As one who has closely followed the emergence of nanotechnology, I am sure I was not alone several years ago in welcoming what appeared to be a refreshingly new attitude among a broad range of stakeholders toward the introduction of this new set of technologies and materials.  Calls from my organization to "get nanotech right the first time" were echoed widely.  Perhaps the most frequently used metaphor, though, was that a "window of opportunity" had opened to do things differently this time.  But I increasingly fear that the window is closing.

Not long ago, the debate over nanotechnology seemed to reflect a willingness to learn from past failures in how our society had approached the introduction of other novel technologies like genetically modified organisms.  Many called for an inclusiveness that provided a seat at the table for all stakeholders.  And all parties, the industry included, tacitly if not always overtly agreed that a more cautious approach was needed, one that would identify and forthrightly address potential risks alongside the development – that is to say, the responsible development – of nanotechnology.

Perhaps the first sign of trouble came about 18 months ago, when officials charged with overseeing the National Nanotechnology Initiative testified before Congress to the effect that all the hoopla about nano risks was overblown and the result of shoddy science.  Then a year ago February, the White House felt obliged to issue its so-called "Principles for Nanotechnology Environmental, Health, and Safety Oversight," addressed to all federal departments and agencies, that seemed primarily intended to rein in any renegade federal officials hell-bent on over-regulating nanotechnology.

The latest signs that the window of opportunity is closing fast are coming from some among the legions of lawyers whose business it is to protect nano-enabled companies from legal actions.  As Rick Weiss reported last week in a piece titled "The Big Business of Nano Litigation," industry lawyers are sending mixed messages to their clients, some of them now apparently advising their clients to forget all the warm fuzzy stuff.  The latter group's messages:

• Don't rush to line up to work voluntarily with government agencies.
• Don't volunteer to turn over your data to government.
• Don't do any testing that you aren't required to do. (Rick Weiss quotes George Burdock, president of the Burdock Group, as advising clients not to overdo it: "Don't test yourself out of a product.")

That kind of advice might help to explain the low level of participation in both the basic and in-depth components of EPA's voluntary Nanoscale Materials Stewardship Program.

I certainly don't want to imply this is the only or even the predominant message reaching or emanating from nano companies, but these kinds of statements seem to signal an unfortunate shift toward a more defensive strategy and away from one that would keep that window of opportunity open at least a while longer.

In some nanotechnology circles, it is almost a mantra that, once released to the environment, nanoparticles will inevitably aggregate or agglomerate into larger masses and thereby lose their nanoscale-related properties and, by implication at least, any associated risks.

But can we count on nanoparticles released to the environment to self-regulate their own risk so conveniently?

For example, the National Nanotechnology Initiative prominently features on its website an article it commissioned, titled "Understanding Risk Assessment of Engineered Nanomaterials:  How can we know what is a risk and what is not?"  In a section designed to lead readers to question published studies that suggest nanomaterials might pose risks, the article says: "In solution or in air, it's quite difficult to keep nanomaterials separate, as they tend to clump in larger aggregates or agglomerates."  This is a point the author of this rather short article felt compelled to repeat twice more.

An FAQ issued by Germany's Federal Institute for Risk Assessment states that "nanoparticles tend to aggregate into larger unions which are generally larger than 100 nm. The toxic effects of nanoparticles linked to their small size and higher reactivity are then no longer relevant."

And a recent post on the blog of the nanotechnology practice group at Porter and Wright asserts that nanoparticles "have been shown to have fewer potential adverse health effects when they occur in cluster form (aggregates and/or agglomerates).  In the 'good news' department, scientists studying aerosol dispersion of nanoparticles have found they tend to cling together when dispersed into the environment." 

I won't even begin to try to lay out here how much more complex and unpredictable than this nanoparticle aggregation and environmental fate and transport are in the real-world.  Instead, let me just cite two excellent papers that do so:  see Maynard and Weisner et al.

But I do want to briefly discuss and cite some recent studies supporting three reasons why we can't count on nanoparticles released to the environment to self-regulate their own risk so conveniently: 

1.  Some nanomaterials can be stabilized as nanoscale particles in solution under environmental conditions.  A number of studies have found that carbon-based nanomaterials – despite their inherently very low water solubility – can be "solubilized," that is, can enter and remain in stable suspensions upon interaction with water or with other common, naturally occurring substances.  The latest study, authored by Salonen et al. and published in the journal Small, finds that C₇₀ fullerenes can form "stable, homogeneous suspensions" in water through interaction with ubiquitous phenolic acids that are present in and released from virtually all plant matter.  It appears that individual C₇₀ fullerenes first become coated with the phenolic acid, and then form small, loose clusters with diameters on the order of a few nanometers.  This study merited a "spotlight" on the Nanowerk website.

Earlier work has found similar behavior:  Fortner et al. identified the formation of stable suspensions of "nanocrystals" of C₆₀ fullerenes in water – nanoscale (25-500 nm diameter) aggregates they call "nano-C₆₀" that have entirely shed the extreme hydrophobicity of the individual fullerenes.  Hyung et al. found that multi-walled carbon nanotubes could be stabilized as individual particles through interaction with natural organic matter found in river waters; the natural material actually worked better than commonly used surfactants selected to serve that same solubilizing function.

2.  For performance reasons, nanoparticles are being actively engineered not to clump.  For most nanomaterial applications, optimal performance depends on minimizing any disordered clumping or even maximizing dispersal, so that the properties of individual nanoparticles or highly ordered nanostructures can fully exert themselves.  For this reason, researchers are working overtime to coat, cap, chemically modify or otherwise force nanoparticles not to aggregate or agglomerate.  See, for example, Yang et al.'s use of special capping agents to prevent aggregation of platinum nanoparticles, and Nadagouda and Varma's similar work with silver and palladium nanoparticles.  Similar efforts have been mounted to chemically modify ceramic nanoparticles to ensure dispersal.

So even to the extent that native or current forms of nanoparticles do readily clump or retain their hydrophobicity, any assumption that engineered nanomaterials entering commerce and the environment will inevitably do so is wholly unwarranted.

3.  Even agglomerated or clumped nanoparticles can be toxic.  The assumption that aggregated nanoparticles lose all of their nanoscale properties or become benign is also unwarranted.  Maynard and Kuempel have amply demonstrated that even large aggregates on individual nanoparticles typically retain many of their nanostructural features and properties.  But what about toxicity?

Fortner et al. found that their fullerene nanocrystals exhibited antimicrobial activity, suppressing bacterial growth and respiration.  In addition to confirming nano-C₆₀'s antibacterial activity, a recent paper by Lyon and Alvarez cited a number of studies demonstrating that the formation of these nanoscale aggregates in water yields a material with high toxicity to aquatic invertebrates, fish and the cells of higher organisms.  The aggregates have also been shown to enter and accumulate in those cells and to adhere to lipids.

Finally, Salonen et al. showed that their phenolic acid-coated C₇₀ clusters could readily translocate across the membranes of human cells in culture and enter the membrane surrounding the cell nucleus.  Moreover, they induced the contraction and ultimate death of those cells – ironically, apparently by aggregating into micro-sized particles through interaction with the cell membranes.

Once again, we find that nanomaterials' actual behavior confounds conventional wisdom and, when approaching their toxicology, forces us to question or abandon our assumptions and biases.

Yesterday the U.S. House of Representatives overwhelmingly passed the National Nanotechnology Initiative Amendments Act of 2008 (H.R. 5940), by a vote of 407-6.  Among other changes, the bill calls for a number of much-needed improvements in how the NNI addresses health and environmental concerns associated with nanotechnology.  See EDF’s news release issued today.

Just when you thought it might never emerge, the National Nanotechnology Initiative’s (NNI) Strategy for Nanotechnology-Related Environmental, Health and Safety Research [2.2 MB PDF] finally hit the streets last week.

It’s got good, bad and ugly. The good news is that here, at last, is a report from NNI that actually reads more like a strategy and less like yet another laundry list of research needs. The bad news is that key elements of a full strategy are still nowhere to be found.

As a depiction of what the NNI’s research agencies have been up to, the report advances publicly available information considerably. For the first time, NNI has provided a detailed, if somewhat dated, list of projects – 246 in all – completed or in progress during FY2006. For each project there is even a handy hyperlink to a more detailed abstract of the project. That’s good to see, and took a lot of work to compile, no doubt.

But here’s the bad news: No dollar figures are provided for the individual projects, only aggregated funding estimates for broad categories of research – despite the maddening fact that NNI obviously must have had such raw data in order to provide the aggregated totals. And the list of projects includes ones that are clearly not directly relevant to understanding risk; for just one example, see project A2-4 Diffraction Studies of Glasses, Liquids, and Nanoclusters.

Even NNI admits its tally includes tangential projects, though the disclaimer is buried in the fine print and far removed from the dollar figures, which are displayed prominently in the Executive Summary and NNI’s press release. This obfuscation is hardly a way to quell the longstanding suspicion that NNI routinely over-counts what it is spending on risk-relevant research.

The report usefully describes the state of research efforts under each of its 25 research priorities, identifying which aspects are getting ample attention and which are not. A good start, but that’s essentially where it stops. A real strategy would take it the next step, by indicating how much more actually needs to be spent in each area to address the identified deficiencies or gaps, how the funding will be provided, and who will take responsibility for ensuring the work gets done.

Indeed, NNI seems so averse to putting someone in charge that it can’t even bring itself to identify lead agencies for each major research area, instead designating them as merely “coordinating agencies.” There’s no indication as to how decisions will get made or how funding will be allocated or shifted to research areas not currently receiving enough, other than the usual lip service paid to the need for a “coordinated interagency approach.”

Now for the ugly. A disturbing sentence appears in the report’s description of its strategy implementation framework (on page 46): "Gaps identified in the research that supports regulatory decision making should not be addressed at the cost of broad-based fundamental research – to do so would ultimately undercut the U.S. nanotechnology initiative as a whole."

In other words, NNI says it’s okay with them if gaps persist on the risk questions, if filling them would mean taking money away from research to advance nanotechnology. This is another clear indication of the lower priority NNI actually gives to the risk side of the equation, and of the growing conflict of interest between the promotional and oversight roles NNI has been charged with.

These shortcomings in NNI’s new strategy reinforce how essential it is to have an independent, expert body – the National Academy of Sciences – step in, not only to review the strategy report (that’s soon to get underway), but also to help craft an effective federal nano risk research strategy and oversee its implementation. Happily, Congress has requested just that, calling on the U.S. Environmental Protection Agency to contract, by March 21^st, with NAS for this much-needed more extended involvement.