1. This report which essentially consists of abbreviated notes from a number of sessions from the nanotechnology study workshop is welcome in concept particularly as a multi-disciplinary approach was employed. However, the text reads simply as a précis of the meeting with the assumption that the reader had been involved in the original meeting – the provision of explanatory footnotes would have helped enormously.
   
   
2. This whole field is truly multi-disciplinary, but, and this comes through occasionally in the odd comment in the report, each individual involved in the meeting had their own particular area of expertise and a varying degree of knowledge in the other areas. Consequently if the final report of this workshop is to be used as a cross- disciplinary resource then the text needs to be expanded to include context and explanations for those not familiar with specific areas within this field.
   
   
3. To that extent a preliminary preamble on the background of why the working group was set up including some basic information such as definitions would help the flow of the document.
   
   
4. I come from a health-based background with a particular interest the health effects of airborne particles in ambient air and the possibility that ultrafine (sub 300 nanometre) particles when inhaled may be a route for therapeutic intervention. I am not an engineer and therefore it is difficult if not impossible for me to comment on some of the physico-chemical aspects of this report.
   
   
5. In addition, these comments are mine as an individual and do not represent the thoughts of the Department of Health’s Committee on Medical Effects of Air Pollution (COMEAP) which I chair.
   
   
   Specific comments
   
   Nano-Engineering and Measurement
   
6. Although not my particular area, I would agree with the comment under “applications” that networks are important in the context of the development of strategies for the development of nano-technology. However it is important to stress, as is mentioned later in the document, that such networks need to be truly cross-disciplinary and perhaps incorporated within the strategy should be some process either virtual or real, for being able to see what others are doing in the diverse fields in this broad area.
   
   Nano Materials
   
7. Section e ix
   One existing technology is in the generation of therapeutic aerosols which, while mostly concentrating on much larger particles do contain a very significant ultrafine component (see below).
   
   
8. Section d vi
   
   8.1
   I would agree that it is important to assess the properties of the individual chemical components that make up nano materials as well as size, concentration and surface area, but of particular importance may well prove to be the disposition of the constituents of nano-particles on the surface of the particles. This is particularly true in terms of health effects/toxicity where it is the surface of the particle that first comes into contact with the biological surface. The interaction of nano particles with fluid interfaces such as the epithelial lining fluid in the respiratory tract and then again with cellular interfaces is key in understanding the toxicity or toxic potential of nano particles.
   
   8.2
   In the same area it is important to flag up that novel imaging techniques of the intact organism - not just at a cellular level - would be eminently suitable for exploring the whole area of toxicity.
   
   ELECTRONICS AND OPTO-ELECTRONICS
   
9. I would fully endorse the comments on the development of good multi-disciplinary teams (Section d) rather than developing inter-disciplinary people. While training at a masters level is the logical way to take this forward it is essential that this whole area is embraced at first degree level.
   
   BIO NANO-TECHNOLOGY AND NANO-MEDICINE
   
10. This is the only section of the report that made specific comments on addressing definitions and was the only place in the report where I came across any idea of what definitions were being offered in the first instance! I would agree broadly with their definition of nano-technology but am a little less happy with their definition of nano-science. Specifying that nano-science is “on the scale of atoms and molecules” suggests that nano-science is limited to atoms and molecules and not to structures developed from them. This may seem pedantic but I would favour going to back to some broad assessment of the upper limit in terms of length scale rather than a comparator.
    
    
11. Section b ii
    While there is some comment at various points about dermal application of, for example, creams containing nano-particles, nowhere (apart from inferentially) is there any mention of the inhaled route as probably the major way in which nano-particles enter the body either deliberately – as in therapeutic aerosols – or obligatorily such as inhaling ambient air. It is all very well concentrating on cellular uptake of drugs but in order to be taken up by specific target cells the vehicle has to get there and deposition within the lung is key from that point of view particularly as this is majorly affected by the presence of intrinsic lung disease.
    
    
12. Section c
    It is intriguing that no mention is made of therapeutic aerosols. 3M have produced over the past few years an inhaled corticosteroid drug (QVAR) which has a spread of particle sizes which is much smaller than the conventional metered dose aerosol. We have undertaken work which shows that all medical aerosols in fact contain many particles below 100 nano-metres in size. What is not known is how much of the therapeutic potential lies in the ultrafine fraction compared to the larger fraction (say >1micron). The assumption has always been that it is in the larger size particles but as no-one has delivered ultrafine particles containing drugs as yet (we are in the process of trying this) we do not yet know how useful ultrafine/nano-technology would be in targeting the lung for drug delivery as opposed to getting the drug into the lung for systemic use.
    
    
13. Section e
    I would fully agree that research councils need to have overlapping remits and to be fair they are, in general, trying to do this. However, when trying to apply for such overlap funding one often gets told by one of the funding partners that the application is less suitable for them and more suitable for the other partner and vice versa!
    
    I am not sure what lies behind the statement that the RAE is hindering collaboration specifically within nano-technology, I suspect this is partly because of the stresses in encouraging individual departments to focus in an enormous blinkered fashion of their own area of research as the units of assessment tend not to be able to embrace the essential nature of nano-technology, ie. multi/disciplinary working.
    In the fifth bullet point (funding) in this section I am not entirely sure what the first sentence means (apart from being bad English!).
    
    HEALTH, SAFETY ENVIRONMENTAL AND SOCIAL ISSUES
    
14. I can see why these were pulled together as a joint heading but it would reasonable to separate out health and safety from the environmental and social issues in my view as there are different strands of argument for each.
    
    
15. I fully agree with the concerns about carbon nano-tubes and their similarity to asbestos. This is a good analogy but one must bear in mind that not all fibrous type materials do have the same lethal implications as has asbestos. For instance glass fibre is much less toxic (hardly at all) and on the spherical particle side of things carbon black workers have only very minimal (entirely non-dangerous) effects of persistent exposure to high levels of nano-particles. However, I would agree with the participants that further study into the potential durability and toxicity of nano-tubes is undertaken but non-tubular particles need also to be addressed.
    
    
16. It is quite true that the most likely agent for the adverse aspects of air pollution are sub-100nm particles and the statement that “the background concentration of many tens of thousand (of particles) in urban air” should be corrected to: ..”..tens of thousands of particles in each millilitre of urban air”.
    
    
17. Section c
    I would agree that mass per unit volume is probably not the most important metric for assessing dose when considering toxicity. However, at this stage it is difficult to know exactly what the best metric would be. Particle size, particle surface area and fractal properties may all have their role as may the concentration of specific components of the particles and/or their disposition over the surface of a core particle.
    This raises the whole issue of the importance on the negative side of inhaling of ultrafine particles either of pure drug or of a carrier with a drug on them for therapeutic purposes as the mere size of the particles in themselves may be deleterious. This equation is I think extremely important and one that is not easily addressed at the present stage until such products are available.
    
    
18. Section d
    18.1
    Getting the messages that are required across to the public is clearly the key. Much comment is made throughout the report on public perceptions implying that again the public have got it wrong having been stirred up by the media! The trouble is that quite often the public are right and I think it would be wrong of us to sit and believe that nano-particles are inherently safe and a splendid addition to our modern world. We need to be crucially careful about the potential deleterious effects of nano-particles particularly where they get into a situation where they could inadvertently enter the human body in some form or have an adverse effect on the environment in general.
    
    18.2
    However the concern about the innate suspicion that the public has about industry is undoubtedly true. While in the pharmaceutical industry the relationship between public and the pharmaceutical industry seems to have improved somewhat over the last decade or so, nevertheless there is still quite a substantial issue of the relationship between the public and the pharmaceutical industry. Indeed, some doctors also express concerns regularly on this area. In my view a confrontational approach does not help and again this needs to be dealt with I think by some form of approach where these worries could be allayed.
    
    18.3
    One possibility is that industry puts money into a central fund aimed at addressing specific areas within the whole area of nano-technology with control over that fund being through an independent group. Industry would then seem to be contributing in an unselfish way in trying to address issues not only on the basic science but also on applications, safety and public communication.

Jon Ayres
Professor of Environmental & Occupational Medicine
University of Aberdeen