join the discussion of the previous post

It’s happening on Twitter.

There is a Storify here to catch up.

I am looking for examples of convincing experimental demonstration of nanoparticles diffusing through membranes (if there are any). Please tweet your suggestions to  or add in the comments sections of this post.

We are doomed…

not because of the risks of nanotechnology but because of a broken scientific system.

Last week, I had the privilege of opening, as the first invited speaker, a symposium on ‘Converging technology for nanobio applications’. This was my first slide:

Collage of various images. See links in the paragraph below for reference and credits.

Collage of various images. Credits: top left “Shutterstock”, top right “Cathy Wilcox”, bottom left “Jeremy M. Lange for The New York Times, A scientist at Duke University measures silver nanoparticles”, bottom center “Terminator 3: Rise of the Machines – a vision surely now only decades away. Photograph: Observer”, bottom right “image courtesy of Oregon State University”. See links in the paragraph below for original publication.

 

I started my talk by asking the audience what these images had in common (I did point out that the one in the top right corner was, in my experience, scientifically accurate).   The answer? These pictures had all been used to illustrate nanoparticle news in the previous week.

Exotic Nanomaterials Claimed Their First Major Workplace Injury said Stephen Leahy, writing for Motherboard on Tuesday about a worker injured by nanonickel while working without protection. The same day, Andrew Maynard, in Slate, published a more reasonable viewpoint on this same event. On Thursday, the Sydney Herald Tribune reported that a ‘Green group [had] called for ban of nano-materials in food’. This has been amplified in various outlets and, Andrew Maynard (again!) attempted to correct the record in the Conversation. On Friday, Deborah Blum, writing on the New York Times blog said that “Silver [is] Too Small to See, but Everywhere You Look”. The same day, Ben Baumont-Thomas informed us in  the Guardian blog that scientists had created bionic particles ‘inspired by Terminator’. Apparently, the latter piece was tongue in cheek, but it is rather difficult to differentiate the satire from the real thing these days (see for example Salon‘s coverage of the same story here).

While these stories are very different, they all originate in peer reviewed scientific research.

The “inspired by Terminator” piece originally comes from a press release by the University of Michigan. The authors of the article and their PR department were seeking this kind of publicity: the original article (very interesting BTW) uses the word “bionic” and the press release starts with “Inspired by fictional cyborgs like Terminator…”. Good to get coverage but it is highly debatable whether this kind of analogies really help improve the general understanding of science.

Deborah Blum article is measured and well researched – as we would expect from this award-winning science journalist – and based on multiple interviews with scientists. Yet in some ways, it also reflects the deep problems we are facing with establishing solid evidence in support of scientific understanding, and, eventually, policy making.

Deborah Blum article quotes Elisabeth Loboa as saying that “There’s evidence that the particles penetrate into plasma membranes, and they can disrupt cell function” [link in the original article, which is excellent practice!]. The idea that nanoparticles can go through the membrane of cells is so often repeated that it must be true, right? Scientists making those sorts of claim should provide a very high level of proof (unfortunately, this does not happen during peer review) because there are at least two fundamental reasons to be highly skeptical of such claims, one related to evolution, and another one related to physical chemistry and thermodynamics.

Nanoparticles are of similar size to viruses. If viruses could so easily penetrate cells, we would not be here discussing the risk of nanoparticles. Thankfully, during evolution, cells have developed very advanced mechanisms to protect themselves from foreign objects. Viruses too have developed very advanced mechanisms to get in there. Quite simply none of the nanomaterials made in the lab today seriously approach the level of sophistication that viruses use to get access to the interior of the cell (see this movie for an example). The linked article by AshaRani et al provides no evidence of particles penetrating through the plasma membrane (apart from the table of content cartoon). The dose used in this particular study is huge: 200 micrograms of nanomaterials per mL of medium (the equivalent of 100 grams of silver for a 50 kg person). In line with many other studies (including our own work), AshaRani et al show nanoparticles overwhelmingly in endosomes, i.e. in bags inside cells where they are isolated from the cell machinery. Endosomal trapping also remains a major limiting factor to siRNA delivery (even using nanoparticles).

Ignoring now the biology, at the simplest level, the membrane of cells is made of a bilayer of lipids. It has an hydrophobic interior and two hydrophilic surfaces. For an object to diffuse through the membrane, it would need to have no significant repulsive or attractive interactions with any of these components (otherwise it would be repelled and not go through, or attracted and then get stuck). It is hard to imagine any nanoparticle that would fulfill such criteria (see also post and comments here for more details). While it is unclear that any nanoparticle can diffuse through the membrane, many small molecules can. We therefore have this strange situation where the supposed capability of nanoparticles to go through the cell membrane is presented as a reason to be particularly worried even though this is unproven, unlikely for nanomaterials, and common for many smaller compounds (e.g. DAPI).

I am not blaming Deborah Blum nor  Elisabeth Loboa for this confusion. Such statements have become the norm. Although a more detailed investigation would be necessary (and I am not qualified to do it though I’d be happy to collaborate), my hypothesis is that the confusion results from a combination of nano hype (both in terms of risks and potential applications – see the Terminator for one striking example), bias towards the publication of positive findings, absence of post-publication peer review and debate, and poor scientific standards in an interdisciplinary area where editors and referees often lack some of the skills to properly evaluate the work (e.g. material scientists with very little understanding of biology, etc).

The situation is however now extremely serious since it has reached the point where it affects understanding of science for both basic scientists and the general public. It is our responsibility to try to fix the system.

‘Nanoscience debate rages on’ by Jon Cartwright

Writing for Physics World, the member magazine of the Institute of Physics, Jon Cartwright sums up the history and current state of the stripy nanoparticles controversy.

Here is one excerpt:

Stellacci himself was notably absent from the online discussions, but they did prompt him in October last year to publish work in collaboration with two independent groups led by Christoph Renner at the University of Geneva in Switzerland and Steven De Feyter at the University of Leuven in Belgium. The works, which were published in the journals ACS Nano (8529) and Langmuir (29 13723), sought to corroborate Stellacci’s original evidence with more advanced STM techniques. Unfortunately, they muddied the water even more: despite the images appearing almost stripe-free at first glance, the authors claimed that their analysis had indeed shown the stripe-like features to be present.

You can read the entire article here.

The above excerpt is particularly important if you consider this (unfortunately anonymous and therefore impossible to confirm) comment published at PubPeer:

As a reviewer of one of the recent papers, I asked specifically for the authors to address the discrepancy between the stripes so easily visible in the original paper and the stripes that I struggled to see in the present work. It’s disappointing that this wasn’t really addressed.

 

 

Big tussle over tiny particles, by Lauren K. Wolf , C&EN

Lauren K. Wolf has written a nice overview of the stripy nanoparticle controversy for Chemical & Engineering News, the weekly magazine published by the American Chemical Society. It starts like this:

AS TRUTH SEEKERS, scientists often challenge one another’s work and debate over the details. At the first-ever international scientific conference, for instance, leading chemists argued vociferously over how to define a molecule’s formula. A lot of very smart people at the meeting, held in Germany in 1860, insisted that water was
OH, while others fought for H 2 O.

That squabble might seem tame compared with a dispute that’s been raging
in the nanoscience community during the past decade. [...]

Read it all here… if you have access. If you don’t, email me and I will send you a pdf.

 

9th of May is Open Access day at the IIB

I am delighted to announce that we will have two external speakers on the 9th of May:

Stephen Curry, Open Access for Academics – the problems and the potential

Michelle Brook,  The cost of academic publishing

 

The talks will take place from noon in LT2, Biological Sciences building. They will be followed by sandwiches and discussions in the common room. University Librarian Phil Sykes will join us too (see him talking about open access here).
At 2 pm, IIB academics will also be invited to a University of Liverpool open access roadshow (SR6). See below for details.

Stephen Curry

Stephen Curry

Stephen Curry is Professor of structural biology at Imperial College London. He is an open access advocate. He blogs at the Reciprocal Space and at the Guardian. You can find him on Twitter@Stephen_Curry.

Michelle

Michelle Brook

Michelle Brook blogs at Quantumplations and works with the Open Knowledge Foundation where she recently published a blog about the cost of academic publishing. You can find her on Twitter @MLBrook.

 

 

* University of Liverpool Open Access roadshow

Presentations from the library (Martin Wolf) and Research Policy (Jane Rees) will explain current funder requirements for OA, and explain how the new institutional repository can help make your publications OA compliant. In addition, we will be high-lighting some of the issues to be considered in developing an Institutional Policy on Open Access. There will be time for questions during the session.

April in Singapore – First Month, First Impressions

I am PhD student in Raphaël’s group, now in Singapore, where I will spend two years of my PhD working at the Institute of Materials Research and Engineering (IMRE).

In a couple of days it will be a month since I moved here. On my farewell night out in Liverpool, Raphaël asked me if I was going to write a post for his blog once in Singapore, I thought, why not! The idea of a blog post from Singapore then became a monthly blog from Singapore and I am now writing about my April in Singapore.

The first thing I want to talk about is quite obvious: the food. The food is great and inexpensive. According to The Economist, Singapore is the most expensive city in the world, but I am sure they haven’t considered the food prices when they came to this conclusion (they might have considered the cheese prices though ;) ). Here there are food courts, which are food centers with stalls selling food ranging from pig’s organ soups to the five different types of Chinese noodles, from Indian fish head curry served with paratha to Singaporean chicken rice and Japanese tempura. The food courts can be fancy ones when inside air-conditioned shopping malls or open-air with more traditional dishes. And when I said that the food is inexpensive I meant that with £2 you can eat a proper dish! I am then not surprised that people here do not use to cook!
The Institute where I am working is inside the National University of Singapore campus and so far I have been in three different canteens that are basically food courts inside different departments (almost as it is in Liverpool ;) ).
Also, the first time I went to the supermarket I was surprised to see all the products that Singapore imports from Europe; I found many Italian and French brands that I have never found in Liverpool. Huge modern shopping malls are everywhere with quite impressive lists of restaurant/fast food chains inside. I have also found the French bakery Paul and it brought back nice memories of when I used to live in Paris.
On one hand I find Singapore deeply Westernized, the number of shopping malls is something unbelievable (and somehow scary) and in each of them  there are the same fast food chains and more or less the same shops, but on the other hand I think that the culture of  food here is great and different from any other place! The food traditions of the different ethnic groups who migrated and live here (Singapore is 74% Chinese, 13% Malay, 9% Indian, and 3% Eurasian) have resisted the westernization of the country and made the Singaporean food very unique; I would even say that Singaporean cuisine is the coexistence of other Asian countries cuisines over 710 km²!

The Parkroyal Hotel Garden in Singapore. I found it very suggestive with gardens and plants merged in the glass and steel.

.