Hwang affair

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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]

Contents

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, a 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. 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

Related Research Articles

<span class="mw-page-title-main">Cloning</span> Process of producing individual organisms with identical genomes

Cloning is the process of producing individual organisms with identical genomes, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction; this reproduction of an organism by itself without a mate is known as parthenogenesis. In the field of biotechnology, cloning is the process of creating cloned organisms of cells and of DNA fragments.

<span class="mw-page-title-main">Dolly (sheep)</span> First cloned mammal (1996–2003)

Dolly was a female Finn-Dorset sheep and the first mammal that was cloned from an adult somatic cell. She was cloned by associates of the Roslin Institute in Scotland, using the process of nuclear transfer from a cell taken from a mammary gland. Her cloning proved that a cloned organism could be produced from a mature cell from a specific body part. Contrary to popular belief, she was not the first animal to be cloned.

<span class="mw-page-title-main">Human cloning</span> Creation of a genetically identical copy of a human

Human cloning is the creation of a genetically identical copy of a human. The term is generally used to refer to artificial human cloning, which is the reproduction of human cells and tissue. It does not refer to the natural conception and delivery of identical twins. The possibilities of human cloning have raised controversies. These ethical concerns have prompted several nations to pass laws regarding human cloning.

<span class="mw-page-title-main">Stem cell</span> Undifferentiated biological cells that can differentiate into specialized cells

In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage. They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type.

<span class="mw-page-title-main">Chimera (genetics)</span> Single organism composed of two or more different populations of genetically distinct cells

A genetic chimerism or chimera is a single organism composed of cells with more than one distinct genotype. In animals and human chimeras, this means an individual derived from two or more zygotes, which can include possessing blood cells of different blood types, and subtle variations in form (phenotype). Animal chimeras are produced by the merger of two embryos. In plant chimeras, however, the distinct types of tissue may originate from the same zygote, and the difference is often due to mutation during ordinary cell division. Normally, genetic chimerism is not visible on casual inspection; however, it has been detected in the course of proving parentage. In contrast, an individual where each cell contains genetic material from two organisms of different breeds, varieties, species or genera is called a hybrid.

<span class="mw-page-title-main">Somatic cell nuclear transfer</span> Method of creating a cloned embryo by replacing the egg nucleus with a body cell nucleus

In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a body cell and an egg cell. The technique consists of taking a denucleated oocyte and implanting a donor nucleus from a somatic (body) cell. It is used in both therapeutic and reproductive cloning. In 1996, Dolly the sheep became famous for being the first successful case of the reproductive cloning of a mammal. In January 2018, a team of scientists in Shanghai announced the successful cloning of two female crab-eating macaques from foetal nuclei.

<span class="mw-page-title-main">Blastocyst</span> Structure formed around day 5 of mammalian embryonic development

The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the embryoblast which subsequently forms the embryo, and an outer layer of trophoblast cells called the trophectoderm. This layer surrounds the inner cell mass and a fluid-filled cavity known as the blastocoel. In the late blastocyst, the trophectoderm is known as the trophoblast. The trophoblast gives rise to the chorion and amnion, the two fetal membranes that surround the embryo. The placenta derives from the embryonic chorion and the underlying uterine tissue of the mother.

<span class="mw-page-title-main">Embryonic stem cell</span> Type of pluripotent blastocystic stem cell

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Hwang Woo-suk is a South Korean veterinarian and researcher. He was a professor of theriogenology and biotechnology at Seoul National University until he was dismissed on March 20, 2006. He was considered a pioneering expert in stem cell research and even called the "Pride of Korea". However, he became infamous around November 2005 for fabricating a series of stem cell experiments that were published in high-profile journals, the case known as the Hwang affair.

<span class="mw-page-title-main">Stem-cell line</span> Culture of stem cells that can be propagated indefinitely

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Gerald Schatten is an American stem cell researcher with interests in cell, developmental, and reproductive biology. He is Professor and vice-chair of Obstetrics, Gynecology and Reproductive Sciences and Professor of Cell Biology and of Bioengineering in the Schools of Medicine and Engineering at the University of Pittsburgh, where he is also Director of the Division of Developmental and Regenerative Medicine at the university's School of Medicine. Additionally, he is deputy director of the Magee-Women's Research Institute and Director of the Pittsburgh Development Center.. He is a member of the NCI-designated University of Pittsburgh Cancer Center and the McGowan Institute for Regenerative Medicine.

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Stemagen is a corporation headed by Dr. Samuel Wood, notable for cloning adult skin cells On January, 2008, Dr. Andrew French, Stemagen's chief scientific officer and Wood in California, announced that they successfully created the first 5 mature human embryos using DNA from adult skin cells, aiming to provide a less-controversial source of viable embryonic stem cells. Dr. Wood and a colleague donated skin cells, and DNA from those cells was transferred to human eggs. It is not clear if the embryos produced would have been capable of further development, but Dr. Wood stated that if that were possible, using the technology for reproductive cloning would be both unethical and illegal. The 5 cloned embryos, created in Stemagen Corporation lab, in La Jolla, were later destroyed to confirm the nuclear transfer process.

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The laws and policies regarding stem cell research in the People's Republic of China are relatively relaxed in comparison to that of other nations. The reason for this is due to different traditional and cultural views in relation to that of the West.

<span class="mw-page-title-main">Cell potency</span> Ability of a cell to differentiate into other cell types

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<span class="mw-page-title-main">Yi Zhang (biochemist)</span> Chinese-American biochemist

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References

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