Nanotechnology in the New Straits Times

My friend, colleague and collaborator from across the road in the chemistry department here at Sheffield, Tony Ryan, went to Malaysia and Singapore the week before last, and one result was this article in the New Straits Times, in which he gives a succinct summary of the current state of play in nanotechnology. He was rewarded by a mildly cross email this morning from K. Eric Drexler. Actually I think Tony’s interview is pretty fair to Drexler – he gives him a big place in the history of the subject, and on the vexed question of nanobots, he says “This popular misconception has been popularised by people who misunderstood the fantastic book Engines of Creation by K. Eric Drexler.”

There was also a useful corrective to those of us worried that nanotechnology is getting overexposed. The writer describes how the article originated from a “short, balding man in the public relations industry” who said about nanotechnology that it’s “”the latest buzzword in the field of science and is making waves globally”. On the contrary, our journalist says… “Buzzword? It most certainly is not. My editor and I looked at each other and agreed that it is more a word that one hears ONLY ever so occasionally. “

The Stalinists of public engagement…

The recent pamphlet from Demos on the need for public engagement about nanotechnology and other new technologies has received forthright criticism from the editor of Research Fortnight, William Bown. The original editorial raised the spectre of Lysenko, and accused advocates of public engagement of being “worse than Stalinists”. One of the authors of the Demos paper, James Wilsdon, has energetically responded. The resulting exchange of letters will be published in Research Fortnight, but those readers who unaccountably have forgotten to renew their subscription to that organ can read them on the Demos blog.

I’m not going to attempt to summarise Bown’s argument here (mainly because I find it rather difficult to follow). But I will single out one statement he makes to take issue with. Arguing that public engagement simply provides a mechanism to help governments avoid making difficult decisions, he says “The question for these two [Tony Blair and Gordon Brown], and their companions in Parliament, is not whether they think science is shiny and exciting; it is whether they back the deployment of nanotechnology.” This seems to me to combine naiveity about politics with a real misunderstanding of the nature of the science. All the debates about nanotechnology should have made one thing absolutely clear: nanotechnology is not a single thing (like nuclear power, say) that we can choose to use or to turn away from. It’s a whole variety of different technologies and potential technologies, with an equally wide range of potential applications. Choices need to be made – are being made right now, in fact – about which research avenues should be pursued, and which should be left to others, and one of the key roles of public engagement is to inform those choices.

Swimming strategies for nanobots

Physics works differently at the nanoscale, and this means that design principles that are familiar in the macro-scale world may not work when shrunk. A great example of this is the problem of how you would propel a nanoscale swimmer through water. To a human-scale swimmer, water resists forward motion by virtue of the fact that it has inertia. But on the nanoscale, it is the viscosity of water that is the dominant factor. To imagine what it feels like trying to swim at the nanoscale, you need to imagine being immersed in a vat of the most sticky molasses.

The mathematics of this situation is intriguing, and it’s been known for a while that any simple, back-and-forth motion won’t get you anywhere. Imagine a scallop, trying to swim by opening its shell slowly, and then shutting it suddenly. This strategy works fine in the macroscopic world, but on the nanoscale you can show that all the ground the scallop gains when it shuts its shell is lost again when it opens it, no matter how big the difference in speed between the forward and backward strokes. To get anywhere, you need some kind of non-reciprocal motion – a motion that looks different when time-reversed. In 2004, Ramin Golestanian and coworkers showed that three spheres joined together could make a nanoscale swimmer. Here’s an article about this work in Physical Review Focus, with a link to a neat animation; here’s another article in Technology Review: Teaching Nanotech to Swim.

This story has moved forward in two ways since this report. Earlier this year, Ramin Golestanian, together with Tannie Liverpool, from Leeds University, and Armand Ajdari, from ESPCI in Paris, analysed another way of propelling a nanoscale submarine. In this work, published in Physical Review Letters in June this year (abstract here, subscription required for full article), they considered a nanoscale vessel with an enzyme attached to the hull at one point. The enzyme catalyses a chemical reaction that produces a stream of reactants like a rocket’s exhaust. Like a rocket, this has the effect of propelling the vessel along, but the physics underlying the effect is quite different. It’s not the inertia of the exhaust that propels the vessel forward; instead it is the effect of the collisions of the reactant molecules as they undergo random, Brownian motion that have the effect of propelling our nanobot forward.

And today, Nature published an experimental report of a miniature swimmer (editor’s summary; full paper requires subscription) which illustrates some of these principles. In this work (from Bibette and coworkers, also at ESPCI, Paris), chains of magnetic nano-particles form a tail which wiggles when an oscillating magnetic field is applied, pulling a payload along.

Ramin has just joined us in the physics department at Sheffield, so I look forward to working with him to take some more steps on the road to a swimming nanobot.

Nanomedicine gets clinical

Everyone agrees that some of the key applications of nanotechnology will be in medicine. Within medicine, drug delivery is an obvious target. So when can we expect to see nano-enabled medicines on the pharmacy shelves? The answer, as usual, depends on what you mean by nanotechnology. Many people have welcomed Abraxane™, which received FDA approval for use for breast cancer earlier this year, as the first nano-drug. But a number of other drugs already in clinical use have just as much right to the nano- label.

Ruth Duncan gives a useful list of nano-medicines in current clinical use in an article in Nano Today – Nanomedicine gets clinical (I’ve already referred to this article here). We can summarise the key functions that nano-engineering confers on these products as packaging and targeting – the active drug molecules need to be protected from the body’s systems for repelling foreign materials, and if possible they need to be actively targetted to the parts of the body at which the therapy is directed. For the anti-cancer therapeutics that dominate this list, this target is the tumour.

One approach to targetting is to wrap the molecule up in a liposome – a nanoscale container that is formed, by self-assembly, when soap-like lipid molecules form a bilayer sheet which folds over on itself to make a bag. These are the same structures that are already incorporated in some cosmetics. DaunoXome® consists of the anti-cancer drug daunorubicin encapsulated in liposomes, and is used for the treatment of HIV–related Kaposi’s sarcoma. Doxil® and Caelyx® are liposomal preparations of the related drug doxorubicin, and are used for advanced ovarian cancers. Simple liposomes have quite a short lifetime in the body; in Doxil the surfaces of the liposome are modified by being coated by the water soluble polymer polyethylene glycol.

Rather than putting the drug in a liposome, and then coating the liposome with polymer, it is possible simply to attach polyethylene glycol directly to the drug. This is the basis of “polymer therapeutics” (this is Ruth Duncan’s own field). Examples in clinical use include Oncaspar®, for acute lymphoblastic leukemia, and Neulasta®, used to decrease infection in patients receiving chemotherapy. Both these drugs consist of a protein drug molecule which is disguised from the body by being coated in a diffuse cloud of polyethylene glycol (PEG). How PEG works is still not entirely clear, but the basis of the effect is that it forms a diffuse layer which resists protein adsorption.

Mylotarg®, a drug licensed in the USA for acute myeloid leukemia, is a (currently rather rare) example of a targetted drug. The drug itself – a potent anti-tumor antibiotic – is chemically linked to an antibody – a protein molecule which specifically binds to chemical groups on the outside of the target cells. In Abraxane™, it is the drug molecule itself, paclitaxel, that is nanoengineered – it is prepared in a nanoparticulate form to improve its solubility; the nanoparticles are coated with the blood protein albumin.

So what we see now are a number of products which use individual tricks of nanoengineering to improve their effectiveness. What we will probably see in the future is the combination of more than one of these functions in a single product – moving beyond clever formulation to integrated nanodevices.

Self-replicating (macro-)bots

A brief communication in this week’s Nature reports (macroscopic) machines that autonomously self-replicate from randomly positioned components. The work is from Saul Griffith and colleagues at MIT’s Media lab. Self-replication is done in a two stage process; there’s a recognition step, in which when two correctly oriented building blocks randomly collide they latch together, and there’s an error correction step, in which incorrectly joined sub-units are separated.

A movie (9 MB Quicktime movie – I think this works without a subscription) shows the self-replication happen. The blocks are placed on an air-table and agitated to bring blocks randomly into contact with each other. Of course, this is just a macroscopic analogue of the random, Brownian motion that is so important at the nanoscale. It’s interesting to compare this with another, much publicised, example of a macroscale, self-replicating system reported earlier this year in Nature. In that case, self-replication was a deterministic process that relied on its components being supplied in a well-ordered way. Griffith’s approach (see his web-site for more context) consciously mimics the self-assembly processes used in biological systems; the architecture of the structure is encoded in each of its components, and assembly depends on random interactions between these components. The combination of these two features is what leads to the huge potential advantage of this approach to self-replication over more deterministic techniques – the potential to make the process massively parallel and inherently scalable. This is fascinating and thought-provoking work.

More on Nanojury UK

Here are a few more links about Nanojury UK, the citizens’ jury on nanotechnology which has just reported its verdict.

The press release about the results, from Greenpeace.
An article about it, from the German newspaper die Tageszeitung (in German). Thanks to author Niels Boeing for letting me know about this.
Detailed commentary on the results and the launch day from David Berube (research director of NanoScience and Technology Studies at the University of South Carolina).

Finally, here’s a complete list of my posts on the process as it unfolded:
The launch
Week 1
Week 3
Finalising the conclusions
The verdict.

Nanojury UK – the final verdict

Nanojury UK – the citizens’ jury on Nanotechnology that has been deliberating over the summer – delivered its verdict on Wednesday at an event in London. In full, there were twenty recommendations which attracted various degrees of support. But at the launch, four jurors attended in person, and they singled out four recommendations which they felt the whole jury felt most strongly about. After presenting these four key recommendations, they took questions from a large audience, and then the sponsors of the process gave their reactions.

The four recommendations were:
1. Health – nano-enabled medicines had big potential for reducing the time people spent in hospital. These should be developed via improved funding mechanisms and should be available without discrimination on the National Health Service.
2. The Government should support those nanotechnologies that bring jobs to the UK by investment in education, training and research.
3. Scientists should learn to communicate better – some of the jury felt sometimes patronised, they didn’t like all the long words scientists used, and scientists didn’t always agree with each other.
4. Products containing manufactured nanoparticles should be labelled in plain English.

The questions threw up some interesting insights. The most direct and straightforward came from the Guardian reporter – after this process, what was their general impression of nanotechnology. All four were in agreement; if safety could be assured, they were very positive. Another journalist asked them what they felt were the most exciting applications, and again they agreed on medicine and renewable energy. A Greenpeace person asked them a rather leading question about whether they would agree with the proposition that he claimed many scientists held, that if the public only understood the science they would support it. They answered this by saying that as they learned about the science, they got excited about it and talked about it to their friends. One juror told a story about how his daughter was at school and the class was asked about nanotechnology. She said “oh, yes, I know loads about nanotechnology”, to which the teacher replied along the lines of “how can you know about that, your dad’s just a taxi driver”, to which she was able to say that her father was taking part in this citizens jury and was telling her all about it.

One thing was absolutely clear – the jurors were tremendously positive about the process itself. They even managed to say some positive things about the scientists involved, despite conclusion 3. One juror rather accurately identified the problem with the upstream nature of the process – commenting that “some of this stuff is so far ahead that even the scientists aren’t sure where it is going”. This positive view chimed well with the independent evaluation made by Nick Pidgeon, a social scientist from UEA who assessed the ill-fated GM nation project. His view was also very positive, and he noted as good features the very representative jury, the very strong multi-stakeholder oversight panel, and the direct link into government. He noted as a challenge for upstream approach precisely the problem that the juror had pointed out.

From the sponsors, Mark Welland, from the Cambridge Nanotechnology IRC, talked a lot about the importance of the integrity of the process, and pronounced himself very satisfied with this. Doug Parr, from Greenpeace, sounded a slight air of disappointment. He didn’t think the recommendations reflected the richness of the discussions, he noted the importance of discussing, beyond pure technology, the wider issues of economics and the wider disconnects between science, government, industry and the public. He noted that there had been no mention of the idea of a moratorium on the new technology. I should note here, of course, that Jim Thomas, of the ETC group, which has been calling for a moratorium, was one of the witnesses and presented the case for one to the jury.

For the Government, the reaction was given by Adrian Butt, Chair of the Nanotechnology Issues Dialogue Group, the multi-department body set up to coordinate nanotechnology policy across government. He gave an explicit commitment to table the recommendations in the policy meetings of the NIDG and report back the outcome of discussions. He seemed really rather pleased with the outcome, which he took as being not far from endorsing the approach the government was taking. Nonetheless, he did exercise a certain amount of “expectations management” about how seriously the government would take this. In his words, “the results of this kind of exercise will not by themselves directly determine policy, but will provide social intelligence on the wider environment in which policy is made”

For nanobusiness, Barry Park, COO of Oxonica, expressed broad comfort with the balanced tone of the recommendations.

What of my personal recollections and feelings? I found it one of the most stressful things I’ve done in my career. I have massive admiration for Becky Willis, who chaired the oversight panel and kept the whole thing together in the face of what seemed at times overwhelming centrifugal forces (I composed one unsent resignation letter, and I suspect I wasn’t the only one who came close to walking out on the whole thing). The facilitators have immense power in this kind of exercise, and I ended up with immense respect for the professional effectiveness of Tom Wakeford and his team. But Tom has his own strong political views, which as he himself conceded in his own self-critique, he doesn’t always rigorously exclude from the process, and these aren’t calculated to make life easy for the scientists. It would be impossible for me not to take the criticisms of scientists communication skills personally, but I honestly don’t think the scientific witnesses should have done anything differently. I think the jurors got a very honest, unspun and unvarnished impression of the science, and in return I found the interactions with the jurors very rewarding.

At the end of it all, one thing that is disappointing was the very low level of press coverage – this perfunctory piece in the Guardian was the only thing in the nationals. There are some mitigating circumstances for the lack of press interest – the fact that the Guardian was the media sponsor limited the appeal for other papers, while the Guardian itself basically lost interest as a result of the decision to drop its weekly science section when the paper relaunched as a near-tabloid. But I can’t help feeling that there would have been a lot more coverage if the result had been different. There were approving words in an editorial in this weeks Nature (subscription required). Its conclusion is a good place to finish: “The results of the citizens’ jury suggest that nanotechnology is not perceived as a serious threat to the values of anyone but die-hard anti-technologists”.

Nanotechnology Engagement Group

I was in London on Monday for the first meeting of the Nanotechnology Engagement Group (NEG), a body funded by the UK government to coordinate activities around public engagement and the discussion of social and ethical issues in the context of nanotechnology. The establishment of the body was announced in a rather low-key way in the summer, when the government issued its draft strategy public engagement on nanotechnologies. The group is being run by the think-tank Involve, and I’m chairing it.

Here are a few first impressions, mostly of the potential pitfalls that it’s easy to imagine this enterprise falling into. The first is that it might cement the trend already identified by Demos, and contribute to a simultaneous professionalization and marginalization of the public engagement field. One can easily imagine NEG developing as a forum in which the professionals cheerfully discuss at length the methodological advantages of citizens’ juries against consensus conferences or focus groups, while failing to make any real impact either on the development of science policy or on the wider public discourse about technology as it’s carried out through the media.

The second is the tension that exists between the idea of public engagement and the idea of “engaging stakeholders”. A very popular way of doing some sort of wider consultation about something like technology is to assemble a bunch of “stakeholders” – regulators, industry groups, consultancy organisations, and advocacy groups. I have deep worries about the representativeness of such groups on all sides. There’s an unwillingness of the private sector to put its collective head above the parapet, on the one hand, and on the other there’s a tendency to assume that NGOs, sometimes representing very narrow constituencies, have a mandate to represent the concerns of a wider public. It’s tempting to view the results of such consultations as being much more representative than they are; when so many people are unwilling or unable to speak the voice of anyone who is willing and motivated to say anything at all ends up with far too much weight. This, to my mind, is one of the main strengths of processes like citizens’ juries – done well, you should get something that represents the views of the public much more accurately than an advocacy group.

Finally, there is the question of what the public, in these engagement exercises, are actually being asked to decide on. The drawback of this kind of upstream engagement is that it is not clear what the outcomes of the technology might be. Maybe we need to start doing some serious scenario construction to try and present a range of plausible futures to focus the discussion down a bit.

All these issues come into sharp focus with the launch of the findings of Nanojury UK (see here for previous reports on this), which took place today at the headquarters of the Guardian. I’ll be writing my impressions about the launch event tomorrow.

‘Twas on the good ship Venus…

If you’ve enjoyed the bout of transatlantic name-calling that my piece on public engagement produced (generally along the well-worn lines of Europeans from Venus versus Martian Americans), you might want to look at this exchange on the Foresight Institute’s Nanodot blog. Here Foresight VP Christine Peterson enthusiastically agrees with my not wholly serious suggestion that the origin of the UK’s aversion to the positive vision of Drexlerian nanotechnology can be traced to the generally pessimistic and miserabilist disposition of the inhabitants of this rain-sodden archipelago, and I desperately try and extract myself from the hole I’ve dug myself into.

Model Railways

I’ve been in Leeds for a few days for the biennial conference of the Polymer Physics Group of the UK’s Institute of Physics. Among many interesting talks, the one that stood out for me was the first – an update from Andrew Turberfield on his efforts to make a molecular motor from DNA.

Turberfield, who is at the Oxford IRC in Bionanotechnology, is building on the original work from Ned Seeman, exploiting the remarkable self-assembling properties of DNA to make nanoscale structures and devices. A few years ago, Turberfield, working with Bernie Yurke at Lucent Bell Labs, designed and built a DNA nano-machine (see here for a PDF preprint of the original Nature paper), and in 2003 they published a paper describing a free-running motor powered by the energy released when two complementary strands of DNA meet to make a section of double helix (abstract here).

This motor doesn’t actually do anything, apart from sit around in solution cyclically changing shape. What Turberfield wants to do now is make something a bit like the linear motors common in cell biology, in which the motor molecule moves along a track, often carrying a cargo. To make this kind of molecular railway, Turberfield’s scheme is to prepare a track along a surface by grafting strands of DNA to it. The engine is another DNA molecule; what needs to be done is get some scheme whereby the engine molecule is systematically passed along from strand to strand.

His first effort, in collaboration with Duke University’s John Reif, involves using enzymes to alternately cut DNA strands and rejoin them in a sequence that has the effect of making a short strand of DNA move linearly in one direction. In this case, it’s the energy used by the enzyme that joins two bits of DNA that makes the motor run. The full paper is here (PDF). In motor mark 2, it’s a so-called nicking enzyme that makes the engine move, and the directionality is imposed by the fact that the track is destroyed in the path of the engine (abstract here, subscription probably required for full article). What Andrew really wants to do, though, is have a motor that is solely powered by the energy released when DNA strands make a helix, which doesn’t chew up the track behind it, and which doesn’t involve the use of any biological components like enzymes. He has a scheme, and he is confident that it’s not far off working.

These motors are inefficient and slow in their current form. But they are important, because they work on the same basic principles as biological motors, principles which are very different to the mechanical principles that underly the motors we are familiar with. They rely on the Brownian motion and stickiness of the nanoscale environment. But because of the simplicity of the base pair interaction, the calculations you need to do to predict whether the motor will work or not are feasibly simple. By learning to make model railways from these simple, modular components, we’ll learn the design rules that will enable us to make a wider variety of practical nanoscale motors.