Foresight Update 14 (page 2)
A publication of the Foresight Institute
Open Conference on Nanotechnology
Although Foresight has sponsored two conferences
for nanotechnology researchers, we have yet to hold a major meeting at which
all Foresight participants can learn more about the subject, meet each other,
and share perspectives. This meeting--the First General Conference on Nanotechnology:
Development, Applications, and Opportunities--will be held this fall in
Palo Alto, California, on November 11-14, and will cover technical, business,
and policy issues.
Speakers will be drawn from the extended Foresight community. We plan to
ask representatives of the following groups to address the meeting:
- researchers (e.g. Eric Drexler and IMM Advisor Ralph Merkle),
- policy strategists (e.g. CCIT president Jim Bennett),
- authors (e.g. Chris Peterson and Gayle Pergamit of Unbounding
the Future: the Nanotechnology Revolution),
- advisors to business and industry (e.g. Global Business Network principals
Peter Schwartz and Stewart Brand, who also serve on the advisory board of
the Foresight Institute), and
- business and industry leadership (e.g. IMM board member Neil Jacobstein,
VP of the Knowledge Systems Division of Cimflex Teknowledge).
From our experience with the scientific meetings, we've learned that conference
participants like to have plenty of time to interact informally, and we'll
try to include that as well as scheduled presentations.
We will be contacting selected organizations regarding financial sponsorship
of the meeting. If your organization would like to be considered for such
participation, call the Foresight Institute office.
The Foresight leadership look forward to meeting as many of you as possible
at this first conference for the interested layperson, and we cannot urge
you too strongly to attend. We believe that years from now, this meeting
will be regarded as a seminal event in both the industrial development and
policy planning for nanotechnology.
[Editor's note: See Update
15 for a brief review
and for selected photos
from this conference. The proceedings of this conference have been published
in book form.]
Table of Contents - Foresight
Update 14
Gerald Feinberg
We regret to report the recent loss of Prof. Gerald Feinberg, a member of
the Foresight Board of Advisors, to cancer. Formerly Chairman of the Columbia
University Department of Physics, Prof. Feinberg brought both scientific
expertise and a profound concern for humanity to the Foresight effort (see
his interview in Update No. 9). He will be greatly missed.
Table of Contents - Foresight
Update 14
Upcoming Events
Atomic & Nanoscale Modification of Materials, August
16-21, Doubletree Hotel, Ventura, CA. Primarily a "top-down" approach
to miniaturization, but includes some STM work. Contact the Engineering
Foundation, 212-705-7835.
American Aging Association, October 20, St. Francis Hotel,
San Francisco. Eric Drexler will speak on medical nanotechnology applications
to aging. Contact AGE, 402-559-4416.
First General Conference on Nanotechnology: Development, Applications,
and Opportunities, November 11-14, 1992, Holiday Inn Stanford/Palo
Alto, Palo Alto, CA. A meeting for Foresight participants, addressing nanotechnology:
the technology itself, policy issues, and business opportunities. For the
interested layperson; not a research-only conference. Contact the Foresight
office at 415-324-2490 or email foresight@cup.portal.com. Registration forms
will be posted on our MessagePost when available, 415-948-8310 (call from
the handset on your fax machine). [See above
article.]
[Editor's note: Foresight's current email address is inform@foresight.org.]
Table of Contents - Foresight
Update 14
Recent Progress: Steps Toward Nanotechnology
by Russell Mills
I have a poor memory. That's not to say that I can't remember my friends,
or anything as bad as that. It's just that my mind behaves like a sieve
with regard to specifics, such as the biochemical explanation I just read
yesterday, or the street I'm supposed to take to get to a friend's house.
A second-rate memory did not prevent me from getting a broad education or
from acquiring a good general understanding of a variety of technical areas.
But it has been a major impediment to doing noteworthy scientific research.
I have recently taken actions which may change all this. The first hurdle
was to convince my doctor that a problem really exists. She began to believe
me only after I suggested an EEG (electro-encephalograph) test, and the
test results came back showing significant abnormalities. The next step
was an MRI (Magnetic Resonance Imaging) brain scan to check for large-scale
problems; these images have not yet been analyzed as of this writing.
The EEG results were exactly what I wanted, but I am hoping that the MRI
images show nothing awry. Why? Because EEG irregularities mean that nerve
cells are misfiring in my brain--a condition for which there are drug treatments.
Anything that shows up on the MRI, on the other hand, is likely to require
brain surgery if it can be treated at all. I'd much rather subject my brain
to a treatment based on nanometer-sized tools (i.e., drugs) than centimeter-sized
tools (e.g., scalpels). True, both kinds of tools are crude and dangerous
compared with their 21st Century counterparts; nevertheless, I feel that
drug molecules are more advanced than knives. I look at it this way: the
distinction between drug treatment and surgery may someday disappear as
drug molecules of greater size and complexity are developed. Tomorrow's
physicians will use medicinal nanomachines equipped with computers, sensors,
and moving parts--like the ones described in Engines
of Creation, and Unbounding the Future. These nanomachines
are more likely to evolve from drugs than from scalpels, in my opinion.
In this sense, scalpels may be an evolutionary dead end.
Medicinal nanomachines
Until recently nearly all drugs, whether synthetic or biological in origin,
have been small molecules consisting of fewer than 300 atoms--too small
even to span, let alone to refurbish, their biological targets. That situation
is changing as proteins make their way onto the pharmaceutical stage. Nucleic
acids, too, are now being readied for roles as drugs. Why proteins and DNA?
Because they are polymers (molecular chains) made from readily available
components; with the limitations of today's technology, polymers are much
easier to assemble than molecules containing the same number of atoms connected
in nonlinear patterns. The ultimate in pharmaceuticals (medicinal nanomachines)
may be nonpolymeric and unavailable until nanotechnology provides assemblers
to make them.
Presumably tens of thousands of useful protein and DNA drugs are waiting
to be discovered. But identifying them has been a problem. Which of the
10390 different protein chains 300 amino acids long correspond
to useful protein drugs? Which of the 1016 different DNA molecules
27 nucleotides long should be investigated for their ability to bind to
proteins or other molecules? One approach to this problem is suggested by
recent advances in the synthesis and handling of large molecular "libraries".
A research group at Gilead Sciences in California
has used a DNA library to identify DNA sequences that bind and inactivate
a target protein. (Nucleic acids that bind to specific molecular targets
are called "aptamers".) The researchers first synthesized a pool
of 1013 different DNA 96-mers (i.e., molecules 96 nucleotides
long). Each molecule contained a different 60-nucleotide random subsequence
and two 18-nucleotide sequences recognized by polymerase enzymes used in
replicating the DNA. The pool of DNA was allowed to interact with the target
protein--in this case a blood coagulator called thrombin--attached to a
solid support. A small fraction of the DNA molecules stuck to the thrombin;
the rest were washed away. The bound DNA was recovered, replicated many-fold,
and allowed to interact again with the thrombin. Repeating this selection
cycle five times led to a pool of effective aptamers in sufficient quantity
for analysis. A "consensus" sequence of 12 nucleotides was found
to occur with only minor variations in the 32 best aptamers. Presumably
the next step will be to use the consensus sequence as an aptamer to prove
that it can bind thrombin by itself. This technique seems well suited to
designing DNA drugs quickly without computer simulation. [Nature
355:564-566, 6Feb92]
Similar work by researchers at Massachusetts
General Hospital used a DNA pool of 157-mers, containing 120-nucleotide
random subsequences. Dye compounds, rather than a protein, were used as
selection agents. An 18-nucleotide consensus sequence was identified after
five cycles of selection. [Nature 355:850-852, 27Feb92]
An ingenious method for generating peptide
libraries and screening them for binding to target molecules has been developed
by investigators in Arizona. (A "peptide" is a chain of amino
acids. Proteins are peptides.) Millions of resin beads were divided into
19 portions and placed into 19 reaction vessels, each containing a different
amino acid. The beads' surfaces reacted with the amino acids, forming a
coating one molecule deep. The beads were collected, randomized, and redistributed
to the vessels, whereupon a second amino acid attached to the first. Continuing
in this manner produced a collection of beads, each carrying a layer of
peptides of uniform composition and length. Using a sufficient number of
beads ensures that all possible peptides of the desired length are represented
in the collection with high probability. The researchers in this study synthesized
chains of five amino acids on their beads, then exposed the beads to a target
compound to which a fluorescent dye had been chemically attached. Beads
whose peptide chains had affinity for the target compound became intensely
stained and could be removed with tweezers for analysis--i.e., the
sequence of amino acids responsible for affinity could be determined. The
amount of peptide required for analysis turned out to be only a small portion
of the peptide on a single bead; therefore the beads with their attached
peptide library could be used multiple times on different target compounds.
[Nature 354:82-84, 7Nov91]
What may be a major breakthrough in the search
for DNA drugs has been made at the Panum and the H.C. Ørsted Institutes
in Copenhagen. Researchers there have developed a remarkable new form of
anti-sense DNA--a DNA-like polymer that is intended to bind and inactivate
segments of normal RNA or DNA. Anti-sense DNA is a hot research area and
dozens of different modifications of the DNA structure have been made and
tested in laboratories throughout the world. Among the properties an anti-sense
drug must have are: nuclease resistance (nuclease enzymes must not degrade
it before it reaches its target inside cells); sequence-specific recognition
(it must inactivate only the desired nucleotide sequence in the target molecules);
binding affinity (drugs targeted to RNA must remain bound until the target
is degraded by nucleases in the normal course of cell maintenance; drugs
targeted to DNA (i.e., to chromosomal genes), should not have to
be renewed too often during therapy. The need for nuclease resistance immediately
disqualifies normal DNA and RNA as potential anti-sense drugs.
The Copenhagen group used computer modeling to develop a radically different
backbone for DNA, substituting a pair of amides for the normal chain of
alternating phosphates and sugars that holds DNA together. The resulting
PNA (polyamide nucleic acid) not only met the above criteria, its binding
affinity far exceeded that of any other anti-sense compound. Unlike other
anti-sense structures, which interact with double-stranded DNA by associating
with the double helix, PNA pushes between the strands of the helix, displacing
one strand and forming its own double helix with the other. If PNA continues
to show good sequence specificity, and if it proves able to pass through
membranes into the cell nucleus, then it may be the long-sought tool for
turning off faulty genes and tuning up chromosomes. [Science
254:1497-1500, 6Dec91]
Dr. Vivian Cody conducts some of her drug
binding studies by using virtual reality, enabling her to "virtually"
reach out and feel the forces between a drug and its protein target. As
she moves a small organic drug molecule near one of the protein's amino
acid side chains, she can "feel" inner repulsion or attraction
between the molecules. Dr. Cody, a researcher at the Medical Foundation
in Buffalo, New York, works in what is called a molecular docking "virtual
reality" system, located in the Department of Computer Science at the
University of North Carolina in Chapel Hill. This new computer technology
simulates reality as it is thought to exist at the molecular level. She
manipulates graphic representations of compounds and proteins projected
onto a 4x5 foot screen. As she moves the molecules the electrostatic force
between them is calculated by a computer and fed into an arm. When resistance
is felt in the grip it means the binding is not favorable; ease of movement
means the position is promising. [Genetic Engineering News
XII:8:1]
Protein machines
Thomas D. Pollard, in a report on the Proteins as Machines
symposium at Indiana University last October, defines protein machines as
"the driving units that produce macromolecular movement in living organisms".
These include the rotary motors of bacterial flagella, the linear motors
responsible for muscle contraction and for transportation of materials within
cells, the polymerases that copy DNA and RNA, and the pore structures that
selectively move molecules through membranes. Pollard says that in every
case we lack sufficient information to explain the mechanisms operating
at the molecular level. A central question is exactly how energy is used
by the motors. In one hypothesis, the motors randomly attach and detach
to a substrate (or "track"); during attachment they undergo an
energy-consuming change of shape that moves their center of mass along the
track. Another suggestion is that the energy biases the affinity of the
motor for its substrate, causing the motor to attach preferentially when
random thermal vibration puts it in an extended position. [Nature
355:17-18, 2Jan92]
Protein design
A group at UC Berkeley has developed a general method for incorporating
"unnatural" amino acids into proteins, using components of the
protein synthetic apparatus taken from bacteria and yeast, and a gene taken
from a virus. In a preliminary application of their technique they made
several versions of the much-studied enzyme T4 lysozyme. In each version
an unusual amino acid was substituted for the amino acid alanine at position
82 along the protein chain--a position at which two helical segments of
the molecule are joined together. A comparison of the thermal stabilities
of the resulting proteins gave insight into the effect of structural details
upon the behavior of a protein. Information gained through this technique
will be of use in designing proteins out of normal amino acids; it is not
a practical method for manufacturing modified proteins. [Science
255: 197-200, 10Jan92]
Nanosensing and manipulation
A new breed of scanning tunneling microscope (STM) has been developed at
Sandia National Laboratories in New Mexico. Called the interfacial-force
microscope (IFM), it overcomes the STM's tendency to become unstable when
scanning at certain distances from a sample. The IFM owes its stability
to a capacitor and force-feedback electronics which replace the mechanical
cantilever that hold the probe tip in STMs. This arrangement permits the
measurement of forces between probe and sample over the entire range of
separations, including contact. Unfortunately an inverse relation exists
between tip radius and sensitivity; this translates into a trade-off between
resolution along the z-axis (perpendicular to the sample) and that along
x and y. Thus, the tips presently being used are about 500 nm in radius;
they can sense surface irregularities along the z-axis of about 0.2 nanometers
(about the size of an atom), and are expected to improve soon by a factor
of 100, but their x-y resolution is limited to several tens of nanometers.
[Nature 356:266-267, 19Mar92]
John A. Sidles at the University of Washington,
Seattle, has designed a microscope based on nuclear magnetic resonance (NMR),
the phenomenon on which medical magnetic resonance imaging is based. It
is hoped that such a device, when built, would enable mapping of individual
hydrogen nuclei in a surface, providing enough information to determine
the three-dimensional structure of proteins and other complicated molecules.
[Science News 141:150, 7Mar92]
Carbon structures
The use of carbon as a structural material for nanotechnology was originally
proposed by Eric Drexler based on what was then known about diamond. As
luck would have it, the past few years have seen a surge of research interest
in the chemistry of pure carbon. One goal of this research has been to find
easier ways to make diamond, since diamond is of increasing industrial importance.
More recently, attention has focused on fullerenes, highly stable chemical
structures related to graphite. Whereas graphite consists of carbon atoms
bonded in a hexagonal lattice (like chickenwire) to form flat sheets, fullerenes
are closed cage-like molecules in which the lattice is curved and contains
pentagons as well as hexagons. Carbon's versatility is proving to exceed
all expectations, adding weight to the argument for a carbon-based nanotechnology.
From the NEC Corporation in Tsukuba, Japan,
comes a report of graphitic microtubules collected from the negative end
of a carbon electrode used for making fullerenes. Upon examination with
a transmission electron microscope the tubules proved to consist of a series
of two to fifty coaxial cylindrical layers. Individual layers were hexagonal
lattices of carbon atoms separated by 0.34 nanometers. The smallest cylinders
were 2.2 nm in diameter, which would make them roughly 50 to 60 carbon atoms
in circumference. (It would be interesting if someone could now measure
the strengths of the microtubules and the friction generated by differential
rotation between the layers.) [Nature 354:56-57, 7Nov91].
Making diamonds out of graphite requires pressures
of 30-50 GPa (gigapascals) or heating to 1200 K in the presence of a catalyst.
Researchers at CNRS in Grenoble, however, recently discovered that diamonds
can be made more easily by compressing the fullerene C60 to a
pressure of 20 GPa at room temperature. C60 is a closed "cage"
of 60 carbon atoms; it has a spherical shape. [Nature 355:237-239,
16Jan92]
Table of Contents - Foresight
Update 14
Foresight thanks Dave Kilbridge for converting Update 14 to html for
this web page.
From Foresight Update 14, originally published 15
July 1992.
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