The Hwang affair,[1] or Hwang scandal,[2] or Hwanggate,[3] is a case of scientific misconduct and ethical issues surrounding a South Korean biologist, Hwang Woo-suk, who claimed to have created the first human embryonic stem cells by cloning in 2004.[4][5] Hwang and his research team at the Seoul National University reported in the journal Science that they successfully developed a somatic cell nuclear transfer method with which they made the stem cells. In 2005, they published again in Science the successful cloning of 11 person-specific stem cells using 185 human eggs.[6] The research was hailed as "a ground-breaking paper" in science. Hwang was elevated as "the pride of Korea",[7] "national hero" [of Korea],[8] and a "supreme scientist",[9] to international praise and fame.[10][11] Recognitions and honours immediately followed, including South Korea's Presidential Award in Science and Technology, and Time magazine listing him among the "People Who Mattered 2004"[12] and the most influential people "The 2004 Time 100".[13]

Suspicion and controversy arose in late 2005, when Hwang's collaborator, Gerald Schatten at the University of Pittsburgh, came to know of the real source of oocytes (egg cells) used in the 2004 study.[14] The eggs, reportedly from several voluntary donors, were from Hwang's two researchers, the fact which Hwang denied. The ethical issues made Schatten immediately break his ties with Hwang. In December 2005, a whistleblower informed Science of reuse of the same data. As the journal probed in, it was revealed that there was a lot more data fabrication.[14] The SNU immediately investigated the research work and found that both the 2004 and 2005 papers contained fabricated results. Hwang was compelled to resign from the university,[15] and publicly confessed in January 2006 that the research papers were based on fabricated data.[14] Science immediately retracted the two papers.[16]

In 2009, the Seoul Central District Court convicted Hwang for embezzlement and bioethical violations, sentencing him to a two-year imprisonment.[17] The incident was then recorded as the scandal that "shook the world of science,"[6] and became "one of the most widely reported and universally disappointing cases of scientific fraud in history".[18]

Background

Hwang Woo-suk was a professor of veterinary biotechnology at the Seoul National University and specialised in stem cell research. In 1993, he devised an in vitro fertilisation method with which he made the first assisted reproduction in cows.[19] He rose to public notice in 1999 when he announced that he had successfully cloned a dairy cow, named Yeongrong-i, and a few months later, a Korean cow, Jin-i (also reported as Yin-i[8]). The following year, he announced the preparation for cloning an endangered Siberian tiger.[8] It was a failed attempt, but nonetheless, his popularity in the Korean public escalated from wide media coverage. In 2002, he claimed creation of a genetically modified pig that could be used for human organ transplant.[6] In 2003, he announced the successful cloning of a BSE (bovine spongiform encephalopathy)-resistant cow.[20] However, science sceptics raised concern over the absence of research papers for any of his claims.[19]

2004 human cell cloning

In 2004, Hwang announced the first complete cloning of a human embryo.[13][21] The research, published in the 12 March 2004 issue of Science, was reported as "Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst."[22] For its potential medical value to replace diseased and damaged cells, several scientists had previously tried to clone the human embryo, but in vain.[23] Hwang's team had developed an improved method of somatic cell nuclear transfer using which they could transfer the nuclei of somatic (non-reproductive) cells into egg cells which had their nuclei removed.[24] They used human egg cells and cumulus cells, which are found in ovaries near the developing eggs and are known to be good source of nuclear transfer. After emptying an egg of its nuclues, they transfer the nucleus of the cumulus cell into it. The new egg cell divided normally and grew into blastocyst, an early embryo characterised by a hollow ball of cells. The isolated the outer trophoblast cells that are destined to become the placenta, discarding the inner cell mass that would form the placenta. When the trophoblast cells were cultured, they could divide and form different tissues, indicating that they were viable stem cells.[25] The report concluded: "This study shows the feasibility of generating human ES [embryonic stem] cells from a somatic cell isolated from a living person."[22] It was the first instance of cloning of adult human cells and human embryonic stem cells.[25]

Hwang publicly reported the research at the annual meeting of the American Association for the Advancement of Science (AAAS) in Seattle on 16 February 2004.[24] He specified that they used 242 eggs from 16 unpaid volunteers, creating about 100 cells from which 30 embryos were developed.[26] Since the embryos had adult DNA, the resulting stem cells became clones of the adult somatic cells. From the embryos, the stem cells were collected and grafted into mice in which they could grow into various body parts including muscle, bone, cartilage and connective tissues.[23] The method ensured that immune rejection would be avoided so that it could be used for the treatment of genetic disorders, as Hwang explained: "Our approach opens the door for the use of these specially developed cells in transplantation medicine."[26]

2005 human cell cloning

Hwang's team reported another successful cloning of human cells in the 17 June 2005 issue of Science, in this case, embryonic stem cells derived from skin cells.[27] Their study claimed the creation of 11 different stem cell lines that were the exact match of DNA in people having a variety of diseases. The experiment used 185 eggs from 18 donors.[28] The report explicitly stated that: "Patients voluntarily donated oocytes and somatic cells for therapeutic cloning research and relevant applications but not for reproductive cloning ... no financial reimbursement in any form was paid."[27]

Initial receptions

The 2004 report

When the 2004 research was announced, it was received with praise and admiration. Donald Kennedy, editor-in-chief of Science, remarked: "the generation of stem cells by somatic cell nuclear transfer methods involving the same individuals may hold promise for advances in transplantation technology that could help people affected by many devastating conditions."[26] Michael S. Gazzaniga, neuroscientists and bioethicist at Dartmouth College, who had supported therapeutic cloning, commented it as "a major advance in biomedical cloning".[29] American scientists took the news to criticise the weakness of US government in stem cell research and its prohibitive attitude.[26][30] As Helen Pearson reported in Nature, the cloning accomplishment turned Asians into "scientific tigers".[24]

Time reported that as a consequence of the achievement, "a medical and ethical door that had remained mostly closed was kicked wide open."[31] Hwang and his colleague Shin Yong Moon were listed by Time at number 84 in its list of most influential people "The 2004 Time 100" in April 2004.[13]

The critical issue was on bioethics, as the method ultimately wasted many human embryos[32] and could be used to create full human clones, as John T. Durkin argued in Science: "the developmental events leading from fertilized ovum, to blastula, to embryo, to fetus, to fully formed adult constitute a continuum."[33] Hwang claimed that the purpose was for medical applications only, and said in Seattle, "Reproductive cloning is strictly prohibited [in South Korea]."[30] At the time, South Korea was developing its "Bioethics and Biosafety Act" to be enforced in 2005. The regulations proscribed human reproductive cloning and experimental fusion of human and animal embryos; even therapeutic cloning for diseases would require authorised approval. Based on this situation, Sang-yong Song of the Hanyang University, criticised Hwang for not waiting the forthcoming regulations and social consensus in Korea.[34] Howard H. Kendler, psychologist at the University of California, had an unbiased viewpoint, commenting: "Although individuals will differ in their opinions, a democracy can decide whether the benefits of embryonic stem cell research outweigh any disadvantages. Science can assist in making this decision, but cannot dictate it."[35]

Circle of influences

Hwang loved public attention and tried to establish a network of bureaucrats. To name his second cloned cow, he requested President Kim Dae-jung, who gave the name after a celebrated Korean geisha "Hwang Jin-i."[6] As he announced the cloning of a BSE-resistant cow in 2003,[20] President Roh Moo-hyun visited his laboratory and was shown a dog cured from its injury using stem cell transfer, to which the president applauded, "this is not a science; this is a magic."[6] It was from the point that Hwang received escalated research funding from the government that peaked in 2005 at around US$30 million.[3] That year, Korean Ministry of Science and Technology officially honoured him the "Supreme Scientist" for the first time in Korea; the title carried US$15 million.[36] The government set up the World Stem Cell Hub at Seoul National University Hospital on 19 October 2005, created and directed by Hwang.[37][38] On the day of opening, 3,000 people registered for willingness to take stem cell therapy.[6]

Scientific flaws

In the 2004 report, Hwang's team prudently remarked that "we cannot completely exclude the possibility that the cells had a parthenogenetic origin."[22] Reference to parthenogenesis, the ability of embryo development from egg cells without fertilisation, was relevant because it had been documented that stem cells are capable of such transformation. Way back in 1984, an experiment demonstrated that a genetic mixture (chimera) of nuclei from the stem cells, one-cell-stage embryos of mouse could develop into full embryos.[39] Researchers at Advanced Cell Technology (ACT) in Worcester, Massachusetts, further showed in 2002 that primate (in this case crab-eating macaque, Macaca fascicularis) stem cells grew into the blastocyst stage.[40] The ACT subsequently announced that they created the human parthenogenetic cells, although the cells could not reach the blastocyst stage.[41] In 2003, Gerald Schatten of the University of Pittsburgh and his team reported a failed attempt of stem cell cloning in rhesus monkey, the cell divisions were always erratic and produced abnormal chromosomes.[42] Schatten declared: "This reinforces the fact that the charlatans who claim to have cloned humans have never understood enough cell or developmental biology."[43]

Documentary

In June 2023, Netflix released the documentary film King of Clones, which covered Hwang Woo-suk and this affair.

See also

References

  1. ↑ Kim, Jongyoung; Park, Kibeom (2013). "Ethical Modernization: Research Misconduct and Research Ethics Reforms in Korea Following the Hwang Affair". Science and Engineering Ethics. 19 (2): 355–380. doi:10.1007/s11948-011-9341-8. ISSN 1353-3452. PMID 22218997. S2CID 255432950.
  2. ↑ Fuyuno, Ichiko (2006). "Hwang scandal hits Korean biotech hard". Nature. 439 (7074): 265. Bibcode:2006Natur.439..265F. doi:10.1038/439265a. ISSN 1476-4687. PMID 16421542. S2CID 5413877.
  3. 1 2 Saunders, R.; Savulescu, J. (2008). "Research ethics and lessons from Hwanggate: what can we learn from the Korean cloning fraud?". Journal of Medical Ethics. 34 (3): 214–221. doi:10.1136/jme.2007.023721. ISSN 1473-4257. PMID 18316467. S2CID 38183620.
  4. ↑ Kim, Jongyoung (2009). "Public feeling for science: The Hwang affair and Hwang supporters". Public Understanding of Science. 18 (6): 670–686. doi:10.1177/0963662508096778. ISSN 0963-6625. S2CID 145094651.
  5. ↑ Rincon, Paul (2006-01-10). "Science takes stock after clone row". BBC. Retrieved 2023-04-27.
  6. 1 2 3 4 5 6 Hong, Sungook (2008-03-01). "The Hwang Scandal That "Shook the World of Science"". East Asian Science, Technology and Society. 2 (1): 1–7. doi:10.1215/s12280-008-9041-x. ISSN 1875-2160.
  7. ↑ Sample, Ian (2006-01-11). "Stem cell pioneer accused of faking all his research. Apart from the cloned dog". The Guardian. ISSN 0261-3077. Retrieved 2023-04-27.
  8. 1 2 3 Kakuk, Péter (2009). "The legacy of the Hwang case: research misconduct in biosciences". Science and Engineering Ethics. 15 (4): 545–562. doi:10.1007/s11948-009-9121-x. ISSN 1471-5546. PMID 19247809. S2CID 38704110.
  9. ↑ Sudworth, John (2009-10-26). "S Korea clone scientist convicted". BBC. Retrieved 2023-04-27.
  10. ↑ Prasad, R. (2009-10-28). "The future for Hwang Woo Suk does not look gloomy". The Hindu. ISSN 0971-751X. Retrieved 2023-04-27.
  11. ↑ Lalchhandama, Kholhring (2020). "The making of scientific ethics – lessons from unethical conducts". Science Vision. 20 (3): 118–131. doi:10.33493/scivis.20.03.03. ISSN 2229-6026. S2CID 229527301.
  12. ↑ "People Who Mattered 2004". Time. December 27, 2004. Archived from the original on 2004-12-30. Retrieved March 16, 2013.
  13. 1 2 3 Kluger, Jeffrey (2004-04-26). "The 2004 TIME 100 - TIME". Time. ISSN 0040-781X. Retrieved 2023-05-01.
  14. 1 2 3 Resnik, David B.; Shamoo, Adil E.; Krimsky, Sheldon (2006). "Fraudulent human embryonic stem cell research in South Korea: lessons learned". Accountability in Research. 13 (1): 101–109. doi:10.1080/08989620600634193. ISSN 0898-9621. PMC 1892198. PMID 16770863.
  15. ↑ "S Korea cloning research was fake". BBC. 2005-12-23. Retrieved 2023-04-28.
  16. ↑ "Journal retracts Hwang research". BBC. 2006-01-13. Retrieved 2023-04-28.
  17. ↑ Cyranoski, David (2009). "Woo Suk Hwang convicted, but not of fraud". Nature. 461 (7268): 1181. doi:10.1038/4611181a. ISSN 0028-0836. PMID 19865133. S2CID 205049062.
  18. ↑ Cyranoski, David (2014). "Cloning comeback". Nature. 505 (7484): 468–471. Bibcode:2014Natur.505..468C. doi:10.1038/505468a. ISSN 0028-0836. PMID 24451524. S2CID 4402662.
  19. 1 2 Cyranoski, David (2006). "Who's who: A quick guide to the people behind the Woo Suk Hwang story". Nature. Online: news060109–9. doi:10.1038/news060109-9. ISSN 0028-0836.
  20. 1 2 "Cattle clones resist BSE, claim Koreans". The Guardian. 2003-12-18. ISSN 0261-3077. Retrieved 2023-05-01.
  21. ↑ Dreifus, Claudia (2004-02-17). "A CONVERSATION WITH/Woo Suk Hwang and Shin Yong Moon; 2 Friends, 242 Eggs and a Breakthrough". The New York Times. ISSN 0362-4331. Retrieved 2023-05-01.
  22. 1 2 3 Hwang, Woo Suk; Ryu, Young June; Park, Jong Hyuk; Park, Eul Soon; Lee, Eu Gene; Koo, Ja Min; Jeon, Hyun Yong; Lee, Byeong Chun; Kang, Sung Keun; Kim, Sun Jong; Ahn, Curie; Hwang, Jung Hye; Park, Ky Young; Cibelli, Jose B.; Moon, Shin Yong (2004). "Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst". Science. 303 (5664): 1669–1674. Bibcode:2004Sci...303.1669H. doi:10.1126/science.1094515. ISSN 1095-9203. PMID 14963337.
  23. 1 2 Pilcher, Helen R. (2004-02-12). "Cloned human embryos yield stem cells". Nature: news040209–12. doi:10.1038/news040209-12. ISSN 0028-0836.
  24. 1 2 3 Pearson, Helen (2004). "Cloning success marks Asian nations as scientific tigers". Nature. 427 (6976): 664. doi:10.1038/427664b. ISSN 0028-0836. PMID 14973443. S2CID 4354771.
  25. 1 2 Vogel, Gretchen (2004-02-13). "Human cloning. Scientists take step toward therapeutic cloning". Science. 303 (5660): 937–939. doi:10.1126/science.303.5660.937. ISSN 1095-9203. PMID 14963293. S2CID 83934241.
  26. 1 2 3 4 Graham, Sarah (2004). "Cloned Human Embryos Yield Stem Cells". Scientific American. Retrieved 2023-05-01.
  27. 1 2 Hwang, Woo Suk; Roh, Sung Il; Lee, Byeong Chun; Kang, Sung Keun; Kwon, Dae Kee; Kim, Sue; Kim, Sun Jong; Park, Sun Woo; Kwon, Hee Sun; Lee, Chang Kyu; Lee, Jung Bok; Kim, Jin Mee; Ahn, Curie; Paek, Sun Ha; Chang, Sang Sik (2005-06-17). "Patient-Specific Embryonic Stem Cells Derived from Human SCNT Blastocysts". Science. 308 (5729): 1777–1783. Bibcode:2005Sci...308.1777H. doi:10.1126/science.1112286. ISSN 0036-8075. PMID 15905366. S2CID 86634281.
  28. ↑ Kirk, Jeremy (2005-05-29). "The scientist behind stem cell success story / South Korean's lab announced major breakthrough this month". SFGATE. Retrieved 2023-05-07.
  29. ↑ Gazzaniga, Michael S. (2004). "Human being redux". Science. 304 (5669): 388–389. doi:10.1126/science.304.5669.388c. ISSN 1095-9203. PMID 15087527. S2CID 41038049.
  30. 1 2 Paulson, Tom (2004-02-13). "U.S. scientists fear losing out on cloning". Seattle Post-Intelligencer. Retrieved 2023-05-01.
  31. ↑ Kluger, Jeffrey (2004-04-26). "Woo Suk Hwang & Shin Yong Moon". Time. ISSN 0040-781X. Retrieved 2023-05-01.
  32. ↑ Landry, Donald W.; Zucker, Howard A. (2004). "Embryonic death and the creation of human embryonic stem cells". The Journal of Clinical Investigation. 114 (9): 1184–1186. doi:10.1172/JCI23065. ISSN 0021-9738. PMC 524233. PMID 15520846.
  33. ↑ Durkin, John T. (2004-09-03). "The Case Against Stem Cell Research". Science. 305 (5689): 1402. doi:10.1126/science.305.5689.1402a. ISSN 0036-8075. PMID 15353781. S2CID 8641776.
  34. ↑ Song, Sang-yong (2004). "Stem cell research in Korea". Science. 305 (5686): 944–945, author reply 944–945. doi:10.1126/science.305.5686.944. ISSN 1095-9203. PMID 15310877. S2CID 37571392.
  35. ↑ Kendler, Howard H. (2004-11-19). "Assisting, but not dictating". Science. 306 (5700): 1289. doi:10.1126/science.306.5700.1289b. ISSN 1095-9203. PMID 15550642. S2CID 5148760.
  36. ↑ Kim, Manjae; Jun, Bang-Ook (2015). "Hwang Woo-Suk Scandal Reconstructed Based on Mass Mobilization" (PDF). Eubios Journal of Asian and International Bioethics. 25 (2): 34–37 – via PhilPapers.
  37. ↑ "South Korea Rolls Out Stem Cell Hub". Science. 310 (5747): 419. 2005-10-21. doi:10.1126/science.310.5747.419b. ISSN 0036-8075. S2CID 84225806.
  38. ↑ "World stem cell hub launched in Seoul". cordis.europa.eu. 20 October 2005. Retrieved 2023-05-05.
  39. ↑ McGrath, J.; Solter, D. (1984). "Completion of mouse embryogenesis requires both the maternal and paternal genomes". Cell. 37 (1): 179–183. doi:10.1016/0092-8674(84)90313-1. ISSN 0092-8674. PMID 6722870. S2CID 26447702.
  40. ↑ Cibelli, Jose B.; Grant, Kathleen A.; Chapman, Karen B.; Cunniff, Kerrianne; Worst, Travis; Green, Heather L.; Walker, Stephen J.; Gutin, Philip H.; Vilner, Lucy; Tabar, Viviane; Dominko, Tanja; Kane, Jeff; Wettstein, Peter J.; Lanza, Robert P.; Studer, Lorenz (2002). "Parthenogenetic stem cells in nonhuman primates". Science. 295 (5556): 819. doi:10.1126/science.1065637. ISSN 1095-9203. PMID 11823632. S2CID 46414300.
  41. ↑ Holden, Constance (2002). "Stem cell research. Primate parthenotes yield stem cells". Science. 295 (5556): 779–780. doi:10.1126/science.295.5556.779a. ISSN 1095-9203. PMID 11823611. S2CID 82265912.
  42. ↑ Simerly, Calvin; Dominko, Tanja; Navara, Christopher; Payne, Christopher; Capuano, Saverio; Gosman, Gabriella; Chong, Kowit-Yu; Takahashi, Diana; Chace, Crista; Compton, Duane; Hewitson, Laura; Schatten, Gerald (2003). "Molecular correlates of primate nuclear transfer failures". Science. 300 (5617): 297. doi:10.1126/science.1082091. ISSN 1095-9203. PMID 12690191. S2CID 19363117.
  43. ↑ Vogel, Gretchen (2003). "Misguided Chromosomes Foil Primate Cloning". Science. 300 (5617): 225–227. doi:10.1126/science.300.5617.225. ISSN 0036-8075. PMID 12690154. S2CID 86255567.
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