Tag Archives: mesothelioma

The yin and the yang of carbon nanotubes and toxicity

 

Illustration courtesy of the University College of London (UCL). Downloaded from http://www.ucl.ac.uk/news/news-articles/0113/130115-chemistry-resolves-toxic-concerns-about-carbon-nanotubes

Illustration courtesy of the University College of London (UCL). Downloaded from http://www.ucl.ac.uk/news/news-articles/0113/130115-chemistry-resolves-toxic-concerns-about-carbon-nanotubes

Researchers at the University College of London (UCL), France’s Centre national de la recherche scientifique (CNRS), and Italy’s University of Trieste have determined that carbon nanotube toxicity issues can be addressed be reducing their length and treating them chemically. From the Jan. 15,2013 news item on ScienceDaily,

In a new study, published January 15 [2013] in the journal Angewandte Chemie, evidence is provided that the asbestos-like reactivity and pathogenicity reported for long, pristine nanotubes can be completely alleviated if their surface is modified and their effective length is reduced as a result of chemical treatment.

First atomically described in the 1990s, carbon nanotubes are sheets of carbon atoms rolled up into hollow tubes just a few nanometres in diameter. Engineered carbon nanotubes can be chemically modified, with the addition of chemotherapeutic drugs, fluorescent tags or nucleic acids — opening up applications in cancer and gene therapy.

Furthermore, these chemically modified carbon nanotubes can pierce the cell membrane, acting as a kind of ‘nano-needle’, allowing the possibility of efficient transport of therapeutic and diagnostic agents directly into the cytoplasm of cells.

Among their downsides however, have been concerns about their safety profile. One of the most serious concerns, highlighted in 2008, involves the carcinogenic risk from the exposure and persistence of such fibres in the body. Some studies indicate that when long untreated carbon nanotubes are injected to the abdominal cavity of mice they can induce unwanted responses resembling those associated with exposure to certain asbestos fibres.

In this paper, the authors describe two different reactions which ask if any chemical modification can render the nanotubes non-toxic. They conclude that not all chemical treatments alleviate the toxicity risks associated with the material. Only those reactions that are able to render carbon nanotubes short and stably suspended in biological fluids without aggregation are able to result in safe, risk-free material.

Here’s a citation and link for this latest  research, from the ScienceDaily news item where you can also read the lead researcher’s comments about carbon nanotubes, safety, and unreasonable proposals to halt production,

Hanene Ali-Boucetta, Antonio Nunes, Raquel Sainz, M. Antonia Herrero, Bowen Tian, Maurizio Prato, Alberto Bianco, Kostas Kostarelos. Asbestos-like Pathogenicity of Long Carbon Nanotubes Alleviated by Chemical Functionalization. Angewandte Chemie International Edition, 2013; DOI: 10.1002/anie.201207664

The article is behind a paywall. I have mentioned long carbon nanotubes and their resemblance to asbestos fibres in several posts. The  Oct. 26, 2009 posting [scroll down about 1/3 of the way] highlights research which took place after the study where mice had carbon nanotubes injected into their bellies; in this second piece of research they inhaled the nanotubes.

ETA Jan. 21, 2013: Dexter Johnson gives context and commentary about this latest research into long multiwalled nanotubes (MWNTs) which he sums up as the answer to this question “What if you kept the MWNTs short?”  in a Jan. 18, 2013 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website)

Health science writing? Australian writer accuses gym equipment of killing you through nanotechnology

Toby McCasker’s Sept. 30, 2012 article for news.com.au  is one of the more peculiar pieces I’ve seen about nanotechnology and its dangers. From the article,

Is gym equipment killing you?

THE nanofibres that make up sports and gym equipment just might be doing you more harm than good.

McCasker then blesses us with this wonderful, wonderful passage where he explains his concern,

Why is this (maybe) bad? Nanotechnology sounds awesome, after all. Very cyberpunk. Inject them into your dude piston and become a thrumming love-machine, all that. [emphases mine] They’re maybe bad because researchers from the University of Edinburgh in the UK have just discovered that some nanofibres bear a resemblance to asbestos fibres, which can cause lung cancer.

You can’t inject nanotechnology. Since it’s a field of study,  it would be the equivalent of injecting biology or quantum mechanics.

As for nanotechnology being cyberpunk, here’s how Cyberpunk is defined  in The Free Dictionary,

Noun   1.         cyberpunk – a programmer who breaks into computer systems in order to steal or change or destroy information as a form of cyber-terrorism

cyber-terrorist, hacker

act of terrorism, terrorism, terrorist act – the calculated use of violence (or the threat of violence) against civilians in order to attain goals that are political or religious or ideological in nature; this is done through intimidation or coercion or instilling fear

coder, computer programmer, programmer, software engineer – a person who designs and writes and tests computer programs

terrorist – a radical who employs terror as a political weapon; usually organizes with other terrorists in small cells; often uses religion as a cover for terrorist activities

2.         cyberpunk – a writer of science fiction set in a lawless subculture of an oppressive society dominated by computer technology

author, writer – writes (books or stories or articles or the like) professionally (for pay)

3.         cyberpunk – a genre of fast-paced science fiction involving oppressive futuristic computerized societies

science fiction – literary fantasy involving the imagined impact of science on society

The closest definition that fits McCasker’s usage is this description (the passage by Lawrence Person) of cyberpunk, a post-modern science fiction genre, in Wikipedia,

Cyberpunk plots often center on a conflict among hackers, artificial intelligences, and megacorporations, and tend to be set in a near-future Earth, rather than the far-future settings or galactic vistas found in novels such as Isaac Asimov’s Foundation or Frank Herbert’s Dune. The settings are usually post-industrial dystopias but tend to be marked by extraordinary cultural ferment and the use of technology in ways never anticipated by its creators (“the street finds its own uses for things”). Much of the genre’s atmosphere echoes film noir, and written works in the genre often use techniques from detective fiction.

“Classic cyberpunk characters were marginalized, alienated loners who lived on the edge of society in generally dystopic futures where daily life was impacted by rapid technological change, an ubiquitous datasphere of computerized information, and invasive modification of the human body.” – Lawrence Person

It’s the part about “invasive modification of the human body” which seems closest to McCasker’s ” inject them into your dude piston”  (dude piston is my new favourite phrase).

As for the reference to nanofibres, McCasker is correct. There are carbon nanotubes that resemble asbestos fibres and there is concern for anyone who may ingest them. As far as I know, the people at greatest risk would be workers who are exposed to the carbon nanotubes directly. I have not heard of anyone getting sick because of their golf clubs where carbon nanotubes are often used to make them lighter and stronger.

The research (mentioned in my Aug. 22, 2012 posting)  at the University of Edinburgh that McCasker cites is important because it adds to a body of substantive research work on this issue regarding carbon nanotubes, asbestos, and the possibility of mesothelioma and bears no mention of gym equipment.

It’s the length, not the size that matters with nanofibres such as carbon nanotubes

The Aug. 22, 2012 news item on Nanowerk by way of Feedzilla features some research at the University of Edinburgh which determined that short nanofibres do not have the same effect on lung cells as longer fibres do. From the news item, here’s a description of why this research was undertaken

Nanofibres, which can be made from a range of materials including carbon, are about 1,000 times smaller than the width of a human hair and can reach the lung cavity when inhaled.

This may lead to a cancer known as mesothelioma, which is known to be caused by breathing in asbestos fibres, which are similar to nanofibres.

I wrote about research at Brown University which explained why some fibres get stuck in lung cells in a Sept. 22, 2011 posting titled, Why asbestos and carbon nanotubes are so dangerous to cells. The short answer is: if the tip is rounded, the cell mistakes the fibre for a sphere and, in error, it attempts to absorb it. Here’s some speculation on my part about what the results might mean (from my Sept. 22, 2011 posting),

The whole thing has me wondering about long vs. short carbon nanotubes. Does this mean that short carbon nanotubes can be ingested successfully? If so, at what point does short become too long to ingest?

The University of Edinburgh Aug. 22, 2012 news release provides answer to last year’s  speculation about length,

The University study found that lung cells were not affected by short fibres that were less than five-thousandths of a millimetre long.

However, longer fibres can reach the lung cavity, where they become stuck and cause disease.

We knew that long fibres, compared with shorter fibres, could cause tumours but until now we did not know the cut-off length at which this happened. Knowing the length beyond which the tiny fibres can cause disease is important in ensuring that safe fibres are made in the future as well as helping to understand the current risk from asbestos and other fibres, [said] Ken Donaldson, Professor of Respiratory Toxicology.

Sometimes, I surprise myself. I think I’ll take a moment to bask. … Done now!

Here’s my final thought, while this research suggests short length nanofibres won’t cause mesothelioma, this doesn’t rule out  other potential problems. So, let’s celebrate this new finding and then get back to investigating nanofibres and their impact on health.

Why asbestos and carbon nanotubes are so dangerous to cells

Sphere or spear? Apparently cells can’t tell that an asbestos fibre or long carbon nanotube are spears due to their rounded tips according to researchers at Brown University. From the Sept. 18, 2011 news item on Nanowerk,

Through molecular simulations and experiments, the team reports in Nature Nanotechnology that certain nanomaterials, such as carbon nanotubes, enter cells tip-first and almost always at a 90-degree angle. The orientation ends up fooling the cell; by taking in the rounded tip first, the cell mistakes the particle for a sphere, rather than a long cylinder. By the time the cell realizes the material is too long to be fully ingested, it’s too late.

Here’s a representation of what the scientists mean,

 

Something perpendicular this way comes Cells ingest things by engulfing them. When a long perpendicular fiber comes near, the cell senses only its tip, mistakes it for a sphere, and begins engulfing something too long to handle. Credit: Gao Lab/Brown University

Here’s what happens when a cell encounters a carbon nanotube, asbestos fibre, gold nanowires, and other materials that are long and perpendicular with rounded tips,

Like asbestos fibers, commercially available carbon nanotubes and gold nanowires have rounded tips that often range from 10 to 100 nanometers in diameter. Size is important here; the diameter fits well within the cell’s parameters for what it can handle. Brushing up against the nanotube, special proteins called receptors on the cell spring into action, clustering and bending the membrane wall to wrap the cell around the nanotube tip in a sequence that the authors call “tip recognition.” As this occurs, the nanotube is tipped to a 90-degree angle, which reduces the amount of energy needed for the cell to engulf the particle.

Once the engulfing — endocytosis — begins, there is no turning back. Within minutes, the cell senses it can’t fully engulf the nanostructure and essentially dials 911. “At this stage, it’s too late,” Gao [Huajian Gao] said. “It’s in trouble and calls for help, triggering an immune response that can cause repeated inflammation.”

I gather this is the starting point for mesothelioma. Here’s a description of the process (from the Brown University Sept. 18, 2011 news release,

“We thought the tube was going to lie on the cell membrane to obtain more binding sites. However, our simulations revealed the tube steadily rotating to a high-entry degree, with its tip being fully wrapped,” said Xinghua Shi, first author on the paper who earned his doctorate at Brown and is at the Chinese Academy of Sciences in Beijing. “It is counter-intuitive and is mainly due to the bending energy release as the membrane is wrapping the tube.”

Here’s a video from Brown illustrating the process,

Cells bite off more than they can chew from Brown PAUR on Vimeo.

The whole thing has me wondering about long vs. short carbon nanotubes. Does this mean that short carbon nanotubes can be ingested successfully? If so, at what point does short become too long to ingest? It doesn’t seem like my questions are going to be answered too soon since the team would like to go in this direction (from the Brown news release),

The team would like to study whether nanotubes without rounded tips — or less rigid nanomaterials such as nanoribbons — pose the same dilemma for cells.

“Interestingly, if the rounded tip of a carbon nanotube is cut off (meaning the tube is open and hollow), the tube lies on the cell membrane, instead of entering the cell at a high-degree-angle,” Shi said.

Nanomaterials and health: the good, the bad, and the ugly?

One of the things I’ve noticed about the nanomaterials safety debate is how quickly it devolves to:  nanomaterials are good (some media reporters, business and corporate lawyers) vs nanomaterials are bad (some media reporters and civil society groups). Unfortunately, we still don’t know much about nanomaterials and their possible effects on health and the environment but there is enough evidence to support a single position if you’re willing discount evidence that doesn’t support your case. There are even people (pro and con) who will use evidence that doesn’t support their case very well unless they leave out details.

Take for example, this interview with Pat Roy Mooney (executive director of the ETC Group) at the Elevate Festival, October 2009 in Austria. Much of what he has to say is quite right (more work needs to be done to ensure safety) but you might get the impression that all this nanotechnology research that’s been talked about has resulted only in consumer products such as sunscreens and cosmetics. At about 4 mins., 15 secs., the reporter challenges Mooney and points out that the research may be very helpful in cleaning water (vital in some areas of the world) and could have other benefits. Mooney concedes the point, grudgingly.

Oddly, Mooney spends quite a bit of time suggesting that gold nanoparticles are a problem. That may be  but the more concerning issue is with silver nanoparticles which are used extensively in clothing and which wash off easily. This means silver nanoparticles are ending up in the water supply and in our fish populations. Studies with zebrafish strongly suggest far more problems with silver nanoparticles than gold nanoparticles. You can check this paper (which compares the two nanoparticles), this paper (about silver only) and this paper (about silver only) or run a search.

Mooney goes on to describe problems with other nanomaterials that I’m unfamiliar with, but I don’t know how far I can trust the information he’s giving me.

Mooney isn’t the only one who likes to remove nuance and shading. In a recent interview on the Metropolitan Corporate Counsel website, one of the interview subjects, William S. Rogers, Jr., essentially dismisses concerns about carbon nanotubes with this:

Rogers: Before the EPA announcement in January, 2010 concerning the proposed SNUR, a series of studies was done beginning in the United Kingdom with a study led by Poland, et al. (2008). That study involved the injection of multi-walled nanotubes into the abdomen of mice, the mucosal lining of which is identical to the mesothelium of the pleura or chest. The injection directly into the abdomen was intended to simulate exposure of the mesothelium in the chest due to inhalation exposure. Approximately 90 days later they examined the biological changes who had taken place as a result of exposure of the abdominal mesolthelial lining to the carbon nanotubes. They reportedly found evidence of inflammation that was consistent with the type of inflammation that had traditionally been recognized in people who had inhalation exposure to asbestos fibers and who later developed mesothelioma. They did not find actual mesothelioma in the mice, but rather what were thought to be precursors to such cancers. The result of publication of these findings was an alarmist reaction that carbon nanotubes posed a danger to humans analogous to that of asbestos fibers. This became headline news.

Up to this point I could agree with him, but now Rogers goes on to point out the study’s shortcomings,

The problem with the study was that the mice were exposed to massive doses of nanotubes by injection, which is not a natural or likely cause of human exposure. The test methodologies were a poor analog for what likely human exposure would be in any setting. Many commentators criticized the study’s findings and suggested that its conclusions about a potential relationship between carbon nanotubes and asbestos fibers was flawed because it rested largely on their shape similarity (long and thin); however, for the last two years there has been talk in the popular media about whether the risks associated with all nanomaterials are akin to those associated with asbestos fibers. The only similarities between carbon nanotubes and asbestos fibers is their long aspect ratio, unlike other nanomaterials. There has been more focus on carbon nanotube toxicity than on other nanomaterial substances, which has percolated up to the EPA. EPA has now decided to treat carbon nanotubes separately from other nano-objects.

Rogers fails to mention that this was a pilot study which was intended to lay the basis for further research. Dr. Andrew Maynard, one of the authors of the study, noted in a March 26, 2009 posting on his blog (2020 Science) further work had been done,

I’m looking at an electron microscope image of a carbon nanotube – as I cannot show it here, you’ll have to imagine it. It shows a long, straight, multi-walled carbon nanotube, around 100 nanometers wide and 10 micrometers long. There is nothing particularly unusual about this. What is unusual is that the image also shows a section of the lining of a mouse’s lung. And the nanotube is sticking right through the lining, like a needle through a swatch of felt.

The image was shown at the annual Society of Toxicology meeting in Baltimore last week, and comes from a new study by researchers at the National Institute for Occupational Safety and Health (NIOSH) on the impact of inhaled multi-walled carbon nanotubes on mice. [You can find out more about the NIOSH study here]

It’s highly significant because it takes scientists a step closer to understanding whether carbon nanotubes that look like harmful asbestos fibers, could cause asbestos-like disease…

Both the carbon nanotube studies mentioned here are studies of long, multi-walled carbon nanotubes. This distinction is important as substances at the nanoscale can behave differently from each other depending on their shape and size. Both Maynard and the NIOSH researchers suggest that more study is required but clearly the evidence is mounting.

Interestingly, the Good Nano Guide (GNG)* page on carbon nanotubes mentions the Poland study but not the NIOSH Study. The page also notes that at least one study indicates issues with single-walled and multi-walled carbon nanotubes as well as C60 (fullerenes). I wonder if there’s a policy about including only studies that have been published in peer-reviewed journals.

(*a ‘best practices for nanomaterials’ wiki hosted by the International Council on Nanotechnology ETA (April 12, 2010: From Dr. Kristen Kulinowski, “As to your question about our policy for posting information at the GNG, there is no policy that states we only publish peer-reviewed papers.” Dr. KK has offered this and  more information about the GNG in the comments.)

The media also are playing a role in this discussion. I’ve noted before Andrew Schneider’s nanotechnology series for AOL News, from his article Obsession with Nanotech Growth Stymies Regulators,

Separately, the NIOSH team discovered that beyond the well-documented lung damage that comes from inhalation of carbon nanotubes, [emphasis mine] those heavily used carbon structures were causing inflammation of the brain in the test animals.

Except for the fact that “well-documented lung damage that comes from inhalation” is an over statement, Schneider’s article is a good read although as I’ve noted elsewhere I don’t know how far to trust his information. [ETA: April 21, 20010, Schneider also fails to note the the type of carbon nanotube (likely the long, multi-walled ones) on which he bases his unsubstantiated claim. ]

After writing all this, I’m torn. On the one hand,  I do think that if people like Schneider and Mooney had their way, none of us would be eating potatoes, tomatoes, or eggplants. After all, they’re members of the nightshade family and the ill effects of ingesting other members of that family, belladonna (deadly nightshade) and datura (jimson weed), are well documented. On the other hand, folks like William Rogers are all too willing dismiss some very troubling research as their clients strive to bring products to market, seemingly regardless of any consequences.

ETA: Happy Weekend!

Art conservation and nanotechnology; the science of social networks; carbon nanotubes and possible mesothelioma; Eric Drexler has a few words

It looks like nanotechnology innovations in the field of art conservation may help preserve priceless works for longer and with less damage. The problem as articulated in Michael Berger’s article on Nanowerk is,

“Nowadays, one of the most important problems faced during the cleaning of works of art is the removal of organic materials, mainly acrylic polymers, applied in the past as consolidants or protective coatings,” explains Piero Baglioni, a professor of Physical Chemistry at the University of Florence. “Unfortunately, their application induces a drastic alteration of the interfacial properties of the artwork and leads to increased degradation. These organic materials must therefore be removed.”

Baglioni and his colleagues at the University of Florence have developed “… a micro-emulsion cleaning agent that is designed to dissolve only the organic molecules on the surface of a painting …”

This is a little off Azonano’s usual beat (and mine too) but Rensselaer Polytechnic Institute’s Army Research Laboratory is launching an interdisciplinary research center for the study of social and cognitive networks.  From the news item,

“Rensselaer offers a unique research environment to lead this important new network science center,” said Rensselaer President Shirley Ann Jackson. “We have assembled an outstanding team of researchers, and built powerful new research platforms. The team will work with one of the largest academic supercomputing centers in the world – the Rensselaer Computational Center for Nanotechnology Innovations – and the leading visualization and simulation capabilities within our new Experimental Media and Performing Arts Center. The Center for Social and Cognitive Networks will bring together our world-class scientists in the areas of computer science, cognitive science, physics, Web science, and mathematics in an unprecedented collaboration to investigate all aspects of the ever-changing and global social climate of today.”

The center will study the fundamentals of social and cognitive networks and their roles in today’s society and organizations, including the U.S. Army. The goal will be to gain a deeper understanding of these networks and build a firm scientific basis in the field of network science. The work will include research on large social networks, with a focus on networks with mobile agents. An example of a mobile agent is someone who is interacting (e.g., communicating, observing, helping, distracting, interrupting, etc.) with others while moving around the environment.

My suspicion is that the real goal for the work is to exploit the data for military advantage, if possible. Any other benefits would be incidental. Of course, a fair chunk of the technology we enjoy today (for example, tv and the internet) was investigated by the military first.

I’ve mentioned carbon nanotubes and possible toxicology before. Specifically, some carbon nanotubes resemble asbestos fibers and pilot studies have suggested they may behave the same way when ingested by one means or another  into the body. There is a new confirmation of this hypothesis with a study where mice inhaled carbon nanotubes. From the news item on Nanowerk,

Using mice in an animal model study, the researchers set out to determine what happens when multi-walled carbon nanotubes are inhaled. Specifically, researchers wanted to determine whether the nanotubes would be able to reach the pleura, which is the tissue that lines the outside of the lungs and is affected by exposure to certain types of asbestos fibers which cause the cancer mesothelioma. The researchers used inhalation exposure and found that inhaled nanotubes do reach the pleura and cause health effects.

This was one exposure and the mice recovered after three months. More studies will be needed to determine the effects of repeated exposure. This study (Inhaled Carbon Nanotubes Reach the Sub-Pleural Tissue in Mice by Dr. James Bonner, Dr. Jessica Ryman-Rasmussen, Dr. Arnold Brody, et. al.) can be found in the Oct. 25, 2009 issue of Nature Nanotechnology.

On Friday (Oct. 23, 2009) I mentioned an essay by Chris Toumey on the forthcoming 50th anniversary of Richard Feynman’s seminal talk, There’s plenty of room at the bottom. Today I found a response to the essay by Eric Drexler.  From Drexler’s essay on Nanowerk,

Unfortunately, yesterday’s backward-looking guest article in Nanowerk reinforces the widespread but quite mistaken idea that my views are essentially the opposite of what I’ve stated above, and that those perverse ideas are also those of the Foresight Institute. I cannot speak for that organization, or vice versa, because I left it years ago. Contrary to what the article may suggest, I have no affiliation with the organization whatsoever. Regarding terminology, it is of course entirely appropriate to use the term “nanotechnology” to describe nanoscale technologies. The idea that there is a conflict between progress in the field and future applications of that progress is puzzling. This idea appears to stem from a strange episode that came to a head during the political push for the bill that established and funded the U.S. National Nanotechnology Initiative, an episode in which some leading science spokesmen quite properly rejected a collection of popular fantasies, but quite improperly attributed those fantasies to me. Reading claims by confused enthusiasts and the press that “Drexler says this” or “Drexler says that” is no substitute for reading my journal articles, or the technical analysis in my book, Nanosystems, and in my MIT dissertation). The failure of these leaders to do their homework has had substantial and lingering toxic effects.

(My own focus was on the ‘origin’ story for nanotechnology and not on Drexler’s theories.) If I understand the situation rightly, much of the controversy has its roots in Drexler’s popular book, Engines of Creation. It was written over 20 years ago and struck a note which reverberates to this day. The irony is that there are writers who’d trade places with Drexler in a nano second. Imagine having that kind of impact on society and culture (in the US primarily). The downside as Drexler has discovered is that the idea or story has taken on its own life. For a similar example, take Mary Shelley’s book where Frankenstein is not the monster’s name, it’s the scientist’s name. However, the character took its own life and name.