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.

Harvard Sued Over Stem Cell Paper Misconduct Investigation

Dr Piero AnversaBrigham and Women’s Hospital cardiac stem cell researcher Piero Anversa along with collaborator Annarosa Leri (pictured) are suing both the hospital and Harvard Medical School as well as leaders at the institutions over a research misconduct investigation focused on Anversa and Leri.

Boston Globe reporter Carolyn Johnson has been covering Anversa and for background on this new lawsuit she wrote:

Work overseen by Dr. Piero Anversa, a professor of anesthesia at the Brigham, was thrust into the spotlight earlier this year when one of his papers investigating the heart’s ability to regenerate itself was retracted after an internal probe revealed it had used compromised data. Another study overseen by Anversa that reported on an early clinical trial testing the use of heart stem cells in patients was flagged due to the ongoing investigation into the “integrity of certain data.”

Annarosa Leri

The issues with these studies prompted Brigham and Harvard to start investigating.

A key point of the suit against Harvard alleges that problems such as data manipulation in the publications were the sole responsibility of a former scientist in the Anversa lab, Dr. Jan Kajstura, and that Anversa and Leri are not responsible for these issues.

Remarkably, according to the Globe the investigation at the heart of the suit apparently examined and may have found evidence of alleged misconduct in more than 15 papers on which these scientists were authors.

The suit, which can be read here, asserts that the investigation has harmed the careers of Anversa and Leri. For example, the suits argues that the defendants:

“have caused and are causing ongoing harm to Plaintiffs Dr. Piero Anversa and Dr. Annarosa Leri’s (collectively, “Plaintiffs”) reputations and careers by conducting a procedurally and legally flawed investigation into alleged research misconduct at a Brigham laboratory”

There is a great deal of interesting information in the lawsuit document itself. For example, it provides a window into how Harvard investigates matters. It also details three initial allegations of misconduct against Anversa and Leri:

  • “Allegation 1 states that Drs. Anversa and Leri falsified and/or fabricated the C-14 measurements in the 2012 Circulation paper by (1) reporting 108 distinct data points when
    LLNL provided data for only 88 distinct measurements and (2) reporting 8 data points with values inconsistent with the measurements provided by LLNL.
  • Allegation 2 states that Drs. Anversa and Leri falsified and/or fabricated data in the 2012 Circulation paper by assigning isotope ratios to samples that have not been measured or reported by LLNL.
  • Allegation 3 states that Drs. Anversa and Leri “falsified and/or fabricated data relating to the characterization of stem cells” and notes that “[q]uestions have arisen regarding the reproducibility of the phenotyping of cell populations.”

A fourth issue apparently also arose later:

“On March 8, 2013, Dean Brodnicki informed Drs. Anversa and Leri that the inquiry would be expanded to include a fourth allegation relating to Dr. Kajstura’s apparent
manipulation of confocal microscope images in an unpublished manuscript submitted to The Lancet and Science in 2013.”

It’s not known if the examination of 15 additional papers has led to yet additional allegations, but it is possible and the plaintiffs dispute the expansion of the investigation:

“On October 2, 2014, Drs. Anversa and Leri were informed that the investigation would look into additional allegations concerning even more papers.”

The suit further alleges conflicts of interest by those doing the investigating and harmful delay in the investigation as well as other claims including breaches of confidentiality.

It’s unclear what the still ongoing investigation might conclude. Without all the facts it is impossible for us in the wider community to have a clear sense of this lawsuit and the misconduct investigation itself at this time.

Could this Anversa case have implications for the STAP cell paper situation as well where two Nature stem cell papers were retracted, which involved Brigham and Women’s and Harvard Medical School too? It’s not known whether these institutions are even investigating STAP.

What is clearer is the likelihood in a broader sense for more future lawsuits related to biomedical sciences publication issues and investigations.

Stem cell crystal ball: how did my 2014 predictions fare?

stem cell crystal ball

Every year I look into my stem cell crystal ball and make a top 10 list of stem cell predictions for the coming year.

My predictions for 2015 will be coming up soon and I may bump them up to 20 predictions instead of 10 because there’s so much going on in the field.

Stay tuned.

If you are curious, you can read my past top predictions for 2011, 2012 and 2013. You can also see how much the stem cell field has changed based on these past predictions. Generally the changes have been for the positive, which is encouraging!

Towards the end of last year, I posted my stem cell predictions for this year of 2014.

How did I do?

Below are my 10 predictions (including short blurbs I wrote about each) for stem cells for 2014 that I made about a year ago and my hopefully semi-objective assessment of whether I was right or wrong as indicated by color in each case. I got roughly eight out ten correct.

10. Academic Programs in Physician Training in Stem Cells Come Closer to Reality. In 2014, we hear about plans for the first ever academic physician training program in the US in stem cell and cellular/regenerative medicine. Such a program would be a 1-year fellowship or subspecialty program at a school of medicine or hospital. More and more doctors tell me they want such training. I’m just waiting for some institution to have the courage to be the first. What an amazing thing that’ll be. Somebody please step up!

Assessment: Right. A number of programs are in the works including this one. They are still small and experimental, but I find it heartening. I know of more in the works.

9. The “it’s a small world” globalization of stem cells accelerates for both the positive and negative. We see ties between Stamina in Italy and US players. We see that Celltex, that stem cell clinic originally from Texas, gets more heavily involved in stem cell interventions in Mexico, possibly buying an existing facility or company there such as Integrative Stem Cell Institute in Cancun. At the same time the company continues to face scrutiny from the FDA in the US. Other companies continue to do business in a number of countries. We hear more about non-compliant or even illegal exports and imports of human stem cell products. To be clear there’s nothing wrong per se with stem cell companies doing international business as long as it is for the good of patients and the field.

Assessment: Right. More and more legit and also dubious stem cell companies are going international. Stay tuned for more on this in the coming months. Globalization of stem cell and regenerative medicine can be a good thing and builds on collaborations, but many dubious operations take advantage of international operations to do harm to make money.

8. FDA prevails in US v. Regenerative Sciences appeals case and we see more stem cell-related lawsuits in 2014. I’m hearing a lot through the grapevine about conflicts that seem likely to bubble up into actual litigation. Some of this is likely to be company vs. company, while some may be patient vs. doctor, perhaps due to lack of proper training mentioned above. Others may be organizations/companies/patients vs. the FDA over regulatory issues.

Assessment: Right. However, this seemingly major victory for the FDA hasn’t really translated into more assertive action by the agency. Let’s see what develops in 2015.

7. One of the hottest trends in 2014 is organ/tissue growth from stem cells as we saw in the 2nd half of 2013 with livers, brains, kidneys and such. Some of the hottest publications in 2014 are on growth of actual organs and tissues that are functional.

Assessment: Right. Many stem cell-based organ advancements were reported this year including small intestine, liver, and others. For example, Organovo’s “Ex-Vive” Liver was hailed as the 7th top biotech development by The Scientist Magazine.

6. Cell Surgical Network and/or Stem.MD make big news. I’m guessing it won’t be something that they are happy about, but let’s see.

Assessment: RightCell Surgical Network was featured on the NBC Nightly News on December 5th. The report was fairly skeptical and raised numerous concerns, although it did contain one error on FDA regulation of stem cell treatments. Still, admittedly, on the regulatory front I’m not aware of any actions involving these stem cell clinic chains in 2014.

5. The stem cell biotech, California Stem Cell, will make major positive news in 2014. The company is developing stem cell therapies for cancer, spinal cord injury and other conditions. They have FDA approval already for some trial work.

Assessment: Right. They were bought by NeoStem. This was a huge deal for the Cali company. 

4. CIRM hires its new President, who was someone mentioned on this blog as a candidate. A big question mark remains–will a new proposition (a la Prop 71) be launched in 2014 for more CIRM funding in the future beyond 2017?

Assessment: Wrong. Randy Mills was not mentioned as a candidate on this blog before his choice was announced. I guess nobody is perfect in their predictions, huh? 

3. Big announcement from “Big Pharma” on stem cells or regenerative medicine. This could be in the form of their own research or acquisition of a smaller biotech in the stem cell arena. Any bets on takeover targets?

Assessment: Right. We saw J&J put up hundreds of millions for Capricor and more such big pharma stem cell developments this year.

2. More criminal charges filed against dubious stem cell organizations in 2014 or “legit” organizations finding themselves in hot water in the media related to stem cells. I’m hearing about quite a few investigations still ongoing. Some organizations that have “good reputations”, which may even include academic institutions or “legit” biotechs, may find themselves in hot water in the media (even if not going all the way to criminal charges) related to dabbling with non-compliants in the pursuit of easy cash (e.g. for fee for service agreements).

Assessment: Right. In Italy, a prosecutor filed indictments against many people (including a number of doctors) connected to the controversial Stamina Foundation. According to Science, the prosecutor described Davide Vannoni, who leads Stamina, as “the head of a criminal organization”. Whoa. We also in the US saw one indictment of a guy working for stem cell company Organogenesis (the company was not implicated) for allegedly stealing skin. There are quite a number of potential criminal cases percolating around under the surface related to stem cell clinics, but one never knows if they’ll poop out or turn into something important.

1. The US FDA takes at least one of two positive actions: approves its first breakthrough designation for a cellular therapy (most likely an adult stem cell-related therapy) OR approves an iPS cell-related IND. I hope both.

Assessment: Wrong. The FDA is going to do this some day, but 2014 (so far at least) wasn’t the year for it. Call me an eternal optimist, but I believe we can have our innovation in stem cell-based medicine and have it be evidence-based medicine too.

Paul Allen Gives $100 Million for New Institute for Cell Science with Major Focus on Stem Cells

Allen Institute for Cell ScienceFor the worlds of biology and cell biology including the stem cell field more specifically, the holidays came early with some fantastic news.

Philanthropist and Microsoft co-Founder Paul Allen will give $100 million to form a new institute focused on cell biology in Seattle.

The Allen Institute for Cell Science has an ambitious mission dedicated to making transformative discovers about cells and stem cells will be a major area of focus.

The Director of the Allen Institute is Dr. Rick Horwitz, who was formerly at the University of Virginia where he did cutting edge working on cell biology including cell migration. Horwitz described the new Institute as being akin to a “Manhattan Project for cells”.

You can see Horwitz (on the right) pictured with Institute CEO Allan Jones from the Institute’s Facebook page.

Allen Institute for Cell Science

The Institute will reportedly launch with an inaugural project called the “Allen Cell Observatory” to create detailed visual models of cells, focusing at least in part on human induced pluripotent stem cells (IPSC). This observatory has been described as developing into a “Google Maps for cells”. It makes me think of an astronomical observatory probing the stars with telescopes, but instead in this case turning to microscopes and turning inward to probe the workings of cells. Very exciting.

See the official fact sheet on the new Institute here. It will start up in 2015 and eventually have about 70-75 scientists all studying cells. If you potentially want to be part of that team you can contact them here to express your interest.

Allen has a long track record of supporting science including via the Allen Institute for Brain Science. Given my own experience with cancer, I find it notable that he also knows what it is like to be a cancer patient too as he battled lymphoma two times.

From a Forbes piece on the new Institute:

“Cell institute director Horwitz said Allen realized after quizzing biologists there were no good predictive models for the behavior of cells. “He’s a quantitative guy,” he said, and Allen had the insight to realize that understanding cells might provide a new route to understanding cancer.

But the biologists say the cell research could impact any number of diseases. As Allen Institute CEO Allan Jones puts it, “Cells are a battleground for every disease known to humankind.”

Part of what is so cool about the Allen Institute for Cell Science is its focus on determining in great detail the inner workings of cells and building models to explain how cells work. It’s a relatively unique and ambitious goal.

I can’t wait to see what they find.

STAP 2.0? New stem cell paper controversy ready to erupt

STAP2.0

Did you eventually get sick of the whole STAP mess and all the baggage that came with it?

Stay tuned for STAP 2.0 or perhaps I should say STAP junior.

Just as STAP is starting to fade a bit from our radar screens, there is unfortunately a new very problematic stem cell paper situation coming soon that has some parallels to the STAP cell fiasco.

As this new STAP junior mess inevitably marches toward blowing up sometime in the next few months in the public domain, should we be asking ourselves what’s the best way for the field to handle this new mess and other future large-scale messes?

In this new situation, not yet publicly revealed, there are some very serious issues invoked and some of these seem (at least preliminarily) to be similar to STAP. The potential commonalities include unusual stem cell claims and published papers with arguably very fundamental problems. In other ways, it is quite different.

I don’t expect this new stem cell publishing mess to be as epically bad as STAP in a general sense given various circumstances, but it won’t be a picnic either.

How should the field deal with this and more more importantly future such controversies? Is there anything that can be learned from STAP to help here?

Is the assertive, open approach at a scientific level that generally was applied to STAP the best one overall?

I wonder if STAP has made us more wary of big or unusual claims and made us more skeptical. I also wonder how the field will handle new messes such as this new one that is bubbling under the surface at the moment.