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Coal and diamonds, sand and computer chips, cancer and healthy tissue:
throughout history, variations in the arrangement of atoms have
distinguished the cheap from the cherished, the diseased from the
healthy. Arranged one way, atoms make up soil, air, and water; arranged
another, they make up ripe strawberries. Arranged one way, they make up
homes and fresh air; arranged another, they make up ash and smoke.

Our ability to arrange atoms lies at the foundation of technology. We
have come far in our atom arranging, from chipping flint for arrowheads
to machining aluminum for spaceships. We take pride in our technology,
with our lifesaving drugs and desktop computers. Yet our spacecraft are
still crude, our computers are still stupid, and the molecules in our
tissues still slide into disorder, first destroying health, then life
itself. For all our advances in arranging atoms, we still use primitive
methods. With our present technology, we are still forced to handle
atoms in unruly herds. But the laws of nature leave plenty of room for
progress, and the pressures of world competition are even now pushing us
forward. For better or for worse, the greatest technological
breakthrough in history is still to come.

Two Styles Of Technology

Our modern technology builds on an ancient tradition. Thirty thousand
years ago, chipping flint was the high technology of the day. Our
ancestors grasped stones containing trillions of trillions of atoms and
removed chips containing billions of trillions of atoms to make their
axheads; they made fine work with skills difficult to imitate today.
They also made patterns on cave walls in France with sprayed paint,
using their hands as stencils. Later they made pots by baking clay, then
bronze by cooking rocks. They shaped bronze by pounding it. They made
iron, then steel, and shaped it by heating, pounding, and removing
chips. We now cook up pure ceramics and stronger steels, but we still
shape them by pounding, chipping, and so forth. We cook up pure silicon,
saw it into slices, and make patterns on its surface using tiny stencils
and sprays of light. We call the products “chips” and we consider them
exquisitely small, at least in comparison to axheads. Our
microelectronic technology has managed to stuff machines as powerful as
the room-sized computers of the early 1950s onto a few silicon chips in
a pocket-sized computer. Engineers are now making ever smaller devices,
slinging herds of atoms at a crystal surface to build up wires and
components one tenth the width of a fine hair. These microcircuits may
be small by the standards of flint chippers, but each transistor still
holds trillions of atoms, and so-called “microcomputers” are still
visible to the naked eye. By the standards of a newer, more powerful
technology they will seem gargantuan. The ancient style of technology
that led from flint chips to silicon chips handles atoms and molecules
in bulk; call it bulk technology. The new technology will handle
individual atoms and molecules with control and precision; call it
molecular technology. It will change our world in more ways than we can
imagine. Microcircuits have parts measured in micrometers – that is, in
millionths of a meter – but molecules are measured in nanometers (a
thousand times smaller). We can use the terms “nanotechnology” and
“molecular technology” interchangeably to describe the new style of
technology. The engineers of the new technology will build both
nanocircuits and nanomachines.

Molecular Technology Today

One dictionary definition of a machine is “any system, usually of rigid
bodies, formed and connected to alter, transmit, and direct applied
forces in a predetermined manner to accomplish a specific objective,
such as the performance of useful work.” Molecular machines fit this
definition quite well. To imagine these machines, one must first picture
molecules. We can picture atoms as beads and molecules as clumps of
beads, like a child’s beads linked by snaps. In fact, chemists do
sometimes visualize molecules by building models from plastic beads
(some of which link in several directions, like the hubs in a Tinkertoy
set). Atoms are rounded like beads, and although molecular bonds are not
snaps, our picture at least captures the essential notion that bonds can
be broken and reformed. If an atom were the size of a small marble, a
fairly complex molecule would be the size of your fist. This makes a
useful mental image, but atoms are really about 1/10,000 the size of
bacteria, and bacteria are about 1/10,000 the size of mosquitoes. (An
atomic nucleus, however, is about 1/100,000 the size of the atom itself;
the difference between an atom and its nucleus is the difference between
a fire and a nuclear reaction.) The things around us act as they do
because of the way their molecules behave. Air holds neither its shape
nor its volume because its molecules move freely, bumping and
ricocheting through open space. Water molecules stick together as they
move about, so water holds a constant volume as it changes shape. Copper
holds its shape because its atoms stick together in regular patterns; we
can bend it and hammer it because its atoms can slip over one another
while remaining bound together. Glass shatters when we hammer it because
its atoms separate before they slip. Rubber consists of networks of
kinked molecules, like a tangle of springs. When stretched and released,
its molecules straighten and then coil again. These simple molecular
patterns make up passive substances. More complex patterns make up the
active nanomachines of living cells. Biochemists already work with these
machines, which are chiefly made of protein, the main engineering
material of living cells. These molecular machines have relatively few
atoms, and so they have lumpy surfaces, like objects made by gluing
together a handful of small marbles. Also, many pairs of atoms are
linked by bonds that can bend or rotate, and so protein machines are
unusually flexible. But like all machines, they have parts of different
shapes and sizes that do useful work. All machines use clumps of atoms
as parts. Protein machines simply use very small clumps. Biochemists
dream of designing and building such devices, but there are difficulties
to be overcome. Engineers use beams of light to project patterns onto
silicon chips, but chemists must build much more indirectly than that.
When they combine molecules in various sequences, they have only limited
control over how the molecules join. When biochemists need complex
molecular machines, they still have to borrow them from cells.
Nevertheless, advanced molecular machines will eventually let them build
nanocircuits and nanomachines as easily and directly as engineers now
build microcircuits or washing machines. Then progress will become swift
and dramatic. Genetic engineers are already showing the way. Ordinarily,
when chemists make molecular chains – called “polymers” – they dump
molecules into a vessel where they bump and snap together haphazardly in
a liquid. The resulting chains have varying lengths, and the molecules
are strung together in no particular order. But in modern gene synthesis
machines, genetic engineers build more orderly polymers – specific DNA
molecules – by combining molecules in a particular order. These
molecules are the nucleotides of DNA (the letters of the genetic
alphabet) and genetic engineers don’t dump them all in together.
Instead, they direct the machine to add different nucleotides in a
particular sequence to spell out a particular message. They first bond
one kind of nucleotide to the chain ends, then wash away the leftover
material and add chemicals to prepare the chain ends to bond the next
nucleotide. They grow chains as they bond on nucleotides, one at a time,
in a programmed sequence. They anchor the very first nucleotide in each
chain to a solid surface to keep the chain from washing away with its
chemical bathwater. In this way, they have a big clumsy machine in a
cabinet assemble specific molecular structures from parts a hundred
million times smaller than itself. But this blind assembly process
accidentally omits nucleotides from some chains. The likelihood of
mistakes grows as chains grow longer. Like workers discarding bad parts
before assembling a car, genetic engineers reduce errors by discarding
bad chains. Then, to join these short chains into working genes
(typically thousands of nucleotides long), they turn to molecular
machines found in bacteria. These protein machines, called restriction
enzymes, “read” certain DNA sequences as “cut here.” They read these
genetic patterns by touch, by sticking to them, and they cut the chain
by rearranging a few atoms. Other enzymes splice pieces together,
reading matching parts as “glue here” – likewise “reading” chains by
selective stickiness and splicing chains by rearranging a few atoms. By
using gene machines to write, and restriction enzymes to cut and paste,
genetic engineers can write and edit whatever DNA messages they choose.
But by itself, DNA is a fairly worthless molecule. It is neither strong
like Kevlar, nor colorful like a dye, nor active like an enzyme, yet it
has something that industry is prepared to spend millions of dollars to
use: the ability to direct molecular machines called ribosomes. In
cells, molecular machines first transcribe DNA, copying its information
to make RNA “tapes.” Then, much as old numerically controlled machines
shape metal based on instructions stored on tape, ribosomes build
proteins based on instructions stored on RNA strands. And proteins are
useful. Proteins, like DNA, resemble strings of lumpy beads. But unlike
DNA, protein molecules fold up to form small objects able to do things.
Some are enzymes, machines that build up and tear down molecules (and
copy DNA, transcribe it, and build other proteins in the cycle of life).
Other proteins are hormones, binding to yet other proteins to signal
cells to change their behavior. Genetic engineers can produce these
objects cheaply by directing the cheap and efficient molecular machinery
inside living organisms to do the work. Whereas engineers running a
chemical plant must work with vats of reacting chemicals (which often
misarrange atoms and make noxious byproducts), engineers working with
bacteria can make them absorb chemicals, carefully rearrange the atoms,
and store a product or release it into the fluid around them. Genetic
engineers have now programmed bacteria to make proteins ranging from
human growth hormone to rennin, an enzyme used in making cheese. The
pharmaceutical company Eli Lilly (Indianapolis) is now marketing
Humulin, human insulin molecules made by bacteria.

Existing Protein Machines

These protein hormones and enzymes selectively stick to other molecules.
An enzyme changes its target’s structure, then moves on; a hormone
affects its target’s behavior only so long as both remain stuck
together. Enzymes and hormones can be described in mechanical terms, but
their behavior is more often described in chemical terms. But other
proteins serve basic mechanical functions. Some push and pull, some act
as cords or struts, and parts of some molecules make excellent bearings.
The machinery of muscle, for instance, has gangs of proteins that reach,
grab a “rope” (also made of protein), pull it, then reach out again for
a fresh grip; whenever you move, you use these machines. Amoebas and
human cells move and change shape by using fibers and rods that act as
molecular muscles and bones.

A reversible, variable-speed motor drives bacteria through water by
turning a corkscrew-shaped propeller. If a hobbyist could build tiny
cars around such motors, several billions of billions would fit in a
pocket, and 150-lane freeways could be built through your finest
capillaries. Simple molecular devices combine to form systems resembling
industrial machines. In the 1950s engineers developed machine tools that
cut metal under the control of a punched paper tape. A century and a
half earlier, Joseph-Marie Jacquard had built a loom that wove complex
patterns under the control of a chain of punched cards. Yet over three
billion years before Jacquard, cells had developed the machinery of the
ribosome. Ribosomes are proof that nanomachines built of protein and RNA
can be programmed to build complex molecules. Then consider viruses. One
kind, the T4 phage, acts like a spring-loaded syringe and looks like
something out of an industrial parts catalog. It can stick to a
bacterium, punch a hole, and inject viral DNA (yes, even bacteria suffer
infections). Like a conqueror seizing factories to build more tanks,
this DNA then directs the cell’s machines to build more viral DNA and
syringes. Like all organisms, these viruses exist because they are
fairly stable and are good at getting copies of themselves made. Whether
in cells or not, nanomachines obey the universal laws of nature.
Ordinary chemical bonds hold their atoms together, and ordinary chemical
reactions (guided by other nanomachines) assemble them. Protein
molecules can even join to form machines without special help, driven
only by thermal agitation and chemical forces. By mixing viral proteins
(and the DNA they serve) in a test tube, molecular biologists have
assembled working T4 viruses. This ability is surprising: imagine
putting automotive parts in a large box, shaking it, and finding an
assembled car when you look inside! Yet the T4 virus is but one of many
self-assembling structures. Molecular biologists have taken the
machinery of the ribosome apart into over fifty separate protein and RNA
molecules, and then combined them in test tubes to form working
ribosomes again. To see how this happens, imagine different T4 protein
chains floating around in water. Each kind folds up to form a lump with
distinctive bumps and hollows, covered by distinctive patterns of
oiliness, wetness, and electric charge.

Picture them wandering and tumbling, jostled by the thermal vibrations
of the surrounding water molecules. From time to time two bounce
together, then bounce apart. Sometimes, though, two bounce together and
fit, bumps in hollows, with sticky patches matching; they then pull
together and stick. In this way protein adds to protein to make sections
of the virus, and sections assemble to form the whole. Protein engineers
will not need nanoarms and nanohands to assemble complex nanomachines.
Still, tiny manipulators will be useful and they will be built. Just as
today’s engineers build machinery as complex as player pianos and robot
arms from ordinary motors, bearings, and moving parts, so tomorrow’s
biochemists will be able to use protein molecules as motors, bearings,
and moving parts to build robot arms which will themselves be able to
handle individual molecules.

Designing with Protein

How far off is such an ability? Steps have been taken, but much work
remains to be done. Biochemists have already mapped the structures of
many proteins. With gene machines to help write DNA tapes, they can
direct cells to build any protein they can design. But they still don’t
know how to design chains that will fold up to make proteins of the
right shape and function. The forces that fold proteins are weak, and
the number of plausible ways a protein might fold is astronomical, so
designing a large protein from scratch isn’t easy. The forces that stick
proteins together to form complex machines are the same ones that fold
the protein chains in the first place. The differing shapes and kinds of
stickiness of amino acids – the lumpy molecular “beads” forming protein
chains – make each protein chain fold up in a specific way to form an
object of a particular shape. Biochemists have learned rules that
suggest how an amino acid chain might fold, but the rules aren’t very
firm. Trying to predict how a chain will fold is like trying to work a
jigsaw puzzle, but a puzzle with no pattern printed on its pieces to
show when the fit is correct, and with pieces that seem to fit together
about as well (or as badly) in many different ways, all but one of them
wrong. False starts could consume many lifetimes, and a correct answer
might not even be recognized. Biochemists using the best computer
programs now available still cannot predict how a long, natural protein
chain will actually fold, and some of them have despaired of designing
protein molecules soon. Yet most biochemists work as scientists, not as
engineers. They work at predicting how natural proteins will fold, not
at designing proteins that will fold predictably. These tasks may sound
similar, but they differ greatly: the first is a scientific challenge,
the second is an engineering challenge. Why should natural proteins fold
in a way that scientists will find easy to predict? All that nature
requires is that they in fact fold correctly, not that they fold in a
way obvious to people. Proteins could be designed from the start with
the goal of making their folding more predictable. Carl Pabo, writing in
the journal Nature, has suggested a design strategy based on this
insight, and some biochemical engineers have designed and built short
chains of a few dozen pieces that fold and nestle onto the surfaces of
other molecules as planned. They have designed from scratch a protein
with properties like those of melittin, a toxin in bee venom. They have
modified existing enzymes, changing their behaviors in predictable ways.
Our understanding of proteins is growing daily. In 1959, according to
biologist Garrett Hardin, some geneticists called genetic engineering
impossible; today, it is an industry. Biochemistry and computer-aided
design are now exploding fields, and as Frederick Blattner wrote in the
journal Science, “computer chess programs have already reached the level
below the grand master. Perhaps the solution to the protein-folding
problem is nearer than we think.” William Rastetter of Genentech,
writing in Applied Biochemistry and Biotechnology asks, “How far off is
de novo enzyme design and synthesis? Ten, fifteen years?” He answers,
“Perhaps not that long.” Forrest Carter of the U.S. Naval Research
Laboratory, Ari Aviram and Philip Seiden of IBM, Kevin Ulmer of Genex
Corporation, and other researchers in university and industrial
laboratories around the globe have already begun theoretical work and
experiments aimed at developing molecular switches, memory devices, and
other structures that could be incorporated into a protein-based
computer. The U.S. Naval Research Laboratory has held two international
workshops on molecular electronic devices, and a meeting sponsored by
the U.S. National Science Foundation has recommended support for basic
research aimed at developing molecular computers. Japan has reportedly
begun a multimillion-dollar program aimed at developing self-assembling
molecular motors and computers, and VLSI Research Inc., of San Jose,
reports that “It looks like the race to bio-chips [another term for
molecular electronic systems] has already started. NEC, Hitachi,
Toshiba, Matsushita, Fujitsu, Sanyo-Denki and Sharp have commenced
full-scale research efforts on bio-chips for bio-computers.” Biochemists
have other reasons to want to learn the art of protein design. New
enzymes promise to perform dirty, expensive chemical processes more
cheaply and cleanly, and novel proteins will offer a whole new spectrum
of tools to biotechnologists. We are already on the road to protein
engineering, and as Kevin Ulmer notes in the quote from Science that
heads this chapter, this road leads “toward a more general capability
for molecular engineering which would allow us to structure matter atom
by atom.”

Second-Generation Nanotechnology

Despite its versatility, protein has shortcomings as an engineering
material. Protein machines quit when dried, freeze when chilled, and
cook when heated. We do not build machines of flesh, hair, and gelatin;
over the centuries, we have learned to use our hands of flesh and bone
to build machines of wood, ceramic, steel, and plastic. We will do
likewise in the future. We will use protein machines to build
nanomachines of tougher stuff than protein. As nanotechnology moves
beyond reliance on proteins, it will grow more ordinary from an
engineer’s point of view. Molecules will be assembled like the
components of an erector set, and well-bonded parts will stay put. Just
as ordinary tools can build ordinary machines from parts, so molecular
tools will bond molecules together to make tiny gears, motors, levers,
and casings, and assemble them to make complex machines. Parts
containing only a few atoms will be lumpy, but engineers can work with
lumpy parts if they have smooth bearings to support them. Conveniently
enough, some bonds between atoms make fine bearings; a part can be
mounted by means of a single chemical bond that will let it turn freely
and smoothly. Since a bearing can be made using only two atoms (and
since moving parts need have only a few atoms), nanomachines can indeed
have mechanical components of molecular size. How will these better
machines be built? Over the years, engineers have used technology to
improve technology. They have used metal tools to shape metal into
better tools, and computers to design and program better computers. They
will likewise use protein nanomachines to build better nanomachines.
Enzymes show the way: they assemble large molecules by “grabbing” small
molecules from the water around them, then holding them together so that
a bond forms. Enzymes assemble DNA, RNA, proteins, fats, hormones, and
chlorophyll in this way – indeed, virtually the whole range of molecules
found in living things. Biochemical engineers, then, will construct new
enzymes to assemble new patterns of atoms. For example, they might make
an enzyme-like machine which will add carbon atoms to a small spot,
layer on layer. If bonded correctly, the atoms will build up to form a
fine, flexible diamond fiber having over fifty times as much strength as
the same weight of aluminum. Aerospace companies will line up to buy
such fibers by the ton to make advanced composites. (This shows one
small reason why military competition will drive molecular technology
forward, as it has driven so many fields in the past.) But the great
advance will come when protein machines are able to make structures more
complex than mere fibers. These programmable protein machines will
resemble ribosomes programmed by RNA, or the older generation of
automated machine tools programmed by punched tapes. They will open a
new world of possibilities, letting engineers escape the limitations of
proteins to build rugged, compact machines with straightforward designs.
Engineered proteins will split and join molecules as enzymes do.
Existing proteins bind a variety of smaller molecules, using them as
chemical tools; newly engineered proteins will use all these tools and
more. Further, organic chemists have shown that chemical reactions can
produce remarkable results even without nanomachines to guide the
molecules. Chemists have no direct control over the tumbling motions of
molecules in a liquid, and so the molecules are free to react in any way
they can, depending on how they bump together. Yet chemists nonetheless
coax reacting molecules to form regular structures such as cubic and
dodecahedral molecules, and to form unlikely-seeming structures such as
molecular rings with highly strained bonds. Molecular machines will have
still greater versatility in bondmaking, because they can use similar
molecular motions to make bonds, but can guide these motions in ways
that chemists cannot. Indeed, because chemists cannot yet direct
molecular motions, they can seldom assemble complex molecules according
to specific plans. The largest molecules they can make with specific,
complex patterns are all linear chains. Chemists form these patterns (as
in gene machines) by adding molecules in sequence, one at a time, to a
growing chain. With only one possible bonding site per chain, they can
be sure to add the next piece in the right place. But if a rounded,
lumpy molecule has (say) a hundred hydrogen atoms on its surface, how
can chemists split off just one particular atom (the one five up and
three across from the bump on the front) to add something in its place?
Stirring simple chemicals together will seldom do the job, because small
molecules can seldom select specific places to react with a large
molecule. But protein machines will be more choosy. A flexible,
programmable protein machine will grasp a large molecule (the workpiece)
while bringing a small molecule up against it in just the right place.
Like an enzyme, it will then bond the molecules together. By bonding
molecule after molecule to the workpiece, the machine will assemble a
larger and larger structure while keeping complete control of how its
atoms are arranged. This is the key ability that chemists have lacked.
Like ribosomes, such nanomachines can work under the direction of
molecular tapes. Unlike ribosomes, they will handle a wide variety of
small molecules (not just amino acids) and will join them to the
workpiece anywhere desired, not just to the end of a chain. Protein
machines will thus combine the splitting and joining abilities of
enzymes with the programmability of ribosomes. But whereas ribosomes can
build only the loose folds of a protein, these protein machines will
build small, solid objects of metal, ceramic, or diamond – invisibly
small, but rugged. Where our fingers of flesh are likely to bruise or
burn, we turn to steel tongs. Where protein machines are likely to crush
or disintegrate, we will turn to nanomachines made of tougher stuff.

Universal Assemblers

These second-generation nanomachines – built of more than just proteins
– will do all that proteins can do, and more. In particular, some will
serve as improved devices for assembling molecular structures. Able to
tolerate acid or vacuum, freezing or baking, depending on design,
enzyme-like second-generation machines will be able to use as “tools”
almost any of the reactive molecules used by chemists – but they will
wield them with the precision of programmed machines. They will be able
to bond atoms together in virtually any stable pattern, adding a few at
a time to the surface of a workpiece until a complex structure is
complete. Think of such nanomachines as assemblers. Because assemblers
will let us place atoms in almost any reasonable arrangement (as
discussed in the Notes), they will let us build almost anything that the
laws of nature allow to exist. In particular, they will let us build
almost anything we can design – including more assemblers. The
consequences of this will be profound, because our crude tools have let
us explore only a small part of the range of possibilities that natural
law permits. Assemblers will open a world of new technologies. Advances
in the technologies of medicine, space, computation, and production –
and warfare – all depend on our ability to arrange atoms. With
assemblers, we will be able to remake our world or destroy it. So at
this point it seems wise to step back and look at the prospect as
clearly as we can, so we can be sure that assemblers and nanotechnology
are not a mere futurological mirage.

Nailing Down Conclusions

In everything I have been describing, I have stuck closely to the
demonstrated facts of chemistry and molecular biology. Still, people
regularly raise certain questions rooted in physics and biology. These
deserve more direct answers. ° Will the uncertainty principle of quantum
physics make molecular machines unworkable? This principle states (among
other things) that particles can’t be pinned down in an exact location
for any length of time. It limits what molecular machines can do, just
as it limits what anything else can do. Nonetheless, calculations show
that the uncertainty principle places few important limits on how well
atoms can be held in place, at least for the purposes outlined here. The
uncertainty principle makes electron positions quite fuzzy, and in fact
this fuzziness determines the very size and structure of atoms. An atom
as a whole, however, has a comparatively definite position set by its
comparatively massive nucleus. If atoms didn’t stay put fairly well,
molecules would not exist. One needn’t study quantum mechanics to trust
these conclusions, because molecular machines in the cell demonstrate
that molecular machines work. Will the molecular vibrations of heat make
molecular machines unworkable or too unreliable for use? Thermal
vibrations will cause greater problems than will the uncertainty
principle, yet here again existing molecular machines directly
demonstrate that molecular machines can work at ordinary temperatures.
Despite thermal vibrations, the DNA-copying machinery in some cells
makes less than one error in 100,000,000,000 operations. To achieve this
accuracy, however, cells use machines (such as the enzyme DNA polymerase
I) that proofread the copy and correct errors. Assemblers may well need
similar error-checking and error-correcting abilities, if they are to
produce reliable results. ° Will radiation disrupt molecular machines
and render them unusable? High-energy radiation can break chemical bonds
and disrupt molecular machines. Living cells once again show that
solutions exist: they operate for years by repairing and replacing
radiation-damaged parts. Because individual machines are so tiny,
however, they present small targets for radiation and are seldom hit.
Still, if a system of nanomachines must be reliable, then it will have
to tolerate a certain amount of damage, and damaged parts must regularly
be repaired or replaced. This approach to reliability is well known to
designers of aircraft and spacecraft. ° Since evolution has failed to
produce assemblers, does this show that they are either impossible or
useless? The earlier questions were answered in part by pointing to the
working molecular machinery of cells. This makes a simple and powerful
case that natural law permits small clusters of atoms to behave as
controlled machines, able to build other nanomachines. Yet despite their
basic resemblance to ribosomes, assemblers will differ from anything
found in cells; the things they do – while consisting of ordinary
molecular motions and reactions – will have novel results. No cell, for
example, makes diamond fiber. The idea that new kinds of nanomachinery
will bring new, useful abilities may seem startling: in all its billions
of years of evolution, life has never abandoned its basic reliance on
protein machines. Does this suggest that improvements are impossible,
though? Evolution progresses through small changes, and evolution of DNA
cannot easily replace DNA. Since the DNA/RNA/ribosome system is
specialized to make proteins, life has had no real opportunity to evolve
an alternative. Any production manager can well appreciate the reasons;
even more than a factory, life cannot afford to shut down to replace its
old systems. Improved molecular machinery should no more surprise us
than alloy steel being ten times stronger than bone, or copper wires
transmitting signals a million times faster than nerves. Cars outspeed
cheetahs, jets outfly falcons, and computers already outcalculate
head-scratching humans. The future will bring further examples of
improvements on biological evolution, of which second-generation
nanomachines will be but one. In physical terms, it is clear enough why
advanced assemblers will be able to do more than existing protein
machines. They will be programmable like ribosomes, but they will be
able to use a wider range of tools than all the enzymes in a cell put
together. Because they will be made of materials far more strong, stiff,
and stable than proteins, they will be able to exert greater forces,
move with greater precision, and endure harsher conditions. Like an
industrial robot arm – but unlike anything in a living cell – they will
be able to rotate and move molecules in three dimensions under
programmed control, making possible the precise assembly of complex
objects. These advantages will enable them to assemble a far wider range
of molecular structures than living cells have done. ° Is there some
special magic about life, essential to making molecular machinery work?
One might doubt that artificial nanomachines could even equal the
abilities of nanomachines in the cell, if there were reason to think
that cells contained some special magic that makes them work. This idea
is called “vitalism.” Biologists have abandoned it because they have
found chemical and physical explanations for every aspect of living
cells yet studied, including their motion, growth, and reproduction.
Indeed, this knowledge is the very foundation of biotechnology.
Nanomachines floating in sterile test tubes, free of cells, have been
made to perform all the basic sorts of activities that they perform
inside living cells. Starting with chemicals that can be made from
smoggy air, biochemists have built working protein machines without help
from cells. R. B. Merrifield, for example, used chemical techniques to
assemble simple amino acids to make bovine pancreatic ribonuclease, an
enzymatic device that disassembles RNA molecules. Life is special in
structure, in behavior, and in what it feels like from the inside to be
alive, yet the laws of nature that govern the machinery of life also
govern the rest of the universe. ° The case for the feasibility of
assemblers and other nanomachines may sound firm, but why not just wait
and see whether they can be developed? Sheer curiosity seems reason
enough to examine the possibilities opened by nanotechnology, but there
are stronger reasons. These developments will sweep the world within ten
to fifty years – that is, within the expected lifetimes of ourselves or
our families. What is more, the conclusions of the following chapters
suggest that a wait-and-see policy would be very expensive – that it
would cost many millions of lives, and perhaps end life on Earth. Is the
case for the feasibility of nanotechnology and assemblers firm enough
that they should be taken seriously? It seems so, because the heart of
the case rests on two well-established facts of science and engineering.
These are (1) that existing molecular machines serve a range of basic
functions, and (2) that parts serving these basic functions can be
combined to build complex machines. Since chemical reactions can bond
atoms together in diverse ways, and since molecular machines can direct
chemical reactions according to programmed instructions, assemblers
definitely are feasible.


Assemblers will bring one breakthrough of obvious and basic importance:
engineers will use them to shrink the size and cost of computer circuits
and speed their operation by enormous factors. With today’s bulk
technology, engineers make patterns on silicon chips by throwing atoms
and photons at them, but the patterns remain flat and molecular-scale
flaws are unavoidable. With assemblers, however, engineers will build
circuits in three dimensions, and build to atomic precision. The exact
limits of electronic technology today remain uncertain because the
quantum behavior of electrons in complex networks of tiny structures
presents complex problems, some of them resulting directly from the
uncertainty principle. Whatever the limits are, though, they will be
reached with the help of assemblers. The fastest computers will use
electronic effects, but the smallest may not. This may seem odd, yet the
essence of computation has nothing to do with electronics. A digital
computer is a collection of switches able to turn one another on and
off. Its switches start in one pattern (perhaps representing 2 + 2),
then switch one another into a new pattern (representing 4), and so on.
Such patterns can represent almost anything. Engineers build computers
from tiny electrical switches connected by wires simply because
mechanical switches connected by rods or strings would be big, slow,
unreliable, and expensive, today. The idea of a purely mechanical
computer is scarcely new. In England during the mid-1800s, Charles
Babbage invented a mechanical computer built of brass gears; his
co-worker Augusta Ada, the Countess of Lovelace, invented computer
programming. Babbage’s endless redesigning of the machine, problems with
accurate manufacturing, and opposition from budget-watching critics
(some doubting the usefulness of computers!), combined to prevent its
completion. In this tradition, Danny Hillis and Brian Silverman of the
MIT Artificial Intelligence Laboratory built a special-purpose
mechanical computer able to play tic-tac-toe. Yards on a side, full of
rotating shafts and movable frames that represent the state of the board
and the strategy of the game, it now stands in the Computer Museum in
Boston. It looks much like a large ball-and-stick molecular model, for
it is built of Tinkertoys. Brass gears and Tinkertoys make for big, slow
computers. With components a few atoms wide, though, a simple mechanical
computer would fit within 1/100 of a cubic micron, many billions of
times more compact than today’s so-called microelectronics. Even with a
billion bytes of storage, a nanomechanical computer could fit in a box a
micron wide, about the size of a bacterium. And it would be fast.
Although mechanical signals move about 100,000 times slower than the
electrical signals in today’s machines, they will need to travel only
1/1,000,000 as far, and thus will face less delay. So a mere mechanical
computer will work faster than the electronic whirl-winds of today.
Electronic nanocomputers will likely be thousands of times faster than
electronic microcomputers – perhaps hundreds of thousands of times
faster, if a scheme proposed by Nobel Prize-winning physicist Richard
Feynman works out. Increased speed through decreased size is an old
story in electronics.


Molecular computers will control molecular assemblers, providing the
swift flow of instructions needed to direct the placement of vast
numbers of atoms. Nanocomputers with molecular memory devices will also
store data generated by a process that is the opposite of assembly.

Assemblers will help engineers synthesize things; their relatives,
disassemblers, will help scientists and engineers analyze things.

The case for assemblers rests on the ability of enzymes and chemical
reactions to form bonds, and of machines to control the process. The
case for disassemblers rests on the ability of enzymes and chemical
reactions to break bonds, and of machines to control the process.
Enzymes, acids, oxidizers, alkali metals, ions, and reactive groups of
atoms called free radicals – all can break bonds and remove groups of

Because nothing is absolutely immune to corrosion, it seems that
molecular tools will be able to take anything apart, a few atoms at a

What is more, a nanomachine could (at need or convenience) apply
mechanical force as well, in effect prying groups of atoms free.

A nanomachine able to do this, while recording what it removes layer by
layer, is a disassembler. Assemblers, disassemblers, and nanocomputers
will work together.

For example, a nanocomputer system will be able to direct the
disassembly of an object, record its structure, and then direct the
assembly of perfect copies, And this gives some hint of the power of

The World Made New

Assemblers will take years to emerge, but their emergence seems almost
inevitable: Though the path to assemblers has many steps, each step will
bring the next in reach, and each will bring immediate rewards. The
first steps have already been taken, under the names of “genetic
engineering” and “biotechnology.” Other paths to assemblers seem
possible. Barring worldwide destruction or worldwide controls, the
technology race will continue whether we wish it or not. And as advances
in computer-aided design speed the development of molecular tools, the
advance toward assemblers will quicken. To have any hope of
understanding our future, we must understand the consequences of
assemblers, disassemblers, and nanocomputers. They promise to bring
changes as profound as the industrial revolution, antibiotics, and
nuclear weapons all rolled up in one massive breakthrough. To understand
a future of such profound change, it makes sense to seek principles of
change that have survived the greatest upheavals of the past. They will
prove a useful guide.

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