, even for perhaps the world’s most high-profile scientific publication. “In a sense it has been unlike anything else.”

John Gearhart, a stem-cell expert at Johns Hopkins University and a member of Science’s board of reviewers said:

“Should reviewers have caught some of this? Yeah, probably they should have,” said “Obviously great claims require great proof, and maybe more people should review such a paper,”

Arthur Levine, dean of the University of Pittsburgh medical school, where a committee is investigating the work in the Science article for possible misconduct, said he agreed that Science’s referees “might have been more critical, but that is hindsight.” He added, “Almost six months have elapsed since the paper was published, and it had been widely read by many fine scientists without challenge.” Levine said he saw “terribly important lessons” in the Hwang incident, chiefly that the senior author of an article is responsible for its integrity and must therefore must be “intimately familiar” with the data. However, the true test of science is replication of a claim by others, Levine said.

Donald Kennedy, editor of Science, said:

Unlike readers, a journal’s reviewers can demand more data on points that do not convince them. But reviewers are unpaid, and their main task is to judge whether the data presented to them support the claim being made. Kennedy said that the reviewers could not be expected to detect deliberate falsehoods and that he could not see any generic fault in the peer-review system.

Brooks Hanson, a deputy editor of Science, was quoted as saying that the affair showed that peer review worked:

But others said that the fraud discovery showed the scientific process of peer-review worked. Brooks Hanson, a deputy editor at Science, said the magazine would not change the way it reviews publications. “The problem was picked up within weeks,” said Ira Black, a neuroscientist and founder of the Stem Cell Institute of New Jersey. “In a perverse way, this is quite positive.”

A blog discussion entitled Dr Hwang and the Bad Apple Theory of Scientific Misconduct is here.

On Dec 25, Nicholas Wade of the New York Times reviewed the matter again here

On Dec 26, the Times of India, among others, called for improved oversight.

The Washington Post pointed to the pressures on researchers as contributing to the ethical lapse:

“There is tremendous pressure today to be first. If you do something first, all the money and fame will come to you,” said Adil E. Shamoo, a biomedical ethicist at the University of Maryland. “All that is an obvious seduction for doing something like this.”…

“Unfortunately, research institutions and universities have not taken this issue seriously,” said Shamoo, who edits the journal Accountability in Research. “They pay lip service to responsible conduct and research integrity.” “It’s unconscionable” they don’t do more, he said. Beyond education, independent auditors could make spot checks in labs to verify data in much the same way the Internal Revenue Service polices taxpayers. If the IRS never conducted audits, what do you think would happen to people paying taxes in this country? If the public knows the IRS never conducts audits, don’t you think there will be an increase in problems?” Shamoo said.

A Closing Comment
I’ll comment some more on Nature and Science procedures. The unveiling of the fabrication was not done by their peer reviewers or even by Western scientists. All of the heavy lifting in detecting the fabrication was done in Korea, mostly reported on blogs. I obviously think that disclosure is one of the best and easiest ways of making fraud harder. From my experience with paleoclimate, neither journal applies “best practices” in respect to archiving data and methods and both journals have been unresponsive or ineffective in responding to requests for data. So they are vulnerable to criticism. More on this later.