stripy revisited

Three little (nano) controversies and their morals

This post is a translation of an article originally published in French in Médecine/Sciences. The Editorial of the same issue (also in French) by Pierre Corvol is entitled Scientific integrity: the need for a systemic approach (open access).  You can download a pdf of my article, or, read at the publisher’s website (subscription). For citation, please refer to the original article as follows:

Trois petites (nano) controverses et leurs morales; Raphaël Lévy; Med Sci (Paris), 33 8-9 (2017) 797-800; Publié en ligne : 18 septembre 2017; DOI: https://doi.org/10.1051/medsci/20173308027

« Selon que vous serez puissant ou misérable, les jugements de cour vous rendront blanc ou noir » [1] [Depending on your social height, The law will see your crime as black—or else as white.] Thus concludes the Fable, by Jean de La Fontaine, The Animals sick of the plague : the donkey, guilty of the theft of a few blades of grass, is condemned to death, whilst the Lion and other powerful animals guilty of much more serious crimes are treated to praise and flattery. It is tempting and comforting to think that scientific judgments are of an altogether different nature. Seen in this light, science would reside outside of power struggles and the few mishaps (mistakes, frauds, conflicts of interest) would be rapidly corrected since the reality of the material world would quickly come back to us through experimental results if we were to try to ignore it for too long. The truth is however very different. A large fraction of published scientific results cannot be reproduced. It is not a few mishaps but structural problems which affect the foundations of the scientific enterprise [2, 3]. Peer evaluations seems to encourage the publication of extraordinary stories in high impact factor journals rather than careful and rigorous experimental studies. Contradictory or “negative” data are rarely published: scientific journals are not really interested, and us, scientists, are not particularly motivated by publicly stating our doubts on the work of colleagues who could be in charge of evaluating our next article or grant application. It is particularly urgent to repair our knowledge production system because science is at the center of numerous challenges critical for the future of human beings and the planet. The (real) problems of reproducibility have already been harnessed by lobbies to attack the credibility of scientists [4]. After the election for president of the largest scientific and military power of the world of a man who denies climate change, is very positive about the use of the atomic bomb, and, more broadly wages an open war against science and truth [5], we have a paramount need for science to be open, robust, capable of defending its independence, integrity and universal values. This seems a distant prospect.

The near absence of critical discussion in the scientific literature in many areas of science could make us forget that controversies are an essential aspect of the quest for knowledge, allowing to identify weak points of experiments and theories, thus enabling to consolidate or invalidate them [6]. They are consubstantial to the scientific practice [7]. The analysis of controversies is also a tool to “symmetrically map” the actors to better understand the roles of individuals and social processes [8]. In this piece, I describe three recent controversies in my area of research: gold nanoparticles applied to biology and medicine. This is no “symmetric map”: I am not a neutral observer but a scientist active, to various degrees, in each of those. I am trying nevertheless to draw some lessons and suggestions to improve the ways we work as scientists.

Stripy Nanoparticles

In 2004, Francesco Stellacci’s group at the Massachusetts Institute of Technology (MIT) published in the prestigious journal Nature Materials an article describing gold nanoparticles covered by a mixture of two molecules that self-assemble to form stripes that are observed by scanning probe microscopy [9]. This article and the numerous other ones that will follow in the same journal and in others just as prestigious such as the Journal of the American Chemical Society [10], Science [11] and Proceedings of the National Academy of Sciences (PNAS) [12], suggest that, thanks to their stripes, these nanoparticles have unique properties in terms of wetting, self-organization, interaction with proteins, penetration in cells, with lots of potential applications for biomolecular sensing, or even drug delivery. These articles certainly contributes to the progress of their authors’ careers, but the stripes are an experimental artefact well known by users of scanning probe microscopy. How to explain then that more than 20 “stripy” articles were published between 2004 and 2012? It is obvious that specialists (and even enlightened amateurs) had identified the problem as early as 2004. Yet, the articles and reviews of that period show no sign of it. One now knows that Predrag Djuranovic has been the first to engage into a scientific investigation aiming at testing, and eventually, contesting, the evidence for the the existence of the stripes. In 2005, this rigorous and brave scientist was a student in Francesco Stellacci’s lab. His experimental results and numerical simulation showing how the stripes originate from a poorly adjusted feedback control system were unambiguous but MIT ensured that these results would remain secret [13]. In 2007, I submitted a technical comment responding to the Science article. This first attempt, limited in its scope to the Science article itself, was unsuccessful: Science did ask Francesco Stellacci to respond but then decided not to publish the exchange of views [14]. In 2008, a new article from the MIT group, again in Nature Materials, report that, thanks to their stripes, these nanoparticles can cross the cell membrane and directly access the cytosol [15]. This is accompanied by a commentary entitled “Particles slip cell security” [16]. After discussions with several of my students, we decide to propose a more exhaustive answer. A few months later, the article “Stripy Nanoparticles Revisited” is ready. It includes a new analysis of the stripy images concluding that the stripes are a scanning artefact as well as a critical discussion of the physicochemical and biological properties which, together with experimental results, contradict the claim of direct access to the interior of cells. The article is first submitted to Nature Materials (rejected), then NanoLetters (rejected), and, finally, Small… where it is published after an editorial process that lasted three years [17-19]. The publication of our article, in November 2012, does not end the controversy. Instead, it expands in the scientific literature (a little) and it also takes new forms (in particular on my blog and others [20-23]). Problems with the reuse of images in different publications emerge and eventually lead to two corrections ([12] and [15]). After a number of requests, Philip Moriarty and Julian Stirling (School of Physics and Astronomy, university of Nottingham, UK) are given access to the original data of the 2004 article. They demonstrate, among other things, that the stripes are present in the entire image, i.e. even between the gold nanoparticles [24], a conclusion still rejected by Francesco Stellacci [25].

Homeopathic nanoparticles

The laboratory of Molly Stevens at Imperial College is one of the most prestigious in the field of biomaterials. In 2012, two articles from the group relate the particularly interesting properties of nanoparticles for diagnostic applications. The first one, published in Nature Materials, reports a phenomenon which is entirely extraordinary in which the signal detected increases when the concentration of molecules to detect decreases (“inverse sensitivity”) [26]. Even more incredible, this phenomenon extends to the point where there is less than a molecule of enzyme, on average, in the volume under study. The second article published in Nature Nanotechnology goes further : no need for instruments, the detection of concentration of analytes in the same range is achieved thanks to a colour change visible with the naked eye [27]. Detailed critiques of these articles are available on the website PubPeer [28, 29] as well as in a preprint authored by Boris Barbour; the objections are both simple and profound but the authors have chosen not to respond. One can note that the Avogadro number includes lots of zeros (630 000 000 000 000 000 000 000) and that the detection of a macroscopic change of property due to the presence of a single molecule is therefore an achievement that requires extremely solid proofs. One of the posts on PubPeer indicates that someone contacted the Editor of Nature Nanotechnology in January 2013, but, four years later, no doubts are expressed on the journal website, in the traditional scientific literature nor in the newspapers that had covered this story (e.g. Le Monde and the Daily Mail) when it was initially published [30, 31].

Spherical Nucleic Acids

The laboratory of Chad Mirkin at Northwestern University (USA) is one of the most prestigious in the field of nanosciences applied to biology and medicine. One major theme of their research are the Spherical Nucleic Acids (SNAs), a term introduced by Mirkin to describe gold nanoparticles functionalised with DNA (or RNA) strands. These SNAs are supposed to have properties very different from linear DNA [32]. In particular, they can access the cytosol of live cells, where they could detect and regulate, the presence and quantity of mRNAs. One could ask why this solution did not appear during evolution : to access the cell machinery, viruses and bacteria would have only needed to package themselves within their genetic materials. The first articles (in Science [33], the Journal of the Americal Chemical Society [34], NanoLetters [35], ACS Nano [36]) proposing this surprising theory do no mention the mechanism of the SNAs into cells whatsover. The following one, e.g. [37], propose that the particles enter by endocytosis, but do not explain the mechanism by which the SNAs would escape endosomes. After several dozens of articles on this topic, the proportion of particles reaching the cytosol is still to be measured and reported (in spite of the fact that gold nanoparticles have been used since the 1950s to study intracellular trafficking; such a study would not be difficult). One article from the Mirkin group suggests that SNAs are degraded in the endosomes and that a “small unquantifiable portion escapes […]” [38]. Nevertheless, the particles are now commercially available under the name SmartFlares (Merck Millipore) to detect RNA inside cells. We have studied the entry of nanoparticles in cells and their ability to detect RNA. Given our difficult experience with the publication of Stripy Nanoparticle Revisited, we decided to adopt a different strategy. The project has been open and we have shared our results in quasi real time on our blog. In contradiction with the descriptions made by Mirkin and by Merck Millipore, we have observed that the SmartFlares were degraded in endosomes and were not able to detect mRNA.  Mirroring the tale of Predrag Djuranovic and the stripy nanoparticles, we were not the first to have doubts about the technology: Luke Armstrong, who had been in charge of developing the SmartFlares at Merck Millipore in California (before leaving the company) had reached the same conclusion [39]. To ensure speedy publication and transparency, we published our article on the (not so prestigious) ScienceOpen platform where peer review occurs after publication [40]. We invited comments by Mirkin to no avail. Another article by the same group in PNAS describe a new version of the SmartFlares [41]. Our analysis of the raw data (obtained after multiple insistent requests) show that the signal comes from endosomes. Our letter submitted to PNAS has been rejected by the editorial board because it “[did] not contribute significantly to the discussion of this paper” [42].

 Morals

Access to raw data is essential and guaranteed by clear rules adopted by Universities, scientific journals and funding agencies. It is therefore generally possible to access data with some efforts. It is obviously preferable to publish data at the same time as the articles. This is already the norm for some categories of results and it should become generalised. Researchers should also adopt the Manifesto for reproducible research [43]. The tools are in place to improve the practice of science.

Evaluations of science and scientists must imperatively be based on a critical analysis of their work and the robustness or their results, not on the prestige of the institutions or journals. This requires a change of mind and a clear commitment from researchers who are in positions of power, i.e. everyone who features on promotion or recruitment committees. To say that an article is good because it has been published in a prestigious journal is a moral and logical error which needs to be challenged.

Institutions and scientific journals are not motivated by the quest for scientific truth. The decisisons taken by MIT (keeping Predrag Djuranovic’s findings secret), by Nature Materials (not publishing the exchange with Francesco Stellacci [14]), and by PNAS (not publishing [42]) have directly impacted progress of knowledge. These institutions have commendable principles but, in practice, they aim first at defending their reputation and finances [44]. The latter objective only partially aligns with scientific progress which requires rapid and open discussion of results and conclusions. The Worldwide Web, invented for the sharing of science, enables this discussion. Researchers therefore should embrace the following tools: 1) Pubpeer to comment on articles; 2) Preprints to publish rapidly, minimise the influence of editors, and, dissociate publication, i.e. sharing of information, from evaluation, i.e. peer review; 3) Social networks, e.g. Twitter and blogs, which constitute an ongoing scientific conference to discuss experiments, results, methods, analyses, and new publications.

Acknowledgements: I thank Marianne Noel (IFRIS) for her critical reading of this piece, and, Marianne Lévy for comments on the grammar and style [French version] very necessary after 14 years in an English-speaking country…

Conflicts of interest: The author declares that he has no conflict of interest related to this article.

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A welcome Nature Editorial

I reproduce below a comment I have left on this Nature editorial entitled “Go forth and replicate!“.

Nature Publishing Group encouragement of replications and discussions of their own published studies is a very welcome move. Seven years ago, I wrote a letter (accompanying a submission) to the Editor of Nature Materials. The last paragraph of that letter read: “The possibility of refuting existing data and theories is an important condition of progress of scientific knowledge. The high-impact publication of wrong results can have a real impact on research activities and funding priorities. There is no doubt that the series of papers revisited in this Report contribute to shape the current scientific landscape in this area of science and that their refutation will have a large impact.” [1]

The submission was “Stripy Nanoparticles Revisited” and it took three more years to publish it… in another journal; meanwhile Nature Materials continued to publish findings based on the original flawed paper [2]. The ensuing, finally public (after three years in the secret of peer review), discussions on blogs, news commentary and follow up articles were certainly very informative on the absolute necessity of changing the ways we do science to ensure a more rapid discussion of research results [3].

One of the lessons I draw from this adventure is that the traditional publishing system is, at best ill suited (e.g. Small: three years delay), or at worst (e.g. Nature Materials) completely reluctant at considering replications or challenges to their published findings. Therefore, I am now using PrePrints (e.g. to publish a letter PNAS won’t share with their readers [4]), PubPeer and journals such as ScienceOpen where publication happens immediately and peer review follows [5].

So whilst I warmly welcome this editorial, it will need a little more to convince me that it is not a complete waste of time to use the traditional channels to open discussions of published results.

[1] The rest of letter can be found at https://raphazlab.wordpress.com/2012/12/17/letter-to-naturematerials/
[2] The article was eventually published in Small (DOI:10.1002/smll.201001465

2 comments on PubPeer

); timeline: https://raphazlab.wordpress.com/2012/12/20/stripy-timeline/
[3] https://raphazlab.wordpress.com/stripy-outside/
[4] https://raphazlab.wordpress.com/2015/11/16/pnas-your-letter-does-not-contribute-significantly-to-the-discussion-of-this-paper/
[5] https://raphazlab.wordpress.com/2015/11/17/the-spherical-nucleic-acids-mrna-detection-paradox/

Nanoparticles & cell membranes: history of a (science) fiction?

One of the reason scientists, journalists and the general public are excited about nanoparticles is their supposed ability to cross biological barriers, including, the cell membrane. This could do wonders for drug delivery by bringing active molecules to the interior of the cell where they could interact with key components of the cell machinery to restore function or kill cancer cells. On the opposite side of the coin, if nanoparticles can do this, then there are enormous implications in terms of their potential toxicity and it is very urgent to investigate. But is it true? What is the evidence? How did this idea come into the scientific literature in the first place? I have been intrigued by this question for some time. It is the publication of an article about stripy nanoparticles magically crossing the cell membrane that led me to engage in what became the stripy nanoparticles controversy. It is this same vexing question that led me to question Merck/Mirkin claims about smartflare/nanoflare/stickyflare.

In the introduction of our article “The spherical nucleic acids mRNA detection paradox“, we describe the long history of the use of gold nanoparticles (“gold colloids”) in cell biology and conclude that

…, more than five decades of work has clearly established that nanoparticles enter cells by endocytotic mechanisms that result in their entrapment inside intracellular vesicles unless those nanoparticles are biological in nature and have acquired through evolution, advanced molecular tools which enable them to escape.

In the paragraph that followed, we were trying to make the point, in part using citation data of one of these 1950s pioneering articles, that this solid knowledge has been ignored in some of the thousands of recent articles on interactions of nanoparticles with membranes and cells that have appeared in the past 15 years. In his review of the first version of our article, Steve Royle criticises that latter paragraph (in his word, a “very minor” point):

I’m not a big fan of using number of Web of Science search results as an argument (Introduction). The number of papers on Gold Nanoparticles may be increasing since 2007, but then so are the number of papers on anything. It needs to be normalised to be meaningful. It’s also a shame that only 5 papers have cited Harford et al., but it’s an old paper, maybe people are citing reviews that cover this paper instead?

This is a fair point. While normalisation as well as more detailed and systematic searches might shed some light, it is rather difficult to quantify an absence of citation. Instead, I have tried to discover where the idea that nanoparticles can diffuse through membranes comes from. Here are my prime suspects (but I would be more than happy to update this post to better reflect the history of science and ideas so please leave comment, tweet, email), Andre Nel and colleagues, in Science, 3rd of February 2006, “Toxic Potential of Materials at the Nanolevel” :

“ Moreover, some nanoparticles readily travel throughout the body, deposit in target organs, penetrate cell membranes, lodge in mitochondria, and may trigger injurious responses.”

This claim is not supported by a reference, but later in the article Nel et al refer to an earlier paper entitled “Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells” by Marianne Geiser and colleagues. These two papers, Nel et al, and, Geiser et al, have been cited respectively 5000 times and 850 times according to PubMed.

As early as 2007, Shayla Banerji and Mark Hayes had already challenged this idea of transport of nanoparticles across membranes in an elegant experimental and theoretical study which was a direct response to the two papers cited above “Examination of Nonendocytotic Bulk Transport of Nanoparticles Across Phospholipid Membranes“:

In accordance with these health concerns, Nel et al. have described some phenomena that can only potentiate fear of the negative health risks associated with nanotechnology.

[…]

Non-endocytotic transmembrane transport of large macromolecules is a significant exception to what is presently known about cell membrane permeability. Most early studies show that lipid bilayers are essentially impenetrable by molecules larger than water under physiological conditions: transport of most molecules across cell membranes is specifically cell-mediated by endocytosis.34 Endocytosis, unlike proposed passive, non-endocytotic transport, is an active cell-mediated process by which a substance gains entry into a cell. Specifically, a cell’s plasma membrane continuously invaginates to form vesicles around materials that originated outside the membrane: as the invagination continuously folds inward, the cell membrane constituents simultaneously reorganize in such a way that the material being transported into the cell is completely enclosed in a lipid bilayer, forming an endosome.35,36

[…]

The results suggest that a diffusive process of transport is not likely.

Figure 8 is particularly telling (!).

Capture

The article by Shayla Banerji and Mark Hayes has been cited 44 times.

 

Do nanoparticles deliver? Merck’s SmartFlares and other controversies

Leonid Schneider’s article starts with a summary of the stripy controversy and then moves on to the SmartFlare. Of particular interest is the quote from Luke Armstrong, formerly at EMD Millipore, which demonstrates that the company ought to be well aware that the probes detect nucleases rather than mRNAs. This begs the question of why they are still selling and advertising this product. Unfortunately, they did not provide a statement to Leonid. [Picture above is from Leonid’s post]

For Better Science

A large body of scientific nanotechnology literature is dedicated to the biomedical aspect of nanoparticle delivery into cells and tissues. The functionalization of the nanoparticle surface is designed to insure their specificity at targeting only a certain type of cells, such as cancers cells. Other technological approaches aim at the cargo design, in order to ensure the targeted release of various biologically active agents: small pharmacological substances, peptides or entire enzymes, or nucleotides such as regulatory small RNAs or even genes. There is however a main limitation to this approach: though cells do readily take up nanoparticles through specific membrane-bound receptor interaction (endocytosis) or randomly (pinocytosis), these nanoparticles hardly ever truly reach the inside of the cell, namely its nucleocytoplasmic space. Solid nanoparticles are namely continuously surrounded by the very same membrane barrier they first interacted with when entering the cell. These outer-cell membrane compartments mature into endosomal and then…

View original post 2,353 more words

Towards the end of the stripy controversy?

Last week saw the publication in PloS One of Quy Khac Ong and Francesco Stellacci’s response to Stirling et al “Critical Assessment of the Evidence for Striped Nanoparticles” published a year earlier (November 2014, I am one of the co-authors).

The controversy had started with our publication of Stripy Nanoparticles Revisited after a three year editorial process (2009-2012) and was followed by a large number of events at this blog, on PubPeer and a few other places.

Here is a short statement in response to Ong and Stellacci. Since theirs  was a response to Stirling et al, Julian Stirling was invited to referee their submission (report).

We are pleased that Ong and Stellacci have responded to our paper, Critical assessment of the evidence for striped nanoparticles, PLoS ONE 9 e108482 (2014). Each of their rebuttals of our critique has, however, already been addressed quite some time ago either in our original paper, in the extensive PubPeer threads associated with that paper (and its preprint arXiv version), and/or in a variety of blog posts. Indeed, arguably the strongest evidence against the claim that highly ordered stripes form in the ligand shell of suitably-functionalised nanoparticles comes from Stellacci and co-authors’ own recent work, published shortly after we submitted our PLOS ONE critique. This short and simple document compares the images acquired from ostensibly striped nanoparticles with control particles where, for the latter (and as claimed throughout the work of Stellacci et al.), stripes should not be present. We leave it to the reader to draw their own conclusions. At this point, we believe that little is to be gained from continuing our debate with Stellacci et al. We remain firmly of the opinion that the experimental data to date show no evidence for formation of the “highly ordered” striped morphology that has been claimed throughout the work of Stellacci and co-workers, and, for the reasons we have detailed at considerable length previously, do not find the counter-claims in Ong and Stellacci in any way compelling. We have therefore clearly reached an impasse. It is thus now up to the nanoscience community to come to its own judgement regarding the viability of the striped nanoparticle hypothesis. As such, we would very much welcome STM studies from independent groups not associated with any of the research teams involved in the controversy to date. For completeness, we append below the referee reports which JS submitted on Ong and Stellacci’s manuscript.

Julian Stirling, Raphaël Lévy, and Philip Moriarty November 16 2015

 

 

The death of Nanonymous

Before you worry: nobody died.
But it is really with great regret that I relay here Nanonymous’ decision “to retire the moniker” [see below]. Nanonymous was a clever handle and his/her comments have constituted important and enjoyable contributions to the stripy nanoparticles controversy. We first encountered Nanonymous in October 2013 at ChemBark commenting on the Response to ACS Nano Editorial on Reporting Misconduct where he/she defended post-publication peer review as a legitimate form of scientific discussion and urged authors to engage, notingIf this keeps up, “nano”science will get the reputation it deserves. What a shame.
Nanonymous became interested in the controversy; he/she was at the beginning undecided and looking at the scientific issues with an open mind, asking, still in the ChemBark thread

Raphael,
Do you have a response to (what I understand to be) the latest Stellacci article?
http://pubs.acs.org/doi/pdf/10.1021/la403546c

I mean, as someone who knows very little about this field I have a hard time understanding how one could demonstrate “stripiness” as a a scanning artifact…unless a bunch (more) people were wrong:
http://pubs.acs.org/doi/pdf/10.1021/la403546c

Since then Nanonymous made numerous contributions here and at PubPeer, with great scientific insights, many questions to me/Julian/Philip, forcing us to clarify our thinking further, as well as outstanding dissection of “unreg”[…] arguments and argumentative strategies.
Below is the last comment of Nanonymous, left this morning on the previous post.
nanonymous |

Raphael,
The latest post on pubpeer:

https://pubpeer.com/publications/58199FBEA31FB5755C750144088886#fb23615

falsely attributes authorship to my handle. It is certainly the same troll who has been spamming recently. My response isn’t showing up on pubpeer yet, I post it below. My, this is getting quite silly. I’m afraid the “encyclopedia dramatica” aspects will detract from the serious nature of the debate. I will probably sign up as registered peer to avoid this.
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The above post (Unreg February 1st, 2015 6:04pm UTC ) was not written by the real nanonymous (me). The poster (who is quite clearly associated with all the gish galloping) uses a deliberately sacchrin tone, perhaps for the purposes provoking a “spot the impostor” cliche:

http://tvtropes.org/pmwiki/pmwiki.php/Main/SpotTheImposter

The persistence of anonymous handles is a measure of how untrustworthy a forum can be, the fact that the above Unreg has approriated a handle that is not his/her own (this was already done once on the fakerapha site, there is no doubt that it is the unreg above is the same identity that is responsible for that site).

This is an attack against the utility of PubPeer since we must presume that the vast majority of comments that do not mention Russian brides, Nigerean banks or viagara are written in good faith and that no one would appropriate an established handle in good faith. This clearly demonstrates that we need to figure out ways around these attacks, we all knew this was inevitable. While the PubPeer admins certainly don’t have time, one could envision some sort of digital signature type scheme in PubPeer 2.0. (there are probably a few good reasons we don’t want mere registered usernames).

Suppose I don’t have much choice but to retire the moniker, any further posts labelled “nanonymous” are not written by me, the identity that assumed the (relatively) novel name during the course of learning about the stripy saga. I may consider joining as a regular Peer with my academic address, but will need to consider carefully for a bit.

I always thought that no one could possibly vest so much time and effort into trying to obfuscate facts about (what are to that vast majority of people) obscure subjects like nanoparticles but fakerapha/unreg/bionanochair/ProfSTM/gustav/weichen/etc. has proven me wrong. Learning that one is wrong anout something is perhaps the part that is most fun about internet discussions.

Identity theft: a new low in the stripy nanoparticles controversy

If you are familiar with the controversy and wonder why a PloS One comment thread disappeared today, skip directly to recent events.


Jackson et al, Nature Materials 2004

Jackson et al, Nature Materials, published 18 April 2004

In 2004, Alicia Jackson (now deputy director of the Biological Technologies office at DARPA), Jacob Myerson and Francesco Stellacci (now Constellium Professor at EPFL) mis-interpreted a common scanning probe microscopy artefact for a real structure. They submitted their results to Nature Materials, which published the work. This error was to become the starting point of a controversy which, more than 10 years later, is still unraveling.

Predrag Djuranovic

Predrag Djuranovic was a PhD student in Stellacci’s group at MIT

In 2005, concerns were raised by Predrag Djuranovic, then a student in Francesco Stellacci’s group. According to Lauren Wolf writing for Chemical & Engineering News last year:

he discussed his concerns with his department head at MIT […]. A few months later, an official investigation of Stellacci launched at MIT and Djuranovic left Stellacci’s research group. MIT closed its review three years later, in 2008, finding Stellacci not guilty of academic misconduct. The university did, however, suggest that Stellacci should do additional work to substantiate his 2004 findings.”

MIT's Building 10 and Great Dome; adapted from this  pic

MIT’s Building 10 and Great Dome; adapted from this pic

MIT was not convinced by the published data but instead of sharing those concerns with the scientific community, they kept them secret and Stellacci was asked to “substantiate” what he had published. This –trying to substantiate a structure which had been postulated to explain an experimental artefact– is what he has now been doing for more than 10 years… with over 30 articles published.

stripy nanoparticles revisited

Stripy Nanoparticles Revisited, published 23 Nov 2012

The controversy entered the public domain in 2012 with the publication of our article entitled Stripy Nanoparticles Revisited in Small: I was not aware of Predrag’s work but had come to the same conclusion. Francesco Stellacci published his response alongside our paper. He, and co-authors, also published several other articles around the same period. At the end of last year, Julian Stirling, and co-authors, published in PloS One an extensive Critical Assessment of the Evidence for Striped Nanoparticles which demonstrates that there is no evidence for the existence of the stripy nanoparticles. A response from Francesco Stellacci is still expected at PloS One.

Scientists interested in the details of the scientific arguments can refer to the articles linked to above (and references therein) as well as the blog posts and PubPeer discussions.

I wish this was all about science and differences of interpretation. I have touched previously on the re-use of figures in different articles. This eventually led to two corrections, one at Nature Materials and one at PNAS.  An EPFL investigation was triggered, opened, and, eventually, following the report of an international independent panel, closed. A third article, pretty much entirely based on data re-use, has not been corrected.

I decided to start blogging about the controversy after the publication of our article in 2012. I used the blog to present our paper, discuss the response (without having to wait three years), publish an invited post from Predrad Djuranovic, other experts (Philip Moriarty, Mathias Brust, and Quanmin Guo), and many other things . Other blogs and the post-publication peer review platform PubPeer also became important fora.

Unfortunately, just as the traditional literature has its flaws and can be gamed by scientists who do not respect the rules, so do these new modes of scientific communication. I have argued earlier that the stripy controversy was a window into the scientific process revealing the serious failures of self correction mechanisms. It is also a window into the frightening flaws of online post-publication peer review – I say this as a strong and determined supporter of post-publication peer review.

Those who believe in stripes have never engaged openly in the online debate (they have even vigorously complained that it was taking place, likening it to cyberbullying). Instead, we’ve had, in chronological order:

  • a troll posting over a period of two days a large number of comments on this blog… he eventually was identified as an Editor of the journal.
  • A fakerapha blog (that still exists) and a fakerapha twitter (the account has been removed) who impersonated me on the Chembark blog.
  • A text book case of Gish Gallop by “unreg” (a debating technique named after, and often used by, creationists) at PubPeer, It is to their immense credit that Julian Stirling, Philip Moriarty and several anonymous peers have engaged, repeatedly and honestly with “unreg”… until it became absolutely beyond doubt that this was no ordinary – if a little heated – discussion. Maybe best to let Nanonymous, an anonymous but insightful and regular commentator of the controversy describe that thread:

    Wow, the same thing again and again, in spite of being addressed again and again.

    and later

    […] it is interesting to reflect on the motivations for comments like these. They seem to come from an identity that either: 1)Does not understand basic scientific reasoning.2)Is vested in obfuscating some fairly straightforward arguments against clear and obvious errors in scientific work.Perhaps both. It could be just some random troll, but clear evidence that there are people acting in very bad faith out there.   Nanonymous

  • Possibly that thread also includes sockpuppetry with “unreg” and “ProfSTM/BioNanoChair” being the same person.

These things happened on blogs or at PubPeer, i.e. platforms which accept anonymous writing. It is hard to think of how they could be completely avoided while retaining anonymous comments.  The discussions of the costs/benefits of anonymous post-publication peer review is ongoing (I agree with Peer 1 in that thread).

In the last few weeks, the stripy nanoparticles discussion has moved to PloS One which enables comments directly on the article. Plos One has a clear policy requiring contributors to “unambiguously identify themselves with their first and last names, their geographic location, […] Any registered user who is found to have provided false name or location information will have their account suspended and any postings deleted.” In spite of this:

  • A “Gustav Dhror” posted over 10 comments (Gish Gallop again) about “Problems with Fig 4”. There is simply no doubt that Gustav is not a real person but instead a sockpuppet. There is no person with that name who has ever published any article on anything, let alone STM, nanoparticles or surface science. Even first year PhD students get their names listed on some website in academic institutions but  “Gustav Dhror” draws zero hits on Google, or more precisely two: the PloS One thread and a baby name website. After I posted a comment (and contacted PloS One) raising the issue of false identity, that thread stopped… but a few days later…
  • A “Dr Wei Chen” started another thread entitled “Multiple flaws with this paper“. The user profile linked to a real and existing Wei Chen, Professor at Suzhou Institute of Nano-Tech and Nano-Bionics in China. Given the context and previous events, I eventually took the liberty of calling Wei Chen to check whether he was “Wei Chen”, commenter at PloS One. And he was not. He had no idea. He had never posted anything at PloS One. Someone had stolen his identity to post these comments. Someone who wanted to discredit our paper (with flawed pseudo-scientific arguments), was not prepared to do it under their own name, but was prepare to steal someone else’s identity to do it.

PloS One has been contacted and has now removed the “Dr Wei Chen” thread. They have been in contact with “Gustav Dhror” and should post a statement regarding that thread tomorrow. In the paragraphs above, I have used links to WebArchives where you can see how the pages looked like this morning.