The war on (scientific) terror…

I’ve been otherwise occupied of late so the blog has had to take a back seat. I’m therefore coming to this particular story rather late in the day. Nonetheless, it’s on an exceptionally important theme that is at the core of how scientific publishing, scientific critique, and, therefore, science itself should evolve. That type of question doesn’t have a sell-by date so I hope my tardiness can be excused.

The story involves a colleague and friend who has courageously put his head above the parapet (on a number of occasions over the years) to highlight just where peer review goes wrong. And time and again he’s gotten viciously castigated by (some) senior scientists for doing nothing more than critiquing published data in as open and transparent a fashion as possible. In other words, he’s been pilloried (by pillars of the scientific community) for daring to suggest that we do science the way it should be done.

This time, he’s been called a…wait for it…scientific terrorist. And by none other than the most cited chemist in the world over the last decade (well, from 2000 – 2010): Chad A Mirkin. According to his Wiki page, Mirkin “was the first chemist to be elected into all three branches of the National Academies. He has published over 700 manuscripts (Google Scholar H-index = 163) and has over 1100 patents and patent applications (over 300 issued, over 80% licensed as of April 1, 2018). These discoveries and innovations have led to over 2000 commercial products that are being used worldwide.”

With that pedigree, this guy must really have done something truly appalling for Mirkin to call him a scientific terrorist (oh, and a zealot, and a narcissist), right? Well, let’s see…

raphaportrait2The colleague in question is Raphael Levy. Raphael (pictured to the right) is a Senior Lecturer — or Associate Professor to use the term increasingly preferred by UK universities and traditionally used by our academic cousins across the pond — in Biochemistry at the University of Liverpool. He has a deep and laudable commitment to open science and the evolution of the peer review system towards a more transparent and accountable ethos.

Along with Julian Stirling, who was a PhD student here at Nottingham at the time, and a number of other colleagues, I collaborated closely with Raphael and his team (from about 2012 – 2014) in critiquing and contesting a body of work that claimed that stripes (with ostensibly fascinating physicochemical and biological properties) formed on the surface of suitably functionalised nanoparticles. I’m not going to revisit the “stripy” nanoparticle debate here. If you’re interested, see Refs [1-5] below. Raphael’s blog , which I thoroughly recommend, also has detailed bibliographies for the stripy nanoparticle controversy.

More recently, Raphael and his co-workers at Liverpool have found significant and worrying deficiencies in claims regarding the efficacy of what are known as SmartFlares. (Let me translate that academically-nuanced wording: Apparently, they don’t work.) Chad Mirkin played a major role in the development of SmartFlares, which are claimed to detect RNA in living cells and were sold by SigmaMilliPore from 2013 until recently, when they were taken off the market.

The SmartFlare concept is relatively straight-forward to understand (even for this particular squalid state physicist, who tends to get overwhelmed by molecules much larger than CO): each ‘flare’  probe comprises a gold nanoparticle attached to an oligonucleotide (that encodes a target sequence) and a fluorophore, which does not emit fluorescence as long as it’s near to the gold particle. When the probe meets the target RNA, however, this displaces the fluorophore (thus reducing the coupling to, and quenching by, the gold nanoparticle) and causes it to glow (or ‘flare’). Or so it’s claimed.

As described in a recent article in The Scientist, however, there is compelling evidence from a growing number of sources, including, in particular, Raphael’s own group, that SmartFlares simply aren’t up to the job. Raphael’s argument, for which he has strong supporting data (from electron-, fluorescence- and photothermal microscopy), is that the probes are trapped in endocytic compartments and get nowhere near the RNA they’re meant to target.

Mirkin, as one might expect, vigorously claims otherwise. That’s, of course, entirely his prerogative. What’s most definitely not his prerogative, however, is to launch hyperbolic personal attacks at a critic of his work. As Raphael describes over at his blog, he asked the following question at the end of a talk Mirkin gave at the American Chemical Society meeting in Boston a month ago:

In science, we need to share the bad news as well as the good news. In your introduction you mentioned four clinical trials. One of them has reported. It showed no efficacy and Purdue Pharma which was supposed to develop the drug decided not to pursue further. You also said that 1600 forms of NanoFlares were commercially available. This is not true anymore as the distributor has pulled the product because it does not work. Finally, I have a question: what is the percentage of nanoparticles that escape the endosome?

According to Raphael’s description (which is supported by others at the conference — see below), Mirkin’s response was ad hominem in the extreme:

[Mirkin said that]…no one is reading my blog (who cares),  no one agrees with me; he called me a “scientific zealot” and a “scientific terrorist”.

Raphael and I have been in a similar situation before with regard to scientific critique not exactly being handled with good grace. We and our colleagues have faced accusations of being cyber-bullies — and, worse, fake blogs and identity theft were used –to attempt to discredit our (purely scientific) criticism.

Science is in a very bad place indeed if detailed criticism of a scientist’s work is dismissed aggressively as scientific terrorism/zealotry. We are, of course, all emotional beings to a greater or lesser extent. Therefore, and despite protestations to the contrary from those who have an exceptionally naive view of The Scientific Method, science is not some wholly objective monolith that arrives at The Truth by somehow bypassing all the messy business of being human. As Neuroskeptic described so well in a blog post about the stripy nanoparticle furore, often professional criticism is taken very personally by scientists (whose self-image and self-confidence can be intimately connected to the success of the science we do). Criticism of our work can therefore often feel like criticism of us.

But as scientists we have to recognise, and then always strive to rise above, those very human responses; to take on board, rather than aggressively dismiss out of hand, valid criticisms of our work. This is not at all easy, as PhD Comics among others has pointed out:

One would hope, however, that a scientist of Mirkin’s calibre would set an example, especially at a conference with the high profile of the annual ACS meeting. As a scientist who witnessed the exchange between Raphael and Mirkin put it,

I witnessed an interaction between two scientists. One asks his questions gracefully and one responding in a manner unbecoming of a Linus Pauling Medalist. It took courage to stand in front of a packed room of scientists and peers to ask those questions that deserved an answer in a non-aggressive manner. It took even more courage to not become reactive when the respondent is aggressive and belittling. I certainly commended Raphael Levy for how he handled the aggressive response from Chad Mirkin.

Or, as James Wilking put it somewhat more pithily:

An apology from Mirkin doesn’t seem to be forthcoming. This is a shame, to put it mildly. What I found rather more disturbing than Mirkin’s overwrought accusation of scientific terrorism, however, was the reaction of an anonymous scientist in that article in The Scientist:

“I think what everyone has to understand is that unhealthy discussion leads to unsuccessful funding applications, with referees pointing out that there is a controversy in the matter. Referee statements like these . . . in a highly competitive environment for funding, simply drain the funding away of this topic,” he writes in an email to The Scientist. He believes a recent grant application of his related to the topic was rejected for this reason, he adds.

This is a shockingly disturbing mindset. Here we have a scientist bemoaning that (s)he did not get public funding because of what is described as “unhealthy” public discussion and controversy about an area of science. Better that we all keep schtum about any possible problems and milk the public purse for as much grant funding as possible, right?

That attitude stinks to high heaven. If it takes some scientific terrorism to shoot it down in flames then sign me up.


[1] Stripy Nanoparticle Controversy Blows Up

[2] Peer Review In Public: Rise Of The Cyber-Bullies? 

[3] Looking At Nothing, Seeing A Lot

[4] Critical Assessment of the Evidence for Striped Nanoparticles, Julian Stirling et al, PLOS ONE 9 e108482 (2014)

[5] How can we trust scientific publishers with our work if they won’t play fair?

 

 

 

Author: Philip Moriarty

Physicist. Metal fan. Father of three. Step-dad to be. Substantially worse half to my fiancée Lori, whose patience with my Spinal Tap obsession goes to far beyond 11...

6 thoughts on “The war on (scientific) terror…”

  1. “I think what everyone has to understand is that unhealthy discussion leads to unsuccessful funding applications, with referees pointing out that there is a controversy in the matter.” I’ve long assumed that this consideration – how “forward-moving” and clear-cut a field of research appears to the public – was one of the main reasons for the stubborn refusal of journals to publish critical commentary – leading to the invention of alternative platforms. This is a side-effect of relying on bureaucrats to determine who gets to be a “scientist,” and it selects for self-promoters, for fraud, both intellectual and outright, and for generations of uncritical thinkers who, e.g. in the case of visual neuroscience, are willing to settle comfortably into ancient paradigms that defy both logic and fact (e.g. https://mythsofvisionscience.wordpress.com/2018/09/13/shadlen-kiani-2013-explain-sdt-and-i-respond/). I believe the desire for apparently risk-free approaches has led to the general acceptance of post hoc – “data-driven” – analysis (correlation-fishing of data generated via simplistic, uncritically-adopted assumptions) , which is in principle the same – just as invalid – as p-hacking etc.

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  2. “Better that we all keep schtum about any possible problems and milk the public purse for as much grant funding as possible, right?”

    Actually that’s exactly the impression I got from interactions with some American PIs in the biomed area (not all, of course, but this attitude appears to be quite popular).

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  3. How such discussions impact funding seems to explain the hostility better than other reasons. It seems everyone is rabidly protecting their careers in an environment where mistakes seem fatal. Maybe the older scientists can give a word about the problems of authoritarianism and vanity, but the pragmatic understanding seems to go through the careers and funding: there is a material concern in the end.

    Being a small fish in the field, and knowing some of the people involved, well, I beg for my anonymity. But didn’t Raphael just voice what Merck already put to practice? Has Mirkin called Merck “terrorists” too? Also, another lesson on thinking very hard about who gets labelled as “terrorists” in this world….

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