A birthday question

A rather one sided debate on stripy nanoparticles is taking place over on PubPeer and on Raphaël’s blog

An individual (“unregistered”) is engaging a good old Gish Gallop, having a hard squint in the dark and seeing patterns. It happens.

I have suggested that “unregistered” should turn their efforts to something more mundane, which is to explain the re-use of data across a number of paper from the Stellacci group.

To recap, in the papers from the Stellacci lab, there were a worrying number of instances of re-use of data, something Raphael and myself posted about in the past, e.g., here

These instances included re-using a figure in a subsequent paper to describe a completely different experiment. It is well worth noting that two of these instances of data re-use resulted in corrections, albeit after a degree of pressure was placed on editors (see here and here)

The timeframe for the implementation of the corrections was rapid, since it occurred between the acknowledgement of a problem by the editors and the publication of the correction. Yet the timeframe for accessing even a modicum of original data was slow and only occurred when Philip Moriarty contacted the Ombudsman at EPFL; moreover, access to these data, as people have noted on PubPeer and on Raphaël’s blog, is no longer possible.

Happy birthday
It is over a year since the data re-use problem was brought to the attention of all the editors concerned. In two instances (re-use of a figure between main paper and SI of a JACS article and re-use from JACS and J Phys Chem in JSPM article) there has been no acknowledgement in these papers that the data are not original. This correlates perfectly with editors failing to engage when they were first contacted. It also suggests that the authors will not correct the record unless pushed to do so by editors. A conclusion would be that the authors are not too fussed about correcting their record, unless pressured to do so.

If one takes a look at the wider literature, it would seem that there are three outcomes possible for the same issue of data re-use:
Nothing happens
A correction
A retraction

So my post on the inconsistencies of journal reactions to data re-use, Correct Corrections, is still valid and certainly highlights the major inconsistencies that exist, not just in stripy nanoparticles, but across the entire science publishing edifice.

A year down the line and I still await an explanation as to why data re-use occurred in these papers on stripy nanoparticles and why only some instances have been corrected. It would also be useful if journals more logical in science publication and settled for one or two of the three options above when faced by data re-use.

Gradually, the structural problems in sciences are making their way to the surface. There have been articles in newspapers, The Economist and other magazines around the world on the subject. These are stimulated by the constant dripping of information and studies that sit awkwardly with the perceived notion of how science functions.

The high profile controversies tend to catch our attention, simply because of a sense of outrage amongst the wider community that nothing has been done to fix the problem, or that the fixes have been inadequate. Despite the outrage, it remains the case that only a very few are willing to put their head above the parapet and say something. There has been an interesting discussion of this on Athene Donald’s blog here.

Not surprisingly, the “reproducibility question” has gained quite a lot of traction( e.g., here and here). This leads to a simple question: what qualifies as a reproduction?

I argue that an important aspect of reproduction is that it is not necessarily actual reproduction, but a re-examination of observations made with better methods, which includes analytical tools. I have two examples of how scientists deal with the changing landscape of data and their interpretation in these circumstances. The first example is an instance of good practice and is common (or should be). The second seems to ignore the past and the clear message provided by the new data.

Example 1
This is from an excellent 2012 paper in Journal of Biological Chemistry that we discussed (again) in a recent lab meeting. It deals with the molecular basis for one member of the fibroblast growth factor family, FGF-1, being a universal ligand. That is, FGF-1 can bind all FGF receptor isoforms, whereas other FGFs show clear restriction in their specificity. These differences must lie in the structural basis of the recognition of the FGF ligand, the FGF receptor and the heparan suflate co-receptor. The first model put forward by Moosa Mohamadi was superseded in his 2012 paper, when he and his group obtained higher resolution structures of the complexes. This is a great step forward, as FGFs are not just important to basic biology, but they also impact on a wide range of diseases, as well as tissue homeostasis and regeneration. I highlight the following from the paper:
To quote (page 3073, top right column)
“Based on our new FGF1-FGFR2b and FGF1-FGFR1c structures, we can conclude that the promiscuity of FGF1 toward FGFR isoforms cannot be attributed to the fact that FGF1 does not rely on the alternatively spliced betaC’-betaE loop of FGFR for binding as we initially proposed (31).”

This paper provides a great example of how science progresses and is how we should all deal with the normal refinement of data and the implications of such refinements.

Example 2
This is from the continued discussions on whether the ligands on the surface of gold nanoparticles can phase separate into stripes. This has been the subject of a good many posts on Raphael Lévy’s blog (from here to here), following his publication a year ago of his paper entitled “Stripy nanoparticles revisited“, as well as commentary here and elsewhere.

Some more papers from Stellacci and collaborators have been published in 2013. The entire oeuvre has been examined in detail by others, with guest posts on Raphael Lévy’s blog (most recent here) and comments on PubPeer relating to a paper on ArXiv that takes apart the entire body of evidence for stripes.

What is quite clear, even to a non-specialist, is that the basics of experimental science had not been followed in the Stellacci papers on the organisation of ligands on nanoparticles published from 2004 to 2012. These basics include the importance of signal being greater than noise and ensuring that experimental data sample at sufficient depth to avoid interpolation; note that in no cases did instrumentation limitation require interpolation. This might happen to any of us, we are, after all “enthusiasts”.

To conclude, I refer to my quote from Seneca “Errare humanum est sed perseverare diabolicum

This excellent advice is clearly being followed by one FGF lab. It would be good if this advice was adopted more generally across science. When we see real data and analysis (the hard stuff) that challenges our previous data and interpretations, we should all be happy to change these. This is how science (should) move forward. If everyone did this, then there would be no discussion regarding reproducibility. When we see more of the same stuff, without a clear hypothesis testing experiment, we are veering towards metaphysics.

Metaphysics is not science. I note that when data are hidden, so that analysis is restricted, we again enter the realm of metaphysics – hence, for example, the call for open access to clinical trials data.

Links with some relevance to the Seneca’s advice, reproducibility and so on:
There is an excellent post at The Curious Wavefunction’s Sci Am blog
PubPeer: here and here
Neuroskeptic’s post at Discover
Chembark’s post in response to an ACS Nano editorial on reporting misconduct.

Last post of the year, perhaps – I have a couple of others brewing, but they need some thought. This has been an unusual year in some ways. First, a big thanks to all my readers – I know a few of you and I hope that my occasional posts are of some interest to you.

To start at the end, I enjoyed this year’s Royal Institution Christmas lectures, though I have a whinge. Why was hyaluronic acid called a protein. It isn’t. It is a glycosaminoglycan, polysaccharide, sugar, carbohydrate, polymer, but NOT a protein. Crucially, it is a secondary gene product. Polysaccharide synthesis is the consequence of the activity of enzymes, primary gene products, but the regulation of polysaccharide synthesis is at the whim of cell and organism physiology and only indirectly by the genome. This, I think, makes the entire business of the mole rat living longer than equivalent rodents and being cancer free even more interesting. If one can have “p53″ named in the lecture, why not define hyaluronic acid correctly? Or is there a fear amongst those working with the central dogma of the messiness of things beyond? Generally, where things are messy in science is where the most interesting stuff is. Glycobiology is certainly messy, sticky and most interesting and I recommend it strongly to all – it is likely also to contribute to getting us out of the mess of global warming. Continue Reading »

Small world

This post highlights links to the American Civil war that I have unknowingly walked by in two European cities at different stages in life. Continue Reading »

I’ve had a few requests for the recipe for roast leg of lamb. This is rather simple. Total roasting time, 1 h per kg, at half time, turn leg.
Put the oven on high, (gas 8), put leg in roasting tray with ample fat (I use margarine), after 10 min put in 1 onion and 1 carrot chopped and turn down to gas 7.
When there is 1 h left, shift roast to bottom of oven, turn oven up to 8 and start the roast vegetables (I use a mix of parsnips, sweet potatoes and half boiled King Edwards).

Letting the roast stand and gravy follow standard procedures.

However, in my opinion, a far more interesting seasonal recipe is one I received some dozen years ago, which celebrates elements of my Irish-French heritage!

This is the “Recette Irlandaise pour préparer une bonne dinde au Whisky” set out below.
Continue Reading »

Lots of tweets on the subject of great reads in the run up to Christmas, and, reflecting my preponderance for following science, most have been science flavoured. At the start of October this year I came across an article in the Guardian on a new translation of Herodotus’ Histories.
This is my Christmas read and I am extremely impressed. I knew of Herodotus, but had never read his work. Not without controversy in the ancient and modern world, there is no doubt that he does indeed present evidence and the source, and often weighs up the quality of the evidence. I find this refreshing, because in science now we seem to have drifted into territory where the quality of data are often ignored and the conclusion, regardless of the quality of the data is all. The truth is the opposite; data are everything, though truth remains awkward at the best of times.

This impacts directly on the growing debate on the reproducibility of science, also called the replication problem, which has recently elicited a fair amount of discussion, e.g., here and here. Continue Reading »

Many have been deeply offended by the reaction of one “Ofek”, whose request for free posting on Biology Online in return for ‘exposure’ was met by the prospective author , DN Lee, with a very polite “Thanks, but no thanks”. Ofek’s response was to call the prospective author a “whore”.

Unbelievable. But true.

It gets worse. Continue Reading »


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