2009-04-07

Mud-slinging among Korean researchers

This week's Nature has a news article entitled "Retracted paper rattles Korean science", which anounces a retraction of a paper published in Nature in 2000. The data presented in the original paper promised an advance in diabetes treatment using gene therapy.

The paper's authors, led by Hyun Chul Lee of Yonsei University in South Korea, claimed to have created a treatment for type 1 diabetes, a condition in which the immune system destroys the insulin-producing cells needed to regulate glucose levels. Lee's team constructed a recombinant virus that contained a gene for an insulin analogue, which was expressed in response to blood glucose levels. By introducing the gene construct into diabetic rats and mice, they succeeded in alleviating symptoms, according to the paper published in 2000. Their result, however, has not been reproduced.

According to the news article,

Now, having yet to repeat the experiment, Lee has asked Nature to retract the paper (see page 660). I don't know the reason why the experiments are not reproducible, says Lee. He suggests that the original gene construct, pLPK-SIA, a combination of the virus vector, the insulin analogue and a promoter that regulates the expression of the analogue in response to glucose levels — might have mutated after the original experiment.
According to Lee, the reason they cannot repeat the experiment is that some unknown mutation might have occured to their gene construct. However, an anonymous researcher who had worked in Lee's laboratory to repeat the experiment is claiming that the laboratory did not have the gene construct in the first place.
The background to the retraction is contentious. A researcher who joined the laboratory in 2001 tried and failed to initiate preclinical trials in bigger animals such as dogs and monkeys. But the researcher, who does not want to be identified for fear that acting as a whistleblower could harm his career, says he didn't find any pLPK-SIA in the laboratory, so with another researcher in the lab he tried to remake it according to the methods section from the original paper. Lacking essential ingredients, they eventually gave up.
A co-author of the paper who had created the gene construct were working in Canada, but she did not give the construct to the anonymous researcher.
The anonymous researcher says one of the paper's authors, Su-Jin Kim, who created the gene construct before moving to the University of Calgary in Canada, refused to send him samples. Kim says she deferred on this matter to her new boss, Ji-Won Yoon. The researcher, however, says that in e-mail exchanges, Yoon told him to ask Kim for samples. Yoon, also a co-author on the Nature paper, died in 2006.
It seems that the anonymous reseacher and Lee are now mud-slinging at each other.
Lee fired the anonymous researcher in August 2005, citing unhappiness with his work. Lee says that in 2008 the researcher threatened to disclose faults in the paper unless given money, grants and a new job. The researcher admits that he asked for a new position as compensation for losing what he calls four-and-a-half years trying to reproduce the results. He alleges that he was fired after advising Lee to retract the paper, which Lee denies.
In April 2008, Yonsei University started an investigation.
On 30 December the committee recommended a retraction based on multiple points, including the apparent duplication of figures and the fact that it could not confirm the key construct existed when the experiment was carried out. Won-Yong Lee says that the committee members examined Kim's lab notes and thesis, and alleges that the duplication was more than a simple mistake, including the reuse of data as well as cutting, pasting and otherwise adjusting figures.
Kim is now trying to stop the university from releasing its full report.
The committee says that Kim and Yoon tried to reproduce the experiments; Kim, who is now at the University of British Columbia in Vancouver, says she did not, and didn't know there was a problem until last year. She says she has some of the pLPK-SIA and that the problems with figures were probably a mistake made when forwarding to colleagues, or in labelling. She faults the committee for choosing to rely on the memory of witnesses who were testifying about experiments that took place 8–10 years ago. Kim refused to sign the retraction letter, calling the original experiment a success, based on lab notes. She also filed an injunction, currently under consideration in the Seoul District Court, to prevent the university releasing its full report.
According to the news article, Kim says she will resolve the situation by reproducing the experiment.