Sunday, January 01, 2006

Timeline of Hwang problems

Pajamas Media has a discussion: The cloning scandal: how did it happen?

There is a reference to a timeline available at Nature.

The first entry for the Nature timeline is:

February 12, 2004, the date of Hwang's FIRST publication in Science in 2004, as distinct from his publication in June 2005:
Woo Suk Hwang from Seoul National University in South Korea and colleagues announced that they have cloned 30 human embryos and harvested stem cells from one of them (W. S. Hwang et al. Science 303, 1669-1674; 2004). The work makes headlines worldwide, as a step towards stem-cell therapies for diseases such as Parkinson's. Other groups have claimed to clone human embryos, but the supporting evidence has been sketchy. This success will also need further supporting evidence.

The Nature timeline further notes:
Biologists say that the South Korean breakthrough has alerted Western researchers to the pace of scientific and technological progress in East Asia. Hwang and colleagues attribute their success to a supportive cultural environment, well-funded laboratories, and legislation permitting human embryos to be cloned for research. Also critical to the researchers' success was their collection of 242 human eggs from 16 female volunteers.

The second dated entry (May 22, 2004) concerns ethics issues:
The annual meeting of the Korean Bioethics Association calls on Hwang and a review board to answer questions about funding sources and the recruitment of egg donors. The association wants the National Human Rights Commission, an independent investigative body funded by the government, to pursue the case. But the commission's bioethics task force was not intended to investigate specific research projects.

There is an entry for Jan. 13, 2005:
The South Korean government approves Hwang's embryonic stem cell research. It is the first approval issued under the nation's new bioethics law.

The Nature timeline does NOT have an entry date for the SUBMISSION of the Hwang 2005 paper. It does have an entry date for the online appearance of the Science paper, although it is not identified as such:

May 19, 2005
Hwang's team at the Seoul National University in South Korea reports it has established 11 embryonic stem-cell lines derived from the skin cells of individual patients (W. S. Hwang et al. Science 308, 1777-1783; 2005). The experiment is hailed as a huge step towards the medical use of person-specific cell lines. It also backs up the embryo-cloning claims in the team's February 2004 paper.

[LBE note: Nature does NOT mention the post on a confidential internet board maintained by MBC which occurred days after the May 19 publication.
According to a Dec. 21 article, it was an anonymous post on a confidential Internet bulletin board maintained by ''PD Notebook,'' South Korea's leading investigative news show that got the ball rolling on an investigation into Hwang's research.

The next entry is for August 3, 2005:

Cloned dog

Hwang and colleagues announce the first cloned dog - Snuppy, an Afghan hound (Lee B. C. et al. Nature436, 641; 2005). Some scientists hail his birth as a feat of ingenuity and perseverance, others question its value.

The next entry is for October 19:

South Korea's government launches the World Stem Cell Hub, an international network for exchanging embryonic stem-cell lines and cloning technology. Hwang is to be its head.

There is a general entry for October:
Hwang resumes research, ending his voluntary suspension of activities.

The next dated entry is for November 10:
According to Science, Gerald Schatten, a biologist at the University of Pittsburgh and co-author of the May 2005 Science paper, alerts them to Korean press reports alleging that researcher Sun Il Roh has illegally traded ova. Schatten reassures Science that "none of the oocytes used in Professor Hwang's '04 or '05 Science papers were obtained from reimbursed women donors."

The next dated entry is for November 11:

According to Science, Schatten tells them he has stopped working with Hwang, because he believes Hwang misrepresented facts about consent issues related to the 2004 paper. Science asks Hwang to inform them of any concerns regarding his research. Hwang says he is looking into the matter.

The next dated entry is for November 12:

Schatten publicly cuts all ties to Hwang and his team at Seoul National University.

Mistake in the 2005 paper

The 2005 paper's authors provide Science with corrections to data in the paper's table 2, which are not thought to significantly alter the work's conclusions. The corrected table is published.

The next dated entry is for November 21:
Sun Il Roh, a fertility expert at MizMedi Hospital in Seoul and a co-author of the landmark paper, admits that 20 eggs he procured and gave to Hwang for his 2004 study were paid for. Roh, a co-author on the 2005 paper, insists that Hwang did not know this.

The next dated entry is for November 22, which is the first entry mentioning MBC:
Seoul-based Munhwa Broadcasting Corporation (MBC) aired an investigative news programme showing further evidence that Hwang used eggs from junior members of his lab - the PD Diary program was called "The Myth of Hwang Woo-suk and Suspicions over Eggs."

The next dated entry is for November 24:
Admission of payments for eggs

Hwang admits that his stem-cell research used eggs from paid donors and junior members of his team. He resigns from his official positions, saying he will continue his research.

The next dated entry is for December 1:

Accusation of mis-matched DNA

The MBC challenges the credibility of Hwang's data. Pursuing a tip-off, MBC gets five samples of patient-specific cell lines from Hwang and sends them, together with corresponding tissue samples, to an independent lab for DNA analysis. The programme reports that the DNA in one cell line does not match the tissue sample as it should. There are many possible explanations for MBC's findings, such as contamination. But the mismatch also raises the possibility that the embryonic stem-cell lines were not cloned from the stated patients. Hwang stands by his science.

According to Science, Moon Il Park, Director and Chair of the Institutional Review Board (IRB) on Human Subjects Research and Ethics Committees at Hanyang University Hospital, reveals to them the results of an investigation by the hospital IRB and Seoul National University IRB. It finds that: "1) two researchers under Dr. Woo Suk Hwang's supervision donated oocytes voluntarily without any coercion and 2) approximately US$1,445 was paid for direct expenses." This was not illegal or in violation of the Helsinki Guidelines of 1964, which prohibit coercion of research subjects. Park also told Science: "We strongly believe that the identified concerns have no impact on the validity of the scientific conclusions."

The next dated entry is for December 4:

Media outlets report that the MBC has apologized for the reporting tactics used in their 22 November programme on Hwang.

Mistake in the 2005 paper

According to Science editors, Hwang contacts them to alert them to erroneous duplications in some images published as part of the Supporting Online Material for the 2005 paper. "We made some unintentional error by using about 4 pictures redundantly," he says. Science determines that the redundant images did not appear in the PDF version of the accepted paper, but were inserted later, and says the mistake does not affect the paper's scientific conclusions. [LBE note: the date of the communication from Hwang to Science was Dec. 5, and the discussion by Science was on Dec. 6. Separately, Nature's rendition is not an accurate rendition of what Science said on Dec. 6, which is that the INITIAL MS contained photos of all 11 cell lines, but there was a redundancy in LATER REQUESTED HIGHER RESOLUTION photos (ie, the problem was with photos submitted AFTER March 15)]

The next dated entry is Dec. 5:
Investigation opened

University of Pittsburgh officials say they have opened a preliminary inquiry into the 2005 paper.

The next dated entry is Dec. 11:

Investigation opened

Seoul National University announces an investigation of Hwang's research, as requested by Hwang himself. The university hospital treats Hwang for stress and exhaustion

The next dated entry is Dec. 13:
Schatten asks Hwang to retract their May 2005 Science paper. Schatten claims he has news of allegations from someone involved with the experiment that make him want his name removed from the paper. According to a release from the University of Pittsburgh, Schatten writes to Science and his co-authors: "My careful re-evaluations of published figures and tables, along with new problematic information, now casts substantial doubts about the paper's accuracy."

Stem-cell scientist asks for retraction

A letter from eight scientists, including Ian Wilmut, the cloner of Dolly the sheep, is published in Science calling for validation of Hwang's results: "We encourage Hwang's laboratory to cooperate with us to perform an independent test of his cell lines."

The next dated entry is Dec. 15:
Scientific American removes Hwang from his position as a Research Leader of 2005.

Accusation of fake data

News stations across Korea report allegations from one of Hwang's collaborators that the work from May 2005 was based on fabricated data. Roh tells the MBC and two other television stations that Hwang had told him "there are no cloned embryonic stem cells".

The next dated entry is Dec. 16:

Science announces that Hwang and Schatten have written to request a retraction of their 2005 paper. Science editor Donald Kennedy says the journal received the letter hours before Hwang's press conference in South Korea (see entry below). Kennedy quoted from the letter during a press conference with reporters: "After analyzing the data, our team concludes the results...could not be trusted... Therefore we are requesting to withdraw the paper." Science says it must wait for the entire research team to consent to the retraction - a process that Kennedy says should take "days or weeks - not months."

[LBE note: Nature does not mention other pertinent information from Science:
In an article in the Dec. 16, 2005 issue of Science (Vol. 310 at pp. 1748-1749), there is a mention of a DIFFERENT internet post, specifically one on the Biological Research Information Center [BRIC] website. This post was on or about December 5, 2005, and thus was much after the post on "PD Notebook" site. Shortly after the post on the BRIC site (ie, a span of hours), Dr. Hwang emailed the journal Science about problems with duplicate images in the May 2005 paper.

Apology and defense

Hwang tells a press briefing that he and his team did create stem cells matched to individual patients, but that there were "mistakes made, human errors, in taking photographs and in the preservation of the stem cells''. Hwang says he will seek agreement from his co-authors to retract the Science paper, and will investigate how the mistakes were made. He adds that his team is thawing some frozen stem-cell lines from the study to authenticate them.

The next dated entry is Dec. 23:
A rapid investigation of Hwang's work at Seoul National University delivers a damning initial verdict: large amounts of the data in his 2005 landmark paper on patient-specific stem cells were fabricated. The university's investigating team announces in a televised press conference that the data in the 2005 Science paper came from just two cell lines, not 11 as claimed. This "cannot be some error from a simple mistake, but can only be seen as a deliberate fabrication", the panel says. Hwang says that these two stem cell lines, which are frozen in his lab, were derived from cloned embryos from specific patients. The university is doing tests to validate this. Investigation says Hwang lied Korean scandal will have global fallout.

The next dated entry is Dec. 29:
The Seoul National University (SNU) team that has been investigating the South Korean researcher reports that there is no evidence that Woo Suk Hwang's stem cells came from patient-specific clones. Last week the investigators said that at least nine of eleven stem-cell lines in Hwang's 2005 Science paper were not what the paper claimed them to be (see 23 December entry below). Now they add that the remaining two lines also do not match the DNA of patients, as they were meant to. Instead they match cells from other, normal embryos created by in vitro fertilization. "Currently, we cannot find stem cells that have identical DNA fingerprint traces with patients and Hwang's team does not have scientific data to prove they did harvest patient-specific stem cells," says Jung-Hye Roe, director of research at SNU, in a press conference.

Science issues a statement saying: "There is no question in our minds that the stem-cell paper published 19 May 2005 by the journal Science needs to be retracted, and we are proceeding swiftly but appropriately in that direction." Science adds that they have not yet received official notification of the SNU investigation results, nor do they have all of the co-authors' signatures on a retraction agreement. They give the authors a deadline of 30 December, after which they say they will move towards an editorial retraction.

There is another timeline.

[IPBIz post 1111]


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