Bad news for regenerative medicine enthusiasts, the data manipulating biologist Suchitra Sumitran-Holgersson and her surgeon partner Michael Olausson, both professors at the University of Gothenburg (GU) in Sweden. They were previously found guilty of breach of medical ethics and patient abuse for their experiments with “regenerated” decellurised veins, which incidentally serve as basis for an EU-funded clinical trial currently prepared by the Gothenburg-based company VeriGraft (founded by Sumitran-Holgersson and her husband Jan Holgersson, also a GU professor, read here). There was even a trachea transplant: that patient died very soon after, the paper later retracted for data manipulation and absent ethics vote. It was a decellurised cadaveric graft by method very similar to that of Paolo Macchiarini. Another tracheal graft was prepared for one of Macchiarini’s patients at Karolinska Institutet (KI) after her plastic trachea failed, but it was sent back unused. Because of such expertise in misconduct and medical ethics breach, Olausson and his GU colleague Hasse Ejnell served as experts who helped Swedish prosecutor drop manslaughter charges against Macchiarini (read all that here).
Now that Sumitran-Holgersson’s research funding was withdrawn, with the new decision by the Expert Group at the Swedish Central Ethical Review Board (CEPN) she becomes even more of a liability for GU: eight out of her ten analysed papers with Olausson are set for retraction, due to data manipulation by the corresponding author Sumitran-Holgersson (while all her co-authors were made co-responsible to various degrees). I reported the evidence before, on my site, after my readers notified me and posted it on PubPeer. The 2012 paper in The Lancet describing a regenerated vein transplant was however not earmarked for retraction, despite that among other things it contained a fake ethics vote (see my earlier reporting), which the journal The Lancet couldn’t care less about.
The original misconduct report was written for GU in September 2017 by the external investigator Ole Didrik Laerum, medicine professor at University of Bergen in Norway, who was appointed exactly one year before that. Sumitran-Holgersson didn’t like his results and demanded from CEPN a revision by the Expert Group on Research Misconduct, in which she was supported by her GU colleague Kristoffer Hellstrand. This now proved to be her big mistake, because what Sumitran-Holgersson et al got now, was findings of research misconduct and instructions for retractions. The Swedish original of CEPN Expert Group report is available here, (Update 21.03.2018: English version here), these are its findings:
” The matter has been thoroughly and diligently analysed by the external investigator Ole Didrik Laerum. The Expert Group has reviewed Ole Didrik Laerum’s reports and conclusions, and conducted an independent review of the material, among other means by conducting its own analyses of the images. In summary,
it can be found that there are many remarkable striking inaccuracies in the articles, in the form of inaccurate images. The Expert Group has, with their review, essentially come to the same conclusions as Ole Didrik Laerum. In some cases, where Ole Didrik Laerum has stopped because there was only serious departure from generally accepted scientific practice, the Expert Group, however, come to the conclusion that the deviations are so serious that it is a matter of misconduct in research”.
These are the papers (some were previously corrected), with the relevant quoted comments of the Expert Group:
I. Meghnad Joshi, Pradeep B Patil, Zhong He, Jan Holgersson, Michael Olausson and Suchitra Sumitran-Holgersson. Fetal liver-derived mesenchymal stromal cells augment engraftment of transplanted hepatocytes. Cytotherapy, 14 (2012): 657-669.
“there are inaccuracies contained in this whose purpose is to create a better impression for the reader than what the reality actually shows.”
2. Pradeep B Patil, Priti B Chougule, Vijay Kumar Kuna, Stefan Almström, Henrik Bäckdahl, Debashish Banerjee, Gustaf Herlenieus, Michael Olausson och Suchitra Sumitran-Holgersson. Recellularization of a-cellular human small intestine using bone marrow stem cells. Stem Cells Trans Med, 2 (2013): 307-315.
“there is at least one image that is clearly manipulated”.
3. Michael Olausson, Pradeep B Patil, Vijay Kumar Kuna, Priti B Chougule, Nidia Hernandez, Ketaki Methe, Carola Kullberg-Lindh, Helena Borg, Hasse Ejnell and Suchitra Sumitran-Holgersson. Transplantation of an allogeneic vein bioengineered with autologous stem cells: a proof-of-concept study. Lancet, 380 (2012): 230-237.
“Ole Didrik Laerum changed his opinion after Suchitra Sumitran-Holgersson having explained that the disputed image is correct, but it is an incorrect magnification. The Expert Group has reviewed the relevant image and although the explanation seems a bit odd, it can not be established that it is false”.
4. Pradeep B Patil, Setara Begum, Meghnad Joshi, Marika Kleman, Michael Olausson and Suchitra Sumitran-Holgersson. Phenotypic and in vivo functional characterization of immortalized human fetal liver cells. Scandinavian Journal of Gastroenterology 49 (2014): 705-714.
” contain images which have been manipulated for the purpose of presenting the study in a better light than is the case”.
5. RETRACTED. Malin Berg, Hasse Ejnell, Anikö Kovåcs, Nikhil Nayakawde, Pradeep B Patil, Meghnad Joshi, Luaay Aziz, Göran Rådberg, Shahin Hajizadeh, Michael Olausson and SuchitraSumitran-Holgersson. Replacement of a tracheal stenosis
with a tissue-engineered human trachea using autologous stem cells: A case report. Tissue Eng Part A 20 (2013): 389-397.
” a reproduction of the study has not been able to be done due to that the patient has
passed away. The study thus has a weak scientific value. Via the improper placement of the images however, the scientific value is intended to appear stronger than it actually is. Suchitra Sumitran-Holgersson states that the exchanged images do not change the conclusions of the study. The Expert Group has reached the opinion, in agreement with Ole Didrik Laerum, that the new images give a much better impression than what there is support for.”.
6. Priti B Chougule, Gustaf Herlenieus, Nidia Maritza Hernandez, Pradeep B Patil,
Bo Xu and Suchitra Sumitran-Holgersson. Isolation and characterization of human primary enterocytes from small intestine using a novel method. Scandinavian Journal of Gastroenterology, 47 (2012): 1334-1343.
“contains a number of erroneous images. Collectigvely, these inaccuracies provide an overall much better impression than would have been the case without them”.
7. Meghnad Joshi, Mihai Oltean, Pradeep B Patil, David Hallberg, Marika Kleman, Jan Holgersson, Michael Olausson and Suchitra Sumitran-Holgersson. Chemokine-mediated robust augmentation of liver engraftment: a novel approach. Stem Cells Transl Med, 4 (2015): 21-30.
“there are a number of inaccuracies in the images. Suchitra Sumitran-Holgersson asserts that the images are correct, even if in some cases they exhibit rotational inaccuracies. The Expert Group’s view is that the images have been adjusted in order to create a better impression than what the research actually showed”.
8. Setara Begum, Meghnad Joshi, Monica Ek, Jan Holgersson, Marika I Kleman and Suchitra Sumitran-Holgersson Characterization and engraftment of long-term serum-
free human fetal liver cell cultures. Cytotherapy, 12 (2010): 201-211.
“contains, as far as the Expert Group has been able to find, no irregularities that can be regarded as scientific misconduct”.
9. Pradeep B Patil, Meghnad Joshi, Vijay Kumar Kuna, Bo Xu, Liza Johannesson, Michael
Olausson och Suchitra Sumitran-Holgersson. CD271 identifies functional human hepatic stellate cells, which localize in pen-sinusoidal and portal areas in liver after partial hepatectomy. Cytotherapy, 16 (2014): 990-999, under “temporary removal“.
“there is at least one inaccurate image, the purpose of which seems to be to give a
better impression of the study”.
10. Vijay Kumar Kuna, Antonio Rosales, Jonny Hisdal, Eivind K Osnes, Jon 0 Sundhagen, Henrik Bäckdahl, Suchitra Sumitran-Holgersson and Jörgen J Jörgensen. Successful tissue engineering of competent allogenic venous valves. Journal of Vascular Surgery, 3 (2015), 421-430.
“there are two incorrectly placed and compressed images which, as in most of the other articles, results in giving a better impression of the study than is the case in reality”.
The Expert group concluded:
“As far as the Expert Group has been able to find, there are false or misrepresented images in eight of the reported articles. A large number of images have been reused, enlarged, condensed or rotated incorrectly, and there are pure manipulations of images. Suchitra Sumitran-Holgersson concedes there are some errors, however asserts that these have been excusable, and that they did not affect the results. According to the Expert Group’s assessment, the false images essentially gives a better impression of the various studies than what was shown in reality. The assertion that the errors are not made consciously stands, against the background, as scarcely credible. The fact that the reported articles are collectively contain numerous strikingly remarkable and sometimes serious inaccuracies indicate that this has not been achieved via negligence but rather by deliberate manipulation, i.e. by intent. An additional factor that speaks for conscious manipulation or editing is that the general good order of Suchitra Sumitran-Holgersson’s computer appear to have been proper. The Expert Group concludes that the inaccuracies have been made for the purpose of fabricating research data.
Against now reviewed background, the Expert Group is of the view that the image
manipulations in all articles, except articles three and eight, constitute scientific misconduct. The dishonesty and misconduct appears to be intentional. If the closest systematic inaccuracies would have arisen been unintentionally or inadvertently, they must in any case have been preceded by gross negligence. Irrespective of matter which of these explanations is the correct one, Expert Group makes the assessment that the manipulations of the images constitutes misconduct in research”.
As for individual authors’ responsibility, the Expert group declared this:
“In all the outlined articles containing scientific misconduct, Suchitra Sumitran-Holgersson is the corresponding author and research director. In addition, she has also taken on the responsibility for the many inaccuracies, which is why her responsibility undoubtedly outweighs other participating authors. Suchitra Sumitran-Holgersson has taken responsibility for the many mistakes, which is why her responsibility is doubtless heavier than other participating authors.
As mentioned above, the Expert Group’s fundamental starting point is that all co-authors are responsible for an article in its entirety. However, in the cases where each and every contribution to the article has been specified, this general rule may be modified. Accordingly, the Expert Group considers that Luaay Aziz, Setara Begum, Malin Berg, Henrik Bäckdahl, Priti B. Chougule, Hasse Ejnell, Shahin Hajizadeh, Zhong He, Gustaf Herlenius, Nidia Hernandez, Jonny Hisdal, han Holgersson, Meghnad Joshi, Jörgen J Jörgensen, Marika I Kleinan, Anikö Koväcs, Vijay Kumar Kuna, Nikhil Nayakawde, Michael Olausson, Eivind K Osnes, Pradeep B. Patil, Antonio Rosales, Göran Rådberg, Suchitra Sumitran-Holgersson, Jon O Sundhagen and Bo Xu have had such roles in their article writing that they will be deemed to have been guilty of scientific misconduct”.
One of these co-authors listed above is the Sahlgrenska surgeon Gustaf Herlenius, who actually reported Sumitran-Holgersson and Olausson for unethical human experimenting to GU’s former Vice-Chancellor Pam Fredman, who then opened an investigation, which led the two cheaters to be found guilty of medical misconduct (see my article here). This was the final statement of the Expert Group on their newly determined scientific misconduct:
“In conclusion, the Expert Group finds that the matter clearly shows the systemic deficiencies in the research group’s composition and function, and an almost dysfunctional research environment. There has been a lack of proper meetings and people have come and gone, often on unclear grounds. These circumstances are likely to be one of the primary reasons for the shortcomings of the research. The Expert Group directs strong criticism towards the research culture that is found in the group around Suchitra Sumitran-Holgersson.
According to the Expert Group’s view, all items except Articles 3 and 8 are withdrawn. “
Update 27.03.2018. I now received the first version of investigative report by the external investigator Ole Didrik Laerum from February 3rd 2017 (in English, here), his PubPeer evidence file (here), and the long rebuttal written by GU professor Kristoffer Hellstrand from April 5th 2017 (here); not sure in which capacity, Hellstrand is neither any kind of GU-appointed counter-expert nor accused co-author of Sumitran-Holgersson’s papers. Laerum is Norwegian, but Hellstrand’s letter to him is in Swedish (why, actually?), here is a Google translation. I also have Laerum’s detailed reply to Hellstrand from June 29th 2017, in English (here, the cover letter is in Norwegian).
Hellstrand claims Laerum’s misconduct report is wrong, mostly because the investigator initially counted duplicated images in two different papers as two separate cases of data manipulation, a mistake which Laerum acknowledged and corrected. Otherwise, Hellstrand gives his expert opinion that such allegedly unintentional image duplication is perfectly normal and nothing malicious, and denies that images were adjusted to avoid detection of duplications.
An interesting extra finding (here) by Laerum for Patil et al, Stem Cells Trans Med, 2 (2013): 307-315, not discussed on PubPeer:
“KEY IMAGES ARE PRESENTED WITH SO LOW MAGNIFICATION THAT IT IS
NOT POSSIBLE TO DISTINGUISH EPITHELIAL CELL BORDERS ( In new microphotographs with higher magnification of intestinal mucosa it is evident that there are no viable cells on the villi) […] IMAGE OF “KEY FINDING” IS BASED ON A MICROSCOPIC SLIDE WITH ONE SINGLE, VERY SMALL, NECROTIC TISSUE PIECE”
After Laerum obtained original histochemistry slides of the intestine sections, he saw instead of preserved villi “only dead cells on the villous surface and no clear cell membranes, conformal with coagulation necrosis“.
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It is really good that common sense finally prevailed. One can only regret that this did not happen many years earlier after first investigations. Sweden seem to be one of few countries where real work against fraud is possible now.
Slowly, very slowly, sooner or later many cheated papers from well positioned researchers will be either corrected or retracted
The warning signs were in the scientific literature as long ago as 2011.
Blood. 2005 Oct 1;106(7):2347-55. Epub 2005 Jun 28.
Only a specific subset of human peripheral-blood monocytes has endothelial-like functional capacity.
Elsheikh E1, Uzunel M, He Z, Holgersson J, Nowak G, Sumitran-Holgersson S.
Division of Transplantation Surgery, Karolinska Institutet, Karolinska University Hospital-Huddinge, Stockholm, Sweden.
2011 retraction notice.
“The Karolinska Institutet, the signed authors, and the editors retract the article cited above. An investigation performed by the Swedish Research Council has concluded that the results as published cannot be considered reliable.
The following authors agreed to the retraction: Elzafir Elsheikh, Mehmet Uzunel, and Grzegorz Nowak.
The following authors did not agree to the retraction: Zhong He, Jan Holgersson, and Suchitra Sumitran-Holgersson.
© 2011 by The American Society of Hematology”
I am glad that Sumitran-Holgersson finally has been stopped, but it is outrageous how long it took before a decision was made. They knew that something was terribly wrong many years ago and in the meantime these guys could continue their malicious practice. Grants have been wasted, many researchers have been misled and even a company has been started based on this nonsense.
I really don’t understand how the leadership at Karolinska, GU and Sahlgrenska could be so stupid and naive. Hopefully they will learn after the Macchiarini case and now this case. The new rector at Karolinska has recently appointed an Ombudsman to deal with questionable behavior, which is a step in the right direction.
Naivity have little to do with the case at Karolinska. In a recent seminal paper entitle Knifed with a smile ethicist Carl Elliot describes the moral collapse of the leadership at Karolinska. The paper also highlights the refusal of the past and current leadership to try to make amends with the relatives of the deceased patients or the Whisleblowers that they tried to silence. I fear that the Karolinska have taken a path towards darkness and that appointing an Ombudsman is simply to little to late.
Here is this article: http://www.nybooks.com/articles/2018/04/05/experiments-knifed-with-smile/
Okay, I agree. However, they may have been naive when they recruited Macchiarini.
Later they behaved arrogantly and irresponsibly, and tried to sweep the many problems under the carpet. Much like other top institutions like MD Anderson and Weizmann Institute.
Indeed is quite unfair how there are many high profile researchers getting millions in grants with cheated publications
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Did they evaluate the other issue (link below) with the Lancet paper? Perhaps it was part of the investigation into the Journal of Vascular Surgery paper, but it seems strange that they didn’t bring it up during the discussion of the Lancet paper as well. https://pubpeer.com/publications/2C2ED756F7081A05DA772B8693B016#10
So, what’s happening now? Suchitra Holgersson is still professor at Goteborg University.
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