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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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« Happy Fourth of July, 2014 | Main | Catalyst Voodoo, Yielding to Spectroscopy? »

July 7, 2014

That Retracted Stressed Stem Cell Work

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Posted by Derek

This article from David Cyranoski at Nature News is an excellent behind-the-scenes look at all the problems with the "STAP" stem-cell work, now retracted and apparently without any foundation at all. There were indeed problems with all of it from the start, and one of the key questions is whether these things could have been caught:

The committee was more vexed by instances of manipulated and duplicated images in the STAP papers. Obokata had spliced together gel lanes from different experiments to appear as one. And she had used an image of cells in a teratoma — a tumorous growth that includes multiple types of tissue — that had also appeared in her PhD dissertation. The captions indicated that the image was being used to represent different types of cell in each case. The committee judged that in both instances, although she might not have intended to mislead, she should have been “aware of the danger” and therefore found her guilty of misconduct. Obokata claimed that they were mistakes and has denied wrongdoing. . .

. . .Philip Campbell, editor-in-chief of Nature, says: “We have concluded that we and the referees could not have detected the problems that fatally undermined the papers.” But scientists and publishers say that catching even the less egregious mistakes raises alarm bells that, on further investigation, can lead to more serious problems being discovered.

Many say that the tests should be carried out on all papers. Christopher says that it takes about one-third of her working week to check all accepted manuscripts for the four journals published by EMBO Press. At Nature and the Nature research journals, papers are subjected to random spot-checking of images during the production process. Alice Henchley, a spokeswoman for Nature, says that the journal does not check the images in all papers because of limitations in resources, and that the STAP papers were not checked. But she adds that as one outcome of this episode, editors “have decided to increase the number of checks that we undertake on Nature’s papers. The exact number or proportion of papers that will be checked is still being decided.”

A complication is that some of the common image manipulations (splicing gel lanes, for example) are done in honest attempts to present the data more clearly, or just to save space in a figure. My guess is that admitting this up front, along with submitting copies of the original figures to the editors (and for inclusion in the Supplementary Material?) would help to clear that up. The article raises another good point - that editors are actually worried about confronting every example of image manipulation that they see, for fear of raising the competence of the average image manipulator. There's an evolutionary-arms-race aspect to all this that can't be ignored.

In the end, one gets the impression that Nature's editorial staff (a separate organization from the News people) very much regret ever having accepted the work, as well they might. Opinion seems divided about whether they could have caught the problems with the papers themselves - this was one of those cases where a number of reputable co-authors, at reputable institutions, all screwed up simultaneously when it came to cross-checking and verification. What remains is a portrait of how eager people can be to send in groundbreaking results for publication, and how eager editors can be to publish it. Neither of those are going to change any time soon, are they?

Update: from the comments, see also this timeline of events for a look at the whole story.

Comments (14) + TrackBacks (0) | Category: The Dark Side | The Scientific Literature


COMMENTS

1. Anonymous on July 7, 2014 8:11 AM writes...

I still don't really get how the reviewers were happy with what passed as the 'independent' replication.

For something that would inevitably make a big splash, wouldn't it not make sense to really make sure this is possible by trying it at multiple sites? This study in particular doesn't really require expensive equipment and years to replicate and is probably why the truth came out so quickly.

Were the editorial team afraid to put off future submissions in the same way the did with Mitalipov.

Permalink to Comment

2. MoBio on July 7, 2014 9:02 AM writes...

Some journals are now mandating that the original full and uncut Western blots be provided and,for instance, the Journal of Clinical Investigation has instituted a number of other items for data integrity:

http://www.jci.org/kiosk/publish

Permalink to Comment

3. Erebus on July 7, 2014 9:54 AM writes...

The Knoepfler Lab's "Stem Cell Blog" has been excellent and relentless about covering this story, and they've just published a sort of synopsis. Very interesting indeed.

www.ipscell.com/2014/07/a-detailed-stap-cell-timeline-from-this-blog-elsewhere/


That aside, the reviewers dropped the ball bigtime. Their excuses ring hollow, especially given how miraculously easy the technique was said to be...

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4. matt on July 7, 2014 10:13 AM writes...

" we and the referees could not have detected the problems that fatally undermined the papers"

That's baloney. Any person in the embryonic stem cell/reprogramming field (people who I hope reviewed the paper) should have been able to tell that this paper does not pass the stink test, even if they didn't catch the actual image manipulation. Nothing about the experimental design or experimental workflow made any sense.

It kind of sounds like the reviewers knew this, but gave them the benefit of the doubt because a few highly respected Japanese PIs were authors on the paper...

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5. Vaudaux on July 7, 2014 10:19 AM writes...

The figures were fraudulent, which is reason enough to retract the paper.

It's not clear from what I have read that the STAP phenomenon has been shown to be fictitious. Considering the recent post on categories of fraud: some of the alternatives are sloppy work, self-deluding scientists, or a phenomenon that is real but much more difficult to reproduce than the authors realized.

If the cut-and-paste blots had not been so obvious, would the widely reported difficulty in reproducing the observation have led to an investigation of the experimental work rather than of the manuscript? Should it?

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6. Witold on July 7, 2014 10:24 AM writes...

Repercussions for the author? Journal? Limited.

How much time and research money was wasted by other groups, huge.

This is egregious.

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7. Anonymous on July 7, 2014 10:26 AM writes...

There *must* be some software out there that can automatically scan images for signs of manipulation, such as sudden changes in background noise. Or at least there should be.

Permalink to Comment

8. Derek Freyberg on July 7, 2014 10:51 AM writes...

As a number of commenters here and elsewhere have said, some of the manipulation, such as the electronic "cut-and-paste" of a gel, was obvious to people in the field. In fact, RIKEN's own report notes that a reviewer for Science, where one of the papers had been unsuccessfully submitted before its submittal to Nature, had mentioned it in his review. That the Nature reviewers either didn't see it or didn't care to address it does not speak well for the quality of their, or Nature's review.
It all comes down to "extraordinary claims require extraordinary proof"; but it seems that in too many instances "extraordinary claims require quick publication". I am reminded here not merely of the Hwang stem-cell debacle - it's easy to see why stem cells are a big deal - but also of the more recent arsenic-DNA bacteria debacle, where it seems that "making a splash" took precedence over thinking seriously about the science.

Permalink to Comment

9. Anonymous on July 7, 2014 10:59 AM writes...

Journals should give a limited (e.g., 2 year) ban on any authors they catch manipulating data and/or images, as that would surely act as a deterrent to even try.

Permalink to Comment

10. Toad on July 7, 2014 1:05 PM writes...

Derek,

The link for the Update needs to be corrected (clean up href).

Permalink to Comment

11. Anonymous on July 7, 2014 10:34 PM writes...

I remember reading the papers the day they came out and it was obvious that one of the gels had, at least, one lane spliced-in. Since the gel was not meant to be quantitative, I saw no problem with the data being presented that way.

Reviewers/PIs that demand "perfect" gels, elemental analysis (discussed here extensively), or NMR spectra (also discussed here extensively) contribute to the problem of selection bias when it comes to presenting a "representative figure". I am sure that many manipulated images and excluded data points are due to the stress of obtaining a "figure-quality" result that is consistent with the hypothesis.

Since it is so easy to misrepresent what a sample is, there will have to be some degree of trust (unless independent reproduction the results becomes a requirement for publication).

Permalink to Comment

12. Derek Freyberg on July 8, 2014 11:55 AM writes...

@11 (Anonymous)
It seems that the Science reviewer didn't have a problem with the gel as such either - all that was wanted was that the figure show gaps between the inserted lane and the other lanes of the gel to make it clear that the inserted lane was indeed an inserted lane. RIKEN's report, however, suggested that there was another and more serious issue with the inserted lane - that it was shorter in the gel it was taken from and had been "stretched" to fit, without any assurance that a "stretch" would not have misrepresented the data (as I recall, and I haven't gone back to the report, they thought that it would misrepresent it, in the sense that an assumption of linearity was not justified).

Permalink to Comment

13. exchemist on July 9, 2014 5:59 AM writes...

I question the Nature News article and how independent they are of criticizing Nature. For one thing, they don't explain how bloggers and Pubpeer blew the paper out of the water and shredded it in days. Also, they don't discuss the general topic of how the Glamour mags have a habit of these kinds of papers with retractions (And I know of dishonest ones not retracted).

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