Richard Jones – Page 44 – Soft Machines, by Richard Jones

A cross-section of science at the Royal Society

I’ve been attending the New Fellows seminar at the Royal Society, the UK’s national academy of science. This is the occasion for the 44 new fellows that are elected each year (one of whom, this year, was me) to give a brief talk about their research. The resulting seminar is a fascinating snapshot of the whole breadth of current science and technology, of a kind that one rarely sees in today’s world of science specialization. Here are some impressions of the first day.

Biology is strongly represented, with a cluster of talks on various aspects of cell signaling, ranging from the details by which signaling molecules are switched on and off, to the ways stem cells are regulated. A revealing talk showed how electron microscopy could unravel the mechanism by which the remarkable machines that ensure proteins fold correctly – chaperonins – work. From environmental and earth science we had talks on the effects on our environment both of the forces of nature – in the shape of the relationship between long term climate change and variations in the sun’s activity – and of the effects of man, through the impact of our industrial society on atmospheric chemistry. In physics, there was a spread from the most pure aspects of the subject (how to measure the spin of a black hole) to the applied and commercially important (the molecular beam epitaxy technique that underlies much of current semiconductor nanotechnology). One thing that comes out very strongly from the talks are the unexpected unifying threads that run through what appear on the face of it to be very different pieces of science. Ideas from statistical mechanics, like entropy, are obviously important for understanding self-assembly in soft matter, but they also cropped up in talks about signal processing in the brain and in modelling the growth of cities.

The important relationship between science and society was highlighted in two contrasting talks about the application of science to solve problems in the developing world. In one, the talk was at an abstract level, highlighting the problems of governance and economics in Africa that made it difficult to apply existing science to solve pressing problems. These abstract ideas were made very concrete in a fascinating talk about the development of new combination therapies to overcome the problems caused by drug-resistance in malaria. The foundation of these therapies is a new anti-malarial, artemesinin, recently discovered by Chinese scientists on the basis of a remedy from traditional chinese herbal medicine. Now that effective remedies are available, the problems to overcome are the social, economic and political barriers that prevent them from being universally available.

A round-up of nano-blogs

To mark the growing popularity of science-based blogs, here’s a quick roundup of some blogs devoted to nanotechnology. Nanotechnology means many things to different people, and this diversity of points of view is reflected in the wide variety of perspectives on offer in the blogs.

From the point of view of business and the financial markets, TNTlog comes from Tim Harper, of the European consulting firm Cientifica. His posting frequency has dropped off recently, which is a pity, since this is a blog that manages to be both entertaining and well-informed, with a healthy scepticism about some of the wilder claims made on behalf of the “nanotechnology industry”. The web-portal nanotechnology.com hosts a contrasting pair of blogs. blog | nano, by Darrell Brookstein, is at the shriller end of the nanobusiness spectrum, while Steve Edwards’s blog combines commentary on nano financial markets with the odd extract from his (rather good) book – The Nanotech Pioneers.

Among blogs written by academics, there are those that come from scientists working inside the field, and some from social scientists whose interests run more towards the social issues surrounding nanotechnology. In the first category we have Nanoscale Views, by academic nanophysicist Doug Natelson. This combines capsule reviews of new condensed matter preprints and conference reports with more general observations about life as a junior faculty, and is at quite a high technical level. Martyn Amos is a computer scientist; his blog covers issues such as synthetic biology and chemical computing. The authors of Molecular Torch seem to be keen to keep their identities quiet, but from what they cover I’m guessing they work in the field of nanochemistry, with a particular interest in quantum dots. If you want to know what Soft Machines is about, just look around.

From the social science side of things, David Berube’s Nanohype casts a sceptical eye on the scene, leavening fairly detailed commentary on various reports and conferences with his enjoyably acerbic humour. Nano|Public, Dietram Scheufele, similarly covers public engagement issues from an academic point of view. Nanotechbuzz by George Elvin, is more general in its coverage, which reflects the interests of its author, an architecture professor with interest the relationship between nanotechnology and design.

A couple of blogs reflect the views of those interested in Drexler’s vision of molecular nanotechnology. The current market leader in the faith-based end of this space is Responsible Nanotechnology, from the Center for Responsible Nanotechnology, aka Mike Treder and Chris Phoenix. This pair have the most impressive output in terms of sheer volume. Their analysis is predicated on the unsupported assertion that desktop nanofactories could be with us in 10-15 years; any dissent from this view is met, not with rational argument, but with accusations of bad faith or scientific fraud. Nanodot, from the Foresight Nanotech Institute’s Christine Peterson, represents the more acceptable face of Drexlerism, combining reporting on current nanoscience developments and commentary about social and economic issues, with discussion of longer-ranged prospects, albeit in a framework of thorough-going technological determinism.

Finally, we have a couple of blogs written by professional writers. Howard Lovy’s Nanobot was a useful source of nano- commentary, particularly strong on charting the influence of nanotechnology on popular culture, before Howard’s move to the darkside of public relations led to a quiet period. Nanobot has recently gently restarted. A very welcome newcomer is homunculus from my favourite science writer, Philip Ball. The scope of homunculus goes well beyond nanotechnology, covering aspects of chemistry and physics ranging from the application of statistical mechanics to financial markets to the historical links between chemistry and fine arts. His most recent post contains much of the useful background information that didn’t make it into his recent news piece for Nature about the potential neurotoxicity of nanoscale titania.

My apologies to anyone I’ve missed out.

Soft soaping hard matter

Self-assembly is an elegant and scalable way of making complex nanoscale structures. But it only works for soft matter – the archetypal self-assembling systems are bars of soap and pots of hair gel; they’re soft because the energies that cause their components to stick together are comparable with the energies of thermal agitation. Is there a way of overcoming this limitation, and using self-assembly to make complex nanoscale structures from hard materials, like ceramics and (inorganic) semiconductors? There is – one can use the soft structure to template the synthesis of the harder material, so that the hard material takes up the intricate structure of the soft, self-assembled structure one starts with. It’s possible to use this templating technique to make glass-like materials, using so-called sol-gel chemistry. But up to now it’s not been possible to make templated, nanostructured elemental semiconductors like silicon or germanium. Two papers in this week’s Nature (Editor’s summary, with links to full articles and commentary, for which subscription is required) report the achievement of this goal for the case of germanium.

To do this, the first requirement is a chemistry for synthesising germanium that works in solution at moderate temperatures. No such chemistry exists that uses water, so another solvent system is needed, together with a compatible surfactant that self-assembles in this solvent. The two papers manage to overcome these barriers in ways that are different in detail, but similar in principle. Sarah Tolbert’s group, from UCLA, uses ethylene diamine as the solvent and the cationic surfactant CTEAB (a very similar molecule to that found in some mild domestic disinfectants) to form the self-assembled nanostructures, which in their case took the form of hexagonally packed rods. Mercouri Kanatzidis’s group at Michigan State used formamide as the solvent and a somewhat different cationic surfactant (EMBHEAB). Both groups used variants of the so-called Zintl salts, in which germanium is combined with a reactive metal like potassium or magnesium.

In both cases the germanium is disordered on the atomic scale, but with good long-ranged order on the larger length-scales, that reflects the relative perfection of the original self-assembled soapy structure. The UCLA group manage to remove the surfactant, leaving a nicely hydrogen-terminated germanium. The Michigan State group were unable to get rid of their surfactant, but on the positive side the structure they formed was the very beautiful and potentially useful gyroid phase, a high-symmetry structure (see the picture) in which both the material and the pores are continuous. Immediate uses of these structures follow from the fact that the optoelectronic properties of the material are strongly affected by its nanostructured form, and can be further changed by adsorption of matter on the semiconductor’s surfaces, offering potential sensor applications.

the gyroid phase

The gyroid phase, a cubic bicontinuous structure formed by some self-assembling surfactant systems. This structure has now been formed from elemental germanium using a templating process.

Debating Radical Nanotechnology

Philip Moriarty reports that the Nottingham Nanotechnology Debate can now be viewed on streaming video here. The debate, held last summer, featured two proponents of Drexler’s vision of molecular nanotechnology, Josh Storrs Hall and David Forrest, discussing the feasibility of these visions with a couple of more sceptical observers, myself and Saul Tendler, a bionanotechnologist from Nottingham University. The audience included many distinguished nanoscientists, and even with the video available, it’s worth reading the transcript of the debate, which can be downloaded from The Nottingham Nanoscience Group’s webpages, if only to identify the authors of the many perceptive questions.

The aftermath of the debate included these additional points from David Forrest, which attracted some discussion on Soft Machines here. For my part, I organised my thoughts on the problems which I think the MNT program needs to address and overcome in this post: Six Challenges for Molecular Nanotechnology.

So where does the debate go now? I can’t conceal my disappointment that the MNT community has reacted with complete indifference to this set of challenges, which I set out in as constructive and concrete way as possible. Nanodot, the blog of the Foresight Nanotech Institute, simply ignored it. The most vocal proponents of the MNT position are now to be found in the Centre for Responsible Nanotechnology, but rational discussion of MNT in that forum is hampered by the fact that its proprietors simply refuse to engage in debate with informed critics such as myself and Philip Moriarty, preferring simply to assert, in the absence of any evidence, that the MNT revolution comes ever nearer. The usual outcome of a refusal to engage with people outside one’s own circle of believers is, of course, complete marginalisation. I regret this situation, because even though I think many of the ideas underlying MNT are flawed, Drexler’s writings have been very valuable in highlighting the potential of radical nanotechnology, and the process of thinking through what might work and what won’t is likely to be a very productive way of establishing research directions.

Printing devices

I spent a couple of days earlier this week at a conference in Manchester called “Printing of Functional Materials”. The premise of this meeting was the growing realisation that printing technologies, both the traditional, like silk-screen and gravure, and modern, like ink-jet, offer scalable, cheap and flexible ways of precisely depositing small quantities of materials on surfaces. Traditional inks are just vehicles for pigments to create static images, but there’s no reason why you can’t use printing to deposit materials that are conductors or semiconductors of electricity, which are electro-luminescent, or which have some biological functionality. Indeed, as one of the organisers of the conference has shown, one can even use ink-jet printing to deposit living human cells, with potential applications in tissue engineering.

The degree of commercial interest in these technologies was indicated by the fact that, unusually for an academic conference, more than a third of the attendees were from the commercial sector. Many of these were from the cluster of small and medium companies developing ink-jet technologies from around Cambridge, but European and American concerns were well represented too. My impression that the sector that is closest to maturity in this area is in electrically functional devices, where there’s a great deal of momentum to drive down the cost of RFID and to develop cheap, flexible displays. But there are still many materials issues to solve. It’s not easy to get a complex fluid to flow in the right way to form the tiny, well-defined droplets that make it ink-jet well, and formulating the ink in a way that makes it dry to give the best properties is awkward too. Silver inks illustrate the problems – commercial inks to write conducting lines sometimes use silver nanoparticles. Making the silver particles very small is helpful in making them coalesce well to make a continuous silver layer; the melting point of materials is lowered when they are in nanoparticulate form, making them sinter at lower temperatures. But then you have to work hard to stop the particles aggregating in the ink (it’s particularly undesirable, or course, if they aggregate in the ink-jet nozzle and block it up). To stabilise them, you need to coat them with surfactants or polymer molecules. But then this organic coating needs to be driven off by a heating step to get good conduction, and this compromises your ability to print on paper and plastics, which can’t take much heating. It seems to me that this technology has a huge amount of promise, but there’s a lot of materials science and colloid science to be done before it can fulfill its potential.

Ken Donaldson on nanoparticle toxicology

I’ve been running in and out of a three day course on nanotechnology intended for chemists working in the chemistry industry (Nanotechnology for Chemists), organised by me and my colleagues at Sheffield on behalf of the Royal Society of Chemistry. Yesterday I swapped from being a lecturer to being a pupil, to hear a lecture about nanoparticle toxicity, given by Ken Donaldson of the University of Edinburgh, the UK’s leading toxicologist specialising in the effects of environmental nanoparticles. This is a brief summary of his lecture as I understood it (all misunderstandings and misapprehensions are my fault, of course).

His lecture began with the disclaimer that most nanotechnology won’t pose a health risk at all; what’s at issue is the single class of free (i.e. not incorporated in a matrix, as happens in a nanocomposite material), manufactured, insoluble nanoparticles. Of the potential portals of entry – the lungs, the gut and the skin – he felt that the main danger was the lungs, so the main potential danger, both for industrial workers and users, was nanoparticles in the air.

It’s been known for a long time that particles cause lung disease; he gave a number of examples (illustrated by gruesome photographs), including coal miner’s lung, cancer and silicosis from quartz particles and asbestos. The latter causes a number of diseases, including mesothelioma, a particularly nasty cancer seen only in people exposed to asbestos, characterised by long latency period and with a uniformly fatal final outcome. So it’s clear that particles do accumulate in the lungs.

In terms of what we know about the effect of nanoparticle exposures, there are four distinct domains. What we know most about are the nanoparticles derived from combustion. We also know a fair amount about bulk manufactured particles, like titanium dioxide, which have been around a long time and which typically contain significant fractions of nanosized particles. Of course, the effects of nanoparticles used in medical contexts have been well studied. The final area is the least studied – the effect of engineered free nanoparticles.

So what can we learn from environmental nanoparticles? The origin of these particles is overwhelmingly from combustion; in the UK only 13% of exposure comes from non-combustion sources, usually the processes of natural atmospheric chemistry. The most important class of nanoparticles by far are those deriving from traffic exhaust, which account for 60% of exposure. These particles have a basic size of tens of nanometers, though they clump with time into micron sized aggregates, which are very easily respirable.

These particles have no problem getting deep within the lungs. Of the 40 nm particles, perhaps 30% can get to the very delicate tissues in the periphery of the lung, where they deposit very efficiently (smaller particles actually are less effective at getting to the lung as they tend to be taken up in the nose). The structures they interact with deep in the lung – the bronchal epithelial cells – are very small and fragile, and the distances separating airways from the blood are very small. Here the particles cause inflammation, which is essentially a defense reaction. We’re familiar with inflammation of the skin, marked by swelling – fluid bathes the region and white blood cells engulf damaged tissue and microbes, leading to pain, heat, redness and loss of function. Of course in the lung one can’t see the inflammation, and there are no pain receptors, so inflammation can be less obvious, though the swelling can easily cut off air flow leading to very disabling and threatening conditions.

It’s believed that there is a generic mechanism for lung inflammation by combustion-derived nanoparticles, despite the wide variety of different kinds of chemistry in these particles. All these have in common the production of free radicals, which leads to oxidative stress, which in turn leads to inflammation. DIfferent types of nanoparticles cause oxidative stress through different mechanisms. Metal nanoparticles – as found in welding fumes – yield one mechanism, surface born organics (as are found in soot), have another, and materials like carbon black, titanium dioxide and polystyrene latex, which are not very intrinsically toxic, operate through some generic surface mechanism. Clearly it is the surface area that is important, so nanoparticles cause more inflammation than the same mass of fine respirable particles, in the 2-3 micron range, composed of the same materials. In passing one can note that diesel fumes are particularly harmful, dealing a triple blow through their combination of surfaces, metals and organics. These pathways to oxidative stress are very well understood now, so this is a well-found paradigm.

Inflammation due to the oxidative stress caused by nanoparticles from pollution then leads to a number of different diseases, including cardiovascular diease, asthma, scarring, cancer and chronic obstructive pulmonary disease). Their involvement in cardiovascular disease is perhaps unexpected, and to understand it we need to understand where the nanoparticles go. We have some rather hypothetical toxicokinetics based on a few experiments using radioactive, insoluble tracer particles. Having entered the nose or lung, a few studies suggest that they can go directly to the brain. The route from the lung to the blood is well understood, and once in the blood there are many possible ultimate destinations. It’s doubtful that nanoparticles could enter the blood directly from the gut or skin. A mechanism for the involvement of nanoparticles in cardiovascular disease is suggested by studies in which healthy Swedish student volunteers rode a bike in an atmosphere of diesel fumes (at levels comparable to highly polluted city streets). This leads to measurable vascular dysfunction throughout the whole body, and a reduction in the ability to dissolve blood clots (similar effects will be observed in smokers, who self-administer nanoparticles). This suggests that pollution nanoparticles could cause cardiovascular disease either through lung inflammation or through the direct effect of bloodborn particles, leading to the worsening of coronary artery disease or increased blood clotting.

A study using radioactive carbon has suggested that nanoparticles can enter the brain directly from the nose, via the olfactory bulb – this is the route into the central nervous system used by the polio virus, and it doesn’t required crossing the blood-brain barrier. Studies of brain tissue in people living in highly polluted cities like Mexico City have shown pathological changes simiilar to those seen in victims of Parkinson’s and Alzheimer’s occurring as a result of the effect of pollution-derived nanoparticles.

The potential comparison between carbon nanotubes and asbestos is worth considering. Very large exposures to asbestos in the past have caused many cases of fatal lung disease. The characteristics of asbestos which cause this disease – and these characteristics are physical, not chemical – are that they are thin, persistent in the body, and long. Carbon nanotubes certainly match the first two requirements, but it is not obvious that they fulfill the third. Asbestos fibres need to be 20 microns long to demonstrate toxic effects; if they are milled to shorter lengths the toxicity goes away. Carbon nanotubes of this length tend to curl up and clump. On the other hand rat experiments on the effect of nanotubes on the lungs show distinctive fibrosing lesions. Donaldson has just written an extensive review article about nanotube toxicity which will be published soon.

From the regulatory point of view there are some difficulties as regulations usually specify exposure limits in terms of mass concentration, while clearly it is surface area that is important. In the USA NIOSH thinking of reducing limits by a factor of 5 for ultrafine TiO2. Fibres, though, are regulated by number density. The difficulties for carbon nanotubes are that they are probably too small to see by standard microscopy, and they curl up, so although they should be classifed as fibres by WHO definitions probably aren’t going to be detected. In terms of workplace protection local exhaust ventilation is much the best, with almost all masks being fairly useless. This applies, for example, to the masks used by some cyclists in polluted cities. They can, however, take comfort from the fact that their exposure to nanoparticles is significantly smaller than the exposure of the people inside the vehicles who are causing the pollution.

My conclusion, then, is if you are worried about inhaling free nanoparticles (and you should be) you should stop travelling by car.

Regulatory concerns about nanotechnology and food

The UK Government’s Food Standards Agency has issued a draft report about the use of nanotechnology in food and the regulatory implications this might have. The report can be downloaded here; the draft report is now open for public consultation and comments are invited by July 14th.

Observers could be forgiven some slight bemusement when it comes to the potential applications of nanotechnology to food, in that, entirely according to one’s definition of nanotechnology, these could encompass either almost everything or almost nothing. As the FSA says on its website: “In its widest sense, nanotechnology and nanomaterials are a natural part of food processing and conventional foods, as the characteristic properties of many foods rely upon nanometre sized components (e.g. nanoemulsions and foams).” To give just one example, the major protein component of milk – casein – is naturally present in the form of clusters of molecules tens of nanometers in size, so most of the processes of the dairy industry involve the manipulation of naturally occurring nanoparticles. On the other hand, in terms of the narrow focus that has developed at the applications end of nanotechnology on engineered nanoparticles, the current impact on food is rather small. In fact, the FSA states categorically in the report: “The Agency is not aware of any examples of manufactured nanoparticles or other nanomaterials being used in food currently sold in the UK.”

In terms of the narrow focus on engineered nanoparticles, it is clear that there is indeed a regulatory gap at the moment. The FSA states that, if a food ingredient were to be used in a new, nanoscale form, then currently there would be no need to pass any new regulatory hurdles. However, the FSA believes that a more general protection would step in as a backstop – ” in such cases, the general safety articles of the EU Food Law Regulation (178/2002) would apply, which require that food placed on the market is not unsafe.” So, how likely is it that this situation, and subsequent problems, might arise? One needs first to look at those permitted food additives that are essentially insoluble in oil or water. These include (in the EU) some inorganic materials that have been used in nanoparticulate form in non-food contexts, including titanium dioxide, silicon dioxide, some clay-based materials, and the metals aluminium, silver and gold. Insoluble organic materials include cellulose, in both powdered and microcrystalline forms. The latter is an interesting case because it provides a precedent for regulations that do specify size limits – the FSA report states that ” The only examples in the food additives area that specifically limits the presence of small particles is the specification for microcrystalline cellulose, where the presence of small particles (< 5 microns) is limited because of uncertainties over their safety. " The FSA seems fairly confident that if necessary similar amendments could quickly be made in the case of other materials. But there remains the problem that currently there isn’t, as far as I can see, a fail-safe method by which the FSA could be alerted to the use of such nanomaterials and any problems they might cause. On the other hand, it’s not obvious to me why one might want to use these sorts of materials in a nanoparticulate form in food. Titanium dioxide, for example, is used essentially as a white pigment, so there wouldn’t be any point using it in a transparent, nanoscale form.

The Nanotech Pioneers – Where are They Taking Us?

My review of The Nanotech Pioneers : Where Are They Taking Us?, by Steve Edwards, will be published in the June edition of Physics World. Although one needs a subscription to read the full magazine, my review is freely available in full here. As you can see, my views on the book are fairly positive.

Synthetic biology – the debate heats up

Will it be possible to radically remodel living organisms so that they make products that we want? This is the ambition of one variant of synthetic biology; the idea is to take a simple bacteria, remove all unnecessary functions, and then patch the genetic code for the functions we want. It’s clear that this project is likely to lead to serious ethical issues, and the debate about these issues is beginning in earnest today. At a conference being held in Berkeley today, synthetic biology 2.0, the synthetic biology research community is having discussions on biosecurity & risk, public understanding & perception, ownership, sharing & innovation, and community organization, with the aim of developing a framework for the self-regulation of the field. Meanwhile, a coalition of environmental NGOs, including Greenpeace, Genewatch, Friends of the Earth and ETC, has issued a press release calling on the scientists to abandon this attempt at self-regulation.

Some of the issues to be discussed by the scientists can be seen on this wiki. One very prominent issue is the possibility that malevolent groups could create pathogenic organisms using synthetic DNA, and there is a lot of emphasis on what safeguards can be put in place by the companies that supply synthetic DNA with a specified sequence. This is a very important problem – the idea that it is now possible to create from scratch pathogens like the virus behind the 1918 Spanish flu pandemic frightens many people, me included. But it’s not going to be the only issue to arise, and I think it is very legitimate to wonder whether community self-regulation is sufficient to police such a potentially powerful technology. The fact that much of the work is going on in commercial organisations is a cause for concern. One of the main players in this game is Synthetic Genomics, inc, which was set up by Craig Venter, who already has some form in the matter of not being bound by the consensus of the scientific community.

In terms of the rhetoric surrounding the field, I’d also suggest that the tone adopted in articles like this one, in this weeks New Scientist, Redesigning life: Meet the biohackers (preview, subscription required for full article), is unhelpful and unwise, to say the least.