Biologist’s research under investigation in Sweden after being questioned on PubPeer

The University of Gothenburg in Sweden is investigating several papers co-authored by biologist Suchitra Sumitran-Holgersson after they were challenged on PubPeer.

Sumitran-Holgersson already has one retraction under her belt — of a 2005 Blood paper, after another investigation concluded the results “cannot be considered reliable.” Sumitran-Holgersson and her husband, co-author Jan Holgersson, did not sign the retraction notice. Both were based at the Karolinska Institutet (KI) at the time, but have since moved to the University of Gothenburg.

Now, the University of Gothenburg has launched its own investigation of the papers questioned on PubPeer, according to spokesperson Ann-Charlotte Schützer, who noted the institution will be unable to comment on the case whilst the inspection is ongoing.

Sumitran-Holgersson also confirmed the investigation to us:

The Gothenburg University has already initiated an investigation into this matter. All the laboratory journals and original data with the correct dates and timings for the experiments have already been handed over to the University authorities for inspection.

I am confident that none of my students or postdocs have manipulated the results. But I will let the proper authorities come to the right decision.

When asked about her own involvement, she added:

I confirm that I have not manipulated the results. The laboratory journals and original data will confirm this. In some cases human errors have been made while the rest is completely false.

As reported by Leonid Schneider on his blog For Better Science, Sumitran-Holgersson has been investigated before.

In August 2008, KI conducted an internal investigation into Sumitran-Holgersson’s work and concluded on 2 December 2008 that there was a “strong suspicion of scientific misconduct and falsification of data by Suchitra Holgersson.” Around this time, Sumitran-Holgersson moved to the University of Gothenburg. A spokesperson from KI provided us with a document that outlines the events in chronological order.

In December 2008, the KI and the University of Gothenburg requested an expert group at the Swedish Research Council (VR) to investigate the allegations.

According to the document provided to us by KI, in September 2010, the group concluded:

Suchitra Holgersson had committed scientific fraud by adding fabricated data to an article in Blood 2005, adding fabricated data to a manuscript by one of her PhD students, by adding fabricated data to a thesis by another PhD student, by adding fabricated data to a report by one of her co-workers and for deliberately trying to mislead the Expert Group by submitting false documentation.

Following this, KI handed the case over to a law firm, which concluded in February 2011 that Sumitran-Holgersson was guilty of committing scientific fraud.

But in September 2011, the Swedish Research Council withdrew its report, saying that the case had not been properly managed by the expert group. Then, in December 2011, the research council decided not to resume its investigation, and stated that the organization will no longer assist universities with misconduct investigations.

The case was then passed to the Central Ethical Review board, which concluded in October 2012:

Suchitra Holgersson has not committed scientific fraud or misconduct and urges KI to withdraw its decision made on 15 February 2011.

The KI vice-chancellor then assigned an ethics council at the institution to evaluate the report from the Central Ethical Review Board.

The vice-chancellor concluded on 22 April 2013:

…changing the decision made by KI on 15 February 2011 requires that new facts have emerged, that would be sufficient grounds for a new and well-founded position in the case of scientific misconduct. The vice-chancellor states that no such facts and circumstances have been added to the case and that KI therefore has no reason to take further measurements or to change its standpoint in the matter. The case is closed.

The Swedish government is currently re-evaluating its system for investigating allegations of misconduct.

For a closer look at the current situation with the work of Sumitran-Holgersson, let’s consider some of the papers being questioned on PubPeer.

We’ll start with perhaps the most high profile of the bunch, a 2012 paper in The Lancet that claimed to have transplanted a vein graft using donor tissue seeded with a patient’s own stem cells. (If this type of procedure feels familiar, it’s because it is — another former KI investigator, Paolo Macchiarini, has been under fire after claiming success from a similar procedure transplanting trachea seeded with autologous cells. Macchiarini was dismissed from KI earlier today.)

On PubPeer, commenters have questioned whether one figure in “Transplantation of an allogeneic vein bioengineered with autologous stem cells: a proof-of-concept study” is an enlarged version of one section of another figure in the same paper. An author has responded to the thread. The paper has been cited 44 times, according to Thomson Reuters Web of Science.

A figure in a 2004 Circulation paper, “Expression of Vascular Endothelial Growth Factor Receptor-2 or Tie-2 on Peripheral Blood Cells Defines Functionally Competent Cell Populations Capable of Reendothelialization,” was also criticized on PubPeer. It’s been cited 74 times.

Carrie Thacker from the American Heart Association, which publishes Circulation, said the organization is aware of the allegations and is looking into the matter.

Users on PubPeer have also questioned images from “Replacement of a Tracheal Stenosis with a Tissue-Engineered Human Trachea Using Autologous Stem Cells: A Case Report,” published in Tissue Engineering Part A in 2013 (with 12 cites). This paper describes the transplantation of a donor trachea seeded with autologous stem cells, but notes the patient died less than one month after surgery.

Peter Johnson, co-editor-in-chief of the journal, told us:

We handle these issues internally, but with great attention.

Three of Sumitran-Holgersson’s papers published in Cytotherapy have received queries on the site, including a 2012 paper, “Fetal liver-derived mesenchymal stromal cells augment engraftment of transplanted hepatocytes,” which users suggest contains similar figures. It’s received 17 citations so far.

One of the co-authors of the paper commented on the thread:

…the home institution has been informed. Many errors have been made BUT we have all the original data to show that the expts. have been performed, with dates and timings and all log books to prove that this is not intentional but carelessness. We of course sincerely apologize for this carelessness and will submit all data for examination to our institute’s chiefs.

Next, A 2010 paper with eight citations, “Characterization and engraftment of long-term serum-free human fetal liver cell cultures,” was accused of image recycling with another paper.

Similarly, a 2014 study (cited three times), “CD271 identifies functional human hepatic stellate cells, which localize in peri-sinusoidal and portal areas in liver after partial hepatectomy,” was accused of “data recycling.”

Next on the list are two papers from the Scandinavian Journal of Gastroenterology:

“Phenotypic and in vivo functional characterization of immortalized human fetal liver cells,” published in 2014 (with only one citation so far), which a PubPeer thread suggests contains images that reappear in later publications.

“Isolation and characterization of human primary enterocytes from small intestine using a novel method,” a 2012 study with seven citations, also contains images questioned on the site. 

Helge Waldum, the editor-in-chief of the journal from the Norwegian University of Science and Technology in Trondheim, Norway, told us:

We have written to the author about this, but will not do anything more about it. After all, the pictures used twice only made up a minuscule part of the figures, and we do not find this error of such a degree to do anything more.

Here are the next two, which were published in Stem Cells Translational Medicine:

Commenters on PubPeer are suggesting a 2013 paper, “Recellularization of Acellular Human Small Intestine Using Bone Marrow Stem Cells,” has similar figures to another 2008 paper that is also co-authored by Sumitran-Holgersson, and uses a different cell type altogether.

An author of the paper — which has been cited 10 times — commented on the thread, referring to the situation as a “sincere mistake”:

We have now contacted the editors and will send in all the raw data as proof that a sincere mistake was made.

The 2008 paper, “Evidence for no relevance of anti–major histocompatibility complex class i–related chain a antibodies in liver transplantation,” has eight citations and was published in Liver Transplantation.

In “Chemokine-Mediated Robust Augmentation of Liver Engraftment: A Novel Approach,” a 2014 paper published in Stem Cells Translational Medicine with only one citation so far, PubPeer users thought there were some issues with images. 

Finally, a user has questioned an image in “Human liver sinusoidal endothelial cells induce apoptosis in activated T cells: a role in tolerance,” published in Gut in 2007 and cited 32 times.

We’ve also contacted editors of The Lancet, Cytotherapy, and Stem Cells Translational Medicine.

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