Communications of the ACM
Technical opinion
Nanoscience Fact Versus Fiction
Nanofiction. In his novel, Prey, Michael Crichton writes of a swarm of nanobots released in the Nevada desert, terrorizing the very scientists who developed them. Unfortunately, this deepening vision of "grey goo" coating our landscape as the nanobots replicate uncontrollably is the picture some people have of the risk from nanotechnology. Such a picture, though titillating, is a scientific fantasy, more in the tradition of King Kong than the realms of scientific plausibility. The actual risks from nanotechnology, as seen by those of us working in this field, are less dramatic, but nonetheless, are potentially real.
Nanofacts. There has been a great deal of public and scientific interest in the so-called nanotechnology revolution. Nanotechnology can be defined as the manipulation, precision placement, measurement, modeling, or manufacture of sub-100 nanometer (nm) scale matter (1nm equals 1/1,000,000,000th of m). This manipulation of matter at the nano level will greatly influence most areas of our life, such as manufacturing, engineering, health, pharmaceuticals, and (of special interest here) information technology. There is a wide range of nanoparticles of different types and different properties currently in production that may be applied in a variety of ways. It is envisaged that nanoparticle types found useful will be further developed by large-scale production.
The greatest risk to human health and to the environment lies in this rapid expansion of different types of nanoparticles under development and the potential for their production. It brings with it the possibility of large-scale human exposure predominantly in the work place as these nanoparticles are incorporated into products of every conceivable type from IT to food. Additionally, the particles can be released during wear and destruction throughout the life of a product. Such diversity in use (with numerous potential scenarios for exposure) means that nanoparticles are likely to make contact with the body via the lungs, intestines, and skin.
The lungs are an obvious and critical route of entry to the body, especially during the manufacturing process where dust clouds can be generated. The intestines provide a route of entry for nanoparticles contained both within processed foods and in mucus cleared from the lungs. Nanoparticles have been found to accumulate in cells of the gut wall and the effects of this are not yet known. Entry of nanoparticles through the skin via cosmetics such as sunblock is also feasible, but has not yet been demonstrated. These tiny particles with their huge surface reflect light, thereby mediating the sunblock effect.
Another critical area where nanoparticles might cause potent harm is in medicines. Ironically, much has been written and surmised about the future benefits of these particles introduced in the body to deliver drugs, track disease progressions, or to encourage healing. However, a question mark hangs over the fate of these particles and what they might do in addition to their intended function.
Nanoparticles are so small they will easily become airborne and remain airborne where they can be inhaled into the lungs. How might such small particles harm the lungs? There is a considerable history of dust particles of various types causing problems to human lungs; some of these particles are well known to cause disease, for example, silica (stone) dust and diesel exhaust which are, in fact, nanoparticles. Another disease-causing dustasbestosmight actually help us understand the risks from nanotubes.
The Lungs and Particles
The lungs are well defended against particles of the type to which we have always been exposed, such as bacteria, soil, dust, and certain kinds of smoke. The airways are a branching system of pipes that lead from the back of the throat to the oxygen exchanging part of the lungs. To protect them against particles in the air, there is an upwardly moving carpet of mucus that traps particles. The mucus is wafted up and out of the lungs mostly to be swallowed and sent through the intestines for expulsion from the body. However, deeper down in the oxygen exchange area of the lung there is a different form of defense. Here, cells from the immune system move around on the surface and consume any particle they find before moving to the mucus carpet in order to be swept out of the lungs and to the gut. Thus, a proportion of particles that enter via the lung are transported to the intestines where the effects of particles are far less understood. Figure
Very small particles pose problems to the lungs because there are so many of them that the "eater cells" of the lung cannot locate and ingest all of them. Also, the surface area of nanoparticles is great, and this sets up a situation where chemical reactions may transpire leading to lung injury. Particles tend to escape from the surface of the lungs and penetrate into the body. This can occur in several different situations as shown in the accompanying figure; harmful effects are likely to be different according to the final location of the particle.
- The lungs. Particles passing into the walls of the air passages can worsen existing airway disease, such as asthma and bronchitis, requiring patients to be hospitalized or even hastening their death.
- The brain. Recent evidence suggests that nanoparticles landing in the nose can move upward into the base of the brain. The effect this has on the brain and nervous system is under investigation.
- The blood. Nanoparticles that reach the bloodstream can affect the blood clotting systema critical repercussion since the irregularities of the clotting system may have been linked to heart disease, which is the most frequent cause of death in the Western world. Particles could also reach the heart and liver with a number of unforeseen consequences.
The very properties that make nanoparticles useful for new applications are also the very properties that can increase their harmfulness.
Medical Uses of Nanoparticles
The medical applications of nanoparticles have involved utilizing our knowledge of the human body and how it changes during disease, coupled with processes that alter the nanoparticle surface properties allowing the particles to reach key areas of the body. For example, it is possible to alter the surface of a nanoparticle to direct it toward a specific organ such as the liver or brain, thus allowing drugs to be targeted to a specific spot rather than working through the entire body. This is not only more efficient for the patient, but it results in fewer side effects. It suggests the way in which nanoparticles travel around the body and ultimately settle also depends on the surface chemistry of the particles. And where do the particles go after they have fulfilled their delivery function? What affect to they have on the various organs they target?
Nanotubes are like extended buckyballs (a molecule of carbon-60); that is, they are very thin (a few tens of nm), but can be very long (in the order of mm). They are extremely strong, able to maintain their structure and not break down in the lung. Nanotubes are similar to fibers like asbestos and glass, and as such could be very harmful to the lungs causing scarring and cancer. Therefore, adequate toxicological studies of nanotubes must be conducted to fully understand the potential risks.
Toxicology is the study of how physical and chemical agents damage the body. The authors and fellow colleagues have recently suggested we must recognize a new science of Nanotoxicology to specifically examine the products of the nanotechnology revolution for their likely adverse effects. We are not suggesting that further advancement of nanotechnology, nor the development of nanoparticles, should be halted; in fact, this field promises great benefit, especially for the IT and communications industries. We only suggest that proper toxicology testing be carried out to ensure such products are being handled safely and there is no undue risk to the makers and users of nanoparticles.
The dramatic change in the properties of materials seen when they reach nanoscale is the engine of the nanotechnology revolution, but this is not confined to chemistry and physics. It appears the human body also experiences these very small particles differently. Indeed, the very properties that make nanoparticles useful for new applications are also the very properties that can increase their harmfulness. Toxicologists are largely in the dark over what nanoparticles do, where they go in the body, and what effects they might have when they get there. It is a situation that must be addressed to support a safe nanotechnology industry.
Figures
Figure. Tracing how nanoparticles (obviously not to scale) can be inhaled and travel to the brain, the airways to the lungs, and the bloodstream where they can be transported throughout the body, with potentially harmful results.
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