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November 16, 2012 | Posted By Zubin Master, PhD

This blog will have two parts. In this first entry, I present will discuss a recent case of stem cell fraud and the subsequent blog entry will discuss possible lessons to learn appearing next month.

The tale begins when Woo-Suk Hwang, a once celebrated hero of South Korea, claimed to have made the first, patient-specific human embryonic stem cell (hES) line through a technique called somatic cell nuclear transfer (commonly referred to as research or therapeutic cloning). This study was soon after proven to be fraudulent. Not to get into too many details, but this technique requires obtaining ova from women providers, enucleating its genetic material, and placing the nucleus from a somatic cell and parthenogenically activating the egg. This initiates embryonic development and at about day 3-4 of development (where the embryo is at the blastocyst stage), hES cells can be isolated from the inner cell mass of blastocysts. This incredible feat in stem cell research was published in Science in 2004 and another study in 2005. In 2006, Hwang was discredited for fabricating results and after an investigation, he was convicted for embezzlement and bioethical allegations. He embezzled approximately 830 million won (US $700,000) of government funds and apparently used 2,200 eggs obtained from his female postgraduate students and junior researchers. All wasted!

The stem cell fraud saga continues with a recent account by researcher Hisashi Moriguchi. I think I would summarize this case to include alleged fabrication or falsification of data, what seems to be providing false affiliation of research institutions, plagiarism, and poor publication practices. This story made headlines days after Shinya Yamanaka won a Nobel prize for discovering induced pluripotent stem (iPS) cells. iPS cells have revolutionized stem cell research. To simplify, differentiated somatic cells obtained, for example, from patients’ skin can be genetically manipulated to behave with greater potential similar to hES cells in order to then differentiate them into other cell types. Scientists, ethicists and even George Bush Jr hailed the discovery of iPS cells because they avoid many of the intractable ethical issues associated with deriving hES cells and transplanting them into patients – namely the moral status of human embryos, and harms to women as egg providers; the latter issue being especially pertinent in the context of using somatic cell nuclear transfer since the technique remains inefficient and requires lots of eggs.

So what did Moriguchi do?

First, he claimed to have derived patient-specific iPS cells, differentiated them into cardiac muscle cells, and transplanted them into several patients with terminal heart failure. While attending the annual research conference of The New York Stem Cell Foundation in New York City, Moriguchi presented a poster of this research along with co-author Chifumi Sato. So did this research actually take place? Moriguchi claimed to have used a technique of reprograming somatic cells using only two factors, which has never been done before. He also claimed to have differentiated the cells into cardiac cells using a supercooling method he developed. More will follow below to question whether this research actually happened.

Second, while publishing his two chemical method to generate iPS cells, he plagiarized paragraphs verbatim from other papers, one even from Yamanaka. His response when interviewed by Nature reporters was “We are all doing similar things so it makes sense that we’d use similar words”. I am however unclear whether he did cite the other papers he copied. As for his supercooling method to derive cardiac cells, this was published in a paper by him in Scientific Reports. But the data reported here is about supercoiling of human ovaries, not the differentiation of iPS cells. Moriguchi’s response here was that the referee had recommended that he leave that experiment out of the publication. To determine whether this research is bogus or not, Moriguchi also claims to have done most of the work himself and would not name his collaborators. A look into his education only adds further incredulity to his research claims. Moriguchi studied nursing during his undergrad and health promotion for his master’s. He obtained a PhD from the University of Tokyo for work related to hepatitis C.  Inquiry from the University of Tokyo confirmed Moriguchi held a position from 2006-2009 in which he studied medical economics and the evaluation of clinical technologies and until recently, he was a researcher working in the university’s hospital in the laboratory of Makoto Mihara.

Third, Moriguchi claimed to have affiliation at Harvard Medical School and Massachusetts General Hospital (MGH). This occurred in 1999 as Ray Chung invited Moriguchi to work in his MGH lab. This affiliation was written in several of Moriguchi’s publications including his poster at the New York Stem Cell Foundation’s conference. Although Moriguchi showed a letter claiming an open and extended invitation as a Visiting Lecturer from Harvard Medical School and MGH, this doesn’t seem to be the case as the letter clearly writes “during your visit” but not specifying dates. 

Fourth, Moriguchi had several publications with Chung and his master’s advisor Chifumi Sato at the Tokyo Medical and Dental University. According to a spokesperson for MGH, Chung did not see the final manuscripts of the 9 articles he co-authored. Chung was there to provide “editorial assistance” and to ensure the English was correct but no proofs were sent to Chung; moreover, as Sato was senior author on all the papers co-authored by MGH researcher Chung, he didn’t have any cause to doubt the accuracy of the manuscripts. Sato also indicates that Moriguchi sent him papers to overlook which were rejected and published as smaller correspondence pieces to journals. There are other researchers and co-authors involved in this fiasco. Although the extent of involvement in the research and the credibility of the publications remain unclear from the reports, as a researcher who studies authorship ethics, this all smells a bit fishy. Personally, it seems like Moriguchi’s so-called colleagues are distancing themselves from the accused. Perhaps rightfully so, or perhaps his collaborators do not want too much of the light to focus on their potentially questionable publication practices.

Let’s summarize. Possible fabrication of data, providing false affiliation, plagiarism, and poor publication practices seem to be the ethical issues in this particular case of stem cell research. There’s more: a lack of ethics review at different institutions but papers indicating ethics approval was obtained, and filing of patents potentially containing questionable science and then later having them retracted. But we don’t need to go into all the details to understand some of the lessons we can learn from this case. Stay tuned…

The Alden March Bioethics Institute offers a Master of Science in Bioethics, a Doctorate of Professional Studies in Bioethics, and Graduate Certificates in Clinical Ethics and Clinical Ethics Consultation. For more information on AMBI's online graduate programs, please visit our website.

1 comments | Topics: Misconduct, Plagiarism, Publication Ethics, Research Integrity, Stem Cell Research

Comments

John Kaplan

John Kaplan wrote on 11/16/12 2:52 PM

There certainly seem to be plenty of charlatans working in stem cells.

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BIOETHICS TODAY is the blog of the Alden March Bioethics Institute, presenting topical and timely commentary on issues, trends, and breaking news in the broad arena of bioethics. BIOETHICS TODAY presents interviews, opinion pieces, and ongoing articles on health care policy, end-of-life decision making, emerging issues in genetics and genomics, procreative liberty and reproductive health, ethics in clinical trials, medicine and the media, distributive justice and health care delivery in developing nations, and the intersection of environmental conservation and bioethics.
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