Abstract In recent times, nanotechnology has been included in a number of the debates considering emerging technology and developing countries. However, the literature considering nanotechnology's application to the developing world has often varied in its interpretation of what nanotechnology really is. Furthermore, despite a wide range of perspectives as to the relevance, appropriateness and potential impact of nanotechnology for developing countries, the key debates have often remained

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... aged. This paper attempts to clarify understandings of nanotechnology and synthesize discussions on issues of relevance, appropriateness and distribution with respect to developing countries. In support, recent developments in nanotechnology and healthcare are provided. Background In recent times, a number of research groups have stimulated debate on nanotechnology's possible applications and implications for developing countries [see, for example, 1, 2, 3]. However, many of the subsequent papers have failed to distinguish theoretical-from currently feasible-nanotechnology [see, for example, 3, 4, 5]. In international debates, distinction between the near-term, possible reality and theoretical science is crucial to the efficient Nanotechnology and Developing Countries -Part 1: What Possibilities Saved from URL: http://www.azonano.com/article.aspx?ArticleID=1428 P /11 1 exchange of information. Furthermore, amongst those considering developing country engagement with nanotechnology, a range of perspectives are held concerning 'appropriateness' and nanotechnology's likely impact on the developing world. Some individuals challenge a pervasive acceptance of nanotechnology, expressing concern about developing country exploitation [Shiva cited in 6], insubstantial consideration for issues of risk and regulation [7], the loss of traditional markets [8] and an identification of nanotechnology applications that fails to consider historical trends and current barriers to technology distribution [9]. Others adopt a more utilitarian approach, linking nanotechnology applications in water, energy, health, food and agriculture to the fulfilment of the United Nation's (U.N.) Millennium Development Goals a [4, 10], despite earlier recognition of its potential to stimulate a greater divide between the 'haves' and 'have-nots' [1]. Despite surprising levels of nanotechnology research and development (R&D) in the developing world [1], arguments concerning nanotechnology's role as a protagonist or antagonist to sustainable development b remain disengaged. In this paper we seek to clarify understandings of nanotechnology and synthesize discussions on issues of relevance, appropriateness and equity with respect to developing countries. With infectious and parasitic disease remaining the greatest cause of death in the developing world [12] and nanotechnology predicted to affect half of the world's drug production by 2011 [13], examples relevant to health are commonly cited. What is Nanotechnology and How is it New? For citizens in the developed world already exposed to the term 'nanotechnology', associated impressions may be that it deals with 'very small things', concerns 'submarine robots in the bloodstream' and brings with it the threat of 'grey goo' c . The latter, more popular ideations, essentially stem from K. Eric Drexler's proposal that atoms and molecules could act as self-assembling machinery, performing production tasks at the nanoscale d [15]. However, what is now universally accepted as 'nanotechnology', yet sometimes less noted, is an area evolving somewhat independently of Drexler's visions. Following challenges from the general scientific community, on the basis of technological feasibility, Drexler renamed his understanding and aspirations for nanotechnology: 'molecular manufacturing'. Thus, in the 21 st Century, the term 'nanotechnology', whilst similar to molecular manufacturing in that it involves work on the level of atoms and molecules, refers to an applied science, focussed upon exploiting novelties arising from size-dependent phenomena exhibited in nanoscale matter. When dealing with matter below approximately 50 nanometres, the laws of quantum physics supersede those of traditional physics, resulting in "...changes to a substance's conductivity, elasticity, reactivity, strength, colour, and tolerance to temperature and pressure" [16]. Such changes are useful to all industrial sectors where nanotechnology will enable smaller, faster, 'smarter', cheaper, lighter, safer, cleaner and more precise solutions [17-19]. For example, in the field of drug delivery, Peppas notes that nanoscale pH-sensitive hydrogels for treating patients with multiple sclerosis, "release at varying rates depending on the pH of the surrounding environment", suggesting that "...these nanoparticle carriers may protect drugs from being broken down in the body until they reach the small intestine" [20]. Furthermore, progressing from the micro-to nano-scale involves inherent increases in a material's surface area and surface-to-volume ratio that can be used to manufacturing advantage. Ancient Origins of Nanotechnology Yet, utilising science at the nanoscale is not new. For example, in the 4th Century A.D., the Romans applied gold and silver nanoparticles to colour glass cups [21]. The resulting artefacts were red in transmitted light and green in reflected light -a sophistication not reproduced again until medieval times. There are many scientists today who would argue they have been conducting research in the realms of the nanoscale since well before 1990. Reasons Why Nanotechnology has only Come to the Fore in Recent Times Nanotechnology and Developing Countries -Part 1: What Possibilities Saved from URL: http://www.azonano.com/article.aspx?ArticleID=1428 P /11 So how come more and more people are talking about nanotechnology as the 'next big thing' if it has 'existed' for such a long time? There are three main reasons. Firstly, only in the past few decades have we really had the experimental means to conduct work focussed on activity at the nanoscale. Emerging tools, including scanning probe microscopy, quantum mechanical computer simulation and soft X-ray lithography, have combined with new synthesis methods, such as chemical vapour deposition, leading to a significantly greater, ever accelerating understanding of scientific endeavour at the nanoscale. These progressions have been paralleled by the discovery of materials such as fullerenes and nanotubes and, in more recent years, stimulated by a flood of government nanotechnology funding in countries such as the U.S., China and Japan. Secondly, nanotechnology has, as its underlying aim, the desire to manufacture with ultimate precision on the atomic scale in a 'bottom-up' manner. This means that, rather than the traditional approach to manufacturing whereby bulk materials are whittled down, nanotechnology aims to produce devices commencing with the self-assembly of individual atoms into precise configurations, as has been the case with combinational chemistry for many years. Whilst a great deal of nanotechnology continues to utilise 'top-down' processes such as lithography, the gradual trend is towards 'bottom-up' approaches that hold numerous, long-term manufacturing, financial and environmental advantages. Thirdly, and arguably most importantly, the recognition of nanotechnology as an emerging field demands and creates new levels of multi-disciplinary collaboration and cross-fertilisation amongst the sciences. Practically, this happens because of the integrated exploitation of biological principles, physical laws and chemical properties at the nanoscale [22]. The increasing desire and need to classify technology resulting from nanoscale manipulation and the progressive integration of scientific disciplines at a unifying length-scale, has led to the accepted term 'nanotechnology', under which new research is growing and existing research is often re-classified. Whilst nanotechnology is projected by the U.S. National Science Foundation (NSF) to have a global market value of $1 trillion e by 2011 [23], early signs in the information and communications technology (ICT) and textile industries are that nanotechnology is more complementary, than displacing. According to a UNESCO-sponsored study in 1996, "nanotechnology will provide the foundation of all technologies in the new century" [24]. However, basket-casing nanotechnology as 'another biotechnology' runs the risk of disregarding novel implications (both advantageous and detrimental). For those involved in the development of nanotechnology policy, one of the greatest challenges will be the efficient use of time; distinguishing and dealing with novel ethical, legal and social implications whilst ensuring appropriate contextualisation. Relevant, Appropriate Applications for Developing Country Healthcare? Given the 'capital intensive, high-tech, science fiction' branding it has received from much of the developed world media, nanotechnology would appear highly incongruous with sustainable development practices. In response to a recent study that ranked nanotechnology applications, from social development cluster areas f , according to their potential benefit for developing countries [10], Invernizzi and Foladori, cite the ability of China and Vietnam to significantly reduce malaria in the last century without the use of emerging technologies [9]. Furthermore, Brown notes that, "within development circles there is a suspicion of technology boosters as too often people promoting expensive, inappropriate fixes that take no account of development realities" [26]. Others believe the promotion and debate about nanotechnology in countries such as India, China and Brazil, threatens to divert and detract resources, political will and attention from the needs of the poor [27] and could inhibit research necessary to "address society's problems in a systemic manner" [Mulvaney cited in 6]. In addition to nanotechnology possibly promoting a 'technical fix' approach [28], there is a concern that high entry prices for new procedures and skills are "very likely to exacerbate existing divisions between rich and poor" [Healy, cited in, 28]. Dispelling Misconceptions about Nanotechnology Yet much of the early commentary from research groups and developing countries engaging in nanotechnology discussions has been united in the identification of relevant applications in areas such as solar cell technology, water purification; and health-related diagnostics and therapeutics [1, 4, 29-32]. At an international policy level there has Nanotechnology and Developing Countries -Part 1: What Possibilities Saved from URL: http://www.azonano.com/article.aspx?ArticleID=1428 P /11 Many believe nanotechnology offers new ways to address residual scientific concerns for Mycobacterium tuberculosis (TB). Declared a global emergency by the World Health Organisation (WHO) in 1993, the re-emerging threat of TB continues to be technically compounded by significant increases in the prevalence of multi-drug resistance (MDR), in a number of settings [38]. Treatments with improved sustained release profiles and bioavailability can increase compliance through reduced drug requirements and therein minimise MDR-TB [39]. Additionally, improved diagnostic tools are required to meet the needs of the WHO's expansion of the Directly Observed Treatment Short-course, MDR and co-infection with HIV [40]. In India, the country with the highest estimated number of TB cases [41], research is underway into the role nanotechnology can play in addressing such concerns. A nanotechnology-based TB diagnostic kit, designed by the Central Scientific Instruments Organisation of India and currently in the clinical trials phase, does not require skilled technicians for use [42] and offers efficiency, portability, user-friendliness and availability for as little as 30 rupees [43] (less than US$1). In the Medical Sciences division of the U.S. Department of Energy, researchers are investigating an optical biosensor for rapid TB detection [44]. Furthermore, a group at RMIT University, in Australia, is conducting research into the application of novel tethered nanoparticles as low-cost, colour based assays for TB diagnosis [45]. Polylactide co-glycolide nanoparticles are being investigated by groups at Harvard University (U.S.), the Research (South Africa), as drug carriers for treating TB [46-48]. So far, all groups have registered high levels of drug encapsulation efficiency, whilst both the Indian and South African groups have demonstrated sustained release profiles. Furthermore, the Indian group have reported increased bioavailability and "undetectable bacterial counts in the lungs and spleens of Mycobacterium tuberculosis-infected mice" 21 days post-inoculation [49]. The South Nanotechnology and Developing Countries -Part 1: What Possibilities Saved from URL: http://www.azonano.com/article.aspx?ArticleID=1428 P /11 TB is just one example of current nanotechnology research relevant to infectious diseases most prevalent in the developing world. Inter alia, science ministers from South Africa, Brazil and India have been working together on identifying ways in which nanotechnology can assist HIV/AIDS [3]. An Australian company, Starpharma™, is developing a preventative, clear, HIV microbicide gel, based on dendrimer nanotechnology, that would remain effective when applied by women up to four hours in advance of sexual intercourse [51]. Also in Australia, the Austin Research Institute has conducted successful trials into nano-vaccines for malaria [52]. Researchers at the State University of Campinas, Brazil, are investigating drug and vaccine delivery for leishmaniasis [53]. At the Chidicon Medical Center in Nigeria, researchers are studying nanoscale copolymer assemblies for diagnostic imaging and therapeutic management of infectious diseases [54]. Furthermore, in a joint project between the Rensselaer Polytechnic Institute (U.S.) and Banaras Hindu University (India), scientists are investigating easy-to-manufacture, carbon nanotube filters that remove nano-scale germs, such as the polio viruses, E. coli and Staphylococcus aureus bacteria, from water [55]. Long Term Effects of Nanoparticles Whilst Barker comments that "any helpful technologies should be brought into service..." for developing countries [4], others caution about the unknown risks associated with nanoparticle accumulation, toxicology and permeation [2]. As a report to the European parliament noted, "the state of research concerning [sic]... The behaviour of nano-particles is actually rather limited, preliminary as well as contradictory" [56]. Whilst the comprehensive 2004 report by the Royal Society and Royal Academy of Engineering (U.K.) recommends that "factories and research laboratories treat manufactured nanoparticles and nanotubes as if they were hazardous waste streams" [28], many traditional Chinese medicines are now known to have contained metal nanoparticles [57]. Hoet et al. argue that "...producers of nanomaterials have a duty to provide relevant toxicity test results for any new material, according to prevailing international guidelines on risk assessment" [58], leaving others disturbed that the cosmetic industry has refused to release test data into the public domain g , despite claiming that products such as sunscreen lotions are safe [59]. Furthermore, early suggestions from the U.S. and U.K., that nanotechnology is inherently regulated [56], have encountered stiff opposition from the action group on erosion, technology and concentration (ETC group), and others, who believe nanotechnology enters a 'regulatory vacuum' and that some new properties of nanoparticles are not covered by existing chemical regulations [2, 60]. Risk versus Benefits of Nanotechnology and its Effect on Applications However, in light of the debate surrounding Genetically Modified foods, Court et al. argue that an exclusive focus from the developed world upon issues of risk threatens to divert attention from identifying and applying nanotechnology to the developing world [1]. An engagement with 'risk' and the consideration of nanotechnology's application to the developing world need not be mutually exclusive. In fact, although technological 'risk' affects countries in different ways depending on the nature of their engagement with change, it remains a universal consideration and a crucial factor in ensuring the appropriateness of new technology, to any setting. Although in-depth discussions about health risks and the contribution of developing country perspectives are beyond the scope of this paper, it is clear that a number of issues remain unresolved and require greater consideration that incorporates truly global perspectives. Nanotechnology and Developing Countries -Part 1: What Possibilities Saved from URL: http://www.azonano.com/article.aspx?ArticleID=1428 P /11 5 The Potential Nature of Developing Country Engagement with Nanotechnology The nature of nanotechnology's global impact will largely depend on the answers to five, key questions surrounding nanotechnology innovation: who? what? when? where? and why? Developing countries will experience differing forms of engagement with nanotechnology but can we comment on any overall impacts? Will nanotechnology, as Daar suggests, be "a profitable industry for countries in the South h " [61]? Or will it "exploit the South" [Shiva cited in 6] and threaten developing country markets in primary production areas such as cotton, rubber and minerals [8]? Will developing countries play the role of the 'manufacturing-base' for nanotechnology innovation, as suggested by Whittingham and Bateman's 2003 'cost-benefit analysis of moving nanotechnology R&D and manufacturing to Eastern European and developing countries' [62]? Already, Malaysia and South Africa have been highlighted as countries with comparative advantage in manufacturing for nanotechnology [32, 63]. Which Countries will Manufacture and which Will become Nanotechnology Importers Perhaps the nature of developing country engagement with nanotechnology is believed as largely given? Salvarezza argues that an identification of Northern-based nanotechnology applications for the developing world predisposes participants to a scenario where "developing countries appear as passive actors... turning them into NT [nanotechnology] importers", widening economic and technological dependence [36]. Yet others point to the effective development of biotechnology R&D in China, India, Brazil and Cuba, suggesting an early developing country engagement with nanotechnology innovation could reduce the possibility of these countries being net importers of the technology [25, 64]. Given that domestic innovation and technological advance have been identified as the most important mechanism for the ability of countries to improve economically and ultimately close the rich-poor divide [65], nanotechnology has been promoted by a recent UNESCO report as important to developing country innovation [3]. Developing Countries Active in Nanotechnology Development With this in mind, a 2003 report by the University of Toronto Joint Centre for Bioethics claimed a number of developing countries are exhibiting a "surprising amount of nanotechnology activity" [1]. The study noted that China, India and South Korea had established national activities in nanotechnology; Thailand, The Philippines, South Africa, Brazil and Chile had some form of government support and national funding programs were being developed; whilst Mexico and Argentina had some form of organised nanotechnology activity but no specific government funding [1]. Some see nanotechnology enabling developing countries "to 'leap frog' their way to leadership" [66], with the Indian government looking to use nanotechnology to 'catch up' in global economic terms [67, 68]. Patent Applications as an Indicator of Nanotechnology Activity However, with patents known to be a useful indicator of "technology development" [69], an assessment of 2003 figures from the U.S. Patent and Trademark Office (USPTO) highlighted the commanding lead held by the U.S. in nanoscale science and engineering patenting, with 42% of the overall share. Germany followed with 15.3%, and Japan was placed 3 rd , with 12.6% [69]. Fast growth was said to be occurring in South Korea, the Netherlands, Ireland and China. A report later that year claimed China was ranked 3rd in general nanotechnology patents behind the U.S. and Japan [70]. Furthermore, of all the U.S. patent applications in nanotechnology, 90% are held by the private sector, with the remainder split amongst the public sector (roughly 7% from universities and 3% from government agencies and collaborative research centres) [71]. In recent times, companies such as '3M', 'IBM' and 'Hewlett Packard' are Nanotechnology and Developing Countries -Part 1: What Possibilities Saved from URL: http://www.azonano.com