Nanotechnology: An Industrial Revolution?
by David Kennell

One of the fastest, if not the fastest, growing industries in the world today is based on nanotechnology.  The U.S. government spends $1.5 billion a year on nanoresearch funded by 25 federal agencies under the National Nanotechnology Initiative of 2003.  There are many new journals with "nano" in their titles and dozens more journals that publish many papers on nanotechnology.  There are more than 13,000 U.S. patents with "nano" in their titles, and more than 1,000 consumer products contain nanoparticles.  Global revenues from products using nanotechnology are estimated to reach $2.8 trillion by 2015, according to Global Industry Analysts Inc., while Lux Research estimates $3.1 trillion in five years.1

In spite of efforts by a handful of consumer/environment-friendly organizations, the general public is unaware of the meaning of nanotechnology, let alone the enormous influences it is already having on society.  A committee representing the U.S. National Academy of Sciences reported in December 2008 "serious weaknesses in the government's plan for research on the potential health and environmental risks posed by nanomaterials, which are increasingly being used in consumer goods and industry."

What is nanotechnology?  It is the technology of extremely small particles that retain basic chemical properties of the larger bulk material but may not have its physical properties.  Particles whose dimensions are in the range of 100 nanometers (about 1,000 times smaller than the diameter of your hair) are nanoparticles.  A nanometer (1 millionth of a millimeter) is about an averaged sized molecule and there is a quantitative to qualitative transition from classical to quantum physics when matter decreases to nanoparticle size because a much larger fraction of the atoms are on the surface.

The volume of a spherical particle is proportional to the cube of its diameter while the area of its surface is only proportional to the square of its diameter.  Thus, as the sphere gets smaller, a larger fraction of the molecules are on the surface (the volume decreases faster than the surface area).  The same relationship holds for other molecular shapes such as cylinders and cubes.  A cube one inch on each side has a surface area of one foot by one-half inch.  That same cubic inch volume filled with spheres of 100 nanometers diameter would have a surface area of one foot wide and more than a mile long or >120,000 times as much surface for the same (actually slightly less) volume!

Why is this of interest?  A substance whose activity is determined or carried by its surface would be many thousands of times more active on nanoparticles than the same volume or mass as a single aggregated unit.  An analogous case is bacteria whose sizes approach nanoparticle dimensions and, of all life forms, are by far the most adaptable to changing environments.  About 25% of their active genes code for membrane (surface) proteins which include receptors for outside molecules, some of which can then be transported by "chaperone" proteins to specific sites in the bacterial cell.

How will this technology affect society?  It certainly has economic significance.  As has been noted in many Monthly Review articles, the normal economy of an advanced capitalist society is one of stagnation.  Periods of relative economic health are only achieved by wars or by introduction of new technologies or kinds of production, e.g., auto industry after World War II and electronics boom in the 1990s.  Nanotechnology has been hailed as the "next industrial revolution" and could provide such a stimulus in the first period of the 21st century.

In our capitalist economy the economic incentive for production is profits.  As in past cases, this new productive technology will certainly lead to new social relations between classes in society.  Also, as long as profitable, some applications will be used to improve living conditions while others will worsen them.  Examples of both kinds of applications can be seen in the new technology of nanoparticles.  First, consider the positive.

Medical Applications of Nanotechnology

The characteristics of nanoparticles hold great promise for medical therapies.  Many of the most devastating diseases, such as heart, stroke, cancer, and neurological disorders may become curable in the near future with new technologies such as stem cell and nanoparticle therapies.  Therapeutic agents are rarely completely target-specific and can cause serious side-effects on non-targeted tissues or organs.  Concentrated thousands of times into a very small volume, the bound agents can be directed with much greater specificity, such as by direct injection, to the intended target tissue.

In some cases, nanoparticles can have specific compounds attached to them that recognize unique receptors on a class of cells.  They can also be loaded with imaging contrast agents that allow detection of specific targets by MRI (iron nanoparticles), nuclear and ultrasound imaging, or CT scanning when the targets are still very small.  Nanoparticles travel smoothly in the circulation by forming a suspension rather than sinking or floating, since the large surface area charge interacts with water.  Dozens of examples have been published and a few are described here.  The major challenge in these procedures is to be able to hit the specific target cells without damaging healthy tissues.

Cancer cells stimulate multiplication of blood vessels.  Rabbits were injected with nanoparticles containing both the fungal toxin, fumagillin, a chemotherapeutic agent, and molecules designed to bind to cell receptors on growing blood vessels.  Growth of the targeted tumors was slowed markedly.  Fumagillin, like many chemotherapeutic agents, has serious neurotoxic side-effects, but the rabbits did not show toxicity, since being concentrated into an extremely small volume and targeted to specific sites, its concentration was about 1,000 times lower than the usual dosage to the whole body.  The same technology has been used to detect and treat artherosclerotic plaques that could form blood clots.2  Preliminary human trials are planned this year.

Dozens of private companies are developing new therapeutic treatments using nanoparticles with some already approved for human use.

Abraxis BioScience introduced the world's first protein-bound nanoparticle chemotherapeutic compound (ABRAXANE®).3  The FDA approved product is used for the treatment of metastatic breast cancer and is now approved in 36 countries.

Nanoparticles, carried in inhalants, have been used successfully in animal studies to deliver antibiotics against lethal gram-negative bacteria that cause pneumonia.  The antibiotic-bound nanoparticles become incorporated into macrophages that kill bacteria and greatly improve the effectiveness compared to conventional antibiotic administration.

Recently, AMAG Pharmaceutical Inc. received an oft-delayed marketing approval for its Feraheme anemia treatment.  The company uses nanoparticle technology with therapeutic iron compounds to treat anemia, as well as novel imaging agents to aid in the diagnosis of cancer and cardiovascular disease.

Injected Feraheme can treat iron deficiency anemia in adults with chronic kidney disease.  It increased hemoglobin levels significantly compared to oral iron ingestion.4

Nanoparticles composed of fat molecules can carry a variety of drugs, antibodies and imaging molecules.  A chemotherapeutic agent (daunomycin), that has been of limited use because it is toxic to the heart, has been approved recently by the FDA for cancer treatment when transported on a nanoparticle.5  These "liposome" nanoparticles also carry antibodies specific for binding to the cancer cells thus avoiding heart toxicity.  Other immunoliposome nanoparticles have been packaged with radioactive tracers for imaging tumors along with powerful alpha-particle emitters that kill the targeted cancer cells in mice with metastatic breast cancer.

Most studies using nanoparticles for molecular imaging have been in cellular and animal models.  The coupling of iron nanoparticles with MRI can detect smaller deposits of cancer than do PET scans.  Researchers in London are also using nanoparticles of iron oxide in animal studies to target and treat cancers that are refractory to conventional chemotherapy.  Once directed to the cancer cells the particles are heated 6 degrees centigrade by an alternating magnetic field which kills the cells.

In a related better known procedure after its presentation on TV's 60 Minutes, the Kanzius Machine, invented by the late John Kanzius, is an experimental cancer treatment that combines either gold or carbon nanoparticles and radio waves to heat and destroy cancer cells without damaging healthy cells.  The metals absorb this energy much more efficiently than tissue; progress has been reported at two medical centers and human trials may be coming soon.6

Commercial Applications of Nanotechnology

The unique physical characteristics of nanoparticles have been used in production of hundreds of commercial products.  The Project on Emerging Nanotechnologies lists more than 1,000 nanoparticle products voluntarily listed by manufacturers.  Since no labeling is required by the U.S. Food and Drug Administration, the number could be much higher.

By increasing concentrations in extremely small volumes, nanoparticles with specific bound molecules make more potent food additives, stronger flavorings, antibacterial activities, etc.  Friends of the Earth has conducted extensive research on the current commercial uses of nanoparticles.  They reported that more than 100 foods and food-related products, such as food packaging, contain them.  For example, lipophilic nanoparticles can encapsulate preservatives, as well as vitamins, coenzymes, omega-3 fatty acids, flavinoids, or other supplements that increase their absorption.7  A chocolate drink for infants includes 300 nm particles of iron supplement.  One rationale for nanoparticles in food is to increase the consumption of nutritious foods while maintaining the pleasure of foods harmful to our health.  Our whole wheat toast can have the taste and smell of sirloin steak.        

Nanoparticles were first used in the food industry for packaging.  To retard spoilage, some packaging uses nanoparticles of titanium dioxide in the wrapping to reduce UV exposure or of silica to block oxygen penetration.  Package wraps can release nanoparticles into the food contents that enhance flavor, aroma, or contain antioxidants, nutritionals, antibiotics, etc.  Even more esoteric packaging can include nano-surveillance that can detect microbial growth and trigger release of other nanoparticles with antimicrobial activity, such as oxides of silver or zinc.8  Nanoparticles of titanium dioxide are used to whiten and brighten cheeses and in sunscreens to make clear rather than white while blocking UV.  More than 300 sunscreens have nanoparticles of zinc or titanium oxides.9

Nanoparticles are used in agriculture to increase potency per weight by encapsulating pesticides, fungicides, soil treatments, time release compounds, compounds active only under certain conditions such as alkalinity inside an insect, e.g., the Bt toxin used in genetically-modified seeds.

Nano-solar cells could increase efficiencies for energy transfer from sunlight.  One application under development is their incorporation into paints which could then be sprayed directly onto buildings to convert them to "solar factories."10

Miniaturization has been the hallmark of progress in the information technology/electronics industry.  The first "chip" introduced by Intel in 1971 contained 2,300 transistors with a "clock speed" of 108 KHz.  Early in 2008 Intel was producing a chip with 820 million transistors (357,000 more) with clock speeds of 3.2 GHz (almost 30 thousand times faster) with a manufacturing process of 45 nanometers (half distance between two wires in a memory cell) compared to 10,000 nanometers in 1971.11

Planned are nanosensors with increased selectivities and sensitivities for monitoring air quality, detecting stresses in buildings, bridges, water pollution, as well as disease symptoms in people.  Combining sensors and memory with motor functions within a nanoparticle would create an entity that could respond to a specific stimulus, search its memory banks, and then respond with a specific action.  This comes close to a synthetic organism.  The circle would be complete if the particle could derive energy from the environment and could repair its parts and reproduce itself.  All of these functions are present in bacterial species, including chemoautotrophs that can derive energy and grow on air plus oxidation of inorganic compound such as iron or ammonia.  One of Michael Crichton's creative science fiction thrillers, Prey, involved such nanoparticles that swarmed as a cloud and threatened the planet.12

In fact, the most complex known nanomachines are components of living cells.  A 45 nanometer rotary propeller motor of bacterial flagella powers rapid bacterial movement.  Even the annealing/denaturing cycles of complementary DNA strands with the aid of small complementary oligonucleotides is considered a kind of "tweezer" machine by investigators.

Potential Risks of Nanotechnology for Health and Environment

Laboratory studies suggest hazards from widespread use and absence of oversight.  Of the $1.5 billion federal funding of nanotechnology research, only 1% to 2.5% goes to risk assessment.  Nanoparticle size allows easy uptake by cells and organs.  Less than 300 nm can penetrate a cell and less than 70 nm its nucleus.  They can be translocated from the lungs after inhalation, or from the intestine after ingestion, to distant parts of the body.  Inhalation of particles <100 nm has been shown to cause lung damage as well as development of arterial plaques that lead to stroke and heart attacks in mice.  In urban areas, a major source of nanoparticles is in diesel fuel and defective or cold catalytic converters.

Possibly the first documented case of serious human toxicity from nanoparticle  exposures was published in October 2009.  Seven young Chinese female workers (aged 18–47 yrs) who had been working with nanoparticles for 5–13 months in an industrial facility developed shortness of breath and pleural effusions.  Surveys of the workplace detected polyacrylate nanoparticles, which were also found in lung tissue and the chest fluid.13  Two of the victims have died.

While there is controversy regarding penetration through intact skin, damaged skin is an ineffective particle barrier, so that cuts, eczema, or severe sunburn could allow skin uptake of nanoparticles.  Once in the blood stream, they would be transported to organs and tissues.  Nanoparticles of titanium dioxide or zinc oxide are in some sunscreens to give a clear coating instead of a white one.

Carbon nanotubes are atom-thick sheets of graphite formed into cylinders and are called the "wonder material of the 21st Century."  Light as plastic and stronger than steel, they are being developed for use in new drugs, energy-efficient batteries and futuristic electronics.  NASA is looking into the possibility of using carbon nanotubes in the construction of the Orion Crew Exploration Vehicle and future spacecraft to replace the aging Space Shuttles.  The less a vehicle weighs, the more fuel it can conserve.  Using carbon nanotubes, the weight of Orion could be reduced by up to 50% of current vehicles.  "Single-walled carbon nanotubes are one material of particular interest.  These tubular, single-layer carbon molecules -- 100,000 of them braided together would be no thicker than a human hair -- display a range of remarkable characteristics.  Possessing greater tensile strength than steel at a fraction of the weight, the nanotubes are efficient heat conductors. . ."14  Forecasters predict sales of nanotubes could reach $2 billion annually within the next four to seven years, according to an article in Chemical & Engineering News.

Carbon nanotubes measuring 0.6 to 3.5 nm diameter were taken up by nuclei of cultured human immune cells resulting in significant cell mortality.  While the diameter of a nanotube can be only a few nanometers, they can be hundreds or even thousands of nanometers long.  They have physical characteristics of asbestos fibers which are thin enough to penetrate deep into the lungs, but sufficiently long to confound the lungs’ built-in clearance mechanisms.

Exposure to asbestos has been described as the worst occupational health disaster in U.S. history with health costs expected to exceed $200 billion, according to the RAND Corporation.  Since the development of mesothelioma from asbestos fibers takes about 20 years, direct evidence from laboratory animals is hard to prove since most, such as mice, have shorter life spans.  However, injection into the abdominal cavity of mice can predict long-term response in the lung lining.

Researchers, at the University of Edinburgh 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.  Experiments showed that long, thin carbon nanotubes showed the same effects as long, thin asbestos fibers.  In an August 2008 report Friends of the Earth Australia called for a moratorium on commercial uses of carbon nanotubes citing further evidence for the risk of mesothelioma.15

Any risk assessments should also evaluate the impact on the environment.  Products contain nanosilver particles to disinfect, to kill odor-causing bacteria in socks, and even embedded in keyboards of laptop computers manufactured by Samsung.16  A recently published paper reported on its extreme toxicity and release into our surface and ground waters as well as wastewater treatment tanks where it could kill the bacteria that are necessary for treatment.17  Similarly, nanoparticles of titanium dioxide or zinc oxide used in many sunsreens, simply to make them clear, produce free radicals and DNA damage in vitro but are finding their way into our air and water, and as noted, possibly into our bodies through damaged skin.

Regulation and Labeling Is Needed

There is no international regulation of nanoproducts or nanotechnology or any internationally agreed definitions of nanotechnology, no internationally agreed protocols for toxicity testing or evaluating the environmental impacts of nanoparticles.  The Environmental Protection Agency and Food and Drug Administration in the U.S. and Health & Consumer Protection Directorate of the European Commission have started dealing with the potential risks posed by nanoparticles.  The Bush administration in 2007 decided that no special regulations or labeling of nanoparticles are required, reflecting corporate power over public welfare.  Since there is no mandatory labeling, consumers have no clue as to whether or not a product has nanoparticles and, more generally, are not even aware that a nanoparticle industry exists, let alone the meaning of nanoparticle.

A major challenge for regulators is whether or not nanoparticles should be identified as "new" entities.  The Royal Society recommended that the UK government assess chemicals in the form of nanoparticles or nanotubes as new substances.18  For example, carbon nanotubes are composed of graphite.  Graphite is used in a variety of products from "lead" pencils to artificial heart valves, and it replaced asbestos in brake linings.  Assessing risk of nanotubes on the basis of being graphite would ignore the extreme hazards of nanotubes based on their unique physical properties.  While this recognition with respect to hazard is contentious, there is no hesitation to provide intellectual property rights via patents to each new kind of nanoparticle to identify it as "new."

In January 2009, the California EPA sent formal notices to manufacturers, including academia, who produce or import carbon nanotubes in California, as well as manufacturers outside California who export them to California, for information regarding their analytical testing, fate and transport in the environment, and other relevant information.  Berkeley, California is currently the only city in the U.S. to regulate nanotechnology.

After considerable delay, in November 2009 the U.S. Environmental Protection Agency, under the Toxic Substances Control Act (TSCA), "Proposed Significant New Use Rules on Certain Chemical Substances."  The new rules would apply to single- and multi-walled nanotubes and expressly acknowledge that they represent "new" products on the market.  They request information from nanotube manufacturers, within 90 days of activity, about safety measures in the workplace, release into water, record-keeping, etc.  Most important, they provide EPA authority to prohibit or limit proposed activity.19

One troubling provision of the order is that if the EPA has regulated a substance under TSCA, states are preempted from imposing additional requirements concerning public health and the environment.20  It is not clear how this provision would affect past or future enforcement of regulations at the state level, such as those in California.  One is reminded of the conflict between California and the federal government regarding air pollution.

The entry of the EPA and analogous agencies in the U.K. and other nations is welcome, but the EPA is underfunded, depends on industry itself to do the testing, and has a long history of "revolving doors" of retiring EPA officials taking jobs in the same chemical industries which they had been monitoring.21  Lax regulation of many health and environmental toxins, such as pesticides, atrazine in water supplies, formaldehyde in buildings, etc., has not instilled confidence in the prospect that the EPA will be able to control excesses within this huge new industrial enterprise.22  Furthermore, if regulations are stringently enforced, companies could drop the "nano" word from their products and go "underground" as is already happening according to Andrew Maynard of the Woodrow Wilson International Center for Scholars' Project on Emerging Technologies.23  This "escape hatch" is another reason why, besides providing for consumer awareness and choice, there needs to be mandatory labeling of all products containing nanoparticles.

A first step in generating meaningful oversight is to inform and educate the public of the significance of nanotechnology for human health and welfare and for its impact on the environment.

 

Notes

1  Nanotechnology Law Report.  Summer (2009).   p. 9.

2  Winter, PM, Caruthers, SD, Zhang, H, Williams, TA, Wickline, SA, Lanza, GM.  "Antiangiogenic Synergism of Integrin-Targeted Fumagillin Nanoparticles and Atorvastatin in Atherosclerosis."  J Am Coll Cardiol Img 1:624-634 (2008).

3  Miele, E, Spinelli, GP, Miele, E, Tomao, F, Tomao, S.  "Albumin-bound Formulation of Paclitaxel (Abraxane® ABI-007) in the Treatment of Breast Cancer."  International Journal of Nanomedicine 4: April (2009).

4  Provenzano R, Schiller B, Rao M, Coyne D, Brenner L, Pereira BJ.   "Ferumoxytol as an Intravenous Iron Replacement Therapy in Hemodialysis Patients."  Clinical Journal of the American Society of Nephrology 4(2):386-93(2009).

5  Tan, C, Tasaka, H, Kou-Ping, Y, et al.  "Daunomycin, an Antitumor Antibiotic, in the Treatment of Neoplastic Disease.  Clinical Evaluation with Special Reference to Childhood Leukemia."  Cancer 20: 333-353 (1967).  Haley, B. and Frenkel, E.  "Nanoparticles for Drug Delivery in Cancer Treatment."  Urologic Oncology: Seminars and Original Investigations 26: 57-64 (2009).

6  Gannon, CJ, Patra, CR, Bhattacharya, Priyabrata R., Mukherjee, and Curley, SA.  "Intracellular Gold Nanoparticles Enhance Non-invasive Radiofrequency Thermal Destruction of Human Gastrointestinal Cancer Cells."  Journal of Nanobiotechnology 6:2 (2008).

7  Friends of the Earth.  Out of the Laboratory and onto Our Plates: Nanotechnology in Food & Agriculture.  (2008).

8  The Royal Society: Science Policy Section.  Nanoscience and Nanotechnologies:  Opportunities and Uncertainties.  (2004).

9  Garber, C and Berger, M.  "Nanoparticles and Sunscreen Safety."  Nanowerk LLC.  August 3 (2006).

10  Lovgren, S.  "Spray-on Solar-Power Cells Are True Breakthrough."  Natl' Geographic News.  Jan. 14, (2005).

11  The Royal Society, op. cit.

12  Crichton, M.  Prey.  Harper Collins.  (2002).

13  Song Y, Li X, Du X.  "Exposure to Nanoparticles Is Related to Pleural Effusion, Pulmonary Fibrosis and Granuloma."  Eur Respir J 34(3): 559-567 (2009).

14  "NASA-developed Methods Reduce Cost, Enhance Quality of Carbon Nanotubes."  Nanowerk News, November 9, (2009).

15  Friends of the Earth, Australia.  "Mounting Evidence That Carbon Nanotubes May Be the New Asbestos."  Aug. (2008).

16  Nanotechnology Law Report.  Summer (2009).  p. 8.

17  Choi, O. and Hu, Z.  "Size Dependent and Reactive Oxygen Species Related Nanosilver Toxicity to Nitrifying Bacteria."  Environ. Sci. Technol. 42: 4583-4588 (2008).

18  The Royal Society, op. cit.

19 Monica, JC Jr. & Monica, JC.  "Examples of Recent EPA Regulation of Nanoscale Materials Under the Toxic Substances Control Act."  6 Nanotechnology Law & Business 388.  Fall (2009).

20  Ibid.

21  Fagin, D, Lavelle, M.  Toxic Deception:  How the Chemical Industry Manipulates Science, Bends the Law and Endangers Your Health.  Common Courage Press.  (1999).

22  Denison, R.  "Hiding a Toxic Nanomaterial's Identity: TSCA's Disappearing Act."  Environ. Defense Fund.  July 14, (2009).

23  Maynard, A.  EU News, Policy Positions, and EU Actions.  June 15 (2009).


David Kennell is Professor Emeritus of Molecular Microbiology at Washington University School of Medicine, St. Louis.
URL: mrzine.monthlyreview.org/kennell111209.html
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