Carbon Nanotubes That Look Like Asbestos, Behave Like Asbestos, Could Lead To Asbestos-related Disease

A major study published in Nature Nanotechnology suggests some forms of carbon nanotubes -- a poster child for the "nanotechnology revolution" -- could be as harmful as asbestos if inhaled in sufficient quantities.The study used established methods to see if specific types of nanotubes have the potential to cause mesothelioma -- a cancer of the lung lining that can take 30-40 years to appear following exposure. The results show that long, thin multi-walled carbon nanotubes that look like asbestos fibers, behave like asbestos fibers.

Discovered nearly 20 years ago, carbon nanotubes have been described as the wonder material of the 21st Century. Light as plastic and stronger that steel, they are being developed for use in new drugs, energy-efficient batteries and futuristic electronics. But since their discovery, questions have been raised about whether some of these nanoscale materials may cause harm and undermine a nascent market for all types of carbon nanotubes, including multi- and single-walled carbon nanotubes. Leading forecasting firms say sales of all nanotubes could reach $2 billion annually within the next four to seven years, according to an article in the U.S. publication Chemical & Engineering News.

"This study is exactly the kind of strategic, highly focused research needed to ensure the safe and responsible development of nanotechnology," says Andrew Maynard, Chief Science Advisor to the Project on Emerging Nanotechnologies and a co-author on the paper. "It looks at a specific nanoscale material expected to have widespread commercial applications and asks specific questions about a specific health hazard. Even though scientists have been raising concerns about the safety of long, thin carbon nanotubes for over a decade, none of the research needs in the current U.S. federal nanotechnology environment, health and safety risk research strategy address this question."

Widespread exposure to asbestos has been described as the worst occupational health disaster in U.S. history and the cost of asbestos-related disease is expected to exceed $200 billion, according to major U.S. think tank RAND Corporation.

Anthony Seaton, MD, a co-author on the paper and a professor emeritus at the University of Aberdeen in the United Kingdom, says, "The toll of asbestos-related cancer, first noticed in the 1950s and 1960s, is likely to continue for several more decades even though usage reduced rapidly some 25 years ago. While there are reasons to suppose that nanotubes can be used safely, this will depend on appropriate steps being taken to prevent them from being inhaled in the places they are manufactured, used and ultimately disposed of. Such steps should be based on research into exposure and risk prevention, leading to regulation of their use. Following this study, the results of which were foreseen by the Royal Society in the U.K. in 2004, we can no longer delay investing in such research."

Researchers, led by Professor Kenneth Donaldson at the University of Edinburgh in the United Kingdom, examined the potential for long and short carbon nanotubes, long and short asbestos fibers, and carbon black to cause pathological responses known to be precursors of mesothelioma. Material was injected into the abdominal cavity of mice -- a sensitive predictor of long fiber response in the lung lining.

"The results were clear," says Donaldson. "Long, thin carbon nanotubes showed the same effects as long, thin asbestos fibers."

Asbestos fibers are harmful because they are thin enough to penetrate deep into the lungs, but sufficiently long to confound the lungs' built-in clearance mechanisms for getting rid of particles.

Donaldson stresses there are still pieces of the puzzle to fill in. "We still don't know whether carbon nanotubes will become airborne and be inhaled, or whether, if they do reach the lungs, they can work their way to the sensitive outer lining. But if they do get there in sufficient quantity, there is a chance that some people will develop cancer--perhaps decades after breathing the stuff," states Donaldson.

There is a silver lining to this research. According to Donaldson, "Short or curly carbon nanotubes did not behave like asbestos, and by knowing the possible dangers of long, thin carbon nanotubes, we can work to control them. It's a good news story, not a bad one. It shows that carbon nanotubes and their products could be made to be safe."

But Donaldson added that the present study only tested for fiber-like behavior and did not exonerate carbon nanotubes from damaging the lungs in other ways. "More research is still needed if we are to understand how to use these materials as safely as possible," he notes.

Carbon nanotubes are atom-thick sheets of graphite formed into cylinders. They may be formed from a single layer of graphite or they may consist of multiple concentric layers of graphite, resulting in multi-walled carbon nanotubes. While the diameter of a nanotube can vary from a few nanometers up to tens of nanometers, they can be hundreds or even thousands of nanometers long. Carbon nanotubes come in many forms, with different shapes, different atomic arrangements, and varying amounts and types of added chemicals--all of which affect their properties and might influence their impact on human health and the environment.

"This is a wakeup call for nanotechnology in general and carbon nanotubes in particular," says Maynard. "As a society, we cannot afford not to exploit this incredible material, but neither can we afford to get it wrong--as we did with asbestos."

Technique Tricks Bacteria Into Generating Their Own Vaccine

Scientists have developed a way to manipulate bacteria so they will grow mutant sugar molecules on their cell surfaces that could be used against them as the key component in potent vaccines.Any resulting vaccines, if proven safe, could be developed more quickly, easily and cheaply than many currently available vaccines used to prevent bacterial illnesses.

Most vaccines against bacteria are created with polysaccharides, or long strings of sugars found on the surface of bacterial cells. The most common way to develop these vaccines is to remove sugars from the cell surface and link them to proteins to give them more power to kill bacteria.

Polysaccharides alone typically do not generate a strong enough antibody response needed to kill bacteria. But this new technique would provide an easy approach to make a small alteration to the sugar structure and produce the polysaccharide by simple fermentation.

“We are showing for the first time that you don’t have to use complicated chemical reactions to make the alteration to the polysaccharide,” said Peng George Wang, Ohio Eminent Scholar and professor of biochemistry and chemistry at Ohio State University and senior author of the study. “All we need to do is ferment the bacteria, and then the polysaccharides that grow on the surface of the cell already incorporate the modification.”

The research is scheduled to appear in the online early edition of the Proceedings of the National Academy of Sciences.

In vaccines, polysaccharides linked with carrier proteins are injected into the body. That sets off a process that causes the release of antibodies that recognize the sugars as an unwanted foreign body. The antibodies then remain dormant but ready to attack if they ever see the same polysaccharides again – which would be a signal that bacteria have infected the body.

Polysaccharides are chains of sugars, or monosaccharides, and they are targeted for vaccine development because they are the portion of bacterial cells that interact with the rest of the body.

Escherichia coli was used as a model for the study. Wang and colleagues used one of the existing monosaccharides present on the E. coli cell surface polysaccharides, called fucose, to generate this new modification. They manipulated the structure of the fucose to create 10 different analogs, or forms of the sugar in which just one small component is changed.

The scientists then manually introduced these altered forms of fucose to a solution in which bacterial cells were growing, and the bacterial cells absorbed the altered fucose as they would normal forms of the sugar. The presence of these altered forms of fucose then altered the properties of the polysaccharides that grew on the surface of the cells.

“This way, we don’t have to do anything to modify the polysaccharides. We let bacteria do it for us,” Wang said.

“Bacteria grow lots of polysaccharides – it’s similar to the way humans grow hair. But for a vaccine, you need to make the molecules more active, or energetic,” he said. “In our method, we feed the bacteria these chemicals while they are growing, and those chemicals end up in the polysaccharides and that makes them more immunogenic. That’s the technology.”

Wang said the approach is likely to be applicable to many different kinds of bacteria. But each type of pathogen must be tested individually with the alteration of sugars unique to its surface.

“If you want to prevent one type of bacteria, you have to find something very unique for this bacteria because different microbes have different characteristics,” he said. “You have to find the oddest thing on the cell surface. It has to be on surface because what the body sees first is the surface.”

His lab will next be testing the method’s effectiveness on the pneumococcus bacteria under an exploratory $100,000 grant from the Bill & Melinda Gates Foundation. The current vaccine to prevent pneumonia in babies and the elderly combines 23 strains of bacteria, making it complex and expensive to produce. Each injection costs about $50 in the United States. A less expensive way to develop the vaccine would increase its availability in the developing world, Wang said.

This published research was supported by an endowed Ohio Eminent Scholar Professorship on Macromolecular Structure and Function in the Department of Biochemistry at Ohio State.

Co-authors of the work are Wen Yi, a recipient of a Ph.D. from the Ohio State Biochemistry Program who is now at the California Institute of Technology; Xi Chen of the University of California, Davis; Jianjun Li of the Institute for Biological Sciences at National Research Council of Canada; Chengfeng Xia, Guangyan Zhou and Wenpeng Zhang of Ohio State’s Departments of Biochemistry and Chemistry; Yanhong Li of the University of California, Davis; Xianwei Liu of Shandong University, China; and Wei Zhao of Nankai University, China.