The Guardian today ran a piece about the Citizen’s Jury on Nanotechnology that I’ve been involved in, which has now had its final meeting. I’ve reported on the way the project has unfolded here (the launch), here (week 1), and here (week 3). The Guardian’s piece does a good job of conveying the diversity of points of view that are represented amongst the members of the jury. I’m looking forward to the publication of the jury’s conclusions and recommendations in September.
A better alligator clip for molecular electronics
The dream of molecular electronics is to wire up circuits using individual molecules as the basic components. A basic problem is how you connect your (typically semiconducting) molecules to the metallic connectors; the leading candidate at the moment is to use molecules with a terminal thiol (-S-H) group. Thiols stick very effectively to the surface of gold; this thiol-gold chemistry has quietly become one of the most widely used tools of today’s nanotechnologists, and has been referred to as a molecular alligator clip. But it’s not without its drawbacks; rather than bonding to a single metal ion the thiol group complexes with a group of neighbouring gold atoms, and the electrical properties of the bond through the single linking sulphur atom aren’t ideal. Two papers in this week’s Science magazine suggest an alternative.
The two papers – by Siaj and McBreen (Université Laval, Québec) and Nuckolls and coworkers (Columbia University) (subscription required for access to the full articles) both describe ways of getting a molecule linked to a metal surface by a double bond (i.e. M=C- where M is a metal atom and C is the terminal carbon of an organic molecule). The surface bonded organic molecule can then be used to initiate polymerisation by a method known as ring opening metathesis polymerisation (ROMP). This is vey interesting because ROMP provides a way of growing organic semiconducting molecules with great precision. In short, we have here a better alligator clip for wiring up molecular electronics.
Soft Machines at the Foresight Conference
The newly relaunched Foresight Institute – now officially the Foresight Nanotech Institute, with a mission of “Advancing Beneficial Nanotechnology” – holds its annual conference from October 22 to 27th in San Francisco. I was very pleased to get an invitation to talk in the first part of the meeting – the Vision Weekend. I’ll be taking the opportunity to set out some of my more speculative thoughts about how we might learn lessons from nature to make a radical nanotechnology based on some of the design principles used by cell biology.
Bacterial nanowires
Electrical phenomena are important in biology, as Galvani discovered long ago when he learnt to make dead frogs twitch. But in biology electrical currents are generally carried by currents of ions rather than electrons. The transport of electrons is important in processes like photosynthesis, but the distances over which the electrons are transported are very small – the nanometer or two that defines the thickness of a lipid membrane. So the discovery of what look like electrically conducting nanowires in a soil bacterium is rather surprising. The discovery, from a group at UMASS Amherst (press release here), was reported in Nature (subscription required for full article) a few weeks ago.
The bacteria in question are soil bacteria that make their living by metabolising iron; to do this they seem to have evolved electrically conducting filaments called pili that allow them to do electrochemistry at a distance on a particle of iron oxide. Pili are common in many types of bacteria; they’re used by pathogenic bacteria to inject toxins into host cells, and for transfer of DNA between bacteria. They’re composed of protein molecules which self-assemble into long filaments, which are anchored into the bacterial cell wall by a large protein complex.
This report still leaves some unanswered questions in my mind. The conductivity of the pili was measured using atomic force microscope based conductance mapping of a graphite surface decorated with pili that had been broken off bacterial surfaces; it would be more convincing (though much more difficult) to quantify the conductivity along the length of the filament, rather than across the thickness. More importantly, perhaps, it doesn’t yet seem to be clear what is the structural feature of the pilus-making protein in this particular bacteria that leads to its electrical conductivity (as opposed to pili from other types of bacteria, which are shown in the paper to be non-conductive). It’s still a remarkable and suggestive result, though.
Thanks to Jim Moore for a comment drawing my attention to this press release.
Nano cosmetics make the headlines
This week’s Sunday Times ran a story headlined “Safety fears over ‘nano’ anti-ageing cosmetics”. The story highlights the company L’Oreal, which, it says, is “marketing a range of skin treatments containing tiny nano- particles, despite concerns about their possible long-term effects on the human body “, and singles out the product Revitalift, which apparently contains “nanosomes” of pro-retinol A. The article quotes both the FDA and the Royal Society on potential unknown health effects, quoting the latter as saying “We don’t know whether these particles are taken down through the skin and what the long-term effects might be in the bloodstream.” There’s an important point that needs clarifying here.
We need to distinguish between manufactured nanoparticles, like the zinc oxide particles mentioned as being used in some sunscreens, and self-assembled nanostructures, like nanosomes, which are the major subject of the article. It’s the manufactured nanoparticles that have given rise to the health anxieties; nanosomes are quite different. Nanosomes are formed from soap like molecules which self-assemble into water into sheets. If you can persuade these sheets to curve round and make a closed surface you have a liposome; a bag in which you can trap useful molecules like the various vitamins and vitamin precursors that companies like L’Oreal like to put in their products (see here for L’Oreal’s own description of this technology). A nanosome is simply a small liposome. The idea is that these molecular delivery bags will both protect the active molecules and help them penetrate the skin. Should we worry that these nanoparticles will enter the human body and lead to long-term adverse effects? Probably not, because the molecules that make up the bag are identical to or very similar to naturally occuring lipids (in fact, the starting point for most liposomes is lecithin, a naturally occurring mixture of phospholipids that’s very commonly used as food emulsifier), and the structures they form are held together by rather weak forces. Liposomes have been much studied as possible drug delivery agents, and this research shows that most liposomes have a rather short life-time in the body. In fact, from the point of view of drug delivery, the lifetimes are rather too short and special tricks are needed – such as the so-called stealth lipsome technology – to prevent the body recognizing and destroying them.
I’m not sure where this piece has come from – it’s written, not by a science correspondent or an environment correspondent, but by the “Social Affairs” editor. I think “Social Affairs” is a rather pretentious categorisation for all those lifestyle pieces that Sunday newspapers are plagued by, and sure enough the “Style” supplement has a consumer review of non-surgical anti-ageing treatments. Perhaps someone in the lifestyle department saw the nano- word, dimly remembered that nanotechnology had been “derided by the Prince of Wales as ‘grey goo’ “, and saw the chance to get a serious story in the paper for a change.
Will the association of these cosmetics with scare stories about the dangers of nanotechnology be bad for their sales? Somehow I doubt it. Given the popularity of botox, it seems that a combination of outrageous expense and the suggestion of danger is exactly what sells an anti-ageing treatment.
An open debate about radical nanotechnology
A public debate about nanotechnology – Nanotechnology: Radical New Science or Plus ca Change? – has been organised by Philip Moriarty at the University of Nottingham as part of a Surface Science Summer School at 4.30 pm on Wednesday 24th August . The themes of the debate are:
The panel includes myself and J. Storrs Hall, author of the recently published book Nanofuture: What’s next for nanotechnology
The primary audience for the debate will be young graduate students doing PhDs in nanoscience, so we can be sure that there’ll be a vigorous technical discussion. But anyone’s welcome to turn up (Philip asks that you drop him an email – see his personal web-page for an address – if you want to come). And if you can’t make it in person, submit your question online via this link.
(Updated 13 July following Philip’s information below that Dave King can’t now come to the Summer School)
Nanotechnology in the developing world – an emerging south-south gap?
Critics of nanotechnology like the ETC group worry about the potential for this new technology to lead to a divergence in wealth between rich countries and poor countries – the North-South gap. A different perspective emerges from an interesting recent commentary in the July 1 edition of Science Magazine by Mohamed Hassan of The Academy of Sciences for the Developing World (TWAS), Trieste – Small Things and Big Changes in the Developing World (subscription required). The article makes clear just how energetically and effectively some developing countries are pursuing nanotechnology. But, the article adds, “On the downside, there is a disturbing emergence of a South-South gap in capabilities between scientifically proficient countries (Brazil, China, India, and Mexico, for example) and scientifically lagging countries, many of which are located in sub-Saharan Africa and in the Islamic world”.
The big story, is of course, China. The same issue of Science has a very bullish article by Chunli Bai, Executive VP of the Chinese Academy of Sciences in Beijing – Ascent of Nanoscience in China (subscription required), which highlights both the investments going into nanoscience and the results in terms of scientific outputs, which have already placed China into the first rank of nanoscience nations (for example, on some measures their output has already surpassed the UK). But other countries, like India, Mexico, Brazil and South Africa, are making significant investments. Hassan’s article quotes the Nigerian Minister of Science and Technology for the rationale: “developing countries will not catch up with developed countries by investing in existing technologies alone. [In order] to compete successfully in global science today, a portion of the science and technology budget of every country must focus on cutting-edge science and technologies”.
The danger that Hassan sees is that the research goals of the developing nations that are successful in developing nanotechnology will become too closely aligned with those of the rich countries (i.e. creating lucrative goods for consumer markets) rather than focusing on the those issues that are particularly important for the developing world.
All things begin & end in Albions ancient Druid rocky shore
Soft Machines is taking a short break – I’m going to the seaside with my family for a week and will be away from internet contact. My apologies in advance for any comment spam that gets through the filters.
I always like to be on vacation on July 4th; it’s both my wedding anniversary and my son’s birthday. For any readers who might have any other reason to celebrate that day, have a happy holiday.
Debating the feasibility of molecular manufacturing
The Soft Machines blog is getting some visitors referred from a page on the new Foresight Institute website discussing the various debates there have been on the feasibility of Drexler’s version of a radical nanotechnology. For their convenience, and for anyone else who is interested, here is a quick summary of some the relevant posts on Soft Machines. When I get a moment, I will move a version of this summary to a more permanent home.
Biomimetic nanotechnology with synthetic macromolecules
This is a draft of a piece I’ve been invited to write for the special edition of Journal of Polymer Science: Polymer Physics Edition that is associated with the March meeting of the American Physical Society. The editors invited views from a few people about where they saw the future of polymer science. Here’s my contribution, with themes that will be familiar to readers of Soft Machines. Since the intended audience consists of active researchers in polymer science, the piece has more unexplained technical language than I usually use here.
In the first half of the twentieth century, polymer science and biochemistry developed together. With synthetic polymer chemistry in its infancy, most laboratory examples of macromolecules were of natural origin, and the conceptual foundations of polymer science, such as Staudinger’s macromolecular hypothesis, were as important for biology as for chemistry. Techniques for the physical characterisation of macromolecules, like Svedberg’s ultracentrifuge, were applied as much to biological macromolecules as synthetic ones. But with the tremendous development of the field of structural biology that x-ray protein crystallography made possible, the preoccupations of polymer science increasingly diverged from those of what was now being termed molecular biology. The issues that are so central to protein structure – secondary and tertiary structural motifs, ligand-receptor interactions and allostery, had no real analogue in synthetic polymer science. Meanwhile, the issues that exercised polymer scientists – crystallisation, melt dynamics and rheology – had little relevance to biology. Of course there were exceptions, but conceptually and culturally the two disciplines had become worlds apart.
I believe that the next fifty years we need to see much more interaction between polymer science and cell biology. In polymer science, we’ve seen the focus shift away from the properties of bulk materials to the search for new functionality by design at the molecular level. In cell biology, the new methods of single molecule biophysics permit us to study the behaviour of biological macromolecules in their natural habitat, rather than in a protein crystal, allowing us to see how these molecular machines actually work. Meanwhile synthetic polymer chemistry has started to give us access to control over molecular architecture. This is not yet at the precision that we obtain from biology, but we are already seeing the exploitation of non-trivial macromolecular architectures to achieve control over structure and function. The next stage is surely to take the insights from single molecule biophysics about how biological molecular machines work and design synthetic molecules to perform similar tasks.
We could call this field biomimetic nanotechnology. Biomimetics, of course, is a well-known field in material science; what we are talking about here is biomimetics at the level of single molecules, at the level of cell biology. Can we make synthetic analogues of molecular motors and other energy conversion devices? Can we learn from membrane biophysics to make selective pumps and valves, which would allow the easy and energy-efficient separation and sorting of molecules? Will it be possible to create any synthetic analogue of the systems of molecular sensing, communication and computation that systems biology is just starting to unravel? It’s surely only by achieving this degree of nanoscale control that the promise of molecular medicine could be fulfilled, to give just one example of a potential application.
What are the areas of polymer science that need to be advanced to enable these developments? Obviously, in polymer chemistry, synthesis with precise architectural control is key, and achieving this goal in water-soluble systems is going to be important if this technology is going to find wide use, particularly in medical applications. Polymer physicists are still much less comfortable dealing with systems involving water and charges than with polymer solutions in simple non-polar solvents, and we’ll need more work to ensure that we have a good understanding of the physical environment in which our devices will be operating.
The importance of self-assembly as a central theme will continue to grow. This way of creating intricate nanostructures by programmed interactions in macromolecules is well known to polymer science; the richness of the morphologies that can be obtained in block copolymer systems is well-known. But in comparison with the sophistication of biological self-assembly, synthetic self-assembly still operates at a very crude level. One new element that we should import from biology is the exploitation of secondary structure and its coupling to nanoscale morphology. Another important idea is to exploit the single chain folding of a sequenced copolymer in an analogue of protein folding. This, of course, would require considerable precision in synthesis, but theoretical developments are also necessary. We have learnt from the theory of protein folding theory that only a small fraction of possible sequences are foldable, so we will need to learn how to design foldable sequences.
Another important principle will be exploiting molecular shape change. In biology, this principle underlies the operation of most sophisticated nanoscale machines, including molecular motors, ion channel proteins and signalling molecules. In polymer physics the phenomenon of the coil-globule transition in response to changing solvent conditions is well known and has its macroscopic counterpart in thermoresponsive gels. To be widely useful, we need to engineer responsive systems with much more specific triggers and with a more highly amplified response. One promising way of doing this uses the coupling between transitions in secondary structure and global conformation; however we’re still a long way from the remarkable lever arms of biological motor proteins, in which rather subtle changes at a binding site produce a large overall mechanical response.
Some of the most powerful ideas from biology still remain essentially unexploited. An obvious one is, of course, evolution. At the molecular level, evolution offers a spectacularly powerful way of searching multidimensional parameter spaces to find efficient design solutions. It’s arguable that, given the combinatorial complexity that arises with even modest degrees of architectural control and our unfamiliarity with the design rules that are appropriate for the nanoscale environment, that significant progress will positively require some kind of evolutionary approach, whether that is executed in computer simulation or with real molecules.
Perhaps the most fundamental difference between the operating environments of biology and polymer science is the question of thermodynamic equilibrium. Polymer scientists are used to systems at, or perturbed slightly away from, equilibrium, while biological systems are driven far from equilibrium by a continuous energy input. How can we incorporate this most basic feature of life into our synthetic devices? What will be our synthetic analogue of life’s universal energy currency, adenosine triphosphate?
Ultimately, what we are talking about here is the reverse engineering of biology. It’s obvious that the gulf between the crudities of synthetic polymer science and the intricacies of cell biology is currently immense (certainly quite big enough to mean that the undoubted ethical issues that would arise if we could make any kind of reasonable facsimile of life are still very distant). Nonetheless, even rudimentary devices inspired by cell biology would be of huge practical benefit. Potentially even more significant a benefit than this, though, would be the deep understanding of the workings of biology that would arise from trying to copy it.