STAP cells (stap細胞) are real deal says new Vacanti patent declaration

STAP is back?vacanti-stap-figure-2017

Really?

No, I don’t believe so, but there’s an interesting development and twist on the STAP cell front.

Just a few days ago on January 4, 2017 Dr. Charles Vacanti, the originator of the STAP cells concept, submitted a declaration to the USPTO affirming the belief that STAP cells are real and requesting that the patent office allow the rejected STAP patent application to be reconsidered.

I find a number of aspects of this development notable:

  • The declaration says they have generated new data supporting STAP, but the two figures shown are in my opinion unconvincing. More specifically, just showing some floating spheres and an image of a single cell (not even stained for a marker) doesn’t really prove anything. You can see a snapshot of Figure 1 above. Note that in May 2016 an Obokata-associated website posted some supposed STAP validation data as well, but in my view it too wasn’t at all convincing.
  • qPCR results on induced expression of pluripotency genes are mentioned, but I didn’t see that actual data in the document or other related documents so as far as I can tell it can’t be evaluated at this point. Update: I’m still searching to see if I can find a patent document that shows the new qPCR and it may be in there somewhere. Stay tuned. BTW, you can look at the patent documents directly yourself at this USPTO website. Plug in patent application #14/397,080 and click on the tab at the top that reads “Image File Wrapper”. I’m not a patent expert so there may be other useful tabs at the top as well where for instance the qPCR data could be found or other information.
  • The declaration expresses concern with how Nature handled the STAP cell situation with the retractions, indicating that in the view of some of the authors there should have been an indication that the authors believed the concept was real.
  • Why do some of the STAP authors believe in it still but many others in the stem cell field don’t? Apparently, according to the declaration, the other labs who tried the STAP method just didn’t use the proper technique. I have doubts about that explanation. For instance, Vacanti’s own Harvard/B&W’s colleague George Daley and other top stem cell scientists published two BCA pieces in Nature refuting the existence of STAP. Reportedly they even did some of this work in Vacanti’s own lab with someone who was an author on the STAP papers.
  • The STAP cell patent application has been transferred to a private company called Vcell Therapeutics, Inc., which seems somewhat obscure. A Japanese blog has dug into this situation and mentions a J. Kelly Ganjei, a name I’m not familiar with, as a leader of Vcell. There’s even some speculation that Vcell may be short for “Vacanti cell”, but I don’t know about that. Given the sound of the company’s name I can’t help but think of VSELs, another controversial kind of stem cell, when reading the word “Vcell”.

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The Niche top posts of 2016

stem cell fireworksWhat were the top posts here on The Niche for the past year? I’ve listed some of them below along with some posts from 2015 that remain highly read.

Some top 2016 posts

2015 and older posts that remain highly read every day

Haruko Obokata (小保方 晴子) website posts dubious STAP cell validation data

Haruko Obokata is most well-known for her role as first author of the now retracted two STAP cell Nature papers. These manuscripts claimed to have made pluripotent and even totipotent stem cells simply by stressing cells out with acid treatment or in other ways. Nobody else could get this method to work to create the so-called STAP cells.

It was an all around scientific disaster and I don’t know anyone who believes that STAP cells are real, but Obokata and another one of her mentors, Dr. Charles Vacanti have still at times indicated their belief in STAP.

STAP cell Obokata 2016

Screenshot from STAP Hope website

Obokata appears to have launched a new website at the end of March of this year and there was a sense that this site along with her memoir-like book would together tell her side of the story plus might continue to push the notion that STAP is real. Update: it is formally possible that Obokata is not running this website so I have made a few change to this post.

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Haruko Obokata (小保方 晴子) launches new website with STAP claims

ObokataWebsiteStory

Image courtesy of Dr. Bob Geller from Nikkan Gendai (on sale April 1, official date April 2)

Even as the book of Haruko Obokata (小保方 晴子) had been fading in popularity on Amazon Japan (update: it is now increasing again), there is some other news with her as she has launched a new website.

The website, STAP Hope Page, seems to often not work now, but you can also see it here via Wayback Machine.

Hat tip to several readers and people on Twitter including Buvery and Bob Geller.

JIJI Press has confirmed that the site is real as some had speculated it might be a parody site. My impression just from reading it earlier today even before I knew about JIJI’s findings was that it felt real. I’m not sure why the site is now down.

JIJI has an interesting quote:

“On the site, Obokata, 32, says she hopes to help other scientists succeed in creating STAP cells.
According to her representative, lawyer Hideo Miki, Obokata sent him an email informing him of the establishment of the site a few days ago. In the message, she insisted that parts of the original STAP cell experiments she undertook were successful.”

The inclusion of the word “Hope” seems appropriate as I think she must be hoping that she still can redeem STAP even if only indirectly.

On the website are a number of things including more on her side of the STAP story (still hinting it seems at blaming Teru Wakayama) and even a STAP protocol. This protocol feels reminiscent of when Vacanti posted a new STAP protocol on the Brigham and Women’s website may 18 months or so back when no one else seemed to get it to work.

The Obokata website includes an apology for STAP. There is also some text on the announcement page related to her thesis:

“My Ph.D thesis that was reintroduced to Waseda University is still under advisement with relevant people about lawsuits or readmission to other universities.

While it is not clear what decision will be reached, it has been decided that the public opening of my Ph.D thesis is to be postponed for this reason.

I apologize in advance for this.

March 25, 2016
Haruko Obokata”

Her statement to end her homepage is this:

“I am unable to further continue my own STAP research. All I can do is to leave my recipe to create STAP cells here. My fervent hope is that someone will open the next door to the secrets of life. STAP phenomenon may be the key to the door. I believe that STAP phenomenon will prove to be a great contribution to humanity in the future.”

It seems at this point that Obokata and Vacanti both, despite having gone their separate ways, still to some extent believe in STAP based on what they’ve written or has been quoted from them recently.

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.