Sonia Melo case: PhD advisor Esteller sham-investigated, postdoc PI Kalluri with $ 80Mio COI

Sonia Melo, Portuguese cancer researcher and recipient of the prestigious EMBO Installation Grant, now has her publications investigated by EMBO for suspected image manipulations. Her current and former research institutions are apparently actively avoiding any attempts to scrutinise her papers, some due to very heavy financial conflicts of interest. Yet my information suggests that Melo’s former PhD advisor and co-author, Manel Esteller, is being presently investigated by his research centre in Barcelona.

Melo already had to retract a first-author publication from her PhD period with Esteller from the journal Nature Genetics. The retraction notice admits image duplications:

“We have recently become aware of the presence of duplicated images in the Figures 3 and 4 and Supplementary Figures 5 and 6 in our publication Nat. Genet. 41, 365–370, 2009, that were assembled according to the specified author contributions. We therefore retract the publication for the sake of the high standards we expect for research and scientific journals. All the authors have signed this statement”.

Melo herself told RetractionWatch:

“As for further comments/concerns, which arose on PubPeer, the authors and respective institutions have not ignored them. All concerns were addressed, raw data registered on notebooks was analysed and reports developed for each case. The data was shown to be correct so no further action was taken”.

It appears, she spoke the truth. These are three important stations of Melo’s career in academic research institutions, and none of them is apparently interested in taking a closer look at her papers:

1. IPATIMUP, University of Porto

Here, Melo has only recently established her own research lab, at the Instituto de Patologia e Imunologia Molecular da Universidade do Porto (Ipatimup). The Ipatimup scientists and directors remained unresponsive to my inquiries. One could therefore speculate that Melo’s research is not being investigated there. Why? Generally, scientists under ongoing investigation do not communicate with media, they are often specifically forbidden to do so.  Yet Melo was able to freely share her views with RetractionWatch, even to publicly declare the absence of institutional investigations at her current and former places of work.

 2. University of Texas MD Anderson Cancer Center

Melo used to work as postdoctoral scientist at the lab of Raghu Kalluri, Chair of the Department of  Cancer Biology and specialist for exosome (extracellular secreted vesicles) research. Kalluri has five publications featuring Melo as first or second author listed on PubPeer, including in prestigious journals Nature and Cancer Cell. Here an example from the latter paper:

However, also some other Kalluri papers, where Melo was not co-author, were flagged. Earlier corrections acknowledged inappropriate figure assembly which has happened “accidentally”, e.g. this LeBleu et al 2013 paper in Nature Medicine:

Most importantly, there are reasons to worry that any MD Anderson investigation into Kalluri’s publications with Melo might be compromised by a large financial conflict of interest. Melo’s and Kalluri’s 2015 common paper in Nature is the basis of an $80 million investment into a biotech company Codiak Biosciences, as Forbes reports:

“The little company is announcing today it has raised $80 million in committed venture capital spread over two installments. Two venture firms known for creating ambitious biotech companies, ARCH Venture Partners and Flagship Ventures, pieced it together to build on exosome biology from the lab of Raghu Kalluri at MD Anderson Cancer Center in Houston, Tex. Fidelity Management and Research, the Alaska Permanent Fund and Alexandria Venture Investments joined the financing […]

The initial focus of Codiak will be pancreatic cancer. It’s a notoriously tough-to-treat cancer, and it’s often diagnosed late in the game. People usually only have a few months to live after diagnosis. The company will seek to build on research Kalluri’s team published in Nature in June. At that time, Kalluri said his team had identified a proteoglycan (a protein covered with lots of carbohydrate molecules) called Glypican-1, which was present on the surface of exosomes.  […]

Gillis [managing director at Arch Venture Partners, -LS] said Kalluri’s group has generated more data from animal tests, which hasn’t yet been published. “It’s about being able to target various oncogene targets that have previously failed to be targetable via small molecules,” Gillis said. Kalluri, he said, “has gotten some dramatic data in animal models. If we can rapidly exploit that clinically, it would be a big win””.

How exactly is MD Anderson involved into Codiak Biosciences research on endosomes? According to information available to the industry news site FierceBiotech, rather directly:

“MD Anderson–which has been busily spinning out new biotechs–signed off on an IP [Intellectual Property Rights, -LS] license and a sponsored research agreement, keeping the big cancer center directly engaged in the R&D work ahead”.

In fact, Codiak Biosciences was apparently (officially or unofficially) founded by Raghu Kalluri himself, as the website GenomeWeb reports:

“The firm has licensed exosome-related technology that Kalluri developed at MD Anderson, including using the small, extra-cellular vesicles to deliver therapies and analyzing their nucleic acid and protein contents for diagnostic purposes”.

The other, official, company founder is none other than Eric Lander, president of the Broad Institute of MIT and Harvard. Lander is a top scientist and also well versed in money issues: he was recently widely criticized for his article in Cell , where Lander attempted to exclusively assign the CRISPR discovery credit to his Broad Institute, which accidentally is also a key contender for the potentially billions-dollar worth patent on CRISPR genome editing technology.

Should this Nature paper (image below) or other Kalluri publications, especially those featuring Melo, be retracted, the big investors will likely lose trust in Codiak Biosciences and might be asking MD Anderson for their money back, with interest. Neither the Texan Cancer Center nor the biotech company can afford to be caught with wasting investors’ money on any questionable research, especially if tainted by misconduct and data manipulation.

Thus, Melo was probably telling the truth that MD Anderson decided not to investigate her publications with Kalluri. With $80 Million at stake, it was probably a financially very wise decision, maybe less so in the sense of academic research integrity.

 3. IDIBELL in Barcelona

Melo performed her PhD studies in the lab of Manel Esteller, director of strategic projects at the Institut d’Investigació Biomèdica de Bellvitge (IDIBELL). Three of Melo’s papers with Esteller were flagged on PubPeer. About the now retracted paper in Nature Genetics, Esteller announced on PubPeer in November 2015:

“Dear PubPeer Colleagues,

Thanks for your informative messages and insightful comments. I acknowledge the obviously serious nature of the case. The matter will be promptly and thoroughly investigated and appropriate action will be taken. The first author, that left the lab years ago, has been contacted to ask for a formal and detailed explanation. The conclusions will be disclosed in the journal and in this forum. I also take the opportunity to stress that the collaborators that coauthor the manuscript or myself as corresponding author have absolutely nothing to do with the issues raised.

As I have always done in my twenty-three years research career, truth and science should always come first.

Keep the good work,

Dr. Manel Esteller”

When asked about any institutional investigations happening, Esteller wrote to me in an email in December 2015:

“We do not have currently a formal ombudsman for this issues in our place, it is in the making”.

It seems now, Esteller himself will be the first case whom IDIBELL’s new Ombudsmen will be investigating.

Like Kalluri, he also has a number of problematic papers where Melo is not an author. Band duplication’s were suspected by PubPeer commenters in Esteller’s papers in Cancer Research, Oncogene and Nature Communications, like this here:

Now, the director of IDIBELL, Jaume Reventós, wrote to me:

“As you know, since many years, Sonia Melo is not any longer in our institution and she is pursuing her career elsewhere. Concerning the publications in which Dr. Melo is not an author, I want to let you know that we will pursue our inquiry following our standard procedures for those matters.

We support a fair and clean science from our scientists and believe that fraud doesn’t not have place in our institution”. 

This on-going IDIBELL investigation might also explain why Esteller has not replied to my emails since. I asked Reventós for clarifications, but received none. My interpretation is then, that IDIBELL will not be investigating Melo’s papers from Esteller lab, since those are likely already being analysed by the EMBO commission, as EMBO director Maria Leptin announced. Instead, IDIBELL will probably focus their investigative efforts on other papers by Esteller, sans Melo, which were flagged on PubPeer. Thus, EMBO is seemingly indeed the only institution investigating Melo’s publications for suspected data manipulations.

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Update 29.08.2016. In fact, the IDIBELL investigation of Manel Esteller’s work was a sham (hence correction to the title of this article). As described in my follow-up article, IDIBELL declared Esteller as not responsible for data integrity in his lab’s papers  and tasked him with investigating himself.

Recent news may explain such peculiar attitude of IDIBELL. There was a major financial COI hindering any attempt at investigation: just as MD Anderson with Kalluri, the Spanish institute has similar business interests with Esteller. Together with the also Barcelona-based pharma company Ferrer, Esteller has developed a cancer diagnostics test called EPICUP (see press release and The Lancet Oncology paper Moran et al 2016). A patent was filed in 2012 and approved in January 2016, the inventor is Esteller and the applicant is IDIBELL. Unlike with Kalluri and his Codiak Biosciences, Sonia Melo was not part of this research by Esteller and IDIBELL.

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