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The Ethical and Regulatory Problems in the Stem Cell Scandal
Aera Han
Harvard Law School
LL.M. Candidate, Class of 2006
*This paper is submitted in satisfaction of both the course requirement of the Food and Drug Law (Winter 2006) and the LL.M. written work requirement.
*Abstract :
The recent stem cell scandal of fabrication of two papers published in Science by Dr. Hwang Woo Suk shocked the world and devastated the South Korean society. Investigations conducted by the South Korean government have revealed a variety of ethical and regulatory failures. In this paper, I first explain the South Korean regulatory background to research conducted on human subjects in general and on biotechnological research in particular, and then analyze the ethical and regulatory problems affecting the research for the two papers published in 2004 and 2005, respectively. These problems can be summarized as: 1) problems regarding egg donation (lack of informed consent and donation by vulnerable subjects), 2) ambiguous record-keeping of research funding, 3) insufficient reviews by the two local IRBs (an already established IRB and a newly established IRB, both deferred to the principal scientist's heavy-handed influence), 4) too close ties between the research team and government officials, and 5) the National Bioethics Committee's inertia and lack of impartiality.
The Ethical and Regulatory Problems in the Stem Cell Scandal
Han, Aera [*]
*This paper is based on the facts investigated and disclosed by May 2006. Though the overall picture is likely to remain the same, some of the details may require modification of this paper in accordance to reflect results of further investigations.
The recent stem cell scandal surrounding Dr. Hwang Woo Suk’s research and publication shocked the scientific world and devastated the South Korean society. After the outbreak of the scandal, the National Bioethics Committee (“NBC”), [1] Seoul National University, [2] the Board of Audit and Inspection, [3] and the Seoul Central District Prosecutors’ Office of the Republic of Korea, [4] respectively, began to investigate various aspects of the scandal; and, its details have mostly been revealed. Though the outright fabrication of scientific research and discoveries is the most shocking part of this scandal, the ethical problems underlying Dr. Hwang's actions also send a clear warning signal.
Ethicists, religious groups and human right activists have consistently raised ethical questions regarding the progress of the research. The concerns were obvious from a layperson’s point of view, even though it might have been difficult for Dr. Hwang's “peers” to notice the scientific fabrication of his highly specialized papers. However, in South Korea, experts and government officials who were supposed to supervise his research showed too much enthusiasm about his alleged success and, in the process, forgot prudence and caution. Instead, they shared the benefits, and even issued an official indulgence for Hwang’s team, until it was revealed that most of the research was fake. If the research itself were truthful, the government and scientific peers, focusing only on the seemingly fabulous outcome, would still have ignored ethical and procedural injustice, and the research would have gone on for at least a while without significant supervision, until a real tragedy broke out, such as the death or severe injury of an egg donor.
South Korea does have a regulatory system to oversee clinical trials and biotechnological research. However, no safeguards that were in effect were unable to prevent Dr. Hwang's ethical misconduct or his forgery of the data. The NBC, removed from the daily workings of the local research labs, could not properly oversee their behaviors. What they could do was impose retrospective remedies such as the issuance of an investigative report, suspension of the researchers’ qualifications, or recommendation of stricter regulatory rules. The responsibility to prevent ethical misconduct prospectively rested with the researchers themselves and the local Institutional Review Boards ("IRBs"), but in this case, they dramatically failed.
Some people might mistakenly believe that this kind of scandal cannot occur in developed countries that have well-established regulatory systems known for their highest level of bioethical concern. However, most of the ethical problems shown in this scandal are neither new to nor unheard of in scientific research. [5] Rather, when success is near at hand, there have always been a few researchers who surrendered to the temptation to bypass ethical considerations, hoping that nobody would uncover their ethical misconduct, and even if they were caught later, they would be forgiven if the outcome were successful. Therefore, a regulatory scheme to protect and prohibit researchers from giving in to such temptations is especially crucial in ethical matters, in which, the traditional safeguards that guarantee the truthfulness of the research, i.e., peer review, the referee system and the process of replication,[6] might break down. This scandal provides an opportunity to review current regulations in the biomedical and biotechnological fields and to seek remedies in the hope of preventing such ethical crises.
The purpose of this paper is twofold. One is to elicit what caused the ethical failures of this scandal to readers who do not speak Korean. Though the overall story has been disclosed in English, many small details, which are important to understand how those minor wrongdoings culminated in this huge scandal, have not yet been fully interpreted. The other purpose is to prevent similar scandals from occurring again. To prevent another ethical failure, of any proportion, we need to articulate the problems and establish a safer regulatory regime. The South Korean authorities, though had once failed in many aspects to supervise Dr. Hwang's research, did not hesitate to reveal even their own problems and sins, realizing that if they tried to cover up or turn their eyes from the misconduct again, the trust of the public toward scientific research would never recover, and the price would be huge. This paper owes much to their swift and through investigations.
In this paper, I first summarize the regulatory background and structure related to the scandal surrounding Dr. Hwang’s stem cell research fabrication, and then focus on the ethical problems revealed thus far. In conclusion, I recommend several reform proposals to strengthen research ethics.
1. A brief overview of stem cell research regulations in South Korea
Stem cell research in South Korea has been regulated in two different areas. One is the general regulation of clinical trials and protection of human subjects, which has gradually developed from the late 1980s. The other is the more specific regulation of biotechnology, which has been intensely discussed since the late 1990s. These two areas of regulation partly overlap, but their main focuses and objectives differ.
a. General regulations of research on human subjects
Regulating research on human subjects in South Korea increased substantially from the early 1990s, mainly in response to burgeoning clinical trials for new drugs. In 1986 the South Korean government, as a settlement for bilateral trade disputes with the United States, agreed to offer higher patent protection for medicines and chemical compounds.[7] Within a year, the National Assembly of South Korea amended the Korean Patent Act to accord with the above agreement. The amended Patent Act broadened patent rights for chemical compounds and drugs, and admitted alien non-residents’ standing to sue in patent infringement lawsuits.[8] Until then, most Korean pharmaceutical companies had concentrated on manufacturing and selling generic drugs for which the patent had already expired, or copying drugs that were chemically identical to the patented drugs but produced by different methods to avoid lawsuits for infringement of method patents.[9] However, intellectual property protection for drugs has been enhanced by the amended Patent Act and later by the Agreement on Trade Related Aspects of Intellectual Property Rights (TRIPs),[10] making it more difficult for South Korean pharmaceutical companies to earn revenue from their former practices. Realizing the changing environment of the industry, they began to develop new drugs from the early 1990s forward, and their efforts came to fruition in the late 1990s.[11]
The South Korean government acknowledged the necessity to regulate clinical trials and offer protection to human subjects. The Ministry of Health and Welfare (MHW) of South Korea issued the Guidelines for Korean Good Clinical Practice (KGCP) [12] on December 28, 1987 as non-binding guidelines applying to pharmaceutical companies and research institutes who conducted clinical trials for new drugs; amended them on January 5, 1995 as binding regulations;[13] and last amended them on January 4, 2000[14] to adopt the Guidelines for Good Clinical Practice (“ICH-GCP”) E6 version issued by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.[15] With this last amendment, the KGCP became almost identical to the ICH-GCP and could meet the international standards, especially pertaining to IRBs.
In addition to the administrative regulations on clinical trials, civil case laws and ethical self-regulation by the medical community have also improved. After the end of an almost forty-year-long dictatorship in 1987, justice and ethics have again been emphasized. The medical profession was no exception. Medical malpractice lawsuits have increased rapidly, and the notion of “informed consent” has been adopted in contracts and torts through the interpretation of the Civil Code of South Korea. Since the late 1980s, the Supreme Court of South Korea began to apply this principle vigorously.[16] Informed consent is now an established doctrine, and even if the plaintiff cannot prove the causality between the lack of informed consent and the actual harm, if she proves the lack of informed consent itself in the medical treatment in question, she may be awarded at least compensatory damages for the emotional distress caused by the deprivation of self-determination or loss of the right to choose.[17] The Korean Medical Association (KMA) declared the Guidelines of Ethics for the Medical Profession as self-regulatory rules.[18] They reiterated doctors’ general ethical duty[19] and the doctrine of informed consent,[20] prohibited trading in human eggs for in vitro fertilization,[21] limited research on human cloning to the cure and prevention of specific diseases,[22] and recommended the establishment of a local ethics committee in each hospital and research institution.[23] As the KMA held the power to sanction member doctors who violated the mandatory clauses of the guidelines, the guidelines gained some degree of binding force. Thus, at least facially, the regulatory structure for clinical trials and protection of human subjects was established.
b. Special Regulations on Biotechnology and Stem Cell Research
The first law on biotechnology enacted in South Korea is the Genetic Technology Support Act[24] (later renamed the Biotechnology Support Act, [25] hereinafter “Biotechnology Support Act”). However, its focus was not on restricting but on promoting the biotech industry and its research efforts. [26] Art. 15 of the Act mandated that the government announce guidelines on biotechnological research to prevent biohazards and ethical problems,[27] but the "Guidelines on Recombinant DNA Experiments" according to Art. 15 of the Act had not been issued until South Korea joined the Convention on Biological Diversity in 1997. When the Guidelines were issued in accordance with the Convention, it contained only one very ambiguous article on ethics in biotechnological research.[28] Human embryonic stem cell research found itself in a regulatory vacuum for a while, as the KGCP applied only to the clinical trials on human subjects, and the Guidelines on Recombinant DNA Experiments offered no further guidelines on that matter.
It was the birth of “Dolly the Sheep” that evoked a public outcry for further regulation of stem-cell research. On February 22, 1997, a research team led by Dr. Ian Wilmut and Dr. K.H.S. Campbell of Roslin Institute in Scotland announced that they succeeded in cloning a sheep by somatic cell nuclear transfer (SCNT), [29] in which “a cell is placed in a de-nucleated ovum, the two cells fuse and then develop into an embryo.”[30] This was the first successful mammalian cloning, and everyone realized that human cloning might succeed in the near future. One episode of an alleged human cloning by Dr. Lee Boyeon and his coresearchers at the fertility clinic of Kyunghee University in South Korea,[31] other researchers' cloning successes on other mammals [32] and rising concerns regarding various ethical issues also necessitated a new comprehensive bioethics law. [33] Three different amendments to the Biotechnology Support Act were proposed by congressmen from 1997 to 1999,[34] and two different drafts of an independent act on bioethics were proposed by the Ministry of Health and Welfare (2000) and then, by the Ministry of Science and Technology (2002).[35] Later the debates evolved mainly around the governmental drafts. Biotechnological researchers and the biotech industry supported the Ministry of Science and Technology version, while bioethicists and NGOs strongly supported the Ministry of Health and Welfare version.[36] It seemed impossible to reach a uniform bill. While the legislative process stalemated under endless debates, guidelines issued by several associations were the only, insufficient, safeguards against unethical human embryonic stem cell research. [37]
However, when the South Korean branch of CLONAID™[38] announced that they had already cloned human embryos and implanted them in three Korean surrogate mothers’ uteruses[39] and later declared that a cloned baby named "Eve" had been born, both ministries and legislators recognized the dire need to prohibit human cloning, and agreed on a single draft,[40] mostly following the Ministry of Health and Welfare version, but leaving some possibilities for therapeutic cloning.[41] The Bioethics and Safety Act passed the National Assembly on December 29, 2003, was promulgated on January 29, 2004, and took effect on January 1, 2005. [42] Important provisions of the Act include: 1) establishment of the National Bioethics Committee to deliberate on matters concerning the establishment of major policies respecting bioethics and safety in biotechnology, under the President;[43] 2) general prohibition of human cloning;[44] 3) prohibition of human sperm or egg trading;[45] 4) permission of stem cell research using residual embryos[46] and by transplanting the nucleus of a somatic cell into a human egg[47] for treatment of rare or incurable diseases under the review of the National Bioethics Committee and the approval of the Minister of Health and Welfare;[48] 5) regulation of gene therapy and the DNA bank, and 6) criminal punishment for the violations of the Act. [49]
The National Bioethics Committee was formed on April 7, 2005, more than three months after the Bioethics and Safety Act and its Presidential Decree took effect on January 1, 2005. Following the Act[50] and the Decree[51] the NBC was formed, composed of seven Ministers form related government departments; seven persons with much professional knowledge and research experience in the life sciences or medicine who represented academic, research or industrial circles, or scientists; and seven persons who represented religious, philosophical, ethical, social science or legal circles, non-governmental organizations or women.[52] This was the regulatory structure in place when Dr. Hwang and his team conducted stem cell research.
2. The regulatory and ethical problems of Dr. Hwang's Human Embryonic Stem Cell research
Dr. Hwang’s human embryonic stem cell research began in 2002. It was a transitional period when biomedical and scientific policies changed from a laissez faire approach to promulgation of stricter regulations, but people’s attitudes had not progressed as rapidly. This discrepancy caused many problems in executing the laws and regulations.
Dr. Hwang Woo Suk, a former professor of the College of Veterinary Medicine at Seoul National University,[53] had already achieved renown as a veterinary scientist in South Korea, but in 1999 when he announced that his team succeeded in cloning cows, he acquired national fame.[54] It was the fifth success of mammalian cloning by the SCNT in the world, and was praised by the South Korean public as welcome news, boosting national morale that had been quite low since the economic crisis of late 1990s. As he did not submit any paper and did not keep scientific records of his research, [55] the results could not be scientifically reviewed.[56] Still, government officials and politicians were eager to support further research and share the accolades with him. From September 1, 1999 to August 31, 2000[57] he was given funding totaling approximately $1.6 million from the Ministry of Science and Technology for a project seeking to mass-produce high-capacity dairy cows by SCNT. Nobody questioned whether it would be proper to offer government funding for research that had not been properly peer reviewed. Though the project failed completely, Dr. Hwang's reputation remained intact. [58]
Unlike many other scientists who confined themselves to the research lab, Dr. Hwang was proved to be talented at public relations. He often invited reporters to his lab and showed them his experiments. He hired professional photographers for his press releases. He announced his research plans regularly, such as his attempt to clone the nearly extinct Siberian tiger, the national symbol of Korea, from a tiger cell donated by the North Korean government,[59] or to produce gnotobiotic (sterilized) miniature pigs, or to make genetically engineered cows that are resistant to mad cow disease.[60] These well-timed announcements kept Dr. Hwang in the public's eye and led to huge amounts of governmental funding and private donations. Dr. Hwang was also proved to be an active public lecturer. He conveyed his message with finesse, suggesting that the future of the nation depended on the development of biotechnology, and more governmental grants and public support should be forthcoming. His often cited comments, such as "though science has no border, a scientist does have a nationality," emphasized his patriotism, while hits remark, "my calendar has only mon-tue-wed-thu-fri-fri-fri -- there is no Saturday or Sunday" underscored his tireless efforts. He also frequently met with patients suffering from incurable diseases and gave them hope, saying that in ten years treatments to help them would be developed through the stem cell research.[61] He acquired national fame through such activities and maintained close ties with the Minister of Information and Communication, the Secretary to the President for Policy Coordination, and the Advisor to the President for Information, Science and Technology. He even met President Roh Mu Hyun in person and secured a promise of support. With such renown and relationships, Dr. Hwang could freely proceed to conduct his research under the auspices of the government.
b. Ethical and Regulatory problems relating to the 2004 paper
On February 12, 2004, Dr. Hwang Woo Suk and his research team announced that they had succeeded in the “derivation of a pluripotent embryonic stem cell line from a cloned human blastocyst.” [62] This meant that they had succeeded in creating a human embryo through cloning, and had extracted embryonic stem cells from it, for the first time in the world. They allegedly used 242 unfertilized human eggs extracted from 16 donors, "removed the genetic material from the eggs and replaced it with genetic material obtained from cumulus cells, the adult cells that cling to eggs." [63] Among them grew 30 blastocysts, of which 20 inner cell masses were removed, and one stem cell line was grown among the masses, according to their announcement and their paper.[64]
Their work stunned the world and was widely accepted as truthful.[65] Some scientists envied the research environment of South Korea where less regulations existed and such a large scale of egg donation was available.[66] Many bioethicists expressed their concern that this success would open the door to the "slippery slope" of human cloning and human enhancement.[67] Dr. Leon Kass, an ethicist famous for his anti human-cloning stance,[68] worried about the looming possibility of actual human cloning in an e-mail interview with the New York Times .[69]
As well as the general opposition on the human embryonic stem cell research, more specific ethical criticism was raised by Korean bioethicists [70] and Nature magazine [71] . They may be summarized as:
1) Suspicions about egg donation, 2) ambiguous records on research funding, 3) insufficient review by the IRB, and 4) too close ties between the research team and the government officials who had the responsibility to oversee the research.
1) Suspicions about egg donation
Dr. Hwang and his team stated in the supporting online material of the 2004 paper, "1) donors were voluntarily donating oocytes and cumulus cell (including DNA) for therapeutic cloning research ... with no financial payment ... 5) neither donors nor their family, relatives, or associates may benefit from this research."[72] However, when he claimed that his team used 242 eggs donated from 16 donors and not a single egg had been purchased, many people argued that it was unrealistic for so many women to had undergone the painful egg procurement procedure without compensation, and raised the possibility that those eggs might have been purchased, violating the then existing guidelines against egg trading.[73] Another claim was egg donations by vulnerable subjects. David Cyranoski of Nature magazine claimed that a female researcher in Dr. Hwang's team stated in an interview with Nature magazine that she, along with another female researcher, had donated eggs themselves.[74]
These were serious assertions and accusations. First, though the Bioethics and Safety Act had not yet been effectuated, which prohibits ova-trading by criminal punishment, many people thought that researchers should restrain themselves from purchasing ova, especially for ethically contentious stem cell research,[75] until the Act took effect on January 1, 2005. In addition, there were other guidelines applicable to Dr. Hwang's research that clearly prohibited researchers from purchasing eggs or sperm. The KMA's Guidelines on Research of Cloning Lives issued in May 1999 strictly prohibited trading of sperm, eggs or somatic cells.[76] As the KMA's guidelines applied at the very least to the co-researchers on Hwang’s team who had medical licenses,[77] they were bound to abide by the guidelines, and paying for the eggs would have been a violation thereof. Also the Stem Cell Research Center Ethics Committee Guidelines for Review of Research Proposals applied to a research that received grants from the Stem Cell Research Center of South Korea, which prohibited egg-trading.[78] As we see 2) infra, it was quite possible that Dr. Hwang’s team had been awarded such grants.
Second, the KGCP stipulated that special attention should be paid to trials that may include vulnerable subjects (individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate, such medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel).[79] It drew its origins from the Declaration of Helsinki, Art. 8,[80] one of the fundamental ethical rules set for the protection of human subjects. Therefore, the accusation of donation from vulnerable subjects invoked stronger reactions from the international scientific society than egg trading. While egg trading has been permitted as an economic activity or a due compensation in some countries including the United States, abuse of vulnerable subjects is too reminiscent of notorious incidents in the history of human experiments.
Dr. Hwang responded that his experiments complied with all existing international and South Korean ethical rules, rebutting, "Nature 's claim is totally groundless. I swear none of my students donated eggs for the research. For some reason, the journal is trying to undermine our study.''[81] He and Dr. Moon also criticized the Korean Bioethics Association as "in our opinion, not neutral and advocates restricting the pace of biomedical advancements, viewing new techniques as threats to society."[82] Nevertheless, Dr. Hwang did not presented any further evidence to back up his assertions, on the ground that the identities of egg donors should be kept confidential to protect them.
Considering all these disputes, the South Korean government and the IRB of Hanyang University Hospital that reviewed Hwang's research should have initiated an investigation on the ethics and legality of the egg donations at that time. But they did nothing. Left alone to launch an investigation, Park Kiyoung, the Advisor to the President for Information, Science and Technology advocated the research herself, asserting "all the ethical issues had already been settled when Dr. Hwang published the paper in Science , and he went through all the regulatory procedures and the IRB review."[83] From then forward, the egg donation issue had never received government attention until the onset of the scandal.
The recent investigation by the NBC[84] and the Seoul Central District Prosecutors' Office[85] has revealed so many problems including egg trading and egg donation from vulnerable subjects. According to the NBC's intermediary report and the Seoul Central District Prosecutors' Office's final report, the following facts were revealed:
The stem cell scandal frustrated and enraged volunteer donors who have endured the pain and ensuing side effects with the pride that they were contributing to finding a cure for serious diseases. Those egg donors, with the help of women's rights activists, filed tort lawsuits against the MizMedi Hospital where the ova had been procured, Hanyang University Hospital to which the reviewing IRB belongs, and the South Korean government who had the responsibility to supervise ova donations.[94] All of these problems could have been prevented, if the regulatory system in place had functioned properly.
2) Ambiguous Records on Research Funding
Many grants offered for stem cell research have restrictions based on the nature of the funds. The source of funding decides what rules and regulations to apply. For example, on August 9, 2001 the Bush Administration decided that federal funds would not be used for the cloning of human embryos for any purpose[95] except for research using the already existing 16 stem cell lines derived under certain specified conditions. This decision, however, does not prohibit stem cell research by a private company using private funds.[96] Therefore, it is crucial to clarify what money has been used for what research. The situation is no different in South Korea.
The 2004 paper elicited in its footnote 30 that their study "was supported by grants from Advanced Backbone IT Technology Development (grant IMT2000-C1-1) to [Woo Suk Hwang] and the Stem Cell Research Center [97] (grant M102KL0100-02K1201-00223) to [Shin Yong Moon]."[98] If so, the research should have followed the Stem Cell Research Center Ethics Committee Guidelines for Review of Research Proposals [99] issued by the Stem Cell Research Center in May 2003. As well as the statements in the 2004 paper's footnote 30 corroborating that the grants from the Stem Cell Research Center had been spent for this research, a government official's proud statement found in the announcement to the 2004 paper, "this world class paper by Dr. Hwang and Dr. Moon is related to the Stem Cell Research Center... the Stem Cell Research Center granted Dr. Moon approximately 1.9 million dollars, and 500,000 dollars of which has been used for this stem cell research."[100]
The Stem Cell Research Center Ethics Committee Guidelines for Review of Research Proposals[101] apply to research awarded the Center's grants.[102] The then current Guidelines (later amended February 2006) stipulated that it was prohibited to produce human embryos for the purpose of stem cell research;[103] embryos donated to the research should be derived from frozen surplus embryos produced for infertility treatment through in vitro fertilization that have been kept for more than five years and are soon to be discarded;[104] and the research involved should be carried out in compliance with the provisions set forth in these guidelines for stem cell research.[105] Therefore, no research by SCNT methods should have been conducted using grants offered by the Stem Cell Research Center.[106] Recognizing the problem, Dr. Hwang and Dr. Moon later denied the use of government grants for their research. They explained that the grant from the Stem Cell Research Center was a mere "technical grant,” [107] and in response to the Korean Bioethics Association as to what the term technical grant meant.[108] have never given a proper answer. This issue has not been investigated by the Stem Cell Research Center or by its Ethics Committee, and the only IRB involved, the IRB of Hanyang University Hospital, did not ask that the source of research funding should be cited in the research protocol.[109] If funding had been properly disclosed, the applicable governing rules might have been determined in the early stage and more oversight might have been conducted.
Dr. Hwang never kept thorough financial records of his research budgets, and even laundered money. This seriously impeded the accountability and transparency surrounding his research monies. In 2006, the Board of Audit and Inspection of Korea investigated governmental funds and private donations[110] awarded Dr. Hwang from 2001 to 2005,[111] and the Seoul Central District Prosecutors' Office also conducted a more thorough investigation of Dr. Hwang and his research team's embezzlement and fraud.[112] Both institutions found him to have inappropriately managed his research grants. He mixed public and private grants and his personal income in private bank accounts under his or third parties' names (all 63 names in total; most of these third parties were subordinate researchers in his lab, graduate students under his direction, and or his relatives) and laundered money for himself by extracting a considerable amount of cash from one account and depositing it to different accounts repeatedly,[113] which made investigation almost impossible. Despite a thorough investigation by the Board of Inspectors, $2.8 million remains unexplained among $16.4 million in governmental grants and $6.2 million in private donations given to Dr. Hwang.[114] According to the investigations conducted by relating authorities, Dr. Gerald P. Schatten of the University of Pittsburgh, the corresponding coauthor of the second paper, was given "honoraria totaling $40,000 within a 15-month period from Dr. Hwang – including $10,000 paid in cash while attending a press conference following publication of the 2005 paper – amounts that seems to us as far above normal honoraria for consultation"; [115] furthermore, Dr. Hwang deposited $700,000 in his private savings account; [116] bought his wife a car worth $27,000;[117] donated $55,000 to politicians;[118] handed $25,000 to $30,000 to the egg broker to purchase eggs; [119] gave $30,000 to Kim Sunjong, Dr. Hwang's junior researcher and main actor in data fabrication at the wake of the stem cell scandal, probably to ensure his secrecy;[120] and distributed the $500,000 of the money left in his checking accounts to his co-researchers arbitrarily when the fabrication was revealed.[121] It is still unclear how much of the sums spent was obtained from the research grants, because there is no way to distinguish public grants, private donations and his personal income combined in the 63 private bank accounts.
3) Insufficient Review by the IRBs
The Bioethics and Safety Act that mandates an IRB review did not directly apply to the 2004 paper.[122] Many people suspected that this clause of one-year delay was inserted by Park Kiyoung, the Advisor to the President, solely to give Dr. Hwang enough time to finish the ongoing human embryonic stem cell research for the 2004 paper. Still, there were other regulations and guidelines to follow, which did not exempt Dr. Hwang's research from the IRB review.
A. IRB Review on egg donation
As extracting unfertilized eggs from women is a non-therapeutic clinical trial on human subjects, the KGCP applied to the egg donation as a binding regulation. Therefore, the local IRB of an institution in which the egg procurements were conducted should have followed the requirements mandated by the KGCP, not least of all the duty to safeguard the rights, safety, and well-being of all trial subjects (especially vulnerable subjects); to obtain and review important documents such as written informed consent form(s) and consent form updates that the investigator proposes for use in the trial, subject recruitment procedures (e.g. advertisements), written information to be provided to subjects;[123] and to conduct continuing reviews for at least once a year.[124]
It was the IRB of Hanyang University Hospital that reviewed the ethics of egg donations for the 2004 paper.[125] The IRB had already been established and in place when the principal investigator, Dr. Hwang Yunyoung,[126] asked for a review of the research protocol on "establishment and derivation of stem cells through somatic nuclear cell transplant" (the research for the 2004 paper) in November 2002. The board, composed of 15 members, three of whom were not doctors (a reverend, a nurse, and a pharmacist) and one who was independent of the institution (a professor at another medical school), seemed to fulfill the structural requirements of both KGCP Art. 8 §1 and ICH-GCP 3.2.1. The board also had its own internal IRB Guidelines and the Standard Operating Procedure (SOP), fulfilling KGCP Art. 8 §4.[127]
However, there was no obstetrician/gynecologist among the IRB members, although the principal investigator was a respected obstetrician/gynecologist and former Dean of the institution's own medical school.[128] Under this arrangement, a thorough and impartial review by the local IRB was structurally impossible, because an IRB should have both scientific experts and impartial ethicists as its members if it wishes to conduct a balanced review. Furthermore, most of the IRB members were busy doctors or professors who had little time to spare for the extra work. The IRB sessions were held only once in a month and reviewed more than ten protocols within an hour and a half. Subcommittees composed of three board members conducted prior reviews, but it was not sufficient and the main sessions turned formalistic.[129]
At the first review session on November 5, 2002, the IRB, issuing a conditional approval on the research protocol, ordered the principal investigator to submit monthly intermediary reports on the use of donated oocytes and informed consent forms received from the patients.[130] It was a proper order considering the controversial nature of the research and potential adverse side effects that might be experienced by the egg donors. These reports, if submitted, would also have provided bases for continuing review for the propriety of egg donation and might have prevented the researchers' misconduct presented in supra 2). However, the order was never complied with by the investigators nor enforced by the IRB.[131] Instead, on February 10, 2003, the IRB issued an unconditional approval of the protocol, even though the investigators had never submitted a monthly follow-up report so far. The IRB never admonished the investigators for their noncompliance at its subsequent review sessions on protocol amendments held on April 29, 2003 and December 24, 2003, respectively. The IRB could nor detect that ovaria of 29 patients extracted by hysterectomy had been used for the research without any informed consent.[132]
The IRB's hands-off attitude similarly appeared when it reviewed the contents of the first and second protocol amendments.[133] The original protocol stated that only the ova or ovaria extracted by the result of a hysterectomy would be donated, but the amendments extended the range of ova donors to healthy non-patients. If such an important contents of the protocol had been amended, the informed consent forms, the subject recruitment process (e.g. advertisements), and the written information to be provided to subjects should also have been amended and updated. But the IRB issued its approval of the amendments unconditionally, without asking for the requisite amendments.[134]
When the research was completed, a summary of the final paper was submitted to the IRB. Later investigation revealed that all the eggs used for the 2004 paper had been extracted at clinics other than those at Hanyang University Hospital,[135] and not one of the egg procurements were reviewed by the IRB. If the IRB had asked for a full version of the paper, in which Hanyang University Hospital was designated as the only oocyte extraction site,[136] it might have had another chance to correct the researchers' misconduct.
Other problems underlying the IRB review further contributed to the ensuing ethical failure. Though the research protocol lacked information on research funding, the IRB did not request such information.[137] Though the investigator should not participate in the deliberations of the IRB or in the vote/opinion of the IRB except for providing information on an aspect of the trial,[138] investigators were casual about attending the meetings and influencing decisions.[139]
Most of the issues that needed to be redressed, had already been raised by bioethicists, civil rights activists, Nature magazine and several other media outlets shortly after the publication of the 2004 paper. The IRB, however, did not conduct a follow-up review and even refused the demand of the National Human Rights Commission of South Korea to present its records of review sessions relating to the 2004 paper.[140]
These problems are not unique to the South Korean
research environment. In 1998, a report issued by the Office of the
Inspector General of the United States, Institutional Review
Boards: A Time for Reform ,[141] pointed out six major problems in IRBs: 1) they
face major changes in the research environment; 2) they review too
much, too quickly, with too little expertise; 3) they conduct
minimal continuing review of approved research; 4) they face
conflicts that threaten their independence; 5) they provide little
training for investigators and board members; and 6) neither IRBs
nor HHS devote much attention to evaluating IRB
effectiveness.[142] These concerns encompass all failures that took
place in the IRB of Hanyang University Hospital.
B. IRB Review on the Ethics of Human Embryonic Stem Cell
Research
No IRB, government agency or committee reviewed the ethical aspects of the stem cell research by SCNT for the 2004 paper, even though guidelines applicable to the research and ethical principles mandated that they should.[143]
The researchers’ stance was that as they had spent only private money, there were no binding guidelines to their research, and therefore no IRB review would be required. Nevertheless, the Bioethics and Safety Act mandating an IRB review on human embryonic stem cell research had already been promulgated and was waiting for effectuation. Therefore, the main research institution, the College of Veterinary Medicine, Seoul National University, to which Dr. Hwang and his research lab belonged, should have formed its own IRB or should have made a review agreement with an outside IRB on this issue. However, nobody in the college asked for it. Dr. Hwang was a superstar in the College of Veterinary Medicine. It would have been practically impossible for other professors to raise ethical issues about his work or his methods. What the IRB of the College of Veterinary Medicine did, or rather, did not do regarding the 2005 paper,[144] well illustrates this point.
Another body that could have reviewed the ethics of Dr. Hwang's stem cell research was the Stem Cell Research Center Ethics Committee. Despite Dr. Hwang's claim that his lab spent only private money, there was a growing suspicion that they used public grants.[145] The Stem Cell Research Center Ethics Committee should have investigated the source of research funding, and if Dr. Hwang and his research team spent grants awarded by the Stem Cell Research Center, it should have exercised its review and oversight authority over his stem cell research.
Why had it not done so? One possible reason might be the close connection between the Stem Cell Research Center and the researchers. Dr. Moon Shin Yong[146] had been the director of the Stem Cell Research Center since its establishment,[147] and both Dr. Hwang and Dr. Moon were members of the Stem Cell Research Center Ethics Committee. Another reason could be the general lack of oversight power of the Stem Cell Research Center Ethics Committee over the Stem Cell Research Center and the researchers. The discrepancy between the Center and its Ethics Committee has been a chronic problem. The Center has awarded grants to research projects that had not been properly reviewed by its Ethics Committee or that had not followed the order of the Ethics Committee to further complement the research plan. According to an investigation by the Democratic Labor Party of South Korea[148] Policy Committee, the Stem Cell Research Center granted approximately $33 million aggregate to 232 research projects from 2002 to August 2005. Its Ethics Committee issued conditional approval or complement-needed approval to 163 projects, but the grants have been executed regardless of the follow-up complements or fulfillments of the imposed conditions. For example, in 2005, among 32 projects that had been ordered to correct ethical defects, only 23 projects actually rectified the problems.[149]
Another presumable review body on ethics of stem cell research was the KMA. If it had wanted, it could have exercised its sanction power over doctors who participate in research. However, this was also another practical improbability, because the KMA restrain itself from sanctioning its members too often, as the American Medical Association have done to its member doctors. For such a controversial, philosophical and unclear issue as stem cell research, it would have been quite difficult for the KMA investigatory committee to reach a consensus to sanction a doctor.
This regulatory and attitudinal loophole shows the necessity of universal governmental regulation of stem cell research regardless of the source of funding. After the effectuation of the Bioethics and Safety Act of 2005, the researchers have tried at least to meet this formality.
4) Too Close a Relationship between Dr. Hwang and the Government Officials
Dr. Hwang maintained good relationships with government officials. His friends or supporters in the government were sometimes criticized for exercising their power too favorably toward Dr. Hwang.
The most conspicuous was Prof. Park Kiyoung. She was a confidant of President Rho Mu Hyun and had been the former Chief Manager of the Presidential Advisory Council on Science and Technology. During 2003 she actively participated in drafting The Bioethics and Safety Act and had had considerable influence on formulating the government's science policy. In early 2004 she was appointed the Advisor to the President for Information, Science and Technology and could now exercise even greater power.[150] Dr. Park had maintained a close relationship with Dr. Hwang. While participating in the drafting of the Bioethics and Safety Act, she also conducted two subprojects for Dr. Hwang and for which she was paid approximately $250,000.[151] Many people suspected that she had changed the minor details of the Act[152] to make it more favorable to Dr. Hwang. She was included as the 13th of the 15 coauthors of the 2004 paper for no known reason;[153] if anything, her citation as coauthor further fueled the suspicion that she had exercised her power to remove regulatory hurdles hindering Dr. Hwang and had received the coauthorship as a payoff.
Dr. Lee Pilryeol, a science historian, environmental activist and professor at Korea National Open University, first questioned her contribution to the article.[154] His criticism was that with her academic background in plant molecular physiology, she could not have contributed scientifically to the human embryonic stem cell research conducted for the 2004 paper. However, Dr. Lee's article did not arrest the attention of the major media until Cyranoski of Nature magazine cited his article, again raising the specter of suspicion.[155] When the Pressian , a progressive Internet newspaper, translated most of Cyranoski's article into Korean and expressed concern that the ethical issues raised by Nature magazine could have a huge impact on the scientific community,[156] Park offered her excuse through Pressian 's online bulletin board that she deserved the authorship because of her participation in reviewing the ethical and scientific sociological aspects of the paper.[157] Though her excuse was insufficient, the major media, the public, and the government ignored the problem thus raised as well as other ethical issues, and did not take any measures in spite of the growing criticism from bioethicists.[158] Dr. Park continued to support Dr. Hwang, and helped him receive an unprecedented number of government grants.[159] Her efforts to protect and save Dr. Hwang continued until the fabrication became undeniable, at which point, she had no other but to resign.[160]
The Minister of Information and Communication Jin Daeje, and the Secretary for President for Policy Coordination Kim Byoungjun, were two other important supporters of Dr. Hwang. As Jin Daeje, Kim Byoungjun, Park Kyoung, and Dr. Hwang had such a noticeably close relationship, people had nicknamed them the "Hwanggeumbakjwi (meaning "golden bats" in Korean pronunciation)", a title coming from the combination of their four surnames with slight twist to the pronunciation. Each had known Dr. Hwang since 2001, and had vigorously supported his efforts. They even circumvented governmental policies and guidelines to support him. For example, the Ministry of Information and Communication awarded Dr. Hwang a $4.3 million grant from the Advanced Backbone IT Technology Development fund (grant IMT2000-C1-1).[161] Dr. Hwang's research had nothing to do with IT technology, and grants for biotechnology were supposed to be executed by other presiding ministries, such as the Ministry of Health and Welfare or the Ministry of Science and Technology. But then Minister Jin awarded this grant to Dr. Hwang to be used for his stem cell research.[162] However, they were not criticized but praised by the majority of the public for their support to Dr. Hwang. Considering that government officials themselves felt free to circumvent the rules to support Dr. Hwang, it would not likely for them to scrutinize his research.
c. Ethical and Regulatory Problems in the 2005 Paper [163]
Dr. Hwang and his research team had declared on February 18, 2004, right after the announcement of their 2004 paper, that they would not continue the stem cell research until the Bioethics and Safety Act took effect the following year because of ethical reasons. However, in direct contradiction to their public statement, they resumed stem cell research in October 2004,[164] largely backed by the enthusiastic support of the public and the major media. Such support enabled Dr. Hwang to overlook many regulations. His team continued to research, and on May 19, 2005, again announced that they had succeeded in creating 11 patient-specific, immune-matched human embryonic stem cells by SCNT of skin cells using 185 unfertilized human eggs. [165] If true, this would have meant the creation of “custom-tailored” stem cells for each patient with remarkably improved efficiency. Producing stem cells for one patient using about seventeen eggs exceeded any expectation and even raised the possibility of commercialization. If the 2004 paper had stunned scientists worldwide, this paper shocked them. Now Dr. Hwang was worshiped by the South Korean people as a national hero. From that time forward, Dr. Hwang acquired a superstar-like authority and popularity that was almost invincible to any criticism. The emerging voices of opponents were still too few and little heeded.[166]
However, the 2005 paper had as many ethical problems as those of the 2004 paper. Though this time the researchers in his lab had paid more attention to regulatory and ethical issues because the newly effectuated Bioethics and Safety Act now criminalized many more forms of misconduct, the new regulatory system still did not work properly. Many problems that already existed in the 2004 paper continued or worsened, while new problems surfaced under the reformed regulatory system.
1) How His Team Bypassed the Regulations
Resuming their research in September 2004, Dr. Hwang's team announced that they would perform SCNT and deriving NT-hESCs under the auspices and oversight of the Hanyang University IRB for Human Subjects Research and Ethics Committee. However, this IRB reviewed only factors concerning egg-donation; the ethics of stem cell research remained untouched by this IRB.[167]
The Bioethics and Safety Act that took effect on January 1, 2005 prohibited any human embryonic stem cell research without the review of the institutional review board (IRB)[168] and the National Bioethics Committee (NBC).[169] It also required final prior approval by the Ministry of Health and Welfare.[170] However, its Addenda (3) allowed an exception, which stated, "if a person who is carrying out research on somatic cell cloning embryos for research purposes...at the time of the entry into force of this Act meets the requirements of the following subparagraphs, he/she may continue to conduct such research with approval therefor from the Minister of Health and Welfare: 1. He/She has been conducting research on somatic cell cloning embryos for not less than three years; and 2. His/Her research on somatic cell cloning embryos has been published in related scientific journal at least once."[171] Dr. Hwang’s team was the only research team in South Korea that could meet the requirement of Addenda (3) when the Act took effect.[172]
His team received approval from the Minister of Health and Welfare on January 12, 2005[173] in accordance with Addenda (3). In fact, it was the first approval issued under the new Act. Dr. Hwang's research was exempted from review by the NBC, which had not yet been formed. The quickly formed IRB of the College of Veterinary Medicine at Seoul National University (hereinafter the “IRB of the College of Veterinary Medicine”), conducted a formalistic review of the ethics of Dr. Hwang's stem cell research and approved it on January 23, 2005.[174] As shown infra 4), the IRB of the College of Veterinary Medicine was rife with ethical problems; some IRB members listed on its documents did not even know that they had been appointed members. Once Dr. Hwang's team was approved, they faced no additional review or supervision.
2) Continuing Problems
Many problems presented supra II. 2. b. were repeated and sometimes worsened in the research for the 2005 paper. Review of egg procurements for the 2005 paper by the IRB of Hanyang University Hospital remained to be insufficient.[175] The IRB did not properly review the incomplete informed consent forms that were used for the egg donors. This time the informed consent forms were disclosed through the supporting online materials for the 2005 paper,[176] but they were severely criticized for lacking critical information fully disclosing side effects that could arise such as infertility or death.[177] Researchers did not comply with the requirement to submit continuing monthly reports on egg donations and serious side effects, if experienced by the donors. Rather, the IRB issued approval regardless of the investigators' lack of compliance.[178] Though the Hanna Women's Clinic received egg donations from its own infertility patients, and provided compensation to 25 of them by discounting or exempting the in vitro fertilization fee (approx. $1,800 to $2,300 per person), such actions went unnoticed by the IRB.[179] The IRB review of the 2005 paper became more formulaic, as Dr. Hwang's popularity and fame had increased substantially. Not one board member was willing to question him or his methods.
Dr. Hwang received more government grants and private donations, but his negligent or intentional spending continued.[180] Most of the private donations that had begun to amass exponentially from 2004 forward were not properly managed or audited.
Again coauthorships were awarded arbitrarily. Oh, Sun Kyung and Kim, Hee Sun, the 21st and 22nd coauthor were cited as coauthors in the 2005 paper,[181] but their contributions had not been for the 2005 paper but for the 2004 paper.[182] Dr. D. H. Chung (Seoul National University Hospital) was acknowledged for teratoma histopathology in the 2005 paper due to a similar reason.[183] The authorship of the other corresponding coauthor, Dr. Schatten of the University of Pittsburgh, was also problematic. Though many criticized that his contribution was not sufficient to be awarded a corresponding coauthorship,[184] Dr. Schatten did not hesitate to emphasize his role in analyzing data and writing the drafts for the 2005 paper. But when the scandal broke, he retracted his previous statements and admitted instead that his role had been very limited only to insignificant matters. The University of Pittsburgh accepted his excuses and concluded that his behavior did not fall into the very narrowly defined category of "misconduct,"[185] but a number of ethicists believed he should have been held to account.[186]
Dr. Hwang's ties with Korean government officials not only continued but strengthened. The government even awarded Dr. Hwang the title of "Supreme Scientist" and $3 million in grants.[187] After the announcement of the 2005 paper, the government offered him 25 billion won (approximately $25 million) to construct a cutting-edge biotech research center to be named the “Hwang Woo Suk Research Center,’’ the future home for the “World Stem Cell Hub.”[188] Many government officials stood by him until the very end.
3) The Structural and Functional Problems of the NBC
The NBC was a new body, and the government had not completely prepared for the new regulatory regime during the one-year waiting period from the promulgation to the effectuation of the Bioethics and Safety Act. When the Ministry of Health and Welfare approved Dr. Hwang’s research on January 12, 2005, its spokesperson commented that this approval was only temporary, and Dr. Hwang would have to again seek approval under the new NBC review guidelines as soon as the NBC was formed and the Presidential Decree on Human Embryonic Stem Cell Research by SCNT was issued.[189] He said that he expected that this would be completed within a month.[190] Instead, it took an additional four months for the government to form the NBC, and the NBC held its first session on July 15, 2005. No Presidential Decree on Human Embryonic Stem Cell Research by SCNT had been issued before the stem cell scandal broke. Dr. Hwang’s 2005 paper as well as other projects on SCNT stem cell research had thus been conducted solely under the discretion of the Ministry of Health and Welfare based on the requirements set forth in Addenda (3).
What could have been the reason for this delay? It is likely that the government focused only on Dr. Hwang’s research, for he had achieved such an unprecedented fame and popularity as a scientist and thus had true political clout. Mesmerized by the overly enthusiastic reports circulated by the major media,[191] most of the Korean public shared the belief that biotechnology, especially stem cell research, would be the magic bullet that could cure any patient and ensure national prosperity. These public sentiments strengthened the government’s blind support of Dr. Hwang's research. Considering the mass hostility against the MBC PD Notebook that had first attacked Dr. Hwang, it would have been difficult for the government to go against such strong public sentiment. Government officials therefore felt that they had no reason to establish any restrictions against Dr. Hwang’s research. However, other prominent research teams such as that at the College of Medicine, Pochon Cha University or Dr. Park Sepil’s team at Maria Infertility Hospital[192] that could not literally meet the requirements of Addenda (3) but had the scientific background and expertise to conduct SCNT stem cell research were statutorily blocked both from gaining Addenda (3) approval and from obtaining NBC approval.[193]
Then, why did the NBC fail to move quick enough to review Dr. Hwang’s research? Wasn’t it the NBC’s role to stop unethical and unreviewed research and to rein in the government’s blind support and funding? However, the NBC could not yet function properly due to structural problems, which Prof. Lee Inyoung[194] pointed out at the Emergency Forum: to Guarantee the Ethics and Integrity of Biotechnological Research held in Seoul by the Korean Bioethics Association on January 24, 2006. The idea put forth by the forum may be summarized as the structural politicization of the committee's members and the limitation of their powers.
First, according to the Bioethics and Safety Act,[195] among 16 to 21 members of the NBC (actually 21 members had been commissioned), one third, i.e., seven Ministers of related departments would be automatically included, seven members would be commissioned from scientists or the industrial sector, and the remaining seven members would be commissioned from “religious, philosophical, ethical, social science or legal circles, non-governmental organizations ... or women” by the President. As all the Ministers were to be appointed by the President, they would be under the direct power of the President, and the scientists would also generally be proponents of less oversight and more support. However, members from other areas would not necessarily advocate the need for strict review, because they came from a variety of various fields and subscribed to a variety of philosophies, especially since the President would commission people sharing similar philosophical and political backgrounds with him.[196] This means that any important decision made by the NBC would tend to be under the full control of the President and the government, and if the government’s position were more favorable to research and development, there would be no meaningful deterrence or review power that could be exercised by the ethicists.[197] What exacerbated the inertia of the NBC was that the committee sessions were to be called either only by the chairperson who was also to be appointed by the President or by at least seven votes of the members.[198] Considering the dynamics among the members, gathering seven votes would not be easy. The fact that the NBC held only two sessions during the first seven months (one in April and one in October) underscores their structural inertia.
Another problem raised by Prof. Lee Inyoung at the above forum[199] was the NBC’s lack of investigatory power. Unlike other statutory committees in Korea, the NBC lacked the power to conduct independent investigations, more specifically, to subpoena witnesses, to call for testimony by related government officials or experts, or to ask for the cooperation of other administrative agencies. Its power was limited to investigation through documents, which was too indirect and too insufficient to enable it to achieve a meaningful outcome. This stemmed largely from origin of the Bioethics and Safety Act. Due to the fact that it was the result of political compromise, the Act had not made it clear whether the NBC should be an advisory committee focusing on setting policy (which was preferred by the scientists and biotech companies), or a supervisory committee that could exercise oversight and sanction powers over researchers (which was preferred by ethicists, religious groups, and civil rights activists).[200] The Act intended the latter, but given the lack of supporting authority, the NBC could only function as a weakened advisory committee.
In sum, under the Bioethics and Safety Act, if several members of the NBC had raised questions regarding Dr. Hwang’s research, they would not have gathered enough votes to hold a session, and even if they could have gotten the necessary seven votes and acquired the necessary consensus to initiate a further investigation, their limited investigatory powers would have prevented them from uncovering Dr. Hwang’s misconduct.
4) The Problems of the IRB of the College of Veterinary Medicine
Conflicts of interest have been always a chronic problem of the IRBs. Can the doctors or professors who are working in the same building with the investigators make neutral and independent decision? Can outside IRB members who are paid by the research institution or eventually by the investigators who provide a large share of budget to the research institution be free from such financial incentives? Would it not be too tempting to pressure the IRB members to overlook some ethical considerations and receive approval as soon as possible, especially when patent rights or other financial interests are at stake? Many safeguards to avoid such conflicts of interest have not worked well, even in the countries with a long history of IRBs.[201] Another chronic problem of the IRBs is the lack of education of its members. Reviewing research from an ethical perspective is very different from conducting a scientific review, but in many cases, the professors or researchers in the same institute dominate the IRB, and they are not necessarily experts on ethics. The IRB of the College of Veterinary Medicine failed in both aspects.
One reason for its disastrous dysfunction or nonfunction was that no IRB had existed at the College of Veterinary Medicine prior to Dr. Hwang’s research. As explained supra II.1.a, most IRBs in Korea were established for the clinical trials of the new drugs. Therefore, their expertise was on protection of human subjects in clinical trials. At the College of Veterinary Medicine where no human experiments had been conducted, an IRB should have been established from nothing. As Dr. Hwang was a superstar in the College, he could choose anyone he liked as an IRB member. The members he chose mostly did not know what the IRB should review, and assumed the IRB was simply a formality. All the problems are well illustrated in the NBC report.[202]
Dr. Hwang and another coresearcher Dr. Lee Byung Chun hurried to form the IRB of the College of Veterinary Medicine in order to be approved under Addenda (3) of the Act.[203] They selected the IRB members and remarkably did not even notify some of them that they had been appointed to the IRB board. Members were mostly colleagues at the College of Veterinary Medicine, and one outside member was a reverend who had a seriously ill daughter and even later donated her somatic cells to the “World Stem Cell Hub” established by Dr. Hwang, hoping Dr. Hwang's research could cure her some day. The IRB’s final approval that was included in the supporting online materials of the 2005 paper was not signed by the chairperson Prof. Lee Youngsun but by someone else, probably someone on Dr. Hwang's team. Prof. Lee Youngsun later admitted that he did not even know he was a member, let alone the chairperson of the IRB until October 2005. Other officially listed members also admitted their total lack of knowledge of their membership. By October 2005, the IRB had held three meetings, but had kept no proper records, so when it was ordered to submit its records to the NBC, its members had to reconstruct them . The members were unaware of the basic principles, for instance, that the investigators should not participate in discussions or decisions; that the members should not delegate their review power to others; that it was the IRB’s duty to require continuing intermediary reports from the investigators; and that the IRB should keep the research protocol with other IRB documents, which the investigators were handed back immediately after the review. Its SOP was identical to that of the Seoul National University College of Medicine, which was solely for the clinical trials of new drugs and lacked any guidance for stem cell research. Above all, no review of the ethics of human embryonic stem cell research by SCNT, one of the main purposes of this IRB, had been conducted.
Another problem highly criticized by the NBC report was the protective attitude the IRB displayed when the issue of egg donation began to rise in November 2005.[204] The IRB of the College of Veterinary Medicine conducted a very formalistic investigation and concluded that there had not been any major ethical violations in Dr. Hwang's research and attributed most controversies to the cultural differences between the Eastern tradition and Western ethics codes.[205] This investigation report was released to the press not by the chairperson of the IRB but by an official of the Ministry of Health and Welfare under the President's Advisor, Park Kiyoung’s order, to make the report appear to be more credible.[206]
It is worth noting how Dr. Hwang's fabrication was revealed and what happened afterwards.
For a while, Dr. Hwang enjoyed worldwide fame. Governmental funding and private donations flowed to him. Scientists all over the world wanted to make joint-research agreements with him.[207] When Hwang declared that he had succeeded in cloning an Afghan hound male puppy named “Snuppy”[208] and released photos of him and the puppy taken by a professional photographer on August 4, 2005,[209] his reputation reached an unprecedented level in Korean science history. Meanwhile, ethical objections were being stronger, especially from the Catholic Church of Korea, which announced its plan to raise a 10 billion won (approximately $10 million) fund for adult stem cell research.[210] Still, until late 2005, most people would have never questioned the ethics and integrity of Dr. Hwang’s papers–they were too overwhelmed by his continuing successes and continued to blindly worship him.
The revelation began by a whistle-blower. Ryu, Young June, coauthor of the 2004 paper, had left the research team in April 2004, disappointed by Dr. Hwang's exaggerated and hasty press releases and other instances of ethical misconduct. When Ryu heard the news of the 2005 paper, he immediately suspected fabrication, because according to his expertise and knowledge, such a quick achievement was technically impossible. He posted the message on the confidential bulletin board of MBC (Munhwa Broadcasting Corporation) that Hwang’s team paid the ova donors for the human eggs, and there was also a possibility that Hwang’s 2005 paper might have been fabricated.[211] Han Haksu, a producer of MBC's newsmagazine “PD Notebook,” received this information on June 1, 2005 and began to investigate.[212] Han's team tried to keep the investigation confidential, but rumors began to spread, and soon other newspapers and government agencies began to pay attention to the issues raised.[213] On November 9, 2005, the police start investigation of the CEO of a company named "DNA Bank," who was also an egg broker and provided ova for Dr. Hwang's team. Acknowledging the suspicion surrounding ova donations, Gerald P. Schatten of the University of Pittsburgh, the corresponding coauthor of the 2005 paper, announced on November 11, 2005 that he was suspending his ties with Dr. Hwang’ s team due to ethical reasons.[214] On November 21, one of the coauthors of the first paper, Dr. Rho Sung-il, confessed that he purchased eggs from donors to conduct the research.[215] It was time for the PD Notebook to strike. On November 22, 2005, the first accusation, “ The Myth of Hwang Woo Suk and the Suspicion over Eggs ” was broadcasted nationwide in South Korea.[216] The first among four in the series focused on the issue of ova donations, especially donations by the female researchers and ova trading. Han also claimed that when his newsmagazine team had conducted DNA tests through a private DNA testing facility comparing the original donors’ somatic cells with the alleged patient-specific stem cell lines cloned from the donors' cells, the result indicated that the stem cell lines were different form the donors' DNA fingerprints.
The backlash was huge. Angry citizens blamed this program for trying to scar a national hero with trivial charges for ignorable ethical misdemeanors and impede the development of biotechnology. Scientists scorned that Han and his team were trying to conduct amateur scientific reviews beyond their ability. Women volunteered to donate their eggs to support Dr. Hwang.[217] Major newspapers, usually the opposite side of the MBC's political spectrum, criticized left-wing producers of the program for having used unethical and coercive measures to investigate with unpatriotic zeal. All of the twelve sponsors of the program canceled their advertisement agreements with the MBC under pressure from consumers. The Ministry of Health and Welfare, based on the investigation of the IRB of the College of Veterinary Medicine at Seoul National University, announced that there were no major ethical violations.[218] Though the National Bioethics Committee’s investigation was still in progress, when the MBC’s board of directors decided to cancel the broadcasting of the second series of PD Notebook, shut the program down, and sanction the producers and journalists for resorting to coercive and unethical investigative methods, it seemed that Dr. Hwang's reputation and research would indeed be saved.
The story did not end here. Young South Korean biotech scientists blogging on the Biological Research Information Center (BRIC) Website began to post their analyses on the 2005 paper.[219] On December 5, 2005, an anonymous blogger posted a message that several allegedly different photos included in Dr. Hwang’s 2005 paper were actually derived and manipulated from a single photo, and the similarity was discernable to anyone.[220] The next day, another person logging in with the username “areung” pointed out that the DNA fingerprint data of the two different cells were so similar in Hwang’s 2005 paper, and that they were an impossibility in the real world. These two messages were rapidly disseminated through the Internet and finally led the science professors at Seoul National University to ask for further investigation.[221] When scientific evidence of falsification became evident, Dr. Hwang tried to defend himself based on the authority of the journal Science .[222] His fate was doomed, however, when his co-researcher, Dr. Rho Sung-il of MizMedi Hospital, confessed, "nine of the 11 stem -cell lines Dr. Hwang claimed to have created in the 2005 paper don’t even exist."[223]
Further revelations followed in the wake of Dr. Rho’s confession. Immediately resurrected, PD Notebook broadcasted the second series, “Why PD Notebook Asked for Reinspection” on the same day. In the program, a junior researcher, Kim Sunjong, confessed that he created 9 non-existing stem-cell-line data from only 2 stem-cell lines upon Dr. Hwang’s order.[224] Seoul National University quickly formed its own investigative committee and declared on December 23, 2005 that the data of 11 stem cell lines described in the 2005 paper were fabricated from only 2 stem cells.[225] The committee announced[226] after further investigation that both the 2005 paper and the 2004 paper were fabricated while the research on “Snuppy” was truthful.[227] This result was confirmed again by the criminal investigation.[228]
According to the investigations conducted by the Seoul National Investigation Committee[229] and the Seoul Central District Prosecutors' Office,[230] the fabrications occurred as follows:[231]
1) The 2004 paper[232]
In February 2003, one of the researchers in Dr. Hwang's team created an embryo using Donor Rho's unfertilized egg and cumulus cells and extracted stem cells from it. However, by mistake, not Donor Rho but Donor Lee was recorded as the donor, and Dr. Hwang believed that this embryo (codenamed NT-1) was created from Donor Lee's cells. When the DNA extraction from the NT-1 stem cell line was delayed (the DNA extraction was necessary for DNA fingerprinting to prove that the stem cell line and the donor's somatic cell had the same DNA), he ordered his subordinate researchers to divide DNA materials extracted from the donor's somatic cell (in this case, Donor Lee's somatic cell) into two tubes and send them to a DNA inspection institute as if one were extracted from the stem cell line and one were from the donor's somatic cell.[233] No doubt the results of DNA fingerprinting of both tubes were identical, and those data were presented in the 2004 paper. Photos of the NT-1 stem cell line or teratoma were substituted with clearer photos of completely different cells, and details of various test results were also changed. It is still unclear whether the NT-1 embryo was created by the autologous nuclear transfer using donor Rho's egg and somatic cells, or by the parthenogenesis resulted from the imperfect nucleus removal from the oocyte and inadvertent input of the polar body into it.
2) The 2005 paper[234]
From September 2004, Dr. Hwang's team began research on creating patient-specific stem cells. They created embryos by SCNT and cultured them to blastocysts, though with a lower success rate, since they had used far more eggs than presented in the paper. The inner cell mass (ICM) of the first successfully grown blastocyst (codenamed NT-2) was seeded in feeder cells (they were mouse feeder cells, not human feeder cells as presented in the 2005 paper) in late September 2004. As Dr. Hwang's expertise was on culturing blastocysts, not on deriving stem cell lines from blastocysts, he completely relied on Kim Sunjong, a junior researcher in Hwang's team and also researcher at MizMedi Hospital. On October 5, 2004, the ICM stopped growing and was separated from the feeder cells, which signaled the experiment had failed. Kim Sunjong, frustrated and desperate, went to MizMedi Hospital and brought a stem cell line (codenamed Miz-4) he had been culturing from a residual embryo made from in vitro fertilization. He secretly mixed this cell line into the NT-2 ICM, and reported that he succeeded in deriving a stem cell. When Dr. Hwang and other coresearchers did not realize his misconduct and praised him instead, Kim became braver and created additional five stem cell lines (codenamed NT-3 to NT-7, that actually had come from MizMedi Hospital) using the same method as he had in December 2004.
In early January 2005 those NT-2 to NT-7 stem cell lines were contaminated by accident, and only NT-2 and NT-3 were left. Though the research team tried to make additional stem cell lines (NT-8 to NT-12; they were in fact created by Kim Sunjong with the same mixing method), no embryo had grown enough to derive stem cell lines in time for the deadline to submit the paper. Dr. Hwang, eager to publish the paper as early as possible to ensure patent rights and fame, ordered Kim Sunjong to duplicate the data and photos of the NT-2 and NT-3 stem cell lines and fabricate data for nine more non-existing stem cell lines. Other data were also fabricated and nobody except Kim Sunjong had known that even NT-2 and NT-3 were not real patient-specific stem cells. In the 2005 paper, Hwang's team proudly claimed that they succeeded in deriving 11 stem cell lines with far more efficiency. When the Seoul National University Inspection Committee conducted the DNA fingerprinting test, it was revealed that NT-3, NT-3, and other stem cell lines derived after the submission of the paper were not patient-specific stem cell lines created by SCNT, but common stem cell lines derived from the fertilized embryos preserved at MizMedi Hospital. This result was reconfirmed by the investigation conducted by the Prosecutors' Office.
The Prosecutors' Office, finalizing the investigation, analyzed the causes of this scandal as resulting from: 1) the researchers' lack of integrity and ethics; 2) the rigid and authoritative research environment; 3) poor management of research records; 4) lack of principles in distributing coauthorships; 5) a formalistic review by the IRBs; and, 6) lack of transparency of the research budget.[235]
The journal Science retracted both the 2004 and the 2005 papers as irrefutable scientific evidence exposed the fraud.[236] Dr. Hwang was dismissed from the university and his team's coresearchers were also sanctioned.[237] Criminal investigations were begun on fraud, embezzlement and egg donation, and six people, including Dr. Hwang have been indicted.[238] The NBC announced their intermediary report on February 2, 2006, in which various ethical wrongdoings were revealed.[239] The Bioethics and Safety Act itself is under scrutiny and destined for total reform. South Korean citizens showed mixed reactions to this scandal initially, but after observing the criminal investigation, most people are now determined to prevent the repetition of similar scandals and to clean up the whole research process. The thorough and relentless investigations conducted by a host of offices, agencies and committees testifies to this determination.
In this scandal, researchers skipped many ethical and regulatory issues to achieve the goal quickly. Financial and research records were insufficient and ambiguous. Two related IRBs did not properly function. The Bioethics and Safety Act of South Korea allowed too many exceptions. The NBC, main governmental oversight body, did not have the structure and resources to oversee the stem cell research. Above all, too much enthusiasm nullified all the regulatory safeguards.
Once we recognize the problems, we can also find their answers. In the United States, scientific misconduct cases at four major research centers in 1980 led to the establishment of the Office of Research Integrity.[240] The Tuskegee syphilis study scandal in 1972 led to the enactment of the National Research Act in 1974[241] and the announcement of the Belmont Report in 1978. [242] We may learn from them.
Three pillars of regulation should come together in research ethics. One is the self-regulation by the researchers, another is the IRB review that can closely follow the conducts of researchers, and the third is the legislative and governmental actions that can facilitate researchers' self-regulation and the IRBs' thorough and timely review.
To encourage self-regulation, first, the education of investigators on research ethics should be reinforced. Though mandatory ethics education might be deemed a formality, the starting point should be to know what is ethical and what is not. Especially, in a field such as biotechnology which raises so many novel issues, for instance, what life is, or how to weigh life, philosophical training and introspection is needed. Second, given the acknowledgement that "university science becomes entangled with entrepreneurship; knowledge is pursued for its monetary value; and expertise with a point of view can be purchased,”[243] honor and conscience-based academic self-regulation should be reconsidered. Strict auditing of research grants and full disclosure of financial interests should be the two mandatory underpinnings of regulation. Third, more equitable and transparent distribution of coauthorship is critical to self regulation. Each researcher should be accountable and responsible for what she does.[244]
It is the role of the IRB to review the ethics of the research. The traditional IRB model is now facing a new challenge. In biotechnological research, the ethics of the project itself and the researchers' social responsibility do matter as well as the protection of human subjects. Therefore, at least some of the IRB members should have the requisite philosophy or ethics background needed to review the fundamental ethics of the research. Another obligation that should be performed by the IRB is risk/benefit analysis. Novel factors should be considered when conducting risk/benefit analyses of biotechnological research projects. Is it okay to use 300 ova to create one stem cell line, which cannot cure disease immediately but will increase the possibility of future success? If it is not okay, how many ova shall be used? If other mammals' ova are used instead, is it riskier in that it might harm human dignity and transfer animal viruses to human beings, or is it less risky in that it causes less harm to ova donors? A risk/benefit analysis is in nature case-specific. Regardless of the existence of laws legislated, the primary analysis should be conducted by the local IRB. The IRB should also put more emphasis on avoiding conflicts of interest. Establishment of joint IRBs or regional IRBs, certification or license of IRB members, and registration of local IRBs may improve the independence of the IRBs. We should certainly study ways to improve IRB performance.
The National Bioethics Committee (or any form of advisory committee or oversight committee at the national level) should set the basic ground rules governing how IRBs should function. Though many major questions, such as whether we should approve therapeutic cloning or ova trading, may be answered by the legislature, many other questions smaller in scope but no less important should be discussed and answered by the NBC. The NBC should be more democratized to avoid politicization and to achieve free and impartial discussion. The function of the NBC should be separated into policy setting and oversight, and for the former, the diversity of members and the independence of the IRB should be increased; its sessions should be more open and accessible to the public; and various interest groups should have an opportunity to speak at the committee's sessions. For the oversight function, an administrative body that has the authority to conduct regular inspections of research institutions and their IRBs and to run educational programs for IRB members (this function may be outsourced) should be established. In establishing and running this regulatory system, we should rely on the principles of respect for persons, beneficence, and justice.[245]
[] * According to the Guidelines for Romanization of Korean (July 7, 2000, Ministry of Culture and Tourism of the Republic of Korea, Public Notice 2000-8), in Romanizing Korean names, surname should go first, and given name, generally composed of two syllables, should be spelled as a single word (e.g., Han Aera). But putting a hyphen between the two syllables of given name is permitted (e.g., Han Ae-ra), and in case a person had already made and used a Romanized name prior to the public notice of the Guidelines, she is permitted to use it continuously despite the current Guidelines. Due to such exceptions, the actual usages of Romanized Korean names are very confusing. E.g., Dr. Hwang's name can be Romanized as 1) Hwang Useog (in accordance with current Guidelines), 2) Hwang Woo Suk (in accordance with the continuous use exception), or 3) Woo Suk Hwang or Woo-suk Hwang (putting the surname last in papers published in English). In this paper, I first follow the general principles of Guidelines, but when the spellings are different from the Guidelines in published documents, respect them as exceptions, and to avoid confusion, sometimes put a comma between the surname and the given name.
[1] National Bioethics Committee, Republic of Korea (hereinafter "NBC"), Hwang Woo Suk Gyosu-Ui Yunlimunje-E Daehan Jungganbogoseo (The Intermediary Report on the Ethical Problems of Dr. Woo Suk Hwang ’ s Research) , 2006. 2. 2. (Language: Korean) (The announcement of the final report has been delayed pending further investigation of lack of informed consent for ovarian donations.)
For an English-version news summary on the committee’ s report, see Kim Jong-won, Hwang ’ s Team in Ethical Minefield over Ova: Panel , The Korea Times, Feb. 2, 2006. Available online at http://times.hankooki.com/lpage/nation/200602/kt2006020218595910510.htm (last visited on March 2, 2006).
[2] Seoul National University Investigation Committee, Final Report on Professor Woo Suk Hwang's Research Allegations , Jan. 10, 2006 (Language: Korean).
[3] The Board of Audit and Inspection, Republic of Korea, Gugga Yeongugaebal Sa-Eob Ji-Won Gwanli Siltae :Hwang Woo Suk Junggan Briefing (An Intermediary Briefing on the Inspection of Government-funded R&D Projects :Pertaining to Dr. Hwang Woo Suk 's Execution of Research Budget) , Feb. 6, 2006, 1-15 (Language: Korean). Available online at http://www.bai.go.kr/jsp/cm/UE_FileDown.jsp?gsSrvPath=/db1fs1/BAICAB/img1/ed/34fed/&gsNewFileName=a50c5.csd&gsOrgFileName=060206±¹°¡¿¬±¸°³¹ß»ç¾÷Áö¿ø°ü¸®½ÇÅ (Ȳ¿ì¼®Áß°£ºê¸®ÇÎ ).csd&gsFileExt=.csd (last visited on April 20, 2006).
[4] Seoul Central District Prosecutors' Office, Republic of Korea, Julgi Sepo Nonmun Jojak Sageon Susa Gyeolgwa (the Result of Investigation on the Fabrication of the Stem Cell Paper) , May 12, 2006 (Language: Korean). By far this is the most thorough and latest investigation. Available online at http://seoul.dpo.go.kr/download.tdf?table=gp_board_file&d_seq=506&d_idx=4&d_board_id=sppo_press (last visited on May 13, 2006).
For an English summary, see Lee Hyo-sik, Hwang Woo-suk Indicted for Fraud , The Korea Times May 12, 2006. Available online at http://times.hankooki.com/lpage/nation/200605/kt2006051217400611950.htm (last visited on May 13, 2006).
[5] For the general overview of research ethics, see Adil E. Shamoo & David B. Resnick, RESPONSIBLE CONDUCT OF RESEARCH (Oxford University Press 2003); and David H. Guston and Kenneth Keniston eds., THE FRAGILE CONTRACT (The MIT Press 1994). For the integrity and accountability problem, see William Broad & Nicholas Wade, THE BETRAYERS OF TRUTH (Simon & Schuster 1982); and Patricia Woolf, Integrity and Accountability in Research 82-101 in THE FRAGILE CONTRACT (Guston & Keniston eds., supra ). For the conflicts of interest problem, see Sheldon Krimsky, SCIENCE IN THE PRIVATE INTEREST (Rowman & Littlefield Publishers, Inc. 2003). For science and media, see Dorothy Nelkin, SELLING SCIENCE: HOW THE PRESS COVERS SCIENCE AND TECHNOLOGY . (2nd revised ed. Freeman 1994).
[6] Broad & Wade, supra footnote 5 at 61-62. Actually the authors of this book are skeptical about this three-step self-regulatory mechanism and well illustrates its insufficiency in preventing scientific misconduct. This stem-cell scandal would be another example.
[7] For the background to the trade disputes between the two countries and its consequences, see Anna Y. Park, International Trade: Agreement Between the United States and the Republic of Korea Concerning Insurance Market Access and Intellectual Property Protection in the Republic of Korea, July 21, 1986 , 28 Harvard Int'l L.J. 166 (1987).
[8] Patent Act of Republic of Korea, Dec. 31, 1986 Act No. 3891 (partially amended)
[9] The situation of South Korea at that time was similar with that of India before the Indian government accepted the western patent system on December 26, 2005. Many executives of South Korean pharmaceutical companies still lament that South Korea conceded to the pressure of the United States too early, and should have been allowed additional time to further develop the domestic pharmaceutical industry.
[10] For changes in intellectual property protection in developing countries, see Philip W. Grubb, PATENTS FOR CHEMICALS, PHARMACEUTICALS AND BIOTECHNOLOGY 37-54 (4th ed. Oxford University Press 2004).
[11] The first new drug that won the approval of the Korea Food and Drug Administration was "Sunpla inj.® ," an anti-cancer agent developed by SK Chemicals. It took nine years from the initiation of the research (May 1990) to approval (July 14, 1999). For the introduction of the drug, see the official website of the company, http://www.skpharm.com/english/product/ProductSunpla.asp (last visited on Mar 23, 2006). After twelve years of research and clinical trials, FACTIVE® , a quinolone antibiotic developed by LG Life Sciences, won the approval of the Food and Drug Administration of the United States in April 2003. For the introduction of the drug, see http://www.lgls.co.kr/eng/rd/wonder.jsp (last visited on March 23, 2006).
[12] The Guidelines for Korean Good Clinical Practice, Dec. 28, 1987. Ministry of Health and Welfare, Public Notice No. 1987-87.
[13] The Guidelines for Korean Good Clinical Practice (Amendment Jul. 27, 1995). Ministry of Health and Welfare Public Notice No. 1995-39. Most IRBs in Korea were established after this 1995 amendment. For the history and status of IRBs in Korea, see Kim Ock-joo et al., Current Status of the Institutional Review Boards in Korea: Constitution, Operation, and Policy for Protection of Human Research Participants , J Korean Med Sci 2003; 18: 3-10. Available online at http://jkms.kams.or.kr/2003/pdf/02003.pdf (last visited on March 24, 2006).
[14] The Guidelines for Korean Good Clinical Practice (Amendment Jan. 4, 2000). Korea Food and Drug Administration Public Notice No. 1999-67.
[15] International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Guidelines For Good Clinical Practice E6 (R1) Version , Jun. 10, 1996. Available online at http://www.ich.org/LOB/media/MEDIA482.pdf (last visited on March 23, 2006).
[16] The first Korean Supreme Court decision that directly acknowledged the informed consent doctrine was Daebeobwon pangyul (Supreme court decision) 86DaKa1136 [Damage] delivered on April 28, 1987. In this case a treating surgeon did not offer full explanation of the expected side effects of tissue transplantation surgery when getting the consent from the patient. The Supreme Court affirmed the lower court’ s decision that awarded full compensatory damages to the patient.
[17] In Daebeobwon pangyul (Supreme court decision) 93Da52402 [Damage] delivered on Feb. 10, 1995, the court decided that "in case the patient claims only compensatory damages for the emotional distress from the loss of the right to choose and self-determination caused by the lack of informed consent, she needs to prove only the fact that the physician provided no or insufficient information to her." This decision has thus far been followed in similar cases.
[18] Korean Medical Association, The Guidelines of Ethics for the Medical Profession , Nov. 15, 2001 (language: Korean). The main catalyst for the issuance of the Guidelines was the so-called "Boramae Hospital case." In 1997, a patient underwent brain surgery at Boramae Hospital (a public hospital run by the Seoul municipal government) and had been recovering, but his family demanded the treating physician to stop further treatment and discharge him, largely due to financial reasons. The physician agreed and discharged the patient, in spite of his knowledge that this discharge would certainly cause the patient's death. The patient died immediately after he arrived home and the artificial respiration was removed, and both the physician and the family members were convicted of murder at the trial. The appeals court affirmed the conviction with minor changes (the murder conviction of the physician was changed to accessory to murder), and the Korean Supreme Court also affirmed it (Daebeobwon 2004. 6. 24. pangyul 2002do995). The trial court decision delivered in 1997 alarmed the medical society and precipitated the issuance of a medical ethics code and the establishment of hospital ethics committees.
[19] Korean Medical Association, The Guidelines of Ethics for the Medical Profession , Art. 5-13.
[20] Id. Art 23.
[21] Id. Art 55 § 3.
[22] Id. Art. 68.
[23] Id. Art. 74, 75.
[24] Genetic Technology Support Act, Republic of Korea. Dec. 31, 1983, Act No. 3718 (new enactment).
[25] Though the title was changed to Biotechnology Support Act (Jan. 5, 1995, Act No. 4938, partial amendment), and there have been eight additional partial amendments, its basic structure has not changed.
[26] Kim, Mikyoung, An Overview Of The Regulation And Patentability Of Human Cloning And Embryonic Stem Cell Research In The United States And Anti-Cloning Legislation In South Korea, 21 Santa Clara Computer & High Tech. L.J. 645, 682-683.
[27] Biotechnology Support Act, supra footnote 25, Art. 15.
[28] Yujeonja Jaejohap Silheom Jichim (The Guidelines on Recombinant DNA Experiments) Art. 23, April 22, 1997, Ministry of Health and Welfare Public Notice No. 1997-22. It stated that the head of the related ministry, agency or research institute on biotechnological study and industry should develop measures to prevent ethical problems that might be caused by biotechnological experiments, but no specific or binding regulation ensued. Other clauses of the Guidelines are mostly on the prevention of biohazards.
[29] I. Wilmut et al., Viable offspring derived from fetal and adult mammalian cells , Nature 385, 810 - 813 (27 February 1997). Available online at http://www.nature.com/nature/journal/v385/n6619/abs/385810a0.html (last visited on March 23, 2006).
[30] From Wikipedia (a free internet encyclopedia) catchword "Dolly the Sheep." Available online at http://en.wikipedia.org/wiki/Dolly_the_sheep#_ref-1 (last visited on March 23, 2006).
[31] Sheryl WuDunn, South Korean Scientists Say They Cloned a Human Cell , New York Times Dec. 17, 1998 A12. It ended as a farce, as the researchers gave up further study and left no scientific record overwhelmed by the domestic and international ethical concerns. For the reaction of the medical profession to this incident, See Kim Jeongsu, Silon: Saengmyeongbogje-Yeongu-E Daehan Daehan-Uisahyeobhoe-Ui Ibjang (The Position of Korean Medical Association on Human Cloning Research) , J. Kor. Med. Association 42-9 (1999) 826, 826-829 (Language: Korean). Available online at http://www.kma.org/windowpopup/pdfpopup.asp?pdfurl=99095.pdf&title=½Ã·Ð /»ý¸íº¹Á¦¿¬±¸¿¡ %20´ëÇÑ %20´ëÇÑÀÇ»çÇùȸÀÇ %20ÀÔÀå &listownseq=26 (last visited on March 25, 2006).
[32] The Korea Times, "First Clone of Calf Born in Korea," Feb. 19, 1999. Dr. Hwang Woo Suk at the College of Veterinary Medicine, Seoul National University announced in Feb. 1999 that he succeeded in cloning a cow named Younglong. Available online at http://search.hankooki.com/times/times_view.php?term=hwang+cloning+cow++&path=hankooki1 &media=kt (last visited on March 26, 2006).
[33] Alarmed by the attempted human cloning by the researchers of Kyunghee University (supra Footnote 29), the Korean Medical Association formed an investigative subcommittee (ironically the subcommittee included Dr. Hwang and he played a major role in prohibiting the researchers of Kyunghee University from conducting further cloning experiments) on December 23, 1998. In January 1999 the subcommittee recommended not to conduct human cloning until a national policy was set, and later issued the "Guidelines on Research of Cloning Lives " (Korean Medical Association, May 1999). The guidelines prohibited any research on human embryos for the purpose of human cloning (Art. 4 ‚ 1.), implantation of cloned embryos in human uterus (Art. 4 ‚ 4.), any experiment with embryos exceeding 14 days after fertilization or nuclear transfer (Art. 4 ‚ 2.), and trading of sperms, eggs or somatic cells (Art. 8 ‚). It also suspended the approval of experiment on embryos that did not exceed 14 days from the fertilization or nuclear transfer until any authoritative government policy was established (Art. 4 ‚ 2). For background to the issuance of the Guidelines, see Kim Jeongsu, supra footnote 31.
[34] Kim, supra footnote 26 at 682.
[35] Id. at 682-683.
[36] They differed in "who or what should be granted the authority: 1) to determine the scope of permissible research employing SCNT; 2) to administer the research and development in biotechnology; and 3) as to what legislative actions should be taken regarding other bioethical issues." Kim, supra footnote 26 at 683.
[37] For example, Korean Medical Association, supra Guidelines on Research of Cloning Lives ; The Korea Health Industry Development Institute (KHIDI), The Guidelines on Human Stem Cell Research and Supervision , Sep. 2001; Ethics Committee on Stem Cell Research Center, Stem Cell Research Center Ethics Committee Guidelines for Review of Research Proposals , May 2003. For further explanation, see Park, Un Jong, BIOETHICS RESEARCH ETHICS AND REGULATION (Seoul National University Press 2005), 112-133.
[38] Clonaid™ is "a self-described human cloning company. It is openly associated with the Raë lian Movement, which sees cloning as part of the path to immortality" (from Wikipedia.com catchword "Clonaid").
[39] Kim Sangjo, Three Koreans are Pregnant: They will be born in Six Months according to Clonaid , Kukminilbo, Jul. 23, 2002 (Language: Korean). However, this news as well as Clonaid's other announcements on success of human cloning has been never verified by scientific evidence, and the company's actual existence itself is under suspicion. Raja Mishra, Little behind Clonaid, Files Reveal , Boston Globe April. 23, 2003.
[40] For the general overview of the law, see Pak, supra footnote 37 at 180-212; and Kim, Mikyoung, supra footnote 26 at 682-685. For more detailed comparison of each draft and legislative process, see Gwak Sunheon, The Legislation of Bioethics and Safety Act and Policy Issues , Technological Trends in Health Industry (2003-winter), 152-162 (Language: Korean).
[41] This was deemed as a major setback by bioethicists who had opposed human cloning generally.
[42] The Bioethics and Safety Act of Korea, Jan. 29, 2004, Act No. 7150 (took effect on Jan. 1, 2005 and was revised in minor detail by Act No. 7413, on March 24, 2005) Available online in English at http://www.moleg.go.kr/english/09/view.html?folder=_04_06_1&code=948773847149.xml (last visited on March 24, 2006).
[43] Id. Art. 6-10.
[44] Id. Art. 11-12.
[45] Id. Art. 13 (3).
[46] Id. Art. 17.
[47] Id. Art. 22 (1).
[48] Id. Art. 23.
[49] One notable clause is its Addenda (3). It states that, "if a person who is carrying out research on somatic cell cloning embryos for research purposes referred to in subparagraph 2 of Article 17 at the time of the entry into force of this Act meets the requirements of the following subparagraphs, he/she may continue to conduct such research with approval therefor from the Minister of Health and Welfare: 1. He/She has been conducting research on somatic cell cloning embryos for not less than three years; and 2. His/Her research on somatic cell cloning embryos has been published in a related scientific journal at least once." As we shall later see, Dr. Hwang got the approval to conduct stem cell research directly from the Minister of Health and Welfare based on this clause, not through the review of National Bioethics Committee.
[50] The Bioethics and Safety Act, supra footnote 42, Art. 7.
[51] Presidential Decree for the Bioethics and Safety Act Art. 2, Dec. 30, 2004, Presidential Decree No. 18621.
[52] Chungwadae (Office of the President, Republic of Korea) Briefing April 7, 2005. Available online in Korean at http://www.president.go.kr/cwd/kr/archive/archive_view.php?meta_id=news_data&id=f5183aa9a3994d5ef9425734 (last visited on March 25, 2006).
[53] He was dismissed from the university on March 20, 2006 due to this scandal.
[54] The Korea Times, supra footnote 32.
[55] Hwang admitted in an interview with a producer of "PD Notebook," a news magazine of MBC (Munhwa Broadcasting Corporation, one of the three major broadcasting corporations in South Korea) that he did not keep careful records of his cow cloning research. According to his own explanation, he thought his research did not have major scientific importance because papers on mammalian cloning had already been published by other researchers; he was not sure the experiment would succeed; and he could not acquire accurate DNA inspection records as there was no molecular biologist who could conduct the DNA fingerprinting in his team at that time. PD Notebook of MBC, "How the Hwang Woo Suk Myth had been Made," broadcasted on Jan. 10, 2006 23:05-24:00 (GMT+9:00) (Language: Korean).
[56] Due to the lack of scientific records, after the outbreak of the scandal, many people began to suspect that this research might have also been faked. But considering the fact that Dr. Hwang succeeded in cloning a dog in 2005, this cow cloning might have also been truthful. The problem here is not its truthfulness but the government's reckless funding based on research that had not been properly peer-reviewed. Academic earmarking or pork-barreling has been criticized in the United States, too. See James D. Savage, Funding Science in America (Cambridge University Press 1999).
[57] The Board of Audit and Inspection of Korea, supra footnote 3 at 1-15.
[58] Dr. Hwang's research lab and the National Livestock Research Institute under Dr. Hwang’ s technical advice produced the alleged cloned cow embryos, and the government readily provided dairy farms with these embryos until September 2001. However, a follow-up inspection by the National Livestock Research Institute in October 2001 revealed that only 77 among 838 embryos had been successfully implanted in the surrogate cows' uteri, from which only 39 calves were born. Further DNA inspections revealed that among those 39 calves only 6 calves were grown from the embryos produced by SCNT, and all other calves were grown from embryos produced by common in-vitro fertilization, because the veterinary technicians implanted multiple embryos produced by different methods in a single uterus to raise the success rate. This plan was eventually abandoned after the inspection. PD Notebook of MBC, "How Hwang Woo Suk Myth had been Made ," supra footnote 55.
[59] Hwang Doo-hyong, Mt. Paektu Tiger to Be Cloned, The Korea Times Oct. 3, 2000. Available online at http://search.hankooki.com/times/times_view.php?term=cow+clone++&path=hankooki1/times/200010/t20001003171221401134.htm&media=kt (last visited on March 27, 2006).
[60] Kim Tae-gyu, Researchers Clone Calves Resistant to Mad Cow Disease , The Korea Times Dec. 10, 2003. Available online at http://times.hankooki.com/lpage/200312/kt2003121016415810160.htm (last visited on March 27, 2006). He had been given $5.5 million in funding for the gnotobiotic (sterilized) miniature pigs and $4.3 million for the cows that supposedly had resistance to mad cow disease. But he submitted no paper on the two alleged successes of research projects and they have been never verified. The Board of Audit and Inspection of Korea, supra footnote 3 at 1-15.
[61] Though he did not directly assure that he was the one who would cure such incurable diseases, many patients believed so based on his lectures and assertions, and gave him unprecedented support.
[62] Hwang, Woo Suk et al., Evidence of a Pluripotent Human Embryonic Stem Cell Line Derived from a Cloned Blastocyst, originally published in Science Express on 12 February 2004; Science 12 March 2004: Vol. 303. no. 5664, pp. 1669 – 1674 (retracted). Hereinafter "2004 paper." Available online at http://www.sciencemag.org/cgi/content/full/303/5664/1669 (last visited on March 10, 2006).
[63] Gina Kolada, Cloning Creates Human Embryos , Feb. 12, 2004 New York Times, A1
[64] Hwang et al., supra footnote 62.
[65] Gina Kolada, supra footnote 63.
[66] Gina Kolada, supra footnote 63. According to the New York Times Interview with Dr. Lanza of The Advanced Cell Technology, the company advertised to pay $4,000 for the unfertilized egg donation, but could get only 19 eggs with "just a few donors."
[67] For a stance of strict regulation of stem cell research, see, e.g., The President’ s Council on Bioethics, Human Cloning and Human Dignity: An Ethical Inquiry . (Washington, D.C.: U.S. Government Printing Office, 2002) Available online at http://www.bioethics.gov/reports/cloningreport/ (last visited on April. 21, 2006). For a more supportive stance, see, e.g., The United Kingdom Parliament Select Committee on Stem Cell Research, Stem Cell Research Report, Feb. 13, 2002. Available online at http://www.parliament.the-stationery-office.co.uk/pa/ld200102/ldselect/ldstem/83/8301.htm (last visited on April 21, 2006).
[68] For his strong anti-cloning argument, see Leon R. Kass, LIFE, LIBERTY AND THE DEFENSE OF DIGNITY (Encounter Books, 2002), especially chapter 5.
[69] Kass said in his e-mail message to the New York Times, "the age of human cloning has apparently arrived: today, cloned blastocysts for research, tomorrow cloned blastocysts for babymaking," and that "in my opinion, and that of the majority of the Council, the only way to prevent this from happening here is for Congress to enact a comprehensive ban or moratorium on all human cloning." Kolada, supra footnote 63.
[70] Korean Bioethics Association, Declaration: Research in medical science and biotechnology must be conducted in accordance with bioethical principles , May 22, 2004 (available online at http://www.koreabioethics.net/pub.htm ). Also see Koo Young-Mo, A research ethics-based analysis of the Korean scientists' human embryonic stem cell research , the Journal of the Korean Bioethics Association 5-1 (Jun. 2004) 1-12 (Language: Korean. Its summary is available in English). Available online at http://www.Koreabioethics.net/5-1/5.pdf (last visited on March 27, 2006); and Song Sang-yong et al., Stem Cell Research in Korea , Science 13 August 2004: 944-945.
[71] David Cyranoski, Korea's stem-cell stars dogged by suspicion of ethical breach, Nature 429, 3 (May 6, 2004). Available online at http://www.nature.com/nature/journal/v429/n6987/full/429003a.html (last visited on May 2, 2006)
[72] Hwang et al., Supplementary Materials for supra 2004 paper at 1. Available online at http://www.sciencemag.org/cgi/data/1094515/DC1/1 (last visited on March 30, 2006)
[73] Korean Bioethics Association, supra footnote 70; Koo Young-Mo, supra footnote 70; Song Sang-yong et al., supra footnote 70; Cyranoski, supra footnote 71; and also Lee Pilryeol, Professors Times , Feb. 23, 2004 (Language: Korean). Prof. Lee said in his column that it was unbelievable that more than ten women voluntarily came to the lab, got the hormone injection, got diagnosed, and later opened their bodies (for egg extraction).
[74] Cyranoski, supra footnote 71. When he first interviewed one female researcher, she said that she and another female researcher had donated their eggs. When the ethical problems related to the donation by vulnerable subjects arose after the interview, she denied her previous statement, and Dr. Hwang explained that there had been no egg-donation by the researchers and her previous answer was due to a misunderstanding of English. Cyranoski, later at an interview with MBC's PD Notebook, stated that when he asked a female researcher how they could get so many eggs to be used for the research, she answered, "I don't know of other cases, but I can say why I donated my eggs," and at his repeated questions, she reconfirmed that she had donated her eggs. PD Notebook of MBC, The Myth of Hwang Woo Suk and Suspicions over Eggs , broadcast Nov. 22, 2005.
[75] The United Kingdom also prohibits egg-trading for human embryonic stem cell research. See Select Committee on Stem Cell Research (under The United Kingdom Parliament), Stem Cell Research Report, Feb. 13, 2002, Chapter 8.23, stating, "we recommend that the separation of clinical and research roles be standard practice for donation of eggs or embryos. The prohibition in the United Kingdom of payment to donors for gametes has been an important element in preventing undesirable commercialisation of this aspect of assisted reproduction and should be strictly maintained." Available online at http://www.parliament.the-stationery-office.co.uk/pa/ld200102/ldselect/ldstem/83/8309.htm (last visited on April 21, 2006).
[76] Korean Medical Association, supra footnote 33 Art. 8 § 2. As well as the egg trading, the KMA suspended any experiment on human embryos until an authoritative governmental policy on this issue is established.
[77] Especially Dr. Moon, Shin Yong, the other corresponding author, was a renowned physician. Hwang et al., supra footnote 62 at 1669.
[78] The Stem Cell Research Center Ethics Committee Guidelines for Review of Research Proposals 1.5) states, "[e]mbryos to be donated for research should not be offered in consideration of monetary or any other compensation." Pak, supra footnote 37 at 128.
[79] The KGCP, supra footnote 12, Art. 7 § 1.
[80] World Medical Association, DECLARATION OF HELSINKI: Ethical Principles for Medical Research Involving Human Subjects Art. 8 states, "special attention is also required for those who cannot give or refuse consent for themselves, for those who may be subject to giving consent under duress... ". Available online at http://www.wma.net/e/policy/b3.htm (last visited on March 30, 2006).
[81] Kim Tae-gyu, Cloning Scientist Rebuffs Nature Journal's Claim , The Korea Times May 9, 2004. Available online at http://times.hankooki.com/lpage/tech/200405/kt2004050917134611780.htm (last visited on March 30, 2006).
[82] Hwang, Woo Suk & Moon, Shin Yong, Stem Cell Research in Korea , Science 13 August 2004: 944-945.
[83] Gang Yanggu & Jeonhong Gihye, Park Kiyoung Bojwagwan "Hwang Woo Suk Gyosu Yeongu Munje Eopseo" (Advisor Park: "There's No Problem with Hwang's Research") , The Pressian, May 27, 2004. (Language: Korean) Available online at http://www.pressian.com/scripts/section/article.asp?article_num=30040527142025&s_menu =»çȸ (last visited on March 30, 2006).
[84] National Bioethics Committee, supra footnote 1 at 1-38.
[85] Seoul Central District Prosecutors' Office, supra footnote 4 at 110-113.
[86] How many eggs were used for each paper is still unclear, because Dr. Hwang's research team have kept no proper records on the receipt, use, and destruction of eggs except for several researchers' personal research notes. National Bioethics Committee, supra footnote 1 at 11. It is at least certain that the total number would far exceed the 350 eggs Hwang claimed to have used for the 2004 and 2005 papers.
[87] MizMedi Hospital paid 71 donors approximately $1,500 per donor from 2002 to 2004. Dr. Rho Sungil, the director of MizMedi Hospital, refused to further cooperate for fear of being criminally charged for illegal egg trading under the Bioethics and Safety Act since January 2005, and Dr. Hwang's team instead relied on the Hanna Women's Clinic, which received egg donations from its own infertility patients, and provided compensation to 25 of them by discounting or exempting them from the in vitro fertilization fee (approx. $1,800 to $2,300 per person). Seoul Central District Prosecutors' Office, supra footnote 4 at 118-120.
[88] National Bioethics Committee, supra footnote 1 at 17. The egg broker (CEO of the DNA BANK) was later convicted for the illegal egg trading, and the director of Hanna Women's Clinic was also indicted for the violation of the Bioethics and Safety Act and is now awaiting trial. Central District Prosecutors' Office, supra footnote 4 at 18-19.
[89] One researcher who had donated her eggs expressed her exasperation in the following e-mail message: "¡¦ though it was I who started it, I'm scared. General anesthesia, self cloning (it's inconceivable--cloning using my own eggs--how tough I am)... I shouldn't have done it this way, not giving up [my position] (in the research team) until the end, not fighting against the professor. I will work harder to forgive myself... ." National Bioethics Committee, supra footnote 1 at 34. Though the Prosecutor's Office concluded that there was no direct coercion of the female researchers by Dr. Hwang, there is no question that the procedures were still highly unethical. Dr. Hwang even requested signatures of the 15 women researchers in his team on the informed consent form for ova donation and kept the form, which suggests that he wanted his female researchers to donate eggs. Id . at 22-24.
[90] Seoul Central District Prosecutors' Office, supra footnote 4 at 120-122.
[91] Among 92 women who donated their eggs through MizMedi Hospital 15 women suffered from Ovarian Hyperstimulation Syndrome and among them two women were even hospitalized. But as donations at Mizmedi have not received any sort of IRB review, these side effects were not reported or ever inspected. And Dr. Hwang let the 15 women researchers in his team sign the informed consent form for ova donation from the beginning. National Bioethics Committee, supra footnote 1 at 22-24.
[92] The informed consent forms that went through the IRB of Hanyang University Hospital for the research of the 2004 paper failed to mention several serious side effects such as infertility. The forms of three other hospitals where most of the egg extractions had been conducted were even less specific, only emphasizing that the ownership of the eggs belonged to the hospital. They presented only some of the possible side effects, or simply stated, "I have received all the information on the side effects. I hereby give my consent." and let the donors sign. National Bioethics Committee, supra footnote 1 at 21. Actually it is not enough for the researchers to simply state the side effects. Recent guidelines on stem cell research ask for the presentation of information on the purpose of the research, how and where the eggs will be used, and the sources of research funding and financial benefits the researchers might receive.
[93] Seoul Central District Prosecutors' Office, supra footnote 4 at 120.
[94] Kim Rahn, Ova Donors to File Compensation Suit , The Korea Times, Feb. 26, 2006. Available online at http://times.hankooki.com/lpage/nation/200602/kt2006020617424810510.htm (last visited on April 1, 2006). And also Kim Miyoung, Nanja chaechwi Geu hu, Hoehangwa Bunnoui 14Gaewol (After the Ova Donation, 14 months of Remorse and Anger), The Hankyoreh, April 21, 2006 (Language: Korean). Available online at http://www.hani.co.kr/arti/society/health/117633.html# (last visited on April 21, 2006).
[95] Press Release, Office of the Press Secretary, Fact Sheet: Embryonic Stem Cell Research (Aug. 9, 2001). Available online at http:// www.whitehouse.gov/news/releases/2001/08/20010809-1.html (last visited on April 1, 2006).
[96] Kim, supra footnote 26 at 661-662.
[97] The Stem Cell Research Center (SCRC) was established in 2002 in Seoul National University for the purpose of organizing and operating nation-wide stem cell research project supported by the Ministry of Science and Technology, and intends to grant $138 million to various stem cell research projects. Another corresponding author of the 2004 paper, Moon Shin Yong, had been the director of the Center since its establishment. See http://www.stem.or.kr/english/ (last visited on April 1, 2006). On February 26, 2006 Dr. Moon was excluded from any further research grant by the Center due to this scandal.
[98] Hwang et al., supra footnote 62 at 1674.
[99] Pak, supra footnote 37 at 128.
[100] Yonhap News, "Gwagibu, Sepo-Yeongu-E 10nyeongan 1cheon-Ssss-Eog-Won Tu-Ib" (Ministry of Technology and Science will fund $150million on Stem Cell Research), Chosunilbo, Feb. 12, 2004 (Language: Korean).
[101] Issued on May 9, 2003 and amended after the stem cell scandal on Feb. 17, 2006.
[102] Pak, supra footnote 37 at 113.
[103] The Stem Cell Research Center Ethics Committee Guidelines for Review of Research Proposals Art. 1 2). Pak, id. at 128.
[104] Id. Art. 1 3).
[105] Id. Art. 2 1)(a).
[106] Ironically, both Dr. Hwang and Dr. Moon were members of the Stem Cell Research Center Ethics Committee.
[107] Koo Young-mo, supra footnote 70 at 7.
[108] Korean Bioethics Association, supra footnote 70.
[109] National Bioethics Committee, supra footnote 1 at 49.
[110] Private donations received by the Korean Science Foundation for Dr. Hwang and later sent to him.
[111] The Board of Audit and Inspection of Korea, supra footnote 3 at 1-3.
[112] Seoul Central District Prosecutors' Office, supra footnote 4 at 89-117.
[113] Seoul Central District Prosecutors' Office, supra footnote 4 at 112-114.
[114] The Board of Inspectors, supra footnote 3 at 9.
[115] University Of Pittsburgh, Summary Investigative Report On Allegations Of Possible Scientific Misconduct on the Part of Gerald P. Schatten, PH.D ., Feb. 8, 2006, p9.
[116] Seoul Central District Prosecutors' Office, supra footnote 4 at 108-109.
[117] Id. at 115.
[118] Id. at 116.
[119] Id. at 120.
[120] Id. at 108.
[121] Id. at 115.
[122] The Bioethics and Safety Act of Korea, supra footnote 42, Addenda (1).
[123] KGCP Art. 7 § 2. This is identical to ICH-GCP 3.1.2.
[124] KGCP Art. 7 § 5. This is identical to ICH-GCP 3.1.4.
[125] Hwang et al., supra footnote 62.
[126] She was an obstetrician/gynecologist at Hanyang University Hospital and also former Dean of Hanyang Medical School. Seoul Central Prosecutors' Office, supra footnote 4 at 121.
[127] National Bioethics Committee, supra footnote 1 at 46-47.
[128] Seoul Central District Prosecutors' Office, supra footnote 4 at 121-122.
[129] Id. at 121-122.
[130] National Bioethics Committee, supra footnote 1 at 48.
[131] National Bioethics Committee, supra footnote 1 at 49.
[132] Seoul Central Prosecutors' Office, supra footnote 4 at 120.
[133] National Bioethics Committee, supra footnote 1 at 44-45.
[134] Id. at 48-49.
[135] Id. at 7-8.
[136] Hwang et al., supra footnote 62 at 1674.
[137] National Bioethics Committee, supra footnote 1 at 49. If the information on research funding had been clarified at an early stage, proper guidelines on human embryonic stem cell research could have been applied, and many ethical problems may have been prevented, as we have already seen in supra 2).
[138] KGCP Art. 8 § 7.
[139] National Bioethics Committee, supra footnote 1 at 47. The principal investigator Hwang Yunyoung has been suspected having exercised her influence on the IRB members (most of whom were her colleagues at Hanyang University Hospital) and later putting her name as a coinventor on Dr. Hwang's stem cell patent application pertaining to the 2004 paper. Dr. Hwang Jung Hye, another investigator and coauthor of the 2004 and 2005 papers (she was a professor of Hanyang University Medical School), also participated in the IRB's decision-making and helped the protocol get the approval of the IRB. Dr. Park Munil, the chair of the IRB of Hanyang University Hospital, later stated in an interview with the MBC news magazine "PD Notebook" that if he had known that those eggs were not donated but purchased, he would have never approved the protocol; all the board members simply believed Dr. Hwang Jung Hye's assertion that there was no problem with the eggs. Gang Yanggu, Hwang Woo Suk Gyosuga Kkog Haemyeonghae-Ya Hal 4 gaji Uihog (The Four Suspicions Dr. Hwang Should Answer) , The Pressian, Nov. 23, 2005 (Language: Korean). Available online at http://www.pressian.com/scripts/section/article.asp?article_num=30051123084502&s_menu=%EC%82%AC%ED%9A%8C (last visited on March 30, 2006).
[140] Korean Bioethics Association, supra footnote 70.
[141] Office of Inspector General, supra footnote 3.
[142] Id. at 4-9.
[143] Regulations permitting human embryonic stem cell research generally mandate an IRB review. For example, California and New Jersey, the states that approved therapeutic cloning, also mandated IRB review to oversee therapeutic cloning and human embryonic stem cell research. S.B. 253, 2001-02 Reg. Sess. (Ca. 2001); S.B. 1909, 210th Leg., 2d Sess. (N.J. 2002), 2003 N.J. Laws 203.
[144] See infra , II.2.c.4)
[145] See supra, II.2.b.2).
[146] Another corresponding author of the 2004 paper. Hwang et al., supra footnote 62.
[147] For the history of the Stem Cell Research Center, see supra footnote 97.
[148] A left-wing party in South Korea. One reason they could have raised ethical problems regarding research funding was that they were comparatively free from the nationalistic and mercantile sentiment that overwhelmed the two major political parties on scientific research and development.
[149] Gang Yanggu, Hwang Woo Suk and his colleagues' illegal research and Government's Acquiescence and Support , Pressian Sep. 28, 2005 (Language: Korean). Available online at http://pressian.com/scripts/section/article.asp?article_num=30050928123652&s_menu=%EC%82%AC%ED%9A%8C (last visited on April 1, 2006).
[150] Korean Bioethics Association, supra Footnote 70; Koo, supra footnote 70 at 8; Cyranoski, supra footnote 71.
[151] One was "The Social Influence of the Analysis of Information on Mad Cow Disease" and the other was "The Ethical Review of Bio-organs and the Research on its Industrial Development." The Board of Audit and Inspection of Korea, supra footnote 3 at 14.
[152] See supra footnote 49.
[153] Hwang et al., supra footnote 62.
[154] Pilryeol Lee, Professors Times , Feb. 23, 2004.
[155] Cyranoski, supra footnote 71.
[156] Gang Yanggu, Nature says "Hwang's Research has Ethical Problems" , The Pressian, May 7, 2004 (Language: Korean). Available online at http://www.pressian.com/scripts/section/article.asp?article_num=30040507111613&s_menu =?? (last visited on March 30, 2006)
[157] Park Kiyoung, "I explain the issue of research participation," the Pressian's Online Bulletin Board, May 8, 2004. (Language: Korean) (The post no longer exists, but it has been copied to many blogs, e.g., the Technologists' Forum (a Korean Website of technologists). Available online at http://www.engforum.org/news/read.php?idxno=446 (last visited on March 29., 2006)) She explained in that posting that even though she had not participated in the scientific research, she had discussed and reviewed the ethical issues of the research, and had the expertise to do that through her experience in drafting the Bioethics and Safety Act, in collaborating with science sociologists and NGOs, and in publishing papers on bioethical issues. She asserted that as extra-scientific issues were very important to this kind of research, her contribution on bioethical and science sociological review of the paper deserved the authorship.
[158] Korean Bioethics Association, supra footnote 70; Koo, supra footnote 70 at 8.
[159] South Korea's grant-allocating system is highly centralized. Many grants are assigned not by peer review but by earmarking popular projects or by related agencies' exercise of discretion. Though such a "selection and concentration" policy has proved very successful in semiconductors and other applied sciences, this stem cell scandal seriously questions the validity of such a policy.
[160] She advocated for Dr. Hwang openly when the egg donation issue arose, and when the IRB of the College of Veterinary Medicine, Seoul National University issued its investigation report, which was actually an 'indulgence' of Dr. Hwang and his coresearchers' ethical wrongdoings; she ordered an official of the Ministry of Health and Welfare announce it instead of the IRB itself to render the indulgence more official. The head of the Bioethics Team under the Ministry of Health and Welfare later admitted it and apologized. Gang Yanggu, Bokjibu "Park Kiyoung Bojwagwani Sikineun Daero Haetda" (Ministry of Health and Welfare admits, "we did as Advisor Park Kiyoung ordered") , The Pressian Feb. 21, 2006 (Language: Korean). Available online at http://www.pressian.com/scripts/section/article.asp?article_num=30060221100351&s_menu =»çȸ (last visited on May 15, 2006).
[161] Hwang et al., supra footnote 62, 1674.
[162] Seoul=Newsis, 'Hwanggeumbakjwi', Hwang Woo Suk eoge IMT2000Gigeum Jiwonharyeo 'BIT' Sinjoeo Mandeureonna (Have "Golden Bats" created 'BIT' to award Dr. Hwang the IMT2000 grants), Chosunilbo Dec. 27, 2005 (Language: Korean). Available online at http://www.chosun.com/economy/news/200512/200512270494.html (last visited on May 16, 2006).
[163] Woo Suk Hwang et al., Patient-Specific Embryonic Stem Cells Derived from Human SCNT Blastocysts , announce online at Science Express on 19 May 2005; and published at Science 17 June 2005: Vol. 308. no. 5729 1777-1783 (retracted). Available online at http://www.sciencemag.org/cgi/content/full/308/5729/1777#REF9 (last visited on Feb. 10, 2006). Hereinafter the “ 2005 paper.”
[164] Id. at Note 8.
[165] Hwang et al., supra footnote 163.
[166] As the 2004 paper, major opponents were bioethicists, civil rights activists and religious leaders. For the summary of the problems, see Kim Tae-gyu, Ethical Debates May Mar Hwang's Achievement, The Korea Times, June 6, 2005. Available online at http://search.hankooki.com/times/times_view.php?term=hwang+stem+cell++&path=hankooki3/times/lpage/tech/200506/kt2005060617191212350.htm&media=kt . And for the general debates of bioethicists against his research, see the online materials of Biotechnology Surveillance Solidarity Forum, Human Embryonic Research, Is It Okay? Aug. 25, 2005 (Language: Korean). Available online at http://www.demos.or.kr/scholar/doc_files/eco_08.pdf (last visited on April 13, 2006).
[167] Hwang et al., supra footnote 163 at Note 8.
[168] Bioethics and Safety Act, supra footnote 42, Art. 9 § 1.
[169] Id , Art. 23 and Art. 24.
[170] Id, Art. 6 and Art. 7.
[171] Id. Addenda (3).
[172] As explained in supra II.1.b., the National Bioethics Committee was formed as late as April 2005, and it did not issue any review guidelines until the stem cell scandal broke. Therefore, it was practically impossible for other research teams to get the review and approval of the NBC on the SCNT research. This addenda had been highly criticized by biotech researchers as a de facto monopoly, narrowly tailored for Dr. Hwang, but it passed the National Assembly with no change.
[173] Hwang et al., supra footnote 163 at Note 8.
[174] This meant that the Minister of Health and Welfare did not wait for even the IRB review of the research institution itself. On the other hand, the IRB of Hanyang University Hospital conducted the review of oocytes and somatic cells donation also for the 2005 paper as well as for the 2004 paper, and it gave its approval on Oct. 19, 2004, under KGCP. Hwang et al., supra footnote 163 at Note 8; and its supporting Online Material 1-3, 18-24 (available online at http://www.sciencemag.org/cgi/content/full/1112286).
[175] National Bioethics Committee, supra footnote 1 at 45-54. Most donated eggs from 2003 to 2005 could not be distinguished clearly for each research, and the problems surrounding egg donations and the IBR review of which were repeated and overlapped with the 2004 paper. See II 2. b. 1), supra .
[176] Hwang et al, supra footnote 163.
[177] David Magnus & Mildred K. Cho, Issues in Oocyte Donation for Stem Cell Research , Science 17 June 2005 Vol. 308. no. 5729, 1747 – 1748. Published online May 19, 2005 (10.1126/science.1114454).
[178] The National Bioethics Committee, supra footnote 1 at 53-54.
[179] Seoul Central District Prosecutors' Office, supra footnote 4 at 118-120. This practice had two problems. First, compensation of any sort exceeding opportunity costs is punishable under the Bioethics and Safety Act. Second, recruiting from its own patients creates tension in the doctor-patient relationship, because patients would feel obliged to volunteer to get better treatment.
[180] The Board of Audit and Inspection of Korea, supra footnote 3 at 1-15.
[181] Hwang et al., supra footnote 163 at 1777.
[182] Seoul Central District Prosecutors' Office, supra footnote 4 at 84.
[183] Id. at 68.
[184] Kim Tae-gyu, 'Hwang Over-shares Credit' , The Korea Times Aug. 4, 2005. Available online at http://times.hankooki.com/lpage/200508/kt2005080420430510440.htm (last visited on May 14, 2006).
[185] University of Pittsburgh, supra footnote 115.
[186] Prof. David Magnus, criticizing Dr. Schatten's behavior, analogized, "[he] may not have been the one who walked in and robbed the bank. But he was the getaway driver who did not ask why his friends wanted him to drive away when they ran out of the bank" at a blog posting of bioethics.net. David Magnus, Professor Schatten Did Suggest the Photographer , blog.bioethics.net Feb. 12, 2006. Available online at http://blog.bioethics.net/2006/02/professor-schatten-did-suggest_12.html (last visited on April 17, 2006).
[187] Kim Tae-gyu, Hwang Honored as "Supreme Scientist" , The Korea Times June 24, 2005. Available online at http://times.hankooki.com/lpage/tech/200506/kt2005062418281611780.htm (last visited on April 17, 2006).
[188] Kim Sung-jin, Construction of Hwang ’ s Laboratory Begins Friday , The Korea Times Aug. 11, 2005. Available online at http://times.hankooki.com/lpage/200508/kt2005081118265810440.htm (last visited on Feb. 11, 2006).
[189] The Bioethics and Safety Act, supra footnote 42, Art. 22 (2). It stated, "the categories, objects and scope of that research provided in paragraph (1) for which an act of transplanting the nucleus of a somatic cell may be performed shall be provided for by the Presidential Decree after being deliberated on by the National Committee," therefore, without a Presidential Decree no stem cell research by SCNT could be approved except for research which came under the Addenda (3) exception.
[190] Choi Youngjun, Bokjibu, Hwang Woo Suk Gyosu team Julgisepo yeongu Seungin (Ministry of Health and Welfare Approved Hwang ’ s Research) , Official Website of the Ministry of Health and Welfare Bulletin Board Jan. 12, 2005 (Language: Korean). Available online at http://mohw.news.go.kr/warp/webapp/news/print_view?id=634dc2ede58a43010f8479c5 (last visited on April 13, 2006).
[191] The Solidarity for Biotechnology Surveillance, an association of 13 civil rights and women’ s rights activists groups held the Forum: "Is the Current Human Embryonic Research Acceptable?" on August 25, 2005 in Seoul, South Korea. The overly enthusiastic attitudes of major media were one topic of the forum. The panelist Kim Myeongjin, lecturer of Sungkonghoe University, criticized that the Korean media mostly ignored the ethical problems and technical barriers of human embryonic stem cell research; praised Dr. Hwang as if he could cure patients in the near future, thus disabling any rational discussion with opponents, and put ethicists on the opposite side of Dr. Hwang, depicting them as obstacles impeding his urgent scientific research and development. He also pointed out that the accolades by the western scientists and media on Dr. Hwang’ s success was partly to stimulate their own conservative governments and politicians, so Koreans should not accept such praise too naively. What he discussed in the forum was later published in a Korean magazine entitled Environment and Life 2005 Fall. However, such criticisms were also ignored by most major media.
[192] His team won a U.S. patent for technology facilitating the extraction of human embryonic stem cells from frozen embryos in Oct. 2005. See Kim Cheong-won, Research Team Gets US Patent for Stem Cell Technology , The Korea Times 10-17-2005. Available online at http://times.hankooki.com/lpage/200510/kt2005101717184810160.htm (last visited on April 17, 2006).
[193] Yonhap News, Chesepo Bokje Baea Yeongu Hwang Gyosu team 'Dokjeom' Wae? (Hwang ’ s Monopoly on SCNT Stem Cell Research, Why?) Chosunilbo 2006. 1. 15 (Language: Korean). Available online at http://www.chosun.com/economy/news/200601/200601150015.html (last visited on April 13, 2006).
[194] Professor of Hanrim University College of Law, South Korea, and also member of the NBC.
[195] Bioethics and Safety Act, supra footnote 42, Art. 7.
[196] Actually Yang Samseung, the chairman of the committee, was President Roh Mu Hyun’ s attorney and also shared the supportive view of the President toward biotechnology and Dr. Hwang. Yang later gave legal advice to Dr. Hwang when ethical issues were raised, and had to resign due to the conflicts of interest.
[197] This is exactly opposite from what happened in the United States. President Bush dismissed Dr. Blackburn and Dr. May from the President’ s Council on Bioethics on February 27, 2004. Both had disapproved the restrictive stem cell policy of the Bush administration. Their seats were filled by persons more supportive of the President. To show the ironic symmetry with the South Korean situation, let me directly cite from the report. "[Dr. Blackburn] was one of only three full-time biomedical scientists on the panel, which, even prior to her dismissal, was weighted heavily to nonscientists with strong ideological views. While no one disputes that nonscientists should play an important role on a bioethics panel, it is equally important that scientists, with strong biomedical expertise, provide the necessary scientific context for the panel." The Union of Concerned Scientists, Scientific Integrity In Policy Making: Further Investigation of the Bush Administration ’ s Misuse of Science, the July 2004 update. Available online at http://www.ucsusa.org/scientific_integrity/interference/reports-scientific-integrity-in-policy-making.html (last visited on April 14, 2006). In the case of the NBC, the bioethicists were outnumbered and overwhelmed by scientists and government officials.
[198] Bioethics and Safety Act, supra footnote 42, Art. 6.
[199] Korean Bioethics Association, Emergency Forum: to Guarantee the Ethics and Integrity of Biotechnological Research, January 24, 2006, Seoul.
[200] See Pak, supra footnote 37 at 180-201.
[201] Daniel K. Nelson, Conflict of Interest: Institutional Review Boards, in Elizabeth A. Bankert & Robert J. Amdur Ed., Institutional Review Board, 177-181 (Jones and Bartlett Publishers 2005, 2nd Ed.)
[202] The National Bioethics Committee, supra footnote 1 at 54-61.
[203] Stem cell research institutions were required to have their local IRBs in order to be approved under Addenda (3).
[204] The National Bioethics Committee, supra footnote 1 at 54-61.
[205] Ministry of Health and Welfare, The Result Of The Investigation On The Ova Donation Of Hwang Woo-Suk Research Team Of Seoul National University (Press Release) , Nov. 24, 2005 (Language: Korean). Available online at http://www.mohw.go.kr/download.tdf?f=/2005/11/20051124182337799088_1.hwp&fn=????????11.24.hwp&table=gp_tb_data_file (last visited March 10, 2006)
[206] Later Kim Heonju, the Chief of the Bioethics Team under the Ministry of Health and Welfare, apologized through an e-mail to the members of the NBC that it had been inappropriate for the Ministry to announce the misleading investigation report of the College of Veterinary Medicine IRB instead of the chairperson of the IRB, and they had been ordered to do so by Park Kiyoung, the advisor to the President. Gang Yanggu, Bokjibu, "Park Kiyoung Bojoagwani Shikineun Daero Haetta" (the Ministry of Health and Welfare did as ordered by the President's Advisor Park Kiyoung) , The Pressian, Feb. 21, 2006 (Language: Korean). Available online at http://www.pressian.com/scripts/section/article.asp?article_num=30060221100351&s_menu =»çȸ (last visited on April 17, 2006).
[207] E.g., Scottish embryologist Ian Wilmut, who cloned the a sheep named Dolly in 1996, made a joint study agreement with Dr. Hwang (it is quite ironic that Wilmut himself is blamed for the dubious coauthorship on Dolly paper now), and Hwang announced that he would cooperate in a joint diabetes study with Harvard University team led by Dr. Douglas Melton. Kim Tae-gyu, Support for Hwang Coverage , The Korea Times 05-23-2005, available online at http://times.hankooki.com/lpage/biz/200505/kt2005052319363411900.htm (last visited on Feb. 10, 2006); Kim Tae-gyu, Hwang to Stage Joint Cloning Research With Harvard Team , The Korea Times Jun. 3, 2005, available online at http://times.hankooki.com/lpage/biz/200506/kt2005060320431911910.htm (last visited on March 11, 2006).
[208] Abbreviation of “ Seoul National University Puppy.”
[209] Gina Kolata, Beating Hurdles, Scientists Clone a Dog For a First , The New York Times, Aug. 4, 2005, A1.
[210] Kim Tae-gyu, Catholic Church Funds Adult StemCell Research , The Korea Times Oct 5, 2005. Available online at http://times.hankooki.com/lpage/200510/kt2005100517255110160.htm (last visited on March 3, 2006).
[211] Seoul Central District Prosecutors' Office, supra footnote 4 at 122-124.
[212] Han Haksu, Myth of Hwang Woo Suk in ourselves , PD Journal of the Broadcasting Producer Association of Korea, 2006-1-11 (Language: Korean). Available online at http://www.pdnet.or.kr/newspaper/newsview.asp?cd=8799 (last visited Mar 9, 2006). He stated in this postscript to the program that when he was first informed of the suspicion he immediately realized the difficulty of the situation but still felt the urgency to investigate. He wrote, "if the fabrication of the paper were true, it would be revealed eventually, and I felt the pressure that it should be done by no other than a Korean news media. It would be an unthinkable humiliation if, say, the New York Times reported it first. The investigation therefore became urgent."
[213] Kim Tae-gyu, Member of Hwang Team Involved in Ovum Scandal , The Korea Times Nov. 8, 2005. Available online at http://times.hankooki.com/lpage/200511/kt2005110817390153460.htm (last visited on March 10, 2006).
[214] Gina Kolata, Scientists' Rift On Stem Cells Surrounded By Mystery , The N.Y. Times, Nov. 15, 2005, A24.
[215] Kim Tae-gyu, Hwang ’ s Stem Cell Team Paid for Eggs , The Korea Times Nov. 21, 2005. Available online at http://times.hankooki.com/lpage/200511/kt2005112117185110440.htm (last visited on March 10, 2006).
[216] English version of this program is unavailable. For the summary of the program, see Kim Tae-gyu, Hwang Faces Renewed Accusations of Using Researcher's Eggs , The Korea Times Nov. 22, 2005. Available online at http://times.hankooki.com/lpage/200511/kt2005112217340610440.htm (last visited on March 10, 2006).
[217] James Brooke And Choe Sang-Hun, South Koreans Rush to Defend Cloning Researcher Against Criticism , The New York Times Nov. 29, 2005, A11.
[218] Ministry of Health and Welfare, The Result Of The Investigation On The Ova Donation Of Hwang Woo-Suk Research Team Of Seoul National University (Press Release) , Nov. 24, 2005. Available online at http://www.mohw.go.kr/download.tdf?f=/2005/11/20051124182337799088_1.hwp&fn=????????11.24.hwp&table=gp_tb_data_file (last visited March 10, 2006) (Language: Korean). As we have seen infra, this announcement itself was problematic.
[219] http://bric.postech.ac.kr/ (Language: Korean).
[220] This "Anonymous" person suggested that on pages 11, 12 of the Supporting Online Materials of Dr. Hwang's 2005 paper (supra note 15, available online at http://www.sciencemag.org/cgi/data/1112286/DC1/1 ) there were several identical pairs of cell photos that should not be identical. Fierce debates ensued. Available in Korean at http://gene.postech.ac.kr/bbs/view.php?id=job&page=91&sn1=&divpage=2&sn=off&ss=on&sc=on&select_arrange=headnum&desc=asc&no=3464 (last visited March 10, 2006).
[221] Nicholas Wade, New Criticism Rages Over South Korean Cell Research , The New York Times Dec. 10, 2005, A6.
[222] The journal Science defended Dr. Hwang in spite of the identical photos and data for a while. Nicholas Wade, Journal Defends Stem Cell Article Despite Photo Slip , The New York Times Dec. 7, 2005, A20.
[223] Kim Tae-kyu, Hwang Faked Stem Cell Research, The Korea Times Dec. 15, 2005. Available online at
http://times.hankooki.com/lpage/tech/200512/kt2005121523572111780.htm
[224] Nicholas Wade et al., Korean Scientist Said to Admit Fabrication in a Cloning Study , The New York Times Dec. 16, 2005, A1.
[225] AP, Faked Research On Stem Cells Is Confirmed By Korean Panel , The New York Times Dec. 23, 2005, A6.
[226] Seoul National University Investigation Committee, supra footnote 2.
[227] Nicholas Wade And Choe Sang-Hun, Human Cloning Was All Faked, Koreans Report , The New York Times, Jan. 10, 2006, A1.
[228] Seoul Central District Prosecutors' Office, supra footnote 4.
[229] Seoul National University Investigation Committee, supra footnote 2.
[230] Seoul Central District Prosecutors' Office, supra footnote 4 at 1-83 .
[231] The following facts are based on the investigation by the Prosecutors' Office. The criminal trial will take a while, and some of the facts may change.
[232] Seoul Central District Prosecutors' Office, supra footnote 4 at 54-69.
[233] Dr. Hwang denies the charge that he ordered the subordinates to do so, and argues that he did not know that the identical DNA fingerprinting results came from the same cell.
[234] Seoul Central District Prosecutors' Office, supra footnote 4 at 9-53, 70-88.
[235] Seoul Central Prosecutors' Office, supra footnote 4 at 135-138.
[236] Donald Kennedy, Editorial Retraction , Science Express on 12 January 2006, Science 20 Vol. 311. no. 5759, p. 335. Available online at http://www.sciencemag.org/cgi/content/full/311/5759/335b (last visited on Mar 20, 2006)
[237] Chung Ah-young, Hwang Dismissed from SNU , The Korea Times March 20, 2006. Available online at http://times.hankooki.com/lpage/nation/200603/kt2006032020471011990.htm
[238] Seoul Central District Prosecutors' Office, supra footnote 4 at 18-20.
[239] National Bioethics Committee of Korea, supra footnote 1.
[240] See http://ori.dhhs.gov/about/history.shtml
[241] A scandal of "government involvement in research on African-American men with syphilis who were left untreated so that the researchers could study the untreated course of the disease." Ken Gatter, Fixing Cracks: A Discourse Norm To Repair The Crumbling Regulatory Structure Supporting Clinical Research And Protecting Human Subjects , 73 UMKC L. Rev. 581, 596.
[242] National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Reserach , April 18, 1979. Available online at http://ohsr.od.nih.gov/guidelines/belmont.html (last visited on April 27, 2006).
[243] Krimsky, supra footnote 5 at 1.
[244] Shamoo & Resnick, supra footnote 5 at 48-50.
[245] National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report, supra footnote 242.