My Nano Year

While chewing recently on some of the ideas that have challenged me in my day job I was thinking about one topic that poses some interesting uncertainties. The current echo-chamber I am wandering into is steeped in the “nano” wave, as in nanomaterials, nanotoxicology, nanomedicine, nanoengineering. Nano, etymologically speaking, is a prefix derived from the Greek word for “dwarf” which has been adopted to mean “one billionth” of a unit. I suppose it could be applied to any sort of unit, like “nano-Joule or “nano-Calorie”, but those scales have little practical use, so it is most often reserved for units of length and time (nanometer and nanosecond). One colloquial definition I found uses the term to mean a very short period of time ("I'll be back in a nano"). And of course the iPod Nano has now become the first association with the term for most Americans. In the case of the emerging technology sector, it relates to the size scale of engineered materials with a length of 1 to 100 nanometers (10e-9 to 10e-7 meters) along at least one dimension.

The precise definition of “nanomaterial” is not nearly so straightforward, as several materials scientists and chemists reveal with their responses to the definition challenge in the inaugural issue of Nature Nanotechnology: http://www.nature.com/nnano/journal/v1/n1/full/nnano.2006.77.html There are already many international standard-setting societies (like ASTM and ISO) hard at work developing formal definitions, but the more you look the murkier it seems to get. It’s easier to put all of this aside by simply generalizing that “nanotechnology” is concerned with:

"…the design, characterization, production, and application of structures, devices, and systems by controlled manipulation of size and shape at the nanometer scale (atomic, molecular, and macromolecular scale) that produces structures, devices, and systems with at least one novel/superior characteristic or property." Nature Nanotechnology

Quite a tortured string of words that rely on intentionality and novelty and use, not just structure. This definition is typical of many that can be found and is intended to avoid including “incidental” (e.g. diesel exhaust) or naturally occurring (e.g. nitrogen dioxide, ultrafine dust) nano-scale materials.

OK, so what?

This comes up for me because of concerns that have emerged among environmental health scientists about the threat of nanomaterials to human health and the environment. After learning that the city of Berkeley recently adopted new rules to regulate nanomaterials the Cambridge City Council voted to request that the Public Health Department recommend a policy to address the health threats posed by nanomaterials manufactured, processed or handled in that city. This sort of request is generally forwarded to the Director of Environmental Health (me). This concern, like most topics that are tied to elusive scientific concepts, is based on an astounding lack of knowledge of the topic. There are popularized ideas about “nano-bots” coursing through your bloodstream to attack a tumor or clear up plaque blocking an artery. There are also stories about miraculous products that use nanomaterials to confer immense strength or UV protection or bullet-proofing while requiring such a trifling amount of this material that it can still be light as a feather. There are dreams of engineeering "vessels" that can efficiently deliver life-saving biopharmaceuticals or discrete genetic materials to fix or kill or even "patch" the genome of specific cells in the body while eluding all immune defenses.

Personally I like the more impressionistic ideas the best, like an army of “nano-bots” that are programmed to punch tiny holes in your brain or alter the activity of your neurotransmitters. Hard not to think of the exploration vessel in The Fantastic Voyage that traveled to the site of a blood clot in the brain of a brilliant Cold War era scientist.

But from a public health and environmental viewpoint there really are so many unanswered questions about nanomaterials and their safety, to wit:

* What happens when a material is composed of such minute discrete units that it can be taken up directly into the blood stream or lymph system or the optic nerve, circumventing our evolved barriers against external agents (xenobiotics)? Our digestive system and skin and ciliated bronchia provide us a great deal of protection from outside chemicals and we rely on the filtering and adhering and acidifying and chopping and conjugating chemistry carried out by our body to shield us from so much of this alien stuff.

* Assuming that some of this nanomaterial does get into our bodies directly, what happens to it then? Do materials that get through our skin then easily reach the bloodstream (translocation)? Do materials that reach our optic nerve then have a clear path to the brain without going through the Blood-Brain-Barrier (a bloodstream mechanism that provides an even more powerful hermetic filter against so many chemicals and pathogens).

* If some of these particles are so small that they can slip past many parts of our immune response and are not identified as foreign by the body, can they then reach the insides of cells through cellular gateways? Are these materials, if inside a cell, capable of damage by producing chemical radicals (unstable chemical forms that cause tissue and genetic damage)? There are many examples of materials that can do this, though the greatest concern is for damage that does not kill the cell and allows it to transform into a proto-oncogene and eventually a cancer cell.

* If the effects that we should be most concerned about arise from chronic exposure (occuring over years or decades) rather than short term exposure (occuring over hours, days or weeks) are we even going to see these effects using affordable short-term toxicity tests?

* Overall, is there reason to assume that the potential threat from these engineered materials is any different from naturally occurring nanomaterials (e.g. inert gases, ultrafine carbon compounds) or incidental nanomaterials (air pollutants from exhaust or off-gassing from a stove)? What special properties would suggest a special threat not already observed from other materials with discernable units on the same size scale?

* It has already been observed that some pure elements, like gold, behave differently in the body when engineered to take the form of nano-scale units (vs. bulk gold as we are familar with it). In such cases it seems that the scale itself has complicated implications for where the materials goes int he body and what it does there. Does this scale-dependent determination of biological effect exist for all nanomaterials, making generalizations based on our knowledge of the macro-scale equivalent of various materials useless in predicting harm?

* Even if there are some data that point to materials and uses that are likely to be safer than other materials or uses, how should we discuss these ideas with policymakers, workers, consumers, or even scientists who made be in harm’s way from exposures to unsafe levels of these materials? There is still so much guesswork and we may be decades away from detailed knowledge of the biological effect and fate of these materials.

* How do you weigh the principle of precaution against statements of known risk based on empirical or experimental knowledge? When is secondary, implied, modeled, or analogy-driven information sufficient to declare that something must be done to limit exposures to these materials? Where is the burden of proof?