Full Text: Korean
Cloning Panel's Report
by
The Eight-Member Seoul National University Investigating Committee -- Chung Myung Hee,
Chairman
Tuesday, January 10, 2006, 9:09 Makka Time, 6:09 GMT; Panel Slams Faked Korean Cloning
An investigating panel at South Korea's Seoul National University (SNU) has
found that scientist Hwang Woo Suk faked his claims of pioneering stem-cell research. The
following is the full text of the Summary of their report, as published on the SNU
website.
[With very light editing for English, since the original Korean-language translation was obviously
not done by a native speaker of English. -- Editor]
Ref.: Hwang WS, Roh SI, Lee BC, Kang SK, Kwon DK, et al., "Patient-Specific Embryonic Stem Cells Derived from Human SCNT Blastocysts," Science Vol. 308, pp. 1777-83 (2005).
This article claimed that 11 human embryonic stem-cell lines have been established through transfer of somatic cell nuclei. In interim reports we issued previously, we already reported that data from only two embryonic stem (ES) cell lines have been used for this publication and that even these two lines were not derived via Somatic Cell Nuclear Transfer (SCNT) but from in vitro fertilized (IVF) eggs. The stem cells that Prof. Hwang claims to have created subsequent to the 2005 publication have also turned out to have originated from frozen fertilized eggs and not from cloned blastocysts. The data in 2005 article including test results from DNA fingerprinting, photographs of Teratoma, Embryoid Bodies, MHC-HLA isotype matches, and Karyotyping have all been fabricated. The method and process of fabrication are described in the report. In conclusion, the research team of Prof. Hwang does not possess patient-specific stem- cell lines or any scientific bases for claiming having created one.
Ref.: Hwang WS, Ryu YJ, Park JH, Park ES, Lee EG, et al., "Evidence of a Pluripotent Human Embryonic Stem-Cell Line Derived from a Cloned Blastocyst," Science, Vol. 303, pp. 1669-74 (2004).
"Therefore, our judgment is that the scandalous case of Woo Suk Hwang and cloned ES cells will not have a large impact on the effort of the scientific community in Korea." The investigation on the 2004 Science paper in which the establishment of the first human ES cell line from cloned blastocyst was reported was initiated in response to various doubts raised in photographs of the cells and results from DNA-fingerprinting analyses.
The Committee has undertaken DNA fingerprinting analyses on the samples obtained from the ES cell line in question (NT-1), Teratoma allegedly derived from NT-1, and the donor (Donor A) of the egg and somatic cell. The DNA samples for the ES cell line included those from 20 subcultured NT-1 cell lines in culture or in frozen state from Prof. Hwang's Laboratory, one deposited to the Korean Cell Line Bank for the purpose of securing a patent, one maintained in Prof. Shin Yong Moon's Laboratory at SNU, and one maintained in the MizMedi Hospital. The 23 samples were examined by three independent test centers, and all three centers have obtained identical results.
This report describes Hwang's actions as 'scandalous.' The Teratoma, the cell line deposited in the Korean Cell-Line Bank, and the cell lines maintained in Prof. Moon's Laboratory and in the MizMedi Hospital all showed identical fingerprinting patterns. Among the 20 independent subcultures from Prof. Hwang's Laboratory, 9 produced an identical pattern to the aforementioned three samples, but the other 11 produced a distinct pattern that was in fact identical to the fingerprinting pattern of MizMedi ES Cell-Line No. 5 derived from IVF eggs. The fingerprinting pattern of NT-1 line is quite distinct from what was reported in the 2004 Science article. While the fingerprinting pattern of the anonymous Donor A, the source of the somatic and egg cells according to Prof. Hwang's team, was identical to what was reported in the Science article, it was clearly different from that of NT-1 line. Therefore, NT-1 ES cell line was not derived from nuclear transfer using somatic cells from the Donor A as claimed in the Report.
NT-1 was shown to be distinct from all of IVF-ES cell lines MizMedi Hospital had produced. The Committee has thus attempted to determine its origin by obtaining blood samples from two other individuals who donated their eggs and cumulus cells at about the same time and comparing their DNA fingerprinting patterns. One of the donors, the anonymous Donor B, appeared to show a certain association with NT-1. That Donor B and NT-1 show an identical mtDNA fingerprinting pattern indicated that she is the donor of the egg. However, of the 48 nuclear polymorphic loci tested, 40 gave results that indicate the nuclear identity of NT-1 cells and Donor B cells while 8 gave results that were contradictory. If NT-1 were derived from Somatic Cell Nuclear Transfer, all 48 polymorphism markers must be identical between the Donor B cells and NT-1 cells. That 8 are inconsistent implies that NT-1 is not an ES cell line derived from a cloned blastocyst. The eight markers were heterozygous in Donor B blood but homozygous in NT-1. These data suggest that there is a high probability that NT-1 resulted from the fusion of a non-enucleated egg and a nearby polar body, which established a parthenogenetic process.
The claim in 2004 article that the DNA fingerprinting pattern of NT-1 and that of Donor A match perfectly was clearly a false report. Given that none of the alleged NT-1 derived cells or tissues matches Donor A, the Committee concluded that NT-1 ES cell line reported in Science in 2004 is not an ES cell line derived from a cloned blastocyst. In addition, claims that photographs of cells in 2004 Science article are those of MizMedi ES cells have also been verified to be true. Therefore, the Committee concluded that results described in 2004 Science article including DNA fingerprinting analyses and photographs of cells have also been fabricated.
The Report Says Snuppy Was a Legitimate Clone
We also carried out DNA fingerprinting analyses on the cloned dog Snuppy whose generation has been published in Nature in 2005
Ref.: Lee BC, Kim MK, Jang G, Oh HJ, Yuda F, et al., Nature, "Dogs Cloned from Adult Somatic Cells," Nature, Vol. 436, No. 7041, p. 641 (August 4, 2005).
We obtained somatic tissue from the egg donor, blood samples from Snuppy, from Tie, the dog that provided somatic cells, and from the Surrogate Mother and engaged three independent test centers for the analyses. Results from analyses of 27 markers that allow us to distinguish amongst extremely-inbred animals and of mtDNA sequencing indicate that Snuppy is a somatic cell clone of Tie.
Information obtained from computer files and notes of Hwang's Laboratory members, from records of egg donation by four hospitals including the MizMedi Hospital, and from interviews with relevant personnel confirmed that from November of 2002 to November of 2005, a total of 2,061 eggs from 129 females have been collected from four hospitals and provided to Prof. Hwang's Team. The exact accounting for the number of eggs used for each of the Science articles is impossible as the initiation date for each project is uncertain and laboratory recording is not sufficiently thorough. However, while the 2005 article claims to have used 185 eggs, laboratory notes indicated that at least 273 eggs have been used from September 17, 2004 to February 7, 2005.
Regarding the article in 2004, Prof. Hwang claimed to have been unaware of the egg donation by the laboratory members. However, the graduate student who donated eggs informed the Committee that the act of donation, while voluntary, was approved by Prof. Hwang. Egg aspiration was carried out by Dr. Sung Il Roh on March 10, 2003 at MizMedi Hospital, and notably, Prof. Hwang accompanied the student to the hospital himself. In May of 2003, Prof. Hwang's research team circulated a form asking consent for voluntary egg donation and collected signatures from female technicians. This is based on information provided by eight current- and former-lab members.
The ES cells from Somatic Cell Nuclear Transfer (SCNT) are established through three main stages: (1) the Nuclear transfer; (2) Blastocyst formation; and (3) Establishment of the cell line. In order to be used for treatment of patients, cells from the established cell lines must be able to differentiate into desired cell types and to function in an effective manner in vivo and must be free of tumorigenic potential.
Prof. Hwang's research team is one of the most active team internationally in performing nuclear transfer using eggs from animals such as pigs and cows. There are approximately 100 technical experts in this procedure in various veterinary institutions in Korea including those in Prof. Hwang's Laboratory. Thus, when it comes to animal cloning, with the added consideration for the successful cloning of a dog, Korea seems to be internationally competitive. The squeezing technique utilized in enucleation of human eggs is highly efficient in Hwang's team, but has long been used for the same purpose in animal eggs and thus cannot be considered unique or novel.
According to Prof. Hwang's record, a success rate of 10 percent is claimed for blastocyst formation following human nuclear transfers. However, a closer examination of the data indicated that most of blastocysts are in poor condition. Some, nevertheless, appear to have successfully developed into blastocysts, implying that the team was in possession of a technique of for creating cloned human blastocysts.
According to the records of Prof. Hwang's research team regarding the stage of cell-line establishment, the scientific bases for claiming any success are "wholly lacking." The establishment of ES cell lines must meet the criteria of being able to differentiate through embryoid body formation or to form Teratoma, for example. However, Prof. Hwang's team regarded the initial formation of cell colony as the successful establishment of ES cell line, and no record of further confirmatory experiments could be found.
Taken together, Prof. Hwang's research team possesses neither the patient-specific ES cell line described in the 2005 publication nor the NT-1 ES cell line, the forerunner cloned cell line described in the 2004 publication. The data in 2004 publication are also fabricated as can be seen by the non-match between the donor A and NT-1. Such an act is nothing less than deceiving the scientific community and the public-at-large. Even the scenario based on switching cell lines cannot explain the parthenogenetically-derived cell line and cannot undo the fabrication of DNA fingerprinting data.
Not all the wrongdoing of all the individuals associated with fabricated publications can be exposed by this Committee. However, that the publications were fabricated alone mandates a severe penalty by the appropriate academic authorities. These individuals cannot be regarded to represent science in South Korea. We have numerous well-qualified researchers whose work is recognized worldwide, and we also have a world-class research capability in the biological sciences that will ensure our successful participation in the field of Stem-Cell Biology. Our judgment is thus that the scandalous case of Hwang Woo Suk and cloned ES cells will not have a large impact on the effort of the scientific community in Korea. Rather, we are certain that this learning experience will be a stepping stone for better execution and management of scientific research and contribute to scientific advancement in this country. The young scientists who courageously pointed out these fabrications and triggered the start of this investigation are our hope for the future. We would like to express our gratitude to those who supported the effort of this Committee and provided critical assistance.
"Cloning Scandal Spotlights
Korea's Obedience Culture"
by
Bo-Mi Lim, Chicago Sun Times
January 8, 2006; Seoul, SOUTH KOREA (AP) -- In this hard-driving, Confucian- influenced society, seniority rules. Challenging bosses is uncommon, and failing to bow to superiors invites reproach. With most men forced to serve a stint in the military, a culture of following orders prevails.
Nowhere is this more evident than in academia, a field that has been roiled by the fraud scandal surrounding the once-esteemed stem-cell scientist Hwang Woo Suk. Blindly obeying lordly professors is seen as the surest way to success. Graduate students compete for coveted, tenured faculty positions known here as an 'iron rice bowl' -- a Chinese idiom meaning a "guaranteed lifetime job."
"In relations with professors, the graduate school students are the absolute weak," said Baek Seung-ki, a fourth-year doctoral candidate in physics at state-run Korea Advanced Institute of Science and Technology. "You must do whatever you are told to do."
But some are now questioning this system. Hwang, 53, rose to international fame in 2004 when he announced the creation of the world's first cloned human embryo at his laboratory at Seoul National University, South Korea's most prestigious school.
Last year, he claimed to have created embryonic stem cells tailor-made to patients, stunning the world and suggesting fast progress toward developing treatments for Alzheimer's disease, paralysis and other afflictions. Kim Sun-jong, a former researcher at Hwang's lab, has told South Korean media that Hwang ordered him to fabricate data for a paper on the designer stem cells published in May.
Hwang resigned last month amid a university investigation. The university has confirmed that all of the research in the 2005 paper was faked. It plans to release final results of its probe in a few days, including the veracity of the 2004 embryo as well as whether Hwang actually cloned the world's first dog, as claimed last year.
'Outdated Lab Culture'
The problem, editorialized The Segye Times newspaper, is "an outdated, premodern lab culture of obeying seniors' orders. While it was Prof. Hwang who should have ensured truth and conscience, it is lamentable the researchers couldn't restrain such misconduct and instead blindly followed the orders." Some experts say Hwang's underlings had no real choice. "Prof. Hwang's researchers followed the only logic of survival available to them... even if it meant faking the research results," said Vladimir Tikhonov, a Professor of Korean studies at the University of Oslo. "Questioning your professor means full loss" of job opportunities, he said.
The MBC television network reported last week that one of the two researchers at Hwang's Seoul lab who donated eggs for research, was pressured to do so for fear Hwang would not list her as a co-author for the paper to be published in Science. "I regret that I didn't stand up against the Professor," MBC quoted the researcher, identified by her surname, Park, as saying in an E-mail message before donating eggs in 2003. Park said she was "exceedingly disgusted" with herself for having to conduct cloning experiments on her own eggs.
[Editor's Note: There are three "Park's listed among the 25 co-authors so it is difficult to tell which Park this is: Sun Woo Park, Ye Soo Park, and Jong Hyuk Park, who was in Pittsburgh, PA, so not likely. It is more likely to be the first one, as the second was with a different university in Seoul, while the first worked directly in the Veterinary School.]
Independent Panel Confirms
Stem-Cell Fraud: Outside Investigators Determine that Cloned Stem-Cell Lines from South
Korean Lab Were Faked
by
Alice Park and Stella Kim, Time Magazine
January 9, 2006; South Korean stem cell researcher Woo Suk Hwang took another hit on Tuesday when an investigative panel concluded that the groundbreaking stem cell cloning research that launched him to international fame was faked. Last month, an 8-member Panel at
Seoul National University (SNU) found no evidence to prove that Hwang had created stem cells by cloning the skin cells of patients - a feat he reported in an article published in Science last year. In a report issued in Seoul on Tuesday, the panel said that Hwang's scientific misconduct extended back to his report from 2004 when he claimed to have created the first stem cell lines cloned from human cells. Members from the panel explained that genetic testing of those stem cells by three different labs did not match the DNA fingerprints of stem cells that Hwang discussed in his 2004 paper.
Hwang maintains that he created the history-making cells, but admits that his lab was plagued by mismanagement. He claims that the stem cells were switched or stolen. The Panel found this explanation highly unlikely, and harshly chastised Hwang for damaging the scientific reputation of South Korean researchers with his actions.
But there was one aspect of Hwang's research that was validated by the panel. Hwang's cloned dog, Snuppy, the first of its kind, stood up to the outside testing. (Last year, Time chose the dog-cloning research as Invention of the Year.) DNA testing of Snuppy confirmed that he is a genetic copy of Tai, the male Afghan hound whose skin cell Hwang cloned to create the cloned puppy.
The verdict on the cloned dog, however, is a small consolation for Hwang, whose discredited studies have left his scientific reputation in shambles. The fakery and flaws in his studies have undermined his contributions to cloning research and have likely caused a setback in worldwide progress in the field of stem-cell research.