The controversial STAP stem cell papers published in Nature had authors both from RIKEN in Japan and Brigham and Women’s Hospital/Harvard.
What is the RIKEN interim take on the STAP cell situation?
We’ve had pretty much silence from Harvard itself on this matter publicly.
Dr. Charles Vacanti, senior author on one of the STAP papers, author on the other paper, and mentor of the first author on both papers, Dr. Haruko Obokata, has, however, been openly talking to the press. He continues to defend the papers and has indicated to the press no need for retraction.
RIKEN launched an investigation weeks ago.
Today RIKEN announced the preliminary findings of their still on-going investigation. The RIKEN press conference was nicely covered here by Karen Kaplan and Monte Morin of the LA Times and also discussed here in the Asahi Shimbun. The actual RIKEN press release (PR) is here.
One of the key statements quoted by Asahi Shimbun from RIKEN:
“We apologize for the confusion that has arisen. The authors seriously accept the fact that the discovery of inconsistencies in the articles damages its credibility and we have begun considering the possibility of withdrawing the articles through communications with our co-authors.”
It’s notable that they apologize for the confusion….not the actual problems.
RIKEN reportedly has focused on 6 issues according to the LA Times and its own PR with two of them having been resolved.
The first resolved issue involves the “unnatural appearance of colored cell parts shown by arrows” in one of the papers. The investigative committee determined that “the process of preparing these images did not constitute fabrication within the context of research misconduct.”
Is this referring to Figure 1f?
That end part of the quote seems very difficult to understand. Did something go wrong, but not serious enough to call misconduct?
The 2nd “resolved” issue was of the apparently duplicated placentas, which Dr. Wakayama has already taken responsibility for as an unintentional error due to the sheer number of files involved in putting the paper together.
The 4 unresolved issues according to the LA Times and the RIKEN PR:
- “1. A figure in one of the papers appears to have been doctored. The figure shows key genetic changes in the reprogrammed cells.
- 2. A sizable portion of the same paper seems to have been copied from a previously published study. The portion in question describes the researchers’ methods for examining chromosomes in the cells.
- 3. The methods described in the section that appears to have been plagairized may not have been followed in the actual experiments.
- 4. A picture of a mouse that was purportedly grown with STAP cells looks like a picture that was used in Obokata’s doctoral thesis, which was published in 2011.”
These are serious issues.
RIKEN also has four broader areas they are focusing on:
- “(1) Confirmation of whether there has been research misconduct
- (2) Reproduction of STAP cells
- (3) Handling of the two papers published in Nature
- (4) Future measures”
The reactions I’ve heard so far from the science community to RIKEN’s statement can be best summed up as great disappointment in it as not being rigorous or direct. One person described it as akin to a kid saying “the dog ate my homework.” Another mentioned concern that RIKEN may try to make Teru Wakayama into a scapegoat.
Looking for a positive side, it seems to me an unprecedented degree of openness for a situation like this and an incredibly rapid investigation.
I am a believer, not fanatic, of STAP. Rather, I prefer the concept of “STAP,” as a collective term, because I think that it can involve many kinds of multi-lineage or pluripotent, artificially reprogrammed cells derived from somatic cells by “stress” burden; such “STAP” cells may be able to include MUSE, Dolly’s mother, udder cells, and whatnot.
I think that researchers, who want to obtain STAP cells, should not solely repeat experiments according to the original methods, but also simultaneously or alternatively examine the conditions comprehensively and suspiciously. For example, is pH 5.7-30 min-treatment optimal? How about pH 6-1h-treatment, etc.? Is the medium saline HBSS the best? Why not MEM and others? Ditto other kinds of “stress.” In addition, trypan-blue exclusion test will be available easily to estimate cell viability or the severity of the “stress” treatment.
Now this: “Riken retracts document comparing STAP, iPS cells after complaint”
http://ajw.asahi.com/article/behind_news/social_affairs/AJ201403190067
The newspaper article is a little confusing. What was retracted was the initial press release which was issued to the media under embargo before the Nature papers were published, and made public immediately after publication of the papers on Nature’s website. Here is the link to Riken’s announcement of the retraction. http://www.cdb.riken.jp/en/04_news/articles/14/140130_stap.html
Here is another account. It seems that Dr. Yamanaka was criticizing RIKEN for over-hyping the “breakthrough” aspect of STAP stem cells because the comparison in the RIKEN press release was made against the original iPS protocols and not the current state of the art- kind of like claiming that a newly developed computer is technologically advanced based on a comparison with an Apple II from the 1980s. The actual reason why the press release was withdrawn (i.e., whether it was because of Dr. Yamanaka’s specific complaint or because of the general situation regarding the Nature papers) is unclear, although RIKEN’s statement posted by Dr. Geller above suggests the latter. The JDP article I have posted below says that the efficiency of iPS cell generation is now over 20% using current protocols. Is that true??
http://japandailypress.com/riken-withdraws-research-comparing-stap-to-ips-cells-after-questions-on-data-1946055/
After watching the first Act of “STAP Incident”
by Nekogu (a believer of STAP)
The “STAP incident” in which two papers published in the scientific journal Nature opened the curtain brilliantly as “Breakthrough of the century in biology” or “Discovery to rewrite the history of biology” tends to put an end to Chapter 1, noting that the papers are the reports which “ridiculed the history of the cell biology over hundreds of years.” Nobody still understands what kind of deployment it becomes after the following chapter(s).
Probably, the Nature side, which had offered the stage of this incident and carried out the production of this incident by the forbearance of the strict examination, has received this dishonor bashfully. Such grudge voice can be leaked and heard out of the Nature headquarters; “It is the talk of ridiculing the history of Nature for 145 years” and “Why did not function the traditional principle, Draconian rule, which our Nature has built for many years?”
With knowledge of a certain amount of life-science, two serious problems of the Nature article, deficit of the germ line band in Fig. 1i and Ext. Fig. 2g, and lacking of DNA analysis data of chimera mice for corroboration, should be immediately indicated. Do the reviewers fail in the knowledge? Or, has they carelessly examined the articles despite having a sufficient amount of knowledge of life-science. What kind of persons are the reviewers really?
Even so, who has thoroughly read the final version of the manuscripts before submission, including Dr. O? Has Dr. S, the co-writer, indeed written those, or actually committed the last draft of the papers? Otherwise it will be an additional serious misstatement, because the Nature papers say that Dr. O and Dr. S wrote the manuscripts.
From a sense of fun, this “STAP incident” will be a plot like one piece of G. K. Chesterton’s collection of short stories, “The paradoxes of Mr. Pond.”
The ‘phantom’ piece says, ” … all the peculiar organizations were functioning perfectly in accordance with the peculiar internal rules.
The matter has, however, stopped entirely progressing well on account of the very perfection by taking advantage of certain trifles. It is just “truth is stranger than fiction.”
I THINK I like and agree with what you have written.
However, I would appreciate a better translation into English.
Dear dr.p
Thank you for your favorable reading of my comments poorly written by my japanese English. You are very welcome to amend, improve or rewrite those with your good and powerful English.
I’m just a casual reader without any bioscience background. It feels that Ms. Obokata is pretty much a victim now. According to the press, she didn’t even know that plagiarism is a bad thing. I’ve heard rumors that there are many PhD students in Japan who’re given a degree “out of sympathy” (e.g. running out of scholarship, expiring visa duration, or simply getting too old to get a normal job in the society, etc.) and am guessing she’s one of those sub-par students, who somehow ended up with a nice position at Riken. Frankly I don’t think that she could come up with all this plot by herself. According to the 11jigen’s blog, her advisor also had suspicious submissions. It could be that she was advised, or even instructed, to “make a good use” of external materials or whatever necessary to cook up a paper. Now she’s the easiest target to hit by every gossipy media, and people are expecting some drama coming out. This is appalling.
“According to the press, she didn’t even know that plagiarism is a bad thing.” is exactly the kind of lame excuse I was referring to when I told our host that such remarks reminded me of “the dog ate my homework.” Might as well fess up, I was the guy quoted anonymously as saying that.
Let’s get real here. Of course she knew plagiarism is forbidden. She is 30 yrs old and a PI at a major international research institute. She might have gotten away with it in the past (and as several commenters have pointed out so may have many other people in Japan) but that’s another story.
According to this Japanese news report, that pink and lemon walls of the lab and kappogi apron were planned by Sasai, Obokata, and the PR department a month prior to the news conference. I also suspected the unique interior is somewhat unnatural since RIKEN is generally very conservative about these things.
http://iryou.chunichi.co.jp/article/detail/20140315070914336
It also claims that the whole STAP idea comes from Vacanti and Yamato and drafting of the paper was done by Sasai. Apparently, this whole thing became a disaster because the “inexperienced PhD” who was supposed to be producing data had whole other expertise of copying-and-pasting. I am not sure if the Chunichi Shinbun news report is correct. But it makes sense and explains why RIKEN appears to be protecting Obokata.
In Japan, it is not uncommon to find people open toed slippers in the lab space, including the culture room. RIKEN’s biosafety department specifically recommends NOT to do this but the tradition continues. In the photo, she is also wearing a kappogi apron. This is something that housewives wear when they cook. It is not a standard protocol in Japan. It is just her publicity stunt.
It would have been very easy for Nature to figure out that the paper contained plagiarized material. They have systems in place to check for this. I always check papers against Google when I review. No one from Nature, not one of the reviewers and not the editor, bothered to check for plagiarism. They wanted this to be published no matter what. Research plagiarism on Obokatas side? Certainly. But also misconduct from Nature! They did not take their responsibility as editors seriously. In the Obokata paper, an entire paragraph is copied from another paper… this would have been so easy to spot!
Also, the whole thing is getting simply ridiculous. Stuff I’m reading from RIKEN: “Appears to have been copied…”, “What seems to be Obokatas PhD thesis…”, “Could not be reached for comment…” Maybe everyone should get their facts and source material straight before making any statements?
Anyone noticed what Obokata was wearing on her feet in the photo of what seems like a cell culture facility at Riken? Linked by Dr Knoepfler from the L.A. Times (http://www.latimes.com/science/sciencenow/la-sci-sn-riken-finds-mistakes-but-no-intentional-misconduct-20140313,0,4953205.story).
Correct me if I’m wrong, but she’s wearing stockings with open toed sleeping slippers in a tissue/cell culture facility. Maybe the photo was just taken for PR purposes but still is this common practice in Japanese labs?
Yes, it is common practice (or at least it was when I was post-doc’ing there). Slippers are worn indoors in many labs (and in many offices/office buildings, restaurants, hotels, etc., not to mention in everyone’s house). In my lab, we would take off our shoes at the entrance to the lab and put on slippers to wear all day. Labs that do a lot of cell culture often have separate slippers (usually rubber and open-toed) for the tissue culture room that you only wear in there (we did). This practice may have arisen from sterile practices in Japanese operating rooms, where operating room staff wear the same rubber open-toed slippers that never leave the OR facility. It is usually surprising to Americans because of OSHA standards regarding footwear (especially open-toed) in the lab and possibly American cultural practice regarding wearing shoes indoors, but I never saw anyone get hurt/doused/stuck. I have also seen labs where gloves are not used for tissue culture- only sterilizing of the hands with 70% ethanol before procedures- and there was no contamination, even by mycoplasma. Generally (but admittedly this is only based on my experience), the Japanese labs I have seen typically were cleaner and had fewer problems with contamination than the American labs I have seen. We had about 40 people sharing 4 incubators and almost never had any problems. What stands out to me more than the slippers in that pic of Dr. Obokata is that the vacuum hose for suction is disrupting the laminar flow in the hood…although as you said, it’s just a PR pic (the serological pipetter does not appear to be connected to the vacuum hose). Still, though, I hope that the hood would not actually be used that way.
We can listen to Riken news conferences all day long.
We can read all the erudite dissections of all the problems of this paper.
We can read interviews with every last Japanese PhD student and critic from all sorts of “very smart” people.
All I want to know NOW is who were the reviewers and why was this paper published by NATURE.
I have heard ZERO about why the reviewers and Nature let this paper out!
The Nature Reviewers should be being interviewed and interrogated!
Otherwise, Nature publishing is a Farce and has nothing to do with science.
What exactly is wrong with the above post that 5 people give it a thumbs down?
or do those 5 people work for Nature?
I wonder if Nature and the reviewers are really as much at fault as suggested. Correct me if I’m wrong, but it seems that the only problems that were initially easy to pick up were the gel splicing and the placenta image duplication, which may or may not have been easy to miss. The other, arguably more serious, issues only arose after detailed scrutiny of the first author’s thesis and other work, and also as a result of the inability of other groups to reproduce the findings. It seems that you are thus suggesting that reviewers have to evaluate authors’ previous work to the level of the dissertation and also successfully repeat the experiments before recommending acceptance. I think of that as unreasonable and not how pre-publication peer review works. Rather, it is a good example of why post-publication peer review (e.g., as done here on Dr. Knoepfler’s blog) is just as important- it allows for more detailed scrutiny of particularly important or controversial results by hundreds of experts, which may not be possible during pre-publication peer review by only 2-4 people who may or may not have expertise in all of the fields of a paper and who do not have the time or resources to dig through dissertations and repeat experiments. The comment above seems to have missed that peer review does not end with publication, and publication alone does not validate a study. This is the reason why the field takes new publications (no matter where they are published) with a grain of salt and does not (or at least should not) accept any new finding until it has been analyzed and replicated in the post-peer-review process. Unfortunately, the lay public and media often do not understand this point and typically report on new findings or findings from only one study in a high-impact journal as if they are fact, which seems to have been particularly problematic in this case. However, for the peer-reviewed publication system to work, journals also have to be open to post-publication peer review and willing to take action once fraud or other problems are discovered. Therefore, I am more interested in what Nature will do next than in how the paper originally got published there.
Thank you, Shinsakan, for the comment. I have to admit when I did my post-pub review of the Nature STAP article I did not note any obvious problems with the article itself. I did not spend a lot of time staring at the images for these kinds of problems, but also I believe I go into reviewing articles with a broader sense of trust that they won’t contain plagiarism or duplicated images, etc. I imagine most reviewers have this trust as well. Are we too naive? I don’t know. I do believe, however, that Nature as a journal should have caught some of these issues. Such things as plagiarized methods text should be simple for Nature to detect with online tools. But hindsight is 20/20.
I heard some journals, such as JCB, routinely examine submitted images to detect wrongful image-manipulation. Maybe Nature will consider something like that, too.
http://www.nature.com/nature/journal/v434/n7036/full/434952a.html
Dr. Knoepfler, thank you for your response. I totally agree with you that the plagiarism should have been easily detectable by online tools; I know that some journals actively use such tools. I wonder if Nature did not run an anti-plagiarism check or if the article that was plagiarized was not in the databases? I suppose that in my comment, I was addressing the most serious data problems that seem to have led to the calls for retraction but that may not actually have been detectable on pre-pub review, even though the publication of a paper with so many flaws seems egregious in hindsight. I also agree with you about the general trusting nature of reviewers. However, I think that trusting our peers as honest professionals unless we have a good reason not to is a necessary part of pre-pub review; otherwise, we would never get past trying to uncover problems with the data (especially for novel or non-intuitive findings) to consider manuscripts on their merits. Once, I was reviewing a manuscript where I knew for a fact from the beginning that the results were impossible, so I spent a really long time digging and finally found an obscure previous paper from the same group from which they had recycled figures and data (for a completely different treatment condition), which resulted in an editorial reject and warning to the authors. However, that extent of pre-pub scrutiny seems impossible to apply for every manuscript unless there are doubts about the veracity of the data from the very beginning, and even then it may not be possible to detect fraud (e.g., in this case, I would not have expected Nature or the reviewers to have access to the dissertation). Rather, I think that situations like this really show the power of post-pub review and new concepts like your crowd-sourcing efforts for replication. I am not totally excusing Nature or the reviewers; as the original poster noted, we don’t know what really happened. I am just wondering how much of this could have actually been picked up prior to publication and how much of it is the result of hindsight outrage.
Hi guys,
I’d like to add a little more on this although pretty good amount of information is presented by other people already. First about me: I’m a UCD graduate and do a research in science but not in bio/life science. I’m a native Japanese speaker and happened to tune in to the web live cast of RIKEN’s report yesterday.
I think Dr. Obakata is no longer a center of attention (she was not there though). What she did on her PhD thesis and Nature papers are far beyond simple mistakes without any doubt. In the report, essentially all of RIKEN managers/personnel admitted that what Dr Obotaka did was unprofessional at best. Also the chair of the investigation committee reluctantly said that putting one of images from Dr Obotaka’s PhD thesis on Nature article must be quite rare if not done intentionally. As one of PhDs, I agree with him that it cannot be. So my impression is that RIKEN is ready to cut her out.
Then I’d like to mention the RIKEN management. As Dr Geller criticized earlier, almost none of them admitted any wrong-doing on their side. Basically they said, ‘Well, each project leader is supposed to check the quality of papers and inform their subordinates to follow sound scientific practices.’ And therefore they were indirectly saying that ‘it’s an isolated incidents which can happen some times.’ Dr Kawai answered to one of questions asked by newspaper reporters, ‘We did all we could right after it came to our attention. We will look back and consider whether we could do better or not later.’ As Dr Geller is worried, I do believe RIKEN won’t be changed at all after all of this mess. In fact, RIKEN manages emphasized that all other ongoing and proposed projects will be carried out normally (as if nothing happened). One thing I want to mention (to be fair) is that the head of CDB center, Dr Takeichi admitted that he was responsible to hire Dr Obokata in the first place. So if RIKEN decides that he must be ‘punished,’ he would accept that. Still he is passive but he feels he’s responsible at least (and probably he is the only one in the management).
Thanks for reading, here I want to say something about STAP cells itself (although I’m not an expert on this at all). There was a pretty good discussion of current status and understanding of STAP cells at RIKEN. I divide key questions into three:
(1) Did Dr Obotaka reproduce what’s claimed on Nature articles?
It sounded like she claimed she did so to some extent. But RIKEN managers were intentionally unclear on this because RIKEN was questioned why they allowed her to continue on the project which was under external investigation. In any case, not many people take her claim seriously at this point.
(2) Did other RIKEN researchers reproduce STAP cells?
RIKEN managers were unclear again for a while but eventually admitted that some of them claimed to confirm OCT-3 florescence part. Few days ago, one of the main authors, Dr Sasai, who was not there, told the press that he heard that someone at RIKEN reproduced STAP cells even after the chain of problems started. After one of reporters asked directly that seeing florescence light did not mean that cells were STAP (here ‘P’ stands for pluri-potency) cells, Dr Takeichi admitted that STAP cells had never been fully reproduced at RIKEN to his best knowledge. Then he said Dr Niwa’s team started ‘independent’ reproduction of STAP cells phenomena but its time scale depends on supply of rare mice.
(3) Did Dr Obokata either intentionally or accidentally contaminate important samples with ES cells?
Maybe or maybe not. Dr Takeichi said that the possibility informed by his colleagues led him to have Dr Obokata leave the lab until the investigation ends (again, she was allowed to do whatever she wanted until then). Also RIKEN confirmed, mouse ES cells can be easily obtained by any member of research teams (restrictions on human ES cells only). So the possibility do exist but it’s impossible to assert that anymore from the existing data samples. Only future ‘independent’ experiments can support or reject it according to them.
In my summary, RIKEN is pretty serious about what Dr Obotaka did. However, it’s not clear to me that what they gonna do to Dr Sasai and others. It’s easy to blame Dr Obotaka’s poor work (yeah, obviously bad), but what were senor RIKEN co-authors doing? Did they read the papers at least once before just putting their names on the articles?? The most importantly, the prospect of STAP cells seems to me rather bleak. Please don’t take me wrong. If STAP cells exist, how great could it be to human beings.
Best regards,
Hello, thank you for sharing the information. I like your post.
Apparently, the reason that nobody claims s/he can reproduce is not so simple. The authors claims too many in their papers. Oct4 or other pluripotent markers activated, teratoma result, germline transmission, different cell types, different treatment conditions, T cell reprogramming, or even tetraploid complementation assay, I don’t think someone can get all the dataset shortly (almost each issue is a big story if referred to iPS history), particularly given that STAP cells are not proliferative (if STAP exists exactly the same as the paper mentioned). Now it’s quite difficult to convince people that STAP cell exists. I agree that the prospect of STAP cells seems rather bleak, which is sad.
Thank you Wei,
As you know STAP cells were prepared by Dr Obakata exclusively for the papers. Even RIKEN co-authors failed to make them as of now. Thus I concluded STAP cells didn’t exist… But as you wrote, the authors claimed too much to prove its pluri-potency. If any part of their claims is right, that could be interesting and useful results to be shared. I think RIKEN is already on the way with Dr Niwa’s team.
Dr Niwa’s team doesn’t include Dr Obokata for apparent reasons. (xxxx edited for content) By the way, once the investigation is over, RIKEN allows the authors (including Dr Obokata) to have a press conference (Dr Obokata e-mailed WSJ without telling RIKEN though). But there is no time scale specified by RIKEN. Dr Niwa will have a report on his effort to reproduce STAP cells once all tests are done as well. Personally, I have no interest to hear what Dr Obokata will say, while I’m curious what Dr Niwa will report.
As I wrote I’m not an expert of the field, and so I may not post my summary of follow-up reports by RIKEN again. I wish RIKEN put out concise summary of Q&A sessions in English to facilitate better understandings…
Best,
WSJ posted an English summary of the press conference.
http://blogs.wsj.com/japanrealtime/2014/03/14/live-riken-addresses-questions-on-stem-cell-research/
Thank you for sharing the link! It’s great to have it although some of details were missing or unclear (to me). But in any case, I don’t claim that my Japanese-English translation skills is better than theirs, as they’re professional while I’m just an amateur.
Cheers,
Here is more information about the four-hour news conference: http://blogs.wsj.com/japanrealtime/2014/03/14/live-riken-addresses-questions-on-stem-cell-research/
Regarding whether it’s repeatable, “The officials said they weren’t aware of any confirmed reports of outside researchers replicating the process”, however, “Dr. Kawai then steps in and says she has heard of people other than Dr. Obokata who were able to replicate the results. She doesn’t say who that was exactly.” Also, “Dr. Takeichi says he so far hasn’t heard of any cases of the technique being successfully reproduced by outside scientists. “I’ve heard from several co-authors that they’ve achieved positive results,” he says, but doesn’t elaborate on who these people are, besides Dr. Obokata.”
Basically, the first author’s scientific career is almost over if the problems of her thesis are true. But whether STAP cells exist is still controversial.
I agree with your analysis. The take-home message of the press conference appeared to be more “we are taking this seriously; the investigation is in progress” than anything else. The Japanese government and media appear to be calling for blood, and owning up to the two least controversial, most apparently honest mistakes (i.e., that a figure “looked strange” and the swapping of placenta pictures) that they can admit to for now without actually admitting misconduct or suggesting that STAP stem cells do not exist, and then indicating that the investigation is still under way for the more serious issues, is a way to appease those calling for immediate blood while buying more time for investigation and at the same time leaving an opening for retreat in case the further investigation does indeed reveal misconduct and that STAP stem cells do not exist. For good measure, the RIKEN execs criticized the researchers as being “immature” and “sloppy” and bowed their heads in apology- this is a big deal in Japan, and seeing Dr. Noyori bow his head actually brought a colleague of mine who used to work at RIKEN CDB to tears. From RIKEN’s perspective, a lot is at stake because they made such a big deal out of STAP stem cells and Dr. Obokata by promoting the unfortunate media frenzy that occurred in Japan when the Nature papers were first published. Now, their main options seem to be to (1) deny misconduct and maintain that STAP stem cells exist and that the Nature papers were only “sloppy,” even though most of the rest of the world (and Japan) is already convinced that misconduct occurred and that STAP stem cells are likely not real, or to (2) admit misconduct and punish the researchers, which would essentially be admitting that the findings and STAP stem cells are bogus. Either option will likely be associated with serious blowback for them, so it is obvious that they would want to take their time before making such a huge decision to maximize damage control; remember that they have only had a few weeks to deliberate thus far. It is particularly interesting that Dr. Niwa has been tasked with trying to reproduce the findings and confirm that STAP stem cells actually exist, as he is a co-author on both papers and employed by RIKEN; I can’t imagine what kind of pressure he must be under. However, I also think that finding a truly impartial outside lab to officially try to replicate the findings would be next to impossible, so I think that this is a difficult issue. Regarding blame, I think it is possible that they could go after Dr. Wakayama as he is no longer employed by them, which would make it easier to externalize the blame. However, he has a stellar reputation and preempted them by saying that the experiments he performed were not problematic when he called for the retraction- he seemed to place the blame back with Dr. Obokata and RIKEN by saying that the materials he was starting with for his experiments were questionable. In the end, because she is the least established, given the “irregularities” that have surfaced regarding her previous papers and PhD dissertation, and given that it is difficult to imagine how someone else could have recycled figure panels from her dissertation, I think it will be easiest for RIKEN to squarely blame Dr. Obokata as a bad apple. Regarding the first issue described in your post, I think that “did not constitute fabrication within the context of research misconduct” probably means that the images were photoshopped to make them prettier but nothing entirely fake was actually inserted or fabricated. This would seem to constitute a deliberate act but not rise to the level of misconduct because false data were not generated and it would not seem to affect the findings. Here is some video of the press conference including Dr. Noyori bowing his head. http://headlines.yahoo.co.jp/videonews/jnn?a=20140314-00000036-jnn-soci
A correction- I mistakenly thought that the first issue of “did not constitute fabrication within the context of research misconduct” was referring to image manipulation rather than the JPEG compression issue. The explanations of Ken and “anonymous” above about the image compression make sense.
fantastic analysis, let’s hope RIKEN is aware that not all of us are so willing to “let it go” if they choose to go the “bad apple” route.
XXXXX (edited for content)
Thanks! The idea of not being inclined to let it go even if a “bad apple” sacrificial lamb (too many metaphors?) is offered is a very interesting point. I think that to date, it has been relatively common around the world for junior researchers to get thrown under the bus in situations like this in an attempt by the institution and more senior authors to protect themselves (in this case, the person catching the most heat is a PI but is still very junior and inexperienced). I wonder if the unprecedented post-publication review and critique in this case may be accompanied by more pressure for institutions and big names to take responsibility and a greater focus on rotten trees rather than bad apples. RIKEN already seems to be advancing the “bad apple” argument; it will be interesting to see how their stance evolves as the investigation progresses. Of course, it is also possible that everything actually happened the way that RIKEN seems to be suggesting, i.e., this was a complicated, trans-Pacific collaboration among four groups where the one person linking the groups and running the study dropped the ball without anyone else knowing enough to fill the holes. Regardless, in an age with increasing public skepticism of science and scientists, it seems to be increasingly important for institutions to act quickly and decisively (and in a way that is believable to people from the outside looking in) to maintain credibility.
let’s hope that they do their jobs with the utmost due-diligence.
further, re “bad trees”: I totally agree.
we’re all talking about the scientific process and the politics surrounding it, however we haven’t even begun to address WHY this is happening, which is simple: money.
science is too big, slow, and often it isn’t even science because it’s riddled with confirmation bias. not all of it, but a healthy majority (over 50%).
obokata is a microcosm of what’s happening in academia. dr knoepfler come on man, how doesn’t this look like a groomed-crony who got caught? seriously man.
obviously you covered this because you take your work seriously. you deserve to have your area “free” of publications that otherwise impede your quest to get into Nature. obviously the goal is to have an industrial application that is backed by scientific rigour. for stem cells, that is especially tantalizing.
clearly the STAP cell article encroached upon your area without having the requisite merit, skill, or dedication. further, the perpetrators have decided for themselves that they have the right to essentially rob others (they are patenting something that doesn’t work, why?), where these people would be better off investing in someone who takes it seriously (like you).
there is so much fat that can be cut. and all those funds can be used to improve and restructure. fewer people, perhaps, but inarguably many more qualified, eager, and willing individuals.
i know that my “long days” never felt like long days–they were all long days– because things need to get done.
i bet Nature will be publishing another Obokata (with claims of lesser gravity, of course).
tired of the Obokata’s being churned out at the expense of journals that are 100s of years old. it’s sad, but that’s “capitalism”.
w/e man
I am no longer working in research but am following the STAP cell situation in Japan.
Regarding figure 1f, the RIKEN officials explained (based on my own non-native understanding of the Japanese-language live broadcast) that they were able to obtain the original video data from the experiment and were able to reproduce a clear version of the image from the video data. They also said there was an original version of the static image that was clearer, but that someone at the Nature journal as part of the preparation process must have applied some compression to the image.
Regarding the apparent digital splicing of a lane into an image, the explanation given by Obakata was that the original raw image data contained several lanes, more than were to be displayed in the final image. One of the lanes was poorly illuminated, so Obakata said she took a different, better-illuminated lane from a different portion of the raw image data and spliced it in. My interpretation is that this constitutes a re-ordering the original data. The RIKEN official said they tried to reproduce the image in the journal following the digital splicing technique and using the same raw data, but that they obtained a slightly different image from that in the journal, so this point was still under investigation.
And regarding apologizing for the confusion but not the issues: the RIKEN officials emphasized this was an interim report and that the investigation was ongoing. Therefore, all the facts, as judged by RIKEN, are not yet discovered. My opinion is that an apology for any root causes can only occur after the investigation is complete.
Paul,
I feel that there is a little bit language barrier here. My impression is that Riken’s investigation is rather thorough and comprehensive, as I hear and read in Japanese. Here are the full report and slides.
http://www.riken.jp/~/media/riken/pr/topics/2014/20130314_1/document-4.pdf
http://www.riken.jp/~/media/riken/pr/topics/2014/20130314_1/document-5.pdf
I’m not aware of English versions. Riken should prepare them, if they haven’t done so. I hope the slides will help you to somewhat understand what they are talking about.
The first issue is about Fig. 1f and their conclusion is that it’s a mere artifact of JPEG compression. A third party (Akihiko Nakano of Tokyo University) was able to reproduce a similar image from raw data by reducing resolution and increasing JPEG compression.
Now Riken has a good idea how each figure and text in question is generated. They need to continue the investigation until they can decide if these were done deliberately or not (i.e. scientific misconduct or not). Not sure why someone got a concern about Teru Wakayama. Dr. Noyori criticized Dr. Obokata very directly and harshly, to my impression.
And regarding Figure 1i? Even if the figure was not manipulated, why they contradict this result later in the detailed protocol?
First, the Riken’s interim report concludes that Fig. 1i was manipulated. Slides 8 through 12 show how it was done. Riken wants to continue the investigation because i) the image couldn’t be reproduced by the method Obokata described and ii) her motive is not clear. Gel 1 as it is could’ve served the purpose of the experiment. She had CD45-positive cells as positive control.
Second, my understanding is that the detailed protocol of March 5 (no TCR rearrangement in STAP stem cells) does not contradict the original Nature papers (i.e. Fig. 1i). TCR rearrangement was reported only in STAP cells in the original papers. They didn’t say anything about STAP stem cells or the chimaera (mind you, STAP cells and STAP stem cells are two different entities). In other words, there has been no direct evidence from the beginning that green fluorescent cells in the chimaera was actually derived from T cells.
Yes, but…
(1) They singled out Dr. Obokata for criticism while failing to subject the more senior co-authors at Riken to similar criticism, and they failed to criticize Riken mgmt (i.e. themselves) for the extravagant publicity given to the papers when they first came out.
(2) They did acknowledge the existence of several instances of undeniable problems but also offered up lame excuses for each one, and they refused to acknowledge any of these as misconduct, just saying the investigation was ongoing.
Not sure about that…
At the conference, Dr. Noyori talked about responsibility of senior faculties and they particularly explained the role Dr. Sasai played in preparation of the manuscript. I felt Sasai’s career was at stake.
The committee, at least, condemned image manipulation of the electrophoresis result. I guess we have to wait until we see their final verdict.
Riken’s report was in-depth with full openness. In the US, you rarely see this kind of report after investigation, partly because federal regulations grant confidentiality. An investigation takes at least months, often a year or two. Riken came up with this quality in just a few weeks. They are doing an admirable job, I think. To me, this is a sign of good management and integrity of Riken.
Well, we have somewhat different views of this, but not completely different. A few additional comments.
First, when you or I say “Riken is..” we both have to be careful because it’s a big organization and full of lots of people including scientists, government officials on loan from the Ministry of Education, etc., etc., and all have different aspirations and agendas,
As for the investigation, Riken was more or less forced into having one by the fact that so many problems with the Obokata et al. paper had already been exposed on the internet. Also, they didn’t announce any conclusions as such at the March 14 press conference, just that the investigation was ongoing. (Although de facto they did in effect acknowledge the existence of problems that will probably be deemed in the end to have been misconduct.)
It’s true that at the press conference there were some personal criticisms of Dr. Sasai and other CDB managers for failure to be sufficiently diligent in exercising supervisory responsibility, but I thought these weren’t nearly as harshly worded s those leveled at Dr. Obokata.
For whatever it’s worth, my view of the Riken press conference was very similar to that of the commentators on various TV news-talk shows, such as “Wake-up Plus” (NNN) on the next morning (Sat. March 15). In contrast, people close to Riken seemed to think they’d done a good job on the presser and seemed to be a little surprised by the generally moderately negative reaction.
If we’re being fair I suppose we should say that while the Riken press conference was not perfect, it was probably better than many similar efforts by other organizations in Japan.
Probably one reason why I had a somewhat negative reaction to the Riken press conference was the fact that they said they would only recognize actions as misconduct if “aku-i” (evil intent, criminal intent) could be established. This is different from my university, for example, where data fabrication, manipulation or plagiarism are considered misconduct offenses without the need to establish intent (although our rules do state that honest mistakes won’t be penalized). Where I thought Riken erred was in considering each individual problem and discussing whether it was intentional or might be explained away as an honest mistake, whereas I would have preferred it if they first listed all the problems and then, taking them collectively, considered whether or not you could explain away the whole thing as being an honest mistake (which I don’t think is possible).
I will comment on the last point, which I completely agree with. Your thought can be dubbed “intent is immaterial” (by Peggy Mason, Chair of the Society for Neuroscience Ethics Committee, Neuroscience Quarterly, Winter 2014 issue; it’s worth reading). The NIH Office of Research Integrity defines research misconduct as “fabrication, falsification, or plagiarism” committed “intentionally, knowingly, or recklessly”.