NANOPARTICLES may be highly problematic for dozens of reasons. WE DO NOT claim otherwise. We examine below how findings from the
"How buckyballs hurt cells." This headline appeared regularly during the last few days and was drawn from some of the findings of the
Having read this study it is important to separate the authors’ conclusions from the rhetoric that is already seeping into the general communication channels. The following conclusions are based on what the quantitative data from the computer simulation shows and not claims made by the authors in either the introduction or discussion.
- Both monomer and aggregate fullerenes can diffuse into the membrane lipid bi-layer, although they do so at different rates.
- Monomer fullerene has little effect on the physical or structural properties of the lipid bilayer.
- Aggregate fullerenes tend to dissociate once in the lipophilic region of the lipid bilayer and can induce membrane stretching, thickening, lipid protrusion, and bilayer bending.
- The aforementioned membrane distortions can lead to membrane stretching causing reduced cell diffusion and potential over-activation of stretch-mediated membrane protein channels. These effects are no different then adding cholesterols, small alcohols, or small lipids to the membrane.
- Aggregate fullerenes do not cause bilayer rupture, micellization, or pore formation that might cause the cell to lyse.
Now let's examine what the article does not say.
- There is NO simulation as to the propensity or rate of flow of the monomer or aggregate fullerenes through the membrane into the cell interior.
- There is NO chemical data or analysis as to how the fullerenes might exhibit toxicity or cell damage either in the cell or in the membrane interior.
- There are NO data directly linking the movement of fullerenes in cell membranes to other selective body barriers (such as the blood-brain barrier).
In the recent study by Wong-Ekkabut (2008) they use a computer chemical modeling simulation to assess the impacts of both single and aggregate fullerenes on cell plasma membranes. It is important to note that these are not in vivo or in vitro experiments, but models based on chemical understandings of the nature of fullerenes and phospholipids bilayers (cell membrane molecules).
Modeling as mode of inquiry shares a long tradition in various fields of science. In a world that offers infinite possible variables, it allows researchers to simplify these complicated interactions into workable processes for which outcomes can be easily observed. These simulated outcomes can then be compared to observed “real-world” phenomena and the resulting comparison allows for an assessment of the strength and validity of the model. If the model is a good approximation of observations then the model becomes a useful tool for prediction. If the model fails, variables must be added, removed, or modified.
As media articles tout the innovative use of the WestGrid computer modeling that modeled the interaction between carbon-60 molecules and cell membranes, the Society of Toxicology still holds that “mathematical and computer models based on the predicted relationship must be validated by tests in animals and humans” because these methods provide limited information that apply “to a very specific test situation and may not fully anticipate the results in a complicated organism (such as humans).”
In the case of the Wong-Ekkabut et al. (2008) study, researchers were investigating the activity of a complex substance, carbon, with multiple characteristics that have to be taken into account when determining toxicity. The computer model demonstrated predictions about the translocation of fullerene clusters through a model lipid membrane but to more accurately demonstrate this possibility and/or probability, the computer model would have to factor in the characteristics of the carbon into the analysis. Other particle properties that are necessary for model prediction include: particle surface area; redox activity; composition/contamination; solubility; durability; particle count; particle size distribution; defect density; length of CNT affecting inhalation, transport, filtering and toxicity; charge; degree of agglomeration and environmentally relevant characterization.
All of these characteristics are important for toxicology studies because toxicology is complex. All chemicals may cause harm, depending on the dose of the exposure. Even some of the most common chemicals in our environment (like silica), exist in our food or water without toxic effects and yet under certain conditions they can be toxic. So, as Esdaile points out, how can we expect a computer model to predict complex outcomes of the interaction of chemicals with biological systems with all the associated problems of absorption, distribution, metabolism and excretion?
Computer prediction modeling is accepted for toxicological endpoints that are based on already well-understood mechanisms (such as skin sensitization). However when the endpoint is more complex, as is the case with nanoscience interaction, toxicities cannot be satisfactorily predicted (Simon-Hettich et al., 2006).
Other types of alternative modeling, such as artificial models of human skin (which replace any in vivo test for skin irritation), have been validated by The European Centre for the Validation of Alternative Methods (ECVAM). However, computer models are further away from validation. Although they are used extensively by industry as screening tools to predict drug toxicity, only one software tool, Lazar, is currently being validated by ECVAM for regulatory use. The lazar (lazy-structure-activity relationship) program is under validation regarding predictions of the rodent cancer bioassay. It is hard to determine though, whether or not the WestGrid software used in the fullerene computer simulation study has undergone any kind of validation from a toxicological organization and on what criteria researchers made their selection.
If there are no current observations with which to assess modeling validity, then the strength of the model is nothing more than a value judgment. There is a dearth of observational data in studies of the toxicology of nanoparticles and therefore, the conclusions drawn from modeling studies must be taken tentatively prior to epidemiological data becoming available to confirm their validity.
Media coverage of this topic has so far only appeared in a series of online scientific news sources including ScienceDaily, DailyTech.com, Eurekalert, Nanowerk, Genopharm, and NanoVIP.com. The University of Calgary also reported the story on its website. As of yet, the story has not appeared in more mainstream news outlets, although it is likely that it will due to the attention received by the carbon nanotube-asbestos metaphor. There is no wonderfully terrifying attention grabbing metaphor to use as a rhetorical device in this particular instance, but as more general publics begin to become more interested in nanotechnology such devices won’t be necessary. The very word “nano” will be enough to grab people’s attention. Since this story is riding on the coattails of the story comparing some carbon nanotubes to asbestos, it is likely that we will experience that effect. The problem here is that once again, “nano” is being associated with “danger”. If the word “nano” continues to be used in this way, then a new area of scientific study with potentially incredible benefits to humanity will be retarded by public fear inspired by media outlets interested in only the most shocking stories guaranteed to attract viewers and sell advertising.
Interestingly, of the seven news sources listed, only one, DailyTech.com, has yet to produce original content. Each other news outlet simply copied the information verbatim from the University of Calgary website. While it is understandable that the purpose of any news outlet, online or otherwise, is to inform the public, this parroting does raise a red flag. This is not a productive discourse of the issue; it is one source controlling the information. Granted, DailyTech.com is to some degree a repackaging of the information using different wording. Such repackaging is important, however, for in the use or omission of data a type of media discourse is enacted in which the most important concepts comet to the fore. This process is not perfect by any means as we have seen time and again in other important issues covered by the media, but it is certainly better than the parroting we see here.
When other news outlets such as the New York Times and the Washington Post pick up this topic, they may reword the story and thus push the discourse forward. However, their list of sources for the study only includes the first run of the information in these online science news outlets. This means that the University of Calgary news release people control the discussion here and we only get one reading of the data. Unfortunately, this means that the asbestos metaphor will continue to live on because it is cited in the story that has been repeated ad nauseum. The negative perception of nano could very well become a cumulative effect of news media stories citing their own laundry lists of shock stories.
Our hope then must turn to the bloggers (read: us), and there is hope. Not only are we doing our very best to bring you alternate readings of dubious content, but there are others as well. The good folks at Gizmodo, an online technology blog, submitted an entry entitled “Study kicks nanotechnology right in the buckyballs”. At least they called the absolute validity of a computer simulation into question as well. They too perpetuate the theme that we should be wary of a technology that we do not understand, which is a good and well worn point, but they introduce dissonance and make people think and that is a very good thing.
Finally, the web articles we examined suggested translocation but then added some speculation which transfers risk profiles from other nanoparticles and other studies to inflate the potential significance of the findings from this one. For example, most add the line “Fullerenes have been shown to cause brain damage in fish and inhaling carbon nanotubes results in lung damage similar to that caused by asbestos.” The first reference is to the Evan Oberdörster study on juvenile largemouth bass that was repeatedly refuted after its publication. The second refers to the