© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999

1.3 The Nanomedical Perspective

1.3.1 Nanomedicine and Molecular Nanotechnology

A mature nanomedicine will require the ability to build structures and devices to atomic precision, hence molecular nanotechnology and molecular manufacturing are key enabling technologies for nanomedicine. The prefix "nano-" (from the Greek root nanos, or dwarf) means one-billionth (10^-9) of something. The term "nanotechnology" refers most generally to technology on the scale of a billionth of a meter, or a nanometer (a nanometer is ~6 carbon atoms wide). Similarly, the words "nanomachine," "nanorobot," "nanomotor" and "nanocomputer" may refer to complex engineered objects fabricated by positioning matter with molecular control.

Molecular engineering was discussed as an extension of bulk technologies in the 1960s and 1970s by von Hippel,²²⁴⁵ von Foester,²²⁴⁶ and Zingsheim.²²⁴⁷ The phrase "Nano-Technology" was first used in print in 1974 by N. Taniguchi²²⁴¹ to refer to the increasingly precise machining and finishing of materials, progressing from larger to smaller scales and ultimately to nanoscale tolerances, following in the path of Feynman's proposed "top-down" approach,¹⁵⁶ a schemata which persisted in Taniguchi's thinking throughout the 1980s²⁸² and 1990s.²²⁴² In 1981, K.E. Drexler¹⁸² described a new "bottom-up" approach involving molecular manipulation and molecular engineering in the context of building molecular machines and molecular devices with atomic precision, a fundamentally different mind-set. Drexler again described molecular technology³¹¹ in 1982 and molecular mechanical devices²²⁴³ in 1983, first using the word "nanotechnology" in 1985²⁵⁹ and 1986⁸ as synonymous with molecular technology, finally settling upon "molecular nanotechnology" in 1991⁹ and "molecular machine systems" in 1992²⁷⁹ to clarify that his concept involved working devices constructed with atomic precision, as distinguished from nanostructured bulk materials, micromachinery, polymeric self-assembly, pure biotechnology, nanolithography, Langmuir-Blodgett thin films, and the like.^154,3262 Drexler's definition -- molecular nanotechnology as the three-dimensional positional control of atomic and molecular structure to create materials and devices with molecular precision -- is the usage adopted in this book. The first known use of the term "nanomedicine" was in 1991 by Drexler, Peterson, and Pergamit in their popular book Unbounding the Future.⁹

Is molecular nanotechnology possible? This question is explicitly addressed in Chapter 2, but the bottom line is that molecular nanotechnology violates no physical laws and there exist many possible technical paths leading to useful results.¹⁰ Even by 1985, for example, G. Yamamoto¹⁶⁴ had reported on molecular gears, describing "compounds that exist in conformations which are regarded as static meshed gears with two-toothed and three-toothed wheels and some of them behave as dynamic gears." H. Iwamura¹⁶³ prepared a system that formed a chain of beveled molecular gears with ~GHz rotation rates. In 1998, it was generally accepted that molecular nanotechnology would be developed, although there was still some disagreement about how long it would take.

It is often noted that molecular biological systems are themselves nanomachines, constituting an existence proof for molecular nanotechnology.^8-10,3261 Indeed, biotechnology is one possible implementation pathway for molecular nanotechnology that is being pursued (Section 2.3.1). Table 1.3 reveals the close functional correspondence between the macroscale components of everyday machines and the molecular components of natural biological systems. Such comparisons have a long history. For example, Marcello Malpighi (1628-1694), a professor of medicine in Pisa who discovered the fine structure of the lungs and the capillaries using the microscope,²²⁰⁴ once observed that "our bodies are composed of strings, thread, beams, levers, cloth, flowing fluids, cisterns, ducts, filters, sieves, and other similar mechanisms."

Parallels to living systems as molecular machines were drawn by Changeau,¹⁶² McClaire,²²⁴⁸ Laing,^2249-2251 Drexler,¹⁸² and Mitchell,²²⁵² inspiring early thinking in molecular manufacturing. For example, in 1991 Drexler⁹ observed:

"Technology-as-we-know-it is a product of industry, of manufacturing and chemical engineering. Industry-as-we-know-it takes things from nature -- ore from mountains, trees from forests -- and coerces them into forms that someone considers useful. Trees become lumber, then houses. Mountains become rubble, then molten iron, then steel, then cars. Sand becomes a purified gas, then silicon, then chips. And so it goes. Each process is crude, based on cutting, stirring, baking, spraying, etching, grinding, and the like."

"Trees, though, are not crude. To make wood and leaves, they neither cut, stir, bake, spray, etch, nor grind. Instead, they gather solar energy using molecular electronic devices, the photosynthetic reaction centers of chloroplasts. They use that energy to drive molecular machines -- active devices with moving parts of precise, molecular structure -- which process carbon dioxide and water into oxygen and molecular building blocks. They use other molecular machines to join these molecular building blocks to form roots, trunks, branches, twigs, solar collectors, and more molecular machinery. Every tree makes leaves, and each leaf is more sophisticated than a spacecraft, more finely patterned than the latest chip from Silicon Valley. They do all this without noise, heat, toxic fumes, or human labor, and they consume pollutants as they go. Viewed this way, trees are high technology. Chips and rockets are not."

Contemplating applications of nanotechnology to medicine, Brian Wowk²⁶¹ concluded that 20th century physicians were in a predicament similar to that which would be faced by 18th-century engineers trying to maintain a 20th-century automobile -- repairs would be crude at best, and breakdowns inevitable:

"Like primitive engineers faced with advanced technology, medicine must `catch up' with the technology level of the human body before it can become really effective. What is the technology level? Since the human body is basically an extremely complex system of interacting molecules (i.e., a molecular machine), the technology required to truly understand and repair the body is molecular machine technology -- nanotechnology. A natural consequence of [our achieving] this level of technology will be the ability to analyze and repair the human body as completely and effectively as we can repair any conventional machine today."

In Engines of Creation,⁸ Drexler drew inspiration from the cell's eye view to recognize that nanotechnology could bring a fundamental breakthrough in medicine. Noting that 20th century physicians relied chiefly on surgery and drugs to treat illness, Drexler explained:

"Surgeons have advanced from stitching wounds and amputating limbs to repairing hearts and reattaching limbs. Using microscopes and fine tools, they join delicate blood vessels and nerves. Yet even the best microsurgeon cannot cut and stitch finer tissue structures. Modern scalpels and sutures are simply too coarse for repairing capillaries, cells, and molecules. Consider `delicate' surgery from a cell's perspective. A huge blade sweeps down, chopping blindly past and through the molecular machinery of a crowd of cells, slaughtering thousands. Later, a great obelisk plunges through the divided crowd, dragging a cable as wide as a freight train behind it to rope the crowd together again. From a cell's perspective, even the most delicate surgery, performed with exquisite knives and great skill, is still a butcher job. Only the ability of cells to abandon their dead, regroup, and multiply makes healing possible."

"Drug therapy, unlike surgery, deals with the finest structures in cells. Drug molecules are simple molecular devices. Many affect specific molecules in cells. Morphine molecules, for example, bind to certain receptor molecules in brain cells, affecting the neural impulses that signal pain. Insulin, beta blockers, and other drugs fit other receptors. But drug molecules work without direction. Once dumped into the body, they tumble and bump around in solution haphazardly until they bump a target molecule, fit, and stick, affecting its function. Drug molecules affect tissues at the molecular level, but they are too simple to sense, plan, and act. Molecular machines directed by nanocomputers will offer physicians another choice. They will combine sensors, programs, and molecular tools to form systems able to examine and repair the ultimate components of individual cells. They will bring surgical control to the molecular domain."

By the end of the 20th century, mainstream military (DoD), NIH, NSF, and other U.S. government and international groups had begun to seriously consider the potential future applications of molecular nanotechnology in medicine. For example, in 1997 a panel of U.S. Department of Defense health science experts known as Military Health Service Systems (MHSS) 2020 concluded in its final report:¹⁰⁹⁵

"If a breakthrough to a [molecular] assembler occurs within ten to fifteen years, an entirely new field of nanomedicine will emerge by 2020. Initial applications will be focused outside the body in areas such as diagnostics and pharmaceutical manufacturing. The most powerful uses would eventually be within the body. Possible applications include programmable immune machines that travel through the bloodstream, supplementing the natural immune system; cell herding machines to stimulate rapid healing and tissue reconstruction; and cell repair machines to perform genetic surgery."

The present book takes as its starting point the assumption that the mass production of nanomachines at modest cost is technically feasible (Chapter 2), and then explores the medical implications of this assumption. Proposed systems presented in this trilogy are intended not as final engineering blueprints but merely as points of departure for further analysis and refinement. All designs and projected capabilities are, for the most part, conservatively drawn with generous safety margins, leaving a considerable volume of design space yet to be explored by more intrepid future investigators.

Last updated on 5 February 2003