Nanotechnology: where it stands today
by K. Eric Drexler

The following essay is adapted from the new Afterword to Engines of
Creation (Doubleday, 1986) written for the British edition to be
published in 1990 by Fourth Estate.

	What would I correct in Engines today, after several years of
discussion, criticism, and technological progress? The first dozen
pages would report recent advances in technology (discussed below),
but the conclusion would remain the same: we are moving toward
assemblers, toward an era of molecular manufacturing giving thorough
and inexpensive control of the structure of matter. There would be no
changes in the central theses, because they seem solid.

Advancing technologies
	Technological progress has, on the whole, been faster than I
had expected. Engines speculates about when we might reach the
milestone of designing a protein molecule from scratch, but avoids
making any rash prediction of a date. In fact, this was accomplished
in 1988 by William F. DeGrado of Du Pont and his colleagues.(*1) They
designed a small protein, (*alpha)(*subscript: 4), which is
substantially more stable than natural proteins of comparable size.
This success, which precedes any general way of predicting what
structure a natural protein chain will assume, and the unusual
stability of the product, confirm predictions which I had published in
1981 regarding the feasibility and capabilities of protein
engineering.(*2) Protein Engineering, now the title of a journal, has
become a major academic and industrial enterprise. Groups around the
world are making small modifications to natural proteins, swapping
sections of natural proteins to build new structures, and building new
designs starting with a clean slate.
	A related area of research has been underway for years and is
picking up speed: the design and synthesis of smaller molecules having
protein-like capabilities, but non-protein-like structures. These
molecules bind other molecules, building up larger structures; some
can serve as enzyme-like catalysts. In 1987, a Nobel prize for
pioneering research in this area (which is commonly referred to as
"molecular recognition") was shared by Charles Pederson of Du
Pont, Donald Cram of UCLA, and Jean-Marie Lehn of the Universite'
Louis Pasteur.(*3)
	Building protein-like chains from molecular structures capable
of "recognition" is a promising technique for use in engineering
molecular systems. Such a chain could fold (or bind a neighbor) in a
manner predetermined by the properties of these building blocks,
simplifying the problems faced by the designer. Building molecules
that resemble proteins, save for differences chosen to aid design, is
an attractive strategy. At Universitat Basel in Switzerland,
Manfred Mutter has had striking successes with protein-like molecules
based on branched--rather than linear--polymer chains. The
potential of such pseudo-proteins has only begun to be explored: to
biochemists they may seem uninteresting, because they differ from
nature; to chemists, they may seem uninteresting, because they attempt
to avoid fascinating (i.e., difficult) problems of structure and
synthesis. But to molecular technologists trying to build ambitious,
functional systems (rather than academically-impressive components),
they have real appeal.
	Computer-based tools for modeling molecules have improved
rapidly.(*4) To describe the behavior of a large molecule requires
calculations which gobble computer time, but the computer power
available for a given price has grown exponentially over the years.
Still, accurate quantum-mechanical calculations are possible only for
very small molecules, because the amount of computer time needed for
such calculations grows sharply as molecular size increases.
Calculations that treat molecules as objects, with size, shape, and
moving parts are practical on a large scale, however. With these
approximations, it is now routine to calculate the behavior of protein
molecules, following the motions of thousands of atoms.
	Design tools, too, have improved. Jay Ponder and Frederic
Richards of Yale University have developed a program that can
determine which sequences of amino acids will be able to form a
stable, tightly-packed protein core. Tom Blundell and his colleagues
at the University of London have developed a program, COMPOSER, which
aims to find parts of known protein structures that will fit together
to form new molecules. These design tools, combined with ever-better
strategies for design and synthesis, promise ever more rapid advances
in engineering molecular objects of kinds which can serve as tools and
components on the path to nanotechnology.
	In a note, Engines mentions the scanning tunneling microscope
(STM), and suggests that it "may be able to replace molecular
machinery in positioning molecular tools." The STM is a device
which can map the bumps and hollows of a conducting surface--often
in atomic detail--by scanning a sharp probe above the surface just
close enough for electrons to jump the gap at an appreciable rate; it
has since been joined by a relative, the atomic force microscope
(AFM), which senses the force between a probe and a surface, rather
than sensing an electrical current. At IBM's Almaden research
center, John Foster's group has observed and modified individual
molecules using the technology of the scanning tunneling
microscope.(*5) A voltage pulse can pin a molecule to a graphite
surface, forming a chemical bond; further pulses can fragment or
remove the pinned molecule, all visible in the STM images.
(The possibility of building a computer memory device immediately
suggests itself.) A group at AT&T Bell Labs has deposited what are
thought to be single atoms of germanium onto a germanium surface,
again using voltage pulses applied to an STM tip; the process does not
work with silicon, despite its similarities to germanium.(*6)
	These processes are, however, relatively uncontrolled in a
molecular sense: neither can reliably produce a particular chemical
change at a particular location, as an assembler must. John Foster,
however, has expressed strong interest in pursuing my suggestion of
using specially-engineered molecular tools on probe tips. The
practical consequences of using such molecules as tools for chemical
synthesis are unclear, since the resulting device could build only one
molecule at a time, but work in this direction could lead to a crude
protoassembler in the not-too-distant future. Sufficiently accurate
positioning mechanisms exist in the AFM and STM; the technology needed
to engineer molecules that bind to other molecules is maturing, and
could likely be adapted to engineer molecules that bind to probe tips.
Putting these developments together into a working system, though a
challenging objective, seems entirely feasible.
	In short, advances toward nanotechnology through molecular
systems engineering have been more rapid than Engines might suggest.
This makes understanding and preparation that much more urgent.

The spread of ideas
	The idea of nanotechnology has spread far, both through
Engines itself (Japanese and British editions are planned for 1990)
and through other publications. A recent summary appears in the 1990
Britannica yearbook, Science and the Future.(*7) The Foresight
Institute has provided a publication medium for news and discussion on
nanotechnology and (to a lesser extent) for news regarding
developments at the frontiers of software technology.
	Interest in the U.S. may be gauged, in part, by the demand for
talks on the subject. I have been invited to speak at most of the top
technical universities and many of the top corporate research
laboratories in the U.S. At Stanford, when I taught the first
university course on nanotechnology, the room and hallway were packed
with students on the first day, and the last to enter enter climbed
through a window. Interest has been strong and growing.

Mutant memes
	As information spreads, so does misinformation. Thus far,
fragmentation has not been a great problem, because the core ideas in
Engines have traveled more-or-less as a package. In particular, the
idea of nanotechnology as powerful, potentially dangerous, potentially
beneficial, and effectively inevitable has remained intact, even in
most presentations in the media. A more common problem has been a loss
of distinctions; this has been especially visible in press coverage.
Since there has now been considerable experience with how these ideas
are distorted, perhaps distortion can be minimized by pointing out the
patterns.
	Minds lacking suitable education seem to have only one mental
pigeon-hole for "invisibly small", hence distinctions of scale
among invisibly small objects tend to collapse. Let's see, are
cells smaller than molecules, or vice versa? Are nanocomputers the
size of atoms? Of molecules? Of cells? These matters have often led to
confusion, though the differences in scale among these objects are
enormous. From the 30 micron scale of a fairly typical human cell to
the 0.3 nanometer scale of a typical atom is a factor of 100,000 in
linear dimension, or a factor of 1,000,000,000,000,000 in volume. This
is the difference between a mountain and a marble. Atoms make up
molecules, which make up cells, with nanocomputers far larger than
typical molecules, and yet far smaller than typical cells.
	In a similar vein, microtechnology is often confused with
nanotechnology, despite the 1,000,000,000-fold difference in the
volume of a typical part, and despite the radical difference between a
technology which miniaturizes bulk processes and one which guides a
series of chemical reactions to build objects with molecular
precision. Microtechnologists in the U.S. have been justifiably upset
by media coverage which first describes their crude, hard-won
micromotors and then says, in effect, "But this is nothing
compared with nanotechnology." Microtechnology is practice;
nanotechnology is still theory. They are hardly comparable. Further,
if (as often happens) nanotechnology is portrayed as an outgrowth of
microtechnology, it seems fanciful, much as if someone asserted that
miniaturizing bulldozers would let us build fine watches out of dirt.
	With a bit more justification, some say that nanotechnology is
"just chemistry," or describe early protein engineering as
nanotechnology. Here, at least, there is a continuum of technologies;
chemistry is indeed moving toward nanotechnology. Nonetheless, there
is a huge gap between present practice and the sort of nanotechnology
described in Engines. The difference between, say, an enzyme and an
assembler-based manufacturing system is as large as the difference
between a transistor and a computer. If one wants to say that
nanotechnology is just chemistry, this is true in the same sense that
computer engineering is just solid-state physics and circuit theory.
	Strategies for making small systems divide into top-down and
bottom-up approaches. In top-down approaches, the challenge is to make
devices smaller and smaller, and the atomic graininess of matter looms
as a growing problem. In bottom-up strategies, the atomic graininess
of matter is fundamental, and the challenge is to build larger and
larger objects while retaining full control of structure. Chemistry
works bottom up; strategies based on STM or AFM positioning mechanisms
will likewise work bottom up. These strategies thus blur into
nanotechnology as conventional microtechnology does not.
	If the word "nanotechnology" is captured to describe
some modest extension of microtechnology or chemistry, then we will
need a new term to describe the technological developments central to
the discussion in Engines. "Molecular manufacturing" might be a
good, descriptive choice.
	In discussing nanotechnology proper, writers have tended to
collapse distinctions among different kinds of nanomachines. Engines
discusses assemblers, nanocomputers, replicators, cell repair
machines, and the prospect of achieving genuine artificial
intelligence with the aid of massively expanded computational
resources. How's that again? Ah, yes, nanotechnology will be
based on self-replicating, artificially-intelligent molecular
machines, right?
	Wrong, obviously. Not all molecular machines will include
assemblers, for the same reason that not all macroscopic machines
include stereophonic sound systems. Likewise, replicators will be a
special class of device, and only a highly-skilled and hardworking
fool would build replication abilities into every piece of machinery.
Even long after nanotechnology matures, genuine artificial
intelligence may not be found in anything whatsoever; it surely will
not be found in the microscopic equivalent of today's microprocessors!
And if the above collapse of distinctions seems too absurd to mention,
I should note that it was represented as my view of nanotechnology by
a social scientist who subsequently made the first presentation on the
subject to the U.S. National Science Foundation.  As one would expect,
it and its mutant relatives also turn up in the popular press.
	In light of the above confusions, it is no surprise that
people collapse the distinction between nanomachines and living cells.
After all, both are small and contain molecular machinery, and they
don't even differ in size by a factor of a billion. Nonetheless,
confusing a bacterium with an Engines-style nanomachine is like
confusing a rat with a radio-controlled model car. One is an evolved,
flexible organic system; the other is a designed, inflexible machine.
One forages in nature; the other requires special fuel. The
differences in style, organization, and abilities run deep. We may
someday learn to make nanomachines that are biological in style and
flexibility without closely copying nature, but this would require a
special research program. The problems involved are far beyond and
quite different from those that will arise in making the computers,
robotic arms, and the rest of conventional nanotechnology.
	Some imagine that small machines will be magical and
omnicompetent--flexible, evolving, intelligent, and the rest. But
making things small will not automatically make them wondrous in all
respects. Small machines will be machines. Making one nanomachine do
something useful will take hard work. Making another do something else
will take yet more work.

Selection pressures
	The idea of nanotechnology has now been in wide circulation
for several years. What has been the reaction of the technical
community--of those best able to find and label erroneous ideas?
There has been a background level of pooh-poohing, much of which no
doubt derives from media-based misimpressions. The interesting
question, however, is not what educated people may say in an off-hand
remark over lunch, but what they say when they grapple with the ideas.
From where I stand (e.g., in front of questioning technical audiences
after giving a technical talk) the central theses of Engines look
solid: They have withstood criticism. This is not to say that everyone
accepts them, but merely that whenever someone has suggested a reason
for rejecting them, that reason has turned out to be faulty. (My
apologies to hidden critics with novel, substantive points--please
step out and speak up!)
	Engines typically argues by example and by the engineering
principle of composition (e.g., since molecular machines do exist,
they can exist, and since simple machines can be composed to make
complex machines, complex molecular machines can likewise exist,
etc.). Such propositions are robust and hard to refute, but they lack
the specificity and mathematical analysis commonly found in technical
argumentation. As a result, some leaders of the scientific and
technological community have found these arguments convincing, while
others still imagine that no argument, much less a convincing
argument, has even been made. For those in search of more technical
and mathematical detail, a variety of technical papers (on mechanical
nanocomputers, molecular gears and bearings, etc.) are available and a
technical book is on the way.(*8)
	After a series of local meetings, the Foresight Institute
sponsored the first major conference on nanotechnology in October 1989
(covered in the 4 November Science News); a proceedings volume is in
preparation. This conference gave participants a chance to hear
presentations from leaders in protein engineering, self-assembling
molecular systems, quantum electronics, scanning tunneling microscopy,
and other relevant fields, all in the context of nanotechnology, its
development, and its consequences. The result was a far better picture
of an issue that Engines left in soft focus: how nanotechnology will
actually be developed.
	At the conference, it also became clear that Japan has for
several years been treating molecular systems engineering as a key to
21st century technology. If the rest of the world wishes to see
cooperative development of nanotechnology, it had best wake up and
start doing its part. It might also be wise not to escalate an
international war of words, tariffs (and more?) over such trivia of
late 20th century industry as cars, VCRs, chips, and whatnot. In the
late 19th century, guano deposits were of enormous economic and
strategic value, but this evaporated in the early 20th century with
the advent of the Haber process for nitrogen fixation. Let us not
disrupt productive alliances over the modern equivalent of guano.

Afterthoughts and further information
	Certain scenarios and proposals in the last third of Engines
could bear rephrasing, but at least one problem is presented
misleadingly. Page 173 speaks of the necessity of avoiding runaway
accidents with replicating assemblers; today I would emphasize that
there is little incentive to build a replicator even resembling one
that can survive in nature. Consider cars: to work, they require
gasoline, oil, brake fluid, and so forth. No mere accident could
enable a car to forage in the wild and refuel from tree sap: this
would demand engineering genius and hard work. Likewise with simple
replicators designed to work in vats of assembler-fluid, making
non-replicating products for use outside. Replicators built in accord
with suitable regulations would not even resemble anything that could
run wild. The problem--and it is enormous--is one not ofaccidents,
but of abuse.
	Some have mistakenly imagined that my aim is to promote
nanotechnology; it is, instead, to promote understanding of
nanotechnology and its consequences, which is another matter entirely.
Nonetheless, I am now persuaded that the sooner we start serious
development efforts, the longer we will have for serious public
debate. Why? Because serious debate will start with those serious
efforts, and the sooner we start, the poorer our technology base will
be. An early start will thus mean slower progress and hence more time
to consider the consequences.

	*	*	*	*	*	*	*

K. Eric Drexler is a researcher concerned with emerging technologies
and their consequences for the future.  He serves as president of the
Foresight Institute.

Notes and References

1. A good review of this and related work may be found in William F.
DeGrado, Zelda R. Wasserman, and James D. Lear, Protein Design, a
Minimalist Approach, Science Vol. 243, pp.  622‹628 (1989).

2. Molecular engineering: An approach to the development of general
capabilities for molecular manipulation, Proceedings of the National
Academy of Sciences (USA) Vol. 78, pp.  5275-5278 (1981).

3. Of particular interest are the Nobel lectures of the two currently
active researchers. See Jean-Marie Lehn, Supramolecular
Chemistry--Scope and Perspectives: Molecules, Supermolecules, and
Molecular Devices, Angewandte Chemie International Edition in English
Vol. 27, pp. 89-112 (1988) and Donald J. Cram, The Design of Molecular
Hosts, Guests, and Their Complexes, Science Vol. 240, pp. 760-767
(1988).

4. Software useful for computer-aided design of protein molecules has
been described by C. P. Pabo and E. G. Suchanek in Computer-Aided
Model-Building Strategies for Protein Design, Biochemistry Vol.  25,
pp. 5987-5991 (1986), and by Tom Blundell et al., Knowledge-based
protein modelling and design, European Journal of Biochemistry Vol.
172, pp. 513-520 (1988); a program which reportedly yields excellent
results in designing hydrophobic side-chain packings for protein core
regions is described by Jay W.  Ponder and Frederic M. Richards in
Tertiary Templates for Proteins, Journal of Molecular Biology
Vol. 193, pp. 775-791 (1987).  The latter authors have also done work
in molecular modeling (an enormous and active field); see An
Efficient Newton-like Method for Molecular Mechanics Energy
Minimization of Large Molecules, Journal of Computational
Chemistry Vol. 8, pp.  1016-1024 (1987). Computational techniques
derived from molecular mechanics have been used to model quantum
effects on molecular motion (as distinct from quantum-mechanical
modeling of electrons and bonds); see Chong Zheng et al., Quantum
simulation of ferrocytochrome c, Nature Vol. 334, pp. 726-728
(1988).

5. J. S. Foster, J. E.  Frommer, and P. C. Arnett, Molecular
manipulation using a tunnelling microscope, Nature Vol. 331, pp.
324-326 (1988).

6.  R. S. Becker, J. A. Golovchenko, and B. S. Swartzentruber,
Atomic-scale surface modifications using a tunnelling
microscope, Nature Vol. 325, pp. 419-421 (1987).

7. K. Eric Drexler, Machines of Inner Space, in 1990 Yearbook
of Science and the Future. Edited by D. Calhoun. pp. 160-177.
(Chicago: Encyclopaedia Britannica, 1989).

8. The following papers will be collected and rewritten as parts of my
forthcoming technical book: Nanomachinery: Atomically precise
gears and bearings, in the proceedings of the IEEE Micro Robots
and Teleoperators Workshop (Hyannis, Massachusetts: IEEE, 1987);
Exploring Future Technologies, in The Reality Club. Edited by
J. Brockman. pp 129-150. (New York: Lynx Books, 1988); and Rod
Logic and Thermal Noise in the Mechanical Nanocomputer, in
Molecular Electronic Devices III. Edited by F. L. Carter and H.
Wohltjen.  (Amsterdam: Elsevier Science Publishers B. V., in press).

For information on the availability of technical papers, please
contact the Foresight Institute.
