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Appendix B. Related Research

B.1. Overview

The present volume analyzes the capabilities of nanomechanical systems, including computers and manufacturing systems able to construct additional nanomechanical systems. There has been an enormous amount of relevant work in chemistry, statistical mechanics, solid-state physics, mechanical engineering, and so forth; portions of that work are cited throughout the previous chapters and form their foundation. Nonetheless, despite prior discussions of biologicalstyle mechanisms (i.e., molecules and polymer-based molecular machines interacting in solution), and numerous proposals, efforts, and successes in building microscale, nanoscale, and molecular devices, there has until recently been little published work by other authors that parallels the direction taken here.1 Accordingly, much of this appendix discusses adjacent fields.

Section B. 2 describes how these fields have been divided in their methods and objectives. Sections B. 3 to B. 6 survey relevant work in the fields of mechanical engineering, microtechnology, chemistry, molecular biology, and protein engineering. Section B. 7 discusses proximal probe experiments that have demonstrated limited forms of molecular manipulation. Finally, Section B. 8 discusses the remarkably foresighted suggestions made by R. Feynman in 1959.

B.2.1. Scientific goals vs. technological goals

The construction of molecular manufacturing systems, like the construction of conventional manufacturing systems, is a technological goal. In many countries (e.g., the U.S.), the study of molecules is usually taught as chemistry and defined as a natural science. As materials science is to integrated circuit design, and as physics is to mechanical engineering, so chemistry is to molecular engineering: a distinct but intimately related discipline. It would be remarkable if materials scientists developed computers, or if physicists developed automobiles; likewise, it is not surprising that chemists have not developed molecular manufacturing systems.

B.2.2. Top-down vs. bottom-up approaches

Engineering systems today range from macroscopic to microscopic, with active research on building electronic and mechanical systems on ever-smaller scales using microtechnologies. The micron scale, however, is volumetrically 10910^{9} times larger than the nanometer scale, and existing microtechnologies provide no mechanism for gaining precise, molecular control of the surface and interior of a complex, three-dimensional structure. A wide gap has separated the top-down path of microtechnology (starting with large, complex, and irregular structures) from the bottom-up path of chemistry (starting with small, simple, and exact structures). In microtechnology, the challenge is to make imprecise structures smaller; in chemical synthesis, the challenge is to make precise structures larger. An engineering discipline is only now forming around the latter goal.

B.2.3. Immediate goals vs. long-term prospects

Science and technology are united by a focus on what can be made or tested within a few years. The molecular sciences are centered around the laboratory, and hence around current capabilities. Engineering is centered around the workshop, again binding creative thought to current capabilities. In most sciences, theoretical work is scarce relative to experimental work (the abundant output of theoretical physics is an outstanding exception). The study of prospects in technology (Appendix A), though based on present scientific knowledge, is a theoretical discipline that falls outside the usual scope of physics, of laboratory science, and of practical engineering.

B.3. Mechanical engineering and microtechnology

When miniaturization is viewed as an incremental, top-down process, as in mechanical engineering and microtechnology, working at the molecular size scale appears to be a distant goal. Current research in top-down miniaturization (usually termed "microtechnology" but sometimes termed "nanotechnology") offers no obvious way to achieve the goals of molecular manufacturing. Precise control of mechanical structures at the molecular scale has only recently begun to be considered as a goal for mechanical engineering.

B.4. Chemistry

Chemistry is usually regarded as a laboratory-centered natural science.2 Lacking the means to design and synthesize complex molecular machines, and also lacking an engineering tradition urging them in that direction, chemists have yet to place the design and analysis of systems of molecular machinery high on their research agenda. Chemical research has nonetheless made progress toward complex molecular systems; the following is a highly fragmentary review.

The early 1980s saw a wave of interest in molecular electronics. In his Nobel lecture (Lehn, 1988), J.-M. Lehn stated:

Components and molecular devices such as molecular wires, channels, resistors, rectifiers, diodes, and photosensitive elements might be assembled into nanocircuits and combined with organized polymolecular assemblies to yield systems capable ultimately of performing functions of detection, storage, processing, amplification, and transfer of signals and information by means of various mediators (photons, electrons, protons, metal cations, anions, molecules) with coupling and regulation.

This paragraph closes with a list of references, of which the earliest are Nagle et al. (1981), which describes experiments on charge-transfer excited states in synthetic molecules; Drexler (1981), which suggests molecular computers as possible products of molecular manufacturing; and an address by J.-M. Lehn (1980). Molecular rectifiers had been proposed by Aviram and Ratner (1974), and other molecular electronic systems had been proposed by F. Carter (e.g., in Carter, 1980).

Most experimental research in molecular electronics has focused on the development of molecules that exhibit useful electronic properties in thin films or in microscale aggregates; some proposals, however, have focused on the construction of computational devices in which individual molecules or moieties would serve as signal carrying and switching elements [e.g., papers in Carter (1982,1987)(1982,1987); also (Robinson and Seeman, 1987) and many others]. These have suggested various combinations of chemical synthesis, protein engineering, and DNA engineering to make self-assembling systems on a broadly biological model. This objective is a form of molecular systems engineering (though not of machines or manufacturing systems) and the capabilities required would resemble those discussed in Chapter 15.

Chemists have constructed molecular devices including sophisticated reagents and catalysts, molecules in which two rotating sections are coupled in a gear-like manner (Mislow, 1989), molecules that self-assemble to form small structures (for examples, see Cram, 1986; Cram, 1988; Diederich, 1988; Lehn, 1988; Rebek, 1987), molecules that self-assemble in a planned manner to form crystals (for example, Fagan et al., 1989), and a molecule that catalyzes the synthesis of copies of itself (Tjivikua et al., 1990). Recent years have seen the development of molecular systems including components that join covalently in a process described as "structure-directed synthesis" (Ashton et al., 1989). Efforts of this kind have been described as steps toward "molecular LEGO" (Kohnke et al., 1989) or "molecular Meccano" (Anelli et al., 1992); synthetic rods have been described as steps toward "molecular Tinkertoys" (Kaszynski et al., 1992). These descriptions, however, have yet to be supported by the necessary system-level analysis: in the cited toy systems, well-known means (e.g., hands) join the building blocks to form complex, aperiodic, functional patterns, but comparable means remain to be described in connection with these molecular structures. Lindsey (1991) provides a useful discussion of the self-assembly principles that might be used to fill this gap (in the absence of direct molecular manipulation).

Chemistry has traditionally followed a forward-chaining strategy (Section 16.2.1), taking solution-phase phenomena and synthetic capabilities as a point of departure. The concepts in this volume result from a backward-chaining analysis that first explores deterministic molecular machine systems as an objective, and then examines present laboratory capabilities as a means of achieving that objective. Since machine-phase systems are quite unlike molecules undergoing Brownian motion in solution, and since they are not immediately realizable in the laboratory, it is natural that molecular manufacturing has been slow to appear on the research agenda of chemistry.

B.5. Molecular biology

Molecular biologists study and modify systems of molecular machines. Genetic engineers reprogram them, sometimes to build novel multinanometer-scale molecular objects with complex functions. Molecular biologists, however, work within the traditions of natural science, and they are seldom system builders. Although observations at the level of "biomolecules might be used as components in some device" appeared sporadically in earlier years, there are apparently no publications that predate Drexler (1981) and argue that devices resembling biomolecular motors, actuators, and structural components could be combined to build molecular machine systems analogous to machine systems in the macroscopic world. (Proposals patterned on living systems, coupling catalytic and regulatory molecules by diffusive transport, while of considerable interest, are in a distinct category of no direct relevance to the goal of molecular manufacturing.)

The chief forms of molecular engineering to emerge from molecular biology have been protein engineering (usually to produce isolated catalysts in solution or immobilized on surfaces), and the engineering of three-dimensional structures from branched DNA (Chen and Seeman, 1991; Seeman, 1982; Seeman, 1991). The use of complementary DNA sequences provides one answer to the question of how to form complex patterns from self-assembling molecular objects, and proposals have been advanced for the application of this work to molecular mechanical and electronic devices (Robinson and Seeman, 1987).

B.6. Protein engineering

Protein molecules constitute much of the molecular machinery found in living systems, and protein engineering has in the last decade become a substantial area of research. It has been suggested that protein engineering can provide a path for developing molecular manufacturing (Drexler, 1981), if pursued with the objective of constructing self-assembling systems of molecular machines.

The journal Protein Engineering, in its "Instructions to Authors," gives a sense of how the field has developed. The MIT School of Engineering (MIT Bulletin, 1988-89) defines engineering as "a creative profession concerned with developing and applying scientific knowledge and technology to meet societal needs," but Protein Engineering states that "the objectives of those engaged in this area of research are to investigate the principles by which particular structural features in proteins relate to the mechanisms through which biological function is expressed, and to test these principles in an empirical fashion by introduction of specific changes followed by evaluation of any altered structural and/or functional properties." In short, the stated objective is scientific knowledge, not the construction of useful new proteins.

Considerable progress has been made in engineering novel objects from proteins. Outstanding examples include what is generally regarded as the first ded e novo structure (DeGrado et al., 1987), the development of synthetic, branched proteinlike structures that depart substantially from biological models (Mutter et al., 1988), and the engineering of a branched, nonbiological protein with enzymatic activity (Hahn et al., 1990).

B.7. Proximal probe technologies

Proximal probe instruments-scanning tunneling microscopes (STMs), atomic force microscopes (AFMs) and their relatives-provide a means for positioning and maneuvering tips near surfaces with atomic precision. The possibility of modifying surfaces with these tips was evident from the earliest years of STM research, since inadvertent contact between tips and surfaces routinely caused such modifications. Suggestions for controlled surface modification have appeared (Farrell and Levinson, 1985), including control based on the precise application of molecular tools (Drexler, 1986a). Experiments have since demonstrated (for example) atomic-scale surface modifications on germanium (Becker et al., 1987), pinning of organic molecules to graphite (Foster et al., 1988), arrangement of 35 xenon atoms to spell "IBM" on a nickel surface (Eigler and Schweizer, 1990) and subsequent positioning of carbon monoxide and platinum atoms on platinum surfaces in the same laboratory. Much of this work has been conducted at IBM, where the objective of developing atomic-scale mechanisms for data storage and processing has been explicitly articulated. Japan's Science and Technology Agency in 1989 initiated the Aono Atomcraft Project to pursue research in this area.

B.8. Feynman's 1959 talk

The mechanical construction of molecules was suggested by R. Feynman in an after-dinner speech, "There's Plenty of Room at the Bottom," given at the 1959 annual meeting of the West Coast Section of the American Physical Society and later published (Feynman, 1960). Most of the talk focused on miniaturization and microtechnology: this section anticipated capabilities like those that emerged in the microelectronics industry, and then proposed an alternative approach to miniaturization that would use machines to build smaller machines, which would build still smaller machines, and so forth. Toward the close of this discussion are four paragraphs that comprise the clearest prior discussion of molecular manufacturing:

At the atomic level, we have new kinds of forces and new kinds of possibilities, new kinds of effects. The problems of manufacture and reproduction of materials will be quite different. I am, as I said, inspired by the biological phenomena in which chemical forces are used in a repetitious fashion to produce all kinds of weird effects (one of which is the author).

The principles of physics, as far as I can see, do not speak against the possibility of maneuvering things atom by atom. It is not an attempt to violate any laws; it is something, in principle, that can be done; but, in practice, it has not been done because we are too big.

Ultimately, we can do chemical synthesis. A chemist comes to us and says, "Look, I want a molecule that has the atoms arranged thus and so; make me that molecule." The chemist does a mysterious thing when he wants to make a molecule. He sees that he has got that ring, so he mixes this and that, and he shakes it, and he fiddles around. And, at the end of a difficult process, he usually does succeed in synthesizing what he wants. By the time I get my devices working, so that we can do it by physics, he will have figured out how to synthesize absolutely anything, so that this will really be useless.

But it is interesting that it would be, in principle, possible (I think) for a physicist to synthesize any chemical substance that the chemist writes down. Give the orders and the physicist synthesizes it. How? Put the atoms down where the chemist says, and so you make the substance. The problems of chemistry and biology can be greatly helped if our ability to see what we are doing, and to do things on an atomic level, is ultimately developed-a development which I think cannot be avoided.

These remarks pointed in the direction explored in this volume. Why was there so little response? Presumably because these long-term goals appeared to lack near-term consequences: they neither defined an accessible scientific problem nor suggested an immediate engineering project. They might have sparked work in theoretical applied science, but the study of long-term technological possibilities has had few serious practitioners.

B.9. Conclusions

Prior work in physics, chemistry, molecular biology, and engineering forms an adequate and essential foundation for the work presented in the previous chapters. Nonetheless, the pre-1991 literature appears to contain few research reports describing studies of molecular mechanical engineering and molecular manufacturing. Although these ideas are, in a sense, an obvious extrapolation of present knowledge and abilities, several circumstances have discouraged sustained analytical efforts in this area. These include the usual time horizons for research funding, the strong laboratory orientation of the molecular sciences, and the gap between the goals of conventional chemistry and those of theoretical applied science.

In light of emerging capabilities in chemistry, protein engineering, and proximal probe technologies, the time appears ripe for design and experimentation aimed at the goal of molecular manufacturing; indeed, a research community has begun to form. The coming effort will draw on the knowledge and skills of disciplines as diverse as chemistry, physics, mechanical engineering, and computer science, and its products will contribute to fields spanning the whole of science and technology. This volume has drawn on fundamental principles from several disciplines to assemble a set of conceptual and mathematical tools adequate for designing and analyzing a limited class of molecular mechanical systems. If it has shown some of the potential of molecular nanotechnology, and given some help to those wishing to enter the field, then it has achieved its major objective.


  1. Diverse work in "nanotechnology" is reviewed by Franks (1987), but the then-new term was taken by that author as possibly including glass polishing and fine-powder technologies. Taniguchi (1974) applied 'Nano-technology' (in this form, with quotes) to processes such as ion sputtering. A broad and uneven survey of pre-1980 speculations regarding small devices of various kinds appears in Schneiker (1989). Recent collections of papers organized around molecular nanotechnology in the present sense appear in the proceedings of the First and Second Foresight Conferences on Molecular Nanotechnology, held in 1989 and 1991 (Crandall and Lewis, 1992; Teague, 1992).

  2. The Department of Synthetic Chemistry at the University of Tokyo, however, is in the Faculty of Engineering.