REPETITION AND PROOF (CALGARY COMPUTER SIMULATION)

If you repeat something often enough, it seems to come true. Nothing works better than repetition to convert speculation into conclusion.

NANOPARTICLES may be highly problematic for dozens of reasons. WE DO NOT claim otherwise. We examine below how findings from the Calgary study published online by Nature Nanotechnology (online 18 May 2008; doi:10.1038/nnano.2998.130) are being discussed by the media, in this situation – the web media.

"How buckyballs hurt cells." This headline appeared regularly during the last few days and was drawn from some of the findings of the Calgary study (above). It is based on a computer simulation which demonstrated the translocation of fullerenes presumably through cell linings. Allegedly, aggregates of fullerenes dissolve in the membrane and enter the lipid membrane composing the cell wall. Subsequently, they may enter the cell at which point they remain as separate entities or re-aggregate. The previous sentences constitute an important supposition given that some of the speculation that appeared on web sites attempts to evaluate the implications of this work by suggesting intra-cellular damage.

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 Poland study we discussed in a previous posting: May 21. Neither of these studies support sthe brain damage in fish nor the inhalation conclusions made in the articles covering the Calgary findings. Other online review unabashedly reference studies that fullerenes “can cross the blood-brain barrier and alter cell functions.” The blood-brain barrier studies which are often repeated involved rats and need to be replicated. This is primarily G. Oberdörster’s work. There is some evidence suggesting some chemicals may cross the blood-brain barrier and this phenomenon has become an important research agenda among those researchers in nano-ceuticals. While the claim that some particles might cross the blood-brain barrier has been supported, it has not been claimed for all particles including those used in the Calgary study (thought this remains the subject of some conjecture).

ON ASBESTOS AND NANOTUBES

Science is objective. Using methodologies that are beyond reproach due to verification, science is clad under a mantle of facts and data. Or is it just “Emperor’s Clothes”?

Science and technology are rhetorical phenomena comparable to political and public address. It’s simply a matter of degree.

When a scientific research article is written, the authors select from the available means of persuasion to craft their language and their claims. Often, they speak to many audiences other than their peers, and when speaking to the media and the public nothing speaks more loudly than strong imagery and rhetorical tropes.

We recently observed just such an occasion. The team from the PCOST (Public Communication of Science and Technology) Project at NCSU put their heads together and is offering this preliminary assessment of the debate “On Asbestos and Nanotubes.” Their collective heads are: Christopher Cummings, Grant Gardner, Kelly Norris, Nick Temple and yours truly—and what a team of doctoral students!

In the Poland et al. (2008) study the researchers are attempting to test whether long straight multi-walled carbon nanotubes (MWCNTs) induce similar early symptoms of mesothelioma to those caused by asbestos fibers. In examining any research study it is important to separate what the quantitative data is actually showing from the authors conjecture or discussion of implications. That is not to say interpreting and expounding scientific data is intrinsically fallacious, but the differences in validity of these assertions must be made clear. For the Poland study, readers must also temper their consideration of the power of the results by noting the relatively small sample size. The following is a brief discussion of interpretive pit-falls to be wary of prior to examining reports of this study.

Although the article relates carbon nanotube (CNT) exposure risks to airborne asbestos, the researchers make no claims as to how easily carbon nanotubes (CNTs) become airborne. In fact, most CNT-manufactured products are likely safe, as they are embedded in structures. The largest concern for airborne particulate CNTs would be in factories manufacturing these products. For the sake of argument if we were to ignore this assumption, if individuals were to be exposed to particulate CNTs, it is unknown how easily they can become lodged in lung tissue. Additionally, uncertainty surrounds how readily they would migrate to the mesothelium. The Poland study bypasses these questions by installing CNTs directly into tissue to examine their effect. It is important to note that the study tissue was not lung mesothelium, but closely-related abdominal peritoneum. In addition, another question is whether CNTs can remain anchored in the tissue and in a concentration significant enough in dosage to cause mesotheliomas. What the study can claim is that asbestos and CNT particles that are long and fibrous tend to induce pre-mesothelioma symptoms when directly injected into mesolthelial tissue layers. For more detail on the science, see the ICON Backgrounder at http://icon.rice.edu/resources.cfm?doc_id=12299.

A word that to most connotes deadly carcinomas and mesothelioma, asbestos can hardly enter a headline without raising concern in readers. However, the media inevitably have to make the comparison between multi-walled carbon nanotubes (MWCNT) the highlight of their stories since this is how the experimental studies were designed. In addition, the media simply gets giddy when offered such a tantalizing headline.

One of the main purposes of the recent studies published in the Journal of Toxicological Sciences (Takagi et al., 1008) and Nature Nanotechnology (Poland et al., 1008) was to determine if mesothelial exposure (in mice) to the needle-like fibre shape of MWCNTs results in pathogenic behavior. The other main purpose, even more heavily marketed by researchers, was to determine if the pathogenic behavior of the MWCNTs was similar to asbestos fibres. This effort to compare the two is interesting since recommendations from the findings would be the same regardless of the comparison. If anything, by releasing the findings, demonstrating how the two are similar and then having to later make distinctions about how they are different only confuses the issue.

News regarding this study did not come from many sources the day it was released. A survey of world, national, and local print news sources revealed only thirteen highly redundant articles. In fact, four of these were the exact same articles simply reprinted in different Associated Press outlets. Other news outlets reporting this story included The New York Times, The Washington Post, and U.S. Newswire. Local reports were less common, including only a story by The Virginian Pilot out of Norfolk, VA and extremely brief three line blurb in Birmingham Evening Mail. Only one strictly web based news source, vnunet.com, ran the story.

The lack of stories may account for some of the redundancy found in the articles. However, this redundancy does set up a frame that may very likely be followed as more articles appear. One would expect the Associated Press to copy the same story to their various outlets. Since many large news outlets rely on the AP to break stories to them, rewrites of that material is also to be expected. As local news sources begin to pick the story up, they too will likely rely on the details from the original stories to guide their work. This is the way the news works.

As we have seen, however, the rhetoric of the original stories is confusing. The media have picked up on the metaphor of linking MWCNTs to asbestos. Considering that asbestos is something of a devil term in the rhetoric of industrial circles, such a metaphor has the power to be extremely powerful in the minds of a public still dealing with the aftermath its cancerous effects. The original study being cited is the one which originates the metaphor since the effects were so similar, but it is the media which carries this metaphor out and enacts its power.

To support this metaphor and discuss it, the media tend to be quoting the same two or three people. Andrew Maynard’s sound bite in which he says “This is a wakeup call for nanotechnology in general and carbon nanotubes in particular” is frequently used. One of the authors of the Poland study, Donaldson, is also frequently quoted as saying “It’s a good news story, not a bad one. It shows that carbon nanotubes and their products could be made to be safe.” Vicki Colvin was also quoted several times as saying that the benefits of nanotechnology are too powerful to ignore, but that this study emphasizes the importance of knowing how to handle it. These were the primary experts put into conversation with one another in the media and as such will logically lead the discussion of this issue as it progresses. It will be interesting to see how the public picks up the issue and what they do with it. The media has touted the metaphor of asbestos but at the same time has attempted to frame the issue as a cautionary tale in which science is on top of the issue now before it becomes a problem as opposed to when scientists dropped the ball on asbestos. However, the memory of asbestos may be too powerful to allow for public trust in anything linked to it, even if the link is primarily a metaphorical one.

Researchers say (even in their abstracts) that they are calling for further research and great caution so that long-term harm is to be avoided. However, the likely public reaction is do away with carbon nanotubes in products all-together in spite of any future research, even research touting positive findings (something we might want to test).

Also, by focusing attention on the similarities between carbon nanotubes and asbestos, less attention is paid to other interesting findings from the studies. For instance, the fact that short, tangled MWCNTs did not cause inflammation in mesothelial tissue, therefore did not suggest pathogenic behavior was not mentioned in most media articles.

Though most articles reporting the studies acknowledge that the greatest danger of exposure is to the workers involved in production of items containing carbon nanotubes and that researchers agree that there is no need to restrict the use of carbon nanotubes in products, by pushing the correlation between asbestos and MWCNTs the lay audience will certainly consider carbon nanotubes a public hazard. Even in the case of workers involved in manufacturing the particles, the articles report that precautions have already been put into place requiring workers to wear respirators. Towards the end of media articles, reporters point out that the study did not look at how likely and/or easily carbon nanotubes become airborne or whether they become lodged in the lungs if inhaled. But this consideration of dosage and exposure is now irrelevant to the public that is concerned with consequences and implications only.

As risk researchers Jenkins-Smith & Silva point out “members of the public appear to be more willing to believe risk increasing signals than risk-decreasing signals” —and pairing nanotubes with asbestos in the headline of a study or media article is definitely a “risk increasing” signal.

The articles continue to perplex as they state that on the one hand, there is minimal risk to consumers in handling products made of carbon nanotubes because the fibres are so embedded, but on the other hand, nanotubes should be subject to the same rules and regulations as asbestos.

Also puzzling, professors say they are “not alarmed” about the results of the studies but still insist products should be better labeled. They back this suggestion with the concern that, like asbestos, the nanotubes could be released later (i.e. construction workers or mechanics inhaling asbestos from concrete or automobile brake pads).

Here again, the language is confusing to the public because at the same time the articles tell people not to distress they also insist on the possibility that nanotubes are asbestos with a “coat of a different color.”

As a rhetorical strategy, telling people they are safe while at the same time making reference to a similar substance that lessened trust in industry and the government, only makes sense if the purpose is to actually heighten concerns and monger fear.

Slovic (1986) warns that merely mentioning possible adverse consequences to the public can make them appear more frightening. Therefore, the rhetorical force of mentioning the consequences of direct exposure to MWCNT while also establishing a direct association to a negatively explosive word like asbestos is enormous.

Because researchers are aware of the reactions the word asbestos triggers in the public, the actual motivation behind comparing the two substances, must be to first, attract the attention of the media and second, to position themselves as rescuers/saviors devoted to the public’s interest (unlike industries who are trying to sneak the hazardous materials into consumer products regardless of health or environmental risks).

Most often the media look for hot button issues while deconstructing academic research findings, in the case of the MWCNTs studies, the experiments were rhetorically designed so that the hot button issue was at the forefront, ensuring a lot of attention at the expense of some of the intricate findings and opportunity for a critical public.

The problem with this rhetorical approach is that the adverse reactions it could instill in the public could be more problematic than the media attention it draws.

Berube with New Pubs

You can get yours hands on the Intuitive Tox article since the Spring book is now out.

Nanotechnology and Society by Fritz Allhoff and Patrick Lin, Springer, 1st edition, June 2008, ISBN - 10: 1404062087.

The article examining risk profile shifts and the FOE report on sunscreens is also avialable from On Line Access at the Journal of Nanoparticle Research. "Rhetorical gamesmanships in the nano debates over sunscreens and nanoparticles," Journal of Nanoparticle Research, 2008. DOI: 10.1007/S11051-008-9362-7.

The article I co-authored with Paul Borm is also out in Nano Today. Me and Paul Borm. "A nanotale of opportunities, uncertainties, and risks, Nano Today, 3:1-2, Feb-Apr 2008, 56-59.

I will be reviewing some new publications soon. Right now, I am working on my new book and a set of articles on "fear".