Foresight Update 12 (page 3)
A publication of the Foresight Institute
Recent Progress: Steps Toward Nanotechnology
by Russell Mills
I am on the mailing list of various companies that sell to biotechnologists.
The advertising they send provides a way to track technological progress.
Could there be any truer indicator of progress than the actual products
available for purchase?
Every few weeks a packet of reply cards arrives, each card describing a
different company's latest offerings. There's a thrill or two lurking in
almost every packet. Here are several recent examples:
- Miltenyi Biotec GmbH is promoting a system for sorting cells by marking
them with magnetic microbeads (70 nanometers or smaller). The user must
first coat the surface of the beads with antibodies specifically tailored
for binding to the target cells. (Precoated beads are also available). The
antibodies will link the beads to the desired cells, permitting a magnetic
sorting device to separate them from a mixture without harming them.
- A card from APEX Industries invites the reader to "Measure Ions
in Living Cells." It states that "The SPEX ARCM Cation Measurement
System lets you monitor intracellular ions in cell suspensions or single
cells ... without damage to the living cell."
- The Rainin Instrument Company proclaims a "Peptide synthesis
cost breakthrough!" and reports that it sells an automated peptide
synthesizer that is "uniquely easy to use ... produces synthetic peptides
in research quantities faster with higher yields, less reagent, and lower
cost than previous instruments." I want one.
- Scripps Laboratories urges readers to send for their catalog. They
say they are "the market leader in the manufacture of bulk human pituitary
hormones, serum proteins, cancer tumor markers, and enzymes."
- I especially like the card from National Biosciences. "CUSTOM
DNA SYNTHESIS" it begins. "$4.00/BASE, NO SET-UP CHARGE. No mixed-base
charges, purification $50. All orders guaranteed & shipped in 4 work
days." The company lists its other molecular biology services including
custom DNA sequencing, RNA synthesis, and gene synthesis. Best of all, new
customers receive a "Free oligonucleotide with comparable purchase!"
Twenty years ago ads like these would have seemed appropriate in science
fiction novels about the 21st century. Twenty years from now I expect to
see ads with titles like these: "COMPLETE GENOME ANALYSIS FOR ANY ORGANISM,
$500" and "CUSTOM ENZYMES--FAST TURNAROUND."
Nanotechnology (i.e., molecular construction with atomic precision) is
the expected outcome of our increasing ability to manipulate individual
atoms. Manipulating atoms is difficult--our tools tend to be either large
and nonspecific, or small and perverse. This difference in tools is what
distinguishes the two main approaches to nanotechnology.
The first approach is exemplified by chemistry, a discipline of large tools--flasks,
stirrers, heaters, and the like. Atoms are manipulated by ingenious choices
of reaction sequence, reagents, catalysts, temperature, and other conditions.
Unfortunately the only structures that can be accurately built this way
are rather simple ones: molecules of a few hundred atoms, and polymers.
To make more complex objects requires more control than can be provided
by any choice of reactions or conditions. Chemists are therefore trying
to "bootstrap" their way to nanotechnology by using the tools
at hand to create molecular-size tools--a challenging task.
The other approach is exemplified by biotechnology, in which many of the
tools are microscopic--cells, viruses, enzymes, antibodies, genes, and other
objects of evolutionary origin. Since they were not designed by us, they
are not easy tools to use. The task here is to modify them, to make them
more versatile and obedient.
Let's look at some recent progress along both of these approaches.
Chemistry
A major advance in polymer synthesis was announced in February by researchers
at Affymax Research Institute (California) [Science 251:767-773,
15Feb91]. Combining methods from the electronics industry with automated
peptide and nucleic acid production techniques, the group was able to carry
out large numbers of simultaneous syntheses in a small area.
The technique makes use of "protector" molecules that serve as
temporary chain terminators for the polymers under construction. The various
monomers ("building blocks") are pretreated with protectors such
that, of a monomer's two reactive groups, one is capped while the other
remains available for chemical reaction. The protectors detach when exposed
to light.
The Affymax procedure starts with a flat piece of glass--a stable working
surface on which polymer chains will be grown. A layer of linker molecules
is chemically bonded to this surface. Protectors are in turn bonded to the
linkers. The system with its linkers and protecting groups is now subjected
to illumination through a mask of the kind used to define electronic elements
in integrated circuits. In illuminated regions, but not elsewhere, the protectors
come off, exposing the underlying linkers. The system is next bathed in
a solution containing the first monomer, which attaches to the exposed linkers
but not to the protected linkers. Since the monomers were pre-equipped with
their own protectors, the working surface of the system is once again completely
covered with protectors. Illumination through a different mask will now
expose a different pattern of attachment sites for a second monomer. In
this way, a large number of different polymer molecules can be synthesized
simultaneously with high precision.
The technique has been shown to work for both nucleic acids and polypeptides,
and it should be applicable to other types of polymers as well. Its inventors
envision it as a tool for exploring biological recognition processes and
for testing compounds in the pharmaceutical industry. With commercially
available photolithography equipment, at least 250,000 different compounds
could be synthesized in a 1 cm2 area, then tested in situ
for their ability to interact with biological receptors or enzymes. When
a promising interaction is detected, the compound responsible can be identified
from its location.
This invention should accelerate the development of protein-based nanotechnology
by enabling protein engineers to make and test millions of different protein
molecules in a matter of days. The time required to home in on a successful
design should be considerably reduced. And some of these engineers will
be designing molecular machines ...
A class of polymers called "starburst
dendrimers" have created a stir among chemists lately. These are molecules
that branch repeatedly from a central core until, at a radius of about 5
nm, the density is high enough to form a closed surface. Although starburst
dendrimers typically contain tens of thousands of atoms, they can be synthesized
with atomic precision. Chemists have discovered a variety of different reaction
schemes and initiator cores, each leading to a different end product.
A dendrimer's shape--spherical or cylindrical--is determined by the pattern
of reactive sites on the initiator; its surface characteristics depend largely
upon the monomer used for the final synthetic step. Some dendrimers are
tightly sealed, others are porous. Australian scientists recently found
a way to grow dendrimers inward from the periphery back to the core, suggesting
that dendrimers with functionally differentiated surfaces may be possible.
[Science 251:1562-64,29Mar91]
Physical interfaces--the region of contact
between dissimilar materials--are of fundamental importance in many areas
of science and technology. The behavior of electronic devices, catalysts,
composites and many other things are determined by the structural details
of interfaces. Yet, in the absence of suitable manipulators for positioning
individual atoms, the preparation of interfaces has been a haphazard affair:
a substrate of one material is exposed to a barrage of atoms of a second
material, causing an overlayer to accumulate. The arriving atoms are often
traveling fast enough to cause damage or undesired chemical bonding, producing
an interface different from the one desired.
Materials chemists at the University of Minnesota have now developed a method
for gently lowering an overlayer onto a substrate. The trick is to create
a protective cushion on the substrate surface by letting a noble gas (like
xenon) condense on it at low temperature. An overlayer is then deposited
on this cushion in the usual manner--by evaporating it from a hot filament,
for example. Increasing the temperature evaporates the cushion, causing
the overlayer to settle upon the substrate. [Science 251:1444-51,22Mar91]
What we have here is a simple nanometer-scale manipulator controlled by
temperature and pressure adjustments. True, the manipulator only works in
one dimension and one direction. And the cushion is so "slippery"
that the overlayer atoms slide around on it uncontrollably and form clusters.
On the other hand, the concept may be generalizable: a substance more dynamic
than xenon might be used--one having responses specific to different overlayer
atoms or to stimuli other than temperature and pressure.
Biotechnology
At New York University Junghuei Chen and Nadrian Seeman report that they
have built a cube-like object out of DNA. Each face of the cube is defined
by a closed strand of DNA; the object therefore consists of six strands.
Each cube's edges are helical segments of double-stranded DNA composed of
the DNA strands of the adjacent faces wrapped around each other. The whole
structure contains 480 nucleotides and is built in several stages from ten
carefully designed DNA strands.
The researchers suggest that DNA might be used to make larger frameworks
to which proteins or other molecules could be attached. A framework would
regularize the positions of such substituents, allowing X-ray diffraction
mapping to be performed even on molecules that resist crystallization. The
study of interactions between molecules occupying adjacent lattice sites
would be another possibility. [Nature 350:631-33,18Apr91]
Ferritin is an iron-storage protein, variants
of which are found throughout much of the animal kingdom. The ferritin molecule,
roughly spherical with a central cavity 8 or 9 nanometers across, is composed
of 24 subunits. Channels in the molecule's walls allow the passage of iron
atoms; an apparatus in the channel oxidizes the iron and transfers it to
crystallization sites inside the cavity. When filled, each ferritin molecule
holds about 2000 molecules of iron oxide, forming what might well be an
atomically precise object.
Ferritin subunits are of two common types: L and H. Since L ferritin crystallizes
easily it was mapped in detail by X-ray diffraction several years ago. H
ferritin, however, resists crystallization. European researchers decided
that the reason lay in the presence or absence of a metal binding site on
the molecular surface--crystals of L ferritin are stabilized by cadmium
atoms at the points of intermolecular contact. A metal-binding site was
therefore introduced into H ferritin by changing a single amino acid. The
resulting molecules crystallized easily and have now been mapped. [Nature
349:541-544,3Feb91]
That a single amino acid substitution can make a drastic difference in how
proteins interact is no surprise; what is remarkable is to see the interaction
so effectively redesigned. Similar techniques might permit other proteins
to be assembled into larger structures or "programmed" to rearrange
themselves in response to changes in their chemical environment.
In other ferritin news, researchers at the
University of Bath (England) used ferritin molecules as reaction vessels
for producing beads of several kinds of materials, including manganese oxide,
uranyl oxyhydroxide, and iron sulfide. The first two products were made
by allowing the reactants to penetrate into empty ferritin spheres; the
metals underwent oxidation and precipitated in the cavity. The iron sulfide
was made by exposing iron-filled ferritin to hydrogen sulfide; the reaction
took place inside the ferritin cavity. Electron microscope analysis showed
all the products to be beads 7-8 nm in diameter. [Nature 349:684-687,21Feb91]
How might ferritin be adapted for nanotechnology? Let's indulge in some
speculation. Genetic engineering applied to ferritin's L and H subunits
would let us create new subunits of our own design. But whereas native ferritin
is assembled out of semi-arbitrary combinations of 24 L and H subunits,
the assembly of engineered ferritin could be controlled by designing the
interfaces between different subunits. The shape of the interior ferritin
cavity would be determined by the design of the corresponding surfaces of
the subunits. The specificities of the catalytic sites might be modified
so that different subunits would sequester different elements or small molecules.
The result: a set of molds for making nanometer-scale machine parts with
controlled shapes and compositions. (Possible drawbacks: crystals of this
size may not be very stable; and small machine parts may be a lot easier
to make than to assemble into a machine.)
Russell Mills directs a small research company in California.
Table of Contents - Foresight
Update 12
Molecular Manufacturing for Space
by Chris Peterson
For decades the space development effort has been plagued
by expensive and unreliable hardware, so it isn't surprising that this community
has shown a strong interest in the molecular manufacturing concept since
its earliest days. To follow up on this interest, the Foresight Institute
and the Institute for Molecular Manufacturing
sent representatives to the International Space Development Conference in
San Antonio in late May. Attending were Jim Bennett, IMM Executive Director
Lynne Morrill, Eric Drexler, and myself. The results were all that we had
hoped, and more.
Foresight and IMM shared an information table, and many of those stopping
by reported that they came to the meeting specifically for the nanotechnology
coverage. A well-attended lecture on that topic was given by Eric Drexler.
That evening IMM held a small gathering of supporters and garnered its first
$1000 donation, from John Baccellieri of Arlington, Texas. (Mr. Baccellieri
told us that he had been unable to attend the main talk himself, since he
was serving as coordinator of volunteers at the conference: his volunteers
had deserted him in order to attend that talk, leaving him on duty alone.)
The next day included another talk relating the old goals of space settlement--familiar
to many in the audience who had been members of the L5 Society--to the new
means of molecular manufacturing. Running concurrently was the National
Space Society Board of Directors meeting, at which a motion in support of
molecular manufacturing (see text below) was unanimously approved. Then
that evening at the Awards Banquet, a Space Pioneer award in the Scientist/Engineer
category was presented to Eric Drexler for his work on nanotechnology.
In parallel, a new special interest group was formed within the National
Space Society: the Molecular Manufacturing
Shortcut Group. They plan to get the needed technology developed sooner
by diverting more government research funds to the relevant enabling science
and technologies. The group is open to any member of the National Space
Society. For more information, write to the president of the new group:
Stewart Cobb, Molecular Manufacturing Shortcut Group, 555 Bryant St. Suite
253, Palo Alto, CA 94301.
[Editor's note: The current mailing address is:
Molecular Manufacturing Shortcut Group, 8381 Castilian Drive, Huntington
Beach, CA 92646.]
As an incentive to new members, IMM distributed souvenir T-shirts with the
IMM logo on the front and the slogan "Ad Astra Per Nanotechnologia"
(To the Stars through Nanotechnology) on the back. A few of these collector's
items are still available; contact IMM.
The following is an abridged version
of the text distributed to the NSS Board:
Improvements in manufacturing capabilities have played an essential role
in opening the space frontier and will continue to do so. The mechanical
manipulation of matter at the molecular level, proposed by Richard Feynman[1],
has now been demonstrated[2]. Molecular manipulation
can be used to construct general structures[3], ultimately
including high-performance, low-cost aerospace systems[4,5].
Concrete examples include the manufacture of structural components with
order-of-magnitude improvements in strength and stiffness, and order-of-magnitude
reductions in cost. This by itself would suffice to make single-stage-to-orbit
vehicles efficient and inexpensive.
Major steps toward this objective are now feasible[6],
requiring perhaps 3 to 5 years with a budget of perhaps $1-2 million per
year. Large-scale space applications will await the emergence of advanced
molecular manufacturing and related nanotechnologies, requiring many years
of goal-oriented research--a long time by some standards, but well within
the 10- to 25-year time horizon that has been traditional in the space movement.
Molecular nanotechnology promises to play a central role in 21st century
industry, both on Earth and in space, but the U.S. is falling behind. The
journal Nature writes[7] of "blossoming
interest in Japan in nanotechnology, a field which with the backing of the
powerful Ministry of International Trade and Industry (MITI) seems destined
to become Japan's next priority target for industrial research."
Proposed resolution
Substantial sentiment on the Board and within the Society favors the promotion
of nanotechnology development as one of several approaches that can accelerate
the achievement of long-term space goals. Because initial results can apparently
be had for a cost that is insignificant relative to that of any major space
project, a small effort today can speed developments with enormous future
payoffs for space technology. Further developments will be more expensive,
but will proceed on the basis of concrete technological achievements, many
with immediate applications. An NSS role in these further developments can
guide them more swiftly toward space applications. To help the Society take
advantage of this opportunity, the following resolution is proposed to facilitate
activities by NSS members:
Whereas, advances in materials, computers, and manufacturing have
in the past led to advances in space technology, and
Whereas, advances in molecular systems engineering, leading to molecular-precision
fabrication and related molecular nanotechnologies, promise to yield dramatic
advances in materials, computers, and manufacturing, be it therefore
Resolved, that the National Space Society encourages the pursuit
of research leading toward molecular nanotechnology as a means of accelerating
space development, and encourages the formation of a group within the Society
to promote efforts in this direction.
References
- Richard Feynman, "There's
Plenty of Room at the Bottom," in Miniaturization,
H. Gilbert, ed., (New York: Reinhold, 1961).
- D. M. Eigler and E. K. Schweizer, "Positioning
single atoms with a scanning tunnelling microscope," Nature
344: 524-526 (1990).
- K. Eric Drexler, "Molecular
engineering: An approach to the development of general capabilities for
molecular manipulation," Proceedings of the National Academy
of Sciences (USA) 78: 5275-5278 (1981).
- K. Eric Drexler, "Molecular Engineering: Assemblers
and Future Space Hardware," American Astronautical Society, AAS-86-415
(1986).
- Stewart Cobb, "Molecular Magic," Ad
Astra 2,6:22-25 (June 1990).
- K. Eric Drexler, "Molecular Tip Arrays for
AFM Imaging and Nanofabrication," Journal of Vacuum Science and
Technology B 9(2): 1394-1397 (March/April 1991).
- David Swinbanks, "Nanotechnology: MITI aims
at small research," Nature 349:449 (1991).
Table of Contents - Foresight
Update 12
Foresight thanks Dave Kilbridge for converting Update 12 to html for
this web page.
From Foresight Update 12, originally published 1
August 1991.
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