Obokata Can’t Reproduce STAP Cells

Obokata press conference

Signaling a nightmare ending to what was originally a fairy tale scientific story, the Japanese press (e.g. here) are reporting that Haruko Obokata has herself been unable to make STAP cells again as part of a RIKEN team testing STAP under watchful supervision.

In advance of a scheduled RIKEN press conference tomorrow, newspapers including Asahi Shimbun are reporting now that RIKEN will announce STAP was not replicated even with the involvement of Obokata.

Earlier this year RIKEN had said their internal investigation had found Obokata committed misconduct in her STAP research published in January as two papers in Nature that were later retracted.

Only three months ago, senior STAP paper author Charles Vacanti and collaborating scientist Koji Kojima of Brigham and Women’s Hospital reaffirmed their belief in STAP and posted a new STAP protocol on-line. They said STAP was a phenomenon in which “we have absolute confidence” and stressed the importance of adding ATP into the mix to make STAP, which had not been previously emphasized. It’s unknown if Obokata’s STAP replication efforts included trying the newer Vacanti protocol with ATP.

It’s unclear at this time what this somewhat final failed replication effort will mean for the STAP authors.

STAP Voted as the Stem Cell Story of the Year for 2014

Stem Cell Story of 2014When I asked the readers of this blog what they felt was the biggest stem cell story of 2014 in a poll, they overwhelmingly picked the STAP cell scandal.

For background on STAP you can toggle through the many STAP cell pieces on this blog here, see a STAP timeline, and a STAP image gallery.

Basically, STAP was a bogus scientific claim about a supposedly simple reprogramming method to make powerful stem cells induced by cellular stress.

Despite many flaws in this STAP research and the fact that it seemed way too good to be true, STAP was published in two Nature papers that came out toward the end of January 2014 that are now retracted.

The STAP mess was the product of many things going wrong, almost a perfect storm of research missteps and some have said even misconduct as well as arguably puzzling editorial decision making at one of the most prestigious journals in the world, Nature. Discussion of STAP pointed to more specific, serious problems. Image and data reuse. Plagiarism. Hype. Rush to publish. Unhealthy competition. Gift authorship. And more.

At some point we need to move on from STAP and thankfully that is happening, but there is still more to discuss before we can really fully move on and focus more squarely on the positive stuff. For example, a few puzzles remain about STAP such as where the supposed STAP cells really came from and also how Nature ended up publishing the STAP work when the scientific reviewers that Nature itself enlisted to review the submitted manuscripts skewered them.

The younger generations of scientists in the stem cell field are also watching how the field handles STAP and other events that invoke similar problems too. What lessons will they and the public take home from all of this? There are so many very real, wonderfully positive developments ongoing in the stem cell and regenerative medicine fields that I would rather be discussing instead of STAP, but we have to be careful. The risk that STAP-like events pose to our field comes in the form of a possible harmful narrative of the stem cell field fundamentally losing the public trust.

The 12 months of stem cell blog mass

12 days of ChristmasInspired by DrugMonkeyBlog, I have gone through and listed the first ipscell.com blog posts of each of the 12 months of 2014. It makes for a surprising summary of the year. Think of it as the 12 months of stem cell blog mass (12 days of Christmas image from Wikipedia).

Just for fun, I’ve included both the blog post title and the first sentence of each post.

2014

Jan: Stem Cell Outreach Success in Spanish: ¿Qué son las células madre? I’ve been working on a stem cell outreach program for education (SCOPE) the last couple years.

Feb: Interview with Charles Vacanti on STAP Cells: Link to Spore Stem Cells & More. The recent publication of two Nature papers on acid treatment produced stem cells (so-called STAP stem cells) has been a blockbuster story in the stem cell field and has grabbed major global media attention as well. 

Mar: Latest STAP stem cell whispers: glimmers of hope or mirages? I’ve heard several reports now that labs can sometimes see some kind of either Oct4-GFP reporter activity or pluripotency gene expression in acid treated cells, but the scientists do not seem particularly encouraged.

April: RIKEN Report Is Virtual Acid Bath of Criticism for Obokata: What’s Next? RIKEN Institute in Japan has formally announced the complete findings of its investigation into the STAP cell research and Nature papers.

May: Welcome CIRM 2.0 and President Mills. The future is now.

June: Human skin stolen from regen med firm? The AP reports that one Gary Dudek of Pennsylvania is facing criminal charges for allegedly stealing more than $350,000 worth of human skin from a Massachusetts regenerative medicine company that was his former employer.

July: The Measures Size Up Stem Cells. Last week I visited NIST, the National Institute for Standards and Technologies in Gaithersburg, Maryland as a member of a review panel.

Aug: STAP cell scandal image galleryWant to go the links associated with specific images? 

Sep: Given a do-over, would you still go to grad school again? Take Our Polls. Science is a wonderful field to be in, but there are many challenges too and in some ways things have gotten more complicated and difficult.

Oct: Home stretch on October deadline NIH grant & I’m…(fill in the blank). Grant deadlines are no picnic.

Nov: Open letter to UK Parliament: avoid historic mistake on rushing human genetic modification. Dear UK Parliament and Science and Technology Committee,

Dec: New Interview with FDA on Key Stem Cell Regulatory Issues & Its Own Research. It’s been a seemingly rather quiet year on the regulatory front in the US when it comes to direct-to-consumer stem cell interventions even as the number of dubious stem cell clinics continues to skyrocket.

STAP Cell Update: New STAP-like paper, Obokata, Vacanti, Real Origin of STAP cells, & More

The STAP cell mess that began in January of this year has in some ways quieted down.

In a broader sense, I believe that STAP is now and will be in the future viewed as a scandal that revealed some less than ideal aspects to the world of biomedical science and publishing.

Where does STAP stand today?

A New STAP-Like Paper?electric iPSC

The most recent development is the publication of a new paper pointed out by a number of people to me as perhaps STAP-like. It is entitled “Electromagnetic Fields Mediate Efficient Cell Reprogramming into a Pluripotent State”. It was published in the journal ACS Nano.

This Baek, et al. paper suggests that you can dramatically more efficiently create induced pluripotent stem cells (iPSC) by exposing somatic cells to an electromagnetic field (see graphical abstract above). My reaction? Let’s see if another lab can reproduce this, but I’m not terribly optimistic. Derek Lowe weighed in on this paper here. The Pubpeer folks have some concerns too and the authors have responded (which is a good thing) there as well.

STAP stem cellsObokata Thesis in Jeopardy

At this time, first author Haruko Obokata is faced with more immediate issues such as her future at RIKEN and her thesis. She must correct her Waseda University thesis or it may be revoked. The University did an abrupt U-turn on this as earlier they had said that while the Obokata thesis had problems it was not that big a deal. Now they are requiring a correction. Given the apparent massive plagiarism in it and re-used figures, I don’t see how a correction is possible frankly.

Vacanti still believes in STAP, issues new protocol

Obokata’s former mentor at Harvard/Brigham Women’s, Charles Vacanti, recently reaffirmed his belief in STAP and along with his lab member Koji Kojima, published yet another STAP protocol this time detailing that the addition of ATP might help other labs make it work. I’m skeptical. I do find it fascinating that Vacanti still believes in STAP despite all the evidence to the contrary. Otherwise in the STAP news, it’s interesting to speculate that during his sabbatical that he may continue working on STAP.

Nature‘s role in STAP

I still think that Nature has not come to terms with its role in STAP. As has been said many times, no journal, editors, or reviewers can catch all problems in a paper, but given the released STAP reviews of previous versions of the STAP papers including one at Nature that wasn’t initially accepted and received pretty harsh reviews, it sure seems the overall review process at Nature should have done better. All things considered, I kinda doubt we’ll hear anything else from the journal on STAP. If the trend of a surging number of overall retractions at Nature continues, however, there may be more of an impetus for change.

Remaining STAP mystery: where did STAP cells really come from?

If acid and other stressors (now perhaps including electricity) do not really make pluripotent or totipotent stem cells, then where did the alleged STAP cells/STAP stem cells come from that seemed in the mouse assays to have pluripotency or totipotency? There have been some indications that STAP cells have a different genetic make up or transcriptomic profile than they were “supposed to” as the authors reported these features in the retracted STAP papers. Were STAP cells actually a mixture of ES cells and trophoblastic stem cells? Some kind of iPS cells? We still do not know.

“Magical” STAP papers were blistered by Nature’s own reviewers, but then accepted just months later

The reviews of a STAP paper submitted to and rejected by the journal Science in 2012 were posted at Retraction Watch yesterday. They filled in some gaps in the puzzle of the series of events that led to such flawed science being published in Nature in January 2014, but the reviews also raised more questions.

Today, more STAP paper reviews have surfaced.

ScienceInsider posted a piece with additional STAP paper reviews with these coming from Nature reviewers commenting on what would later become accepted and published by Nature only months later in seemingly only moderately revised form.

The Nature reviews (you can read them here on the Science website) are very critical of the STAP papers and raise a host of important, largely still unanswered questions about STAP.

STAP magic

My overall sense is that the three reviewers did a thorough and fair job of reviewing these STAP papers. It sure seems that none of the three reviewers were even remotely close to being comfortable with these papers being published in Nature. In each case it would seem that a major revision would have been necessary prior to even having a remote chance at publication. One of the reviewers summed up a STAP cell article as essentially reporting an unproven, “magical” approach (see screenshot above).

The ball is now firmly in Nature‘s court to facilitate a thorough understanding of the STAP situation. It seems reasonable to expect more from Nature than its one editorial that shrugged off any significant responsibility including this key portion:

“We have concluded that we and the referees could not have detected the problems that fatally undermined the papers. The referees’ rigorous reports quite rightly took on trust what was presented in the papers.”

Nature‘s own reviewers’ comments would seem to directly challenge this statement.

I’m not going to go through all of these criticisms and questions raised in these reviews of the originally submitted Nature STAP papers point-by-point, but the overall consensus was that these papers were seriously flawed. This fits well with the gestalt of the reviewer comments on the rejected STAP/SAC paper at Science.

If you look at the published STAP cell Nature papers and think about the details mentioned in these acidic reviews of the original forms of the same papers, there is a sense that not much fundamentally was improved in the papers during that intervening period of months.

The big question remains then: how did these STAP papers go from being rebuffed based on scathing reviews at Nature on April 4, 2013 to acceptance by the same journal on December 20, 2013 and publication about a month later?