First published in Nature Nanotechnology as “Is Novelty Overrated”. Nature Nanotechnology 9, 409–410 (2014) doi:10.1038/nnano.2014.116 [link]

Nanomaterial risks are often considered in terms of novel material behaviours. But does this framing end up obscuring some risks, while overplaying others?

Novelty and nanotechnology are deeply intertwined. The search for nanostructure-enabled materials has driven research funding in nanotechnology for well over a decade now; the exploitation of novel properties has underpinned the commercialization of nanomaterials; and concerns over potential risks has stimulated widespread studies into what makes these materials harmful. Yet ‘novelty’ is an ephemeral quality, and despite its close association with nanotechnology, it may be an unreliable guide to ensuring the long-term safety of materials that emerge from the field. If this is the case, do we need to find alternative approaches to developing advanced materials and products that are safe by design?

Exploiting novel material behaviour is a fundamental driver for global nanotechnology investment for good reason: unusual material properties have been shown globally to be an effective stimulant for cross-disciplinary research, and harnessing these properties has provided opportunities to address societally relevant challenges in areas such as renewable energy and clean water, as well as creating new markets and enabling economic growth. Intuitively, however, novel behaviour comes hand in hand with the possibility of unexpected human health and environmental impacts. Alongside the successes of nanotechnology, there have been fears that if not spotted and corrected early on, novel impacts could undermine public trust in new materials and reduce the anticipated economic, societal and environment benefits they promise.

This is the concern that has stimulated over a decade of research and dialogue on the health and environmental impacts of engineered nanomaterials [1]. And it’s based on the assumption that novel behaviour is potentially correlated with novel risks. In many ways this is a reasonable assumption. Nanoscale science and engineering are certainly enabling the creation of materials that exhibit unique and sometimes counterintuitive properties. These materials are often promoted by nanotechnology proponents as taking advantage of novel physical and chemical behaviours of matter engineered at the scale of 1–100 nm. It isn’t too far of a stretch therefore to speculate that these behaviours could potentially translate into novel biological behaviour. And from there, to novel risks to people and the environment.

This is a compelling line of reasoning and one that is often encountered within nanotechnology risk research and policy circles. It’s certainly one that made sense when engineered nanomaterials first began to be used in commercial products at a time when health and environmental implications were not well understood. But as new materials and the products that rely on engineered nanomaterials become increasingly sophisticated and widespread, it’s a line of reasoning that may ultimately compromise the ability of developers and regulators to ensure their safety. And the reason is the embedded reliance on novel behaviour as an indicator of potential risk.

For materials research and development, novelty has been and remains a powerful driver of progress. Many engineered nanomaterials now emerging take advantage of intrinsic physical and chemical properties that are directly influenced by size and shape, and as a result exhibit behaviours that can legitimately be considered novel compared with more conventional materials. Quantum confinement, material–photon interactions and group electron dynamics, for instance, are all phenomena related to the nanoscale that are being exploited at the macroscale with some success. Novelty in these cases relies on intrinsic properties that are either unique to precisely nanostructured materials, or are amplified significantly in materials with designed features at this scale.

This is the understanding of novelty most often assumed in the context of engineered nanomaterials, and is the type of out of the ordinary behaviour most frequently cited as the reason for addressing their potential risks. For many materials though, the properties that make them interesting are less esoteric. For example, the ability of small particles to penetrate the leaky vasculature around tumours and deliver therapeutic payloads is a useful one. But the ‘novelty’ in this case is the particles’ extrinsic ability to penetrate to areas where larger ones cannot — that is, their behaviour is not necessarily predicated on intrinsic properties that are unique to the nanoscale. Another example is the strength-to-weight ratio of carbon nanotube composites, which depends in part on the length and alignment of the nanotubes in the matrix material rather than the esoteric nature of the material itself.

What constitutes novelty is, as a result, open to interpretation, and because of this, framing the potential risks of new materials in terms of their novelty runs the danger of segregating the world of new materials into behaviours that are considered by some to be novel, and therefore interesting; and behaviours that are considered mundane, and therefore not. Segregation along these lines may be justifiable from the perspective of materials research and development, but it raises serious concerns from a health and environmental perspective, where even mundane risks are important. However, segregation in terms of novelty makes little sense to materials developers and manufacturers, which further undermines its use in approaching risk. For all the emphasis on novelty within nanotechnology, manufacturers are ultimately more interested in material functionality and utility — and whether a new material will allow them to achieve an economically viable, and competitively advantageous, product that could not be made otherwise. The resulting materials and products might be considered novel by some, but it is utility (and the market’s response to utility) that ultimately determines their success.

The distinction between material novelty and utility becomes even more marked when considering the commercial products that utilize new materials. These are typically constructed from many materials working in concert — some of which change or lose their individual identity when incorporated into the product. The functionality of a smart phone for example, or even a piece of clothing or a cosmetic, relies on component materials integrating with each other synergistically to create a viable product. As materials are combined, their properties influence, and are in turn influenced by, those of other materials. And when parts of a product are abraded, detached or otherwise released into the environment, these emitted materials will have a tendency to reflect this history of integration and transformation. In other words, materials are mutable, and as a result their ‘novelty’ is frequently ephemeral.

Novelty as a result is a subjective, transient, and consequently a rather unreliable indicator of potential risk. It tends to obscure the reality that conventional behaviour can sometimes lead to harm, and that mundane risks are still risks. And it favours the interesting (and possibly the headline-grabbing) over the important. But if novelty is an unreliable guide to potential risk, how can approaches be developed that help identify, understand and manage plausible risks associated with emerging materials and the products that use them? This remains a critical question as, without a doubt, some of the increasingly sophisticated materials now being developed will present significant health and environmental risks if not used appropriately [2]. Some of these risks will be new or unusual; others may be conventional but not obvious. In all cases though, sustainable growth and innovation in manufacturing materials that are safe — or safer — by design, and present an increased ability to solve important societal challenges and avoid unacceptable health and environmental impacts, will depend on identifying and managing them.

This though is a complex problem to solve. Materials that are released into the environment, or have the potential to enter the human body, present multidimensional and dynamic health risk challenges. Although research is slowly providing insights into what makes materials — nano or otherwise — more or less hazardous, we are still struggling to develop the broader conceptual frameworks needed to ask useful, and timely, questions about material risks. In part, this has been confounded by an emphasis on the novel behaviour of pristine materials, with relatively little attention being paid on plausible risks presented by incorporation of emerging materials into plausible products. This raises the possibility, though, of developing useful frameworks around potential material risk by focusing more closely on context-specific material behaviour associated with commercially realistic products, rather than novelty per se.

Using an approach, for instance, that is grounded in plausible products and behaviours, it may be possible to construct methodologies that help establish boundaries around likely areas of significant risk. By exploring exposure potentials and characteristics across the life cycle of a product that utilizes new materials, it is, in principle, possible to flag up areas of risk concern that can be used to direct further research and action. And if this approach is applied to prospective, but highly plausible products, it should be possible to map out plausible domains of risk that are associated with likely exposures to realistic materials [3]. From the perspective of health and environmental protection, a more nuanced approach along these lines has the advantage of being aimed at preventing harm however it is likely to be caused, and filtering out plausible modes of harm from the merely speculative and ‘novel’. It would also help promote greater commercial certainty, and reduce regulatory uncertainties for those wanting to invest — or benefit — from such materials and products.

If such an approach is adopted to exploring possible risks associated with emerging materials, one of the consequences is that structures at the nanoscale — and as a result novelty associated with the nanoscale — is relegated to just one of a number factors considered when mapping out potential risks. This is not to say that engineered nanomaterials do not present significant risks in some cases. To the contrary, there is clear evidence that materials such as carbon nanotubes, fine-structured metal and metal oxide particles, and a number of nanoscale drug-delivery vehicles exhibit behaviours in the body and the environment that can lead to harm. But although some new materials clearly do present nanoscale-mediated health and environmental risks, there remains no indication of a bright line at 100 nm that leads to a radically altered potential of a substance to cause harm if crossed [4].

In the absence of a size-based bright line, serious consideration needs to be paid to any material that has the potential for environmental release or ingression into the human body. From the perspective of human health in particular, particles tens of micrometres in diameter and beyond can unintentionally enter the body through the respiratory system and the gastrointestinal tract. Large and small particles alike can potentially lead to exposure to their component chemicals through leaching and dissolution if they deposit on the skin or mucous membranes. (Smaller particles may potentially enter the body if applied to damaged skin, although current evidence indicates healthy skin is a tight barrier to even nanoscale particles [5].) When it comes to intentionally introduced materials, therapeutics several hundred nanometres in diameter may be injected directly into the blood stream, and medical devices/prosthetics up to centimetres in scale and beyond may be implanted within the body. Once in the body, the mechanisms by which these materials may cause harm will be predicated on the hard reality of material–biology interactions, and not on an arbitrary determination of novelty.

Ultimately, the commercial success of any new material will depend on an ability to develop and use it responsibly, with minimal chances of unanticipated health and environmental risks arising from its manufacture, use and/or disposal. Inevitably, there will be materials created — intentionally or not — that present significant hazards, and there is a pressing need for methodologies to identify and address these as early as possible in the research and innovation process. Yet, novel physical and chemical properties would seem to be unreliable sentinels of potential risk, especially where they focus attention on what is interesting above what is relevant, and as a consequence potentially obscure significant threats to human health and the environment. Plausible and context-specific material behaviour may provide a more robust and utilitarian approach to safe and sustainable materials innovation, as it allows a refocusing on possible health and environmental impacts. One downside of this approach is that it de-emphasizes the nanoscale as a primary driver of concern. But as commercial utility leads to increasingly advanced materials that are designed across multiple scales and that are defined by what they do rather than what they are called, perhaps this refocus is a good thing. Especially if the end goal is the long-term safety of materials and products that are of use to society.

References

1. Hansen, S. F., Maynard, A., Baun, A., Tickner, J. A. & Bowman, D. M. in Late Lessons from Early Warnings: Science, Precaution, Innovation 562–591 (European Environment Agency,2013) [Link]

2. Maynard, A. D., Warheit, D. & Philbert, M. A. Toxicol. Sci. 120, S109–S129 (2011). [Link]

3. Maynard, A. D. in Nanotechnology Environmental Health and Safety: Risks, Regulation, and Management (Micro and Nano Technologies) 2nd edn (eds Hull, M. & Bowman, B. M.) 339–365 (William Andrew, 2014).

4. Donaldson, K. & Poland, C. A. Curr. Opin. Biotechnol. 24, 724–734 (2013). [Link]

5. Nohynek, G. J., Lademann, L., Ribaud, C. & Roberts, M. S. Crit. Rev. Toxicol. 37, 251–277(2007). [Link]

Image: Light Scattered by Gold Nanorods.  Courtesy: National Science Foundation.  [Link]

Andrew Maynard