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Acid-bath stem-cell scientist apologizes and appeals

Posted on behalf of David Cyranoski

Haruko Obokata, the Japanese scientist at the centre of a controversy over studies purporting to turn mature cells to stem cells simply by bathing them in acid or subjecting them to mechanical stress, today apologized for her errors in the work.

Kicking off a press conference in Osaka amid a storm of snapping cameras and flanked by two lawyers, Obokata blamed her immaturity and her lack of awareness of research protocols for the errors that were found in her two high-profile papers on the studies, published in Nature in January (Note: Nature’s news and comment teams are editorially independent of its research editorial team). These included the use of a duplicated image.

She took full responsibility for the errors, and apologized to her co-authors for the mess she got them into. Obokata, in her first public statement in more than two months, also apologized to her institute, the RIKEN Center for Developmental Biology, for the embarrassing press the whole ordeal had brought. In addition, she sought forgiveness from the RIKEN committee whose report earlier this month found her guilty of scientific misconduct. She had attacked the report at the time.

Obokata held the press conference for two reasons: to apologize for the errors and to make the case that her research was still valid and that the inaccuracies in the papers were not deliberate. Yesterday, she submitted a formal appeal to RIKEN that their committee retract its misconduct findings. She insisted that the “stimulus-triggered activation pluripotency” or STAP phenomenon, as it has been dubbed, exists. RIKEN has 50 days to respond to her appeal.

In the STAP work, lead author Obokata, along with Japanese and US colleagues, described stunning experiments in which she reprogrammed mature mouse cells to an embryonic state merely by stressing them. But the two papers soon fell under suspicion and last month a RIKEN-appointed investigative committee found in a preliminary report that they contained numerous errors. In a further report on 1 April, the committee announced that two of the errors constituted scientific misconduct. On the same day, Obokata responded aggressively, with a written statement expressing “shock and anger” at conclusions she said had been reached without giving her a chance to explain herself. Today, her tone was very different: pleading for forgiveness and showering apologies. But she maintained that her findings hold true.

Obokata insisted that the two problems which led to the misconduct findings — the duplicated image and the swapping of a diagram of an electrophoresis gel — were only errors. She said she had not been given enough time to explain her side to the committee.

After her five plus minutes of introductory remarks, her lawyer gave a 20-minute presentation to make the case that neither problem added up to misconduct. Defining fraud as fabrication, he countered that in both cases Obokata had the original data that should have been used but merely added the wrong data by mistake. For the more damning finding — an image of teratomas that had appeared in her doctoral dissertation and then again in the recent papers — the committee had found that she had changed a caption, which made it look intentional. The lawyer however traced the image back to a slide, part of a presentation that Obokata had continually updated and reused, until its origin became obscured. (Later, in one of her many apologies, she said, “If I had gone back to carefully check the original data, there wouldn’t have been this problem.”)

After the lawyer’s talk, Obokata responded to journalists’ questions for more than 2 hours. In response to suspicions based on the fact that she only handed two laboratory notebooks over to the committee looking into her research, she said she had four or five more that the committee hadn’t requested. She denied that she ever agreed to retract the papers. She also corrected reports that she had asked to retract her PhD dissertation, saying that she merely sought advice on how to proceed. Her dissertation is under investigation at Waseda University, where she studied for her doctorate.

Obokata also denied the possibility that the STAP cells had resulted from contamination from embryonic stem cells, saying that she had not allowed embryonic cells in the same laboratory and that she had carried out tests which precluded that possibility.

She said that she had created STAP cells more than 200 times, adding that she knows someone who has independently achieved it but refused to give the name (citing privacy). She believes that a RIKEN group trying to demonstrate STAP cells will help her. She has not, she said, been asked to participate in those efforts. She added that she would consider doing a public replication experiment but that it was not up to her whether she could.

Two hours into the questioning, her lawyer cut off journalists, citing concern for Obokata’s frail emotional state, and said she had to return to the hospital where she has been staying. She bowed, apologized, then bowed again and left. The press cameras contined to snap away.



  1. Report this comment

    Tien Lee said:

    She was awarded PhD from Waseda in 2011… The STAP paper was published in 2013… and she successfully created STAP cells more than 200 times…

    Wow, I think she must have really steady hands however recent media attention night have caused her hands to tremble involuntarily…

  2. Report this comment

    Seiichi MYOGA said:

    It seems that what is going to be at stake here in Japan is whether the errors in question were legally “honest.” RIKEN’s relevant policy is something like this: Research misconduct does not include “honest” error or differences of opinion. In my understanding, the Japanese counterpart of “honest” is literally close in meaning to “without malice.” And the lawyer in the investigating committee mentioned on April 1, ‘Malice means something comparable to scienter in a criminal case (my translation).’ This reference to “criminal case” seems to have changed the nature of the matter. It is unlikely that the report of misconduct will be retracted, so the case may go to court.
    My concern is, what would happen if, following the advice of RIKEN, the other two researchers there were to require retraction for the reason of misconduct? I hope that Nature’s final decision depends still on whether or not the authors can “provide evidence to support the main conclusions of the paper,” otherwise we would never know whether the STAP phenomenon could exist.

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    Sergio Stagnaro said:

    “Without malice” one can commit errors which harm the progress of Medicine. However, as shown by the evidence, publishing articles well documented, we are not able to bring to their end epidemics, as CVD, the leading cause of death in western country, T2 DM, and Cancer. Persisting to march down the wrong path is an unbearable mistake.

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    Felix Bast said:

    I am not surprised at all. When I did my PhD from Kochi University, Shikoku, on numerous occations I have seen scientific misconduct of a so called “famous” seaweed biologist. I questioned him that made him to prolong my PhD to an extend that I have to change my guide and research thesis after spending almost 3 years! As Myoga san said, being honest in Japan is being not a criminal and scientific misconduct is not classified as a criminal offense and therefore this lady will get away. Pity!

  5. Report this comment

    Sachi Sri Kantha said:

    In my view, Dr.Obokata should have been more than forthcoming about her “200 times” replications, providing the exact dates for first time observation, and the last time observation, if they had been duly recorded in her lab note book. Why she failed to mention this fact, in January when she appeared in front of the media, for the first time? Did her listed co-authors (epecially her mentor Dr. Teruhiko Wakayama, who was seen near her in that January presentation) checked these ’200 times’ replication, and approve it?

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    Seiichi MYOGA said:

    The question to ask should have been: Is it true that STAP STEM cells exist (as well as STAP cells)? STAP cells are dormant cells that have the potential to develop into almost any other type of cell in the body, but do not proliferate themselves. In contrast, STAP stem cells are active cells that do show pluripotency. It is worth noting that Obokata said on Apr. 9 something to the effect that she is not actually good at converting STAP cells to STAP stem cells and that the existing STAP stem cells are all produced by Wakayama, although she also asserts that she has successfully created STAP cells over 200 times.
    Then exactly what role did Obokata play in the two Nature papers that face retraction? Nature Blog News reported on Feb. 17 that Wakayama “and a student in his laboratory did replicate the experiment independently before publication, after being well coached by Obokata. … Wakayama says that his independent success in reproducing Obokata’s results is enough to convince him that the technique works.” Considering this, we could infer that what Obokata actually means by the technique called STAP is something like this: when exposed to external stimuli of some kind, CD45+ cells can be reprogrammed to become potentially pluripotent cells. Obokata seems to have decided that this is due to reprogramming rather than selection, because she has accepted the idea that CD45+ cells express Oct4 and other pluripotency-related markers only if they are reprogrammed. In other words, Obokata proposed a possible technique for reprogramming somatic cells, and Wakayama proved the veracity of the technique.
    (Curiously enough, the two errors Obokata was found by the RIKEN investigative committee guilty of, seem to have happened outside of what she is suggesting she can do. Not that I’m accusing the scientist, though.)
    Obokata may have found something. Let me explain about this later.

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    Seiichi MYOGA said:

    As I see it, the primary concern of Obokata lies in showing that potentially pluripotent cells can arise from YOUR somatic cells. The problem (or to be exact, the proof) of where freshly acquired pluripotency comes from (namely, either from reprogramming or from selection) may be beyond her capacity, or at least it may be her secondary interest.
    Scientific misconduct is a neon sign that says, “After all, there is no hard evidence to support the authors’ main conclusions.” If that is not what RIKEN meant, the institute should have made it clear first whether the two Nature papers at issue are really worth following up or not.
    Probably, what makes our eyes pop out is this:
    We have established multiple STAP stem cell lines from STAP cells derived from CD45+ haematopoietic cells. Of eight clones examined, none contained the rearranged TCR allele, … (Protocol Exchange (2014), published online Mar. 5, 2014)
    If this description is correct, it means that Obokata et al’s assertion is wrong that the acquisition of pluripotency in question results from reprogramming – a hard blow on the authors. It could also mean that they found that as a result of selection, CD45+ cells that were exposed to some external stimuli can even develop into cells that express pluripotency-related markers – a new discovery (the magnitude of which I don’t know).
    Some scientists entertain the idea that Obokata’s STAP cells belong to or are closely related to MUSE cells. This means that Obokata’s STAP cells may well shed light on the problem of how mammalian (especially human) cells can acquire pluripotency.
    (And attention centers on Obokata’s STAP cells. We should also appreciate Wakayama’s skills that can change potential pluripotency to actual pluripotency.)
    I firmly believe that before officially advising retraction, RIKEN should give Obokata opportunities to create STAP cells. Then all RIKEN has to do is wait and see if Wakayama can engineer STAP stem cells from her STAP cells, using them to create, for example, a chimera mouse successfully. This would be the best way in terms of directness, time-saving and cost-effectiveness.

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