The Global Technology Revolution
Chapter Two: Technology Trends

Genomics

By 2015, biotechnology will likely continue to improve and apply its ability to profile, copy, and manipulate the genetic basis of both plants and animal organisms, opening wide opportunities and implications for understanding existing organisms and engineering organisms with new properties. Research is even under way to create new free-living organisms, initially microbes with a minimal genome (Cho et al., 1999; Hutchinson et al., 1999 [79, 80]).

Genetic Profiling and DNA Analysis

DNA analysis machines and chip-based systems will likely accelerate the proliferation of genetic analysis capabilities, improve drug search, and enable biological sensors.

The genomes of plants (ranging from important food crops such as rice and corn to production plants such as pulp trees) and animals (ranging from bacteria such as E. coli, through insects and mammals) will likely continue to be decoded and profiled. To the extent that genes dictate function and behavior, such extensive genetic profiling could provide an ability to better diagnose human health problems, design drugs tailored for individual problems and system reactions, better predict disease predispositions, and track disease movement and development across global populations, ethnic groups, and other genetic pools (Morton, 1999; Poste, 1999 [21, 23]). Note that a link between genes and function is generally accepted, but other factors such as the environment and phenotype play important modifying roles. Gene therapies will likely continue to be developed, although they may not mature by 2015.

Genetic profiling could also have a significant effect on security, policing, and law. DNA identification may complement existing biometric technologies (e.g., retina and fingerprint identification) for granting access to secure systems (e.g., computers, secured areas, or weapons), identifying criminals through DNA left at crime scenes, and authenticating items such as fine art. Genetic identification will likely become more commonplace tools in kidnapping, paternity, and fraud cases. Biosensors (some genetically engineered) may also aid in detecting biological warfare threats, improving food and water quality testing, continuous health monitoring, and medical laboratory analyses. Such capabilities could fundamentally change the way health services are rendered by greatly improving disease diagnosis, understanding predispositions, and improving monitoring capabilities.

Such profiling may be limited by technical difficulties in decoding some genomic segments and in understanding the implications of the genetic code. Our current technology can decode nearly all of the entire human gene sequence, but errors are still an issue, since Herculean efforts are required to decode the small amount of remaining sequences.{1} More important, although there is a strong connection between an organism's function and its genotype, we still have large gaps in understanding the intermediate steps in copying, transduction, isomer modulation, activation, immediate function, and this function's effect on larger systems in the organism. Proteomics (the study of protein function and genes) is the next big technological push after genomic decoding. Progress may likely rely on advances in bioinformatics, genetic code combination and sequencing (akin to hierarchical programming in computer languages), and other related information technologies.

Despite current optimism, a number of technical issues and hurdles could moderate genomics progress by 2015. Incomplete understanding of sequence coding, transduction, isomer modulation, activation, and resulting functions could form technological barriers to wide engineering successes. Extensive rights to own genetic codes may slow research and ultimately the benefits of the decoding. At the other extreme, the inability to secure patents from sequencing efforts may reduce commercial funding and thus slow research and resulting benefits.

In addition, investments in biotechnology have been cyclic in the past. As a result, advancements in research and development (R&D) may come in surges, especially in areas where the time to market (and thus time to return on investment) is long.

Cloning

Artificially producing genetically identical organisms through cloning will likely be significant for engineered crops, livestock, and research animals.

Cloning may become the dominant mechanism for rapidly bringing engineered traits to market, for continued maintenance of these traits, and for producing identical organisms for research and production. Research will likely continue on human cloning in unregulated parts of the world with possible success by 2015, but ethical and health concerns will likely limit wide-scale cloning of humans in regulated parts of the world. Individuals or even some states may also engage in human or animal cloning, but it is unclear what they may gain through such efforts.

Cloning, especially human cloning, has already generated significant controversies across the globe (Eiseman, 1999 [73]). Concerns include moral issues, the potential for errors and medical deficiencies of clones, questions of the ownership of good genes and genomes, and eugenics. Although some attempts at human cloning are possible by 2015, legal restrictions and public opinion may limit their extent. Fringe groups, however, may attempt human cloning in advance of legislative restrictions or may attempt cloning in unregulated countries. See, for example, the human cloning program announced by Clonaid (Weiss, 2000 [78]).

Although expert opinions vary regarding the current feasibility of human cloning, at least some technical hurdles for human cloning will likely need to be addressed for safe, wide-scale use. "Attempts to clone mammals from single somatic cells are plagued by high frequencies of developmental abnormalities and lethality" (Pennisi and Vogel, 2000; Matzke and Matzke, 2000 [75, 77]). Even cloned plant populations exhibit "substantial developmental and morphological irregularities" (Matzke and Matzke, 2000 [77]). Research will need to address these abnormalities or at the very least mitigate their repercussions. Some believe, however, that human cloning may be accomplished soon if the research organization accepts the high lethality rate for the embryo (Weiss, 2000 [78]) and the potential generation of developmental abnormalities.

Genetically Modified Organisms

Beyond profiling genetic codes and cloning exact copies of organisms and microorganisms, biotechnologists can also manipulate the genetic code of plants and animals and will likely continue efforts to engineer certain properties into life forms for various reasons (Long, 1998 [17]). Traditional techniques for genetic manipulation (such as cross-pollination, selective breeding, and irradiation) will likely continue to be extended by direct insertion, deletion, and modification of genes through laboratory techniques. Targets include food crops, production plants, insects, and animals.

Desirable properties could be genetically imparted to genetically engineered foods, potentially producing: improved taste; ultra-lean meats with reduced "bad" fats, salts, and chemicals; disease resistance; and artificially introduced nutrients (so-called "nutraceuticals"). Genetically modified organisms (GMOs) can potentially be engineered to improve their physical robustness, extend field and shelf life (e.g., the Flavr-Savr™ tomato{2}), tolerate herbicides, grow faster, or grow in previously unproductive environments (e.g., in high-salinity soils, with less water, or in colder climates).

Beyond systemic disease resistance, in vivo pesticide production has already been demonstrated (e.g., in corn) and could have a significant effect on pesticide production, application, regulation, and control with targeted release. Likewise, organisms could be engineered to produce or deliver drugs for human disease control. Cow mammary glands might be engineered to produce pharmaceuticals and therapeutic organic compounds; other organisms could be engineered to produce or deliver therapeutics (e.g., the so-called "prescription banana"). If accepted by the population, such improved production and delivery mechanisms could extend the global production and availability of these therapeutics while providing easy oral delivery.

In addition to food production, plants may be engineered to improve growth, change their constitution, or artificially produce new products. Trees, for example, will likely be engineered to optimize their growth and tailor their structure for particular applications such as lumber, wood pulp for paper, fruiting, or carbon sequestering (to reduce global warming) while reducing waste byproducts. Plants might be engineered to produce bio-polymers (plastics) for engineering applications with lower pollution and without using oil reserves. Bio-fuel plants could be tailored to minimize polluting components while producing additives needed by the consuming equipment.

Genetic engineering of microorganisms has long been accepted and used. For example, E. coli has been used for mass production of insulin. Engineering of bacterial properties into plants and animals for disease resistance will likely occur.

Other animal manipulations could include modification of insects to impart desired behaviors, provide tagging (including GMO tagging), or prevent physical uptake properties to control pests in specific environments to improve agriculture and disease control.

Research on modifying human genes has already begun and will likely continue in a search for solutions to genetically based diseases. Although slowed by recent difficulties, gene therapy research will likely continue its search for useful mechanisms to address genetic deficiencies or for modulating physical processes such as beneficial protein production or control mechanisms for cancer. Advances in genetic profiling may improve our understanding and selection of therapy techniques and provide breakthroughs with significant health benefits.

Some cloning of humans will be possible by 2015, but legal restrictions and public opinion may limit its actual extent. Controls are also likely for human modifications (e.g., clone-based eugenic modifications) for nondisease purposes. It is possible, however, that technology will enable genetic modifications for hereditary conditions (i.e., sickle cell anemia) through in vitro techniques or other mechanisms.

GMOs are also having a large effect on the scientific community as an enabling technology. Not only do "knock-out" animals (animals with selected DNA sequences removed from their genome) give scientists another tool to study the effect of the removed sequence on the animal, they also enable subsequent analysis of the interaction of those functions or components with the animal's entire system. Although knock-outs are not always complete, they provide another important tool to confirm or refute hypotheses regarding complex organisms.

Broader Issues and Implications

Extant capabilities in genomics have already created opportunities yet have generated a number of issues. As more organisms are decoded and the functional implications of genes are discovered, concerns about property and privacy rights for the sequencing will likely continue.

The ability to profile an individual's DNA is already raising concerns about privacy and excessive monitoring. Examples include databases of DNA signatures for use in criminal investigations, and the potential use of genetically based health predispositions by insurance companies or employers to deny coverage or to discriminate. The latter may raise policy issues regarding acceptable and unacceptable profiling for insurance or employment. This issue is further worrisome because the exact code-to-function mechanisms that trigger many disease predispositions are not well understood.

Issues may also arise if a strong genetic basis of human physical or cognitive ability is discovered. On the positive side, understanding a person's predisposition for certain abilities (or limitations) could enable custom educational or remediation programs that will help to compensate for genetic inclinations, especially in early years when their effect can be optimized. On the negative side, groups may use such analyses in arguments to discriminate against target populations (despite, for example, the fact that ethnic distribution variances of cognitive ability are currently believed to be wider than ethnic mean differences), aggravating social and international conflicts.

Although the genetic profiles of plants have been modified for centuries using traditional techniques, questions regarding the safety of genetically modified foods have sparked international concerns in the United Kingdom and Europe, forcing a campaign by biotechnology companies to argue the safety of the technology and its applications. Some have argued that genetic engineering is actually as safe or safer than traditional combinatorial techniques such as irradiated seeds, since there often is strong supporting information concerning the function of the inserted sequences (see, for example, Somerville, 2000 [70]).

Governments have been forced into the issue, resulting in education efforts, food labeling proposals, and heated international trade discussions between the United States and Europe on the importation of GMOs and their seedlings. As genetic modification becomes more common, it may become more difficult to label and separate GMOs, resulting in a forcing function to resolve the issue of how far the technology should be applied and whether separate markets can be maintained in a global economy. This debate is starting to have global effects as populations in other countries begin to notice the impassioned debates in the United Kingdom and Europe.

Some have likened the anti-biotechnology movement to the anti-nuclear-power movement in scope and tactics, although the low cost and wide availability of basic genomic equipment and know-how will likely allow practically any country, small business, or even individual to participate in genetic engineering (Hapgood, 2000 [40]). Such wide technology availability and low entry costs could make it impossible for any movement or government to control the spread and use of genomic technology. At an extreme, successful protest pressures on big biotechnology companies together with wide technology availability could ultimately drive genomic engineering "underground" to groups outside such pressures and outside regulatory controls that help ensure safe and ethical uses. This could ironically facilitate the very problems that the anti-biotechnology movement is hoping to prevent.

Cloning and genetic modification also raise biodiversity concerns. Standardization of crops and livestock have already increased food supply vulnerabilities to diseases that can wipe out larger areas of production. Genetic modification may increase our ability to engineer responses to these threats, but the losses may still be felt in the production year unless broad-spectrum defenses are developed.

In addition to food safety, the ability to modify biological organisms holds the possibility of engineered biological weapons that circumvent current or planned countermeasures. On the other hand, genomics could aid in biological warfare defense (e.g., through improved understanding and control of biological function both in and between pathogens and target hosts as well as improved capability for engineered biosensors). Advances in genomics, therefore, could advance a race between threat engineering and countermeasures. Thus, although genetic manipulation is likely to result in medical advances, it is unclear whether we will be in a safer position in the future.

The rate at which GMO benefits are felt in poorer countries may depend on the costs of using patented organisms, marketing demands and approaches, and the rate at which crops become ubiquitous and inseparable from unmodified strains. Consider, for example, current issues related to human immunodeficiency virus (HIV) drug development and dissemination in poorer countries. Patentability has fueled research investments, but many poorer countries with dire needs cannot afford the latest drugs and must wait for handouts or patent expiration. Globalization, however, may fuel dissemination as multi-national companies invest in food production across the globe. Also, the rewards from opening previously unproductive land for production may provide the financial incentive to pay the premium for GMOs. Furthermore, widely available genomic technology could allow academics, nonprofit small businesses, and developing countries to develop GMOs to alleviate problems in poorer regions; larger biotechnology companies will focus on markets requiring capital-intensive R&D.

Finally, moral issues may play a large role in modulating the global effect of genomics trends. Some people simply believe it is improper to engineer or modify biological organisms using the new techniques. Unplanned side effects (e.g., the imposition of arthritis in current genetically modified pigs) will likely support such opposition. Others are concerned with the real danger of eugenics programs or of the engineering of dangerous biological organisms.

Therapies and Drug Development

Technology

Beyond genetics, biotechnology will likely continue to improve therapies for preventing and treating disease and infection. New approaches might block a pathogen's ability to enter or travel in the body, leverage pathogen vulnerabilities, develop new countermeasure delivery mechanisms, or modulate or augment the immune response to recognizing new pathogens. These therapies may counter the current trend of increasing resistance to extant antibiotics, reshaping the war on infections.

In addition to addressing traditional viral and bacterial problems, therapies are being developed for chemical imbalances and modulation of chemical stasis. For example, antibodies are being developed that attack cocaine in the body and may be used to control addiction. Such approaches could have a significant effect on modifying the economics of the global illegal drug trade while improving conditions for users.

Drug development will likely be aided by various technology trends and enablers. Computer simulations combined with proliferating trends for molecular imaging technologies (e.g., atomic-force microscopes, mass spectroscopy, and scanning probe microscopes) may continue to improve our ability to design molecules with desired functional properties that target specific receptors, binding sites, or markers, complementing combinatorial drug search with rational drug design. Simulations of drug interactions with target biological systems could become increasing useful in understanding drug efficacy and safety. For example, Dennis Noble's complex virtual heart simulation has already contributed to U.S. Food and Drug Administration (FDA) approval of a cardiac drug by helping to understand the mechanisms and significance of an effect noticed in the clinical trial (Noble, 1998; Robbins-Roth, 1998; Buchanan, 1999 [109-111]). For some better understood systems such as the heart, this approach may become a dominant complement to clinical drug trials by 2015, whereas other more complex systems (e.g., the brain) will likely require more research on the system function and biology.

Broader Issues and Implications

R&D costs for drug development are currently extremely high and may even be unsustainable (PricewaterhouseCoopers, 1998 [19]), with averages of approximately $600 million per drug brought to market. These costs may drive the pharmaceutical industry to invest heavily in technology advances with the goal of long-term viability of the industry (PricewaterhouseCoopers, 1999 [37]). Combined with genetic profiling, drug development tailored to genotypes, chemical simulation and engineering programs, and drug testing simulations may begin to change pharmaceutical development from a broad application trial-and-error approach to custom drug development, testing, and prescription based on a deeper understanding of subpopulation response to drugs. This understanding may also rescue drugs previously rejected because of adverse reactions in small populations of clinical trials. Along with the potential for improving success rates, reducing trial costs, and opening new markets for narrowly targeted drugs, tailoring drugs to subpopulations will also have the opposite effect of reducing the size of the market for each drug. Thus, the economics of the pharmaceutical and health industries will likely change significantly if these trends come to fruition.

Note that patent protection is not uniformly enforced across the globe for the pharmaceutical industry.{3} As a result, certain regions (e.g., Asia) may continue to focus on production of non-legacy (generic) drugs, and other regions (e.g., the United States, United Kingdom, and Europe) will likely continue to pursue new drugs in addition to such low-margin pharmaceuticals.

Biomedical Engineering

Multidisciplinary teaming is accelerating advances and products in biomedical engineering and technology of organic and artificial tissues, organs, and materials.

Organic Tissues and Organs

Advances in tissue and organ engineering and repair are likely to result in organic and artificial replacement parts for humans. New advances in tissue regeneration and repair continue to improve our ability to resolve health problems within our bodies.

The field of tissue engineering, which is barely a decade old, has already led to engineered commercial skin products for wound treatment.{4} Growth of cartilage for repair and replacement is at the stage of clinical testing,{5} and treatment of heart disease via growth of functional tissue by 2015 is a realistic goal.{6} These advances will depend upon improved biocompatible (or bioabsorbable) scaffold materials, development of 3D vascularized tissues and multicellular tissues, and an improved understanding of the in vivo growth process of cellular material on such scaffolds (Bonassar and Vacanti, 1998 [130]).

Research and applications of stem cell therapies will likely continue and expand, using these unspecialized human cells to augment or replace brain or body functions, organs (e.g., heart, kidney, liver, pancreas), and structures (Shamblott et al., 1998; Thomson et al., 1998; Couzin, 1999; Allen, 2000 [117-119, 122]). As the most unspecialized stem cells are found in early stage embryos or fetal tissue, an ethical debate is ensuing regarding the use of stem cells for research and therapy (Couzin, 1999; U.S. National Bioethics Advisory Commission, 1999; Allen, 2000 [119, 120, 122]). Alternatives such as the use of adult human stem cells or stem cell culturing may ultimately produce large-scale cell supplies with reduced ethical concerns. Current debates have limited U.S. government funding for stem cell research, but the potential has attracted substantial private funding.

Xenotransplantations (transplantation of body parts from one species to a different species) could be improved, aided by attempts to genetically modify donor tissue and organ antibodies, complements, and regulatory proteins to reduce or eliminate rejection. Baboons or pigs, for example, may be genetically modified and cloned to produce organs for human transplant, although large-scale success may not occur by 2015.

Beyond rejection, the significance of xenotransplants is likely to be modulated by concerns that diseases such as retro viruses might jump from animals to people as a result of the transplantation techniques (Long, 1998 [17]). Ethical (e.g., animal rights) and moral concerns as well as possible patenting issues (see, for example, Walter, 1998 [208]) may also result in regulations and limitations on xenotransplants, limiting their significance.

Artificial Materials, Organs, and Bionics

In addition to organic structures, advances are likely to continue in engineering artificial tissues and organs for humans.

Multi-functional materials are being developed that provide both structure and function or that have different properties on different sides, enabling new applications and capabilities. For example, polymers with a hydrophilic shell around a hydrophobic core (biomimetic of micelles) can be used for timed release of hydrophobic drug molecules, as carriers for gene therapy or immobilized enzymes, or as artificial tissues. Sterically stabilized polymers could also be used for drug delivery.

Other materials are being developed for various biomedical applications. Fluorinated colloids, for example, are being developed that take advantage of the high electronegativity of fluorine to enhance in vivo oxygen transport (as a blood substitute during surgery) and for drug delivery. Hydrogels with controlled swelling behavior are being developed for drug delivery or as templates to attach growth materials for tissue engineering. Ceramics such as bioactive calcia-phosphate-silica glasses (gel-glasses), hydroxyapetite, and calcium phosphates can serve as templates for bone growth and regeneration. Bioactive polymers (e.g., polypeptides) can be applied as meshes, sponges, foams, or hydrogels to stimulate tissue growth. Coatings and surface treatments are being developed to increase biocompatibility of implanted materials (for example, to overcome the lack of endothelial cells in artificial blood vessels and reduce thrombosis). Blood substitutes may change the blood storage and retrieval systems while improving safety from blood-borne infections (Chang, 2000 [108]).

New manufacturing techniques and information technology are also enabling the production of biomedical structures with custom sizing and shape. For example, it may become commonplace to manufacture custom ceramic replacement bones for injured hands, feet, and skull parts by combining computer tomography and "rapid prototyping" (see below) to reverse engineer new bones layer by layer (Hench, 1999 [139]).

Beyond structures and organs, neural and sensor prosthetics could begin to become significant by 2015. Retinas and cochlear implants, bypasses of spinal and other nerve damage, and other artificial communications and stimulations may improve and become more commonplace and affordable, eliminating many occurrences of blindness and deafness. This could eliminate or reduce the effect of serious handicaps and change society's response from accommodation to remediation.

Biomimetics and Applied Biology

Recent techniques such as functional brain imaging and knock-out animals are revolutionizing our endeavors to understand human and animal intelligence and capabilities. These efforts should, by 2015, make significant inroads in improving our understanding of phenomena such as false memories, attention, recognition, and information processing, with implications for better understanding people and designing and interfacing artificial systems such as autonomous robots and information systems. Neuromorphic engineering (which bases its architecture and design principles on those of biological nervous systems){7} has already produced novel control algorithms, vision chips, head-eye systems, and biomimetic autonomous robots. Although not likely to produce systems with wide intelligence or capabilities similar to those of higher organisms, this trend may produce systems by 2015 that can robustly perform useful functions such as vacuuming a house, detecting mines, or conducting autonomous search.

Surgical and Diagnostic Biotechnology

Biotechnology and materials advances are likely to continue producing revolutionary surgical procedures and systems that will significantly reduce hospital stays and cost and increase effectiveness. New surgical tools and techniques and new materials and designs for vesicle and tissue support will likely continue to reduce surgical invasiveness and offer new solutions to medical problems. Techniques such as angioplasty may continue to eliminate whole classes of surgeries; others such as laser perforations of heart tissue could promote regeneration and healing. Advances in laser surgery could refine techniques and improve human capability (e.g., LASIK{8} eye surgery to replace glasses), especially as costs are reduced and experience spreads. Hybrid imaging techniques will likely improve diagnosis, guide human and robotic surgery, and aid in basic understanding of body and brain function. Finally, collaborative information technology (e.g., "telemedicine") will likely extend specialized medical care to remote areas and aid in the global dissemination of medical quality and new advances.

Broader Issues and Implications

By 2015, one can envision: effective localized, targeted, and controlled drug delivery systems; long-lived implants and prosthetics; and artificial skin, bone, and perhaps heart muscle or even nerve tissue. A host of social, political, and ethical issues such as those discussed above will likely accompany these developments.

Biomedical advances (combined with other health improvements) are already increasing human life span in countries where they are applied. New advances by 2015 are likely to continue this trend, accentuating issues such as shifts in population age demographics, financial support for retired persons, and increased health care costs for individuals. Advances, however, may improve not only life expectancy but productivity and utility of these individuals, offsetting or even overcoming the resulting issues.

Many costly and specialized medical techniques are likely to initially benefit citizens who can afford better medical care (especially in developed countries, for example); wider global effects may occur later as a result of traditional trickle-down effects in medicine. Some technologies (e.g., telemedicine) may have the opposite trend where low-cost technologies may enable cost-effective consulting with specialists regardless of location. However, access to technology may greatly mediate this dispersal mechanism and may place additional demands on technology upgrades and education. Countries that remain behind in terms of technological infrastructures may miss many of these benefits.

Theological debates have also raised concerns about the definition of what constitutes a human being, since animals are being modified to produce human organs for later xenotransplantation in humans. Genetic profiling may help to inform this debate as we understand the genetic differences between humans and animals.{9}

Improved understanding of human intelligence and cognitive function could have broader legal and social effects. For example, an understanding of false memories and how they are created could have an effect on legal liabilities and courtroom testimony. Understanding innate personal capabilities and job performance requirements could help us determine who would make better fighter pilots, who has an edge in analyzing complex images,{10} and what types of improved training could improve people's capabilities to meet the special demands of their chosen careers. Ethical concerns could arise concerning discrimination against people who lack certain innate skills, requiring objective and careful measures for hiring and promotion.

Eventually, neural and sensory implants (combined with trends toward pervasive sensors in the environment and increased information availability) could radically change the way people sense, perceive, and interact with natural and artificial environments. Ultimately, these new capabilities could create new jobs and functions for people in these environments. Such innovations may first develop for individuals with particularly challenging and critical functions (e.g., soldiers, pilots, and controllers), but innovations may first develop in other quarters (e.g., for entertainment or business functions), given recent trends. Initial research indicates the feasibility of such implants and interactions, but it is unclear whether R&D and investments will accelerate enough to realize even such early applications by 2015. Current trends have concentrated on medical prosthetics where research prototypes are already appearing so it appears likely that globally significant systems will appear in this domain first.

The Process Of Materials Engineering

New materials can often be critical enabling drivers for new systems and applications with significant effects. However, it may not be obvious how enabling materials affect more observable trends and applications. A common process model from materials engineering can help to show how materials appear likely to break previous barriers in the process that ultimately results in applications with potential global benefits.

Developments in materials science and engineering result from interdisciplinary materials research. This development can be conveniently represented by the schematic description of the materials engineering process from concept to product/application (see Figure 2.1). This process view is a common approach in materials research circles and similar representations may be found in the literature (see, for example, National Research Council, 1989 [123], p. 29). Current trends in materials research that could result in global effects by 2015 are categorized below according to the process description of Figure 2.1. Figure 2.2 provides an example of the development process in the area of electroactive polymers for robotic devices and artificial muscles.

Concept/Materials Design

Biomimetics is the design of systems, materials, and their functionality to mimic nature. Current examples include layering of materials to achieve the hardness of an abalone shell or trying to understand why spider silk is stronger than steel.

Combinatorial materials design uses computing power (sometimes together with massive parallel experimentation) to screen many different materials possibilities to optimize properties for specific applications (e.g., catalysts, drugs, optical materials).

Materials Selection, Preparation, and Fabrication

Composites are combinations of metals, ceramics, polymers, and biological materials that allow multi-functional behavior. One common practice is reinforcing polymers or ceramics with ceramic fibers to increase strength while retaining light weight and avoiding the brittleness of the monolithic ceramic. Materials used in the body often combine biological and structural functions (e.g., the encapsulation of drugs).

Figure 2.1--The General Materials Engineering Process

Figure 2.2--Materials Engineering Process Applied to Electroactive Polymers

Nanoscale materials, i.e., materials with properties that can be controlled at submicrometer (<10-6 m) or nanometer (10-9 m) level, are an increasingly active area of research because properties in these size regimes are often fundamentally different from those of ordinary materials. Examples include carbon nanotubes, quantum dots, and biological molecules. These materials can be prepared either by purification methods or by tailored fabrication methods.

Processing, Properties, and Performance

These areas are inextricably linked to each other: Processing determines properties that in turn determine performance. Moreover, the sensitivity of instrumentation and measurement capability is often the enabling factor in optimizing processing, for example, as for nanotechnology and microelectromechanical systems (MEMS).

Rapid prototyping is the capability to combine computer-assisted design and manufacturing with rapid fabrication methods that allow inexpensive part production (as compared to the cost of a conventional production line). Rapid prototyping enables a company to test several different inexpensive prototypes before committing infrastructure investments to an approach. Combined with manufacturing system improvements to allow flexibility of approach and machinery, rapid prototyping can lead to an agile manufacturing capability. Alternatively, the company can use its virtual capability to design and then outsource product manufacturing, thus offloading capital investment and risk. This capability is synergistic with the information technology revolution in the sense that it is a further factor in globalizing manufacturing capability and enabling organizations with less capital to have a significant technological effect. For the Department of Defense (DoD), it could reduce or eliminate requirements for warehousing large amounts of spares and, for example, could enable the Air Force to "fly before they buy."

Self-assembly refers to the use in materials processing or fabrication of the tendency of some materials to organize themselves into ordered arrays (e.g., colloidal suspensions). This provides a means to achieve structured materials "from the bottom up" as opposed to using manufacturing or fabrication methods such as lithography, which is limited by the measurement and instrumentation capabilities of the day. For example, organic polymers have been tagged with dye molecules to form arrays with lattice spacing in the visible optical wavelength range and that can be changed through chemical means. This provides a material that fluoresces and changes color to indicate the presence of chemical species.

Manufacturing with DNA might represent the ultimate biomimetic manufacturing scheme. It consists of "functionalizing small inorganic building blocks with DNA and then using the molecular recognition processes associated with DNA to guide the assembly of those particles or building blocks into extended structures" (Mirkin, 2000 [106]). Using this approach, Mirkin and colleagues demonstrated a highly selective and sensitive DNA-based chemical assay method using 13 nm diameter gold particles with attached DNA sequences. This approach is compatible with the commonly used polymerase chain reaction (PCR) method of amplification of the amount of the target substance.

Micro- and nano-fabrication methods include, for example, lithography of coupled micro- or nano-scale devices on the same semiconductor or biological material. It is important to note the crucial role played in the development of these techniques by the parallel development of instrumentation and measurement devices such as the Atomic Force Microscope (AFM) and the various Scanning Probe Microscopes (SPMs).

Product/Application

The trends described above will likely work in concert to provide materials engineers with the capability to design and produce advanced materials that will be:

Smart Materials

Technology

Several different types of materials exhibit sensing and actuation capabilities, including ferroelectrics (exhibiting strain in response to a electric field), shape-memory alloys (exhibiting phase transition-driven shape change in response to temperature change), and magnetostrictive materials (exhibiting strain in response to a magnetic field). These effects also work in reverse, so that these materials, separately or together, can be used to combine sensing and actuation in response to environmental conditions. They are currently in widespread use in applications from ink-jet printers to magnetic disk drives to anti-coagulant devices.

An important class of smart materials is composites based upon lead zirconate titanate (PZT) and related ferroelectric materials that allow increased sensitivity, multiple frequency response, and variable frequency (Newnham, 1997 [146]). An example is the "Moonie"--a PZT transducer placed inside a half-moon-shaped cavity, which provides substantial amplification of the response. Another example is the use of composites of barium strontium titanate and non-ferroelectric materials that provide frequency-agile and field-agile responses. Applications include sensors and actuators that can change their frequency either to match a signal or to encode a signal. Ferroelectrics are already in use as nonvolatile memory elements for smart cards and as active elements in smart skis that change shape in response to stress.

Another important class of materials is smart polymers (e.g., ionic gels that deform in response to electric fields). Such electro-active polymers have already been used to make "artificial muscles" (Shahinpoor et al., 1998 [147]). Currently available materials have limited mechanical power, but this is an active research area with potential applications to robots for space exploration, hazardous duty of various types, and surveillance. Hydrogels that swell and shrink in response to changes in pH or temperature are another possibility; these hydrogels could be used to deliver encapsulated drugs in response to changes in body chemistry (e.g., insulin delivery based upon glucose concentration). Another variation on this trend for controlled release of drugs is materials with hydrophilic exterior and hydrophobic interior.

Broader Issues and Implications

A world with pervasive, networked sensors and actuators (e.g., on and part of walls, clothing, appliances, vehicles, and the environment) promises to improve, optimize, and customize the capability of systems and devices through availability of information and more direct actuation. Continuously available communication capability, ability to catalog and locate tagged personal items, and coordination of support functions have been espoused as benefits that may begin to be realized by 2015.

The continued development of small, low-profile biometric sensors, coupled with research on voice, handwriting, and fingerprint recognition, could provide effective personal security systems. These could be used for identification by police/military and also in business, personal, and leisure applications. Combined with today's information technologies, such uses could help resolve nagging security and privacy concerns while enabling other applications such as improved handgun safety (through owner identification locks) and vehicle theft control.

Other potential applications of smart materials that would be enabled by 2015 include: clothes that respond to weather, interface with information systems, monitor vital signs, deliver medicines, and automatically protect wounds; airfoils that respond to airflow; buildings that adjust to the weather; bridges and roads that sense and repair cracks; kitchens that cook with wireless instructions; virtual reality telephones and entertainment centers; and personal medical diagnostics (perhaps interfaced directly with medical care centers). The level of development and integration of these technologies into everyday life will probably depend more on consumer attitudes than on technical developments.

In addition to the surveillance and identification functions mentioned under smart materials above, developments in robotics may provide new and more sensitive capabilities for detecting and destroying explosives and contraband materials and for operating in hazardous environments. Increases in materials performance, both for power sources and for sensing and actuation, as well as integration of these functions with computing power, could enable these applications.

Such trend potentials are not without issues. Pervasive sensory information and access to collected data raise significant privacy concerns. Also, the pace of development will likely depend on investment levels and market drivers. In many cases the immediate benefits and cost savings from smart material applications will continue to drive development, but more exotic materials research may depend on public commitment to research and belief in investing in longer-term rewards.

Self-Assembly

Technology

Examples of self-assembling materials include colloidal crystal arrays with mesoscale (50-500 nm) lattice constants that form optical diffraction gratings, and thus change color as the array swells in response to heat or chemical changes. In the case of a hydrogel with an attached side group that has molecular recognition capability, this is a chemical sensor. Self-assembling colloidal suspensions have been used to form a light-emitting diode (nanoscale), a porous metal array (by deposition followed by removal of the colloidal substrate), and a molecular computer switch.

The DNA-based self-assembly mentioned above (Mirkin, 2000 [106]) was achieved by attaching non-linking DNA strands to metal nanoparticles and adding a linking agent to form a DNA lattice. This can be turned into a biosensor or a nanolithography technique for biomolecules.

Broader Issues and Implications

Development of self-assembly methods could ultimately provide a challenge to top-down lithography approaches and molecular manufacturing approaches. As a result, it could define the next manufacturing methodology at some time beyond 2015. For example, will self-assembly methods "trump" lithography (the miracle technology of the semiconductor revolution) over the next decade or two?

Rapid Prototyping

Technology

This manufacturing approach integrates computer-aided design (CAD) with rapid forming techniques to rapidly create a prototype (sometimes with embedded sensors) that can be used to visualize or test the part before making the investment in tooling required for a production run. Originally, the prototypes were made of plastic or ceramic materials and were not functional models, but now the capability exists to make a functional part, e.g., out of titanium. See, for example, the discussion of reverse-engineered bones in the section on biomedical engineering.

Broader Issues and Implications

As discussed above, agile manufacturing systems are envisioned that can connect the customer to the product throughout its life cycle and enable global business enterprises. An order would be processed using a computer-aided design, the manufacturing system would be configured in real time for the specific product (e.g., model, style, color, and options), raw materials and components would be acquired just in time, and the product would be delivered and tracked throughout its life cycle (including maintenance and recycling with identification of the customer). Components of the business enterprise could be dynamically based in the most cost-effective locations with all networked together globally. The growth of this type of business enterprise could accelerate business globalization.

Buildings

Research on composite materials, waste management, and recycling has reached the stage where it is now feasible to construct buildings using materials fabricated from significant amounts of indigenous waste or recycled material content (Gupta, 2000 [127]). These approaches are finding an increasing number of cost-effective applications, especially in developing countries. Examples include the Petronas Twin Towers in Kuala Lumpur, Malaysia. These towers are the tallest buildings on earth and are made with reinforced concrete rather than steel. A roofing material used in India is made of natural fiber and agro-industrial waste. Prefabricated composite materials for home construction have also been developed in the United States, and a firm in the Netherlands is developing a potentially ubiquitous, inexpensive housing approach targeted for developing countries that uses spray-forming over an inflatable air shell.{11}

Transportation

An important trend in transportation is the development of lightweight materials for automobiles that increase energy efficiency while reducing emissions. Here the key issue is the strength-to-weight ratio versus cost. Advanced composites with polymer, metal, or ceramic matrix and ceramic reinforcement are already in use in space systems and aircraft. These composites are too expensive for automobile applications, so aluminum alloys are being developed and introduced in cars such as the Honda Insight, the Audi A8 and AL2, and the GM EV1. Although innovation in both design and manufacturing is needed before such all-aluminum structures can become widespread, aluminum content in luxury cars and light trucks has increased in recent years. Polymer matrix, carbon-fiber (C-fiber) reinforced composites could enable high mileage cars, but C-fiber is currently several times more expensive than steel. Research sponsored by the Department of Energy (DOE) at Oak Ridge National Laboratory is working to develop cheap C-fibers which could have wider application and effect.

Spurred by California's regulations concerning ultra-low-emission vehicles, both Honda and Toyota have introduced gasoline-electric hybrid vehicles. The U.S. government and industry consortium called Partnership for a New Generation of Vehicles (PNGV) has demonstrated prototype hybrid vehicles that use both diesel/electric and diesel/fuel-cell power plants and has established 2008 as the goal for a production vehicle. These vehicles use currently available materials, but the cost reduction issues described above will be critical in bringing production costs to levels that will allow significant market penetration.

Energy Systems

If the ready availability of oil continues, it may be difficult for technology trends to be much of a driving force in global energy between now and 2015. Key questions have to do with continued oil imports, continued use of coal, sources of natural gas, and the fate of nuclear power. Nevertheless, technology may have significant effects in some areas.

Along with investments in solar energy, current investments in battery technology and fuel cells could enable continued trends in more portable devices and systems while extending operating times.

Developments in materials science and engineering may enable the energy systems of 2015 to be more distributed with a greater capability for energy storage, as well as energy system command, control, and communication. High-temperature superconducting cables, transformers, and storage devices could begin to increase energy transmission and distribution capabilities and power quality in this time frame.

The continued development of renewable energy could be enhanced by the combination of cheap, lightweight, recyclable materials (and perhaps the genetic engineering of biomass fuels) to provide cost-effective energy for developing countries without existing, well-developed energy infrastructures as well as for remote locations.

Significant changes in developed countries, however, may be driven more by existing social, political, and business forces, since the fuel mix of 2015 will still be strongly based on fossil fuels. Environmental concerns such as global warming and pollution might shift this direction, but it would likely require long-term economic problems (e.g., a prolonged rise in the price of oil) or distribution problems (e.g., supplies interrupted by military conflicts) to drive advances in renewable energy development.

New Materials

Materials research may provide improvements in properties by 2015 in a number of additional areas, leading to significant effects.

SiC, GaN, and other wide band gap semiconductors are being investigated as materials for high-power electronics.

Functionally graded materials (i.e., materials whose properties change gradually from one end to the other) can form useful interlayers between mechanically, thermally, or electrically diverse components.

Anodes, cathodes, and electrolytes with higher capacity and longer lifetime are being developed for improved batteries and fuel cells.

High-temperature (ceramic) superconductors discovered in 1986 can currently operate at liquid nitrogen (rather than liquid helium) temperatures. Prototype devices such as electrical transmission cables, transformers, storage devices, motors, and fault current limiters have now been built and demonstrated. Niche application on electric utility systems should begin by 2015 (e.g., replacement of underground cables in cities and replacement of older substation transformers).

Nonlinear optical materials such as doped LiNbO3 are being investigated for ultraviolet lasers (e.g., to enable finer lithography). Efforts are under way to increase damage threshold and conversion efficiency, minimize divergence, and tailor the absorption edge.

Hard materials such as nanocrystalline coatings and diamonds are being developed for applications such as computer disk drives and drill bits for oil and gas exploration, respectively.

High-temperature materials such as ductile intermetallics and ceramic matrix composites are being developed for aerospace applications and for high-efficiency energy and petrochemical conversion systems.

Nanomaterials

This area combines nanotechnology and many applications of nanostructured materials. One important research area is the formation of semiconductor "quantum dots" (i.e., several nanometer-size, faceted crystals) by injecting precursor materials conventionally used for chemical-vapor deposition of semiconductors into a hot liquid surfactant. This "quantum dot" is in reality a macromolecule because it is coated with a monolayer of the surfactant, preventing agglomeration. These materials photoluminesce at different frequencies (colors) depending upon their size, allowing optical multiplexing in biological labeling.{12}

Another important class of nanomaterials is nanotubes (the open cylindrical sisters of fullerenes).{13} Possible applications are field-emission displays (Mitsubishi research), nanoscale wires for batteries, storage of Li or H2, and thermal management (heat pipes or insulation--the latter taking advantage of the anisotropy of thermal conductivity along and perpendicular to the tube axis). Another possibility is to use nanotubes (or fibers built from them) as reinforcement for composite materials. Presumably because of the nature of the bonding, it is predicted that nanotube-based material could be 50 to 100 times stronger than steel at one-sixth of the weight if current technical barriers can be overcome (Smalley, 1999; Service, 2000 [155, 161]).

Nanoscale structures with desirable mechanical and other properties may also be obtained through processing. Examples include strengthening of alloys with nanoscale grain structure, increased ductility of metals with multi-phase nanoscale microstructure, and increased flame retardancy of plastic nanocomposites.

Nanotechnology

Much has been made of the trend toward producing devices with ever-decreasing scale. Many people have projected that nanometer-scale devices will continue this trend, bringing it to unprecedented levels. This includes scale reduction not only in microelectronics but also in fields such as MEMS and quantum-switch-based computing in the shorter term. These advances have the potential to change the way we engineer our environment, construct and control systems, and interact in society.

Nanofabricated Computation Devices

Nanofabricated Chips. SEMATECH--the leading industry group in the semiconductor manufacturing business--is calling for the development of nanoscale semiconductors in their latest International Technology Roadmap for Semiconductors (ITRS) (SEMATECH, 1999 [190]). The roadmap calls for a 35 nm gate length in 2015 with a total number of functions in high-volume production microprocessors of around 4.3 billion. For low-volume, high-performance processors, the number of functions may approach 20 billion. Corresponding memory chips (DRAMs) are targeted to hold around 64 gigabytes. These roadmap targets would continue the exponential trend in processing power, fueling advances in information technology. Although a number of engineering challenges exist (such as lithography, interconnects, and defect management), obstacles to achieve at least this level of performance do not seem insurmountable.

Given unforeseen shortfalls in the economic production of these chips (e.g., because of very high manufacturing costs or unacceptably large numbers of manufacturing defects), several alternatives seem possible. Defect-tolerant computer architectures such as those prototyped on a small scale by Hewlett-Packard (Heath et al., 1998 [186]) offer one alternative. These alternative methods provide some level of additional robustness to the performance goals set by the ITRS.

However, in the years following 2015, additional difficulties will likely be encountered, some of which may pose serious challenges to traditional semiconductor manufacturing techniques. In particular, limits to the degree that interconnections or "wires" between transistors may be scaled could in turn limit the effective computation speed of devices because of materials properties and compatibility, despite incremental present-day advances in these areas. Thermal dissipation in chips with extremely high device densities will also pose a serious challenge. This issue is not so much a fundamental limitation as it is an economic consideration, in that heat dissipation mechanisms and cooling technology may be required that add to total system cost, thereby adversely affecting marginal cost per computational function for these devices.

Quantum-Switch-Based Computing. One potential long-term solution for overcoming obstacles to increased computational power is computing based on devices that take advantage of various quantum effects. The core innovation in this work is the use of quantum effects, such as spin polarization of electrons, to determine the state of individual switches. This is in contrast to more traditional microelectronics, which are based on macroscopic properties of large numbers of electrons, taking advantage of materials properties of semiconductors.

Various concepts of quantum computers are attractive because of their massive parallelism in computation, but they are not anticipated to have significant effects by 2015. These concepts are qualitatively different from those employed in traditional computers and will hence require new computer architectures. The types of computations (and hence applications) that can be quickly performed using these computers are not the same as those readily addressed by today's digital computer. Several workers in the area have devised algorithms for problems that are very computationally intensive (and thus time-consuming) for existing digital computers, which could be made much faster using the physics of quantum computers. Examples of these problems include factoring large numbers (essential for cryptographic applications), searching large databases, pattern matching, and simulation of molecular and quantum phenomena.

A preliminary survey of work in this area indicates that quantum switches are unlikely to overcome major technical obstacles, such as error correction, de-coherence and signal input/output, within the next 15 years. If this were indeed the case, quantum-switch-based computing does not appear to be competitive with traditional digital electronic computers within the 2015 timeframe.

Bio-Molecular Devices and Molecular Electronics

Many of the same manufacturing and architectural challenges discussed above regarding quantum computing also hold true for molecular electronics. Molecular electronic devices could operate as logic switches through chemical means, using synthesized organic compounds. These devices can be assembled chemically in large numbers and organized to form a computer. The main advantage of this approach is significantly lower power consumption by individual devices. Several approaches for such devices have been devised, and experiments have shown evidence of switching behavior for individual devices. Several research groups have proposed interconnection between devices using carbon nanotubes, which provide high conductivity using single molecular strands of carbon. Progress has been made toward raising the operating temperature of these switches to nearly room temperature, making the switching process reversible, and increasing the overall amount of current that can be switched using these devices.

Several major outstanding issues remain with respect to molecular electronics. One issue is that molecular memories must be able to maintain their state, just as in a digital electronic computer. Also, given that the manufacturing and assembly process for these devices will lead to device defects, a defect-tolerant computer architecture needs to be developed. Fabricating reliable interconnects between devices using carbon nanotubes (or some other technology) is an additional challenge. A significant amount of work is ongoing in each of these areas. Even though experimental progress to date in this area has been substantial, it seems unlikely (as with quantum computing) that molecular computers could be developed within the next 15 years that would be relatively attractive (from a price/performance standpoint) compared with conventional electronic computers.

Broader Issues and Implications

Examining the potential for developing qualitatively different computational capabilities from different technology bases is a challenging exercise. The history of computing over the last 50 years has seen one major shift in technology base (from vacuum tubes to semiconductor transistors), with a corresponding shift not just in computational power but also in attitudes about the value of computers. Ideas of computers as simple machines for computation gave way to the use of computers for personal productivity with the advent of the microprocessor. As the power of these microprocessors has grown exponentially, they have also been seen more recently as a vehicle for new media and socialization.

The ramifications of future computing technologies will be determined principally by two factors: the conception, development, and adoption of new applications that require significantly more computational power; and the ability of technology to address these demands. New applications are always difficult to anticipate, but it is less challenging to foresee the likely consequences for diffusion of this technology. Past experience with personal computers and telecommunications has shown that these technologies diffuse more rapidly in the developed world than in the developing world. It is difficult to foresee an increase in the political or ethical barriers to computing technologies beyond those seen today, and these are rapidly vanishing.

On the remaining question of technology development, the odds-on favorite for the next 15 years remains traditional digital electronic computers based on semiconductor technology. Given the virtual certainty of continued progress in this area, it is hard to imagine a scenario in which a competing technology (quantum-switch-based computing, molecular computers, or something else) could offer a significant performance advantage at a competitive price. But the longer-term, traditionally elusive question in the period after 2015 is: How long will traditional silicon computing last? And when, if ever, will a competing technology become available and attractive? If an alternative computing technology becomes sufficiently attractive, the economic effects of technology substitution on the current semiconductor industry and adjacent industries must be considered. For example, major industry players may be faced with a choice between cannibalizing their existing market opportunities in favor of these new, future technologies, competing head-on with new players, or simply acquiring them. Most important, given the very different architectural approaches of these technologies and the classes of problems for which they are best suited, what will be the effect on future applications? The promises of nanotechnology may indeed become a reality in the period after 2015, but it will face these competitive challenges before its significance becomes global.

Integrated Microsystems and MEMS

MEMS is less an application area in itself than a manufacturing or fabrication technique that enables other application areas. Many authors use MEMS as shorthand to imply a number of particular application areas. As it is used here, MEMS is a "top-down" fabrication technology that is especially useful for integrating mechanical and electrical systems together on the same chip. It is grouped in the category of integrated microsystems because these same MEMS techniques can be extended in the future to also help integrate biological and chemical components on the same chip, as discussed below. Thus far, MEMS techniques have been used to make some functional commercial devices such as sensors and single-chip measurement devices. Many researchers have used MEMS technologies as analytical tools in other areas of nanotechnology such as the ones discussed here.

Smart Systems-on-a-Chip (and Integration of Optical and Electronic Components)

Simple electro-optical and chemical sensor components have already been successfully integrated onto logic and memory chip designs in research and development labs. Likewise, radio frequency component integration in wireless devices is already being produced in mass quantities. Some companies have products capable of doing elementary DNA testing. The 1999 ITRS (noted above) predicts the introduction of chemical sensor components with logic in commercial designs by 2002, with electro-optical component integration by 2004, and biological systems integration by 2006. Given these predictions, there is clearly time for relatively complex integrated systems and applications to develop within the 2015 timeline. These advances could enable many applications where increased integrated functionality can become ubiquitous as a result of lower costs and micro-packaging.

Micro/Nanoscale Instrumentation and Measurement Technology

Instrumentation and measurement technologies are some of the most promising areas for near-term advancements and enabling effects. As optical, fluidic, chemical, and biological components can be integrated with electronic logic and memory components on the same chip at marginal cost, drug discovery, genetics research, chemical assays, and chemical synthesis are all likely to be substantially affected by these advances by 2015 (see also the previous section).

Some of the first applications of nanoscale (and microscale) instruments were as basic sensors for acceleration (such as those used in airbags), pressure, etc. Small, microscale, special-purpose optical and chemical sensors have been used for some time in sophisticated laboratory equipment, along with microprocessors for signal processing and computation. Already, companies have produced products that allow for basic DNA analysis, and that can assist in drug discovery. As these sensors become more sophisticated and more integrated with computational capability (with the aid of systems-on-a-chip), their utility should grow tremendously, especially in the biomedical arena.

Broader Issues and Implications

There are several advantages of nanotechnology for integrated systems in general (and instrumentation and measurement systems as a subset of these). First, existing semiconductor technologies will likely allow the volume manufacture of integrated smart systems that can be produced at low enough cost to be considered disposable. Second, the massive parallelism afforded by this same technology allows for the rapid analysis (with integrated computation) of very complex samples (such as DNA), the processing of large numbers of samples, and the recognition of large numbers of agents (e.g., infectious agents and toxins). Devices with these properties are already of tremendous utility in the biomedical arena for drug testing, chemical assays, etc. In addition, they will likely find utility in a variety of industrial applications.

Integrated micro/nanosystems are already starting to affect applications where miniaturization of components, subsystems, and even complete systems is significantly reducing device size, power, and consumables while introducing new capabilities. This area lends itself naturally to the confluence of all the broad areas discussed in this report (biotechnology, materials, and nanotechnology). The next five to ten years will likely see the integration of computational capabilities with biological, chemical, and optical components in systems-on-a-chip. At the same time, advances in biotechnology should drive applications for drug discovery and genomics, as well as the basic understanding of many other phenomena. Advances in biomaterials will likely produce biologically compatible packaging, capable of isolating substances from the body in a time-controlled fashion (e.g., for drug delivery). The confluence of these capabilities could allow for continued development of microscale and nanoscale systems that could continue to be introduced into the body to perform basic diagnostic functions in a minimally invasive way,{14} providing new abilities to remedy health problems.

Other possible applications include: pervasive, self-moving sensor systems; nanoscrubbers and nanocatalysts; even inexpensive, networked "nanosatellites." For example, so-called "nanosatellites" are targeting order-of-magnitude reductions in both size and mass (e.g., down to 10 kg) by reducing major system components using integrated microsystems. If successful, this could economize current missions and approaches (e.g., communication, remote sensing, global positioning, and scientific study) while enabling new missions (e.g., military tactical space support and logistics, distributed sparse aperture radar, and new scientific studies) (Luu and Martin, 1999 [214]). In addition, advances could empower the proliferation of currently controlled processing capabilities (e.g., nuclear isotope separation) with associated threats to international security. Progress will likely depend on investment levels as well as continued S&T development and progress.

Molecular Manufacturing and Nanorobots

Technology

A number of experts (K. Eric Drexler, among others) have put forth the concept of molecular manufacturing where objects are assembled atom by atom (or molecule by molecule).{15} Bottom-up molecular manufacturing differs from microtechnology and MEMS in that the latter employ top-down approaches using bulk materials using macroscopic fabrication techniques.

To realize molecular manufacturing, a number of technical accomplishments are necessary. First, suitable molecular building blocks must be found. These building blocks must be physically durable, chemically stable, easily manipulated, and (to a certain extent) functionally versatile. Several workers in the field have suggested the use of carbon-based diamond-like structures as building blocks for nano-mechanical devices, such as gears, pivots, and rotors. Other molecules could also be used to build structures, and to provide other integrated capabilities, such as chemically reactive structures. Much additional work in the area of modeling and synthesis of appropriate molecular structures is needed, and a number of groups are working to this end. Dresselhaus and others are fabricating suitable molecular building blocks for these structures.

The second major area for development is in the ability to assemble complex structures based on a particular design. A number of researchers have been working on different approaches to this issue. Different techniques for physical placements are under development. One approach by Quate, MacDonald, and Eigler uses atomic-force or molecular microscopes with very small nanoprobes to move atoms or molecules around with the aid of physical or chemical forces. An alternative approach by Prentiss uses lasers to place molecules in a desired location. Chemical assembly techniques are being addressed by a number of groups, including Whiteside's approach to building structures one molecular layer at a time.

A third major area for development within molecular manufacturing is systems design and engineering. Extremely complex molecular systems at the macro scale will require substantial subsystem design, overall system design, and systems integration, much like complex manufactured systems of the present day. Although the design issues are likely to be largely separable at a subsystems level, the amount of computation required for design and validation is likely to be quite substantial. Performing checks on engineering constraints, such as defect tolerance, physical integrity, and chemical stability, will be required as well.

Some workers in the area have outlined a potential path for the evolution of molecular manufacturing capability, which is broken down by overall size, type of fabrication technology, system complexity, component materials used, etc. Some versions of this concept foresee the use of massively parallel nanorobots or scanning nanoprobes to assemble structures physically (with 100 to 10,000 molecular parts). Other, more advanced concepts incorporate chemical principles and use simple chemical feedstocks to achieve much larger devices on the order of 108 to 109 molecular parts.

Ostensibly, as each of these techniques matures (or fails to develop), more systems and engineering-level work must be done before applications can be realized on a significant scale. Although molecular manufacturing holds the promise of significant global changes (such as retraining large numbers of manufacturing workforces, opportunities for new regions to vie for dominance in a new manufacturing paradigm, or a shift to countries that do not have legacy manufacturing infrastructures), it remains the least concrete of the technologies discussed here. Significant progress has been made, however, in the development of component technologies within the first regime of molecular manufacturing, where objects might be constructed from simple molecules and manufactured in a short amount of time via parallel atomic force microprobes or from simple self-assembled structures. Although the building blocks for these systems currently exist only in isolation at the research stage, it is certainly reasonable to expect that an integrated capability could be developed over the next 15 years. Such a system could be able to assemble structures with between 100 and 10,000 components and total dimensions of perhaps tens of microns. A series of important breakthroughs could certainly cause progress in this area to develop much more rapidly, but it seems very unlikely that macro-scale objects could be constructed using molecular manufacturing within the 2015 timeframe.

Broader Issues and Implications

The present period in molecular manufacturing research is extremely exciting for a number of reasons. First, many workers have begun to experimentally demonstrate basic capabilities in each of the core areas outlined above. Second, continued progress and ongoing challenges in the area of top-down microelectronics manufacturing are pushing existing capabilities closer to the nanoscale regime. Third, the understanding of fundamental properties of structures at the nanoscale has been greatly enhanced by the ability to fabricate very small test objects, analyze them experimentally using new capabilities, and understand them more fundamentally with the aid of sophisticated computational models.

At the same time, many visionaries have advanced notions about potential applications for molecular manufacturing. But because experimental capabilities are in their infancy (as many workers have pointed out), it is extremely difficult to foresee many outcomes, let alone assess their likelihood.

International competition for dominance or even capability in cutting-edge nanotechnology may still remain strong, but current investments and direction indicate that the United States and Europe may retain leadership in most of this field.{16} Progress in nanotechnology will depend heavily on R&D investments; countries that continue to invest in nanotechnology today may lead the field in 2015. In 1997, annual global investments in nanotechnology were as follows: Japan at $120 million, the United States at $116 million, Western Europe at $128 million, and all other countries (former Soviet Union, China, Canada, Australia, Korea, Taiwan, and Singapore) at $70 million combined (Siegel et al., 1999 [163]). Funding under the U.S. National Nanotechnology Initiative is proposed to increase to $270 million and $495 million in 2000 and 2001, respectively (National Nanotechnology Initiative, 2000 [179]).

This would not preclude other countries from acquiring capabilities in nanotechnology or in using these capabilities for narrow technological surprise or military means. Given the difficulty in foreseeing outcomes and estimating likelihoods, however, it is also difficult to extrapolate predictions of specific threats and risks from current trends.

Notes

{1} The Human Genome Project and Celera Genomics have released drafts of the human genome (IHGSC, 2001; Venter et al., 2001 [61, 64]). The drafts are undergoing additional validation, verification, and updates to weed out errors, sequence interruptions, and gaps (for details, see Pennisi, 2000, Baltimore, 2001, Aach et al., 2001, IHGSC, 2001, Galas, 2001, and Venter et al., 2001 [57, 59-61, 63, 64]). Additional technical difficulties in genomic sequencing include short, repetitive sequences that jam current DNA processing techniques as well as possible limitations of bacteria to accurately copy certain DNA fragments (Eisen, 2000; Carrington, 2000 [55, 56]).

{2} The Flavr-Savr trademark is held by Calgene, Inc.

{3} Lily Wu, personal communication.

{4} Background information and discussion of some current research can be found at http://www.pittsburgh-tissue.net and http://www.whitaker.org. Descriptions of commercial engineered skin products can be found at http://www.isotis.com http://www.advancedtissue.com, http://www.integra-ls.com, http://www.genzyme.com , and http://www.organogenesis.com .

{5} For example, see the Integra Life Sciences and Genzyme web sites above.

{6} Personal communication with Dr. Buddy Ratner, Director, University of Washington Engineered Biomaterials (UWEB) Center.

{7} See, for example, the annual Workshop on Neuromorphic Engineering held in Telluride, Colorado (http://zig.ini.unizh.ch/telluride2000/). Mark Tilden at Los Alamos National Laboratory (funded by DARPA) has demonstrated robots that locate unexploded land mines. See the in-depth article in Smithsonian Magazine, February 2000, pp. 96-112. Photos of some of Tilden's robots are posted at http://www.beam-online.com/Robots/Galleria_other/tilden.html.

{8} Laser in situ keratomileusis.

{9} For example, current estimates are that humans and chimpanzees differ genetically by only 1.5 percent (Carrington, 2000 [56]).

{10} For example, when do tetrachromats (individuals with four rather than three color detectors) have an edge and how can we identify such individuals?

{11} For an example of the use of spray-forming over an inflatable air shell for housing, see http://www.ims.org/project/projinfo/rubacfly.htm.

{12} See http://www.qdots.com for a description of the applications that Quantum Dot Corporation is pursuing. Note that this approach has advantages over dyes currently in use: Quantum dots do not photobleach nearly as rapidly as dyes, enable multiplexing, and fluoresce tens of nanoseconds later than the auto-fluorescence (thus separating signal from noise). Thus, they may enable rapid processing for drug discovery, blood assays, genotyping, and other biological applications.

{13} For links to nanotube sites and general information, see http://www.scf.fundp.ac.be/~vmeunier/carbon_nanotube.html. Note that Professor Richard Smalley at Rice University has established a production facility (see http://cnst.rice.edu/tubes/).

{14} See, for example, recent advances in wireless capsule endoscopy (Iddan et al., 2000 [210]).

{15} See Drexler, 1987; Drexler, 1992; Nelson and Shipbaugh, 1995; Crandall, 1996; Timp, 1999; Voss, 1999; and Zachary, 2000 [162-168].

{16} See also the longer discussion of international competition in the discussion of meta-technology trends in Chapter Three.

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