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19 Mar 2014 10:43

Nature | News

Stem-cell method faces fresh questions

Papers describing acid-bath technique under more scrutiny after institute’s investigation finds errors in methodology.

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The Asahi Shimbun via Getty

A RIKEN spokesperson talks to reporters after two Nature stem-cell papers by researchers at RIKEN's Center for Developmental Biology in Kobe, Japan, were criticized by other scientists.

The veracity of two papers that detailed a method to reprogram mature cells into an embryonic state by exposing them to stress has come under more pressure. Days after the first author’s institute reported “serious errors” in the papers’ methodology, questions were raised over the same researcher’s doctoral dissertation and the cells used in the study.

On 14 March, RIKEN, Japan’s largest research organization, which runs the Center for Developmental Biology (CDB) in Kobe where first author Haruko Obokata and several of her co-authors work, announced the interim findings of its investigation into allegations of irregularities in the method. One RIKEN investigator advised them to retract the papers. Then, in further developments, Obokata called into question the quality of her own doctoral thesis, which is already under investigation by the university that granted it. And a co-author on the reprogramming papers says that he is sending some of the cells produced in the experiments for independent verification.

The two papers made headlines around the world when they were published in Nature on 30 January (H. Obokata et al. Nature 505, 641–647 and 676–680; 2014). The technique, which the team called stimulus-triggered acquisition of pluripotency (STAP), is important because cells reprogrammed into an embryonic state are ideal for studying the development of disease or the effectiveness of drugs.

But within weeks, the papers were attacked by scientists over their use of several duplicated images and by those who could not reproduce the work, prompting RIKEN to investigate.

At the press conference, a five-person panel, including RIKEN director and Nobel-prizewinner Ryoji Noyori, noted six problems. Two were dismissed as unintentional mistakes. Four others — including an image of an electrophoresis gel that seemed to have had a lane added in later, and plagiarism in part of the methods section — were deemed more serious and are still under investigation. The panel offered no clear answers about whether the STAP phenomenon is real, but noted that RIKEN co-author Hitoshi Niwa was attempting to replicate the method. It added that there were no signs of fraud.

“What did I inject into those blastocysts? This is what I want to know.”

Panel member Masatoshi Takeichi, director of the CDB, also told reporters that the three co-authors from the institute — Obokata, Niwa and Yoshiki Sasai — had agreed to retract the paper at his request. But a statement in Japanese by the trio, delivered at the press conference, said only that they were “considering a retraction and contacting outside authors to discuss that possibility”. Charles Vacanti, of Harvard Medical School in Boston, Massachusetts, who is the senior corresponding author on the first of the two papers (H. Obokata et al. Nature 505, 641–647; 2014), has made it clear that he has no intention of retracting unless there is compelling evidence that the data are incorrect.

To add confusion, the first 20 pages of Obokata’s thesis, completed in 2011 at Waseda University in Tokyo, were found by NatureNews to be taken from a US National Institutes of Health primer on stem cells, and one image in the results section has been reproduced from a commercial website without a citation. Moreover, Vacanti, who was listed on the thesis as a member of the examination committee that approved it, told Nature News: “I was not presented with or asked to read a copy of her dissertation.”

Last week, Obokata wrote to an unnamed professor at Waseda University indicating that she wanted to retract the thesis. She has not, however, formally requested a retraction.

A desire to resolve the STAP controversy has led to an investigation into the identity of the cells in the papers. Teruhiko Wakayama of the University of Yamanashi, a senior author on the second paper (H. Obokata et al. Nature 505, 676–680; 2014), helped to test the pluripotency of Obokata’s STAP stem cells by injecting them into mouse embryos. By turning into different cell types within these mice, the cells proved they had the developmental capacity that STAP promises. But he has now sent the cells that Obokata gave him to an independent institute for genetic analysis to see if they are really STAP cells. “What did I inject into those blastocysts?” Wakayama asks. “This is what I want to know more than anything else.” He hopes to have his answer in the next few months.

Journal name:
Nature
Volume:
507,
Pages:
283
Date published:
()
DOI:
doi:10.1038/507283a
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7 comments Subscribe to comments

  1. Avatar for Toshihito Nakamura
    Toshihito Nakamura
    I was very impressed that so many researchers love the freedom in scientific writing, and now are reading in many foreign languages with great enthusiasm. Because an old sci-fi writer Asimov I. said on his PhD work, ”… I rather dreaded that, since the obligatory style of dissertations is turgid in the extreme, and I had by now spent nine years trying to write well and was afraid I simply might not be able to write badly enough to qualify for my degree...”, and my friend researchers on Healthcare Policy in Japan are sometimes rejected their papers from journals in English with editors’ comments on the importance on commonality. Perhaps now we have a right to write in free for free. But I was not talented for writing. I’m interested in writing what I found, but not how I express it. If I had the public licensed library database on usually used Materials and Methods and / or short histories on some important issues, I may use them, indeed.
  2. Avatar for Leonardo Cabrera
    Leonardo Cabrera
    The debate over the "linguistic facility on written English" is futile. One can choose to submit an article in other language (Japanese journal, in case of Obokata, et al) if there is substantial lack of ability to communicate in written English. Should the findings be good enough, they will eventually be recognized in the international science community.
  3. Avatar for Mugifumi AKIMOTO
    Mugifumi AKIMOTO
    The first comment isn't proposing that everybody should use the stock phrase database, methinks--and I am not sure if availability of stock phrase database would undermine "freedom in scientific writing". His proposal is to help the linguistically underprivileged and help them participate in the scientific dialogue (it WON'T make the equal-ground anyway) and NOT to put a cast on the forms of writing. OR would you rather say, "Well, if you cannot acquire the linguistic facility (especially writing in English), you are simply not good enough to make any scientific contribution here." On a slightly different note, perhaps we can set aside native/non-native difference; there will be a huge gap between those educated in English speaking countries or simply have had more exposures to English speaking/writing community. And, data validity is a separate issue. It's clear that there are many questions to be answered, and I won't be particularly surprised if it at the end was a piece of fiction.
  4. Avatar for H T
    H T
    I second the comment by Leonardo. There is little need for a 'stock phrase' database, as the English language, similar to most human languages, has a rich vocabulary and many sentence forms to permit vastly different constructs. Identification of copyable phrases will only lead to very repetitive and mechanical publications. The bigger issue is to improve the typical format and makeup of a scientific paper. In particular, editors should influence authors to trim their submissions, like in the days of mechanical typesetting when word count really mattered. I mean, do we really need 500 different half-page introductions to the subject of, say, human influenza H3N2 every year?
  5. Avatar for Leonardo Cabrera
    Leonardo Cabrera
    I must disagree with the previous comment, especially on the proposal of stock phrase database. There is a huge difference between the "common phrase heavily used on the introductions/ methods" and "messages authors wish to state on the introduction/ accuracy of the description on the methods section". Setting a writing template may result in more unwanted rigidity in the manuscript therefore causing loss of freedom in scientific writing, a phenomenon not welcome to most of us in the scientific community. And the history of biology research has self-organized in a way that English papers have more value, taking in account for the size of audience they would attract, as well as the credibility of English language based scientific publishers. Putting a cast on the freedom of speech is not an answer to the linguistic handicap that foreigners face (I myself am not an English native). Finally, there are more issues than "just" plagiarism on this stem cell issue. The credibility of their data demonstrated are challenged. What's good is good, and what's bad is bad, period.
  6. Avatar for Guest
    Guest
    I must disagree with the comment above, especially on the proposal of stock phrase database. There is a huge difference between the "common phrase heavily used on the introductions/ methods" and "messages authors wish to state on the introduction/ accuracy of the description on the methods section". Setting a writing template may result in more unwanted rigidity in the manuscript therefore causing loss of freedom in scientific writing, a phenomenon not welcome to most of us in the scientific community. And the history of biology research has self-organized in a way that English papers have more value, taking in account for the size of audience they would attract, as well as the credibility of English language based scientific publishers. Putting a cast on the freedom of speech is not an answer to the linguistic handicap that foreigners face (I myself am not an English native). Finally, there are more issues than "just" plagiarism on this stem cell issue. The credibility of their data demonstrated are challenged. What's good is good, and what's bad is bad, period.
  7. Avatar for Kentaro Iwata
    Kentaro Iwata
    I am by no means in favor of plagiarism and reproduction of 20-page-amount to a thesis is not acceptable. However, I fear this might engender hyper-scrutiny of past articles on "copy and paste" and knit-picky accusations on many scientists, particularly on those whose native tongues are not English. We of course cite facts and data, but may not able to cite style, stock phrases and so on, and the definition of plagiarism can sometimes be tricky and vague. Many scientific sentences look alike, especially in Introduction, Materials and Methods, or at a section on statistical analyses, but I do not think these similarity would affect the value of articles. Technology enables us to do "witch-hunting", and we non-English speakers have to fear false accusation of plagiarism. I overheard that plagiarism is common among Asians. I do not know this notion is true or not, but I have never heard of Asian being overly unethical comparing to the others in any other fields. So why only on plagiarism? Composing articles in English is a handicap to us, and scientific handicap should be overcome by system, not by imposing us to improve our English to the level of natives. Here I propose a production of a database of stock phrases, which are commonly used in scientific literatures, and allow everyone to use them without citation. This encourages non-English speaking scientists to submit more papers, without fearing false accusation of plagiarism.

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