Finally, Vacanti’s side of STAP cell implosion

Obokata Vacanti

Vacanti and Obokata

A great new piece in The New Yorker by Dana Goodyear, The Stress Test, gives us a window into Charles Vacanti’s side of the STAP cell mess and includes recent quotes from him.

It’s a long, fascinating look inside of STAP, the tangled and ultimately tragic scientific implosion that created and then brought down two Nature papers and some careers.

The most notable part of the article is that the stem cell community finally hears from Vacanti, postdoc mentor of lead author Haruko Obokata. We also gain more insight into the working relationship between Vacanti and Obokata, which as the piece tells it became increasingly distant after the STAP papers were published. For instance, even before publication but after Obokata’s return to RIKEN from Vacanti’s lab, her continuing work on STAP, and teaming up with Sasai:

“Obokata’s data were closely guarded—other lab members knew only that she was working on a radical new way to make stem cells. Even Vacanti was excluded from the day-to-day progress. He wrote to Obokata seeking updates, and got responses from Sasai. “Haruko has been so busy over the past two months and, from what I see, got exhausted time to time,” he wrote. “I hope that you may understand such a situation and kindly help her concentrate.” When Obokata did find time to respond to Vacanti, she signed her notes, “With a lot of love,” and reassured him that she just wanted to see him smile.”

and then later after STAP broke and there was basking to do in the positive media glow initially:

“But, by the time the news cycle finished, Vacanti’s fears had been realized. He had vanished from Obokata’s narrative. Nature’s news site carried a recording of her talking about how she had come up with STAP. Like Archimedes, she described her eureka moment as having taken place in the bathtub, when she started to wonder if mammalian cells responded to stress by producing stem cells. “I tried everything I could think of,” she says. “Squeezing cells through a pipette, starving cells, and so on.” Martin Vacanti called his brother. “Chuck, have you listened to her description of the eureka moment?” he said. Chuck hadn’t. “She gave the same description I give about the sporelike cells,” Martin said. She was using his eureka moment.”

STAP stem cells

STAP spheres nice and green?

The New Yorker piece starts the STAP story as an idea of Vacanti’s from years ago related to his notion of spore stem cells. This was mentioned in my early interview with Vacanti right after the STAP papers were published.

Obokata arrived on the scene in his lab and ran with the idea. Ultimately it seems from Goodyear’s piece that Vacanti felt in the end that Obokata ran away with the idea to some extent.

When the whole thing started unraveling, Goodyear reports that Vacanti contacted Obokata to ask what the real deal was:

“As the questions mounted, Vacanti says, he called Obokata and said, “Haruko, I have to know, because people are losing their careers on this. Is any of this data fabricated?” She assured him that everything was legitimate. He recalls that she said, “If I was going to fake this, I wouldn’t have spent hours and hours collecting data.” Vacanti thought that she was too smart to cheat so brazenly, and certainly too smart to get caught.”

stap cellsIt’s hard to know exactly how to take this passage as it is not exactly a reassuring account of what happened. Too smart to get caught? That’s a dangerous mentality.

Overall the narrative in this article paints Vacanti as a perhaps over exuberant, true believer in STAP (even to this day perhaps), and the quotes seem to place most of the responsibility for STAP related to experimental issues back in Japan either with Obokata or if she is to be believed (e.g. in her new book) with Teru Wakayama.

What’s next for Vacanti?

It seems that his lab may soon close:

“At the end of July, Vacanti invited me to Boston. Because of the embarrassment around STAP, he had taken a sabbatical from his chairmanship, and would soon retire from his position. His lab would eventually run out of money, and then close. But his faith in the basic principles of STAP was unshakable. “I will go to my grave still being absolutely certain that it’s correct,” he said.”

I find it striking that Vacanti and his protegé Koji Kojima, another STAP author, were still working on STAP-related experiments as of the writing of Goodyear’s article. Amazing.

Where does this leave STAP?

There are still a number of open questions, but overall it feels closer to closure.

Anyone can make mistakes. Falling in love with a hypothesis is not unheard of. Hyping a story happens. Trusting someone and finding that trust misplaced.

But STAP went beyond more commonplace glitches in the scientific process. It seems to have been a perfect storm case of several big things all on one project going terribly wrong including evidence in RIKEN’s view of misconduct by Obokata.

The tragedy of Dr. Sasai’s suicide after STAP should also highlight the seriousness of these kinds of situations and the fact that scientists are people too with feelings. Many other scientists were hurt by the STAP situation including some with no substantive link to it.

As for the science side of things, there may be a link between stress and cellular plasticity, but it’s not going to be what was claimed as STAP.

Today and into the future, STAP serves mainly as a cautionary tale of the types of problems to try one’s best to avoid as a scientist.

Overall responsibility for STAP, even if in very different ways, resides both in the U.S. and Japan. Goodyear’s article has made this reality clearer.

Obokata claims she was framed for STAP cell scandal

Obokata press conference

Obokata late presser

The Japan Times has the first detailed account in English about Haruko Obokata’s new book, “That Day”. HT to blog reader Shinsakan. (update: another helpful piece on this from the WSJ).

In the book, Obokata (who was widely blamed for the STAP cell fiasco) seeks to shift the blame to others according to the paper.

Obokata’s book just came out and you can see more details here.

According The Japan Times, in the book Obokata largely blames one of her mentors Teruhiko Wakayama for the STAP cell problems. She even goes so far as to say she was framed:

“Obokata claims in the book that she was “framed” as the individual who mixed in ES cells. She said she received the cells used in the experiments from Wakayama, and directs suspicions at him instead.”

To my knowledge there is absolutely no evidence to support this claim.

I still haven’t heard if the book mentions one of Obokata’s other mentors, Charles Vacanti of Brigham and Women’s Hospital. To my knowledge neither Obokata nor Vacanti have been publicly critical of each other since STAP erupted.

Perspectives on final RIKEN report on STAP cell scandal & what comes next

STAP cells FigureThe Japanese research institute RIKEN has come full circle in a way on the STAP cell scandal. Note that the STAP papers included not only authors from RIKEN, but also from Brigham and Women’s Hospital/Harvard Medical School.

With its final report released today (also a powerpoint of images were released including the one showing a figure posted here of reportedly made up data published in a STAP paper), RIKEN seems to now have handled this complicated mess in a relatively rigorous, scientific manner that paves the way for moving on from it.

What would you have done in RIKEN’s shoes? It’s not a pleasant thing to contemplate.

As a research institution, what do you do if a potential major scientific scandal is cropping up under your roof? It’s unpredictable and dangerous and couldn’t have come at a worse time for RIKEN. So how do you handle it? What would you have done?

RIKEN was faced with this kind of unpleasant reality early this year. A very high moment for RIKEN with the publication of two seemingly groundbreaking Nature papers including numerous RIKEN authors quickly headed the other direction and began unraveling.

By February, only weeks after the STAP cell papers were published supposedly reporting the creation of power stem cells called “STAP cells”, there were signs that the research was plagued with profound problems including signs of potential misconduct.

At that point in February and March, what should the leaders at RIKEN do/have done? I’m sure they were asking themselves this tough question.

There have been ups and downs as to how RIKEN has handled STAP, but in the new report there are indications of a sober, objective and more thorough approach to STAP. I think this is a positive, constructive step even if the conclusions are negative and sad.

Dennis Normile has a nice summary over at Science News of the RIKEN report:

“The committee determined that 3 supposed STAP stem cell lines were actually likely to be 3 previously existing embryonic stem (ES) cell lines. “It is unlikely that there was accidental contamination by three different ES cells, and it is suspected that the contamination may have occurred artificially…”

This new RIKEN report on STAP has concluded that what were claimed to be STAP cells were almost certainly embryonic stem cells (ESCs) instead. It cannot be sure if the ESCs were intentionally and fraudulently used, but it says that is probable. If it was done on purpose RIKEN also cannot be sure who did it.

The report concludes that STAP first author Haruko Obokata, who RIKEN earlier had determined committed certain STAP-related misconduct, committed additional misconduct over certain data, but the report also lays some of the blame for STAP to lack of proper supervision by senior STAP authors Yoshiki Sasai, Teruhiko Wakayama, and Hitoshi Niwa. One remaining thing we do not know is what this report means for Wakayama or Niwa, the latter still being at RIKEN.

So what does all of this mean and where do things go from here?

While there is still some more to resolve on the Japan side of STAP, my impression is that this report along with Obokata’s resignation allows for RIKEN to really begin to move on from STAP.

Normile’s article concludes pointing towards where the STAP-related focus may turn next:

One of the papers’ co-authors has been beyond the reach of RIKEN investigators: Charles Vacanti, a tissue engineer at Brigham and Women’s Hospital in Boston, an affiliate of Harvard Medical School. Obokata initiated her work on STAP cells while a post-doc in Vacanti’s lab. Mutsuhiro Arinobu, a RIKEN executive director, said that although they have been in contact with Harvard, input from Vacanti “is not included in this investigation.”

Harvard and Brigham and Women’s Hospital may or may not be conducting STAP investigations of their own. However, certainly at this point relatively speaking key unanswered questions remain on the Harvard side of STAP.

Newly Update Comprehensive STAP Cell Timeline with Key Events & Links

Here is an updated timeline for the major events (and links) for the STAP fiasco. If you think absolutely critical events are missing, let me know in the comments and I’ll consider adding them.

Jan 29Nature publishes STAP papers online
Jan 29Postpub review of papers on ipscell.com
Jan 30First STAP polling starts: respondents mostly positive
Feb 2Surprising interview w/Vacanti: STAP easy to make, same as spore cells
Feb 4First key Pubpeer comment on splicing in Figure 1i
Feb 6Top 5 reasons for doubts on STAP
Feb 7STAP crowdsourcing experiment starts
Feb 13First Pubpeer comment on STAP placenta issue
Feb 13JuuichiJigen first post on STAP problems
Feb 14RIKEN & Nature begin STAP investigations
Feb 27Wakayama interview
Mar 10Wakayama calls for STAP paper retraction
March 13JuuichiJigen post on Obokata Ph.D. thesis problems
March 14RIKEN alleges that Obokata committed misconduct
Mar 24Nature rejects Ken Lee’s STAP paper showing that STAP doesn’t work
Apr 1Vacanti Harvard STAP talk for this fateful day was cancelled
Apr 1RIKEN announces Obokata guilty of misconduct
Apr 9Obokata admits mistakes, but not misconduct
April 25Head of RIKEN STAP investigation committee, Shunsuke Ishi, resigns amid allegations of his own paper problems
May 8F1000 Publishes Lee Lab Paper showing STAP fails
May 27Call for Nature retraction of STAP papers
May 28Obokata OKs letter, but not article retraction
Jun 3Obokata agrees to retract STAP article too
June 12Committee calls for restructuring of Riken CDB
Jun 16Genetics data suggest STAP cells involved mix or switch
July 2STAP Nature papers retracted
Aug 5Yoshiki Sasai, commits suicide
Sept 3Vacanti & Kojima reaffirm absolute confidence in STAP but issue new STAP protocol
Dec 19Obokata and Niwa fail in STAP final replication effort
Dec 20Obokata resigns from RIKEN
Sept 23, 2015Nature publishes refutations of STAP
Jan 28, 2016Obokata book claims she was framed for STAP

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.